Antioxidants stimulate blood flow in tumors

 Vitamin C and other antioxidants stimulate the formation of new blood vessels in lung cancer tumours, a new study from Karolinska Institutet published in The Journal of Clinical Investigation shows. The discovery corroborates the idea that dietary supplements containing antioxidants can accelerate tumour growth and metastasis.

"We've found that antioxidants activate a mechanism that causes cancer tumours to form new blood vessels, which is surprising, since it was previously thought that antioxidants have a protective effect," says study leader Martin Bergö, professor at the Department of Biosciences and Nutrition and vice president of Karolinska Institutet in Sweden. "The new blood vessels nourish the tumours and can help them grow and spread."

Antioxidants neutralise free oxygen radicals, which can damage the body, and are therefore commonly found in dietary supplements. But overly high doses can be harmful.

"There's no need to fear antioxidants in normal food but most people don't need additional amounts of them," says Professor Bergö. "In fact, it can be harmful for cancer patients and people with an elevated cancer risk."

Previously unknown mechanism

Professor Bergö's research group has previously shown that antioxidants like vitamin C and E accelerate the growth and spread of lung cancer by stabilising a protein called BACH1. BACH1 is activated when the level of free oxygen radicals drops, which happens, for example, when extra antioxidants are introduced via the diet or when spontaneous mutations in the tumour cells activate endogenous antioxidants. Now the researchers have been able to show that the activation of BACH1 induces the formation of new blood vessels (angiogenesis).

While low oxygen levels (hypoxia) are known to be required for angiogenesis to occur in cancer tumours, the new mechanism identified by the researchers demonstrates that tumours can form new blood vessels in the presence of normal oxygen levels as well. The study also shows that BACH1 is regulated in a similar way as the HIF-1α protein -- a mechanism that was awarded the 2019 Nobel Prize in Physiology or Medicine and that allows cells to adapt to changes in oxygen levels. HIF-1α and BACH1 work together in the tumours, the new research shows.Hoping for more effective drugs

"Many clinical trials have evaluated the efficacy of angiogenesis inhibitors, but the results have not been as successful as anticipated," says Ting Wang, doctoral student in Professor Bergö's group at Karolinska Institutet. "Our study opens the door to more effective ways of preventing angiogenesis in tumours; for example, patients whose tumours exhibit high levels of BACH1 might benefit more from anti-angiogensis therapy than patients with low BACH1 levels."

The researchers used a range of cell-biological methods and concentrated most of their work on lung cancer tumours by studying organoids -- small cultivated microtumours from patients. But they also studied mice and samples of human breast and kidney tumours. Tumours in which BACH1 was activated, either via ingested antioxidants or by overexpression of the BACH1 gene, produced more new blood vessels and were highly sensitive to angiogenesis inhibitors.

"The next step is to examine in detail how levels of oxygen and free radicals can regulate the BACH1 protein, and we will continue to determine the clinical relevance of our results," says Ting Wang. "We'll also be doing similar studies in other cancer forms such as breast, kidney and skin cancer."

The study was conducted in close collaboration with KI researchers Susanne Schlisio, Staffan Strömblad and Eckardt Treuter and researchers at the First Affiliated Hospital of Zhengzhou University. The research was financed primarily by grants from the Swedish Cancer Society, the Swedish Research Council, the Sjöberg Foundation, the Knut and Alice Wallenberg Foundation, the Centre for Innovative Medicine (CIMED) and Karolinska Institutet. There are no reported conflicts of interest.

Journal Reference:

1. Ting Wang, Yongqiang Dong, Zhiqiang Huang, Guoqing Zhang, Ying Zhao, Haidong Yao, Jianjiang Hu, Elin Tüksammel, Huan Cai, Ning Liang, Xiufeng Xu, Xijie Yang, Sarah Schmidt, Xi Qiao, Susanne Schlisio, Staffan Strömblad, Hong Qian, Changtao Jiang, Eckardt Treuter, Martin O. Bergo. Antioxidants stimulate BACH1-dependent tumor angiogenesis. Journal of Clinical Investigation, 2023; DOI: 10.1172/JCI169671

https://www.sciencedaily.com/releases/2023/08/230831142816.htm

Red blood cells exposed to oxygen deficiency protect against myocardial infarction

Red blood cells exposed to oxygen deficiency protect against myocardial infarction, according to a new KI study published in the Journal of Clinical Investigation. The study also shows that the protective effect is enhanced by a nitrate-rich vegetable diet.

Red blood cells carry oxygen from the lungs to all of the body's cells and carbon dioxide back to the lungs. A new study, conducted at Karolinska Institutet in collaboration with Karolinska University Hospital, now shows that red blood cells have an intrinsic function of protecting against heart injury caused by myocardial infarction.

The effect is enhanced by a diet containing nitrate-rich vegetables, such as arugula and other green leafy vegetables.

"This effect was also shown in a clinical study in patients with high blood pressure who were randomly assigned to eat nitrate-rich vegetables or a diet low in nitrates," says John Pernow, Professor of Cardiology at the Department of Medicine, Karolinska Institutet in Solna and senior physician at Karolinska University Hospital, and the study's corresponding author together with Jon Lundberg, professor at the Department of Physiology and Pharmacology, Karolinska Institutet.

Part of the study was conducted through experiments with red blood cells from mice that were added to a myocardial infarction model with hearts from mice. Before the experiment, the red blood cells were exposed to low oxygen pressure, while nitrate was added to the drinking water.

In a clinical study, red blood cells were collected from patients with high blood pressure who were randomly assigned a nitrate-rich diet with green leafy vegetables or a diet with nitrate-poor vegetables. These red blood cells were given to the corresponding myocardial infarction model with hearts from rats.

"The results show both that the red blood cells convey protection against injury in the heart in the event of low oxygen levels, and how that protection can be enhanced through a simple dietary advice. This may be of great importance for patients at risk of myocardial infarction," says the study's first author Jiangning Yang, a researcher at the Department of Medicine, Solna, Karolinska Institutet.

The next step in the research is to develop additional drugs that can activate the protective signalling mechanism in red blood cells to provide protection to the body's tissues and cells in the event of oxygen deficiency.

"In addition, we need to map how the blood cells transmit their protective signal to the heart muscle cells," says John Pernow.

The study is a collaboration between researchers from, among others, Karolinska Institutet, Karolinska University Hospital, Tohoku University, Japan, Heinrich-Heine-University, Germany, and Ruhr-University Bochum, Germany.

The research was funded by the Swedish Heart-Lung Foundation, the Swedish Research Council and Region Stockholm's ALF project funds. Jon Lundberg and Eddie Weitzberg hold patents related to therapies based on inorganic nitrate. Other researchers report no conflicts of interest.

Journal Reference:

1. Jiangning Yang, Michaela L. Sundqvist, Xiaowei Zheng, Tong Jiao, Aida Collado, Yahor Tratsiakovich, Ali Mahdi, John Tengbom, Evanthia Mergia, Sergiu-Bogdan Catrina, Zhichao Zhou, Mattias Carlström, Takaaki Akaike, Miriam M. Cortese-Krott, Eddie Weitzberg, Jon O. Lundberg, John Pernow. Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP. Journal of Clinical Investigation, 2023; 133 (17) DOI: 10.1172/JCI167693

https://www.sciencedaily.com/releases/2023/09/230901124039.htm

Link between memory and appetite in human brain may help explain obesity

 Disrupted connections between memory and appetite regulating brain circuits are directly proportional to body mass index (BMI), notably in patients who suffer from disordered or overeating that can lead to obesity, such as binge eating disorder (BED), according to new research from the Perelman School of Medicine at the University of Pennsylvania. Published today in Nature, the research notes that individuals who are obese have impaired connections between the dorsolateral hippocampus (dlHPC) and the lateral hypothalamus (LH), which may impact their ability to control or regulate emotional responses when anticipating rewarding meals or treats.

"These findings underscore that some individual's brains can be fundamentally different in regions that increase the risk for obesity," senior author, Casey Halpern, MD, an associate professor of Neurosurgery and Chief of Stereotactic and Functional Neurosurgery at Penn Medicine and the Corporal Michael J. Crescenz Veterans Affairs Medical Center. "Conditions like disordered eating and obesity are a lot more complicated than simply managing self-control and eating healthier. What these individuals need is not more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain."

The dlHPC is located in the region of the brain that processes memory, and the LH is in the region of the brain that is responsible for keeping the body in a stable state, called homeostasis. Previous research has found an association with loss of function in the human hippocampus in individuals with obesity and related disordered eating, like BED. However, outside of imaging techniques such as magnetic resonance imaging (MRI), the role of the hippocampus has been difficult to study in humans with obesity and related eating disorders.

In this study, researchers were able to evaluate patients whose brains were already being monitored electrically in the Epilepsy Monitoring Unit. Researchers monitored brain activity as patients anticipated and then received a sweet treat (a chocolate milkshake). They found that both the dlHPC and the LH activated simultaneously when participants anticipated receiving the rewarding meal. These researchers confirmed using stimulation techniques pioneered by coauthors, Kai Miller, MD, PhD, and Dora Hermes Miller, PhD, from Mayo Clinic, that this specific zone of the hippocampus, the dlHPC, and LH exhibited extremely strong connectivity, as well.

In individuals with obesity, researchers found that the impairment of this hypothalamus-hippocampus circuit was directly proportional to their BMI. That is, in participants with a high BMI, the connection was even more disturbed.

To further validate the connection, Halpern's team used a technique called "brain clearing," to analyze brain tissue. The technique revealed melanin-concentrating hormone, a hormone known to regulate feeding behavior that is produced in the LH. They found the presence of MCH in the dlHPC, and nowhere else, confirming a link between the two regions.

"The hippocampus has never been targeted to treat obesity, or the disordered eating that can sometimes cause obesity," said Halpern. "We hope to be able to use this research to both identify which individuals who are likely to develop obesity later in life, and to develop novel therapies -- both invasive and not -- to help improve function of this critical circuit that seems to go awry in patients who are obese."

This research was funded by the Foundation for OCD Research, the National Institute of Health (R01 MH124760, K23 MH106794, R01 NS095985), the Natural Sciences and Engineering Research Council of Canada (#40306) and the Canadian Institutes of Health Research (#41916).

Journal Reference:

1. Daniel A. N. Barbosa, Sandra Gattas, Juliana S. Salgado, Fiene Marie Kuijper, Allan R. Wang, Yuhao Huang, Bina Kakusa, Christoph Leuze, Artur Luczak, Paul Rapp, Robert C. Malenka, Dora Hermes, Kai J. Miller, Boris D. Heifets, Cara Bohon, Jennifer A. McNab, Casey H. Halpern. An orexigenic subnetwork within the human hippocampus. Nature, 2023; DOI: 10.1038/s41586-023-06459-w

https://www.sciencedaily.com/releases/2023/08/230830131943.htm

'Dem hopes for Michelle Obama in 2024 another sign of Biden’s vulnerability'

Michelle Obama’s name keeps surfacing on the wish list of some Democrats as an alternative to President Biden in 2024, an aberration that conservatives say is partly driven by fear among liberals and the media that probes of Hunter Biden will turn up more damaging information about the Biden family’s finances before the election.

Polls consistently show at least half of Democratic voters don’t want Mr. Biden, at age 80 already the nation’s oldest president, to run for a second term. The level of dissatisfaction has remained high as fresh allegations emerge that he may have been involved in pay-to-play influence through his son’s foreign business deals.

Even if Mr. Biden does drop out, there’s no emerging consensus on who should replace him. Even less support exists in the party for alternatives such as California Gov. Gavin Newsom, Vice President Kamala Harris and Transportation Secretary Pete Buttigieg.

Some anxious Democrats keep returning to the notion of Mrs. Obama, who was generally more popular among Democrats than her husband during their eight years in the White House.

She remains a favorite among Democrats, more so than Mr. Biden, as shown in a poll last month.

https://www.washingtontimes.com/news/2023/sep/1/some-democrats-keep-hoping-for-michelle-obama-in-2/

FDA, CDC Hid Data On Spike In COVID Cases Among The Vaccinated: Documents

 by Zachary Stieber via The Epoch Times (emphasis ours),

COVID-19 cases among vaccinated seniors soared in 2021, according to newly disclosed data that was acquired by U.S. health agencies but not presented to the public.

Humetrix Cloud Services was contracted by the U.S. military to analyze vaccine data. The company performed a fresh analysis as authorities considered in 2021 whether COVID-19 vaccine boosters were necessary amid studies finding waning vaccine effectiveness.

Humetrix researchers found that the proportion of total COVID-19 cases among the seniors was increasingly comprised of vaccinated people, according to the newly disclosed documents.

For the week ending on July 31, 2021, post-vaccination COVID-19 cases represented 73 percent of the cases among people 65 and older, the company found. The elderly were 80 percent fully vaccinated at the time.

Breakthrough infection rates were higher among those who were vaccinated early, the researchers found. They estimated that the rates were twice as high in those who had been vaccinated five to six months prior, when compared to people vaccinated three to four months before.

The breakthrough cases started in January 2021, according to the data.

Protection against hospitalization was also fading, researchers discovered.

In the week ending on July 31, 2021, 63 percent of the COVID-19 hospitalizations in seniors were among the fully vaccinated, according to the documents. The same pattern of weaker protection among people who were vaccinated early was found.

Researchers calculated that the vaccine effectiveness (VE) against infection was just 33 percent while the effectiveness against hospitalization had dropped to 57 percent.

Seniors who previously had COVID-19 and recovered were more likely to avoid hospitalization, the researchers also found. Risk factors included serious underlying conditions such as obesity and being in the oldest age group, or older than 85.

The cohort analysis was completed on 20 million Medicare beneficiaries, including 5.6 million seniors who received a primary series of a COVID-19 vaccine.

"Our observational study VE findings show a very significant decrease in VE against infection and hospitalization in the Delta phase of the pandemic for individuals vaccinated with either the Pfizer or Moderna vaccine for those 5–6 months post vaccination vs. those 3–4 months post vaccination," Dr. Bettina Experton, Humetrix's president and CEO, said in a Sept. 15, 2021, email to top U.S. Food and Drug Administration (FDA) officials.

Humetrix also found that among the beneficiaries, there had been 133,000 cases, 27,000 hospitalizations, and 8,300 intensive care admissions among the fully vaccinated since the start of the COVID-19 pandemic.

Dr. Experton disclosed that Humetrix shared the data with the U.S. Centers for Disease Control and Prevention (CDC) in August 2021.

"It would have been nice to know [the military] was conducting this prior to now. Also might have been nice for CDC to share the data," Dr. Peter Marks, one of the FDA officials, told colleagues in response.

"This is more worrisome than the other data we have in my opinion," Dr. Janet Woodcock, the FDA's acting commissioner at the time, said in reply.

The presentation and emails were obtained by the Informed Consent Action Network, a nonprofit that seeks to provide transparency around medical issues, through the Freedom of Information Act (FOIA).

"It is hard to see this as anything other than a failure of our health authorities to assess, share, make public, and act upon valuable, real-world data in the midst of a so-called pandemic," Del Bigtree, founder of the network, told The Epoch Times via email. "And without FOIA, the public likely would never be made aware of these failures which, of course, allows them to be perpetrated again and again."

The FDA and CDC declined to comment.

Dr. Francis Collins, the director of the U.S. National Institutes of Health at the time, wrote in a separate email obtained through FOIA that the results of the study provided "pretty compelling evidence that VE is falling 5–6 months post vaccination for both infection and hospitalization for those over 65."

He added, "Even for those 3–4 months out there is a trend toward worsening VE.”

The CDC, FDA, and National Institutes of Health did not share the data with the public as they considered whether to clear and recommend COVID-19 vaccine boosters.

The CDC held a meeting with its vaccine advisers on Aug. 30, 2021. During the meeting, CDC officials went over emerging data on waning vaccine effectiveness. But the military study was not included.

The FDA held a similar meeting on Sept. 17, 2021. The CDC participated. The Humetrix analysis was also not presented during that meeting.

Both agencies have aggressively promoted COVID-19 vaccines throughout the pandemic, including hyping them as strongly protective against severe disease even after their own data have suggested that is not the case.

The CDC did present (pdf) data from COVID-NET, one of its systems, that showed effectiveness against COVID-19-associated hospitalization was falling among the elderly since the emergence of the Delta variant but that data still showed 80 percent effectiveness.

The presentation also included data from outside researchers and Israel that estimated the protection during the Delta era against infection ranged from 39 percent to 84 percent and that the effectiveness against hospitalization ranged from 75 to 95 percent.

The FDA ended up clearing a Pfizer booster for many Americans. The CDC advised most people to receive it. The agencies later expanded booster clearance and recommendations to virtually all Americans aged 5 and older, with Moderna's shot as another option. Authorities have since replaced the old shots due to their lack of durability, and are preparing to roll out another slate of shots this fall.

https://www.zerohedge.com/markets/fda-cdc-hid-data-spike-covid-cases-among-vaccinated-documents

Rallybio Presents Phase 1 Data on PNH Therapy

 First-In-Human Single Ascending Dose Clinical Data for RLYB116 Demonstrated a Reduction in Free C5 Greater than 99% at 24 Hours for the 100 mg dose and at 12, 24, and 72 Hours for the 300 mg dose in Healthy Participants --

-- Mean Estimated Elimination Half-Life for RLYB116 was > 300 Hours --

-- No Severe or Serious Adverse Events with Single-Dose Administration of RLYB116 --

-- Phase 1 Multiple Ascending Dose Study of RLYB116 Ongoing; Preliminary Safety, PK, and PD Data Expected in 4Q 2023 --

https://finance.yahoo.com/news/rallybio-presents-phase-1-single-160000787.html

Russia signs 280,000 for contract military service this year -Medvedev

 Some 280,000 people have signed up so far this year for professional service with Russia's military, the deputy chair of the Russian Security Council, former President Dmitry Medvedev, said on Sunday.

Visiting Russia's Far East, Medvedev said he was meeting local officials to work on efforts to beef up the armed forces.

"According to the Ministry of Defence, since Jan. 1, about 280,000 people have been accepted into the ranks of the Armed Forces on a contract basis," including reservists, state news agency TASS quoted Medvedev as saying.

Last year Russia announced a plan to expand its combat personnel more than 30% to 1.5 million, an ambitious task made harder by its heavy but undisclosed casualties in Moscow's war against Ukraine.

Some Russian lawmakers suggested Russia needs a professional army 7-million strong to ensure the country's security - a move that would require a huge budget allowance.

President Vladimir Putin ordered a "partial mobilisation" of 300,000 reservists in September 2022, prompting hundreds of thousands of others to flee Russia to avoid being sent to fight. Putin has said there is no need for any further mobilisation.

https://www.marketscreener.com/news/latest/Russia-signs-280-000-for-contract-military-service-this-year-Medvedev--44761842/