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Thought Provoking

Posted on April 1, 2023 by Ken

Since Slow Joe was just there to eat Chocolate Chip Ice Cream.

President Joe Biden opened up a speech Monday to celebrate Women’s History…

Month by ranting about his love of ice cream.

Biden was hosting an event at the White House to recognize the U.S. Small Business Administration Women’s Business Summit, announcing additional resources to help women small business owners and expanding the number of Women Business Centers networks.

The transcript reads: “Thank you. My name is Joe Biden. (Laughter.) I’m Dr. Jill Biden‘s husband. (Laughter.) And I eat Jeni’s Ice Cream, chocolate chip. (Laughter.) I came down because I heard there was chocolate chip ice cream. (Laughter.)”

Shortly after addressing others in the audience, including some children in attendance, the president went on to talk about the school shooting in Nashville.

President Joe Biden Accidentally Calls Mississippi Town Rolling Fork

instead ‘Rolling Stone’ In Latest Awkward Mix-Up (msn.com)

“Before I begin to speak, and the reason I spent a little time on the kids, I — I just want to speak very briefly about the school shooting in Nashville, Tennessee,” the president said. Since it was only a passing moment in Biden’s Day. I thought I would exhibit proper condolence to family & friends of the victim of Covenant Grade School in Nashville Tennessee.

Yesterday was meant to be a day that 9-year-old Evelyn Dieckhaus was going to be singing Louis Armstrong’s “What a Wonderful World” in a play about jazz at her school. The Wonderful World she was going to sing about doesn’t exist. Because sadly, her life was taken away by the Trans Shooter. Never forget Evelyn Dieckhaus Love For Life!!!

Sarah McLachlan – I Will Remember You (Live)

A few days ago, was #TransDayOfVisibility where we saw Trans activists use violence, anger and hatred to push their ideology. They had no regard or thought for little Evelyn who should have been in her school jazz play. Instead, her life was cut short because of Radical Trans Ideology. And yes. LGBQ+ is an unfortunate curse by GOD, because of Sin. Sinful fleshly desires. God gave them over to these. Not sinning is Not giving into these desires. And asking the Lord for help staying strong and uncorrupted. But, there is still sin on both sides.

𝗧𝗵𝗲𝘀𝗲 𝗹𝗶𝘃𝗲𝘀 𝗺𝗮𝘁𝘁𝗲𝗿𝗲𝗱 #NeverForget as Biden celebrates #TransDayOfVisibility #TransgenderDayofVisibility
The unimaginable horror from the reports from affected families leave my heart broken. Whatever the motive for this heinous act, it is up for interpretation…We may never know, but what we do know for a fact, six innocent lives were eliminated.
Moment of silence for the victims

God knows my/our hearts are broken

Can you imagine this angel’s family & friends?!

Isaiah 59:1-21 KJV

King James Version 59 Behold, the Lord’s hand is not shortened, that it cannot save; neither his ear heavy, that it cannot hear: Read full chapter Isaiah 59:1 Behold, the Lord’s hand is not shortened, that it cannot save; neither his ear heavy, that it cannot hear: [2] But your iniquities have separated between you and your God, and your sins have hid his face from you, that he will not hear. [3] For your hands are defiled with blood, and your fingers with iniquity; your lips have spoken lies, your tongue hath muttered perverseness. [4]
None calleth for justice, nor any pleadeth for truth: they trust in vanity, and speak lies; they conceive mischief, and bring forth iniquity. [5] They hatch cockatrice’ eggs, and weave the spider’s web: he that eateth of their eggs dieth, and that which is crushed breaketh out into a viper. [6] Their webs shall not become garments, neither shall they cover themselves with their works: their works are works of iniquity, and the act of violence is in their hands. [7] Their feet run to evil, and they make haste to shed innocent blood: their thoughts are thoughts of iniquity; wasting and destruction are in their paths. [8]
The way of peace they know not; and there is no judgment in their goings: they have made them crooked paths: whosoever goeth therein shall not know peace. [9] Therefore judgment is far from us, neither does justice overtake us: we wait for light, but behold obscurity; for brightness, but we walk in darkness. [10] We grope for the wall like the blind, and we grope as if we had no eyes: we stumble at noonday as in the night; we are in desolate places as dead men. [11] We roar all like bears and mourn sore like doves: we look for judgment, but there is none; for salvation, but it is far off from us. [12]

For our transgressions are multiplied before thee, and our sins testify against us: for our transgressions are with us; and as for our iniquities, we know them; [13] In transgressing and lying against the Lord, and departing away from our God, speaking oppression and revolt, conceiving and uttering from the heart words of falsehood. [14] And judgment is turned away backward, and justice standeth afar off: for truth is fallen in the street, and equity cannot enter. [15] Yea, truth faileth; and he that departeth from evil maketh himself a prey: and the Lord saw it, and it displeased him that there was no judgment. [16]
And he saw that there was no man, and wondered that there was no intercessor: therefore his arm brought salvation unto him; and his righteousness, it sustained him. [17] For he put on righteousness as a breastplate, and a helmet of salvation upon his head; and he put on the garments of vengeance for clothing, and was clad with zeal as a cloke. [18] According to their deeds, accordingly he will repay, fury to his adversaries, recompense to his enemies; to the islands he will repay recompense. [19] So shall they fear the name of the Lord from the west, and his glory from the rising of the sun.

When the enemy shall come in like a flood, the Spirit of the Lord shall lift up a standard against him. [20] And the Redeemer shall come to Zion, and unto them that turn from transgression in Jacob, saith the Lord. [21] As for me, this is my covenant with them, saith the Lord; My spirit that is upon thee, and my words which I have put in thy mouth, shall not depart out of thy mouth, nor out of the mouth of thy seed, nor out of the mouth of thy seed’s seed, saith the Lord, from henceforth and forever.

Absolutely. The falling away is real and it is happening right now. In fact it was already working in Paul’s day. Once the reprobates realize God’s Word is the root of their problem, and is what’s stopping reality from becoming a full blown habitation of devils with every foul spirit and a cage of every unclean bird, they will war with us. Matthew 24:8-9 KJV

All these are the beginning of sorrows. [9] Then shall they deliver you up to be afflicted and shall kill you: and ye shall be hated of all nations for my name’s sake.

ALERT Lightning bolt strikes One World Trade Center New York City April 1 2023 – YouTube

Doesn’t this happen every year or two?

2018 https://youtube.com/shorts/463pix3y…

2017 https://youtu.be/E-zWRx-PPXM

2014 https://youtu.be/zOC0nmcKPco

2015 https://youtube.com/shorts/rAYv8SkQ…

A year ago https://youtu.be/hI7ev5YcErQ

3 years ago, https://youtu.be/Ue1Q4IPLnz8 Etc.… there’s more.

42AVCM38P@42AVCM38P·37mReplying to @JackPosobiec

My wife and I were attending the 1700 mass today and as you know it’s Palm Sunday. During the Passion of Christ there came heavy thunder followed by a downpour. Lititz PA And signs and portents will appear in the heavens It’s a sign that he is sending all of us to either get this evil administration out of office or to return and burn this shit hole to the ground. It’s our responsibility to get this country back to God or He’s going to destroy it once and for all.

The storm is here:
That’s a Huge Positive Discharge of over 3 billion volts with 4 secondary discharges and a fireball in the middle of the return stroke on the first one, neutralizing negative effusion in the atmosphere for 50 miles in all directions in the severe front as it moves off the coast.
That was a discharge from the building. From the building it spread out everywhere. Either it’s fake or it came from that tower in my opinion. Lightning doesn’t strike like that. Maybe the frequency from the tower promoted the strike…. Pretty weird though.

This is a rare phenomenon over NYC in this form.
They try to persecute President Trump during the Holy Week just like Jesus was persecuted, The Father from Heaven will not leave them alone.

Trump will rise from the Dead heads Acts 2:19.

Please humble yourselves, turn from your wicked ways and pray!

Lunar eclipses 2023 — When, where & how to see them | Space

In 2023, Earth will experience two lunar eclipses. The next lunar eclipse will be a penumbral lunar eclipse on May 5 and will be visible across parts of Africa, Asia and Australia. The second will be a partial lunar eclipse on October 28 and will be visible across parts of E. Americas, Europe, Africa, Asia and Australia. Lunar eclipses occur when Earth is positioned between the sun and the moon and casts a shadow across the surface of the moon.

They can only occur during a full moon and make for an interesting skywatching target. The last total lunar eclipse that occurred on November 8, 2022, thrilled skywatchers worldwide, the next total lunar eclipse — also known as a blood moon lunar eclipse — won’t happen until March 13/14, 2025. So that God will look down from heaven and heal our land. You do realize not everyone believes in your god nor should they have to. People keep shoving religion down people’s throats and that’s just going to push them away. I feel bad for what happened to this girl and yes while the shooter was trans, that does not define everyone. Lyrics If this World by Jaci Velasquez – YouTube

Sodom Gomorrah – Search (bing.com)

34 “Can you shout to the clouds and make it rain? 35 Can you make lightning appear and cause it to strike as you direct? 36 Who gives intuition to the heart and instinct to the mind? 37 Who is wise enough to count all the clouds? Who can tilt the water jars of heaven 38 when the parched ground is dry, and the soil has hardened into clouds?

Job 38:34-38 His lightning lights up the world; the earth sees and trembles. Psalm 97:94 He is who makes the clouds rise at the end of the earth, who makes lightnings for the rain and brings forth the wind from his storehouses. Psalm 135:7 Our God is an awesome God. The heavens declare the glory of the Lord!

The Love of God – YouTube

The Love of God w/ Lyrics (Mercy Me) – YouTube

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NO April’s Fools Joke

Posted on April 1, 2023 by Ken

America and the Taliban’: 3-Part Docuseries Premieres April 2023 | FRONTLINE

GOVERNMENT AND BUSINESS HAS A SINISTER SIDE TO IT IN THIS COUNTRY 🙁
There is no story in twentieth-century history more important to understand than Hitler’s rise to power and the collapse of civilization in Nazi Germany. With *The Coming of the Third Reich*, Richard Evans, one of the world’s most distinguished historians, has written the definitive account for our time. A masterful synthesis of a vast body of scholarly work integrated with important new research and interpretations, Evans’s history restores drama and contingency to the rise to power of Hitler and the Nazis, even as it shows how ready Germany was by the early 1930s for such a takeover to occur. The Coming of the Third Reich: Richard J. Evans: Amazon.com: Books is a masterwork of the historian’s art and the book by which all others on the subject will be judged.

CORRUPTION AT THE D.A. Office in N.Y.C.
NYC District Attorney Alvin Bragg – Bing video

**Alvin Leonard Bragg Jr.** (born October 21, 1973) is an American politician and
lawyer from New York City who is serving as the New York County District Attorney, covering Manhattan. In 2021, he became the first African American elected to that office.^[1] Bragg had previously served as chief deputy Attorney General of New York and as an assistant United States Attorney in the Southern District of New York.

Early life and education
Bragg is from Harlem, and grew up on Striver’s Row.^[2] In an interview with *The American Prospect*, Bragg said that he had been “deeply affected by the criminal justice system – most directly through three gunpoint stops by the NYPD.”^[3] He graduated from the Trinity School^[4] before attending Harvard College. He graduated from Harvard *cum laude* with a Bachelor of Arts in government in 1995,^[2][5] and earned his Juris Doctor from Harvard Law School, where he was an editor of the *Harvard Civil Rights–Civil Liberties Law Review*.^[5][4]

Early career
Bragg clerked for federal district judge Robert P. Patterson Jr. before he joined the law firm Morvillo Abramowitz Grand Iason & Anello as an associate, where his work focused on white collar fraud and civil rights issues. In 2003, he joined the office of the Attorney General of New York under Eliot Spitzer before becoming the chief of litigation and investigations for the New York City Council. In 2009, Bragg left the city council to
serve as assistant United States Attorney in the Southern District of New York.^[6]

In 2017, Eric Schneiderman, then serving as attorney general, appointed Bragg Chief Deputy Attorney General of New York.^[7] Bragg ran the criminal justice and social justice divisions, overseeing lawsuits brought by the state against the Donald J. Trump Foundation, Harvey Weinstein and The Weinstein Company, and the addition of a citizenship question on the 2020 United States Census.
He left the position in December 2018^[8] and became a professor at the New York Law School, where he was co-director of the Racial Justice Project.^[6] Bragg is a member of the board of directors for the Legal Aid Society. He has represented the families of Ramarley Graham and Eric Garner in civil litigation against New York City.^[9]

New York County District Attorney
In June 2019, Bragg started his candidacy for the 2021 Democratic Party nomination for New York County District Attorney, then held by Cyrus Vance Jr.,^[8] who did not to
run for reelection.^[10]
Following the June 22, 2021, Democratic primary, Bragg led in the reported vote count and Tali Farhadian Weinstein conceded the primary to Bragg on July 2.^[11] On November 2, 2021, Bragg defeated Republican Thomas Kenniff in the general election, becoming the first African American to be elected New York County District Attorney.^[1]
Bragg was sworn into office on January 1, 2022.^[12]

Policies on low-level offenses
On January 4, 2022, after three days in office, he announced that his office would no longer prosecute low-level offenses such as fare evasion, resisting arrest, prostitution, and cannabis-related misdemeanors unless accompanied by a felony charge. He also decided to seek lesser charges for burglaries and store robberies where the offender “displays a dangerous instrument but does not create a genuine risk of physical harm”.^[13] On January 20, Bragg disputed what he described was a “legalistic” interpretation of his prosecution policy memo and indicated that he supported a zero tolerance policy for violent crimes.^[14]

Donald Trump prosecution
Main articles: New York criminal investigation of The Trump Organization
and Indictment of Donald Trump. On February 23, 2022, Carey R. Dunne and Mark F. Pomerantz, the lead prosecutors in the New York County District Attorney’s investigation into Donald Trump and his businesses, resigned abruptly after Bragg “indicated to them that he had doubts about moving forward with a case against Mr. Trump”.^[15]
In his letter of resignation, Pomerantz wrote that the “team that has been investigating
Mr. Trump harbors no doubt about whether he committed crimes,^[16] including falsifying business records, and that it was “a grave failure of justice”^[16] not to pursue criminal charges.^[17]

*The New York Times* reported that Bragg “balked at pursuing an indictment against
Mr. Trump” and lacked confidence proving in court that Trump “knowingly falsified the value of his assets on annual financial statements.”^[17]
*The Washington Post* noted that Bragg was slow to meet with Dunne and Pomerantz
after taking office and when they finally met to discuss the case, a source in the D.A.’s
Office commented that Bragg seemed distracted & disengaged, continually checking
his cell phone (allegations Bragg’s spokesperson denied).^[18]

On November 21, 2022, *The New York Times* reported that the district attorney’s
office “has moved to jump-start its criminal investigation” into Trump’s reported
“hush-money payment to a porn star who said she had an affair with Mr. Trump.”^[19]
Bragg confirmed to CNN in January 2023 that the probe was ongoing.^[20]
On January 30, the office presented evidence to a grand jury regarding
Trump’s role in the payment.^[21]

Jose Alba prosecution
On July 7, 2022, Jose Alba, a bodega clerk, was attacked by a customer in a dispute
over a bag of potato chips. Alba attempted to de-escalate, but after being shoved into a wall, defended himself with a knife, killing the assailant.^[22] Bragg, in his prosecutorial discretion, decided to charge Alba and requested bail at $500,000; the judge set it at $250,000.^[23][24] The dead attacker’s girlfriend also stabbed Alba with her own knife, after attempting to turn Alba’s knife back on him. Bragg declined to charge her.^[22] After intense backlash, Bragg ultimately decided to drop the charges against Alba, noting that “a homicide case against Alba could not be proven at trial beyond a reasonable doubt”.^[25]

Steve Bannon prosecution
On September 6, 2022, *The Washington Post* reported that Steve Bannon would be indicted on September 8 by Bragg’s prosecutors on the same charges of fraud that he was federally pardoned for by then-President Trump in 2020.^[26]
On September 8, Bannon was charged with “defrauding Americans who wanted to contribute to construction of a southern border wall, resurrecting a threat Mr. Bannon seemed to have escaped with a 2021 presidential pardon”; Bannon pleaded not guilty.^[27]

Personal life
Bragg married Jamila Marie Ponton in 2003.^[28] They have two children.^[5]
Bragg at one time taught Sunday School at the Abyssinian Baptist Church.^[29]

George Soros and Alvin Bragg.

President Donald Trump, writing on Truth Social, said that the Manhattan District Attorney’s office’s “leader is funded by George Soros.” The leader of that office is Alvin Bragg, the Democratic DA who took office in January 2022, according to Ballotpedia.
In the Truth Social post, Trump also wrote that he expects to be arrested on Tuesday,
and he criticized the prosecutor’s office as being highly political.

Is it true? Was Bragg funded by Soros?
Fox News reported that Soros “funneled $40 million dollars into district attorney campaigns nationwide, and now his beneficiaries represent around 20% of Americans,” including Bragg on that list.
Here’s what you need to know: According to The New York Post, former New York Police Commissioner Bill Bratton spoke out against the “$1 million donation that Hungarian-born philanthropist Soros gave to the Color of Change political action committee, which supported Bragg.”
“If you look at every city in America that has violent crime increases and disorder increases…what is the one common denominator?” Bratton said to The Post.
“District attorneys, almost all of whom are funded phenomenally by George Soros.”
The New York Post reported that “Soros also donated $1 million to Alvin Bragg’s successful DA campaign in Manhattan, funneling the cash through the Color of Change political action committee.”

The Gothamist also reported:
“Color of Change PAC, a group that since 2016 has successfully backed reform-minded prosecutors across the country from Philadelphia to Michigan to Atlanta, announced they’d be pitching in $1 million dollars through their political action committee to put towards mailers, canvassing, and phone-banking on Bragg’s behalf.”
The National Police Association accused Soros of funding “ultra-leftist prosecutors
like Alvin Bragg (New York City), Kim Foxx (Chicago), Larry Krasner (Philadelphia),
and George Gascon (Los Angeles),” blaming the trend for rises in violent crime.

Color of Change endorsed Bragg, writing,
Update: Manhattan DA Alvin Bragg won the November 2021 general election with over 83% of the vote. He assumed office on January 1, 2022, and his current term ends on January 1, 2026.
Alvin Bragg (D) is an experienced attorney and a former chief deputy attorney general of New York. For over twenty years, Bragg has committed himself to defending the rights of New Yorkers without status or power.
He is running to become the next Manhattan District Attorney to bring his professional and lived experiences to the forefront of criminal justice reform. If elected, Bragg would become the first Black District Attorney to lead the Manhattan DA’s office.
As a lifelong Harlem resident and the only Black man in this race, Alvin Bragg has had direct encounters with the criminal legal system that have shaped his understanding of injustices and informed his policy positions.
Growing up in Harlem, Bragg experienced and witnessed violence firsthand.
As a teenage boy, Bragg was repeatedly stopped and frisked by the NYPD, including 3 times at gunpoint. He’s seen loved ones arrested and has opened his own home to support a close family member post-incarceration.

The endorsement post, on a page called Voting While Black, reads:
Alvin Bragg uniquely understands the inequities embedded into our broken criminal justice system, and will work to reverse the effects of mass incarceration. As the next Manhattan DA, Alvin Bragg has pledged to:
Hold police accountable by creating a specialized unit to investigate police misconduct and publicly report findings.
Decline to prosecute low-level offenses for which there is no public safety benefit.
Prioritize harm-reduction strategies, including treatment for mental illness and substance use disorders.
Track racial disparities in our criminal justice system and provide training throughout the DAs office to eliminate them.
Reduce the number of guns on the streets by cracking down on gun trafficking and using outreach programs to engage communities and deter violence.
Create an independent, transparent Conviction Integrity Unit dedicated to reviewing and overturning convictions of innocent people who’ve been wrongfully accused.
Read Bragg’s office biography here. See the campaign finance database here.

Great Depression Lessons For The Coming Hard Times – YouTube
THE GREAT DEPRESSION STARTED ON THURSDAY 11 DEC 1930 WHEN THE FED REFUSED TO LEND MONEY TO THE “BANK OF UNITED STATES” AT 77 DELANCEY STREET IN MANHATTAN, NEW YORK CITY. IN OTHER WORDS, THE FEDERAL RESERVE CAUSED THE GREAT DEPRESSION ! ! ! ...

. Marc J. Metivier

Wow! Anyone else see the similarities to what’s happening in 2022?

One of the best, and I think, most realistic movies chronicling life during the
“dirty thirties” was “The Grapes of Wrath”. My father, who grew up in a farming
family during that period, really identified with the farmers’ plight in that movie.
Henry Fonda deserved an Oscar for his performance in that movie.

My grandma remembered it well as she was born in 1925.
When she was a kid, she told her teacher of how she and her family didn’t
have enough money for food, so her teacher went to the store with her and

bought a full paper bag worth of groceries for her to take home.

As she got older and had kids in the 1940s and 1950s and then later becoming my grandma by 1992, she would always make great depression type meals like noodle dishes, German potato salad, and lime jello with peas in it. Depression food was beans and rice. She must have had a middle class experience, if she was able to stay in school.

The history of Social Security published in the 1970s reported that 30% of the USA population literally starved to death or died from shortages of medical services.
The majority were children. The book explained that is what it took to motivate the creation of Social Security. Because Social Security and unemployment insurance create the foundation of the US economy, depressions are NOT likely here.

That doesn’t make sense. And bad as it was, people definitely went hungry, there wasn’t
a mass famine that killed 30% of the country. Also not lots of rice grown in America, it’s potatoes and corn. And social security and EI while good safety nets are not the foundation of the US economy. That’s crazy talk. If they had paid the farmers for the excess produce and distributed it to the starving, that would not have happened.

It is always about money and greed. There is enough food for everyone, but corruption
and greed intentionally prevent some from having enough to eat. I don’t agree with your statement that government payments can prevent depression. When there are shortages and inflation climbs, if those payments get increased that drives inflation even higher. Food shortages are coming so anyone who likes eating better starts producing or supporting locals who will.

My father told me that the day the market crash they was in town, everyone was running to the bank, he said that my grandfather to started laughing, He never kept money in the bank never trusted the banking system when he was a kid his father lost all his money in a bank robbery, My father said that my grandfather turn to my grandmother laughing really loud and said, well I think we are the richest family in the county now, my grandfather kept all the money in a mason jar buried in the barn, by the time the depression was over they still had money left.

Not during the “coming year,” according to the International Monetary Fund.
They call for a 2 to 4% reduction in the global economy.
That is not enough to start a depression. The World Bank says the worst to come in the next 12 months would be recessions. The window of risk of a Global Great Depression has been pushed back to July 2023 to July 2025. We were warned in June 2021 that we were to be monitoring the global economy from January 2023 to July 2025 for any indications of a developing Global Great Depression.

That Is based on pandemic disruptions of economies.
In December 2021, 40% of the world economy was in recession, including Russia, the Americas but not the USA, 14 nations in Europe, East Asia but not Japan. Afghanistan was not mentioned, but families had reported selling children to meet expenses. When the 35 richest nations reported in spring 2021 that they lacked money to fight the pandemic after 2022, Biden took it upon himself to avert a Global Great Depression.

We have been told in June 2022 that the US economy is now stronger than it has ever been. Consumers have caused inflation by going $16,000,000,000,000 in debt. The USA federal national debt has been reduced by Biden to $1 trillion. That is 1/16th of consumer personal debt. One to 2 relevant articles have been published each month, appearing in smartphone free news app news feeds in cities. Business tab. Rural areas don’t seem to get those.

But a person can check online every week or 2.
Search terms can be ‘ recession predictions’ or ‘Global Great depression.’ A person can add a year number. However, note that during election years, a traditional Republican Big Lie is that the economy is in shambles. They hire financial analysts to write negative articles with economics vocabulary to impress the public. Affluent are hoarding. But they are running out of needs, so retail is starting to tank. Some good sales are said to be Begin by clearing excess inventory.

Because the USA has 40,000,000 who are 18 to 27, the USA is unlikely to have a depression. Another 4,000,000 turn 18 each year through 2035. The USA had 100,000,000 born 1996 to 2020–our largest ever work force. They make any USA depression unlikely! Many of the current homeless are refugees from Red States. Red States experience chronic lack of liquidity in their economies because low wages being offered keep workers poor. We are teetering between hyperinflation and a Great Depression at this point.

What I find crazy is our government was paying farmers not to grow food while China

and The Soviet Union was starving to build their infrastructure.

Its called conserving the soil.
You can’t plant year after year on the same plot, the soil gets depleted. It’s a lesson from the dust bowl. you can but you have to rotate crops so you replenish what one crop depletes. But you can’t grow the same crop on the same land endlessly. To raise the price of the crops beyond the price of growing it. You don’t “conserve soil” by NOT PLANTING, at all. You leave a few acres barren for a couple years, then plant those acres and leave others barren. Kind of like “rotating the tires on your car.

Yeah, and right now the Dutch government wants to get rid of the biggest farming companies, because of so-called environmental reasons…;-/
On the government’s Bureau of Labor Statistics (BLS) web site, there is a category for “No Longer in the WorkForce’. There are currently one hundred million working-age Americans (18-65) listed. That’s four times the maximum unemployment during the Great Depression, and does not include today’s “official” unemployed numbers, which add another 6.7 million. Soon we’ll be remembering the Great Depression as “the good old days”.

That can’t be accurate as the USA only has 113.9 million people in That are group. Your numbers would mean only 7 million people are working and over 94% of the rest are not. H5mind: 5 million are in college/university. 5 million are in community college. 15 million are on Social Security Survivor it Disability. 6 million have retired at 62.

Civil servants, military, public school teachers, and mass transit workers retire after 20 years of service. Those get their pensions as young as about 45 to 50. Many affluent stop working when they become adequate investors. Right now (June 2022), there are 3 vacancies for every person on unemployment. You are not analyzing that 100,000 extensively enough. Grandpappy tells of a farmer who made his fortune with farm subsidies.

He was paid to not grow wheat on 80 acres of his land. Great! But that left the land available for growing corn. But instead, he made more by being paid to not grow corn on those 80 acres. And then, paid again to not grow soybeans on that same land. And again, to not grow canola. And again, to not grow safflower. And again, to not grow sunflowers. And again, to not grow cabbages.

So many young folks who just do not even want to hear about those times. They will be frantic! Those who want easy jobs and think being an influencer, an artist, a home-based worker etc. will be hurting. $100. sneakers, expensive fancy nails and hair care, daily outings to eat, constant fancy fashions, luxury upon luxury will end.

Looking at this very interesting report, I kept wondering why it focused so exclusively on white Americans. Thinking about it I realized that there must not be much film material on the life of black Americans at the time and that there was indeed nothing special to report about their life during the great depression because it was not much different to what they experienced over a whole century after the end of the civil war.

Biden Gifts The Taliban $80 Billion U.S. Military Equipment – Search (bing.com)

Obama’s Connection to the Muslim Brotherhood – Search (bing.com)

Jesus Christ is the son of God who died and rose three days later and loves all of you.
He died for everyone and wants you with Him, to know Him and live for His glory.
Come be saved eternally and spend time with Him to know Him. Be saved, free, forgiven, healed, delivered, baptized, whole and let Him show you how He is everything you need.

Live righteous and Holy because He said to and paid for our way to live like Him. Ask anything in His name and the Father will do it amen hallelujah praise God thank you Jesus.

I lift up everyone’s prayers, wants and needs to You Jesus, please pour out blessings.
May Your favor, grace and mercy be upon the world. In Jesus name come help us all.
You know our needs and everything else about each of us.

In Jesus name amen thank you Jesus praise God

Jesus, Help people to be rooted and grounded in Your love and to obey Your truth.
That they are living in the truth being taught by You.
That they know Your voice and word. Knowing truth from errors, discernment.

We are ambassadors of Christ. We represent God, when we are seen Jesus should be seen, His ways not ours. We should be living for and showing God, living for His glory. We are to be an example of Jesus for the world to see Him and want to know Him and know Him more.

2 Chronicles 7:14 says, if My people humble themselves and pray and seek My face and turn from their wicked ways, I will hear them from heaven and heal their land.

People need to turn from their wicked ways, Jesus paid for it. That’s God stating it in that verse and there are more verses. People need to repent, to be cleansed by His blood and live Holy because He’s Holy and righteous because He’s righteous. Our God said to stop sinning in many, many scriptures and He paid for everyone to be cleansed of sin (Isaiah 53), and to live how He said. He dwells in the Holy temple (your body) and said not to defile the temple. He said to defile the temple is death. He’s always serious about everything He said to do. He’s just as serious about what He said not to do. We live in obedience to His law, every word if it! He dwells within us all to be with and leads us in His ways.

Deuteronomy 28 there are blessings for obedience and curses for disobedience. The whole chapter, and verse 46 is one example of generational curses. These go into the following generations, the 3 and 4th. Our children pay the price for our sin. Stop sinning, you are sending consequences to yourself and to your loved ones, children. By God’s law you are.
If you don’t believe me, ask Him, in Jesus’ name may you see and know the truth in its fullness.

Love your neighbor as you love yourself.

Jesus is worthy of everything He said and paid for, so I implore you to do as God said.
Jesus said If you love me, you will obey my commands. Love Him with all your heart, mind, soul and strength.

Praise God Hallelujah Jesus

In Jesus powerful name

Lawrence Welk Show Jan. 14, 1976 – 200 Years Of American Music, Part 1 – YouTube
Lawrence Welk Show Jan. 24, 1976 – 200 Years of American Music, Part 2 – YouTube
Lawrence Welk Show – A Century of American Music at the Branson Theater in 2000…
“Seven Spanish Angels” Tribute Brings Willie Nelson Close To Tears (pitbullworld.net)

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New Way to Shrink Tumors

Posted on March 31, 2023 by Ken

IMIPRAMINE SHRINKS CANCER TUMORS
*This Blog Post Will Require a Bit more research on your part to fully understand!!*
Find out how an old drug may have a new life-saving purpose when it comes to treating malignant tumors. Good news for the nearly 267 thousand men and women who are diagnosed with breast cancer each year in the United States.

Frontiers | Suppression of EGFR/PKC-δ/NF-κB
Signaling Associated With Imipramine-Inhibited
Progression of Non-Small Cell Lung Cancer (frontiersin.org)

FDA-approved antidepressant may combat deadly form of lung cancer,
study finds | News Center | Stanford Medicine
by Krista Conger is a science writer for the medical school’s
*Office of Communication & Public Affairs.* *in September 26, 2013*

In another study Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway
by Eun Yeong Lim 1,2 , Joon Park 1,2, Yun Tai Kim 1,2,* and Min Jung Kim 3,*

1. Research Group of Functional Food Materials, Korea Food Research Institute,
245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea
2. Department of Food Biotechnology, Korea University of Science & Technology,
217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea
3. Research Group of Natural Materials and Metabolism, Korea Food Research Institute,
245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea
* Authors to whom correspondence should be addressed.

*Molecules* **2020**, 25(20), 4619; https://doi.org/10.3390/molecules25204619
Received: 18 September 2020 / Revised: 9 October 2020 / Accepted: 10 October 2020 / Published: 11 October 2020
(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

**Abstract**
Imipramine (IMI) is a tricyclic synthetic antidepressant that is used to treat chronic psychiatric disorders, including depression and neuropathic pain. IMI also has inhibitory effects against various cancer types, including prostate cancer; however, the mechanism of its anticancer activity is not well understood. In the present study, we investigated the antimetastatic and anti-invasive effects of IMI in metastatic castration-resistant prostate cancer PC-3 cells, with an emphasis on the serine/threonine protein kinase AKT-mediated nuclear factor kappa B (NF-κB) signaling pathway.
While IMI did not induce cell death, it attenuated PC-3 cell proliferation. According to the wound healing assay and invasion assay, migration and invasion in PC-3 cells were significantly inhibited by IMI in a dose-dependent manner. IMI significantly downregulated p-AKT protein expression but upregulated phospho-extracellular signal-regulated kinase (ERK1)/2 protein expression levels.
Furthermore, IMI treatment resulted in decreased AKT-mediated downstream signaling, including p-inhibitor of κB kinase (IKK)α/β, p-inhibitor of κB (IκBα), and p-p65.
Inhibited NF-κB signaling reduced the secretion of several proinflammatory cytokines and chemokine by PC-3 cells. Overall, our study explored the negative correlation between the use of antidepressants and prostate cancer progression, showing that IMI attenuated cell viability, migration, and invasion of PC-3 cells by suppressing the expression of AKT and NF-κB-related signaling proteins and secretion of tumor necrosis factor-α (*TNF-α*), interleukin-1β (*IL-1β*), and monocyte chemoattractant protein-1 (*MCP-1*).

Keywords:
imipramine; antidepressants; prostate cancer; migration; invasion

Graphical Abstract

1. Introduction
Prostate cancer is one of the most common invasive cancers in men,
with 1,276,000 cases and 359,000 deaths worldwide in 2018 [1].
In Korea, the incidence of prostate cancer has more than doubled in the last 15 years due to the aging population and the westernization of eating habits [2]. Patients with localized prostate cancer are managed by radiation therapy, surgery, or hormone therapy, while locally advanced prostate cancer and metastatic prostate cancer are mainly treated with androgen-deprivation therapy (ADT) [3].
ADT leads to the remission of prostate cancer in about 90% of the patients
as evidenced by decreased circulating levels of prostate-specific antigen (PSA) [4].
However, continuous ADT treatment attenuates the response of metastatic castration-sensitive prostate cancer (mCSPC) to ADT within 12–24 months and causes changes in the types of metastatic prostate cancer from mCSPC to metastatic castration-resistant prostate cancer (mCRPC) [5,6].
mCRPC is associated with a high risk of morbidity and mortality, with a short survival time of only 16–18 months [7].

Therefore, it is urgent to suppress mCRPC and develop new efficient chemotherapeutic agents for the treatment of ADT-resistant mCRPC.
Food and Drug Administration (FDA)-approved chemotherapeutic drugs for mCRPC are mitoxantrone, docetaxel, and cabazitaxel. Mitoxantrone, approved in 1996, had a palliative benefit and decreased PSA levels [8,9,10].
Subsequently, docetaxel and cabazitaxel, approved in 2004 and 2010, respectively, replaced mitoxantrone; these drugs relieved symptoms, improved PSA response rate, and led to extended overall survival in mCRPC patients [9,11,12,13].
However, both of these drugs also have limitations because some patients with mCRPC are not controlled by these drugs, and resistance to treatment eventually occurs. To overcome these disadvantages, researchers are constantly exploring new chemotherapeutic agents.
One of the suggestions that resulted from these efforts is to use antidepressants as new mCRPC inhibitors. Several classes of antidepressants exist, such as nonselective monoamine reuptake inhibitors, selective serotonin reuptake inhibitors, nonselective monoamine oxidase inhibitors, monoamine oxidase A (MAO-A) inhibitors, and other antidepressants including tricyclic antidepressants (TCAs) [14,15].

Among these, MAO-A inhibitors are known for their efficacy and mechanisms of prostate cancer suppression [16,17].
MAO-A inhibitors, including clogyline and mocrobemide, suppressed the activation of Shh-interleukin 6-receptor activator of nuclear factor kappaB ligand (Shh–IL6–RANKL) signaling, further suppressed the metastasis of CRPC cells, and prolonged overall survival in patients in preclinical studies [16]. In addition, antiandrogen enzalutamide-resistant mCRPC cells derived by chronic exposure to enzalutamide could be re-sensitized to enzalutamide by treatment with MAO-A inhibitors such as phenelzine and clorgyline [17]. However, the efficacy and mechanisms of action of TCAs in mCRPC cells have been poorly studied.

Imipramine (IMI, 10,11-dihydro-N,N-dimethyl-5H-dibenz[*b,f*]azepine-5-propanamine hydrochloride) is a member of the TCA family and is used in the treatment of depressive disorders, neuropathic pain, and nocturnal enuresis [18,19,20].
In addition to these neurologic properties, IMI has exhibited antiproliferative and anticancer activities in various cancer cells such as myeloma, small-cell lung cancer, pancreatic neuroendocrine cancer, and prostate cancer cells [21,22,23].

However, the mechanism of IMI action in prostate cancer, especially mCRPC, has not been fully studied. The only known mechanisms of IMI action involve the inhibition of the voltage sensitive ether-à-go-go potassium (EAG 1) channel activity in one of the mCRPC cell lines, DU145, reduction of cell proliferation, and induction of apoptosis [23].
Therefore, the aim of this study was to investigate the effects and mechanisms of IMI action during the migration and invasion in PC-3 cells, which can be considered as a cellular model of mCRPC because they are androgen-insensitive and have a high metastatic potential.

2. Results
2.1. IMI Inhibits Proliferation of PC-3 Cells without Causing Cell Death
The antiproliferative properties of IMI were evaluated by exposing the prostate cancer cell line PC-3 to different concentrations of IMI (3.8 × 10−4 to 1.0 × 102 μM) for 12 h and 72 h. IMI treatment resulted in decreased proliferation of PC-3 cells in a dose-dependent and time-dependent manner (Figure 1a). In the IMI-treated group at 12 h, IMI at < 10 μM did not affect cell proliferation; however, concentrations above 10 μM resulted in decreased cell proliferation in a dose-dependent manner.
In the IMI-treated group at 72 h, IMI had a dose-dependent inhibitory effect on cell proliferation over the entire dose range. To confirm cell viability, PC-3 cells were treated with the highest concentration (100 μM) of IMI for a longer period (72 h), and the cell viability was visualized using a LIVE/DEAD kit and quantified (Figure 1b,c).
Although PC-3 cells were exposed to high doses for a long period, the number of live
and dead cells and cell viability in IMI-treated cells did not show significant differences compared to those in the untreated cells. We concluded that IMI did not induce cell death but attenuated the proliferation of PC-3 cells.

**Figure 1.** Effect of imipramine treatment on proliferation of PC-3 cells.

(a) PC-3 cells were treated with 3.8 × 10−4 to 1.0 × 102 μM imipramine (IMI)
for 12 h and 72 h, and cell proliferation was evaluated using a water-soluble tetrazolium salts, WST-1 assay.
(b,c) Cell viability at 100 μM of imipramine treatment for 72 h was visualized and quantified using a LIVE/DEAD kit. Green and red fluorescence indicates live and dead cells, respectively. n.s.: not significant.
2.2. IMI Inhibits PC-3 Cell Migration
To determine whether IMI inhibits migration in PC-3 cells, wound healing was monitored in PC-3 cells treated with different concentrations of IMI (6.25, 12.5, 25, 50, and 100 μM). As shown in Figure 2b,c, IMI significantly decreased the migration of PC-3 cells in a dose-dependent manner compared to that in the control, untreated cells (p < 0.001).
These results demonstrated that IMI suppressed migration in PC-3 cells in vitro.

**Figure 2.** Inhibition of cell migration and invasion by imipramine.

(a) PC-3 cells were treated with imipramine (0–100 μM) for 12 h.
Representative images of the cells treated with the indicated doses
were acquired in an optical microscope after the wounding.
(b) The percentage of wound recovery was normalized to untreated control cells.
(c) PC-3 cells were treated with imipramine (0–100 μM) for 12 h and the effects of imipramine on invasion were analyzed using Matrigel invasion assays.
Representative images were taken in the bottom of the Transwell filter
at indicated time points via phase-contrast microscopy.
(d) Quantitative data of an invasion assay were expressed as the number of invasive cells. Data are presented as the mean ± standard error of the mean (SEM) and analyzed using one-way ANOVA; *** p < 0.001 compared with untreated cells.
2.3. IMI Inhibits PC-3 Cell Invasion
To determine the effect of IMI on cell invasion, PC-3 cells were treated with 12.5, 25, 50, and 100 μM IMI, after which the cells were allowed to invade in Matrigel-coated Transwells for 24 h. The number of invading cells was significantly reduced by the IMI treatment in a dose-dependent manner (Figure 2c,d). Compared to the untreated group, IMI at 50 and 100 μM suppressed cell invasion by 79.8% and 92.5%, respectively. These data clearly show that IMI is a strong suppressor of PC-3 cell invasion.
2.4. IMI Inhibits Phosphorylation of Serine/threonine Protein Kinase (AKT), but Not that of Extracellular Signal-regulated kinase (ERK)1/2 in PC-3 Cells
In order to investigate the mechanism of IMI action, the effects of IMI treatment (6.25, 12.5, 25, 50, and 100 μM) on protein expression levels of AKT and ERK1/2 were evaluated using Western blot analysis in PC-3 cells.
As shown in Figure 3, activation of AKT in PC-3 cells was significantly suppressed by IMI (6.25, 12.5, 25, 50, and 100 μM) at 48 and 72 h, as evidenced by the dose-dependent decrease in AKT phosphorylation. However, the expression of phosphorylated ERK1/2 was upregulated by IMI at 48 h and 72 h.

**Figure 3.** Effect of imipramine on phosphorylation of serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK)1/2 at 48 h and 72 h in PC-3 cells.
(a,d) Protein expression of AKT, p-AKT, ERK1/2, p-ERK1/2, and β-actin in PC-3 cells was detected using Western blotting.
(b,c,e,f) Quantitative data of phosphorylated AKT and ERK were normalized to the untreated cells. Data are presented as the mean ± SEM (n = 3) and analyzed using one-way ANOVA; * p < 0.05, and *** p < 0.001 compared with untreated cells.
2.5. IMI Attenuates Nuclear Factor Kappa B (NF-κB) Signaling and the Expression of Proinflammatory Cytokines and Chemokines in PC-3 Cells
Cancer proliferation is associated with NF-κB signaling pathway and inflammatory cytokines. The protein expression levels of p-inhibitor of κB kinase (IKK)α/β, IKKα, p-inhibitor of κB (IκBα), IκBα, p-p65, p65, and β-actin in the NF-κB signaling pathway, which is downstream to AKT activation, and the secretion of inflammatory cytokines were estimated using Western blotting and RT-PCR, respectively. As a result, IMI inactivated the NF-κB signaling pathway in PC-3 cells (Figure 4a–e). Phosphorylation of IKKα/β, IκBα, and p65 was inhibited by IMI. Concurrently, degradation of IκBα was reduced by IMI. In particular, phosphorylated p65 levels were significantly attenuated in response to IMI treatment (25–100 μM) in a dose-dependent manner.

**Figure 4.** Effect of imipramine on protein phosphorylation during nuclear factor kappa B (NF-κB) signaling and the expression of inflammatory cytokines at 48 h in PC-3 cells.

(a) Protein expression of p-inhibitor of κB kinase (IKK)α/β, IKKα, p-inhibitor of κB (IκBα), IκBα, p-p65, p65, and β-actin in PC-3 cells was detected using Western blotting.
(b) Quantitative data of phosphorylated IKKα/β were normalized to the untreated cells.
(c) Quantitative data of phosphorylated IκBα were normalized to the untreated cells.
(d) quantitative data of IκBα were normalized to the untreated cells.
(e) Quantitative data of phosphorylated p65 were normalized to the untreated cells.
(f–h) The production of tumor necrosis factor–α (*TNF-α*), interleukin-1β (*IL-1β*), and monocyte chemoattractant protein-1 (*MCP-1*) messenger RNA (mRNA) was analyzed using quantitative real-time RT-PCR. Data are presented as the mean ± SEM of three independent experiments and analyzed using one-way ANOVA; * p < 0.05, ** p < 0.01, and *** p < 0.001 compared with untreated cells.
Because protein phosphorylation during NF-κB signaling regulates the expression of inflammatory cytokines, the messenger RNA (mRNA) expression of inflammatory cytokines, including tumor necrosis factor–α (*TNF-α*), interleukin-1β (*IL-1β*), and monocyte chemoattractant protein-1 (*MCP-1*) was quantitatively analyzed using qRT-PCR. The mRNA levels of all three cytokines were significantly suppressed by IMI treatment (Figure 4f–h). The mRNA level of *TNF-α* was significantly inhibited by 100 μM. The mRNA levels of *IL-1β* and *MCP-1* were significantly attenuated by IMI concentrations ranging from 12.5 μM to 100 μM and from 25 μM to 100 μM, respectively.

3. Discussion
This is the first study to demonstrate that IMI attenuates cell proliferation, migration, and invasion of PC-3 cells via inactivation of AKT-mediated NF-κB signaling and activation of ERK-mediated signaling. IMI suppressed the phosphorylation of AKT, IKKα/β, IκBα, and p65 in PC-3 cells in a concentration-dependent manner. Downregulated AKT-mediated NF-κB signaling was associated with decreased gene expression levels of cytokines including *TNF-α*, *IL-1β*, and *MCP-1*. Our findings suggest that imipramine could be a potential candidate for treatment of prostate cancers.
A number of signaling pathways regulate cellular metabolism and cancer progression. The representative mechanisms involved in cell survival, growth, proliferation, migration, and invasion in tumors and tumor cell lines include the phosphatidylinositol 3-kinase (PI3K)/AKT pathway and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway.

These pathways are also important for mCRPC progression. PI3K activation stimulates downstream phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production and further phosphorylation of AKT (Ser473 and Thr308) in the PI3K/AKT pathway [24]. PI3K inactivation by PI3K inhibitor (LY294002) attenuated the protein expression of PI3K (p85) and p-AKT (Ser473) and further suppressed PC-3 cell invasion [25]. Selective inhibition of the PI3K/AKT pathway with the AKT inhibitor, AZD5363, also retards cellular proliferation and tumor progression in CRPC xenografts [26]. In particular, AKT is an attractive therapeutic target to inhibit mCRPC progression because of the following characteristics of PC-3 cells: (1) excessive AKT level, (2) loss of phosphatase and tensin homolog (PTEN), and (3) AKT-induced inhibition of Raf/mitogen-activated protein kinase kinase (MEK)/ERK signaling cascades.

According to phospho-proteomic analysis in metastatic tumor samples, mCRPC contains excessive amounts of AKT protein as the most common tyrosine kinase [27]. PTEN, a tumor suppressor gene that is negatively involved in AKT phosphorylation by PI3K, is lost in ~50% of tumor tissue in mCRPC patients and is known to inhibit cell proliferation and migration in prostate cancer [28,29]. Both excessive AKT accumulation and loss of PTEN accelerate prostate carcinogenesis. Raf/MEK/ERK signaling cascades are upregulated not only by Ras activation but also by AKT inhibition in several types of cancers, such as prostate and breast cancers [30,31]. ERK signaling has two opposing roles: one is associated with cell proliferation, migration, and invasion [32], and the other one is relevant to the proapoptotic action of chemotherapeutics.
Various antitumor agents, including resveratrol, betulinic acid, apigenin, and or oridonin, trigger cancer cell death through ERK activation [33,34,35,36]. This is consistent with other chemotherapeutic agents in which phenethyl isothiocyanate activates MAPK/ERK signaling cascades and induces apoptosis in PC-3 cells [37]. In addition, upregulated MAPK/ERK signaling by AKT inactivation also induced loss of differentiation of PC-3 cells [38]. IMI inhibited AKT phosphorylation, increased ERK activation in PC-3 cells, and attenuated cell proliferation, instead of inducing cell death.

CRPC contains higher levels of AKT and NF-κB than CSPC and other cancers.
The NF-κB family of proteins plays a pleiotropic role in controlling multiple cell functions such as proliferation, survival, cell death, invasion, and angiogenesis; however, this protein family plays a dichotomous role. The canonical NF-κB signaling pathway is executed through the activation of the IKK complex composed of the catalytic subunits (IKKα and IKKβ) and the regulatory subunit (IKKγ/NF-κB essential modifier, NEMO) [39].
Phosphorylated IKK activates IκBα proteins and then phosphorylates IκBα to release the p65(RelA)/p50(NF-κB1) complex, followed by degradation of IκBα by proteasome. The separated p65/p50 complex is translocated into the nucleus to activate gene transcription. Among NF-κB family proteins, not NF-κB/p50 but NF-κB/p65 is constitutively activated in human prostate adenocarcinoma. The NF-κB signaling pathway can be activated by AKT. Several studies have suggested that AKT/NF-κB signaling works together in prostate cancer cells [40,41].
The migration and invasion enhancer 1 (MIEN1) gene, which is highly expressed in prostate cancer cells, regulates AKT/NF-κB signaling. Phosphorylation of AKT stimulates the mechanistic target of rapamycin complex 1 (mTORC1) and the IKK/NF-κB signaling cascade in PC-3 cells. Consistent with these cascades, inactivated AKT by IMI significantly attenuated the expression levels of phosphorylated IKKα/β, IκBα, and p65 in a dose-dependent manner in PC-3 cells. p65, binding to a consensus DNA sequence in the promoter region, regulates cancer metastasis [42].
Previous studies reported that blocking the p65 attenuated metastasis in prostate cancer; on the other hand, activation of p65 promoted invasion and migration of prostate cancer cells [43,44,45,46].

Moreover, suppressed AKT/NF-κB signaling by IMI affected downstream signaling cascades.
Proinflammatory cytokines and chemokines are regulated by NF-κB. Phosphorylation of p65 facilitates its binding to a specific DNA sequence, which triggers the transcriptional activation of NF-κB-regulated genes, including proinflammatory cytokine genes and chemokine genes. We found that IMI-induced deactivation of p65 also attenuated the expression levels of downstream genes, including two proinflammatory cytokine genes (*TNF-α* and *IL-1β*) and one chemokine gene (*MCP-1*). Prostate cancer cells express chemokine and chemokine receptors, as well as endogenously produced chemokines and cytokines such as *MCP-1*, *TNF-α*, *IL-1β*, IL-6, and IL-8 [47,48,49],
some of which are secreted at a higher level in PC-3 cells (mCRPC cell line) than in LNCaP cells (mCSPC cell line). *MCP-1*, a member of the CC chemokine superfamily, is associated with recruitment and activation of monocytes during acute inflammation.
Endogenous *MCP-1*, eliciting both autocrine and paracrine responses, promotes cell growth and invasion in prostate cancer cells including primary prostate epithelia (PrEC), LNCaP, C4-2B, and PC-3 cells [50].
*TNF-α* and *IL-1β*, the major proinflammatory cytokines associated with systemic inflammation, play a critical role in tumorigenesis, tumor progression, and carcinogenesis. Both cytokines also act as autocrine factors; thus, the secretion of endogenously produced *TNF-α* and *IL-1β* promotes cell proliferation and migration in PC-3 cells. In particular, it is proof that the expression of *IL-1β* is stimulated by p65 phosphorylation.
Finally, IMI-induced suppression of the expression of *TNF-α*, *IL-1β*, and *MCP-1* may regulate autocrine signaling and inhibit cell proliferation, migration, and invasion. In this study, we found that imipramine inhibits proliferation, migration, and invasion in a cellular model of mCRPC, which is expected to be related to AKT/NF-κB signaling. Some research suggested that upstream AKT signaling including PI3K, PDK1, and PTEN can be binding targets of imipramine [51], but further study will be needed to know the exact target of imipramine. In addition, it is necessary to observe the suppressive effect of imipramine on metastasis using a xenograft tumor model so that the results of in vitro studies can be confirmed in vivo.

4. Materials and Methods

4.1. Materials
IMI was purchased from Sigma-Aldrich (St. Louis, MO, USA). The antibody against β-actin was purchased from Santa Cruz Biotech (Santa Cruz, CA, USA). Antibodies against p-IKKα/β, IKKα, p-IκB, IκB, p-p65, p65, ERK1/2, p-ERK1/2 (Thr202/Tyr204), AKT, and p-AKT (Ser473) were purchased from Cell Signaling Technology (Beverly, MA, USA).

4.2. Cell Culture
The prostate cancer cell line PC-3 was obtained from the Korean Cell Line Bank (KCLB, Seoul, Korea) and cultured in Roswell Park Memorial Institute (RPMI) 1640 (Gibco, Grand Island, NY, USA) containing 10% fetal bovine serum (FBS; Gibco) and 100 U/mL penicillin/streptomycin (Gibco) at 37 °C and 5% CO2.

4.3. Cell Proliferation Assay
PC-3 cells were seeded in 96-well plates (1 × 103 cells/well) and cultured overnight to allow cell adhesion. PC-3 cells were treated with 0.1% dimethyl sulfoxide (DMSO) or various concentrations of IMI (range: 3.8 × 10−4 to 1.0 × 102 μM) for 12 h or 72 h. Subsequently, 10 μL of water-soluble tetrazolium salts, WST-1 reagent (Roche Diagnostics GmbH, Mannheim, Germany) was added to each well and incubated for 4 h at 37 °C in a humidified 5% CO2 atmosphere. Finally, the absorbance at 450 and 650 nm was measured using a SpectraMax Plus Plate Reader (Molecular Devices, Sunnyvale, CA, USA). PC-3 cells treated with 0.1% DMSO served as a control. The percentage of cell proliferation was calculated using the following equation:Cell proliferation = (OD450 − OD650 of IMI-treated cells)/(OD450 − OD650 of control) × 100.

4.4. Live/Dead Cell Viability Assay
Cell viability was confirmed using a LIVE/DEAD® Cell Imaging Kit (Invitrogen, Waltham, MA, USA). PC-3 cells plated at a density of 1 × 103 cells per well in a 96-well plate were treated with 0.1% DMSO or 100 μM IMI. After 72 h, calcein-AM (live, green) and propidium iodide (PI; dead, red) were added to the cells and incubated for 15 min at room temperature in the dark. Images of live and dead cells were acquired using a fluorescence microscope (Axio Observer A1; Carl Zeiss AG, Oberkochen, Germany).
The percentage of cell viability was calculated according to the following formula:% of cell viability = (the number of viable cells/the total number of cells) × 100.

4.5. Wound Healing Assay
PC-3 cells were seeded at a density of 7 × 105 cells/mL into the two wells of a culture insert (Ibidi GmbH, Martinsried, Germany). After the overnight incubation, cells were grown to full confluence, and the culture inserts were removed to make the wound gap. Cells were washed with phosphate buffered saline (PBS) and incubated with five different concentrations of IMI (0–100 μM) for 12 h. Representative images for each concentration were captured at 10× magnification using a digital camera attached to an inverted microscope to quantify the relative migration of cells (Axio Observer A1). The area of the wound was quantitatively analyzed using MetaMorph software (Molecular Devices, Sunnyvale, CA, USA), and the percentage of wound recovery was evaluated.
Coverage in untreated PC-3 cells was defined as 100%.

4.6. Cell Invasion Assay
The cell invasion assay was performed using 24-well Transwell chambers with polycarbonate filters with 8 μm pore size (Corning Costar, Corning, New York, NY, USA). Transwell chambers were coated with gelatin solution (0.1%) on the lower surface and Matrigel on the upper surface for 30 min. PC-3 cells were seeded at a density of 2 × 104 cells/mL in serum-free medium onto the upper compartment of the Transwell, and the lower chambers were filled with medium containing 10% FBS and various concentrations of IMI (12.5, 25, 50, and 100 μM). After 24 h, the non invaded cells and the Matrigel on the upper chamber were gently removed using a cotton-tipped swab; then, cells at the undersurface of the filters were stained with crystal violet stain solution for 20 min and rinsed several times in distilled water. The number of invaded cells was quantified by visual counting after being photographed using an inverted microscope at 10× magnification.

4.7. Western Blot Analysis
PC-3 cells (4 × 105 cells/dish) were seeded in 100 mm dishes for 24 h and starved with 0.05% FBS overnight. PC-3 cells were incubated with five different concentrations of IMI (3.25, 12.5, 25, 50, and 100 μM) for 48 h or 72 h. After the treatment, the cells were lysed using a cell lysis buffer (Cell Signaling Technology, Beverly, MA, USA) containing a protease inhibitor cocktail from Roche and phosphatase inhibitor (Sigma Aldrich) for 30 min on ice.
After centrifugation, a bicinchoninic acid (BCA) protein assay kit (Thermo Scientific, Rockford, IL, USA) was used to determine the protein concentration. Equal amounts of protein lysate were separated in 10% sodium dodecyl sulfate (SDS) polyacrylamide gels and transferred to a polyvinylidene difluoride (PVDF) membrane (Bio-Rad Inc., Hercules, CA, USA).
The membrane was blocked with 5% skim milk in Tris-buffered saline with 0.1% Tween-20 (TBST) for 1 h at room temperature and then incubated with the specific primary antibodies, including AKT, phospho-AKT (Ser473), ERK1/2, phospho-ERK1/2 (Thr202/Tyr204), phospho-IKKα/β, IKKα, phospho-IκB, IκB, phospho-p65, and p65, overnight at 4 °C. The membranes were washed in TBST three times and incubated with horseradish peroxidase (HRP)-conjugated secondary antibodies at room temperature for 2 h. Protein bands were visualized using a chemiluminescence detection kit (ATTO, Tokyo, Japan). Beta-actin was used as the loading control.

4.8. Total RNA Isolation and Quantitative Reverse-Transcription Polymerase Chain Reaction (RT-qPCR)
Total RNA was isolated using the NucleoPin® RNA Plus XS Kit (Macherey-Nagel, Bethlehem, PA, USA) according to the manufacturer’s instructions. Reverse transcription of RNA was performed using the ReverTra Ace® qPCR RT Master Mix (Toyobo, Osaka, Japan). First-strand complementary DNA (cDNA) was prepared using 1 μg of total RNA. The real-time PCR reaction was performed in a volume of 20 μL containing 0.1 μg of cDNA, 1 μM of each primer (Table 1), and Power SYBR® Green PCR Master Mix (Applied Biosystems, Carlsbad, CA, USA).
Thermal cycling was carried out in a StepOnePlus Real-Time PCR system (Applied Biosystems, Carlsbad, CA, USA) with a program of 95 °C for 5 min, followed by 40 cycles of denaturation at 95 °C for 5 s annealing, and elongation at 60 °C for 10 s. Gene expression levels were normalized to the expression level of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (*GAPDH*). Relative gene expression changes, calculated using the 2−∆∆CT method, were reported as number-fold changes compared to those in the control samples.
**Table 1.** Primer sequences for RT-qPCR.

4.9. Statistics
All experiments were independently performed at least three times and the values were expressed as the mean ± standard error of the mean (SEM). Statistical analysis was performed using GraphPad Prism version 5 (GraphPad Software, Inc., La Jolla, CA, USA). Statistical significance was evaluated by unpaired t-test for comparison between two groups and one-way ANOVA followed by Dunnett’s post hoc test for multiple groups.
A p-value < 0.05 was considered to indicate a statistically significant difference.

5. Conclusions
In conclusion, our results demonstrated that IMI treatment inhibited cell proliferation, migration, and invasion in mCRPC PC-3 cells. The suggested mechanisms of IMI in PC-3 cells include the modulation of AKT/ERK signaling and suppression of the AKT/NF-κB signaling pathway by preventing IκBα degradation, blocking p65 phosphorylation, and regulating chemokine and cytokine production. We suggest that IMI may be a potential chemotherapeutic candidate against metastatic CRPC.
Author Contributions
Formal analysis, E.Y.L. and J.P.; investigation, E.Y.L. and J.P.; methodology, E.Y.L.; writing—original draft, E.Y.L. and J.P.; funding acquisition, Y.T.K.; resources, Y.T.K.; supervision, Y.T.K.; writing—reviewing and editing, Y.T.K. and M.J.K.; conceptualization, M.J.K.; project administration, M.J.K. All authors have read and agree to the published version of the manuscript.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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**MDPI and ACS Style**
Lim, E.Y.; Park, J.; Kim, Y.T.; Kim, M.J. Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway. *Molecules* **2020**, 25, 4619. https://doi.org/10.3390/molecules25204619
**AMA Style**
Lim EY, Park J, Kim YT, Kim MJ. Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway. *Molecules*. 2020; 25(20):4619. https://doi.org/10.3390/molecules25204619
**Chicago/Turabian Style**
Lim, Eun Yeong, Joon Park, Yun Tai Kim, and Min Jung Kim. 2020. “Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway” *Molecules* 25, no. 20: 4619. https://doi.org/10.3390/molecules25204619

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**SOURCE:** Imipramine Shrinks Cancer Tumors – Bing video
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IMIPRAMINE SHRINKS CANCER TUMORS
*This Blog Post Will Require a Bit more research on your part to fully understand!!*
Find out how an old drug may have a new life-saving purpose when it comes to treating malignant tumors. Good news for the nearly 267 thousand men and women who are diagnosed with breast cancer each year in the United States.

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FDA-approved antidepressant may combat deadly form of lung cancer,
study finds | News Center | Stanford Medicine
by Krista Conger is a science writer for the medical school’s
*Office of Communication & Public Affairs.* *in September 26, 2013*

In another study Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway
by Eun Yeong Lim 1,2 , Joon Park 1,2, Yun Tai Kim 1,2,* and Min Jung Kim 3,*

1. Research Group of Functional Food Materials, Korea Food Research Institute,
245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea
2. Department of Food Biotechnology, Korea University of Science & Technology,
217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea
3. Research Group of Natural Materials and Metabolism, Korea Food Research Institute,
245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea
* Authors to whom correspondence should be addressed.

*Molecules* **2020**, 25(20), 4619; https://doi.org/10.3390/molecules25204619
Received: 18 September 2020 / Revised: 9 October 2020 / Accepted: 10 October 2020 / Published: 11 October 2020
(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

**Abstract**
Imipramine (IMI) is a tricyclic synthetic antidepressant that is used to treat chronic psychiatric disorders, including depression and neuropathic pain. IMI also has inhibitory effects against various cancer types, including prostate cancer; however, the mechanism of its anticancer activity is not well understood. In the present study, we investigated the antimetastatic and anti-invasive effects of IMI in metastatic castration-resistant prostate cancer PC-3 cells, with an emphasis on the serine/threonine protein kinase AKT-mediated nuclear factor kappa B (NF-κB) signaling pathway.
While IMI did not induce cell death, it attenuated PC-3 cell proliferation. According to the wound healing assay and invasion assay, migration and invasion in PC-3 cells were significantly inhibited by IMI in a dose-dependent manner. IMI significantly downregulated p-AKT protein expression but upregulated phospho-extracellular signal-regulated kinase (ERK1)/2 protein expression levels.
Furthermore, IMI treatment resulted in decreased AKT-mediated downstream signaling, including p-inhibitor of κB kinase (IKK)α/β, p-inhibitor of κB (IκBα), and p-p65.
Inhibited NF-κB signaling reduced the secretion of several proinflammatory cytokines and chemokine by PC-3 cells. Overall, our study explored the negative correlation between the use of antidepressants and prostate cancer progression, showing that IMI attenuated cell viability, migration, and invasion of PC-3 cells by suppressing the expression of AKT and NF-κB-related signaling proteins and secretion of tumor necrosis factor-α (*TNF-α*), interleukin-1β (*IL-1β*), and monocyte chemoattractant protein-1 (*MCP-1*).

Keywords:
imipramine; antidepressants; prostate cancer; migration; invasion

Graphical Abstract

1. Introduction
Prostate cancer is one of the most common invasive cancers in men,
with 1,276,000 cases and 359,000 deaths worldwide in 2018 [1].
In Korea, the incidence of prostate cancer has more than doubled in the last 15 years due to the aging population and the westernization of eating habits [2]. Patients with localized prostate cancer are managed by radiation therapy, surgery, or hormone therapy, while locally advanced prostate cancer and metastatic prostate cancer are mainly treated with androgen-deprivation therapy (ADT) [3].
ADT leads to the remission of prostate cancer in about 90% of the patients
as evidenced by decreased circulating levels of prostate-specific antigen (PSA) [4].
However, continuous ADT treatment attenuates the response of metastatic castration-sensitive prostate cancer (mCSPC) to ADT within 12–24 months and causes changes in the types of metastatic prostate cancer from mCSPC to metastatic castration-resistant prostate cancer (mCRPC) [5,6].
mCRPC is associated with a high risk of morbidity and mortality, with a short survival time of only 16–18 months [7].

Therefore, it is urgent to suppress mCRPC and develop new efficient chemotherapeutic agents for the treatment of ADT-resistant mCRPC.
Food and Drug Administration (FDA)-approved chemotherapeutic drugs for mCRPC are mitoxantrone, docetaxel, and cabazitaxel. Mitoxantrone, approved in 1996, had a palliative benefit and decreased PSA levels [8,9,10].
Subsequently, docetaxel and cabazitaxel, approved in 2004 and 2010, respectively, replaced mitoxantrone; these drugs relieved symptoms, improved PSA response rate, and led to extended overall survival in mCRPC patients [9,11,12,13].
However, both of these drugs also have limitations because some patients with mCRPC are not controlled by these drugs, and resistance to treatment eventually occurs. To overcome these disadvantages, researchers are constantly exploring new chemotherapeutic agents.
One of the suggestions that resulted from these efforts is to use antidepressants as new mCRPC inhibitors. Several classes of antidepressants exist, such as nonselective monoamine reuptake inhibitors, selective serotonin reuptake inhibitors, nonselective monoamine oxidase inhibitors, monoamine oxidase A (MAO-A) inhibitors, and other antidepressants including tricyclic antidepressants (TCAs) [14,15].

Among these, MAO-A inhibitors are known for their efficacy and mechanisms of prostate cancer suppression [16,17].
MAO-A inhibitors, including clogyline and mocrobemide, suppressed the activation of Shh-interleukin 6-receptor activator of nuclear factor kappaB ligand (Shh–IL6–RANKL) signaling, further suppressed the metastasis of CRPC cells, and prolonged overall survival in patients in preclinical studies [16]. In addition, antiandrogen enzalutamide-resistant mCRPC cells derived by chronic exposure to enzalutamide could be re-sensitized to enzalutamide by treatment with MAO-A inhibitors such as phenelzine and clorgyline [17]. However, the efficacy and mechanisms of action of TCAs in mCRPC cells have been poorly studied.

Imipramine (IMI, 10,11-dihydro-N,N-dimethyl-5H-dibenz[*b,f*]azepine-5-propanamine hydrochloride) is a member of the TCA family and is used in the treatment of depressive disorders, neuropathic pain, and nocturnal enuresis [18,19,20].
In addition to these neurologic properties, IMI has exhibited antiproliferative and anticancer activities in various cancer cells such as myeloma, small-cell lung cancer, pancreatic neuroendocrine cancer, and prostate cancer cells [21,22,23].

However, the mechanism of IMI action in prostate cancer, especially mCRPC, has not been fully studied. The only known mechanisms of IMI action involve the inhibition of the voltage sensitive ether-à-go-go potassium (EAG 1) channel activity in one of the mCRPC cell lines, DU145, reduction of cell proliferation, and induction of apoptosis [23].
Therefore, the aim of this study was to investigate the effects and mechanisms of IMI action during the migration and invasion in PC-3 cells, which can be considered as a cellular model of mCRPC because they are androgen-insensitive and have a high metastatic potential.

2. Results
2.1. IMI Inhibits Proliferation of PC-3 Cells without Causing Cell Death
The antiproliferative properties of IMI were evaluated by exposing the prostate cancer cell line PC-3 to different concentrations of IMI (3.8 × 10−4 to 1.0 × 102 μM) for 12 h and 72 h. IMI treatment resulted in decreased proliferation of PC-3 cells in a dose-dependent and time-dependent manner (Figure 1a). In the IMI-treated group at 12 h, IMI at < 10 μM did not affect cell proliferation; however, concentrations above 10 μM resulted in decreased cell proliferation in a dose-dependent manner.
In the IMI-treated group at 72 h, IMI had a dose-dependent inhibitory effect on cell proliferation over the entire dose range. To confirm cell viability, PC-3 cells were treated with the highest concentration (100 μM) of IMI for a longer period (72 h), and the cell viability was visualized using a LIVE/DEAD kit and quantified (Figure 1b,c).
Although PC-3 cells were exposed to high doses for a long period, the number of live
and dead cells and cell viability in IMI-treated cells did not show significant differences compared to those in the untreated cells. We concluded that IMI did not induce cell death but attenuated the proliferation of PC-3 cells.

**Figure 1.** Effect of imipramine treatment on proliferation of PC-3 cells.

(a) PC-3 cells were treated with 3.8 × 10−4 to 1.0 × 102 μM imipramine (IMI)
for 12 h and 72 h, and cell proliferation was evaluated using a water-soluble tetrazolium salts, WST-1 assay.
(b,c) Cell viability at 100 μM of imipramine treatment for 72 h was visualized and quantified using a LIVE/DEAD kit. Green and red fluorescence indicates live and dead cells, respectively. n.s.: not significant.
2.2. IMI Inhibits PC-3 Cell Migration
To determine whether IMI inhibits migration in PC-3 cells, wound healing was monitored in PC-3 cells treated with different concentrations of IMI (6.25, 12.5, 25, 50, and 100 μM). As shown in Figure 2b,c, IMI significantly decreased the migration of PC-3 cells in a dose-dependent manner compared to that in the control, untreated cells (p < 0.001).
These results demonstrated that IMI suppressed migration in PC-3 cells in vitro.

**Figure 2.** Inhibition of cell migration and invasion by imipramine.

(a) PC-3 cells were treated with imipramine (0–100 μM) for 12 h.
Representative images of the cells treated with the indicated doses
were acquired in an optical microscope after the wounding.
(b) The percentage of wound recovery was normalized to untreated control cells.
(c) PC-3 cells were treated with imipramine (0–100 μM) for 12 h and the effects of imipramine on invasion were analyzed using Matrigel invasion assays.
Representative images were taken in the bottom of the Transwell filter
at indicated time points via phase-contrast microscopy.
(d) Quantitative data of an invasion assay were expressed as the number of invasive cells. Data are presented as the mean ± standard error of the mean (SEM) and analyzed using one-way ANOVA; *** p < 0.001 compared with untreated cells.
2.3. IMI Inhibits PC-3 Cell Invasion
To determine the effect of IMI on cell invasion, PC-3 cells were treated with 12.5, 25, 50, and 100 μM IMI, after which the cells were allowed to invade in Matrigel-coated Transwells for 24 h. The number of invading cells was significantly reduced by the IMI treatment in a dose-dependent manner (Figure 2c,d). Compared to the untreated group, IMI at 50 and 100 μM suppressed cell invasion by 79.8% and 92.5%, respectively. These data clearly show that IMI is a strong suppressor of PC-3 cell invasion.
2.4. IMI Inhibits Phosphorylation of Serine/threonine Protein Kinase (AKT), but Not that of Extracellular Signal-regulated kinase (ERK)1/2 in PC-3 Cells
In order to investigate the mechanism of IMI action, the effects of IMI treatment (6.25, 12.5, 25, 50, and 100 μM) on protein expression levels of AKT and ERK1/2 were evaluated using Western blot analysis in PC-3 cells.
As shown in Figure 3, activation of AKT in PC-3 cells was significantly suppressed by IMI (6.25, 12.5, 25, 50, and 100 μM) at 48 and 72 h, as evidenced by the dose-dependent decrease in AKT phosphorylation. However, the expression of phosphorylated ERK1/2 was upregulated by IMI at 48 h and 72 h.

**Figure 3.** Effect of imipramine on phosphorylation of serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK)1/2 at 48 h and 72 h in PC-3 cells.
(a,d) Protein expression of AKT, p-AKT, ERK1/2, p-ERK1/2, and β-actin in PC-3 cells was detected using Western blotting.
(b,c,e,f) Quantitative data of phosphorylated AKT and ERK were normalized to the untreated cells. Data are presented as the mean ± SEM (n = 3) and analyzed using one-way ANOVA; * p < 0.05, and *** p < 0.001 compared with untreated cells.
2.5. IMI Attenuates Nuclear Factor Kappa B (NF-κB) Signaling and the Expression of Proinflammatory Cytokines and Chemokines in PC-3 Cells
Cancer proliferation is associated with NF-κB signaling pathway and inflammatory cytokines. The protein expression levels of p-inhibitor of κB kinase (IKK)α/β, IKKα, p-inhibitor of κB (IκBα), IκBα, p-p65, p65, and β-actin in the NF-κB signaling pathway, which is downstream to AKT activation, and the secretion of inflammatory cytokines were estimated using Western blotting and RT-PCR, respectively. As a result, IMI inactivated the NF-κB signaling pathway in PC-3 cells (Figure 4a–e). Phosphorylation of IKKα/β, IκBα, and p65 was inhibited by IMI. Concurrently, degradation of IκBα was reduced by IMI. In particular, phosphorylated p65 levels were significantly attenuated in response to IMI treatment (25–100 μM) in a dose-dependent manner.

**Figure 4.** Effect of imipramine on protein phosphorylation during nuclear factor kappa B (NF-κB) signaling and the expression of inflammatory cytokines at 48 h in PC-3 cells.

(a) Protein expression of p-inhibitor of κB kinase (IKK)α/β, IKKα, p-inhibitor of κB (IκBα), IκBα, p-p65, p65, and β-actin in PC-3 cells was detected using Western blotting.
(b) Quantitative data of phosphorylated IKKα/β were normalized to the untreated cells.
(c) Quantitative data of phosphorylated IκBα were normalized to the untreated cells.
(d) quantitative data of IκBα were normalized to the untreated cells.
(e) Quantitative data of phosphorylated p65 were normalized to the untreated cells.
(f–h) The production of tumor necrosis factor–α (*TNF-α*), interleukin-1β (*IL-1β*), and monocyte chemoattractant protein-1 (*MCP-1*) messenger RNA (mRNA) was analyzed using quantitative real-time RT-PCR. Data are presented as the mean ± SEM of three independent experiments and analyzed using one-way ANOVA; * p < 0.05, ** p < 0.01, and *** p < 0.001 compared with untreated cells.
Because protein phosphorylation during NF-κB signaling regulates the expression of inflammatory cytokines, the messenger RNA (mRNA) expression of inflammatory cytokines, including tumor necrosis factor–α (*TNF-α*), interleukin-1β (*IL-1β*), and monocyte chemoattractant protein-1 (*MCP-1*) was quantitatively analyzed using qRT-PCR. The mRNA levels of all three cytokines were significantly suppressed by IMI treatment (Figure 4f–h). The mRNA level of *TNF-α* was significantly inhibited by 100 μM. The mRNA levels of *IL-1β* and *MCP-1* were significantly attenuated by IMI concentrations ranging from 12.5 μM to 100 μM and from 25 μM to 100 μM, respectively.

3. Discussion
This is the first study to demonstrate that IMI attenuates cell proliferation, migration, and invasion of PC-3 cells via inactivation of AKT-mediated NF-κB signaling and activation of ERK-mediated signaling. IMI suppressed the phosphorylation of AKT, IKKα/β, IκBα, and p65 in PC-3 cells in a concentration-dependent manner. Downregulated AKT-mediated NF-κB signaling was associated with decreased gene expression levels of cytokines including *TNF-α*, *IL-1β*, and *MCP-1*. Our findings suggest that imipramine could be a potential candidate for treatment of prostate cancers.
A number of signaling pathways regulate cellular metabolism and cancer progression. The representative mechanisms involved in cell survival, growth, proliferation, migration, and invasion in tumors and tumor cell lines include the phosphatidylinositol 3-kinase (PI3K)/AKT pathway and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway.

These pathways are also important for mCRPC progression. PI3K activation stimulates downstream phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production and further phosphorylation of AKT (Ser473 and Thr308) in the PI3K/AKT pathway [24]. PI3K inactivation by PI3K inhibitor (LY294002) attenuated the protein expression of PI3K (p85) and p-AKT (Ser473) and further suppressed PC-3 cell invasion [25]. Selective inhibition of the PI3K/AKT pathway with the AKT inhibitor, AZD5363, also retards cellular proliferation and tumor progression in CRPC xenografts [26]. In particular, AKT is an attractive therapeutic target to inhibit mCRPC progression because of the following characteristics of PC-3 cells: (1) excessive AKT level, (2) loss of phosphatase and tensin homolog (PTEN), and (3) AKT-induced inhibition of Raf/mitogen-activated protein kinase kinase (MEK)/ERK signaling cascades.

According to phospho-proteomic analysis in metastatic tumor samples, mCRPC contains excessive amounts of AKT protein as the most common tyrosine kinase [27]. PTEN, a tumor suppressor gene that is negatively involved in AKT phosphorylation by PI3K, is lost in ~50% of tumor tissue in mCRPC patients and is known to inhibit cell proliferation and migration in prostate cancer [28,29]. Both excessive AKT accumulation and loss of PTEN accelerate prostate carcinogenesis. Raf/MEK/ERK signaling cascades are upregulated not only by Ras activation but also by AKT inhibition in several types of cancers, such as prostate and breast cancers [30,31]. ERK signaling has two opposing roles: one is associated with cell proliferation, migration, and invasion [32], and the other one is relevant to the proapoptotic action of chemotherapeutics.
Various antitumor agents, including resveratrol, betulinic acid, apigenin, and or oridonin, trigger cancer cell death through ERK activation [33,34,35,36]. This is consistent with other chemotherapeutic agents in which phenethyl isothiocyanate activates MAPK/ERK signaling cascades and induces apoptosis in PC-3 cells [37]. In addition, upregulated MAPK/ERK signaling by AKT inactivation also induced loss of differentiation of PC-3 cells [38]. IMI inhibited AKT phosphorylation, increased ERK activation in PC-3 cells, and attenuated cell proliferation, instead of inducing cell death.

CRPC contains higher levels of AKT and NF-κB than CSPC and other cancers.
The NF-κB family of proteins plays a pleiotropic role in controlling multiple cell functions such as proliferation, survival, cell death, invasion, and angiogenesis; however, this protein family plays a dichotomous role. The canonical NF-κB signaling pathway is executed through the activation of the IKK complex composed of the catalytic subunits (IKKα and IKKβ) and the regulatory subunit (IKKγ/NF-κB essential modifier, NEMO) [39].
Phosphorylated IKK activates IκBα proteins and then phosphorylates IκBα to release the p65(RelA)/p50(NF-κB1) complex, followed by degradation of IκBα by proteasome. The separated p65/p50 complex is translocated into the nucleus to activate gene transcription. Among NF-κB family proteins, not NF-κB/p50 but NF-κB/p65 is constitutively activated in human prostate adenocarcinoma. The NF-κB signaling pathway can be activated by AKT. Several studies have suggested that AKT/NF-κB signaling works together in prostate cancer cells [40,41].
The migration and invasion enhancer 1 (MIEN1) gene, which is highly expressed in prostate cancer cells, regulates AKT/NF-κB signaling. Phosphorylation of AKT stimulates the mechanistic target of rapamycin complex 1 (mTORC1) and the IKK/NF-κB signaling cascade in PC-3 cells. Consistent with these cascades, inactivated AKT by IMI significantly attenuated the expression levels of phosphorylated IKKα/β, IκBα, and p65 in a dose-dependent manner in PC-3 cells. p65, binding to a consensus DNA sequence in the promoter region, regulates cancer metastasis [42].
Previous studies reported that blocking the p65 attenuated metastasis in prostate cancer; on the other hand, activation of p65 promoted invasion and migration of prostate cancer cells [43,44,45,46].

Moreover, suppressed AKT/NF-κB signaling by IMI affected downstream signaling cascades.
Proinflammatory cytokines and chemokines are regulated by NF-κB. Phosphorylation of p65 facilitates its binding to a specific DNA sequence, which triggers the transcriptional activation of NF-κB-regulated genes, including proinflammatory cytokine genes and chemokine genes. We found that IMI-induced deactivation of p65 also attenuated the expression levels of downstream genes, including two proinflammatory cytokine genes (*TNF-α* and *IL-1β*) and one chemokine gene (*MCP-1*). Prostate cancer cells express chemokine and chemokine receptors, as well as endogenously produced chemokines and cytokines such as *MCP-1*, *TNF-α*, *IL-1β*, IL-6, and IL-8 [47,48,49],
some of which are secreted at a higher level in PC-3 cells (mCRPC cell line) than in LNCaP cells (mCSPC cell line). *MCP-1*, a member of the CC chemokine superfamily, is associated with recruitment and activation of monocytes during acute inflammation.
Endogenous *MCP-1*, eliciting both autocrine and paracrine responses, promotes cell growth and invasion in prostate cancer cells including primary prostate epithelia (PrEC), LNCaP, C4-2B, and PC-3 cells [50].
*TNF-α* and *IL-1β*, the major proinflammatory cytokines associated with systemic inflammation, play a critical role in tumorigenesis, tumor progression, and carcinogenesis. Both cytokines also act as autocrine factors; thus, the secretion of endogenously produced *TNF-α* and *IL-1β* promotes cell proliferation and migration in PC-3 cells. In particular, it is proof that the expression of *IL-1β* is stimulated by p65 phosphorylation.
Finally, IMI-induced suppression of the expression of *TNF-α*, *IL-1β*, and *MCP-1* may regulate autocrine signaling and inhibit cell proliferation, migration, and invasion. In this study, we found that imipramine inhibits proliferation, migration, and invasion in a cellular model of mCRPC, which is expected to be related to AKT/NF-κB signaling. Some research suggested that upstream AKT signaling including PI3K, PDK1, and PTEN can be binding targets of imipramine [51], but further study will be needed to know the exact target of imipramine. In addition, it is necessary to observe the suppressive effect of imipramine on metastasis using a xenograft tumor model so that the results of in vitro studies can be confirmed in vivo.

4. Materials and Methods

4.1. Materials
IMI was purchased from Sigma-Aldrich (St. Louis, MO, USA). The antibody against β-actin was purchased from Santa Cruz Biotech (Santa Cruz, CA, USA). Antibodies against p-IKKα/β, IKKα, p-IκB, IκB, p-p65, p65, ERK1/2, p-ERK1/2 (Thr202/Tyr204), AKT, and p-AKT (Ser473) were purchased from Cell Signaling Technology (Beverly, MA, USA).

4.2. Cell Culture
The prostate cancer cell line PC-3 was obtained from the Korean Cell Line Bank (KCLB, Seoul, Korea) and cultured in Roswell Park Memorial Institute (RPMI) 1640 (Gibco, Grand Island, NY, USA) containing 10% fetal bovine serum (FBS; Gibco) and 100 U/mL penicillin/streptomycin (Gibco) at 37 °C and 5% CO2.

4.3. Cell Proliferation Assay
PC-3 cells were seeded in 96-well plates (1 × 103 cells/well) and cultured overnight to allow cell adhesion. PC-3 cells were treated with 0.1% dimethyl sulfoxide (DMSO) or various concentrations of IMI (range: 3.8 × 10−4 to 1.0 × 102 μM) for 12 h or 72 h. Subsequently, 10 μL of water-soluble tetrazolium salts, WST-1 reagent (Roche Diagnostics GmbH, Mannheim, Germany) was added to each well and incubated for 4 h at 37 °C in a humidified 5% CO2 atmosphere. Finally, the absorbance at 450 and 650 nm was measured using a SpectraMax Plus Plate Reader (Molecular Devices, Sunnyvale, CA, USA). PC-3 cells treated with 0.1% DMSO served as a control. The percentage of cell proliferation was calculated using the following equation:Cell proliferation = (OD450 − OD650 of IMI-treated cells)/(OD450 − OD650 of control) × 100.

4.4. Live/Dead Cell Viability Assay
Cell viability was confirmed using a LIVE/DEAD® Cell Imaging Kit (Invitrogen, Waltham, MA, USA). PC-3 cells plated at a density of 1 × 103 cells per well in a 96-well plate were treated with 0.1% DMSO or 100 μM IMI. After 72 h, calcein-AM (live, green) and propidium iodide (PI; dead, red) were added to the cells and incubated for 15 min at room temperature in the dark. Images of live and dead cells were acquired using a fluorescence microscope (Axio Observer A1; Carl Zeiss AG, Oberkochen, Germany).
The percentage of cell viability was calculated according to the following formula:% of cell viability = (the number of viable cells/the total number of cells) × 100.

4.5. Wound Healing Assay
PC-3 cells were seeded at a density of 7 × 105 cells/mL into the two wells of a culture insert (Ibidi GmbH, Martinsried, Germany). After the overnight incubation, cells were grown to full confluence, and the culture inserts were removed to make the wound gap. Cells were washed with phosphate buffered saline (PBS) and incubated with five different concentrations of IMI (0–100 μM) for 12 h. Representative images for each concentration were captured at 10× magnification using a digital camera attached to an inverted microscope to quantify the relative migration of cells (Axio Observer A1). The area of the wound was quantitatively analyzed using MetaMorph software (Molecular Devices, Sunnyvale, CA, USA), and the percentage of wound recovery was evaluated.
Coverage in untreated PC-3 cells was defined as 100%.

4.6. Cell Invasion Assay
The cell invasion assay was performed using 24-well Transwell chambers with polycarbonate filters with 8 μm pore size (Corning Costar, Corning, New York, NY, USA). Transwell chambers were coated with gelatin solution (0.1%) on the lower surface and Matrigel on the upper surface for 30 min. PC-3 cells were seeded at a density of 2 × 104 cells/mL in serum-free medium onto the upper compartment of the Transwell, and the lower chambers were filled with medium containing 10% FBS and various concentrations of IMI (12.5, 25, 50, and 100 μM). After 24 h, the non invaded cells and the Matrigel on the upper chamber were gently removed using a cotton-tipped swab; then, cells at the undersurface of the filters were stained with crystal violet stain solution for 20 min and rinsed several times in distilled water. The number of invaded cells was quantified by visual counting after being photographed using an inverted microscope at 10× magnification.

4.7. Western Blot Analysis
PC-3 cells (4 × 105 cells/dish) were seeded in 100 mm dishes for 24 h and starved with 0.05% FBS overnight. PC-3 cells were incubated with five different concentrations of IMI (3.25, 12.5, 25, 50, and 100 μM) for 48 h or 72 h. After the treatment, the cells were lysed using a cell lysis buffer (Cell Signaling Technology, Beverly, MA, USA) containing a protease inhibitor cocktail from Roche and phosphatase inhibitor (Sigma Aldrich) for 30 min on ice.
After centrifugation, a bicinchoninic acid (BCA) protein assay kit (Thermo Scientific, Rockford, IL, USA) was used to determine the protein concentration. Equal amounts of protein lysate were separated in 10% sodium dodecyl sulfate (SDS) polyacrylamide gels and transferred to a polyvinylidene difluoride (PVDF) membrane (Bio-Rad Inc., Hercules, CA, USA).
The membrane was blocked with 5% skim milk in Tris-buffered saline with 0.1% Tween-20 (TBST) for 1 h at room temperature and then incubated with the specific primary antibodies, including AKT, phospho-AKT (Ser473), ERK1/2, phospho-ERK1/2 (Thr202/Tyr204), phospho-IKKα/β, IKKα, phospho-IκB, IκB, phospho-p65, and p65, overnight at 4 °C. The membranes were washed in TBST three times and incubated with horseradish peroxidase (HRP)-conjugated secondary antibodies at room temperature for 2 h. Protein bands were visualized using a chemiluminescence detection kit (ATTO, Tokyo, Japan). Beta-actin was used as the loading control.

4.8. Total RNA Isolation and Quantitative Reverse-Transcription Polymerase Chain Reaction (RT-qPCR)
Total RNA was isolated using the NucleoPin® RNA Plus XS Kit (Macherey-Nagel, Bethlehem, PA, USA) according to the manufacturer’s instructions. Reverse transcription of RNA was performed using the ReverTra Ace® qPCR RT Master Mix (Toyobo, Osaka, Japan). First-strand complementary DNA (cDNA) was prepared using 1 μg of total RNA. The real-time PCR reaction was performed in a volume of 20 μL containing 0.1 μg of cDNA, 1 μM of each primer (Table 1), and Power SYBR® Green PCR Master Mix (Applied Biosystems, Carlsbad, CA, USA).
Thermal cycling was carried out in a StepOnePlus Real-Time PCR system (Applied Biosystems, Carlsbad, CA, USA) with a program of 95 °C for 5 min, followed by 40 cycles of denaturation at 95 °C for 5 s annealing, and elongation at 60 °C for 10 s. Gene expression levels were normalized to the expression level of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (*GAPDH*). Relative gene expression changes, calculated using the 2−∆∆CT method, were reported as number-fold changes compared to those in the control samples.
**Table 1.** Primer sequences for RT-qPCR.

4.9. Statistics
All experiments were independently performed at least three times and the values were expressed as the mean ± standard error of the mean (SEM). Statistical analysis was performed using GraphPad Prism version 5 (GraphPad Software, Inc., La Jolla, CA, USA). Statistical significance was evaluated by unpaired t-test for comparison between two groups and one-way ANOVA followed by Dunnett’s post hoc test for multiple groups.
A p-value < 0.05 was considered to indicate a statistically significant difference.

5. Conclusions
In conclusion, our results demonstrated that IMI treatment inhibited cell proliferation, migration, and invasion in mCRPC PC-3 cells. The suggested mechanisms of IMI in PC-3 cells include the modulation of AKT/ERK signaling and suppression of the AKT/NF-κB signaling pathway by preventing IκBα degradation, blocking p65 phosphorylation, and regulating chemokine and cytokine production. We suggest that IMI may be a potential chemotherapeutic candidate against metastatic CRPC.
Author Contributions
Formal analysis, E.Y.L. and J.P.; investigation, E.Y.L. and J.P.; methodology, E.Y.L.; writing—original draft, E.Y.L. and J.P.; funding acquisition, Y.T.K.; resources, Y.T.K.; supervision, Y.T.K.; writing—reviewing and editing, Y.T.K. and M.J.K.; conceptualization, M.J.K.; project administration, M.J.K. All authors have read and agree to the published version of the manuscript.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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**MDPI and ACS Style**
Lim, E.Y.; Park, J.; Kim, Y.T.; Kim, M.J. Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway. *Molecules* **2020**, 25, 4619. https://doi.org/10.3390/molecules25204619
**AMA Style**
Lim EY, Park J, Kim YT, Kim MJ. Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway. *Molecules*. 2020; 25(20):4619. https://doi.org/10.3390/molecules25204619
**Chicago/Turabian Style**
Lim, Eun Yeong, Joon Park, Yun Tai Kim, and Min Jung Kim. 2020. “Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant Prostate Cancer PC-3 Cells via AKT-Mediated NF-κB Signaling Pathway” *Molecules* 25, no. 20: 4619. https://doi.org/10.3390/molecules25204619

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Northwestern University. “Tumors dramatically shrink with new approach to cell therapy: Novel technology platform could bring individualized cell therapies to patients.” ScienceDaily. ScienceDaily, 27 January 2022. < www.sciencedaily.com/releases/2022/01/220127114334.htm

Tumors dramatically shrink with new approach to cell therapy: Novel technology platform could bring individualized cell therapies to patients — ScienceDaily

**Story Source:**
Materials provided by **Northwestern University**. Original written by Lila Reynolds. *Note: Content may be edited for style and length.*

**Journal Reference**:
Zongjie Wang, Sharif Ahmed, Mahmoud Labib, Hansen Wang, Xiyue Hu, Jiarun Wei, Yuxi Yao, Jason Moffat, Edward H. Sargent, Shana O. Kelley. **Efficient recovery of potent tumour-infiltrating lymphocytes through quantitative immunomagnetic cell sorting**. *Nature Biomedical Engineering*, 2022; DOI: 10.1038/s41551-021-00820-y

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You Don’t Have to Die

Posted on March 29, 2023 by Ken

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This is Biden’s Administration

Posted on March 28, 2023 by Ken

A KGB fled to the U.S. 39 years ago, what he told in the video below
has been continuously confirmed in the U.S.

**Watch:** a KGB defector’s mid-1980s interview
KGB defector Yuri Bezmenov’s warning to America – YouTube
(If you don’t want to watch the video, the transcript is here.)

Watch this or just listen to a video of Yuri Bezmenov, a KGB defector to Canada, who came to love America and tried to warn Americans about the KGB’s plans. Listening to him is eerie because he spelled out in detail exactly what the Soviet Union was doing — it wasn’t planning to take America down through the military.

Instead, it intended to destroy America from within by infiltrating the education system, three generations of young people to hate this country and each other and then watching them go forth and plant the seeds of self-loathing throughout the nation.

When it came to understanding how the Soviet Union operated, Bezmenov was the
real deal. His father was a high-ranking army officer, so Bezmenov was raised inside the system. He went to KGB schools and worked for the KGB for a decade until he defected to the West, eventually landing in Canada. In the 1980s, Bezmenov was able to move to Los Angeles, where he lived for five years.

It was in L.A., in 1984 or 1985, that he gave an interview to G. Edward Griffin, a conservative writer and thinker. During the interview, Bezmenov explained that the Soviet Union was not interested in fighting America. It was interested, instead, in co-opting it through psychological warfare. It is in that interview that you’ll see above.

An organized thinker, Bezmenov stated the core principles of his talk in the open minute of the video: But in reality, the main emphasis of the KGB is not in the area of intelligence at all. According to my opinion and the opinion of many defectors of my caliber, only about fifteen percent of time, money and manpower is spent on espionage as such. The other eighty-five percent is a slow process which we call either ideological subversion or active measures, or psychological warfare.

What it basically means is, to change the perception of reality, of every American, to such an extent that despite an abundance of information no one is able to come to sensible conclusions in the interest of defending themselves, their family, their community and their country. It’s a great brainwashing process which goes very slow and is divided into four basic stages. The first one being demoralization.

It takes from fifteen to twenty years to demoralize a nation. Why that many years?
Because this is the minimum number of years required to educate a generation of
students in the country of your enemy, exposed to the ideology of the enemy.

In other words, Marxism, Leninism ideology is being pumped into the soft heads
of at least three generations of American students, without being challenged or
contra-balanced by the basic values of Americanism, American patriotism.
A KGB fled to the U.S. 40 years ago, – Search (bing.com)

39 years later, Miles Guo, another hero who kept exposing CCP, was arrested by the FBI, DOJ…… Miles Guo not only kept exposing CCP as a trusted information center, but also united all freedom-loving Chinese to destroy CCP. Who are involved in arresting Mr. Guo, as a #1 saboteur of CCP, absolutely like what the KGB said , are helping CCP because of greed or stupidity. All traitors in the US should watch this Video to know how their end, once CCP achieves their goals, The CCP will kill them like cockroaches because they knew too much.

But all of us, ordinary people can only accept to be a slave to be killed and humiliated.
40 years later, Miles Guo, another hero who kept exposing CCP, was arrested by the FBI, DOJ… Miles Guo not only kept exposing the CCP as a trusted information center, but also united all freedom-loving Chinese to destroy the CCP.
Who is involved in arresting Mr. Guo, as a #1 saboteur of CCP, absolutely like what the KGB said, is helping CCP because of greed or stupidity.

Look if those Dems, leftist and radicals wouldn’t be so insistent in FxxKin up Trump’s life.
Knowingly that one of the top Chinese at the lab, informed the regime of the leak. Instead of sending a world alert, they imprisoned the scientist and hushed the virus as long as they could. There’s no question about it. Fauci has GOUT in both hands and probably from drinking alcohol…because committing crimes against humanity and genocide for profits can be a very stressful and guilt-ridden endeavor…

Prince Li: If the Congress really wants to find out the origin of the CCP virus,
I suggest that the U.S. Congress and the U.S. government investigate the relationship between Anthony Fauci and Wang Yanyi, the director general of the Wuhan Institute
of Virology. They have a very intimate relationship!

0bama gave Wuhan a Grant – Search (bing.com)

Have you noticed several big stores closing down in your city?
You can thank this smooth-talking Devil for what’s going on in our country, and the world right now. Well, this isn’t just happening around your area but around the whole country.
Several big stores are about to shut down this year, and many want to know why.
Big stores such as Macy’s and J.C.Penny have been struggling ever since the pandemic,
and now that the economy is not looking good, these companies are starting to shut down stores all over the country.
Several big-name stores are now switching to online sales as the internet has taken over everything as everybody started ordering things online due to the pandemic. Some of these big stores have been around forever, so it would be sad to see them go. So if you want to see what big stores are about to shut down this year then stick around.

Turn around is fair play stick the juice to that old decrepit mad scientist.
I think it is HIGH time that F U Fauchi ‘Actually’ be given the Death Jab &
at Least 3 Boosters! I believe in appropriate consequences for your actions!!
He forced this on the World… Now Let Him Be Given the REAL Vax!

(Because we all know he Never took it!)

A video deposition given by Dr. Anthony Fauci has been released publicly.
Video Deposition of Fauci in Gov. Censorship Case Released Publicly | Newsmax.com

Fauci Lied & Children Died: Secret CDC Documents confirm 120k Children, Teens & Young Adults ‘Died Suddenly’ in the US by Oct. 2022 after
“Emergency” Use Authorization’ of Covid Vaccines – The Expose (expose-news.com)

#Fauci Lied & #Children Died: Secret #CDC
Documents confirm 120k Children, Teens & Young Adults ‘Died Suddenly’ in the US by Oct. 2022 after ‘“Emergency”
Use Authorization’ of #Covid #Vaccines After that he might have a few months left on this earth, before the Bioweapon He Helped Create takes Him to Meet w/ God & His Eternal Damnation! Pure Justice!

**This is all by design. He was The Destroyer.**
There’s no justice until this POS is indicted, tried
and sentenced for his crimes against America.

Should have listened when he said he wanted to fundamentally transform America.
I always knew and know this guy is evil to the core with his pure hatred of the US.
His contempt for American blacks was obvious.

**I’d go further than that. Damn right !!!**

MOST of our socio-economic-international problems began with this joker.
and his 110 page communist manifesto – Search (bing.com)

“Dilbert Reborn” now exclusively on http://Scottadams.locals.com.
(Subscription) with lots more content.

EXPOSING CORRUPTION & UNITING US on Twitter: “BREAKING: Alvin Bragg’s dog & phony show is another political play straight out of “The Nasty Ass Pelosi Wrap Up Smear Campaign Tactics” 👇🤔 https://t.co/LzVqB29KoY” / Twitter

Steve Bannon’s Warning After Donald Trump’s Indictment (msn.com)
We are watching the Democrat Party Morph into a Fascist-Socialist Regime that feels NO need to explain itself to Americans. Because it was not voted in and won’t be voted in next time. Democrats either don’t believe that people like Adolf Hitler and Joseph Stalin exist today, or they are looking forward to having one in the White House. History is loaded with megalomaniacs… and their followers.

If you knew the crap they do ‘off the books’, black ops, illegal funding from drug running, assassinations, etc… you would be so fuckin scared Yup if we only know the tip of the ice burg… Corrupt Intel Agencies + Corrupt Media + Corrupt Democrat Party = Totalitarian Dystopia. Conspiracy almost always turns out to be fact.

Propaganda opposes alternate views. #WokeMindVirus…c”,)

How much is Joe Biden worth today?

A reported $8 to 9 million…probably Billions laundered away!!!

And these are the people calling Conservatives violent and extremists.

They have not even begun to scratch the surface of how deep this evil goes…

it’s beyond comprehension… Keep thinking there is an epiphany in our future…

Sad truth The problem is when we start telling people about the truth we get Epsteined!

Yes, scary truth versus comforting lies

Enemies within….Absolutely done in overtime!!!
Rome wasn’t destroyed in a day either.

So much miss direction, PSYOP, hidden agendas, down right lies…
The more I spend time on social media, the more I realize I need to spend time
with my Father in Heaven… I think we are to a point that only He can fix this…
What I do here makes little difference…I so agree!!!

Someone gave me a refrigerator magnet as a joke years ago. It says. It is as bad as you think it is. And they are out to get you. My father said to me 20+ years ago, whatever the sickest, craziest, most deplorable thing you can think of-someone, somewhere is doing, they are most likely in government. The man knew.

We know that is why we pray to the force that could help us cope with the evil in this world. Some of us don’t talk about it much because they won’t believe us anyway but we only share it to those who seem serious about it. Full Sean Hannity Interview With President Donald Trump 3/27/2023 – Video – The Last Refuge (theconservativetreehouse.com)

A federal prosecutor admits three D.C. undercover police officers –
acted as provocateurs on J6.

Marxism vs Communism vs Socialism vs Fascism – Bing video
This is just more evidence that the entire operation was planned, paid for,
instigated and carried out by the US government, FBI, DC Police, and NYC police.
The entire riot was also orchestrated and carried out by government operatives.
Ringleader in Jan6 is Nancy Pelosi. Oh, Nancy Pelosi came out with that saying,
didn’t she? She said, “I have a few more arrows in my quiver.”

Sep 19, 2020, House Speaker Pelosi said that another bogus impeachment is one of the “arrows in our quiver” to block President Trump’s Supreme Court Justice nominee. …more.
It met she had a few options, in order to accomplish what she wants to accomplish. Literally, a quiver is an arrow bag. She is saying she has more than one trick up her sleeve. Pelosi: ‘We have arrows in our quiver that I’m not about to discuss right now’, And I believe her. Did you see the look on her face?

Like a cat with a canary in its mouth.

Nancy bought. paid for the mas·quer·ade.

1 a : a social gathering of persons wearing masks and often fantastic costumes b : a costume for wear at such a gathering 2 : an action or appearance that is mere disguise or show **masquerade** 2 of 2 verb masqueraded; masquerading intransitive verb …This is seriously frightening that a governments and agencies associated to government would do this. Way too much corruption. All to keep power, make money for themselves and control everyone.

Apparently, it shut up Congress for good.
What do they do all day besides NOT ARRESTING @JoeBiden et al?
It feels like they’re waiting for something. Dear Useless Congress:
that #Uniparty thing isn’t taking off now or ever.
Give back your bonuses and get to work A******S
.
**We all know what needs to be done.**

The DC police are filth along with the FBI, DOJ, CIA, NAS, ATF you name the government agency, and you see political corruption. They wanted no opposition to a fixed election. Has the FBI been cleaned up?
NO…Will it happen again…. YES!!!

**We are the one going to question.**
Of those people, why they RiGGED the election , and the evidence they made it go away.

**Why are they so corrupted?**

They put whatever they want, not the people’s choices first.
They are so evil and corrupted.

**We need those people to Resigned…NOW!!!**

That’s a lot of feds who interfered in the election process. They need to be dealt with swiftly and severely. Planned by Pelosi & Schumer with assistance from democratic congress Representatives & Senators. As a concerned citizen I really want to know, how does this work?
Your higher up puts out an email asking for volunteers to instigate people at the capitol building to try to cause a riot or an insurrection?

**How does this even come to be??**

The Last Days According to Jesus, Revised and Updated Edition:
When Did Jesus Say He Would Return?: Christianbook.com

“I am.” Hey , gotta’ be me.
I don’t know how to be anyone else.
If you don’t like my opinions,
I’m sorry they are the only ones I got.

*•.¸♡ 𝘓𝘪𝘬𝘦𝘥 & 𝘙𝘦𝘛𝘸𝘦𝘦𝘵𝘦𝘥 ♡¸.•*
✿｡:✿｡:*𝙿𝚕𝚎𝚊𝚜𝚎 𝙵𝚘𝚕𝚕𝚘𝚠*:｡✿
╰☆ GOD BLESS AMERICA ☆╮
»★« #Patriots Assemble »★«
╰☆☆ #𝐕𝐞𝐭𝐭𝐞𝐝𝐏𝐚𝐭𝐫𝐢𝐨𝐭𝐬 ☆☆╮

Posted in Uncategorized | Leave a comment

Fasting for Gut Repair

Posted on March 28, 2023 by Ken

Should You Tell Your Boss You Have IBD?
Plus, More Tips for Coping at the Office
BY ELIZABETH MILLARD

As the human resources director for Family Destinations Guide, a website that offers kid-friendly vacation ideas, Bonnie Whitfield always makes sure employees feel comfortable disclosing their medical conditions so the company can provide accommodations. For Whitfield, it’s not just professional—it’s personal, because she has inflammatory bowel disease (IBD).

“Since I have IBD myself, and I’ve been through a few flare-ups at work,
I know what it’s like to be in that situation,” she says. Employees are often trying to navigate not just the symptoms of a chronic illness, but also anxiety over questions like: Should I tell my employer and coworkers? Will people feel like they can’t count on me? What if I’m embarrassed to talk about it?

These are all common concerns, says Whitfield, and unfortunately, worrying about such issues can actually put you at higher risk for an IBD flare that could affect your work.

IBD encompasses two conditions—Crohn’s disease and ulcerative colitis—that are characterized by inflammation of the gastrointestinal tract, leading to symptoms like diarrhea, abdominal cramping, fatigue, and sudden weight loss. Treatment options help many people go into remission so their condition becomes a non-issue, but even on medication, symptoms may return in a flare-up that can range from mild to debilitating and might last days or weeks. The unpredictability of the disease is another source of potential anxiety when considering how it will affect work performance, Whitfield says.

“Sometimes, pushing yourself can make your flare worse,” she adds. “Having a plan in place beforehand can go a long way toward keeping you productive while still taking care of yourself. It’s important to remember that being sick shouldn’t mean you can’t be an effective employee.” Here are some tips to consider when balancing your health and your workplace, even if your IBD is in remission right now.

**Let your employer know—and put it in writing.**
Although the symptoms of IBD—like frequent trips to the bathroom, gassiness,
and bloating—can feel embarrassing, it’s important to recognize you have a
chronic illness and that it should be handled as such, Whitfield advises.

She suggests telling your direct supervisor and HR director not just about your condition, but also what you need in terms of accommodation and why that will help you function better in the workplace. For example, many people with IBD benefit from having an office or cubicle closer to the bathroom, which can shorten the amount of time spent going back and forth during a flare.

Also, simply being closer might reduce worry about the issue, and in itself that could
tamp down some symptoms. Having to use a wheelchair may also come into play, since side effects used to treat ulcerative colitis can lead to mobility challenges, so letting an employer know that could be a possibility—and ensuring you have access to all the areas you need—is crucial for planning ahead.

There may be multiple doctor visits as well, especially when flares are more dominant, and treatment could include options like surgery in the future. Preparing an employer for that possibility should be part of the conversation about your condition.

Whitfield says putting information like this into writing is the best approach, since it provides the most clarity about what you need. Plus, it ensures that all parties are receiving the same information. “Explain how IBD affects your work performance and how you can still do your job effectively while keeping up with treatment regimens and any other responsibilities required by the company, such as working overtime,” she adds.

“The more specific you can be about what accommodations would help keep you healthy and productive, the better equipped your employer will be to develop a plan that works for both of you.” Another benefit to writing it down: It may feel easier than saying everything in a meeting, particularly with multiple people or those you don’t know well.

For instance, when Los Angeles-based Span Chen was working as a cashier, every day felt like a battle due to pain and the inability to leave a line of customers. Treatment helped reduce flare-ups, but also led to more fatigue. He felt hesitant to bring up his struggles.

“What helped was writing a letter to my boss explaining what was going on, and that
I needed to take time off in order to heal fully,” says Chen. “Because I wrote it down,
I didn’t forget key points, like saying that being able to have more time away from
work would allow me to return to full health.”

**Read More:** *How to Maintain Your Social Life When You Have IBD*

**Establishing some code words and contingency plans.**
Even just having a key phrase can be useful, says Cassie Mahon, who leads client
meetings for her employer in Columbia, Missouri. She informed her boss about her IBD &
together they formulated a plan of action about what to do if Mahon had to leave suddenly.

“If I say that it’s time for a short break, she understands what’s going on and
we don’t have to tell everyone else in the room what’s happening,” she says,
adding that sometimes her boss will step in to continue a presentation if necessary.
That might seem like a minor tweak to the process, but Mahon says it provides much-needed reassurance that her work can continue with minimal disruption.

**Stick to your routine**.
Although IBD might not be predictable, your work schedule still can be, if you have the option of being flexible about location. That means making sure you’re able to work from home occasionally and that there’s a plan in place for those days, including having a home office setup and access to online company resources.

“Stay true to your usual routine as much as possible, which can help take some of the stress out of an IBD flare,” Whitfield says. “This can keep your life feeling normal while also giving your body time to recover.” Of course, not everyone has the option of working from home, but if it’s a possibility for you and can alleviate some of the worry around being in the office, it’s helpful to incorporate at-home time when you can.

If it’s not possible, Whitfield says that creating a more flexible work schedule could be another beneficial strategy. For instance, if being around so many coworkers makes you anxious about flares, you might swap one weekday for working on a weekend day so you’re in the office with fewer people.

**Keep supplies on hand.**
Another part of preparation is knowing what you need so you have items at the ready,
no matter what. For Boston-based Keyla Caba, being anywhere that’s not home can be difficult with her IBD, particularly because she wears an ileostomy pouch—a special bag that collects waste from the colon—which must be emptied regularly.
After years of fretting over the distance between her desk and restroom, she decided to make it a priority to make her experience more comfortable and address her fears about not making it to the bathroom in time.

That has meant always having spare clothes at the office, as well as some sort of deodorizing spray, and a sign she would hang on her desk to let colleagues know
she was having a flare and needed extra time away.

“This was the start of how I transformed the office bathroom into a peaceful experience
for myself, and relieved my restroom anxiety,” Caba says. “Knowing I have what I need
on hand can reduce my fears about flares.”

**Know your rights.**
Even if company management and HR are happy to accommodate your needs
as someone with IBD, it’s still essential to know your rights as an employee, says
Kia Roberts, principal and founder of Brooklyn, New York-based Triangle Investigations, which handles assessments of workplace misconduct. For example, she recently worked on a harassment case for a person with Crohn’s disease who wasn’t given accommodations by her manager.

“Most workplaces today understand the importance of not discriminating against employees based on protected characteristics like race, sexuality, gender, and ethnicity, but many employers do not understand the importance of having a policy on how employees with health issues should be treated within the workplace,” says Roberts.
“If an employee feels they are being singled out for different treatment based on their health issues, that could represent discrimination on the part of the employer.”

Another important aspect of your rights: If your IBD is disabled, it’s protected under the Americans with Disabilities Act, which means your employer must make reasonable accommodations. You may also be covered under the Family and Medical Leave Act, which entitles eligible employees to take unpaid, job-protected leave for medical reasons—up to 12 weeks of leave within a 12-month time period.

**Focus on gut-healthy lifestyle habits.**
Part of being more productive at work comes from what you do outside of the office, and that means implementing the right lifestyle behaviors, according to Dr. Ashkan Farhadi,
a gastroenterologist at MemorialCare Orange Coast Medical Center in Fountain Valley, Calif. In addition to making sure you follow treatment protocols like medication you may be prescribed, you can lower risk of flares by focusing on gut health, he says.

“Diet will, of course, play a major role in your IBD management, but equally important are other habits that improve your gut microbiome,” Farhadi says. “The three most prominent are sleep, stress reduction, and exercise, because if you get those on track along with your diet, it can significantly reduce the frequency and severity of flares.”

For example, there’s a strong association between sleep difficulties and gut function, which can lead to more than just daytime sleepiness or flares at work. A 2018 study in the journal Frontiers in Psychiatry found that insomnia has been linked to poor immune function, difficulty absorbing certain nutrients, and depression.

**Read More:** *These Environmental Factors Increase the Risk of IBD*

**Staying aware of potential overwhelm.**
Stress is another big challenge when it comes to avoiding flares,
adds Dr. Rudolph Bedford, a gastroenterologist at Providence Saint John’s
Health Center in Santa Monica, Calif.

“Chronic stress has a ripple effect on your gut microbiome, which means it can impair your gastrointestinal system and keep it from functioning well,” he says. “When you have IBD, that means it could make your flares more intense, or could cause flares even if they’ve been well managed in the past.”

A significant part of better stress control comes from evaluating all aspects of your everyday activity, and that includes work. If you’re feeling frazzled, that’s another conversation to start with your supervisor and HR.
“When someone has a chronic illness like IBD, remember that it should be a team effort
in terms of management,” Whitfield says. “The more that people around you understand
what’s going on, the more it will benefit you, your company, and your coworkers.”

Your gut is endangered. And that’s not a good thing for your health—
or the health of the rest of the world. © Getty Images

The Human Microbiome Is Going Extinct, Scientists Say.
The End Will Be Devastating. Story by Tim Newcomb.

Researchers say the human microbiome that lives in your gut is now endangered.
The loss of bacteria and microorganisms reduces your chance at a healthy life.
You’re the one killing off your own microbiome. The human microbiome is endangered.
And that’s not a good thing for your health—or the health of the rest of the world.

A new documentary, *The Invisible Extinction*, highlights how the human microbiome—also known as the bacteria and microorganisms living within the human body, most prevalent in the gut—is on the verge of extinct. And it’s all your fault.

The Invisible Extinction Movie: The Quest to Save the Microbiome!

There’s a war raging in our bodies, and the casualties are the bacteria that live in our gut. These bacteria, known as the microbiome, are crucial for our health, but factors like antibiotics, C-sections, and processed foods are threatening their survival. In the new documentary film “The Invisible Extinction,” doctors Martin Blaser and Gloria Dominguez-Bello embark on a mission to save the microbiome.
These tiny organisms help us digest food, make vitamins, and protect us from illness. They can be found all over the body, but most reside in the gut. People with a more diverse microbiome tend to be healthier. Researchers have used poop (yes, you read that right!) to study the microbiome and its connection to diseases like inflammatory bowel disease, multiple sclerosis, liver disease, diabetes, and autism.
Antibiotics can be harmful to the microbiome because they can kill off both good and bad bacteria. To keep our microbiomes happy and healthy, it’s important to eat a varied diet, avoid unnecessary antibiotics, and consider vaginal delivery over C-sections.

In a discussion with *People*, two researchers behind the doc, Martin Glaser and Gloria Dominguez-Bello, say the human microbiome is essential for us to digest food, make vitamins, and train our immune systems. “When we eat,” Blaser tells *People*, “we are nourishing both our human cells and also our microbial cells.”

The slow death of the human microbiome is thanks to our modern way of life. We use antibiotics to kill off bad bacteria. But antibiotics kill off plenty of the good stuff, too. Blaser says the more antibiotics given to a child, the more likely they are to develop a range of illnesses. Blaser adds that the Centers for Disease Control and Prevention
(CDC) estimates about one-third of antibiotic prescriptions are unnecessary,
leading to the overuse.
Then there’s the highly processed, chemical-laden food that’s wreaking havoc on our gut health. “The single most important component of the diet to feed the microbiome is fiber,” Dominguez-Bello says. These fibers feed your microbiome, while processed food removes the fiber, posing a negative result for your microbiome.

The researchers want better options for the antibiotic issue, both with improved testing to see if a bacterial infection is really in play, and by developing new antibiotics that don’t have the “collateral damage that is killing every bacterium inside.”
“We are making a complete mess of biodiversity, including microbes,” Dominguez-Bello says. “Microbes are essential in every ecosystem, not only in humans or animals or plants, but also in the oceans. The whole thing is linked together by the impact of human activities. We need to preserve microbes because they really modulate functions of Earth. They modulate the climate. They modulate everything. They modulate our own gene expression.”

The human microbiome is a big deal. Let’s not kill it.
https://www.theinvisibleextinction.com/

**How Fasting Can—and Can’t—Improve Gut Health**
BY MARKHAM HEID

What is fasting and how does it work. – Bing video
If you spend a lot of time online, you may have noticed that parts of the internet have caught fasting fever. Online message boards are awash in posts touting the benefits of time-restricted eating and other intermittent-fasting approaches that involve going without caloric foods or drinks for an extended period of time—anywhere from 12 hrs.
to several days.

These online testimonials have helped popularize intermittent fasting, and they
often feature two common-sense rationalizations: One, that human beings evolved in environments where food was scarce and meals occurred sporadically; and two, that the relatively recent shift to near round-the-clock eating has been disastrous for our intestinal and metabolic health.

Mining the internet for accurate information, especially when it comes to dieting, can feel like panning for gold. You’ve got to sift through a lot of junk to find anything valuable. But this is one case where nuggets may be easy to find. A lot of the published peer-reviewed research on intermittent fasting makes the same claims you’ll find on those Reddit message boards.

“Until recently, food availability has been unpredictable for humans,” wrote the authors of a 2021 review paper in the *American Journal of Physiology*. “Knowledge of early human evolution and data from recent studies of hunter-gatherer societies suggest humans evolved in environments with intermittent periods of food scarcity.”
They say that fasting regimens may provide a period of “gut rest” that could lead to several meaningful health benefits, including improved gut microbe diversity, gut barrier function, and immune function.

The past decade has witnessed an explosion in fasting-relatedid research. (According to Google Scholar, the last five years alone contain almost 150,000 articles that examine or mention fasting.) While that work has helped establish links between intermittent fasting and weight loss, as well as other benefits, it’s not yet clear when (or if) fasting can help fix a sick gut.

“I would still consider the evidence moderate,” says Dr. Emeran Mayer, a professor of medicine and founding director of the Goodman Luskin Microbiome Center at the University of California, Los Angeles. “[Fasting] looks like a prudent way to maintain metabolic health or reestablish metabolic health, but it’s not a miracle cure.

When it comes to gut conditions such as inflammatory bowel disease (IBD),
he says the research is either absent or inconclusive.
To his point, researchers have found that Ramadan fasting—a month-long religious period when people don’t eat or drink between sunrise and sunset—can substantially “remodel” the gut’s bacteria communities in helpful and healthy ways. However, among people with IBD, studies on Ramadan fasting have also found that a person’s gut symptoms may grow worse.

While it’s too early to tout fasting plans as a panacea for gut-related disorders, experts say there’s still reason to hope these approaches may emerge as a form of treatment. It’s clear that some radical, and perhaps radically beneficial, things happen when you give your body breaks from food.

**How fasting could repair the gut.**
For a series of recent studies, a team of researchers based in the Netherlands and China examined the effects of Ramadan-style intermittent fasting on the gut microbiome—the billions of bacteria that reside in the human gastrointestinal tract. (Ramadan comes up a lot in published research because it provides a real-world opportunity for experts to examine the effects of 12- or 16-hour fasts, which is what many popular intermittent fasting diets espouse.)

“We really wanted to know what intermittent fasting does to the body,” says Dr. Maikel Peppelenbosch, a member of that research team and a professor of gastroenterology at Erasmus University Medical Center in the Netherlands. “Generally, we’ve seen that intermittent fasting changes the microbiome very clearly, and we view some of the changes as beneficial. If you look at fasting in general, not only Ramadan, you see certain types of bacteria increasing.”

When Butyrate Levels are high cancer risk is low.
For example, he says that intermittent fasting pumps up the gut’s population of a family
of bacteria called *Lachnospiraceae*. “In the intestines, bacteria are constantly battling for ecological space,” he explains.
Unlike some other gut microorganisms, *Lachnospiraceae* can survive happily in an empty GI tract. “They can live off the slime the gut makes itself, so they can outcompete other bacteria in a fasting state.”
*Lachnospiraceae* produces a short-chain fatty acid called butyrate, which seems to be critically important for gut health. Butyrate sends anti-inflammatory signals to the immune system, which could help reduce pain and other symptoms of gut dysfunction.

Butyrate also improves the barrier function of the intestines,
Peppelenbosch says. This is, potentially, a very big deal.
Poor barrier function (sometimes referred to as “leaky gut”) is a hallmark of common
G.I. conditions, including inflammatory bowel disease. If intermittent fasting can turn down inflammation and also help normalize the walls of the GI tract, those changes may have major therapeutic implications.

Lachnospiraceae is only one of several types of helpful bacteria that research has linked to fasting plans. But at this point, there are still a lot of gaps in the science. Peppelenbosch says the guts of people with bowel disorders don’t seem to respond to fasting in exactly the same way as the guts of people without these health issues. “In ill people, we see the same changes to the microbiome, but it’s not as clear cut as in healthy volunteers,” he says. “So we are now actually trying to figure out what’s going on there.

”Healthy microbiome shifts aren’t the only possible benefits that researchers have linked to intermittent fasting. UCLA’s Mayer mentions a phenomenon called the migrating motor complex. “This is rarely mentioned in fasting articles today, but when I was a junior faculty it was one of the hottest discoveries in gastroenterology research,” he says. The migrating motor complex refers to recurrent cycles of powerful contractions that sweep the contents of the gut, including its bacteria, down into the colon.

“It’s this 90-minute recurring contractile wave that swoops down the intestine, and its strength is comparable to a nutcracker,” he says. Essentially, this motor complex behaves like a street-cleaning crew tidying up after a parade. It ensures the gut is cleared out and cleaned up in between meals, via 90-minute repeating cycles that fasting allows to become more frequent. It also helps rebalance the gut’s microbial populations so that more of them are residing in the colon and lower regions of the GI tract. “But it’s stopped the minute you take a bite—it turns off immediately,” he says.

Mayer says that modern eating habits—so-called “grazing,” or eating steadily throughout the day—leave little time for the migrating motor complex to do its thing. “This function has been relegated to the time when we sleep, but even this has been disrupted because a lot of people wake up in the middle of the night and snack on something,” he says. “So those longer periods of time when we’re-cleanse and rebalance our gut so that we have normal distributions of bacteria and normal population densities—that has been severely disturbed by these lifestyle changes.

”Ideally, Mayer says people could (for the most part) adhere to the kind of time-restricted eating program that allows a full 12-to-14 hours each day for the motor complex to work. “If you don’t snack, this motor complex would happen between meals, and you’d also get this 12- to 14-hour window at night where the digestive system was empty,” he explains.
In other words, sticking to three meals a day and avoiding between-meal bites (or nighttime snacks) could be sufficient. But again, it’s not clear whether this sort of eating schedule can undo gut damage or treat existing dysfunction.

**Read More:** *The Truth About Fasting and Type 2 Diabetes*

**More potential benefits.**
Another possible perk of fasting involves a biological process called “autophagy.”
During autophagy, old or damaged cells die and are cleared away by the body.
Some researchers have called it a helpful housekeeping mechanism, it occurs
naturally when the body goes without energy (calories) for an extended
period of time.

There’s been some expert speculation, based mostly on evidence in lab and animal studies, that autophagy could help strengthen the gut or counteract the types of barrier problems seen in people with IBD. But these improvements have not yet been demonstrated in real-world clinical trials involving people.

Meanwhile, some experts have found that fasting may help recalibrate the gut’s metabolic rhythms in helpful ways. “By changing the timing of the diet, this will indeed change activity of the microbiome, and that may have downstream impacts on health,”
says Dr. Eran Elinav, principal investigator of the Host-Microbiome Interaction Research Group at the Weizmann Institute of Science in Israel.

Some of Elinav’s work, including an influential 2016 paper in the journal Cell, has shown that the gut microbiome undergoes day-night shifts that are influenced by a person’s eating schedule, and that lead to changing patterns of metabolite production, gene expression, and other significant elements of gut health. “If you change the timing of diet, you can flip the circadian activity of the microbiome,” he says. This is likely to have health implications, though what those are, precisely, remains murky.

**Read More:** *What We Know About Leaky Gut Syndrome*

**Fasting isn’t going anywhere.**

It’s clear that when you eat, including how often you eat, matters to the health of your gut. But the devil’s in the details. At this point, it’s not clear how intermittent fasting can be used to help people with gut-related disorders or metabolic diseases.

“For a condition like IBD, it’s important to differentiate between what you do during a flare and what you do to prevent the next flare,” Mayer points out. The research on people observing Ramadan suggests that, at least during a flare, fasting may make a person’s IBD symptoms worse. Figuring out whether fasting could also lead to longer-term improvements is just one of many questions that needs to be answered.

While plenty of unknowns remain, experts say that common approaches to fasting appear to be safe for most people. Time-restricted eating, for example, involves cramming all your day’s calories into a single six-to-eight-hour eating window. Even among people with metabolic diseases such as Type 2 diabetes, research suggests that this form of fasting is safe, provided a person is not taking blood-glucose medications.

That said, there simply isn’t much work on intermittent fasting as a treatment
for gut problems. Also, there is very little research on more extreme forms of fasting,
such as plans that involve going without calories for several days at a stretch.

These diets may turn out to be therapeutic, but they could also turn out to be dangerous.
If you’re considering any of these approaches, talk with your health care provider first.

“We really need much better studies to compare all the different fasting protocols,”
says Peppelenbosch. “But generally speaking, increasing the space between calorie consumption is a good thing for you. The body is not made to be eaten all day.”

Top Doctor: If You Eat Oatmeal Every Day, This Is What Happens BY GUNDRY MD – Search (bing.com)

Your gut is endangered. And that’s not a good thing for your health—or the health of the rest of the world. — Should You Tell Your Boss You Have IBD?
Plus, More Tips for Coping at the Office
BY ELIZABETH MILLARD

As the human resources director for Family Destinations Guide, a website that offers kid-friendly vacation ideas, Bonnie Whitfield always makes sure employees feel comfortable disclosing their medical conditions so the company can provide accommodations. For Whitfield, it’s not just professional—it’s personal, because she has inflammatory bowel disease (IBD).

“Since I have IBD myself, and I’ve been through a few flare-ups at work,
I know what it’s like to be in that situation,” she says. Employees are often trying to navigate not just the symptoms of a chronic illness, but also anxiety over questions like: Should I tell my employer and coworkers? Will people feel like they can’t count on me? What if I’m embarrassed to talk about it?

These are all common concerns, says Whitfield, and unfortunately, worrying about such issues can actually put you at higher risk for an IBD flare that could affect your work.

IBD encompasses two conditions—Crohn’s disease and ulcerative colitis—that are characterized by inflammation of the gastrointestinal tract, leading to symptoms like diarrhea, abdominal cramping, fatigue, and sudden weight loss. Treatment options help many people go into remission so their condition becomes a non-issue, but even on medication, symptoms may return in a flare-up that can range from mild to debilitating and might last days or weeks. The unpredictability of the disease is another source of potential anxiety when considering how it will affect work performance, Whitfield says.

“Sometimes, pushing yourself can make your flare worse,” she adds. “Having a plan in place beforehand can go a long way toward keeping you productive while still taking care of yourself. It’s important to remember that being sick shouldn’t mean you can’t be an effective employee.” Here are some tips to consider when balancing your health and your workplace, even if your IBD is in remission right now.

**Let your employer know—and put it in writing.**
Although the symptoms of IBD—like frequent trips to the bathroom, gassiness,
and bloating—can feel embarrassing, it’s important to recognize you have a
chronic illness and that it should be handled as such, Whitfield advises.

She suggests telling your direct supervisor and HR director not just about your condition, but also what you need in terms of accommodation and why that will help you function better in the workplace. For example, many people with IBD benefit from having an office or cubicle closer to the bathroom, which can shorten the amount of time spent going back and forth during a flare.

Also, simply being closer might reduce worry about the issue, and in itself that could
tamp down some symptoms. Having to use a wheelchair may also come into play, since side effects used to treat ulcerative colitis can lead to mobility challenges, so letting an employer know that could be a possibility—and ensuring you have access to all the areas you need—is crucial for planning ahead.

There may be multiple doctor visits as well, especially when flares are more dominant, and treatment could include options like surgery in the future. Preparing an employer for that possibility should be part of the conversation about your condition.

Whitfield says putting information like this into writing is the best approach, since it provides the most clarity about what you need. Plus, it ensures that all parties are receiving the same information. “Explain how IBD affects your work performance and how you can still do your job effectively while keeping up with treatment regimens and any other responsibilities required by the company, such as working overtime,” she adds.

“The more specific you can be about what accommodations would help keep you healthy and productive, the better equipped your employer will be to develop a plan that works for both of you.” Another benefit to writing it down: It may feel easier than saying everything in a meeting, particularly with multiple people or those you don’t know well.

For instance, when Los Angeles-based Span Chen was working as a cashier, every day felt like a battle due to pain and the inability to leave a line of customers. Treatment helped reduce flare-ups, but also led to more fatigue. He felt hesitant to bring up his struggles.

“What helped was writing a letter to my boss explaining what was going on, and that
I needed to take time off in order to heal fully,” says Chen. “Because I wrote it down,
I didn’t forget key points, like saying that being able to have more time away from
work would allow me to return to full health.”

**Read More:** *How to Maintain Your Social Life When You Have IBD*

**Establishing some code words and contingency plans.**
Even just having a key phrase can be useful, says Cassie Mahon, who leads client
meetings for her employer in Columbia, Missouri. She informed her boss about her IBD &
together they formulated a plan of action about what to do if Mahon had to leave suddenly.

“If I say that it’s time for a short break, she understands what’s going on and
we don’t have to tell everyone else in the room what’s happening,” she says,
adding that sometimes her boss will step in to continue a presentation if necessary.
That might seem like a minor tweak to the process, but Mahon says it provides much-needed reassurance that her work can continue with minimal disruption.

**Stick to your routine**.
Although IBD might not be predictable, your work schedule still can be, if you have the option of being flexible about location. That means making sure you’re able to work from home occasionally and that there’s a plan in place for those days, including having a home office setup and access to online company resources.

“Stay true to your usual routine as much as possible, which can help take some of the stress out of an IBD flare,” Whitfield says. “This can keep your life feeling normal while also giving your body time to recover.” Of course, not everyone has the option of working from home, but if it’s a possibility for you and can alleviate some of the worry around being in the office, it’s helpful to incorporate at-home time when you can.

If it’s not possible, Whitfield says that creating a more flexible work schedule could be another beneficial strategy. For instance, if being around so many coworkers makes you anxious about flares, you might swap one weekday for working on a weekend day so you’re in the office with fewer people.

**Keep supplies on hand.**
Another part of preparation is knowing what you need so you have items at the ready,
no matter what. For Boston-based Keyla Caba, being anywhere that’s not home can be difficult with her IBD, particularly because she wears an ileostomy pouch—a special bag that collects waste from the colon—which must be emptied regularly.
After years of fretting over the distance between her desk and restroom, she decided to make it a priority to make her experience more comfortable and address her fears about not making it to the bathroom in time.

That has meant always having spare clothes at the office, as well as some sort of deodorizing spray, and a sign she would hang on her desk to let colleagues know
she was having a flare and needed extra time away.

“This was the start of how I transformed the office bathroom into a peaceful experience
for myself, and relieved my restroom anxiety,” Caba says. “Knowing I have what I need
on hand can reduce my fears about flares.”

**Know your rights.**
Even if company management and HR are happy to accommodate your needs
as someone with IBD, it’s still essential to know your rights as an employee, says
Kia Roberts, principal and founder of Brooklyn, New York-based Triangle Investigations, which handles assessments of workplace misconduct. For example, she recently worked on a harassment case for a person with Crohn’s disease who wasn’t given accommodations by her manager.

“Most workplaces today understand the importance of not discriminating against employees based on protected characteristics like race, sexuality, gender, and ethnicity, but many employers do not understand the importance of having a policy on how employees with health issues should be treated within the workplace,” says Roberts.
“If an employee feels they are being singled out for different treatment based on their health issues, that could represent discrimination on the part of the employer.”

Another important aspect of your rights: If your IBD is disabled, it’s protected under the Americans with Disabilities Act, which means your employer must make reasonable accommodations. You may also be covered under the Family and Medical Leave Act, which entitles eligible employees to take unpaid, job-protected leave for medical reasons—up to 12 weeks of leave within a 12-month time period.

**Focus on gut-healthy lifestyle habits.**
Part of being more productive at work comes from what you do outside of the office, and that means implementing the right lifestyle behaviors, according to Dr. Ashkan Farhadi,
a gastroenterologist at MemorialCare Orange Coast Medical Center in Fountain Valley, Calif. In addition to making sure you follow treatment protocols like medication you may be prescribed, you can lower risk of flares by focusing on gut health, he says.

“Diet will, of course, play a major role in your IBD management, but equally important are other habits that improve your gut microbiome,” Farhadi says. “The three most prominent are sleep, stress reduction, and exercise, because if you get those on track along with your diet, it can significantly reduce the frequency and severity of flares.”

For example, there’s a strong association between sleep difficulties and gut function, which can lead to more than just daytime sleepiness or flares at work. A 2018 study in the journal Frontiers in Psychiatry found that insomnia has been linked to poor immune function, difficulty absorbing certain nutrients, and depression.

**Read More:** *These Environmental Factors Increase the Risk of IBD*

**Staying aware of potential overwhelm.**
Stress is another big challenge when it comes to avoiding flares,
adds Dr. Rudolph Bedford, a gastroenterologist at Providence Saint John’s
Health Center in Santa Monica, Calif.

“Chronic stress has a ripple effect on your gut microbiome, which means it can impair your gastrointestinal system and keep it from functioning well,” he says. “When you have IBD, that means it could make your flares more intense, or could cause flares even if they’ve been well managed in the past.”

A significant part of better stress control comes from evaluating all aspects of your everyday activity, and that includes work. If you’re feeling frazzled, that’s another conversation to start with your supervisor and HR.
“When someone has a chronic illness like IBD, remember that it should be a team effort
in terms of management,” Whitfield says. “The more that people around you understand
what’s going on, the more it will benefit you, your company, and your coworkers.”

Your gut is endangered. And that’s not a good thing for your health—
or the health of the rest of the world. © Getty Images

The Human Microbiome Is Going Extinct, Scientists Say.
The End Will Be Devastating. Story by Tim Newcomb.

Researchers say the human microbiome that lives in your gut is now endangered.
The loss of bacteria and microorganisms reduces your chance at a healthy life.
You’re the one killing off your own microbiome. The human microbiome is endangered.
And that’s not a good thing for your health—or the health of the rest of the world.

A new documentary, *The Invisible Extinction*, highlights how the human microbiome—also known as the bacteria and microorganisms living within the human body, most prevalent in the gut—is on the verge of extinct. And it’s all your fault.

The Invisible Extinction Movie: The Quest to Save the Microbiome!

There’s a war raging in our bodies, and the casualties are the bacteria that live in our gut. These bacteria, known as the microbiome, are crucial for our health, but factors like antibiotics, C-sections, and processed foods are threatening their survival. In the new documentary film “The Invisible Extinction,” doctors Martin Blaser and Gloria Dominguez-Bello embark on a mission to save the microbiome.
These tiny organisms help us digest food, make vitamins, and protect us from illness. They can be found all over the body, but most reside in the gut. People with a more diverse microbiome tend to be healthier. Researchers have used poop (yes, you read that right!) to study the microbiome and its connection to diseases like inflammatory bowel disease, multiple sclerosis, liver disease, diabetes, and autism.
Antibiotics can be harmful to the microbiome because they can kill off both good and bad bacteria. To keep our microbiomes happy and healthy, it’s important to eat a varied diet, avoid unnecessary antibiotics, and consider vaginal delivery over C-sections.

In a discussion with *People*, two researchers behind the doc, Martin Glaser and Gloria Dominguez-Bello, say the human microbiome is essential for us to digest food, make vitamins, and train our immune systems. “When we eat,” Blaser tells *People*, “we are nourishing both our human cells and also our microbial cells.”

The slow death of the human microbiome is thanks to our modern way of life. We use antibiotics to kill off bad bacteria. But antibiotics kill off plenty of the good stuff, too. Blaser says the more antibiotics given to a child, the more likely they are to develop a range of illnesses. Blaser adds that the Centers for Disease Control and Prevention
(CDC) estimates about one-third of antibiotic prescriptions are unnecessary,
leading to the overuse.
Then there’s the highly processed, chemical-laden food that’s wreaking havoc on our gut health. “The single most important component of the diet to feed the microbiome is fiber,” Dominguez-Bello says. These fibers feed your microbiome, while processed food removes the fiber, posing a negative result for your microbiome.

The researchers want better options for the antibiotic issue, both with improved testing to see if a bacterial infection is really in play, and by developing new antibiotics that don’t have the “collateral damage that is killing every bacterium inside.”
“We are making a complete mess of biodiversity, including microbes,” Dominguez-Bello says. “Microbes are essential in every ecosystem, not only in humans or animals or plants, but also in the oceans. The whole thing is linked together by the impact of human activities. We need to preserve microbes because they really modulate functions of Earth. They modulate the climate. They modulate everything. They modulate our own gene expression.”

The human microbiome is a big deal. Let’s not kill it.
https://www.theinvisibleextinction.com/

**How Fasting Can—and Can’t—Improve Gut Health**
BY MARKHAM HEID

What is fasting and how does it work. – Bing video
If you spend a lot of time online, you may have noticed that parts of the internet have caught fasting fever. Online message boards are awash in posts touting the benefits of time-restricted eating and other intermittent-fasting approaches that involve going without caloric foods or drinks for an extended period of time—anywhere from 12 hrs.
to several days.

These online testimonials have helped popularize intermittent fasting, and they
often feature two common-sense rationalizations: One, that human beings evolved in environments where food was scarce and meals occurred sporadically; and two, that the relatively recent shift to near round-the-clock eating has been disastrous for our intestinal and metabolic health.

Mining the internet for accurate information, especially when it comes to dieting, can feel like panning for gold. You’ve got to sift through a lot of junk to find anything valuable. But this is one case where nuggets may be easy to find. A lot of the published peer-reviewed research on intermittent fasting makes the same claims you’ll find on those Reddit message boards.

“Until recently, food availability has been unpredictable for humans,” wrote the authors of a 2021 review paper in the *American Journal of Physiology*. “Knowledge of early human evolution and data from recent studies of hunter-gatherer societies suggest humans evolved in environments with intermittent periods of food scarcity.”
They say that fasting regimens may provide a period of “gut rest” that could lead to several meaningful health benefits, including improved gut microbe diversity, gut barrier function, and immune function.

The past decade has witnessed an explosion in fasting-relatedid research. (According to Google Scholar, the last five years alone contain almost 150,000 articles that examine or mention fasting.) While that work has helped establish links between intermittent fasting and weight loss, as well as other benefits, it’s not yet clear when (or if) fasting can help fix a sick gut.

“I would still consider the evidence moderate,” says Dr. Emeran Mayer, a professor of medicine and founding director of the Goodman Luskin Microbiome Center at the University of California, Los Angeles. “[Fasting] looks like a prudent way to maintain metabolic health or reestablish metabolic health, but it’s not a miracle cure.

When it comes to gut conditions such as inflammatory bowel disease (IBD),
he says the research is either absent or inconclusive.
To his point, researchers have found that Ramadan fasting—a month-long religious period when people don’t eat or drink between sunrise and sunset—can substantially “remodel” the gut’s bacteria communities in helpful and healthy ways. However, among people with IBD, studies on Ramadan fasting have also found that a person’s gut symptoms may grow worse.

While it’s too early to tout fasting plans as a panacea for gut-related disorders, experts say there’s still reason to hope these approaches may emerge as a form of treatment. It’s clear that some radical, and perhaps radically beneficial, things happen when you give your body breaks from food.

**How fasting could repair the gut.**
For a series of recent studies, a team of researchers based in the Netherlands and China examined the effects of Ramadan-style intermittent fasting on the gut microbiome—the billions of bacteria that reside in the human gastrointestinal tract. (Ramadan comes up a lot in published research because it provides a real-world opportunity for experts to examine the effects of 12- or 16-hour fasts, which is what many popular intermittent fasting diets espouse.)

“We really wanted to know what intermittent fasting does to the body,” says Dr. Maikel Peppelenbosch, a member of that research team and a professor of gastroenterology at Erasmus University Medical Center in the Netherlands. “Generally, we’ve seen that intermittent fasting changes the microbiome very clearly, and we view some of the changes as beneficial. If you look at fasting in general, not only Ramadan, you see certain types of bacteria increasing.”

When Butyrate Levels are high cancer risk is low.
For example, he says that intermittent fasting pumps up the gut’s population of a family
of bacteria called *Lachnospiraceae*. “In the intestines, bacteria are constantly battling for ecological space,” he explains.
Unlike some other gut microorganisms, *Lachnospiraceae* can survive happily in an empty GI tract. “They can live off the slime the gut makes itself, so they can outcompete other bacteria in a fasting state.”
*Lachnospiraceae* produces a short-chain fatty acid called butyrate, which seems to be critically important for gut health. Butyrate sends anti-inflammatory signals to the immune system, which could help reduce pain and other symptoms of gut dysfunction.

Butyrate also improves the barrier function of the intestines,
Peppelenbosch says. This is, potentially, a very big deal.
Poor barrier function (sometimes referred to as “leaky gut”) is a hallmark of common
G.I. conditions, including inflammatory bowel disease. If intermittent fasting can turn down inflammation and also help normalize the walls of the GI tract, those changes may have major therapeutic implications.

Lachnospiraceae is only one of several types of helpful bacteria that research has linked to fasting plans. But at this point, there are still a lot of gaps in the science. Peppelenbosch says the guts of people with bowel disorders don’t seem to respond to fasting in exactly the same way as the guts of people without these health issues. “In ill people, we see the same changes to the microbiome, but it’s not as clear cut as in healthy volunteers,” he says. “So we are now actually trying to figure out what’s going on there.

”Healthy microbiome shifts aren’t the only possible benefits that researchers have linked to intermittent fasting. UCLA’s Mayer mentions a phenomenon called the migrating motor complex. “This is rarely mentioned in fasting articles today, but when I was a junior faculty it was one of the hottest discoveries in gastroenterology research,” he says. The migrating motor complex refers to recurrent cycles of powerful contractions that sweep the contents of the gut, including its bacteria, down into the colon.

“It’s this 90-minute recurring contractile wave that swoops down the intestine, and its strength is comparable to a nutcracker,” he says. Essentially, this motor complex behaves like a street-cleaning crew tidying up after a parade. It ensures the gut is cleared out and cleaned up in between meals, via 90-minute repeating cycles that fasting allows to become more frequent. It also helps rebalance the gut’s microbial populations so that more of them are residing in the colon and lower regions of the GI tract. “But it’s stopped the minute you take a bite—it turns off immediately,” he says.

Mayer says that modern eating habits—so-called “grazing,” or eating steadily throughout the day—leave little time for the migrating motor complex to do its thing. “This function has been relegated to the time when we sleep, but even this has been disrupted because a lot of people wake up in the middle of the night and snack on something,” he says. “So those longer periods of time when we’re-cleanse and rebalance our gut so that we have normal distributions of bacteria and normal population densities—that has been severely disturbed by these lifestyle changes.

”Ideally, Mayer says people could (for the most part) adhere to the kind of time-restricted eating program that allows a full 12-to-14 hours each day for the motor complex to work. “If you don’t snack, this motor complex would happen between meals, and you’d also get this 12- to 14-hour window at night where the digestive system was empty,” he explains.
In other words, sticking to three meals a day and avoiding between-meal bites (or nighttime snacks) could be sufficient. But again, it’s not clear whether this sort of eating schedule can undo gut damage or treat existing dysfunction.

**Read More:** *The Truth About Fasting and Type 2 Diabetes*

**More potential benefits.**
Another possible perk of fasting involves a biological process called “autophagy.”
During autophagy, old or damaged cells die and are cleared away by the body.
Some researchers have called it a helpful housekeeping mechanism, it occurs
naturally when the body goes without energy (calories) for an extended
period of time.

There’s been some expert speculation, based mostly on evidence in lab and animal studies, that autophagy could help strengthen the gut or counteract the types of barrier problems seen in people with IBD. But these improvements have not yet been demonstrated in real-world clinical trials involving people.

Meanwhile, some experts have found that fasting may help recalibrate the gut’s metabolic rhythms in helpful ways. “By changing the timing of the diet, this will indeed change activity of the microbiome, and that may have downstream impacts on health,”
says Dr. Eran Elinav, principal investigator of the Host-Microbiome Interaction Research Group at the Weizmann Institute of Science in Israel.

Some of Elinav’s work, including an influential 2016 paper in the journal Cell, has shown that the gut microbiome undergoes day-night shifts that are influenced by a person’s eating schedule, and that lead to changing patterns of metabolite production, gene expression, and other significant elements of gut health. “If you change the timing of diet, you can flip the circadian activity of the microbiome,” he says. This is likely to have health implications, though what those are, precisely, remains murky.

**Read More:** *What We Know About Leaky Gut Syndrome*

**Fasting isn’t going anywhere.**

It’s clear that when you eat, including how often you eat, matters to the health of your gut. But the devil’s in the details. At this point, it’s not clear how intermittent fasting can be used to help people with gut-related disorders or metabolic diseases.

“For a condition like IBD, it’s important to differentiate between what you do during a flare and what you do to prevent the next flare,” Mayer points out. The research on people observing Ramadan suggests that, at least during a flare, fasting may make a person’s IBD symptoms worse. Figuring out whether fasting could also lead to longer-term improvements is just one of many questions that needs to be answered.

While plenty of unknowns remain, experts say that common approaches to fasting appear to be safe for most people. Time-restricted eating, for example, involves cramming all your day’s calories into a single six-to-eight-hour eating window. Even among people with metabolic diseases such as Type 2 diabetes, research suggests that this form of fasting is safe, provided a person is not taking blood-glucose medications.

That said, there simply isn’t much work on intermittent fasting as a treatment
for gut problems. Also, there is very little research on more extreme forms of fasting,
such as plans that involve going without calories for several days at a stretch.

These diets may turn out to be therapeutic, but they could also turn out to be dangerous.
If you’re considering any of these approaches, talk with your health care provider first.

“We really need much better studies to compare all the different fasting protocols,”
says Peppelenbosch. “But generally speaking, increasing the space between calorie consumption is a good thing for you. The body is not made to be eaten all day.”

Top Doctor: If You Eat Oatmeal Every Day, This Is What Happens BY GUNDRY MD – Search (bing.com)

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What Percentage of Americans Are Vegetarian

Posted on March 27, 2023 by Ken

What Percentage of Americans Are Vegetarian?
BY ZACH HRYNOWSKI

WASHINGTON, D.C. — According to a 2018 Gallup poll, 5% of U.S. adults consider themselves to be vegetarian.
Nonwhite Americans (9%) are three times as likely as white Americans (3%) to describe themselves as vegetarian.
11% of self-identified liberals identify as vegetarian, compared with 2% of conservatives and 3% of moderates.
Vegetarianism is less prevalent among older Americans: 2% of adults aged 55 and older say they adhere to a vegetarian diet, compared with 8% of 18- to 34-year-olds and 7% of 35- to 54-year-olds.

U.S. Adults Identifying as Vegetarian
In terms of your eating preferences, do you consider yourself to be a vegetarian, or not?
Though plant-based diets and meat alternatives have been featured in some recent high-profile forums, including the United Nations and Democratic presidential debates, and are becoming a staple even on fast food restaurant menus, the percentage of vegetarians has remained stable over the past two decades. A 1999 Gallup survey that asked the same question found that 6% of Americans identified themselves as vegetarian.
Gallup periodically measures vegetarianism in the U.S. as part of its July Consumption Habits poll — one of 12 surveys that make up the Gallup Poll Social Series.
*Gallup’s full trend on vegetarianism is available on the* *Nutrition and Food “Topics A to Z” page*.
*Explore Gallup articles about vegetarianism and other food-related topics on the* *“Health Habits” page*.
*Hrynowski, Z What percentage of Americans are vegetarians – Search (bing.com)*

U.S. Adults Identifying as Vegetarian – Bing images

Dear Dietitian:

LEANNE McCRATE, RD, LD, CNSC, is an award-winning dietitian with more than
17 years of clinical experience in the hospital setting. Her mission is to educate the
public on sound, evidence-based nutrition. Do you have a nutrition question?
Email her at DearDietitian411@gmail.com.

Dear Dietitian does not endorse any products, health programs or meal plans.
By now, you probably know someone who has adopted a vegetarian diet. Estimates put vegetarianism at around 5% of the American population. That may not sound like many, but it comes to roughly 16.5 million. People cite different reasons for converting to vegetarianism, from better health to environmental factors to better treatment of animals.
There are various types of vegetarians, but all base their diets on plant foods.

1. Vegans eat only plant foods.
2. Lacto Vegetarians do not eat red or white meat, fish or shellfish but drink milk and consume cheese and yogurt.
3. Lacto-ovo vegetarians do not eat red or white meat, fish or shellfish but enjoy milk, eggs, cheese, and yogurt.
4. Pescatarian are sometimes considered semi-vegetarian or flexitarian. This group eats fish and shellfish but abstains from red and white meat. Some pescatarians consume milk products and eggs, while others do not.
5. Flexitarian are vegetarians that cheat. No, really, these are people who are in the process of going vegetarian and, on occasion, will eat a meat product.
If you are considering vegetarianism, it may be wise to do some meal planning to get all the nutrients needed for good health. Below are some essential nutrients to consider:
1. Iron is needed to take oxygen to our cells. But have no fear; it is abundant in lentils and leafy greens. Vitamin C aids in iron absorption, so have oranges available.

2. Calcium is needed for strong bones. Our bodies stop building bone between the ages of 18 and 21, making it essential to obtain this nutrient in your diet every day. Plant sources include fortified soy, almond, and rice milk. Be sure to check the label, as not every product is calcium-fortified. You also can get calcium in certain vegetables, like broccoli and bok choy.
3. Vitamin D is needed to lay calcium to the bone and aids in immune health. Our bodies have the capacity to make this vitamin, but it requires consistent sunlight exposure. Keep in mind the sun is also the leading cause of skin cancer, so choosing fortified foods may be a better option. These include plant-based milk, orange juice and breakfast cereals.
4. Vitamin B12 is needed for the proper functioning of the nervous system and in the production of red blood cells. The most reliable source of B12 for vegans is found in fortified foods. However, it is also in dried purple laver, a type of seaweed.
In today’s market, several meat substitutes are fortified with some of the nutrients mentioned above. Again, be a label reader. Of course, there are vitamin and mineral supplements. If you choose this route, be sure to purchase a supplement with USP on the label. USP stands for United States Pharmacopeia, a nonprofit group that tests supplements to be sure they contain what the label claims and can be absorbed by the body.
Until next time, be healthy!

New Study Shows Veganism is up by 300% in US With 9.7 Million Americans Now Plant-Based

Image supplied by Ipsos

A new study exploring the explosion of veganism in the USA shows that the number of Americans following plant-based diets is up nearly 9.4 million over the last 15 years. The research also reveals through an interactive map which states are the most popular for veganism.

The study, conducted by Ipsos Retail Performance reveals how veganism and plant-based diet interest has changed across the US, comparing differences in state-by-state adoption throughout a 15 year period. It shows that over 9.7 Million Americans now follow plant-based diets, increasing from just 290,000 15 years ago.
Illustrated through an interactive timeline and map charting search data between 2004-2019, findings include:
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The **most consistently ‘vegan’ state** is Oregon, achieving the highest search value for 12 years out of 15. This is followed by Vermont, Washington and California.
The **state which is most reluctant to seek out vegan trends** (and therefore the biggest meat-eaters) is Mississippi, followed by South Dakota, Alabama and North Dakota.
**Political leanings correlate with how vegan each state is**, with the top 10 biggest vegan states all largely Democrat voters, and the 10 lowest vegan states all largely Republican.
The **states seeing the biggest change in attitudes** include Nevada (38 point increase in vegan searches) and New Hampshire (31 point decrease in vegan searches).

ipsosThroughout the period covered in the research, the North Eastern and West Coast states

Showed the earliest interest in veganism. More states followed suit in 2013, where there was a significant increase in interest-driven by high profile awareness driven by celebrities and the increased availability of meat alternative products in stores and restaurants.
Commenting on the map, Kelly Fairchild, global business development manager from Ipsos Retail Performance said:
“Plant-based diets are fast becoming mainstream, but the change hasn’t been a steady one. Recent years have seen rapid adoption of vegan diets and more meat-free products making their way onto shelves. As the dialog around veganism shifts from one of animal welfare, to wider concerns around climate change and personal health, we are seeing more and more people adopt this once minority dietary preference.

The full timeline and interactive map is available at the following link:
https://www.ipsos-retailperformance.com/en/vegan-trends/

Vegetarianism and Veganism Demographics | Veggin’ Out (wordpress.com)

HOW BEYONCE’S VEGAN DIET CHANGED MY LIFE – Steve Harvey – YouTube

PBFA’s ‘State of Food Service’ Report Finds 62% Growth of…February 9, 2023
US Plant-Based Sales Smash $7.4Bn as Conventional Dairy…March 24, 2022
Peer Reviewed Paper Proves Plant-Based Meat is Healthier and…July 28, 2022
New PBFI/Kroger Report Shows Health Remains Top Purchase…December 1, 2022
New Study Reveals Consumer Preferences for Plant-Based…May 13, 2022
Moby Endorses Plant-Based Treaty Campaign Demanding Overhaul…September 1, 2021
Getting necessary nutrients in a vegetarian diet Leanne McCrate – Search (bing.com)
What If D-Day Failed? | Alternate History – Bing video

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Ruination 0f Creation

Posted on March 27, 2023 by Ken

The theory of evolution is a shortened form of the term

“Theory of evolution by natural selection,” which was proposed by Charles Darwin and a scientific contemporary of his, Alfred Russel Wallace, proposed that evolution occurs because of a phenomenon called natural selection.

This Blog Post: Written in Abstract to get you to think straight.

In the theory of natural selection, organisms produce more offspring than are able to survive in their environment. Those that are better physically equipped to survive, grow to maturity, and reproduce. Those that are lacking in such fitness, on the other hand, either do not reach an age when they can reproduce or produce fewer offspring than their counterparts. Natural selection is sometimes summed up as “survival of the fittest” because the “fittest” organisms—those most suited to their environment—are the ones that reproduce most successfully, and are most likely to pass on their traits to the next generation.
Ideas aimed at explaining how organisms change, or evolve, over time date back to Anaximander of Miletus, a Greek philosopher who lived in the 500s B.C.E. Noting that human babies are born helpless, Anaximander speculated that humans must have descended from some other type of creature whose young could survive without any help. He concluded that those ancestors must be fish, since fish hatch from eggs and immediately begin living with no help from their parents.
From this reasoning, he proposed that all life began in the sea.

Anaximander was correct; humans can indeed trace our ancestry back to fish. His idea, however, was not a theory in the scientific meaning of the word, because it could not be subjected to testing that might support it or prove it wrong. In science, the word “theory” indicates a very high level of certainty. Scientists talk about evolution as a theory, for instance, just as they talk about Einstein’s explanation of gravity as a theory.
A theory is an idea about how something in nature works that has gone through rigorous testing through observations and experiments designed to prove the idea right or wrong. When it comes to the evolution of life, various philosophers and scientists, including an eighteenth-century English doctor named Erasmus Darwin, proposed different aspects of what later would become evolutionary theory.

But evolution did not reach the status of being a scientific theory until Darwin’s grandson, the more famous Charles Darwin, published his famous book On the Origin of Species.
This means that if an environment changes, the traits that enhance survival in that environment will also gradually change or evolve.
Natural selection was such a powerful idea in explaining the evolution of life that it became established as a scientific theory. Biologists have since observed numerous examples of natural selection influence evolution.

Today, it is known to be just one of several mechanisms by which life evolves. For example, a phenomenon known as genetic drift can also cause species to evolve. In genetic drift, some organisms—purely by chance—produce more offspring than would be expected. Those organisms are not necessarily the fittest of their species, but it is their genes that get passed onto the next generation.

The Edomites were descendants of Esau, the twin brother of Jacob and grandson of Abraham. This family tie should have incited compassion for Israel’s plight; instead.

It made Edom’s actions even more repulsive, since they were opposing not only God’s chosen people but also their own relatives.

(1) The Daily Caller – Posts | Facebook

There is a few time stamps included in this article attributed to the above video.

It’s been about 10 years now that the zombie apocalypse has been ‘mainstream’. Of course, the big spike in popularity can probably be directly linked to The Walking Dead, which premiered back in 2010. Well, the zombie apocalypse is not popular enough that 11% of people have some sort of plan if things were to ever go sideways on us. Well, at least 1 in 10 Brits have a plan. I’m not 100% sure about Americans because the study from YouGov was done by those who were probably a little more freaked out by 28 Days Later.

Here are some of the plans that people have in case of a zombie apocalypse:

45% of people who have a plan said they would find a good place to hole, where it’s hard for zombies to get to you.
43% said to gather supplies like food, water, and first aid stuff.
29% would relocate, especially if they’re in a big city with lots of potential zombies.
23% said they’d find weapons. Of course in Texas, you should already have yours.
Just 15% would meet up with family members and close friends.
13% of people would go Woody Harrelson and just start killing zombies. There were even a few psychos who said they’d kill survivors too. Negan…
And in a sign of people not trusting others, only 6% of people would team up with other random survivors. There were even 9% of people who didn’t want to share their plan.

This is so sad we have to do better as a human race. This is tragic!
If you are a parent and have a child who has gone this way. It’s heartbreaking to see all these videos of people’s children and how our society has not done anything to help save these people from killing themselves. Ask yourself why there is such a need to escape reality? Why are so many people falling this way? More people have died from these drugs than from Covid.
This is tragic! If you are a parent and have a child who has gone this way. It’s heartbreaking to see all these videos of people’s children and how our society has not done anything to help save these people from killing themselves. Ask yourself why there is such a need to escape reality? Why are so many people falling this way?

More people have died from od than from Covid. W.t.h.

Why is it society’s fault if these people want to continue to make bad choices after bad choices? At what point do these individuals take ownership and responsibility for the direction their life has taken. The people who laugh at these homeless people should all be ashamed of themselves. Obviously, they’ve had past traumas or something similar, that’s led them to use drugs in the first place. We don’t know why they’re in the situation they’re in.
Also, these are people who have had people who have loved them and probably, although unsure of what can be done to help, still do. They’re someone’s child, or mother, or sibling. Pray for them instead of laughing at them. We never know what struggles others are going through, and there’s really no guarantee that any of us will always have a home or family. This is so heartbreaking to see.

Everyone has past trauma. They should grow tf and be adults. don’t even have to be a good one. Just stop being the shittiest kind of human. I’m not interested in their whiney excuses about why they decided to be a worthless drain on society. The people who deserve to be laughed at are all the voters who endorse the idiotic, woke and corrupt politicians who are directly responsible for all of this. Those mayors are power-hungry minions of the WEF who are more concerned with the prestigious policies of smart cities and climate change than actually doing their f…g jobs.
Sadly, it is EVERYWHERE within small and big cities. They have the money to get high but not to buy their food. Getting high is their priority rather than addressing their hunger. Can’t understand why anyone laughs at this… it’s horrific… These people need help not ridicule! This is what a failed, corrupt government looks like. Saddens me to see, because these people are a reflection of who we are as a country.

Mirror: Wifi, Microwaves and the Consequences to our Health – Barrie Trower (bitchute.com)

Hey CNN – why not report on Crown Castle – the chinese owned company that OWNS the most cell towers in the United States & sublets them to the phone companies to put the wonderful MICROWAVE TRANSMITTERS at ground level. Assuring a microwave flu directed by — china. see a problem folks? Wake the others & share – we are treating & teaching those already sick from the microwaves who have not moved out of these areas. Global impact 5 Largest Companies in Taiwan investopedia.com)
If China decides to invade Taiwan , America can do nothing to stop it. Putin has taken on the whole of the west and is winning this latest American war. NATO and America will be going away, tail between the legs, another Afghanistan looming up. They picked a wrong run with Putin, because he can lay waste to America, not like all the other banana republics America have run roughshod over who could not bomb American soil. Keep poking away at Putin and America will know what a real war is. China will do the same, American dominance is finished. #Barrietrower #5gmicrowaves #covid #animals #usa #ukraine #radiation #patriots #biden #trump
#Chinas days are numbered; this hell hole will be decoupled. The #marxistdemocrats have been exposed for being agents of an enemy that’s hell bent on trying to destroy America from within. Might quite the understatement, we have China aligned with Russia we have Honduras aligned with China how much closer to the USA can you get. This administration is collapsing us internationally beyond repair. Wake up and put the cell phone down #FUBAR. (bing.com) Dummies!!!

Keep voting blue, Eve of Destruction – Barry McGuire – Bing video

This street in PA is in a neighborhood called Kensington. There is a newer ingredient that they’re cutting the heroin with called Xylazine. It’s an anesthetic that is made to use in animals. It’s more addictive than fentanyl but the high only lasts about 2-3 hours, where the normal cut is usually 6-8 hours. It’s eating through the skin as well and so many ppl walking around with open wounds.
It’s called “Tranq”. Bar and is ineffective as well as it’s not an opioid. Same class of cut with Ketamine. I pray for our world’s mental health crisis as well because this drug is pushing people over the edge. I’m so sorry to see these homeless people. It’s not their fault. It’s the government’s fault for allowing all types of drugs into the country.

It was the pharmaceutical companies that got them addicted in the first place. Read a book. Stop blaming others, these people have to take responsibility for their healing. Everyone experiences trauma, they need the resources to overcome their addictions.

I agree; however, people do need to accept responsibility for their choices.

It’s 100% their fault. Take responsibility for their actions.

It’s my personal responsibility! That’s that! Just say no to drugs!!
We are really living in barbaric times!!!

This is just pathetic that this is even happening…so much for politicians who are supposed to be working for the people…God have mercy on your souls to let this happen…Kensington and Allegheny in Philly! Smh! Failed Society……..poor leadership, poor morals, lack of awareness, and decay all over, this is the new norm in the cities….This video needs to be played in our schools. Prevention is better than cure. Heartbreaking!!!

What is happening in the world today it’s just terrible. Where is our governor? Why is he letting this happen? We need to open up metal hospitals for these poor people to get help. Are the higher ups getting paid from drug cartels this should not be happening in PA.

This is heartbreaking ….
So let’s keep sending our tax payers money to Ukraine and other countries instead of getting help for these people. Addiction is a powerful disease and destroys too many lives. Not a political debate please we all bleed red. #fuckaddiction #theyneedhelp
I blame Biden and his administration for this, they aren’t doing a thing about letting the drugs pass through our borders. Worst president ever!! How do they get the drugs from whom… is anyone getting arrested…it looks like they are just letting it happen. Some of these states have decriminalized it. So u can get arrested but then released quickly once you sober up.

Your government leaders love this so much they allow this but are you?! The results speak for itself…This is a sad commentary of the world in which we live. You can go to jail for drinking in public but is this ok? The government needs to step in and assist these individuals with help, hospitalization, and rehab. They are a danger to themselves and others . People just love taking drugs, that’s why it’s a billion dollar business.

No these aren’t zombies, these are just people that lost their way.

They need God in their life to brighten up their day, their people who couldn’t take life anymore so they are in a very strong substance. Someone needs to film the San Francisco zombies. The government supplies the drugs and needles, thinking they are actually helping.
This is what happens when you close all the Lunatic Asylums; we need to start building Asylums for these people; They will have a bed, food and medical assistance; And eventually be able to get weaned off drugs and put back to live a life; I’ve watched enough zombie movies to be seriously creeped out.

Demonic possession of lost souls so, so sad

They're Not After Me, They're After You. I'm Just In The Way Trump Meme ...

CHINA has won the WAR in the USA, we’re next

The enemy has weaken the US

Our country has gone into a scary place! This isn’t funny, it is disgusting. All States are seeing more of this everyday. Gotten worse in the Democrats’ cities. Blue run cities predominantly. That’s why we need more mental hospitals! Well Democrats infected States and cities, what else can you ask for,.

These cities just encourage drug use! Free injection sites. Free needle exchange. Stop voting Democrat and you could stop this! The same enemy is on both sides of the aisles democratic or republican. Nope, it’s [not] the same enemy. Not at all. Republicans are for law and order. They don’t defund the police. Democrats create this chaos. Period. Mostly blue cities are behind this. Not hard to see how easily the Western world has been destroyed. Drugs are way easier than bullets.

This is what progressive America looks like.

The Democrat party are enablers.

They have created this mess and have allowed it to go unchecked and out of control. Zero accountability. The tax paying citizens that voted these progressives in are to blame. Our tax dollar waste don’t forget this administration is handing crack and pipes along with needles to these ppl unbelievable

LIBERALISM…. FIND a CURE!!

Sadly Democrat America, if you voted for them this is what you get.

Is America better under these liberal idiots?
So sad. So scary. So uncontrollably disgusting. All of these people are missing from themselves. North America has dropped the ball big time with mental health and addiction active or recovery there is nowhere near enough support but 1 million ways they are “allowed” to continue to traumatize themselves and others.

Bidens America
It’s not zombies. It’s drugs and mental illness. Welcome to Democratic control America, this is what they want you to be. Calling this Zombie Apocalypse is just ignorant and cruel…Addicts need help and concern NOT name calling….Looks like California
so much crime and so many strung out just wandering the streets doing whatever they want with little to no consequences. Instead here, our government hands out clean needles so people can shoot up on the streets safely.

Or it could be syphilis. A lot of homeless use dirty needles , they do everything unprotected. I too am in the addiction field and a director in PA and a recovering addict-it’s not syphilis its Fentanyl and Tranq-maybe some flakka for the more energetic ones. You are perpetuating a stigma through stupidity and lack of education.

That is Flakka !Opiates will NOT have you doing this ..for the past 8 1/2 years of being clean and helping all kinds of addicts I can promise you this is NOT anything opiates will do John Schroeder
Imagine bath salts turned out to be the new zombie virus
Tranq and Flakka are the latest Zombie Drugs out there. People start paying attention. This is a drug where you have no control of your body. Kingston Pennsylvania is the worst city known for this and has spread quickly to the West.https://youtu.be/xmfrvs24NmY

Sadly, I can’t believe that it’s happening in the USA, the Dreamland, aiming for the USA is so not worth it, the nation has completely given up on these people … And to see that those people enjoy watching those victims at their lowest… It’s sick and twisted…This is your punishment for all that you have done evil around the world! You will destroy yourself, you only need to be isolated from the whole world!
Just people taking advantage of cheap available drugs thanks to the help of the Biden sick open border policy. They all want to be like Joe. So, this zombie apocalypse which everyone fears; how will you know when it’s actually started?

Whaaaat how did those people get the drugs if it’s illegal!

Gahhhhh can’t believe they aren’t following the law! If only there’s harsher drug laws to prevent this stuff!
This is not compassionate, letting people live like this is inhumane. These poor people need to be in psych hospitals & cared for…Stop saying “zombie” these people are clearly on drugs and need clinical help … nothing funny about bothering them , it could be dangerous too. this is because the $Rich$ sent all the work over sea because $MILLION$ wasn`t enough ..They left know hope for Americans, wanting to HATE someone HATE THE RICH .

I heard that China is the supplier of the fentanyl……That is what the ‘combo’ is doing.

Tr and Fe. Sad. Drugs just take over.

You can’t stop. Drugs and danger are synonymous.
I can’t believe this is the USA it really cannot be like that in America
This is the other side of Amerikkka that the USSA media never shows to US people.
Dumbing down America fully shown at its best, America can’t think they seem to think they are the best voters so very sad. Even though we know there’s an epidemic we shouldn’t laugh at this video because these are someone’s children, mothers, fathers, aunts, uncles, brothers and sisters.
We should look at this as a way of wanting to stop the epidemic and help those who need help. At 1:22 the Know Overdose sign…Natural selection: Illegal drugs mess with people’s mind and soul, the government needs to get on top of this foolishness. The Democrat’s plan is to destroy our cities. Obama’s and Biden’s America! Elections do have consequences it seems.
Haven’t we had a homelessness and drug problem for a while? Don’t think it’s a president thing, think it’s us not wanting to actually handle it. We don’t even talk about plans on fixing it, just say what we think we need. That’s just my view on it though, we can definitely fix a lot of problems just no one’s really doing much.

An Atheist would smugly retort “Well that’s because people don’t run around believing in faeries and Unicorns anymore.” thinking he’s won the argument. In reality he just exposed the true agenda of Atheism, to convert others to their belief system. Just like any other religion.

Trust in the LORD with all your heart, and do not lean on your own understanding. In all your ways acknowledge him, and he will make straight your paths. Be not wise in your own eyes; fear the LORD, and turn away from evil. It will be healing to your flesh and refreshment to your bones… My son, do not despise the LORD’S discipline or be weary of his reproof, for the LORD reproves him whom he loves, as a father the son in whom he delights. Proverbs 3:5-8,11-12 God is the very definition of wisdom and holiness and purity and righteousness. May we always look to Him and Him only for direction in our lives.

Is it fair to your conscience the way you are treating U.S.?
Sweet Jesus please come soon!

I definitely agree it is a left wing problem… Red states don’t have this problem unless they have some woke mega city run byDemocrats inside of them like Chicago. This is Edomites America that’s burning Babylon way before Obama & Biden. What is dis you called edomites what this means??.
Dear Jesus.
All made possible by the Democrats!
AOC’s district is like this, right? What a disgrace….Huh, looks like Downtown Seattle nowadays!!! Sad times we’re living in!!
China loves every moment of this….Unfortunately this is the calm before the storm- when people can find bullets easier than food will be the start. This isn’t the zombie apocalypse, it’s the drug pandemic. Who cares let Darwin’s Theory take hold…
The zombies are always starving and looking to eat
1 Peter 5:8 – Be sober, be vigilant; because your adversary the devil, as a roaring lion, walketh about, seeking whom he may devour:Ephesians 6:11-12 – Put on the whole armour of God, that ye may be able to stand against the wiles of the devil.  Fentonal kills..there on death’s doorstep  1:48 – 1:52
This is why Mental Asylum’s NEED to come back to America, some of these people are too dangerous to others to be allowed to just roam around in public freely!! Legalize drugs they said. It’ll be safe, they said. They’re harmless, they said. It’ll be fun, they said. We can make money on it, they said.  Cocaine and meth I actually kinda get. You have lots of energy. You can party all night. Nothing about heroin or it’s evil twin, fentanyl,  laced with tranq looks fun. They’re going to start doing things like on the Living Dead, putting them out of their misery, you can’t fix people like this
It crossed the border illegally but Biden says look the other way…………… Liberal democrat heaven to destroy America.
These new drugs the zombies are taking are the scariest drugs available right now and even scarier that the new drugs are hitting many cities across our country coming through all our open borders including state borders cartels are welcome & even get paid along with the illegals, it’s called drug addiction that is trendy and all so liberal. I’ve had Resident Evil 4 pre ordered for weeks and they just get it early?
Democratic run filthy cities: This is awful all these people are sick and need help. The same enemy is on both sides of the aisles, democrats or republicans don’t you know that but the enemy’s reign is just about over. I’m thanking God. behind the scenes, yes. But a good percentage of the rank and file Dems are in perfect lock-step with the agenda. So, that is who I was “thanking” . It’s entertaining. Better than the boring ‘burbs.

Men, women and children these Zombies at one time were college students and hard working middle class people because of pandemic loss of jobs and housing , vehicles repossessions now they don’t have transportation to get to and from work the once successful people of our country are homeless drug addicts disease like hepatitis is spreading like wildfire. Biden still refuses to close our borders. This is what the Democrats want you to be living like.. If they cared about Americans at all they would close the border. The drugs are pouring through America killing Americans. God Bless America.