Publisher Health

A combination of remdesivir, a drug currently approved in the United States for treating COVID-19 patients, and repurposed drugs for hepatitis C virus (HCV) was 10 times more effective at inhibiting SARS-CoV-2, the virus that causes COVID-19.
The combination therapy points a way toward a treatment for unvaccinated people who become infected, as well as for vaccinated people whose immunity has waned, for example due to the emergence of virus variants that escape this immune protection.
Four HCV drugs — simeprevir, vaniprevir, paritaprevir, and grazoprevir — in combination with remdesivir boosted the efficacy of remdesivir by as much as 10-fold, the researchers reported today in Cell Reports. The research team included scientists from Icahn School of Medicine at Mount Sinai, the University of Texas at Austin, and Rensselaer Polytechnic Institute (RPI).
Remdesivir targets a range of viruses and was originally developed over a decade ago to treat hepatitis C and a cold-like virus called respiratory syncytial virus (RSV). During the Ebola outbreak, Remdesivir was tested in clinical trials and found to be safe and effective for patients. Early in the pandemic, it was seen as a good therapy for COVID-19 but did not live up to its early promise in studies.
The research team performed protein binding and viral replication studies on SARS-CoV-2, the virus that causes COVID-19, using remdesivir and 10 hepatitis C drugs, some of which are already approved by the Food and Drug Administration.
RPI team had previously identified “striking similarity” between protease structures, or enzymes that are essential for coronaviral replication, in SARS-CoV-2 and HCV. The similarity raised the possibility that existing drugs which bind to and block the hepatitis C protease would have the same effect against SARS-CoV-2.

The COVID-19 vaccine isn’t having any trouble attracting suitors.
But there’s another, older model that’s been mostly ignored by the young men of America: the HPV vaccine.
Using data from the 2010-2018 National Health Interview Surveys, Michigan Medicine researchers found that just 16% of men who were 18 to 21 years old had received at least one dose of the HPV vaccine at any age. In comparison, 42% of women in the same age bracket had gotten at least one shot of the vaccine.
The CDC’s Advisory Committee on Immunization Practices recommends two doses of the vaccine at 11 or 12 years old, but Americans can still benefit from the HPV vaccine if they receive it later, as long as they get three doses by age 26.
In the U-M study, however — even among those who were vaccinated after turning 18 — less than a third of men received all three vaccine doses, and about half of women did.
“Eighteen- to 21-year-olds are at this age where they’re making health care decisions on their own for the first time,” says Michelle M. Chen, M.D., a clinical lecturer in the Department of Otolaryngology-Head and Neck Surgery and the first author of the study. “They’re in a period of a lot of transition, but young adult men especially, who are less likely to have a primary care doctor, are often not getting health education about things like cancer prevention vaccines.”
The HPV vaccine was designed to prevent reproductive warts and cancers caused by the most common sexually transmitted infection in the United States. The FDA approved the vaccine for women in 2006 and expanded it to men in 2009.
Preventing cervical cancer was the primary focus at that time, so girls and women were more likely to hear about it from their pediatricians or OBGYNs. Yet oropharyngeal cancer, which occurs in the throat, tonsils, and back of the tongue, has now surpassed cervical cancer as the leading cancer caused by HPV — and 80% of those diagnosed with it are men.
“I don’t think that a lot of people, both providers and patients, are aware that this vaccine is actually a cancer-prevention vaccine for men as well as women,” Chen says. “But HPV-associated oropharyngeal cancer can impact anyone — and there’s no good screening for it, which makes vaccination even more important.”
Chen believes a dual-prong approach is necessary to up the HPV vaccination rate for those who are male, with renewed pushes from pediatricians to target kids and outreach from university health services and fraternity houses for the young adult population who may have missed getting the vaccine when they were younger. Pharmacists as well as urgent care and emergency room providers could also be helpful allies.
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Materials provided by Michigan Medicine – University of Michigan. Original written by Mary Clare Fischer. Note: Content may be edited for style and length.

In a uniquely deep and detailed look at how the commonly used anesthetic propofol causes unconsciousness, a collaboration of labs at The Picower Institute for Learning and Memory at MIT shows that as the drug takes hold in the brain, a wide swath of regions become coordinated by very slow rhythms that maintain a commensurately languid pace of neural activity. Electrically stimulating a deeper region, the thalamus, restores synchrony of the brain’s normal higher frequency rhythms and activity levels, waking the brain back up and restoring arousal.
“There’s a folk psychology or tacit assumption that what anesthesia does is simply ‘turn off’ the brain,” said Earl Miller, Picower Professor of Neuroscience and co-senior author of the study in eLife. “What we show is that propofol dramatically changes and controls the dynamics of the brain’s rhythms.”
Conscious functions, such as perception and cognition, depend on coordinated brain communication, in particular between the thalamus and the brain’s surface regions, or cortex, in a variety of frequency bands ranging from 4 to 100 Hz. Propofol, the study shows, seems to bring coordination among the thalamus and cortical regions down to frequencies around just 1 Hz.
Miller’s lab, led by postdoc Andre Bastos and former graduate student Jacob Donoghue, collaborated with that of co-senior author Emery N. Brown, who is Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience and an anesthesiologist at Massachusetts General Hospital. The collaboration therefore powerfully unified the Miller lab’s expertise on how neural rhythms coordinate the cortex to produce conscious brain function with the Brown lab’s expertise in the neuroscience of anesthesia and statistical analysis of neural signals.
Brown said studies that show how anesthetics change brain rhythms can directly improve patient safety because these rhythms are readily visible on the EEG in the operating room. The study’s main finding of a signature of very slow rhythms across the cortex offers a model for directly measuring when subjects have entered unconsciousness after propofol administration, how deeply they are being maintained in that state, and how quickly they may wake up once propofol dosing ends.
“Anesthesiologists can use this as a way to better take care of patients,” Brown said.

A new treatment is among the first known to reduce the severity of acute respiratory distress syndrome caused by the flu in animals, according to a new study.
Tests in mice infected with high doses of influenza showed that the treatment could improve lung function in very sick mice and prevent progression of disease in mice that were pre-emptively treated after being exposed to the flu.
The hope is that it may also help humans infected with the flu, and potentially other causes of acute respiratory distress syndrome (ARDS) such as SARS-CoV-2 infection.
Specific cells in mice are less able to make key molecules after influenza invades the lungs, reducing their ability to produce a substance called surfactant that enables lungs to expand and contract. The shortage of surfactant is linked to ARDS, an illness so serious that it typically requires mechanical ventilation in an ICU.
Researchers bypassed the blocked process in mice by re-introducing the missing molecules alone or in combination as an injected or oral treatment. The results: normalized blood oxygen levels and reduced inflammation in mouse lungs — effects that could make a person well enough for hospital discharge.
“The most important and impressive thing in this study is the fact that we have benefits even when we treat late in the disease process. If we could develop a drug based on these findings, you could take somebody who’s going to have to go on a ventilator and stop that completely,” said Ian Davis, professor of veterinary biosciences at The Ohio State University and senior author of the study. “There’s nothing out there now that can do this for ARDS that will bring them back to that degree, and certainly not for flu.”
ARDS can also result from infections, cancer, trauma and many other ailments. Though this therapy has been tested in the context of the flu, Davis said its reliance on fixing a broken cell function in the host rather than killing the virus suggests it has potential to treat virtually any lung injury.

Scientific studies rarely focus on long non-coding RNA molecules (lncRNAs), even though they potentially regulate several diseases. The role of several lncRNAs in anti-viral inflammatory response regulation has recently been reported. Considering their significant regulatory function in immune response, researchers from the Azrieli Faculty of Medicine of Bar-Ilan University sought to identify lncRNAs co-expressed with human genes involved in immune-related processes during severe SARS-CoV-2 infection in the lungs.
Recent studies demonstrated that patients afflicted with severe SARS-CoV-2 infections present increased levels of pro-inflammatory plasma cytokines, as opposed to milder cases, highlighting the release of inflammatory cytokines as being central to COVID-19 severity. However, the underlying molecular mechanisms responsible for dysfunctional immune responses during COVID-19 infection remain elusive.
In a paper recently published in the journal Viruses, the researchers demonstrated that lncRNAs are indeed potential regulators of anti-viral response during severe SARS-CoV-2 infection. Using the available transcriptome data from the lung cells of severely affected COVID-19 patients and SARS-CoV-2 infected lung-cell-lines, they constructed a gene co-expression network that can measure the relationship of gene expression patterns across a group of samples. This analysis enables them to identify four differentially expressed lncRNAs that are found to be strongly correlated to the protein-coding genes in a novel network enriched for different immune-related processes associated with dysregulated cytokine production. These four lncRNAs were also identified as “hubs” — important nodes in this co-expression network, signifying their association with cytokine over-production due to fierce immune response.
The finding suggests that the aberrant expression of lncRNAs can be associated with cytokine storms and anti-viral responses during severe SARS-CoV-2 infection. Thus, the present study uncovers the potential associations of lncRNAs in cytokine and interferon signaling during the response to severe SARS-CoV-2 infection in the lungs. This could provide valuable insight into pro-inflammatory cytokine production and how to mitigate it. It could also potentially be utilized as a future drug target to combat the hyper-inflammation caused by SARS-CoV-2 infection.
“It is remarkable that a major part of the human genome is filled in by non-coding regulatory elements, formerly known as “junk DNA.” Among these are the long non-coding RNAs (lncRNAs). These lncRNAs are receiving more and more recognition as the potential regulators of several diseases,” says Dr. Milana Frenkel-Morgenstern, of Bar-Ilan University’s Azrieli Faculty of Medicine, who led the study with Prof. David Karasik.
This study sheds light on the mechanisms behind COVID-19 severity and dysfunctional immune responses. Understanding the molecular interactions behind the immune dysfunction during severe COVID-19 infection in the lungs should help inform the design and development of novel approaches for treating severe COVID-19 patients.
The researchers plan to validate their findings on human samples in collaboration with several of Israel’s health care centers. Further, they will aim to determine which drugs from their COVID-19 drug database may inhibit the cytokine storm generation in COVID-19, and will design experiments to test the efficacy of those drugs.
This study was supported by a grant from the COVID-19 Data Science Institute (DSI) at Bar-Ilan University and a PBC fellowship for outstanding postdoctoral researchers from China and India (to Dr. Sumit Mukherjee, who participated in the research) from the Israel Council for Higher Education.
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Materials provided by Bar-Ilan University. Note: Content may be edited for style and length.

Cryopreservation, or the long-term storage of biomaterials at ultralow temperatures, has been used across cell types and species. However, until now, the practical cryopreservation of the fruit fly (Drosophila melanogaster) — which is crucial to genetics research and critical to scientific breakthroughs benefiting human health — has not been available.
“To keep alive the ever-increasing number of fruit flies with unique genotypes that aid in these breakthroughs, some 160,000 different flies, laboratories and stock centers engage in the costly and frequent transfer of adults to fresh food, risking contamination and genetic drift,” said Li Zhan, a postdoctoral associate with the University of Minnesota College of Science and Engineering and the Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio).
In new research published in Nature Communications, a University of Minnesota team has developed a first-of-its-kind method that cryopreserves fruit fly embryos so they can be successfully recovered and developed into adult insects. This method optimizes embryo permeabilization and age, cryoprotectant agent composition, different phases of nitrogen (liquid vs. slush), and post-cryopreservation embryo culture methods.
Researchers were able to: show that the method is broadly applicable and easily adopted by non-specialists, with it being successfully implemented in 25 distinct strains for fruit flies from different sources (e.g., laboratories); demonstrate that for most strains, more than 50% of embryos hatch and more than 25% of the resulting larvae develop into adults after cryopreservation; and show that flies retain normal sex ratio, fertility and original mutation after successive crypropreservation through generations and long-time storage in liquid nitrogen.

During the last 30 years, medical and dental research has attracted a large number of scientists and practitioners working on aspects of high medical relevance that involve a combination of genetic and tissue regeneration approaches. These developments in stem cell and tissue engineering have provided medical and dental researchers with new insights and given rise to new ideas as to how everyday clinical practice can be improved. Many research groups are dealing with questions like: How can we help injured tissues and organs heal? Can lost tissue be regenerated? How can we create solid protocols that apply across all stem cell therapies?
Advanced single-cell sequencing technology used
A team of researchers led by Thimios Mitsiadis, professor at the Institute of Oral Biology at the University of Zurich, and Dr. Andreas Moor, professor at the Department of Biosystems Science and Engineering at ETH Zurich, has now created the first-ever single cells atlas of the human teeth. By using advanced single-cell sequencing technology, they were able to distinguish every single cell that is part of the dental pulp and the periodontium. “Our study provides an unprecedented understanding of the composition of these two tissues, which are subject to tooth-specific and bacterially-linked pathologies such as caries and periodontitis. Both the dental pulp and the periodontium contain stem cells that possess a great regenerative potential,” states first co-author Pierfrancesco Pagella, senior researcher in Mitsiadis’ team.
The study identified great cellular heterogeneity in the dental pulp and the periodontium. Unexpectedly, the team found that the molecular signatures of the stem cell populations were very similar. “We think their different behavior is possibly brought about by their distinctive microenvironment,” says Pagella. The findings suggest that the microenvironmental specificity is the potential source of the major functional differences of the stem cells located in the various tooth compartments.
New cell-based dental therapies possible
The study demonstrates the complexity of dental tissues and represents a major contribution to a better understanding of the cellular and molecular identity of human dental tissues. “Single-cell approaches can help us understand the interactions of dental pulp and periodontal cells involved in immune responses upon bacterial insults. Therefore, single-cell analysis could be useful for diagnostic purposes to support the early detection of dental diseases,” last author Thimios Mitsiadis explains. The findings thus open up new avenues for cell-based dental therapeutic approaches.
According to Mitsiadis, these advances in dental research can lead to more appropriate therapies, successful regeneration of damaged parts of the teeth, and even more precise diagnostic tools in case of dental pathologies. “These innovations are the consequence of the fusion between bioinformatics and modern dentistry,” he concludes.
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Materials provided by University of Zurich. Note: Content may be edited for style and length.

Originally, oxygen radicals — reactive oxygen species, or ROS for short — were considered to be exclusively harmful in the body. They are produced, for example, by smoking or UV radiation. Because of their high reactivity, they can damage many important molecules in cells, including the hereditary molecule DNA. As a result, there is a risk of inflammatory reactions and the degeneration of affected cells into cancer cells.
Because of their damaging effect, however, ROS are also deliberately produced by the body, for example by immune or lung epithelial cells, which destroy invading bacteria and viruses with ROS. This requires relatively high ROS concentrations. In low concentrations, on the other hand, ROS play an important role as signalling molecules. For these tasks, ROS are specifically produced by a whole group of enzymes. One representative of this group of enzymes is Nox4, which continuously produces small amounts of H2O2. Nox4 is found in almost all body cells, where its product H2O2 maintains a large number of specialised signaling functions, contributing, for example, to the inhibition of inflammatory reactions.
Researchers at Goethe University Frankfurt, led by Professor Katrin Schröder, have now discovered that by producing H2O2, Nox4 can even prevent the development of cancer. They examined mice that were unable to produce Nox4 due to a genetic modification. When these mice were exposed to a carcinogenic environmental toxin (cancerogen), the probability that they would develop a tumour doubled. Since the mice suffered from very different types of tumours such as skin sarcomas and colon carcinomas, the researchers suspected that Nox4 has a fundamental influence on cellular health.
Molecular investigations showed that the H2O2 formed by Nox4 keeps a cascade going that prevents certain important signalling proteins (phosphatases) from entering the cell nucleus. If Nox4 and consequently H2O2 are absent, those signalling proteins migrate into the cell nucleus and as a consequence, severe DNA damage is hardly recognised.
Severe DNA damage — e.g. double strand breaks — occurs somewhere in the body every day. Cells react very sensitively to such DNA damage, setting a whole repertoire of repair enzymes in motion. If this does not help, the cell activates its cell death programme — a precautionary measure of the body against cancer. When such damage goes unrecognised, as occurs in the absence of Nox4, it spurs cancer formation.
Prof. Katrin Schröder explains the research results: “If Nox4 is missing and there is therefore no H2O2, the cells no longer recognise DNA damage. Mutations accumulate and damaged cells continue to multiply. If an environmental toxin is added that massively damages the DNA, the damage is no longer recognised and repaired. The affected cells are not eliminated either, but multiply, sometimes very quickly and uncontrollably, which eventually leads to the development of tumours. A small amount of H2O2 thus maintains an internal balance in the cell that protects the cells from degeneration.”
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Materials provided by Goethe University Frankfurt. Note: Content may be edited for style and length.

A recent study by the University of Eastern Finland shows that loneliness among middle-aged men is associated with an increased risk of cancer. According to the researchers, taking account of loneliness and social relationships should thus be an important part of comprehensive health care and disease prevention. The findings were published in Psychiatry Research.
“It has been estimated, on the basis of studies carried out in recent years, that loneliness could be as significant a health risk as smoking or overweight. Our findings support the idea that attention should be paid to this issue,” Project Researcher Siiri-Liisi Kraav from the University of Eastern Finland says.
The study was launched in the 1980s with 2,570 middle-aged men from eastern Finland participating. Their health and mortality have been monitored on the basis of register data up until present days. During the follow-up, 649 men, i.e. 25% of the participants, developed cancer, and 283 men (11%) died of cancer. Loneliness increased the risk of cancer by about ten per cent. This association with the risk of cancer was observed regardless of age, socio-economic status, lifestyle, sleep quality, depression symptoms, body mass index, heart disease and their risk factors. In addition, cancer mortality was higher in cancer patients who were unmarried, widowed or divorced at baseline.
“Awareness of the health effects of loneliness is constantly increasing. Therefore, it is important to examine, in more detail, the mechanisms by which loneliness causes adverse health effects. This information would enable us to better alleviate loneliness and the harm caused by it, as well as to find optimal ways to target preventive measures.”
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Materials provided by University of Eastern Finland. Note: Content may be edited for style and length.

Ship movements on the world’s oceans dropped in the first half of 2020 as Covid-19 restrictions came into force, a new study shows.
Researchers used a satellite vessel-tracking system to compare ship and boat traffic in January to June 2020 with the same period in 2019.
The study, led by the University of Exeter (UK) and involving the Balearic Islands Coastal Observing and Forecasting System and the Mediterranean Institute for Advanced Studies (both in Spain), found decreased movements in the waters off more than 70 per cent of countries.
Global declines peaked in April 2020, but by June — as Covid restrictions were eased in many countries — ship movements began to increase.
“As lockdowns came into force, we heard stories and began to see early research findings that suggested reduced boat movements had allowed some marine ecosystems to recover,” said lead-author Dr David March of the Centre for Ecology and Conservation on Exeter’s Penryn Campus in Cornwall.
“There were reports of clearer water in Venice’s canals, and a study showed a reduction in underwater noise at Vancouver.”
Professor Brendan Godley, who leads the Exeter Marine research group, added: “The effects of ships and boats — from noise and pollution to fishing and collisions with animals — have a major impact on marine ecosystems across the world.