Comment

Comment by Dr. Krishna Kumari Challa on February 21, 2022 at 10:00am

Researchers identify protein complex critical in helping control cell death

 Cell death plays an important role in normal human development and health but requires tightly orchestrated balance to avert disease. Too much can trigger a massive inflammatory immune response that damages tissues and organs. Not enough can interfere with the body's ability to fight infection or lead to cancer.

Researchers are studying the complex molecular processes underlying necroptosis, which combines characteristics of apoptosis (regulated or programmed cell death) and necrosis (unregulated cell death).

During necroptosis dying cells rupture and release their contents. This sends out alarm signals to the immune system, triggering immune cells to fight infection or limit injury. Excessive necroptosis can be a problem in some diseases like stroke or heart attack, when cells die from inadequate blood supply, or in severe COVID-19, when an extreme response to infection causes organ damage or even death.

A new preclinical study  identifies a protein complex critical for regulating apoptosis and necroptosis—known as protein phosphatase 1 regulatory subunit 3G/protein phosphatase 1 gamma (PPP1R3G/PP1γ, or PPP1R3G complex). The researchers' findings suggest that an inhibitor targeting this protein complex may help reduce or prevent excessive necroptosis.

Cell death is very complicated process, which requires layers upon layers of brakes to prevent too many cells from dying. If you want to protect cells from excessive death, then the protein complex  identified in this study is one of many steps you must control.

Part 1

Comment by Dr. Krishna Kumari Challa on February 20, 2022 at 12:18pm

Comment by Dr. Krishna Kumari Challa on February 20, 2022 at 11:41am

In the computer simulations, PE particles were found to prefer the center of the lipid membrane as their location. In the PAMPA experiments, PE plastic partially permeated the membrane, but membrane permeability slowed down significantly over time, probably due to the accumulation of plastic in the membrane. In the simulations, the preferred location of PET particles was, to a certain degree, the surface part of the membrane, and in the experiments, they permeated the membrane fairly well. According to this study, the properties of the membrane structures were not significantly affected by individual plastics.

Joni Järvenpää et al, PE and PET oligomers' interplay with membrane bilayers, Scientific Reports (2022). DOI: 10.1038/s41598-022-06217-4

https://phys.org/news/2022-02-nano-sized-plastics-permeate-cell-mem...

Part 2

Comment by Dr. Krishna Kumari Challa on February 20, 2022 at 11:39am

Nano-sized plastics may enter and permeate cell membranes

The occurrence of microplastics in nature has been studied extensively. However, little is known about the health effects of microplastics, and understanding of their transport into the human body is also lacking. Any adverse health effects possibly associated with plastics may be caused by the plastic compound itself, or by the environmental toxins it carries. Many known fat-soluble environmental toxins and heavy metals are known to be able to attach to the surface of small plastic particles. This is why it is important to investigate the transport mechanisms of microplastics into the human body.

With the help of molecular modeling, researchers at the University of Eastern Finland's School of Pharmacy analyzed the behavior and transport of nano-sized microplastics in bilayer membranes which mimic cell membranes. The researchers performed simple molecular dynamics simulations using well-known and widely used polyethylene (PE) and polyethylene terephthalate (PET) particles.

The cell membrane permeability of pulverized PE and PET plastics was also examined using the Parallel Artificial Membrane Permeability Assay method, PAMPA. The method is usually used to investigate passive absorption of medicines, but it hasn't been used to study microplastics before. The PAMPA method was used to investigate the amount of matter permeating the membrane. The amount of plastic permeating the artificial membrane was measured by NMR spectroscopy at certain intervals.

In both experiments, the movement of molecules was controlled only by concentration differences on different sides of the membrane, and by occasional movement induced by heat. In other words, the methods provided information on the passive permeation of molecules through the membranes.

Part 1

Comment by Dr. Krishna Kumari Challa on February 19, 2022 at 12:58pm

Scientists Convert Donor Lungs to Universal Blood Type in a Medical First

Patients can wait a long time for potentially life-saving lung transplants, since the need to find close matches complicates the process. One of the characteristics that need to be matched is patient and donor blood type.

Now new research shows that the blood type of some donated lungs could be altered before transplant, which means there is a bigger pool of universal donor lungs and less time on the waiting list for those in need.

The process works via a pair of enzymes – specifically, FpGalNAc deacetylase and FpGalactosaminidase – that in combination remove the antigens that distinguish red blood cells, converting blood type A lungs into universal type O.

Under lab conditions, scientists treated eight blood type A lungs with the enzyme combination, reporting that 97 percent of blood type A antigens were removed within four hours. What's more, the conversion was achieved without any observable toxicity.

Three of the newly 'neutral' lungs were then placed in plasma to simulate an actual transplant. Observed antibody damage was minimal, meaning the converted lungs were accepted rather than rejected, at least in the crucial, early stages.

The team estimates that the procedure could eventually increase the number of blood group O donor lungs from the current 55 percent to more than 80 percent in the future.

https://www.science.org/doi/10.1126/scitranslmed.abm7190?adobe_mc=M...

https://www.sciencealert.com/lungs-converted-to-a-universal-blood-t...

Comment by Dr. Krishna Kumari Challa on February 19, 2022 at 12:22pm

Mosquitos learn to avoid pesticides after single non-lethal exposure

Female mosquitoes learn to avoid pesticides after a single exposure, according to a study published in Scientific Reports. The authors suggest that this could make pesticides less effective against mosquitoes.

Pesticides are used to limit the spread of mosquito-transmitted diseases. Pesticide resistance has increased among mosquitoes in recent decades, however the extent to which this is due to mosquito behavior has been unclear.

Researchers exposed female Aedes aegypti and Culex quinquefasciastus mosquitoes—which transmit dengue, Zika and West Nile fever—to non-lethal doses of the common anti-mosquito pesticides malathion, propoxur, deltamethrin, permethrin and lambda-cyhalothrin. They then tested whether subsequent exposure to the same pesticide deterred mosquitoes from feeding and resting, and assessed whether this affected mosquito survival.

The researchers found that mosquitoes that had been pre-exposed to a pesticide avoided passing through a pesticide-treated net in order to reach a food source at a higher rate than those who had not been pre-exposed. Only 15.4% of A. aegypti and 12.1% of C. quinquefasciastus that had been pre-exposed passed through the net in order to feed, compared to 57.7% of A. aegypti and 54.4% of C. quinquefasciastus that had not been pre-exposed. Subsequently, the survival rate of pre-exposed mosquitoes was more than double that of mosquitoes that had not been pre-exposed. 38.3% of A. aegypti and 32.1% of C. quinquefasciastus that had been pre-exposed and 11.5% of A. aegypti and 12.9% C. quinquefasciastus that had not been pre-exposed survived exposure to the pesticide-treated net.

The researchers also found that pre-exposed mosquitoes were more likely than mosquitoes that had not been pre-exposed to a pesticide to rest in a container that smelt of a control substance, rather than in a container that smelt of a pesticide. 75.7% of A. aegypti and 83.1% of C. quinquefasciastus that had been pre-exposed to a pesticide rested in the pesticide-free container, compared to 50.2% of A. aegypti and 50.4% of C. quinquefasciastus that had not been pre-exposed.

The findings suggest that mosquitoes that have been exposed to non-lethal doses of pesticides learn to avoid these pesticides and, as a result, may seek out safer food sources and resting sites, allowing them to survive to reproduce.

https://www.nature.com/articles/s41598-022-05754-2

https://researchnews.cc/news/11682/Mosquitos-learn-to-avoid-pestici...

Comment by Dr. Krishna Kumari Challa on February 19, 2022 at 12:19pm

Research discovery could enable broad coronavirus vaccine

Comment by Dr. Krishna Kumari Challa on February 19, 2022 at 12:00pm

The findings of gut microbiome and blood compound changes in patients with one of the three heart disorders, acute myocardial infarction, was validated and extended in a study from Israel that is reported in the same issue of Nature Medicine.

It is now clear that major disturbances occur in the gut microbiome of patients suffering from heart disease and that these alterations may start many years before onset of heart disease symptoms and diagnosis. These microbiome changes are not explained by drug treatments.

The primary limitation of the studies is that the investigators report associations, rather than causal explanations for their observations. However,  in the past decade a number of cellular and animal experiments into specific microbiome-derived compounds—like the ones identified in the present studies—have demonstrated how the imbalanced gut microbiome may play a role in the development of heart disease.

Intervention in both humans and rodents have shown that an imbalanced gut microbiome at various stages of heart disease development can be modified and partly restored by eating a more plant-based and energy-controlled diet, avoidance of smoking and compliance with daily exercise. It is time for translating the accumulated evidence of the role of the gut microbiome to more focused public health initiatives in attempts to prevent or delay morbidity and mortality related to heart  disease.

Sebastien Fromentin et al, Microbiome and metabolome features of the cardiometabolic disease spectrum, Nature Medicine (2022). DOI: 10.1038/s41591-022-01688-4

Yeela Talmor-Barkan et al, Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease, Nature Medicine (2022). DOI: 10.1038/s41591-022-01686-6

https://medicalxpress.com/news/2022-02-scientists-characterize-imba...

Part 3

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Comment by Dr. Krishna Kumari Challa on February 19, 2022 at 11:58am

The researchers recruited 1,241 middle-aged people from Denmark, France and Germany including healthy individuals, individuals with obesity and type 2 diabetes but lacking a diagnosis of heart disease, and patients with either myocardial infarction, angina pectoris or heart failure. The investigators quantified about 700 different bacterial species and estimated their functions in the gut microbiome and compared these findings to more than 1,000 compounds circulating in blood with many of these compounds originating from the inner gut chemistry factory.

The researchers  found that about half of these gut bacteria and blood compounds were modified by drug treatment and not directly related to heart disease or the early disease stages like diabetes or obesity occurring prior to diagnosis of heart disease.

Among the remaining half, about 75 percent of the disturbances of the gut microbiome occurred in the early disease stages of overweight and type 2 diabetes, many years before patients noticed any symptoms of heart disease".

However, the early microbiome changes persisted in patients with heart disease who in addition showed specific heart disease related alterations in the composition and function of the gut microbiome. Both at the early dysmetabolic stage and at the later stages of diagnosed heart disease, the diseased microbiome was characterized by a loss of bacterial cells and bacterial competences. In addition, the patients showed a shift towards fewer types of bacteria known to produce health promoting compounds like short chain fatty acids and more bacteria types producing unhealthy compounds from the metabolism of certain dietary amino acids, choline and L-carnitine. Analyses of the blood compounds mirrored the imbalance of the gut microbiome.

Part 2

Comment by Dr. Krishna Kumari Challa on February 19, 2022 at 11:57am

Scientists characterize the imbalanced gut bacteria of patients with myocardial infarction, angina and heart failure

The human gut contains trillions of bacteria, collectively called the gut microbiome, which may have positive and negative effects on human health. When in balance they function as an inner chemistry factory producing numerous compounds that promote good health. However, an unhealthy lifestyle—poor diet, smoking, lack of physical activity or disease—can disrupt the balance, leading the microbiome to instead produce compounds that may trigger multiple non-communicable chronic disorders in people at high genetic risk, including myocardial infarction, angina or heart failure.

Scientists have already discovered that the gut microbiome is altered in people with chronic heart disease. They subsequently identified compounds that are produced by the diseased microbiome, for instance a bacterial compound called trimethylamine (TMA) that after modification in the liver of the human host  causes arteriosclerosis.

However, these findings of altered gut microbiome are challenged because they were achieved in studies of medicated patients. Patients with heart disease are given several different drugs, each of which are known to modify the gut microbiome. As a result, it was unclear whether  drugs or heart disease itself caused the disrupted gut microbiome of people with cardiovascular disorders.

A further complication lies in the fact that heart disease often develops alongside the early stages of overweight and type 2 diabetes, which are also characterized by having disrupted gut microbiomes. As a result, it remained to be shown whether an imbalanced gut microbiome is a feature of heart disease itself.

To answer these critical questions a European consortium of researchers established the EU-funded MetaCardis research project in 2012 to investigate the role of gut microbes in cardiometabolic disease. Now they published the consortium's findings in in the journal Nature Medicine.

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