Verapamil can preserve beta cell function in Type 1 diabetes

 In 2012, University of Alabama at Birmingham researcher Anath Shalev, M.D., reported that a decades-old blood pressure medication called verapamil completely reversed diabetes in animal models.

In 2018, the team had translated these findings into a randomized, controlled, clinical trial, demonstrating significantly improved beta cell function for one year in human subjects with recent onset type 1 diabetes. By last year, in a small follow-up study, Shalev and colleagues had found that adult type 1 diabetes patients taking oral verapamil required less daily insulin and showed evidence of beneficial immune modulation for as long as two years after first diagnosis.

Now UAB researchers, led by Guanlan Xu, Ph.D., and Shalev drilled down further into the mechanism underlying verapamil's beneficial effect. In a paper published in Diabetes, they show that, in type 1 diabetes patients, verapamil prevented the decline of the hormone insulin-like growth factor 1, or IGF-1, as compared to controls who did not take verapamil. They also found that verapamil promotes IGF-1 signaling in pancreatic beta cells.

Type 1 diabetes is an autoimmune disease that causes loss of the pancreatic beta cells that produce insulin. To replace that insulin—the hormone that helps control blood sugar—patients must take exogenous insulin by shots or a pump and are at risk of dangerous low blood sugar events. There is no current oral treatment for this disease.

Besides Shalev's adult study, a recent independent study of children with type 1 diabetes has also confirmed that verapamil preserves beta cell function, compared with children not taking verapamil.

In the Diabetes study, Xu, Shalev and colleagues did a global proteomics study analysis of serum samples from Shalev's adult study both at baseline and at one year of receiving verapamil or a placebo. They found 59 proteins showed significant changes in abundance over time, and one of the top five differentially changed proteins was IGF-1. The placebo group showed a significant decline of IGF-1 from baseline to one year, but that decline was blunted in the verapamil group.

Others have found that serum IGF-1 correlates with residual beta cell function, a correlation the UAB researchers also found for the verapamil group, as measured by retention of the ability to produce endogenous insulin by the beta cells that are located in pancreatic islets.

RNA sequencing of samples of human pancreatic islets treated with or without verapamil showed that the expression of four IGF binding proteins was significantly decreased by verapamil. Such a decrease in proteins that bind to IGF-1 should allow IGF-1 to interact with its IGF-1 receptor. Binding of IGF-1 to the receptor initiates the IGF-1 signaling pathway that alters gene expression inside the beta cell. As a measure of increased signaling, the researchers indeed found that verapamil did activate the IGF-1 receptor and its downstream effector, AKT, as measured by increased phosphorylation of both.

In contrast, in human islets that were treated with type 1 diabetes-associated inflammatory cytokines, as well as islets from a mouse model of type 1 diabetes, researchers found significantly increased expression of IGF binding protein 3, which is the most abundant of the IGF binding protein family. These results suggest that islet expression of IGF binding proteins is upregulated under type 1 diabetes conditions.

The Shalev team previously has shown increased beta-cell expression of TXNIP—a protein that promotes programmed cell death and dysfunction of beta cells—during diabetes. The team has also showed that verapamil inhibits beta-cell expression of TXNIP, resulting in the beneficial anti-diabetic effects. In the current study, the researchers now have shown that overexpression of human TXNIP significantly increased expression of IGF binding protein 3, while TXNIP-deficient islets had decreased expression of IGF binding protein 3. Furthermore, overexpression of TXNIP significantly decreased the phosphorylation activation of the IGF-1 receptor.

"Thus, our results reveal IGF-1 signaling as yet another previously unappreciated pathway affected by verapamil and TXNIP that may contribute to the beneficial verapamil effects in the context of type 1 diabetes," Shalev said.

More information: Guanlan Xu et al, Verapamil prevents decline of IGF-1 in subjects with T1D and promotes beta-cell IGF-1 signaling, Diabetes (2023). DOI: 10.2337/db23-0256

https://medicalxpress.com/news/2023-08-diabetes-verapamil-decline-igf-beta-cell.html

How being in space impairs astronauts' immune systems

 A new study led by researchers at Karolinska Institutet in Sweden has examined how T cells of the immune system are affected by weightlessness. The results, which are published in the journal Science Advances, could explain why astronauts' T cells become less active and less effective at fighting infection.

The next steps in the exploration of space are human missions to the moon and to Mars. Space is an extremely hostile environment that poses threats to human health. One such threat is changes to the immune system that occur in astronauts while in space and that persist after their return to Earth. This immune deficiency can leave them more vulnerable to infection and lead to the reactivation of latent viruses in the body.

"If astronauts are to be able to undergo safe space missions, we need to understand how their immune systems are affected and try to find ways to counter harmful changes to it," says study leader Lisa Westerberg, principal researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. "We've now been able to investigate what happens to T cells, which are a key component of the immune system, when exposed to weightless conditions."

In the study, the researchers have tried to simulate weightlessness in space using a method called dry immersion. This involves a custom-made waterbed that tricks the body into thinking it is in a weightless state. The researchers examined T cells in the blood of eight healthy individuals for three weeks of exposure to simulated weightlessness. Blood analyses were performed before the experiment started, at seven, 14 and 21 days after the start, and at seven days after the experiment ended.

They found that the T cells significantly changed their gene expression—that is to say, which genes were active and which were not—after seven and 14 days of weightlessness and that the cells became more immature in their genetic program. The greatest effect was seen after 14 days.

"The T cells began to resemble more so-called naïve T cells, which have not yet encountered any intruders. This could mean that they take longer to be activated and thus become less effective at fighting tumor cells and infections. Our results can pave the way for new treatments that reverse these changes to the immune cells' genetic program," says Carlos Gallardo Dodd, Ph.D. student at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet and shared first author with researchers Christian Oertlin and Julien Record at the same department.

After 21 days, the T cells had "adapted" their gene expression to weightlessness so that it had almost returned to normal, but analyses carried out seven days after the experiment ended showed that the cells had regained some of the changes.

The researchers now plan to use Esrange Space Center's sounding rocket platform in Kiruna, Sweden, to study how T cells behave in weightless conditions and how their function is affected.

The study was conducted in close collaboration with Claudia Kutter's research group at Karolinska Institutet/SciLifeLab and collaboration partners at IBMP Moscow and New York University Abu Dhabi.

More information: Carlos Gallardo-Dodd et al, Exposure of volunteers to microgravity by dry immersion bed over 21 days results in gene expression changes and adaptation of T cells, Science Advances (2023). DOI: 10.1126/sciadv.adg1610. www.science.org/doi/10.1126/sciadv.adg1610

https://medicalxpress.com/news/2023-08-space-impairs-astronauts-immune.html

'American study estimates 1.87 m excess deaths in China 2 months after zero COVID policy ended'

 A pair of public health researchers at the Fred Hutchinson Cancer Research Center's Public Health Sciences Division, in Seattle, Washington, working with two independent colleagues, has found that in the two months after China halted its zero COVID policy at the end of 2022, 1.87 million excess deaths occurred in that country.

In their study, reported in JAMA Network Open, the group used obituary data from three Chinese universities along with other data obtained using the Baidu search engine regarding deaths in China likely due to COVID-19.

During the initial phase of the COVID-19 pandemic, deaths from the disease were remarkably lower in China than in other countries. This was due, it is believed, to officials in China enacting a program called the zero COVID policy that placed tight restrictions: People were ordered to quarantine, and authorities enacted a program of regular testing, closed many workplaces and schools and instituted mandatory mask policies.

Such restrictions took a tremendous toll on the Chinese economy, and the government eased restrictions, finally doing away with the zero COVID policy in December 2022. Two months later, the Chinese government reported that approximately 60,000 people had died from the disease up to that point. In this new effort, the research team took another route to assess the Chinese death tally following the lifting of the zero COVID policy.

As has been done in the U.S. and other countries by other teams, the researchers ignored figures cited by official government agencies regarding the number of people that died of COVID-19 over the course of the pandemic. Instead, they analyzed excess deaths derived from sources listing the number of people who died over a given period of time and comparing those numbers against the same period of time in other years. The difference, they suggest, is likely due to COVID-19 deaths categorized as something else.

In this new effort, the research team obtained data published by three universities in China and also used data found using the Baidu search engine for deaths of people over 30 by any cause in the areas where the three universities were located. They used math techniques to estimate deaths across the whole country for the two months following cessation of the zero COVID policy—it came to approximately 1.87 million excess deaths.

More information: Hong Xiao et al, Excess All-Cause Mortality in China After Ending the Zero COVID Policy, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.30877

https://medicalxpress.com/news/2023-08-american-million-excess-deaths-china.html

The State Protects Itself While Crime Against Ordinary People Surges

 by Ryan McMaken via The Mises Institute,

In all the media and regime frenzy over the January 6 riots and the Pentagon Leaker in recent months, it is interesting to examine the contrast between how the regime treats "crimes" against its own interests, and real crime committed against ordinary private citizens. 

Witness, for example, how the Biden administration and corporate media have treated the January 6 riot as if it were some kind of military coup, demanding that draconian sentences be handed down even to small-time vandals and trespassers. Regime paranoia has led the Justice Department to ask for a 30-year sentence for Enrique Tarrio, a man who was convicted of the non-crime of "seditious conspiracy" even though he wasn't even in Washington on January 6. In recent months, Jacob Chansley, the "QAnon Shaman," received a sentence of three-and-a-half years, even though prosecutors admit he did nothing violent. Riley Williams was given three years for simply trespassing in Nancy Pelosi's office. Members of the Capitol Police force have been lionized in the media as great protectors of "sacred" government buildings, and any threat to the property or persons of Washington politicians has been equated with an assault on "democracy." 

Yet, had these supposed insurrectionists inflicted these same actions against an ordinary private individual, there's a good chance the perpetrators would not even be arrested, let alone given years of prison time. Consider, for example, the mobs that ransack private businesses in American cities, stealing tens of thousands of dollars of merchandise while police and prosecutors consider it all to be low priority.  Violent crime and property crime surge in many areas of the United States, with violent crime rising 30 percent in New York City in 2022. Unsolved murders in the US are at a record high. Meanwhile, progressives and social democrats are looking for ways to reduce criminal penalties against violent criminals. Police departments often devote only tiny portions of their budgets to homicide investigations, and if your property is stolen, odds are good you can forget about ever seeing it again. 

The situation is quite different when it comes to protecting the state, its agents, and its property from any threat. During urban riots, such as those which occurred in Ferguson, Missouri and Minneapolis, Minnesota, the police went to great lengths to protect themselves and government property. If you were just a private shopkeeper or ordinary citizen, however, you were on your own. At the Uvalde School shooting in 2022, hundreds of law enforcement officers from all levels of government chose to protect themselves rather than the children who were being murdered inside. When Uvalde parents demanded the police act, the police attacked the parents. 

We find similar phenomena at the federal level. There are, of course, special federal laws against violence perpetrated against federal employees. Ordinary taxpayers receive no such consideration. Note how federal agencies move to arm themselves to the teeth while also seeking to disarm the private-sector. Federal agents will spare no expense finding someone who put his feet up on Nancy Pelosi's desk, but it's another matter entirely when we're talking about serious violent crime against regular people.  Federal agents, of course, allowed 9/11 to occur right under their noses, they refused to investigate known rapist Larry Nasser, and shrugged off reports about the man who would end up slaughtering children at a high school in Parkland, Florida. Contrast this with how long the federal government has been conniving to get revenge on Julian Assange for merely telling the truth about US war crimes.  

Naturally, law enforcement officers rarely face any sanctions for their failures to bother themselves with private property, life, or limb. The federal courts have made it clear that law enforcement officers are not obligated to actually protect the public. In other words, the taxpayers must always pay taxes to hold up their end of the imagined "social contract" or face fines and imprisonment. But the other side of that "contract," the state, has no legal obligation to make good on its end. This, of course, is not how real contracts work. 

The state's fastidious devotion to protecting itself, compared to its casual concern for the safety of mere taxpayers, illustrates an important principle of state behavior. In his essay The Anatomy of the State, Murray Rothbard notes 

We may test the hypothesis that the State is largely interested in protecting itself rather than its subjects by asking: which category of crimes does the State pursue and punish most intensely—those against private citizens or those against itself? The gravest crimes in the State's lexicon are almost invariably not invasions of private person or property, but dangers to its own contentment, for example, treason, desertion of a soldier to the enemy, failure to register for the draft, subversion and subversive conspiracy, assassination of rulers and such economic crimes against the State as counterfeiting its money or evasion of its income tax. Or compare the degree of zeal devoted to pursuing the man who assaults a policeman, with the attention that the State pays to the assault of an ordinary citizen. Yet, curiously, the State's openly assigned priority to its own defense against the public strikes few people as inconsistent with its presumed raison d'etre.

This double standard has been repeatedly on display in recent years as the regime has increasingly been consumed with paranoia over threats to itself—propagandistically termed "threats to democracy"—while attention given to real crime against private citizens is apparently not a priority at all. 

https://www.zerohedge.com/political/state-protects-itself-while-crime-against-ordinary-people-surges

Democrats Have Broken America: Where’s The Outrage?

 by J. Peder Zane via RealClear Wire,

The Democrats have an ace in the hole in their relentless war on the Constitution – conservative America’s reverence for the concept of the rule of the law.

Only their steadfast commitment to this traditional ideal explains why conservatives are allowing   Democrats to flagrantly corrupt our judicial system to destroy their opponents and protect themselves. For all their huffing and puffing, conservatives have effectively taken a let the system play itself out attitude while Democrats nakedly politicize that system through their partisan indictments of former President Trump and their Potemkin Village probes of the Bidens. These are not statements of opinion. These are facts.

Part of me is glad that so many legal analysts have spilled so much ink exposing these charades. But we degrade our country and ourselves when we treat this unspeakable behavior with anything other than horrified contempt. Every good-faith critique normalizes and legitimizes this profoundly un-American conspiracy.

Viewing the obvious forest rather than the tangled trees, the cases against Trump are a continuation of the deceitful effort by Democrats and their deep state allies, especially in the DOJ, to annihilate their chief political opponent. That effort began even before his election when Hillary Clinton’s campaign manufactured false claims that Trump had conspired with Vladimir Putin to steal the 2016 election. When that sham was exposed, they almost immediately made Trump only the third president in the country to be impeached for asking Ukraine’s leader to look into the Biden family’s influence-peddling schemes. They set aside almost every rule and order of business by rushing to impeach him once again after the Jan. 6 attack on the Capitol. While that was going on, Democrats insistently rained down other bogus concerns – that he was violating the Emoluments Clause because wealthy foreigners continued to stay at his hotels, that his alleged mental instability made him unfit – to remove him from office.

The hypocrisy is beyond belief: The party that assails Republicans for questioning the integrity of the highly irregular 2020 election spent years and vast government resources to undo the results of 2016.

The charges Trump now faces are part of the ongoing campaign by Democrats to subvert the rule of law to delegitimize what they see as the greatest threat to their power.

In the meantime, Democrats are blatantly using the criminal justice system to protect President Biden. It is now beyond dispute that Biden lied to the American people when he said he never discussed foreign business with his son Hunter and when he claimed during his final 2020 debate with Trump that Hunter’s laptop, which contained evidence of those corrupt dealings, was a “Russian plant.” Has a candidate ever peddled more consequential falsehoods?

In fact, the president was not only aware of his son’s influence-peddling schemes, whose sole selling point was the connection to his vast power. He was an active participant through phone calls and meetings with clients. Irony does not capture the deviousness of the Democrats’ decision to impeach Trump for asking Ukraine to look into this corruption.

The cover-up of the Bidens’ conduct is equally disturbing. The U.S. attorney in Delaware assigned to the case, David C. Weiss, is a former colleague of Biden’s late son Beau. Although the tax avoidance charges involved are straightforward, Weiss spent more than five years allegedly looking into them – allowing the statute of limitations to run out on millions of unreported earnings Hunter generated in 2014 and 2015. Note that even as the president calls on Americans to pay their fair share, neither he nor his allies have demanded that Hunter pay his.

Indeed, we only know about Weiss’ corruption because of two courageous IRS whistleblowers. In response, Weiss quickly struck a deal with Hunter to settle the matter, crafting a sweetheart deal that would have let him off the hook with a slap on the wrist. All might have been forgiven but for the presiding judge, who rejected the deal last month as “not standard” and potentially unconstitutional.

In response to this scandal, Attorney General Merrick Garland appointed Weiss as special counsel to look into the mess. This move is beyond brazen – Weiss is now apparently in charge of probing his own misconduct. The goal is obvious: Protect the president, and let the statute of limitations run out on other alleged crimes while shutting down any questions about the “ongoing investigation.”

The arrogance is jaw-dropping; the lawlessness is in plain sight. Democrats are not even trying to hide their malfeasance – which is part of their method. If they can make us accept their authority to twist the system so that it is no longer a means of justice but a tool of their political power, then their possibilities are unlimited.

Imagine if the roles were reversed: What if Republican prosecutors had indicted a former Democratic president, who was also the party’s leading candidate in the next election, in four separate cases on 91 questionable charges while a GOP-controlled Department of Justice simultaneously protected its sitting-president boss, who was seeking reelection, by slow-walking a probe of his family’s alleged crimes?

The corporate media would be in high dudgeon about this assault on the Constitution and the streets would be filled with left-wing protestors who would make the BLM riots, the Jan. 6 attack on the Capitol, and the harassment of Supreme Court justices in response to the overturning of Roe v. Wade seem mild.

Here’s the conundrum. While no one wants conservatives to start engaging in direct action, their passivity is allowing Democrats to weaponize the government. On the one hand, I admire their faith in our system. Even Trump, for all his barking, has largely submitted to his gross mistreatment.

But our system is shattered. The rule of law is now more concept than fact. Where’s the outrage?

J. Peder Zane is a RealClearInvestigations editor and columnist. He previously worked as a book review editor and book columnist for the News & Observer (Raleigh), where his writing won several national honors. Zane has also worked at the New York Times and taught writing at Duke University and Saint Augustine’s University.

https://www.zerohedge.com/political/democrats-have-broken-america-wheres-outrage

Alnylam to appeal ruling on patents related to Moderna's COVID vaccines

 Alnylam Pharmaceuticals said on Friday it plans to appeal a ruling by the U.S. District Court for the District of Delaware on two patents asserted against Moderna for the latter's COVID-19 vaccine Spikevax.

Cambridge, Massachusetts-based Alnylam sued both Moderna and Pfizer Inc in Delaware last year, seeking royalties for the lipid nanoparticle (LNP) technology their vaccines use to deliver genetic material known as mRNA.

The cases are part of a wave of patent lawsuits that have been filed over technology used in the COVID-19 shots, including one filed by Moderna against Pfizer last year.

While Alnylam and Moderna have jointly agreed to final judgment over the non-infringement of two patents, Alnylam said it disagrees with the court's ruling.

Alnylam anticipates its second action against Moderna for infringement will move forward in the Delaware Court.

Moderna did not immediately respond to a request for comment.

The Delaware court's ruling did not impact the company's infringement contentions in its two separate suits against Pfizer, Alnylam said.

https://finance.yahoo.com/news/1-alnylam-appeal-ruling-patents-223515179.html

Worker death prompts US FAA to issue aviation ground safety alert

The death of an airline employee in December and another serious injury prompted the Federal Aviation Administration (FAA) to issue a safety alert on Friday to airlines in an effort to prevent more incidents.

The safety alert reiterates that "it is important for workers to remain clear of operating engines until they are shut down," the FAA said.

The alert comes as questions arise about U.S. aviation safety after a series of troubling near-miss incidents. The FAA has said it will hold runway safety meetings at 90 airports over the next few weeks.

In December, a ramp agent was fatally injured at Montgomery Regional Airport in Alabama when the worker was sucked into an engine of an American Airlines regional carrier flight parked at the gate.

The flight was operated by Envoy Air, a wholly-owned subsidiary of American Airlines and the worker was employed by Piedmont Airlines, another American subsidiary.

The Occupational Safety and Health Administration issued Piedmont Airlines a citation for one serious violation in June for exposing ground crew workers to ingestion hazards while performing aircraft marshalling, wing-walking and baggage-handling tasks.

Piedmont faces $15,625 in proposed penalties, the maximum allowed by law. The company has contested the findings before the independent Occupational Safety and Health Review Commission.

Piedmont said on Friday its policies and procedures "are compliant with FAA requirements and actively address all the concerns outlined in the citation."

In another event, a wing walker sustained a serious injury when an aircraft was being repositioned, the FAA said.

https://news.yahoo.com/us-faa-issues-alert-prevent-145516580.html