Category Archives: Molecular Medicine

Rajasekharreddy Pala,1,2 VT Anju,3 Madhu Dyavaiah,3 Siddhardha Busi,4 Surya M Nauli1,2

1Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, Chapman University, Irvine, CA 92618, USA; 2Department of Medicine, University of California Irvine, Irvine, CA 92868, USA; 3Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India; 4Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry, India

Correspondence: Rajasekharreddy Pala; Surya M Nauli Tel +714-516-5462; +714-516-5480Fax +714-516-5481Email rrpala@chapman.edu; nauli@chapman.edu

Abstract: Cardiovascular diseases (CVDs) are one of the foremost causes of high morbidity and mortality globally. Preventive, diagnostic, and treatment measures available for CVDs are not very useful, which demands promising alternative methods. Nanoscience and nanotechnology open a new window in the area of CVDs with an opportunity to achieve effective treatment, better prognosis, and less adverse effects on non-target tissues. The application of nanoparticles and nanocarriers in the area of cardiology has gathered much attention due to the properties such as passive and active targeting to the cardiac tissues, improved target specificity, and sensitivity. It has reported that more than 50% of CVDs can be treated effectively through the use of nanotechnology. The main goal of this review is to explore the recent advancements in nanoparticle-based cardiovascular drug carriers. This review also summarizes the difficulties associated with the conventional treatment modalities in comparison to the nanomedicine for CVDs.

Keywords: cardiovascular diseases, nanoscience, nanoparticles, nanomedicine, nanocarriers, treatment

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Nanoparticle-Mediated Drug Delivery for the Treatment of Cardiovascula | IJN - Dove Medical Press

Naptime is over.

Ilhem Messaoudi Powers, associate professor of molecular biology & biochemistry at UCI, is enjoying a rare weekend at home with her husband, Dr. Michael Powers, when they hear the rustling of their two young children.

He bounds up the stairs to retrieve Owen, 3, and Olivia, 6 months, from a Saturday afternoon slumber. Soon the living room is full of the joyous noises of a toddler and an infant.

When theyre not wearing their mommy and daddy hats, Ilhem and Michael Powers are exploring and immersing themselves in an entirely different world: the COVID-19 pandemic.

A virologist and immunologist, Ilhem Powers leads a team of researchers whove launched a surveillance study of UCI Health workers to determine how many have antibodies against the coronavirus.

Michael Powers is a pulmonologist who works as a critical care doctor at the Naval Medical Center San Diego, caring for patients with COVID-19, as well as others.

Because of his unpredictable schedule, he often stays for days at an apartment in San Diego while his wife, with the assistance of a part-time nanny, juggles kids and career from the couples on-campus home and her laboratory.

Mike and I have been through a lot together, she says. Weve really learned to focus on the now.

Indeed, her husband was just two weeks into medical school at New Orleans Tulane University when Hurricane Katrina hit in late August of 2005. Ilhem Powers had accepted a job at the school as an assistant professor and was getting ready to relocate from their previous home in Portland, Oregon.

The New Orleans duplex that the couple had renovated with most of their savings wound up under 8 feet of water. It took them more than a year to recover.

One of the biggest lessons Ive learned in life is to focus on the things you have some control over, Michael Powers says. You just have to let go of the rest.

Surveillance study

Ilhem Powers lab cohort have pivoted from their usual work to conduct COVID-19 research as members of UCIs Institute for Immunology and Center for Virus Research.

Their surveillance study, funded by a $60,000 UCI grant and expected to last a year, will repeatedly examine 300 healthcare providers. The collection of samples has already begun.

We want to know how many of them may have already been exposed [to COVID-19] and didnt know about it and how many of them potentially have immunity, Ilhem Powers says. Well take blood samples and nose swabs to measure antibodies and T cell responses, which kill infected cells, as well as potential asymptomatic shedding. Its a multipronged approach.

Arriving at UCI in January 2017 after serving as a researcher and assistant professor at UC Riversides School of Medicine, she has years of experience studying how the human immune system interacts with emerging viral diseases such as Ebola, Chikungunya, Zika and monkeypox.

For some viruses, Ilhem Powers explains, antibodies are sufficient [to kill them]. For others, you need more of a T cell response. We dont yet know enough about this novel coronavirus.

More community surveillance needs to be done, she says: How many people have potential COVID-19 antibodies? We also need to look at the immune response in patients those currently in hospitals and then determine the difference between the immune response of those who end up in the ICU versus those who end up being sent home.

Health scare

Michael Powers, who began his residency at the Naval Medical Center San Diego in 2010, says the COVID-19 pandemic has forced him and other doctors to live with a lot of uncertainty.

But he has a stoic air about him despite his relatively new role of treating patients with a little-understood disease. Perhaps experiencing a serious lung-related health scare himself contributes to his even-keeled nature.

During his wifes last year at UC Riverside, Michael Powers went on an outreach mission to Ghana. Shortly after returning home, he developed MRSA in his lungs and had to undergo thoracic surgery. He spent 10 days in the hospital and 30 days in convalescence.

It was a pulmonologists worst nightmare, Ilhem Powers says. It was really scary.

So is COVID-19, her husband says: I think a lot of people have a very romanticized notion of what ICU-level care is and being on a ventilator. The movies definitely dont do it justice.

When people go on ventilators, its not at all uncommon for them to be on them for two weeks or more. Its not a pleasant thing to have a giant plastic tube down your throat and a machine telling you when to breathe.

Enjoying the little moments

Michael Powers says he takes extreme precautions at work and elsewhere in San Diego before driving up to Irvine to spend time with his wife and children.

People ask me all the time, Isnt he worried? Ilhem Powers says. They ask, Shouldnt he just stay in his apartment and not come up here and pose a health risk to you and your kids? And we just say we understand and accept the risk.

She and her colleagues get tested regularly for COVID-19 using equipment in their lab.

Having already weathered a lot of adversity, the couple believe theyre uniquely equipped to cope with COVID-19.

What we both do for a living, and our past experience dealing with crises, has put us in this perfect position to deal with this pandemic, he says.

For many people, she adds, this is the first time that things outside their control have completely dominated their life.

Often, the two will sit down and go over COVID-19 research papers together and compare notes, discussing where the pandemic is headed, possible therapies and longer term potential vaccines.

But they make sure that when theyre together, they shower most of their attention on Owen and Olivia.

When hes home, Ilhem Powers says of her husband, its family time. For us, its all about enjoying the little moments.

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Couple on the coronavirus front lines - UCI News

While in the UK the NHS kept tight control of testing until recently, the Portuguese government quickly realised spreading the load was the answer.

As recently as May 1 to 17, non-state labs were still responsible for more than half of the almost 14,000 tests being conducted daily.

But the roots of Portugals world-class Covid-19 testing regime began much earlier.According to Our World in Data whose testing rates have been cited by the OECD and others Portugal has been among the top 10 countries in the world for testing per capita since mid-April.

On Friday, Denmark (with a GDP per capita 2.7 times that of Portugal) and Lithuania (with a similar GDP per capita to Portugal) were the only nations of more than 2 million people with a higher testing rate.

Like most countries, Portugals initial testing efforts started slowly amid difficulties securing kits in a ferocious global market.

The stress initially was to provide testing, said biology professor Miguel Viveiros, deputy director of IMHT.

We were not prepared for testing in quantity for the speed of transmission. In early March, Portugal was testing less per capita than the UK and much of Europe.

Professor Maria Manuel Mota, director of the institute of molecular medicine at the University of Lisbon, was speaking to doctors at the large university hospital on campus. They were worried about having enough tests to make sure the disease wasnt spreading rapidly in the medical community, let alone for the wider population.

Obviously there will be no testing for everyone, they told her. It is a difficult test, it takes a few hours, you know, it's expensive.

Sitting at home on March 11, Professor Mota quickly discovered that didnt have to be the case, thanks to her institutes experience with PCR-based tests for malaria.

The test we do all the time in almost every single lab in our institute is PCR, so it should not be difficult, she remembered thinking. Instead of relying on expensive kits that come from abroad we could design something.

To lead the project, she called on researcher Vanessa Zuzarte Lus, who had a potential testing protocol in mind within a few hours. The next day they were speaking to a Portuguese company about manufacturing the reagents needed for the tests, one factor UK authorities blamed for testing difficulties.

They were ready and working within a week, leaving only accreditation from the Dr Ricardo Jorge National Institute of Health left to secure.

The Portuguese authorities were fantastic, Professor Mota said. As soon as I called the right people they told us okay, let's validate this together. The accreditation process ran smoothly and the tests were being rolled out to nursing homes by the end of March.

Within two or three weeks, university labs and private institutes across Portugal were using the protocol developed at IMM, or developing their own, to bolster public testing efforts.

In the UK, independent labs trying to take similar steps were still complaining their offers to help were being ignored as late as April 10, well after health secretary Matt Hancock set a target of 100,000 tests a day.

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Why Portugal's Covid-19 test rate is more than double almost every other nation - Telegraph.co.uk

Peng Gao,1,2 Shuo Shen,1,2 Xiaodong Li,3 Dandan Liu,1,2 Yuqing Meng,1,2 Yanqing Liu,1,2 Yongping Zhu,1,2 Junzhe Zhang,1,2 Piao Luo,1,2 Liwei Gu1,2

1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, Peoples Republic of China; 2Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, Peoples Republic of China; 3Institute of Chinese Materia Medica, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, Peoples Republic of China

Correspondence: Liwei Gu Email lwgu@icmm.ac.cn

Background: Leukemia threatens so many lives around the world. Dihydroartemisinin (DHA), as a typical derivative of artemisinin (ART), can efficiently inhibit leukemia, but the controversial mechanisms are still controversial. Many reports showed that tumor cells acquire energy through the glycolysis pathway, pyruvate kinase M2 (PKM2) plays a crucial role in regulating glycolysis. However, it is unclear whether PKM2 or other key molecules are involved in DHA induced cytotoxicity in leukemia cells. Thus, this paper systematically investigated the anticancer effect and mechanism of DHA on human chronic myeloid leukemia K562 cells.Methods: In vitro, cytotoxicity was detected with CCK-8. Glucose uptake, lactate production and pyruvate kinase activity were investigated to evaluate the effect of DHA on K562 cells. To elucidate the cellular metabolism alterations induced by DHA, the extracellular acidification rate was assessed using Seahorse XF96 extracellular flux analyzer. Immunofluorescence, real-time PCR, and Western blotting were used to investigate the molecular mechanism.Results: We found that DHA prevented cell proliferation in K562 cells through inhibiting aerobic glycolysis. Lactate product and glucose uptake were inhibited after DHA treatment. Results showed that DHA modulates glucose uptake through downregulating glucose transporter 1 (GLUT1) in both gene and protein levels. The cytotoxicity of DHA on K562 cells was significantly reversed by PKM2 agonist DASA-58. Pyruvate kinase activity was significantly reduced after DHA treatment, decreased expression of PKM2 was confirmed in situ.Conclusion: The present study implicated that DHA inhibits leukemia cell proliferation by regulating glycolysis and metabolism, which mediated by downregulating PKM2 and GLUT1 expression. Our finding might enrich the artemisinins antitumor mechanisms.

Keywords: tumor, leukemia, glycolysis, DHA, PKM2, GLUT1

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Dihydroartemisinin Inhibits the Proliferation of Leukemia Cells K562 b | DDDT - Dove Medical Press

Cryopreservation has become an indispensable step in the daily routine of scientific research as well as in a number of medical applications, ranging from assisted reproduction and transplantations to cell-based therapies and biomarker identification. It is hardly possible to picture todays scientific and medical advancements without this technique.The successful development and implementation of all the therapeutic and scientific discoveries involving cryopreservation relies on the correct and safe translation of the method from the laboratory to the clinical and manufacturing scale.

With the need to correctly use this technique, more research is focusing on optimizing cryopreservation methods and investigating what the long-term effects and consequences are on the physiology of the cryopreserved material.

An important part of cell therapy research is focused on adult stem cells (ASCs). ASCs can be derived from different sources such as peripheral blood, bone marrow or adipose tissue and display strong promises because of their capacity to differentiate into any cell type of the human body.In recent work3, the team of Michael Pepper at the Institute for Cellular and Molecular Medicine in Pretoria, South Africa, explored the effects of cryopreservation on the differentiation ability of adipose tissue-derived stem cells (ADSCs). After analyzing gene expression of key adipogenic genes and the degree of differentiating cells, characterized with high levels of CD36 and intracellular lipid droplets, the scientists reported that slow freeze cryopreservation of cells shortly after their isolation causes no alterations on their ability to differentiate. Pepper is convinced of the necessity to perform such analysis when cryopreserving important cell pools: It is critical to do a post-thaw analysis of cell function to determine how the cryopreservation may have affected the cells.His team is analyzing the effects of cryopreservation on other cell types largely used in cell-based therapies such as hematological stem cells and peripheral blood mononuclear cells (PBMCs). Although they didnt observe major alterations in terms of immunophenotyping or the post-thaw proliferation of the cells, Pepper expresses his concern that more subtle characteristics might be affected.

Correct cryopreservation of cells intended for therapeutic use is crucial. This is very important particularly as cells may persist for a long time in the recipient. This area of cell therapy research definitely requires more attention, Pepper says. Moreover, his words reflect on the need to evaluate not only the direct post-thaw recovery, but to look deeper into the late-onset effects cryopreservation might have and ensure that transplanted cells have preserved their therapeutic properties.

In contrast to slow freezing, vitrification relies on the fast freezing of the material by putting it in high concentration of cryoprotectant and in contact with liquid nitrogen. This method allows the direct transition of water from liquid to solid state without crystal formation. The highly concentrated cryoprotectant prevents ice formation and therefore there is no need for slow cooling.

Although vitrification has a great potential, there are a couple of parameters that are a point of concern. The quick and drastic freeze is possible thanks to the high concentration of cryoprotectant, but the latter is also associated with higher toxicity. In some cases, an additional limitation is the direct contact of the sample with liquid nitrogen which is a predisposition for viral or bacterial contamination.The team of Christiani Amorim at the Institute for Experimental and Clinical Research in Louvain, Belgium, is approaching the challenges of vitrification in the context of ovarian auto-transplantation. Ovarian auto-transplantation consists of preserving a piece of ovarian tissue with active follicles from the pre-therapeutic ovary of a cancer patient, as chemotherapy often has damaging effects on the reproductive organs. This tissue sample will be conserved and auto-transplanted onto the patients ovary when she has recovered and wishes to become pregnant.In their recent research4, the authors used stepped vitrification, in which the concentration of the cryoprotectant is gradually increased while simultaneously temperature decreases. This avoids ice crystal formation and also prevents cryoprotectant toxicity.Although stepped vitrification has previously given good results in bovine ovarian tissue5, this was not the case for human ovarian tissue. The scientists didnt detect normal follicles following thawing and linked this to high cryoprotectant toxicity. Indeed, they observed all signs of dimethyl sulfoxide (DMSO)-related cell membrane damage: significant organelle damage, cell membrane disintegration and apoptosis. These observations imply on the variability of outcomes that the method could give when applied to the same type of tissue but from a different organism.Amorim is positive about the future of their method and recognizes the need for further research on the topic: I can see a great potential in the stepped vitrification approach, but I also believe that there is a lot we still need to learn before thinking about using it as method of choice for human ovarian tissue cryopreservation. The high cryoprotectant concentration that should be applied in this approach is my first concern. () Our study clearly showed that 50% DMSO is too high, so we need to try lower concentrations or combine it with other cryoprotectants.

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Freezing Life: The Current Trends in Cryopreservation - Technology Networks

Five scientists have been elected to the National Academy of Sciences in recognition of their distinguished and continuing achievements in original research. They are among 120 members and 26 international members elected.

The newly elected members from HMS are:

Joel Habener, professor of medicine and chief of the laboratory of molecular endocrinology at Massachusetts General Hospital

Judy Lieberman, professor of pediatrics and chair of cellular and molecular medicine at Boston Children's Hospital

Margaret Livingstone, the Takeda Professor of Neurobiology in the Blavatnik Institute

Olivier Pourqui, the Frank Burr Mallory Professor of Pathology at Brigham and Women's Hospital and professor of genetics in the Blavatnik Institute

Suzanne Walker, professor of microbiology in the Blavatnik Institute

Get more HMS news here

Other Harvard faculty elected this year include: Dennis Gaitsgory, professor of mathematics, Michael Kremer, the Gates Professor of Developing Societies in the Department of Economics and Wilfried Schmid, professor of mathematics.

The National Academy of Sciences is a nonprofit institution that was established under a congressional charter signed by President Abraham Lincoln in 1863. It recognizes achievement in science by election to membership, andwith the National Academy of Engineering and the National Academy of Medicineprovides science, engineering, and health policy advice to the federal government and other organizations. The National Academy of Sciences charter commits the Academy to provide scientific advice to the government whenever called upon by any government department. The NAS is committed to furthering science in America, and its members are active contributors to the international scientific community.

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Five HMS Faculty Elected to National Academy of Sciences - Harvard Medical School

An Indian American professor has developed the technology behind the Nanolife Disinfectant Tunnel, which successfully uses silver nano-particles to kill off viral infections.

Kattesh Katti, professor of radiology and director of the Institute of Green Nanotechnology at the University of Columbia in Missouri, told India-West the technology has been tested successfully on COVID-related viruses. Currently, the 8-foot-long tunnel has been deployed at three locations in Chennai, including the Tirumala Tirupati Temple, where thousands of devotees worship each day.

Indias Prime Minister Narendra Modi has placed an order for more tunnels, according to Katti, which are distributed in India through the company Nanolife.

Katti discovered the effectiveness of silver nano-particles in killing off viruses 20 years ago, and commercialized the technology via a hand sanitizer that uses no alcohol or chemicals. The technology was also being used as a cleaning agent in Indian hospitals, he said.

Then the COVID-19 pandemic hit; Katti and the team at Nanolife re-purposed their technology to address the global crisis, which has killed more than 214,000 people around the world, and infected more than three million people.

India, currently on a nationwide quarantine ordered by Modi in March, has a relatively low rate of infection and death from COVID-19: the country had reported 937 deaths and approximately 30,000 infections as of April 28.

But the countrys overcrowded conditions which make required social distancing difficult could drastically raise the number of deaths from the virus, predict Indian epidemiologists.

A country like India really needs more resources, Katti told India-West. The very high population density makes the pandemic significantly more dangerous, he said.

Unlike other disinfecting tunnels currently used in India and some other countries, Nanolifes disinfectant tunnel uses no harmful chemicals, which could be toxic. The technology is based simply on silver nano-particles, water and a proprietary herb that keeps the particles intact, said Katti, adding that the product is used in very low concentrations in the tunnels.

Prof. Jagat Ram of the Postgraduate Institute of Medical Education and Research, Chandigarh, and Prof. JS Thakur, chairman, Covid-19 Prevention Committee at PGI, have questioned the efficacy of disinfecting tunnels, stating that they provide people with a false sense of security. But the tunnels to which they were referring to use sodium hypochlorite, which is known to have several serious side effects. Nanolifes tunnels have no side effects, according to Katti.

The Government of India has banned the export of COVID-related technology, citing the huge need within the country for such products. Thus, for the moment, the Nanolife Disinfectant Tunnel is limited to deployment in India, but Katti is aiming to eventually bring the device to the U.S.

The Dharwad native said he envisions the Nanolife Disinfectant Tunnel in front of railway stations, airports, office buildings, and other large gathering places. Demand far outweighs production capability at the moment, he told India-West.

According to his bio, green nanotechnology is at the focal point of Katti's approach to pursuing research in nanotechnology and molecular medicine as he strongly believes in the total elimination of toxic chemicals in the production of engineered nanoparticles.

He uses phytochemicals occurring naturally within plants and herbs for nano constructs in a variety of applications.

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Missouri Indian American Professor Develops Disinfecting Tunnel to Kill Viral Infections Using Silver Nano-particles - India West

Antimicrobial resistance is a global health threat that requires international collaboration between researchers from multiple disciplines

Around the world, millions of people are at risk of contracting infections and illnesses that cannot be treated becausethe causative agents superbugs are resistant to medicines. Antimicrobial resistance (AMR) in which bacteria, parasites, viruses and fungi have developed ways to survive treatments that once killed them is a serious threat to global public health.

At the University of Bristol, researchers from numerous disciplines are working together to understand and control AMR in an effort to save lives at home and abroad. The majority of the worlds efforts to address AMR are around bacteria, says Matthew Avison, a professor of molecular bacteriology at the universitys School of Cellular and Molecular Medicine. In the UK, E. coli causes more deaths than any other bacterium, he says. Over time, it has adapted and becomeresistant to the drugs that doctors had previously used to treat it.

His team investigates E. coli, among other pathogenic bacteria. But simply understanding a bacteriums structure and behaviour is not enough.

Our successes are really due to our work with other disciplines, Professor Avison says. Our discoveries, which would otherwise be fairly basic regarding the behaviour of bacteria, can be applied to useful things.

Professor Avison leads the Bristol AMR interdisciplinary research network, funded by the Wellcome Trust. At Bristol, were good at interdisciplinary work, he says. Because the geography of the university is relatively small, and were close to other departments and schools, we can physically interact with each other.

This is how he and his team came to work with a group of physicists and be instrumental in spinning out a company. There are ways you can visualise and collect data with instrumentation that we in the biological sciences arent familiar with, he says. There were physicists at Bristol, however, who were experts in optics and, through collaboration, developed a device that can visualise individual bacteria and watch them move.

This invention has important implications for testing whether bacteria are resistant to a specific antibiotic. Bacteria move differently in the presence of antibiotics, Professor Avison says. If the antibiotics are working and killing them, the bacteria eventually stop moving.

The bacteriologists supplied the physicists with antibiotics and bacteria, while the physicists provided an imaging technique not initially developed for use in the biological sciences. This technique, Total Internal Reflection Microscopy (TIRM), is the cornerstone of Vitamica, a spin-out company specialising in rapid AMR diagnostics, and is now being trialled in hospitals, testing bacteria in patients urine. TIRM can image how the bacteria behave when in the presence of a specific antibiotic: if they do not die, then they are resistant to that drug.

The reason why its so good is that its rapid, says Profesor Avison. You put a sample in and, in less than an hour, you can tell if the antibiotic will work or not. He reiterates that it is still being trialled, but that it is a potentially very important technology in the fight against AMR.

Another vital collaboration for Professor Avison is with colleagues in veterinary science. Kristen Reyher heads the AMR Force, a research group within the Bristol Vet School that examines key topics about veterinary AMR.

In our projects, weve tried to lead with behaviour and social science, she says. We realised that you can have the best solutions and know all the technical answers, but still not be able to change the situation because you arent communicating in the right way.

One recent project spearheaded a method of farmer peer-to-peer learning, to try and change their behaviour with respect to antibiotics. As a vet, I think about disease all day, every day, Dr Reyher says. I dont think about the myriad things that farmers have to balance, but their peers do. They are the best people to listen and challenge one another to be the best stewards of these important medicines.

This awareness of context is fundamental to Bristol researchers AMR efforts. Maria Paula Escobar, another researcher at Bristol Vet School, is interested in how farmers in different countries use antibiotics and how this has an impact on AMR. She has projects in Colombia and collaborates with Dr Reyher and Professor Avison on one in Argentina.

There is a perception that countries just need more time and more money to address excessive antibiotic usage through targets, says Dr Escobar. This lacks an understanding of the different cultural contexts in which antibiotics are used. Antibiotics are not always used for the same reasons and those involved are not always veterinarians and farmers. In Europe, you cannot get hold of an antibiotic if a veterinarian has not prescribed it. That is not the case in many countries.

Bristol researchers also have AMR projects in Thailand, China, sub-Saharan Africa and more. Were not just looking at this as a UK problem, Professor Avison says. Low-income communities, particularly in developing countries, are disproportionately affected by healthcare problems, including AMR. Overcrowding and poor sanitation, for example, are driving infections, and people cant get access to new antibiotics [that would fight resistant infections] they are stuck with the old ones.

And a global problem, such as AMR, requires global collaboration. We couldnt do our work [in other countries] without great collaborations with local researchers, Professor Avison says. All of the work we do involves people going out and collecting samples from farms, from the environment, from people, which is done by researchers in those countries.

Training local researchers is part of this support, he says. These skills are becoming increasingly vital in an age of AMR a problem which will never go away entirely.

I dont think well ever solve the problem, Professor Avison concludes. Bacteria are very adaptable. They will always evolve and come back to us. That is why researchers have to be adaptable, too.

Find out more about the University of Bristol.

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Taking the fight to superbugs - Times Higher Education (THE)

Four UT Southwestern Medical Center scientists have been elected to the The National Academy of Sciences, one of the top honors for American scientists.

Peer scientists selected Sean Morrison, Kim Orth, Michael Rosen, and Sandra Schmid for their original research and achievements. UT Southwestern now has 25 members of the academy, the most of any institution in Texas.

Election to the prestigious National Academy of Sciences recognizes the pioneering contributions these scientists have made to advance our understanding of basic cellular function and molecular processes with application to addressing a broad spectrum of unmet medical needs including cancer and treatments for bacterial infections, said Dr. Daniel K. Podolsky, President of UT Southwestern Medical Center via release. Their election enriches the National Academy of Sciences efforts to provide data and advice on the nations most critical issues in science, health, and medicine.

Morrison is the Director of the Childrens Medical Center Research Institute (CRI) at UT Southwestern and Professor of Pediatrics and has worked in the fields of stem cell biology and cancer, and has created new methods to purify stem cells and allow them to persist and regenerate after injury. This recognizes, first and foremost, the work of many talented people over the years in my lab, most of whom have now gone on to their own laboratories at UT Southwestern and other institutions. Many of the key insights for the important discoveries that were made came from them so this really recognizes their work. Id also like to acknowledge all my colleagues, all of you at UT Southwestern and at Childrens Health, for the incredible environment that you created for science, Morrison said via release.

Orth is a Professor of Molecular Biology and Biochemistry and has discovered biochemical mechanisms behind many bacterial infections, revealing how pathogens use host cells for their own benefit. I want to thank you all for this wonderful celebration, even though we have to Zoom . Thanks to this amazing institution, UT Southwestern, the wonderful administration including Drs. (Daniel) Podolsky and (David) Russell and the other administrators and staff. As (Chair of Molecular Biology) Eric Olson said, I have moved up the ranks here, starting as a technician, to a student, a postdoc, and now Professor, Orth said via release. And this path has driven my success. Another major key to my success is all of the talented people that have worked in my lab and my mentors, friends, collaborators, and, of course, my family.

Rosen is the Chair of Biophysics and Professor in the Cecil H. and Ida Green Comprehensive Center for Molecular, Computational, and Systems Biology, and investigates how cells compartmentalize processes without the use of membranes. When we began our work on phase separation about a decade ago, it really was not obvious at all whether this was going to be some weird, esoteric little thing that a few proteins did or (if) it was going to become a more general principle in biology. So it wasa tremendous risk that many of us took in making a move in this new direction. More than anything, I want to thank the various people whojoined me in taking this great risk a decade ago that I think has proved to be very much worthwhile, Rosen said via release.

Schmid is the Professor and Chair of Cell Biology and is recognized for her work on endocytosis, or how cells absorb nutrients and other molecules, including the major pathway for uptake within the cell. Ive been lucky to start and end my academic career at two unique institutions, Schmid said via release. As a PhD student in the early 80s, I was supported and challenged by my peers and faculty in the Biochemistry department at Stanford to ask important questions and do the most impactful research. Over decades, the leadership at UT Southwestern has inspired, supported and celebrated the very best research creating a collegial culture that breeds success.

This important recognition by their peers reflects the breadth and quality of research underway at UT Southwestern, and serves as inspiration for new generations of trainees and scientists to carry on the tradition of discovery that is the hallmark of distinguished academic medical centers, said Dr. W. P. Andrew Lee., Executive Vice President for Academic Affairs, Provost and Dean of UT Southwestern Medical School via release.

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Four UTSW Researchers Named to The National Academy of Sciences - D Magazine

In the early 1950s, psychiatrists began treating schizophrenia with a new drug called chlorpromazine. Seven decades later, the drug is still used as an anti-psychotic.

But now scientists have discovered that the drug, also known as Thorazine, can do something entirely different. It can stop the new coronavirus that causes Covid-19 from invading cells.

Driven by the pandemics spread, research teams have been screening thousands of drugs to see if they have this unexpected potential to fight the coronavirus. Theyve tested the drugs on dishes of cells, and a few dozen candidates have made the first cut.

Theyre startlingly diverse. Some, like chlorpromazine, have been used for years not for viral infections, but for conditions including cancer, allergies, arthritis, even irregular menstrual periods. Other drugs have not yet been approved by the Food and Drug Administration, but they have already proven safe in clinical trials. Their track records might help them get approved faster than a drug designed from scratch.

As researchers publish findings on these promising drugs, theyre starting tests on animals and people to see how well they perform. No one should try self-medicating with any of the drugs for Covid-19, the researchers warned, since they may have dangerous side effects and have yet to be proven effective in clinical trials.

Im going to be brutally honest with you: 95 to 98 percent of these are going to fail, said Sumit K. Chanda, a virologist at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Calif. But we only need one or two.

The strategy Dr. Chanda and other researchers are using is known as drug repurposing. It has a history that started decades before Covid-19 appeared. In 1987, for example, the cancer drug zidovudine became the first F.D.A.-approved drug against H.I.V.

The most obvious drugs to repurpose against the new coronavirus are those that work against other viruses. One high-profile antiviral being investigated is remdesivir, which Gilead Sciences previously tested unsuccessfully as an antiviral against Ebola.

But over the years, researchers have found some drugs that originally had nothing to do with viruses turn out to be good antivirals, too. Its just hard to tell in advance which ones have this hidden power.

We dont know a lot about why drugs do what they do, said Matthew Frieman, a virologist at the University of Maryland School of Medicine.

In 2012, another coronavirus disease known as MERS emerged in the Middle East. Dr. Frieman responded by starting a drug-repurposing study. He and his colleagues tested 290 F.D.A.-approved drugs and found that 27 of them blocked the MERS virus from infecting cells. They also proved effective against the related coronavirus that causes SARS.

Dr. Frieman and his colleagues have now tested those drugs against the new coronavirus, and made a preliminary report that 17 of them showed promise. Along with chlorpromazine, they include drugs for disorders as varied as Parkinsons disease and leukemia.

Recently, Dr. Chandas team in California began a mammoth search of their own for drugs to repurpose for Covid-19. They doused infected cells with 13,000 compounds and looked for ones that slowed down the virus. They then narrowed down these candidates by reducing their doses, in order to mimic the levels that would end up in a patients lungs.

On April 17, Dr. Chandas team reported in a preprint, which has not yet been peer-reviewed by a journal, that six drugs showed particular promise, including one for osteoporosis and one thats been investigated as treatment for arthritis.

Yet another team has been trying to find drugs that work against coronavirus and also to learn why they work.

The team, led by Nevan Krogan at the University of California, San Francisco, has focused on how the new coronavirus takes over our cells at the molecular level.

The researchers determined that the virus manipulates our cells by locking onto at least 332 of our own proteins. By manipulating those proteins, the virus gets our cells to make new viruses.

Dr. Krogans team found 69 drugs that target the same proteins in our cells the virus does. They published the list in a preprint last month, suggesting that some might prove effective against Covid-19.

The researchers shipped the compounds to the Icahn School of Medicine at Mount Sinai in New York and at the Pasteur Institute in Paris. Those labs tried them out on infected cells.

Brian Shoichet, a pharmaceutical chemist at U.C.S.F. who helped build the list, was keenly aware of how often drug repurposing fails.

I wasnt that hopeful at all, he said.

It turned out that most of the 69 candidates did fail. But both in Paris and New York, the researchers found that nine drugs drove the virus down.

The things were finding are 10 to a hundred times more potent than remdesivir, Dr. Krogan said. He and his colleagues published their findings Thursday in the journal Nature.

Strikingly, the drugs hit only two targets.

One group temporarily stops the creation of new proteins inside cells. This group includes molecules that are being tested as cancer drugs, such as ternatin-4 and Zotatifin.

Dr. Shoichet speculated that these compounds starve the virus of the proteins it needs to make new copies of itself. This attack may suddenly halt the viral production line.

Viruses are actually delicate beasts, he said.

The other compounds home in on a pair of proteins known as Sigma-1 and Sigma-2 receptors. These receptors are part of the cells communication network, helping the cell withstand stress in its environment.

Why does the new coronavirus need to manipulate Sigma receptors? We dont really know, Dr. Shoichet said.

One possibility is that the virus uses Sigma receptors to make a cell produce more of the oily molecules that form membranes for new viruses.

Among the substances that act on Sigma receptors and block the virus, the researchers found, are the hormone progesterone and the drugs clemastine and cloperastine, both used against allergies.

In addition, Dr. Krogan said that all of Dr. Friemans candidates, including chlorpromazine, target Sigma receptors. A third of Dr. Chandas candidates do too, he said.

The researchers also tested dextromethorphan, a Sigma-receptor-targeting drug in many brands of cough syrup. They were surprised to find that, at least in their cell samples, it actually made infections of this coronavirus worse.

In their paper, the researchers raised the possibility that Covid-19 patients may want to avoid dextromethorphan. Dr. Krogan emphasized that more study would be needed to see if it actually increases coronavirus infection in humans. But if it was me, he said, to be cautious, I would not be taking these cough syrups.

The anti-malaria drugs chloroquine and hydroxychloroquine act on the Sigma receptor. Dr. Krogans team found that they also fought the virus in cells. Those compounds were extolled by President Trump for weeks despite no firm evidence they actually helped cure Covid-19.

Dr. Frieman and Dr. Chanda also found that chloroquine-related drugs worked fairly well in slowing the virus in cell cultures. But Dr. Chanda found they didnt work as well as the six compounds at the top of his list.

Dr. Chanda expressed skepticism about the chloroquine drugs, noting their failure against other viruses.

Weve been down this road multiple times, he said. I would happy to be wrong about this.

Last week, the F.D.A. issued a warning against using hydroxychloroquine or chloroquine for Covid-19 outside the hospital setting or a clinical trial. Thats because the drug has a well-known risk for causing irregular heart rhythms.

In their new study, Dr. Krogan and his colleagues ran an experiment that might explain this risk at the molecular level.

They found that chloroquine and hydroxychloroquine bind not just to Sigma receptors, but to a heart protein called hERG, which helps control heartbeats.

I think its a rational argument, said Dr. Frieman, who was not involved in the Nature study. Chloroquine does a lot of things in the cell.

Dr. Krogan and his colleagues found that other compounds target Sigma proteins in a more promising way.

An experimental anticancer compound called PB28 is 20 times more potent than hydroxychloroquine against the coronavirus, for example. But its far less likely to grab onto the hERG protein.

Dr. Chanda said that PB28 in particular looks really fantastic.

Dr. Krogan said that studies are underway to test the drug in hamsters to see if that promise holds. Dr. Frieman and his colleagues are starting animal studies of their own, as well as testing drugs on a chip lined with human lung cells.

Timothy Sheahan, a virologist at the University of North Carolina who was not involved in the new studies cautioned that it will take more testing to make sure these promising drugs are safe to give to patients ravaged by Covid-19.

Cancer drugs, for example, can be like a sledgehammer to your body, he noted. Are you going to want to do that when someone is really sick?

In addition to animal tests and clinical trials, researchers are now planning to tweak the structure of these drugs to see if they can work even more effectively against the virus.

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Old Drugs May Find a New Purpose: Fighting the Coronavirus - The New York Times