Diabetes can elevate risk of cancer

Agencies
August 26, 2019

Washington, Aug 26: The researchers have identified the reason why people with Type 1 or Type 2 diabetes have an increased risk of developing some forms of cancer. The study to be presented at the 'American Chemical Society Fall 2019 National Meeting' has found that DNA sustains more damage and gets fixed less often when blood sugar levels are high compared to when blood sugar is at a normal, healthy level, thereby increasing one's cancer risk.

"It's been known for a long time that people with diabetes have as much as 2.5-fold increased risk for certain cancers," said John Termini, who is presenting the work at the meeting. These cancers include ovarian, breast, kidney and others. Scientists have suspected that the elevated cancer risk for diabetics arises from hormonal dysregulation.

"In people with Type 2 diabetes, their insulin is not effectively carrying glucose into cells," Termini explained. "So the pancreas makes more and more insulin, and they get what's called hyperinsulinemia."

In addition to controlling blood glucose levels, the hormone insulin can stimulate cell growth, possibly leading to cancer. Also, most people with Type 2 diabetes are overweight, and their excess fat tissue produces higher levels of adipokines than those at a healthy weight.

Termini and his colleagues looked for a specific type of damage in the form of chemically modified DNA bases, known as adducts, in tissue culture and rodent models of diabetes. Indeed, they found a DNA adduct, called N2-(1-carboxyethyl)-2'-deoxyguanosine, or CEdG, that occurred more frequently in the diabetic models than in normal cells or mice.

"Exposure to high glucose levels leads to both DNA adducts and the suppression of their repair, which in combination could cause genome instability and cancer," Termini added. The researchers also wanted to determine the molecular reasons why the adducts weren't being fixed properly by the cells.

They identified two proteins that appear to be involved: the transcription factor HIF1a and the signalling protein mTORC1, which both show less activity in diabetes. According to Termini, several drugs that stimulate HIF1a or mTORC1 already exist. The researchers plan to see if these drugs decrease cancer risk in diabetic animal models and if so, they will test them in humans.

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Agencies
January 26,2020

High-protein diets may help people lose weight and build muscle, but there is a downside to it --a greater heart attack risk. Researchers now report that high-protein diets boost artery-clogging plaque.

The research in mice showed that high-protein diets spur unstable plaque -- the kind most prone to rupturing and causing blocked arteries.

More plaque buildup in the arteries, particularly if it's unstable, increases the risk of heart attack.

"There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years," said senior author Babak Razani, associate professor at Washington University School of Medicine in St. Louis, Missouri.

"But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health," Razani added.

The researchers studied mice who were fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries.

Some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

The mice on the high-fat, high-protein diet developed worse atherosclerosis -- about 30 per cent more plaque in the arteries -- than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

"A couple of a scoop of protein powder in a milkshake or smoothie adds something like 40 grams of protein -- almost equivalent to the daily recommended intake," Razani said.

"To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet -- keeping the fat constant. Protein went from 15 per cent to 46 per cent of calories for these mice".

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by Razani's team and other groups has shown that immune cells called macrophages work to clean up plaque in the arteries.

But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

"In mice on the high-protein diet, their plaques were a macrophage graveyard," Razani informed.

To understand how high dietary protein might increase plaque complexity, Razani and his colleagues also studied the path protein takes after it has been digested -- broken down into its original building blocks, called amino acids.

"This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques," said Razani.

"This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease," he added.

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Agencies
May 14,2020

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

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Agencies
July 7,2020

The World Health Organization (WHO) is reviewing a report that suggested its advice on the novel coronavirus needs updating after some scientists told the New York Times there was evidence the virus could be spread by tiny particles in the air.

The WHO says the Covid-19 disease spreads primarily through small droplets, which are expelled from the nose and mouth when an infected person breaths them out in coughs, sneezes, speech or laughter and quickly sink to the ground.

In an open letter to the Geneva-based agency, 239 scientists in 32 countries outlined the evidence they say shows that smaller exhaled particles can infect people who inhale them, the newspaper said on Saturday.

Because those smaller particles can linger in the air longer, the scientists - who plan to publish their findings in a scientific journal this week - are urging WHO to update its guidance, the Times said.

"We are aware of the article and are reviewing its contents with our technical experts," WHO spokesman Tarik Jasarevic said in an email reply on Monday to a Reuters request for comment.

The extent to which the coronavirus can be spread by the so-called airborne or aerosol route - as opposed to by larger droplets in coughs and sneezes - remains disputed.

Any change in the WHO's assessment of the risk of transmission could affect its current advice on keeping one-metre physical distancing. Governments, which also rely on the agency for guidance policy, may also have to adjust public health measures aimed at curbing the spread of the virus.

"Especially in the last couple of months, we have been stating several times that we consider airborne transmission as possible but certainly not supported by solid or even clear evidence," Benedetta Allegranzi, the WHO's technical lead for infection prevention and control, was quoted as saying in the New York Times.

WHO guidance to health workers, dated June 29, says that SARS-CoV-2, the virus that causes Covid-19, is primarily transmitted between people through respiratory droplets and on surfaces.

But airborne transmission via smaller particles is possible in some circumstances, such as when performing intubation and aerosol-generating procedures, it says.

Medical workers performing such procedures should wear heavy-duty N95 respiratory masks and other protective equipment in an adequately ventilated room, the WHO says.

Officials at South Korea's Centers for Disease Control said on Monday they were continuing to discuss various issues about Covid-19, including the possible airborne transmission. They said more investigations and evidence were needed.

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