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Melatonin produced in the lungs prevents infection by novel coronavirus

The hormone acts as a barrier against SARS-CoV-2, blocking the expression of genes that encode proteins in cells serving as

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The hormone acts as a barrier against SARS-CoV-2, blocking the expression of genes that encode proteins in cells serving as viral entry points, according to a study by researchers at the University of São Paulo

By Elton Alisson | Agência FAPESP – Melatonin synthesized in the lungs acts as a barrier against SARS-CoV-2, preventing expression of genes that encode proteins in cells such as resident macrophages in the nose and pulmonary alveoli, and epithelial cells lining the alveoli, all of which are entry points for the virus. The hormone, therefore, prevents infection of these cells by the virus and inhibits the immune response so that the virus remains in the respiratory tract for a few days, eventually leaving to find another host.

The discovery by researchers at the University of São Paulo (USP), in Brazil, helps understand why some people are not infected or do not manifest symptoms of COVID-19 even when reliably diagnosed as carriers of the virus by RT-PCR. In addition, it offers the prospect of nasal administration of melatonin, in drops or as a spray, to prevent disease from developing in pre-symptomatic patients.

Pre-clinical and clinical trials will be needed to prove the therapeutic efficacy of melatonin against the virus, the researchers stress in an article on the study published in the journal Melatonin Research.

The study was supported by FAPESP.

“We showed that melatonin produced in the lung acts as a barrier against SARS-CoV-2, preventing the virus from entering the epithelium, activating the immune system and triggering the production of antibodies,” Regina Pekelmann Markus, a professor at USP’s Institute of Biosciences (IB) and principal investigator for the project, told Agência FAPESP.

“This action mechanism by pulmonary melatonin must also involve other respiratory viruses such as influenza,” she added.

Markus began researching melatonin in the 1990s. In a study involving rodents, she showed that the hormone, produced at night by the pineal gland in the brain to tell the organism daylight has gone and it should prepare for sleep, can be produced in other organs, such as the lungs.

In a study also involving rodents, published in early 2020 in the Journal of Pineal Research, Markus and collaborators showed that resident macrophages in the pulmonary airspace absorb (phagocytize) particles of pollution. This aggressive stimulus induced the production of melatonin and other molecules by the macrophages, engulfing the particulate matter in the air breathed in by the animals and stimulating mucous formation, coughing, and expectoration to expel the particles from the respiratory tract.

When they blocked melatonin synthesis by resident macrophages, the researchers observed that the particles entered the bloodstream and spread throughout the organism, even invading the brain.

Based on the finding that melatonin produced in the lungs altered the entry points for particulate matter from air pollution, Markus and collaborators decided to investigate whether the hormone performed the same function with regard to SARS-CoV-2. “If so, the virus wouldn’t be able to bind to the ACE-2 receptor on cells, enter the epithelium and infect the organism,” Markus said.

Analysis of gene expression

To test this hypothesis, the researchers analyzed 455 genes associated in the literature with COVID-19 comorbidities, interaction between SARS-CoV-2 and human proteins, and viral entry points. The genes had been identified in studies conducted, among others, by Helder Nakaya, a professor at USP’s School of Pharmaceutical Sciences (FCF) and a co-author of the study on lung melatonin.

From this group of genes, they selected 212 genes involved in viral cell entry, intracellular traffic, mitochondrial activity, and transcription and post-translation processes, to create a physiological signature of COVID-19.

Using RNA sequencing data downloaded from a public database, they quantified the level of expression of the 212 COVID-19 signature genes in 288 samples from healthy human lungs.

They then correlated these gene expression levels with a gene index that estimated the capacity of the lungs to synthesize melatonin (MEL-Index), based on their analysis of the lungs in healthy rodents. They found that the lower the index the higher the level of expression of genes that encode proteins for resident macrophages and epithelial cells.

The index also correlated negatively with genes that modify proteins in cell receptor CD147, a viral entry point in macrophages and other immune cells, indicating that normal lung melatonin production may be a natural protector against the virus.

The results were corroborated by three statistical techniques: the Pearson test, which measures the degree of linear correlation between two variables; a gene set enrichment analysis; and a network analysis tool that maps the connections among the most expressed genes so as to compare the same set of genes in different states. The latter was developed by Marcos Buckeridge, a professor at IB-USP and also a co-author of the study.

“We found that when MEL-Index was high the entry points for the virus in the lungs were closed, and when it was low these ‘doors’ were open. When the doors are shut, the virus wanders around for a time in the pulmonary airspace and then tries to escape in search of another host,” Markus said.

Because lung melatonin inhibits transcription of these genes that encode proteins for viral entry point cells, application of melatonin directly into the lungs in the form of drops or spray could block the virus. More research is required to prove that this is indeed the case, however, the researchers note.

Another idea could be to use MEL-Index, the pulmonary melatonin metric, as a prognostic biomarker to detect asymptomatic carriers of SARS-CoV-2.

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About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

Source: https://bioengineer.org/melatonin-produced-in-the-lungs-prevents-infection-by-novel-coronavirus/

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Sex differences in COVID-19 outcomes

Credit: Mary Ann Liebert, Inc., publishers In a study of more than 10,600 adult patients hospitalized with COVID-19, women had

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In a study of more than 10,600 adult patients hospitalized with COVID-19, women had significantly lower odds than men of in-hospital mortality. They also had fewer admissions to the intensive care unit and less need for mechanical ventilation. Women also had significantly lower odds of major adverse events, including acute cardiac injury, acute kidney injury, and venous thromboembolism, according to an article in the peer-reviewed Journal of Women’s Health. Click here to read the article now.

“This comprehensive analysis is the largest study to date that directly assesses the impact of sex on COVID-19 outcomes,” stated Rachel-Maria Brown, MD, Zucker School of Medicine at Hofstra/Northwell, and coauthors. “Our study strongly demonstrates female sex to be associated with lower odds of in-hospital outcomes, major adverse effects and all-cause mortality as compared to male sex after controlling for confounding variables.” The authors propose some of the protective factors that may contribute to these findings.

In the accompanying editorial entitled “Lessons Learned from COVID-19 Sex Disparities,” Annabelle Santos Volgman, MD, Rush University Medical Center, and coauthors, suggest various mechanisms by which female sex may confer a protective advantage against COVID-19 infection. One advantage may be the extra X chromosome, which carries multiple genes responsible for innate and adaptive immunity.

Volgman and coauthors emphasize that “although women have less mortality risk with COVID-19, we need to exercise caution not to send a message to deliver subpar care to women with COVID-19 or decrease measures to prevent their infection. Our evolving knowledge should not reduce attention paid to women admitted for COVID-19.”

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Research reported in this publication was supported by the National Institutes of Health under Award Number R24AG064191, R01LM012836, R01 NR018443. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About the Journal

Journal of Women’s Health, published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. Led by Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women’s Health, Richmond, VA, the Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women’s healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women’s Health website. Journal of Women’s Health is the official journal of the Society for Women’s Health Research.

About the Publisher

Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. A complete list of the

Source: https://bioengineer.org/sex-differences-in-covid-19-outcomes/

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UTHSC awarded $1.5 million HRSA grant for sexual assault nurse examiner training

Credit: UTHSC Memphis, Tenn. (June 16, 2021) – The University of Tennessee Health Science Center’s College of Nursing has received

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Memphis, Tenn. (June 16, 2021) – The University of Tennessee Health Science Center’s College of Nursing has received a three-year, $1.5 million grant from the Department of Health and Human Services Health Resources and Services Administration (HRSA) to fund a much-needed expansion of Sexual Assault Nurse Examiner (SANE) training and certification in West Tennessee.

SANE programs are designed to train nurses to address survivors’ needs and provide trauma-informed care. The 21 counties of West Tennessee have only five certified SANE nurses, four of whom practice in Shelby County. But the Tennessee Bureau of Investigation received nearly 1,600 reports of sexual assault in West Tennessee in 2019, indicating a significant shortage of nurses certified to meet the need for this care.

Andrea Sebastian, DNP, PNP, SANE-P, an assistant professor in the UTHSC College of Nursing, has worked as a child abuse nurse practitioner for the last seven years at Le Bonheur Children’s Hospital and will serve as project manager of the SANE Training and Education through Partnerships for Underserved Populations (STEP UP) grant.

“During this time, I have recognized the importance of SANE nurses in our community. Currently, we do not have enough SANE nurses in West Tennessee to provide exams and resources to victims,” Dr. Sebastian said. “With this grant, we will be able to increase access to these invaluable resources and help victims of sexual assault in our community.”

The UTHSC team will work with West Tennessee Healthcare, the Shelby County Crime Victims and Rape Crisis Center, and the Whiteville Family Medical Clinic on the project. The team’s goal is to transform the nursing workforce by increasing the supply, distribution, and retention of certified SANEs and improving access to timely, expert care for all sexual assault survivors in West Tennessee.

Assistant Professor Christie Manasco, PhD, RN, is one of the co-investigators on the grant. “The funding from this grant will significantly help us close the gaps to equitable SANE care in West Tennessee. The efforts supported by these funds will help us to reduce inequalities and disparities and promote better outcomes for survivors,” she said.

Beginning in July, the STEP UP grant team will launch a plan to recruit up to 61 registered nurses or advanced practice registered nurses (APRNs) from the West Tennessee counties, with a focus on the rural and underserved areas. The grant will pay for participants to earn certifications through community or academic programs for adult and pediatric patients, known as SANE-A® and SANE-P®.

The grant team will also work with regional stakeholders to develop and implement a regional Sexual Assault Response and Resource Team (SARRT) that will assess the needs for sexual assault services in the area, reduce barriers to SANE training, and coordinate SANE clinical training opportunities. Grant funding also will be used to develop and provide resources for SANE self-care, peer mentoring, continuing education, and recertification.

Dr. Sebastian will be supported on this grant by co-investigators including Dr. Manasco, Assistant Professor Lisa Beasley, DNP, APRN, NP-C, RN; Assistant Professor Sally Humphrey, DNP, ARN, CPNP-PC; and Assistant Professor Diana Dedmon, DNP, FNP-BC, director of Clinical Affairs. College of Nursing Dean Wendy Likes, PhD, DNSc, APRN-Bc, FAANP, will serve as women’s health adviser on the grant, and the program coordinator for the Doctor of Nursing Practice DNP program, Trimika Bowdre, PhD, MPH, will be the evaluation adviser.

“The College of Nursing is very grateful for the funding to support this important work of providing appropriate care to this very vulnerable group of people,” Dr. Likes said. “The need for this in West Tennessee is beyond question. I personally look forward to working with this team in the College of Nursing and our community partners to provide this vital service to our communities.”

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As Tennessee’s only public, statewide, academic health system, the mission of the University of Tennessee Health Science Center is to bring the benefits of the health sciences to the achievement and maintenance of human health through education, research, clinical care, and public service, with a focus on the citizens of Tennessee and the region. The main campus in Memphis includes six colleges: Dentistry, Graduate Health Sciences, Health Professions, Medicine, Nursing and Pharmacy. UTHSC also educates and trains medicine, pharmacy, and/or health professions students, as well as medical residents and fellows, at major sites in Knoxville, Chattanooga and Nashville. For more information, visit http://www.uthsc.edu. Find us on Facebook: facebook.com/uthsc, on Twitter: twitter.com/uthsc and on Instagram: instagram.com/uthsc.

Source: https://bioengineer.org/uthsc-awarded-1-5-million-hrsa-grant-for-sexual-assault-nurse-examiner-training/

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Pioneering chemistry approach could lead to more robust soft electronics

Credit: Udit Chakraborty, Cornell University RESEARCH TRIANGLE PARK, N.C. — A new approach to studying conjugated polymers made it possible

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RESEARCH TRIANGLE PARK, N.C. — A new approach to studying conjugated polymers made it possible for an Army-funded research team to measure, for the first time, the individual molecules’ mechanical and kinetic properties during polymerization reaction. The insights gained could lead to more flexible and robust soft electronic materials, such as health monitors and soft robotics.

Conjugated polymers are essentially clusters of molecules strung along a backbone that can conduct electrons and absorb light. This makes them a perfect fit for creating soft optoelectronics, such as wearable electronic devices; however, as flexible as they are, these polymers are difficult to study in bulk because they aggregate and fall out from solution.

“Conjugated polymers are a fascinating class of materials due to their inherent optical and electronic properties which are dictated by their polymer structure,” said Dr. Dawanne Poree, program manager, U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory. “These materials are highly relevant to a number of applications of interest to Army and DoD including portable electronics, wearable devices, sensors, and optical communication systems. To date, unfortunately, it has been difficult to develop conjugated polymers for targeted applications due to a lack of viable tools to study and correlate their structure-property relationships.”

With Army funding, researchers at Cornell University employed an approach they pioneered on other synthetic polymers, called magnetic tweezers, that allowed them to stretch and twist individual molecules of the conjugated polymer polyacetylene. The research was published in the journal Chem.

“Through the use of novel single-molecule manipulation and imaging approaches, this work provided the first observations of single-chain behaviors in conjugated polymers which lays the foundation for the rational design and processing of these materials to enable widespread application,” Poree said.

Previous efforts to address the solubility of conjugated polymers have often relied upon chemical derivatization, in which the structures are modified with functional groups of atoms. However, that approach can affect the polymer’s innate properties.

“The conjugated polymer is really a prototype,” said Dr. Peng Chen, the Peter J.W. Debye professor of chemistry and chemical biology at Cornell. “You always modify it to tailor it for applications. We are hoping everything we measured – the fundamental properties of synthesis kinetics, the mechanical property – become benchmark numbers for people to think about other polymers of the same category.”

In 2017, Chen’s group was the first to use the magnetic tweezers measurement technique to study living polymerization, visualizing it at the single-molecule level. The technique had already been used in the biophysics field for studying DNA and proteins, but no one had successfully extended it to the realm of synthetic polymers.

The process works by affixing one end of a polymer strand to a glass coverslip and the other end to a tiny magnetic particle. The researchers then use a magnetic field to manipulate the conjugated polymer, stretching or twisting it, and measuring the response of a single polymer chain that grows.

The amounts are so small, they stay soluble in solution, the way bulk amounts normally would not.

The team measured how long chains of conjugated polymers, which consist of hundreds of thousands of monomer units, grow in real time. They discovered these polymers add a new monomer per second, a much faster growth than their nonconjugated analogs.

“We found that while growing in real time, this polymer forms conformational entanglements,” Chen said. “All polymers we have studied form conformational entanglements, but for this conjugated polymer this conformational entanglement is looser, allowing it to grow faster.”

By pulling and stretching individual conjugated polymers, so-called force extension measurements, the researchers were able to assess their rigidity and better understand how they can bend in different directions while remaining conjugated and retaining electron conductivity.

They also discovered the polymers displayed diverse mechanical behaviors from one individual chain to the next-behaviors that had been predicted by theory but never observed experimentally.

The findings highlight both the uniqueness of conjugated polymers for a range of applications as well as the strength of using a single-molecule manipulation and imaging technique on synthetic materials.

“Now we have a new way to study how these conjugated polymers are made chemically and what is the fundamental mechanical property of this type of material,” Chen said. “We can study how these fundamental properties change when you start tailoring them for application purposes. Maybe you can make it more mechanically flexible and make the polymer longer, or adjust the synthesis condition to either synthesize the polymer in a faster or slower way.”

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Visit the laboratory’s Media Center to discover more Army science and technology stories

As the Army’s national research laboratory, ARL is operationalizing science to achieve transformational overmatch. Through collaboration across the command’s core technical competencies, we lead in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more successful at winning the nation’s wars and come home safely. DEVCOM Army Research Laboratory is an element of the U.S. Army Combat Capabilities Development Command. DEVCOM is a major subordinate command of the Army Futures Command.

Source: https://bioengineer.org/pioneering-chemistry-approach-could-lead-to-more-robust-soft-electronics/

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