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Reviving cells after a heart attack

Extracellular vesicles (EVs) -- nanometer-sized messengers that travel between cells to deliver cues and cargo -- are promising tools for the next generation of therapies for everything from autoimmune and neurodegenerative diseases to cancer and tissue injury. EVs derived from stem cells have already been shown to help heart cells recover after a heart attack, but exactly how they help and whether the beneficial effect is specific to EVs derived from stem cells has remained a mystery.

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have unraveled potential mechanisms behind the healing power of EVs and demonstrated their capacity to not only revive cells after a heart attack but keep cells functioning while deprived of oxygen during a heart attack. The researchers demonstrated this functionality in human tissue using a heart-on-a-chip with embedded sensors that continuously tracked the contractions of the tissue.

The team also demonstrated that these intercellular travelers could be derived from endothelial cells, which line the surface of blood vessels and are more abundant and easier to maintain than stem cells.

The research is published in Science Translational Medicine.

"Our organ-on-chip technology has progressed to the point where we can now fight drug targets instead of fighting the chip design," said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at SEAS and senior author of the study. "With this study, we have mimicked a human disease on a chip with human cells and developed a novel therapeutic approach to treat it."

Heart attacks, or myocardial infarctions, occur when blood flow to the heart is blocked. Of course, the best way to treat a heart attack is to restore blood flow but that process actually may cause more damage to the cells in the heart. So-called ischemia-reperfusion injury (IRI) or reoxygenation injury, happens when blood supply returns to tissue after a period of lack of oxygen.

"The cellular response to IRI involves multiple mechanisms, such as calcium and proton overload, oxidative stress, mitochondrial dysfunction and more," said Moran Yadid, a postdoctoral fellow at SEAS and The Wyss Institute for Biologically Inspired Engineering and first author of the paper. "This complex set of processes poses a challenge for the development of effective therapies that can address each of these problems."

That's where the endothelial-derived EVs (EEVs) come in. Because these vesicles are derived from vascular tissue, which is uniquely tuned to sense hypoxic stress, the researchers hypothesized that the cargo they carry could provide direct protection to cardiac muscle.

The researchers mapped the entire set of EEV proteins that are or can be, expressed by the vesicles.

"Surprisingly, even though these vesicles are only a hundred and fifty nanometers in diameter, they contain almost 2,000 different proteins," said Yadid. "A lot of these proteins relate to metabolic processes like respiration, mitochondrial function, signaling, and homeostasis. In other words, a lot of processes that relate to the cardiac response to stress. So, rather than one molecule that is therapeutic, we think that the exosomes contain a cocktail of molecules and proteins that can, all together, help the cell maintain homeostasis, deal with the stress, modify metabolic action and reduce the amount of injury."

The team tested the effect of EEVs on human heart tissue using the heart-on-a-chip model developed by the Disease Biophysics Group at SEAS. Organ-on-chip platforms mimic the structure and function of native tissue and allow researchers to observe, in real-time, the effects of injuries and treatments in human tissue. Here, the researchers simulated a myocardial infarction and reoxygenation on chips that were infused with EEVs and those that were not.

The researchers found that in tissues treated with EEVs, the cardiomyocytes could better adapt to stress conditions and sustain a higher workload. The researchers induced injury by three hours of oxygen restrictions followed by 90 minutes of reoxygenation and then measured the fraction of dead cells and the contractile force of the tissue. The heart tissue treated with EEVs had half as many dead cells and had a contractile force four times higher than the untreated tissue after injury.

The team also found that injured cardiomyocytes that had been treated with EEVs exhibited a set of proteins that was more similar to the uninjured ones compared with untreated cells. Surprisingly, the team also observed that cells treated with EEVs continued to contract even without oxygen.

"Our findings indicate that EEVs could protect cardiac tissue from reoxygenation injury in part by supplementing the injured cells with proteins and signaling molecules that support different metabolic processes, paving the way for new therapeutic approaches," said André G. Kléber, a Visiting Professor of Pathology at Harvard Medical School and co-author of the study.

"Exosomal cell therapies might be beneficial when the traditional model of one molecule, one target just won't cure the disease," said Parker. "With the vesicles we administered, we believe we are taking a shotgun approach to hitting a network of drug targets. With our organ on chip platform, we will be poised to use synthetic exosomes in a therapeutic manner that may be more efficient and amenable to more reliable manufacturing."

The research was co-authored by Johan U. Lind, a former postdoctoral fellow at SEAS and current Assistant Professor at the University of Copenhagen, Denmark; Herdeline Ann M. Ardoña, a former postdoctoral fellow at SEAS and current Assistant Professor at the University of California Irvine; Sean P. Sheehy, Lauren E. Dickinson, Feyisayo Eweje, Maartje M.C. Bastings, Benjamin Pope, Blakely B. O'Connor, Juerg R. Straubhaar and Bogdan Budnik.

It was supported by Harvard Materials Research Science and Engineering Center and the National Science Foundation under grant DMR-1420570, and the National Center for Advancing Translational Sciences of the NIH under award numbers UH3TR000522 and 1-UG3-HL-141798-01.

Story Source:

Materials provided by Harvard John A. Paulson School of Engineering and Applied Sciences. Original written by Leah Burrows. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2020/10/201014171322.htm

Journal Reference:

Moran Yadid, Johan U. Lind, Herdeline Ann M. Ardoña, Sean P. Sheehy, Lauren E. Dickinson, Feyisayo Eweje, Maartje M.C. Bastings, Benjamin Pope, Blakely B. O’Connor, Juerg R. Straubhaar, Bogdan Budnik, Andre G. Kleber, Kevin Kit Parker. Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip. Science Translational Medicine, 2020; 12 (565): eaax8005 DOI: 10.1126/scitranslmed.aax8005

Asthma, Food Sensitivity, and Irritable Bowel Syndrome

News Picture: Study Probes Links in Asthma, Food Sensitivity and Irritable Bowel Syndrome

Teens who had asthma and food hypersensitivity when they were younger are at increased risk of irritable bowel syndrome (IBS), researchers report.

For the study, the investigators examined the health of 2,770 children from birth to age 16. Kids with IBS at age 16 were more likely to have had asthma at age 12 (about 11% versus 7%).

In addition, the researchers found that 16-year-olds with IBS were more likely to have had food hypersensitivity at age 12 (41% versus 29%).

Asthma, food hypersensitivity and eczema (a condition that makes your skin red and itchy) were all associated with an increased risk of concurrent IBS at age 16, the findings showed.

"The associations found in this large study suggest there's a shared pathophysiology between common allergy-related diseases and adolescent irritable bowel syndrome," said study leader Jessica Sjölund, of the Institute of Medicine at the University of Gothenburg, in Sweden.

Sjölund noted that previous studies on allergy-related diseases and IBS have been contradictory.

These new findings could lead to development of new treatments for adolescent IBS, targeting processes of low-grade inflammation seen in the allergy-related diseases, she said.

The study findings were scheduled for presentation Monday at a United European Gastroenterology virtual meeting. Research presented at meetings should be considered preliminary until published in a peer-reviewed journal.

IBS affects more than one in 10 people and is the most common functional gastrointestinal disorder, the study authors noted in a meeting news release. It can cause abdominal cramps, bloating, diarrhea and constipation, and can be extremely disabling for patients.

Hans Törnblom is a leading IBS expert in Europe who was involved in the research. He said, "Even though functional gastrointestinal disorders are common, many patients are, unfortunately, negatively stigmatized and labeled. The fact that many IBS sufferers do not seek medical advice should be of great concern."

-- Robert Preidt

Surce: https://www.medicinenet.com/script/main/art.asp?articlekey=247670

DOH suggests holding of activities in open spaces amid pandemic

MANILA – The Department of Health (DOH) on Monday advised the public to conduct activities in open-air spaces, install exhaust fans in comfort rooms and avoid usage of recirculated air options for vehicles to prevent the possibility of contracting the coronavirus disease 2019 (Covid-19) through airborne transmission.

Health Undersecretary Maria Rosario Vergeire, in a virtual press briefing on Monday, said that while health experts are still studying the possibility of airborne infection, the DOH has issued Department Memorandum 2020-0429 which provides administrative and engineering controls for the improvement of ventilation and air quality in enclosed, indoor spaces and lessen the transmission of the virus.

“When an activity cannot be moved into an open-air setting, opening windows and doors should be put into practice to facilitate the flow of outdoor air into the space, when possible,” the memorandum read.

The DOH advised individuals not to stay where air coming from fans and air-conditioning units flow directly as these may facilitate the transmission of the coronavirus "by directing air from infected individuals to others in the room".

“In non-hospital settings where ventilation is greatly recirculated or access to outside air is not feasible, filters such as high-efficiency particulate air filtration air purifiers can be used to clean recirculated air provided that the unit is adequate for the size of the room in which it is installed in,” it added.

The DOH also suggested the installation of exhaust fans in comfort rooms and closing of the toilet seat lid while flushing to “minimize the release of droplets into air flows after flushing".

“Utilize the car’s vents to bring in fresh outside air and/or lower the vehicle windows,” the DOH said, adding that recirculated air option for the vehicle’s ventilation during passenger transport must be avoided.

Earlier, the US Centers for Disease Control and Prevention said people with Covid-19 seem to have infected others who were more than six feet away in enclosed spaces and inadequate ventilation. (By Ma. Teresa Montemayor, PNA)

Source: https://www.pna.gov.ph/articles/1118297

Does Wearing a Mask Cause CO2 Poisoning?

Wearing a face mask cannot lead to carbon dioxide poisoning, even in people with lung disease, researchers report.

The findings counterclaim that wearing face masks to prevent spread of the new coronavirus may put some people's health at risk.

The authors of the new study assessed changes in oxygen or carbon dioxide levels in healthy people as well as in those with chronic obstructive pulmonary disease (COPD), before and while using surgical masks.

In general, people with COPD must "work harder to breathe," which can lead to shortness of breath and/or a tired feeling, according to the American Thoracic Society.

The study -- published online Oct. 2 in the Annals of the American Thoracic Society -- found "that the effects [of wearing masks] are minimal at most even in people with very severe lung impairment," said lead author Dr. Michael Campos. He's an associate professor in the University of Miami's division of pulmonary, allergy, critical care and sleep medicine.

Campos also addressed the feeling of breathlessness that some healthy people may experience when wearing a mask.

"Dyspnea, the feeling of shortness of breath, felt with masks by some is not synonymous of alterations in gas exchange. It likely occurs from restriction of airflow with the mask in particular when higher ventilation is needed (on exertion)," he said in a society news release.

For example, if you're walking briskly up a hill, you may experience breathlessness, and a mask that is too tight may increase that feeling. The solution: Slow down or remove the mask if you're at a safe distance from other people, Campos advised.

"It is important to inform the public that the discomfort associated with mask use should not lead to unsubstantiated safety concerns as this may attenuate the application of a practice proven to improve public health," the researchers concluded.

"The public should not believe that masks kill," Campos emphasized.

-- Robert Preidt

Source: https://www.medicinenet.com/script/main/art.asp?articlekey=247492

Philippines and UK strengthen S&T cooperation in health

The Department of Science and Technology – Philippine Council for Health Research and Development (DOST-PCHRD) launched the Memorandum of Understating (MOU) with the London School of Hygiene and Tropical Medicine (LSHTM) and University of the Philippines Manila (UP Manila) to strengthen science and technology cooperation in health.

Under the MOU, DOST-PCHRD, LSHTM, and UP Manila will work together on various S&T collaborations focusing on priority research areas including genomics, modelling, diagnostics, clinical trials, epidemiology, and immunology.

The partnership also entails the exchange of scientists, faculty, and specialists interested in scientific and technological cooperation in health. DOST-PCHRD agreed to extend funding to various capacity-building activities such as research fellowship, scholarship, post-doctoral training, research enrichment (sandwich) programs, and staff training.

Professor Martin Hibberd of LSHTM viewed the partnership as a huge opportunity to expand health research ventures in the Philippines. Dr. Jaime Montoya, DOST-PCHRD Executive Director, assured LSHTM and UP Manila the Council’s full support and cooperation in this collaboration.

In attendance to witness the MOU launching were DOST Assistant Secretary for International Cooperation Unit Dr. Leah Buendia, UP National Institutes of Health Executive Director Dr. Eva Cutiongco de la Paz, LSHTM Coordinator Dr. Julius Clemence Hafalla, and DOST-PCHRD Institutional Development Division (IDD) Chief Ms. Carina Rebulanan. (Written by Catherine Joy C. Dimailig)

Source: http://www.pchrd.dost.gov.ph/index.php/news/6600-philippines-and-uk-strengthen-s-t-cooperation-in-health