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Comment by Dr. Krishna Kumari Challa on October 1, 2022 at 12:41pm

First-ever mycobiome Atlas describes associations between cancers and fungi

An international team of scientists has created the first pan-cancer mycobiome atlas — a survey of 35 types of cancer and their associated fungi.
Cancer cells and microbes have a long and enduring association. Both have coevolved within the ecosystems of the human body, often relying on the same resources. Competition for these resources often affects the replication and survival of cancer cells, microbes and the human host.

The association between cancer and individual microbes has long been studied case-by-case, but much recent attention focuses on the whole human microbiome, particularly in the gut, which houses more — and more diverse — communities of bacteria, viruses and fungi than anywhere else in or on the human body.
However, the roles and influence of cancer-associated fungi remain largely unstudied. Fungi are more complicated organisms than viruses and bacteria. They are eukaryotes — organisms with cells containing nuclei. Their cells are much more similar to animal cells than to bacteria or viruses.

The existence of fungi in most human cancers is both a surprise and to be expected. It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community.

Fungi found on the human body come in two main types: environmental fungi, such as yeasts and mold that generally pose no harm to most healthy people, and commensal fungi, which live on or inside the human body and may be harmless, provide a benefit such as improving gut health or contribute to disease, such as yeast infections or liver disease. Fungi also play a role in shaping host immunity, for better or worse, which looms large in immunocompromised persons, including cancer patients.

The new study characterizes the cancer mycobiome — fungi linked to cancers — in 17,401 samples of patient tissues, blood and plasma across 35 types of cancer in four independent cohorts. The researchers found fungal DNA and cells in low abundances across many major human cancers, with differences in community compositions that differed among cancer types.

The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens.

Analyses that compared fungal communities with matched bacteriomes (the bacterial component of the microbiome) and immunomes (genes and proteins constituting the immune system) revealed that the associations between them were often “permissive,” rather than competitive.

For example, one species of fungi was found to be enriched in breast cancer tumors of patients older than 50 years while another species was notably abundant in lung cancer samples.

The researchers said there were significant correlations between specific fungi and age, tumor subtypes, smoking status, response to immunotherapy and survival measures. Whether the fungi are simply correlated or causally associated remains to be determined.

These findings validate the view that the microbiome in its entirety is a key piece of cancer biology.

Ravid Straussman, Pan-cancer analyses reveal cancer type-specific fungal ecologies and bacteriome interactions, Cell (2022). DOI: 10.1016/j.cell.2022.09.005. www.cell.com/cell/fulltext/S0092-8674(22)01127-8

Comment by Dr. Krishna Kumari Challa on October 1, 2022 at 11:27am

Researchers reveal new strategy to prevent blood clots without increasing the risk of bleeding

A nanoparticle therapy developed by investigators  targets overactive neutrophils, a specific kind of white blood cell, to prevent almost all types of blood clots while causing no increased risk for bleeding. The preclinical findings, published in Science Translational Medicine, may lead to safer ways to care for patients impacted by blood clots. 

According to the researchers, neutrophils are key drivers of both arterial and venous thrombosis. And when you target a neutrophil, you do not increase bleeding risk, you only decrease clotting risk. 

Earlier arterial and venous thrombosis have been thought of as distinct molecular events that require separate treatment paradigms. Arterial thrombosis (an artery clot), which can cause heart attack or stroke, is commonly treated with antiplatelet agents like aspirin, while anticoagulants are used to treat venous thrombosis (a vein clot), a cause of pain or swelling in the legs or clots in the lungs.

More recently, however, experts have begun to suspect commonalities between the two events that could be leveraged as novel therapeutic targets.

In the new study, researchers used animal models to show that overactive neutrophils participate in both arterial and venous thrombosis through an increased capacity to migrate and adhere to sites of injury. They also showed that overactive neutrophils increase the production of key factors used as building blocks for clots. In seeking to halt the process, the researchers identified a cluster of receptors unique to activated neutrophils and developed antibody-coated nanoparticles that specifically target those clusters.

Lalitha Nayak et al, A targetable pathway in neutrophils mitigates both arterial and venous thrombosis, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abj7465

Comment by Dr. Krishna Kumari Challa on October 1, 2022 at 9:33am

Genetics of longevity are influenced by both gender and age

A team of researchers reports evidence that the genetics of longevity are influenced by both gender and age. In their paper published in the journal Science, the group describes their study of aging in mice and humans. A relevant  perspective piece  has also been published  in the same journal issue outlining the technical challenges to understanding how aging works and the work done by the team on this new effort.

Scientists have been studying the aging process for many years but still do not have a good explanation for why organisms age and why some live longer than others. In this new effort, the researchers wondered if something in the genome plays a role in how long a species lives on average.

Noting that another team had created a very large dataset of information regarding aging in nearly 3,000 mice, the researchers found that it also contained genetic information. After obtaining access to the database, they analyzed that genetic information—more specifically, they conducted quantitative trait locus mapping. They found multiple loci that they could associate with longevity, some that were specific to one or the other gender. They also found that mice who weighed more during their early years or who had small litter sizes tended to die younger. They suggest the same genes that were associated with aging may have also played a role in the other two traits. The researchers also found that the aging-related genes they isolated appeared to remain dormant until the latter stages of a given individual's life.

The researchers then studied data available in public biobanks and found human genes that appeared to play the same role as the age-associated genes in mice. Next, they looked for and found similar genes in a type of worm—disabling those genes influenced their longevity.

Maroun Bou Sleiman et al, Sex- and age-dependent genetics of longevity in a heterogeneous mouse population, Science (2022). DOI: 10.1126/science.abo3191

João Pedro de Magalhães, The genetics of a long life, Science (2022). DOI: 10.1126/science.ade3119

Comment by Dr. Krishna Kumari Challa on September 30, 2022 at 10:42am

Make cooking safe for all, including those in developing countries, say indoor air pollution experts

Developing countries should focus on keeping unnecessary occupants, such as children, out of kitchens during cooking to help reduce their exposure to dangerous levels of air pollution, recommends a study.

Researchers also highlighted the benefits of using cleaner fuels and electric appliances that help reduce carbon dioxide levels within a kitchen by more than 32 percent, compared to the use of polluting fuels.

The GCARE researchers and their partners found that kitchens that regularly had more than two people present during cooking sessions exhibited higher carbon dioxide levels.

The researchers found that cooking resulted in an average increase of 22 percent in carbon dioxide levels across the 60 homes.

Kitchens with their doors and windows open, that also used extractor fans during cooking were found to be the environments with optimal thermal comfort conditions. Having both kitchen doors and windows open during cooking was shown to reduce carbon dioxide levels by 14 percent when compared with environments that only kept their doors open.

Prashant Kumar et al, CO₂ exposure, ventilation, thermal comfort and health risks in low-income home kitchens of twelve global cities, Journal of Building Engineering (2022). DOI: 10.1016/j.jobe.2022.105254

Comment by Dr. Krishna Kumari Challa on September 30, 2022 at 10:29am

Next-generation liquid biopsy detects nano-sized signs of breast cancer in early-stage patients

A team of scientists has found indications that a special blood test called a liquid biopsy could determine whether a patient has breast cancer at its early stage and if that cancer is unlikely to return.

These high-definition comprehensive liquid biopsies are conducted using a standard blood draw from the arm of a patient in a doctor's office. Once in the laboratory, the sample is examined for signs of cancer. The results raise hopes that one day doctors could detect breast cancer in patients with a simple blood draw.

Researchers tested a theory that the high-definition liquid biopsy could detect multiple cancer biomarkers, including the so-called "oncosomes"—nano-sized, membraned cargo carriers that enrich the body's environment for cancer growth. These oncosomes are secreted by cancer cells as the group has shown previously.

They  found the vast majority of early-stage breast cancer patients have these oncosomes at very robust levels. They're about 5-10 microns in diameter. About the size of a cell. They first identified these large vesicles in prostate cancer about a year-and-a-half ago and showed that they are related to the cancer. They are hiding in plain sight.

If further studies produce similar results, this could mean that the next generation high-definition liquid biopsy may become a diagnostic tool for early breast cancer detection and other cancers. The test also could inform patients who have been treated for cancer that they will most likely remain cancer-free.

Sonia Maryam Setayesh et al, Multianalyte liquid biopsy to aid the diagnostic workup of breast cancer, npj Breast Cancer (2022). DOI: 10.1038/s41523-022-00480-4

Comment by Dr. Krishna Kumari Challa on September 30, 2022 at 8:39am

Comment by Dr. Krishna Kumari Challa on September 30, 2022 at 8:38am

A robotic pill that clears mucus from the gut to deliver meds

RoboCap administers medicine to the intestines and makes its way out of the body

The multivitamin-sized device houses a motor and a cargo hold for drugs, including ones that are typically given via injections or intravenously, such as insulin and some antibiotics. If people could take such drugs orally, they could potentially avoid daily shots or a hospital stay, which would be “a huge game changer". 

Drugs that enter the body via the mouth face a tough journey. They encounter churning stomach acid, raging digestive enzymes and sticky slicks of mucus in the gut. Intestinal mucus “sort of acts like Jell-O". The goo can trap drug particles, preventing them from entering the bloodstream.

The new device, dubbed RoboCap, whisks away this problem. The pill uses surface grooves, studs and torpedo-inspired fins to scrub away intestinal mucus like a miniature brush whirling inside a bottle. In experiments in pigs, RoboCap tunneled through mucus lining the walls of the small intestine, depositing insulin or the IV antibiotic vancomycin along the way,  researchers report September 28 in Science Robotics. After churning for about 35 minutes, the pill continued its trip through the gut and eventually out of the body.

RoboCap is the latest pill-like gadget made to be swallowed.

S. Srinivasan et al. RoboCap: Robotic mucus-clearing capsule for enhanced drug delivery .... Science Robotics. Published online September 28, 2022. doi: 10.1126/scirobotics.abp9066.

Comment by Dr. Krishna Kumari Challa on September 29, 2022 at 9:07am

Nanoparticles can improve stroke recovery by enhancing brain stimulation, study shows

In a recent study, researchers have reported that brain stimulation combined with a nose spray containing nanoparticles can improve recovery after ischemic stroke in an animal model.

The nasal spray is a non-invasive method for delivering magnetic nanoparticles into the brain that the study finds can increase the benefits of transcranial magnetic stimulation (TMS). TMS is a method of non-invasive brain stimulation already used clinically or in clinical trials to treat neurological conditions like stroke, Parkinson's disease, Alzheimer's disease, depression, and addiction.

Rats that were given combined nanoparticle and TMS treatment every 24 hours for 14 days after an ischemic stroke had better overall health, put on weight more quickly and had improved cognitive and motor functions compared to those treated with TMS alone. During TMS treatment, an electrical current runs through an electric coil placed outside the skull, producing a magnetic field that stimulates brain cells by inducing a further electrical current inside the brain. However, the stimulation is often not intense enough to penetrate far enough into the brain to reach the areas needing treatment. In this new study, published in Materials Today Chemistry, the researchers show that magnetic nanoparticles, administered intranasally, can make neurons more responsive and amplify the magnetic signal from TMS to reach deeper brain tissue, aiding recovery. The finding offers new opportunities for treating neurological disorders.

Researchers overcame the blood brain barrier by guiding the magnetic nanoparticles closer to the correct area with a large magnet near the head.

 Y. Hong et al, Enhancing non-invasive brain stimulation with non-invasively delivered nanoparticles for improving stroke recovery, Materials Today Chemistry (2022). DOI: 10.1016/j.mtchem.2022.101104

Comment by Dr. Krishna Kumari Challa on September 29, 2022 at 8:35am

Scientists create 'non-psychedelic' compound with same anti-depressant effect

While illegal for recreational use, psychedelic drugs are showing great promise as treatments for severe depression and anxiety, as well as alcohol addiction and other conditions. Some  scientists think the actual psychedelic trip—hallucinations and profound emotional experiences—is what leads to long-lasting therapeutic effects. Other scientists speculate that if the "trip" could be eliminated from such drugs, then only the therapeutic effects might remain. Researchers have taken a major step toward answering that question.

Research in animal models show it's possible to create a compound that hits the same exact target as psychedelic drugs  hit—the 5-HT2A serotonin receptors on the surface of specific neurons—but does not cause the same psychedelic effects when given to mice. The new compound triggers the same anti-depressant action that researchers have long observed in mice treated with SSRI drugs over the past two decades, with just two differences: the anti-depressant action of the new compound was immediate and long-lasting after just one dose.

Brian Shoichet, Bespoke library docking for 5-HT2A receptor agonists with anti-depressant activity, Nature (2022). DOI: 10.1038/s41586-022-05258-z

Comment by Dr. Krishna Kumari Challa on September 28, 2022 at 11:51am

Tiny Robots Have Successfully Cleared Pneumonia From The Lungs of Mice

Scientists have been able to direct a swarm of microscopic swimming robots to clear out pneumonia microbes in the lungs of mice, raising hopes that a similar treatment could be developed to treat deadly bacterial pneumonia in humans.

The microbots are made from algae cells and covered with a layer of antibiotic nanoparticles. The algae provide movement through the lungs, which is key to the treatment being targeted and effective.

In experiments, the infections in the mice treated with the algae bots all cleared up, whereas the mice that weren't treated all died within three days.

The technology is still at a proof-of-concept stage, but the early signs are very promising. Based on this mouse data, researchers see that the microrobots could potentially improve antibiotic penetration to kill bacterial pathogens and save more patients' lives.

The nanoparticles on the algae cells are made of tiny polymer spheres coated with the membranes of neutrophils, a type of white blood cell. These membranes neutralize inflammatory molecules produced by bacteria and the body's own immune system, and both the nanoparticles and the algae degrade naturally.

Harmful inflammation is reduced, improving the fight against infection, and the swimming microbots are able to deliver their treatment right where it's needed – it's the precision that makes this approach work so well.

The researchers also established that the microbot treatment was more effective than an intravenous injection of antibiotics – in fact, the injection dose had to be 3,000 times higher than the one loaded on to the algae cells to achieve the same effect in the mice.

These results show how targeted drug delivery combined with active movement from the microalgae improves therapeutic efficacy.

https://www.nature.com/articles/s41563-022-01360-9

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