Culture

DALLAS - April 27, 2021 - Researchers with the Peter O'Donnell Jr. Brain Institute at UT Southwestern have identified a new protein implicated in cell death that provides a potential therapeutic target that could prevent or delay the progress of neurodegenerative diseases following a stroke.

Scientists from the departments of pathology, neurology, biochemistry, and pharmacology at UTSW have identified and named AIF3, an alternate form of the apoptosis-inducing factor (AIF), a protein that is critical for maintaining normal mitochondrial function. Once released from mitochondria, AIF triggers processes that induce a type of programmed cell death.

In a study published in the journal Molecular Neurodegeneration, the UT Southwestern team collaborated with researchers at The Johns Hopkins University School of Medicine and found that, following a stroke, the brain switches from producing AIF to producing AIF3. They also reported that stroke triggers a process known as alternative splicing, in which a portion of the instructions encoding AIF is removed, resulting in the production of AIF3. Defective splicing can cause disease, but modifying the splicing process may offer potential for new therapies.

In both human brain tissue and mouse models developed by researchers, AIF3 levels were elevated after a stroke. In mice, the stroke-induced production of AIF3 led to severe progressive neurodegeneration, hinting at a potential mechanism for a severe side effect of stroke observed in some patients. Stroke has been recognized as the second most common cause of dementia, and it is estimated that 10 percent of stroke patients develop post-stroke neurodegeneration within one year.

The molecular mechanism underlying AIF3 splicing-induced neurodegeneration involves the combined effect of losing the original form of AIF in addition to gaining the altered AIF3, leading to both mitochondrial dysfunction and cell death.

"AIF3 splicing causes mitochondrial dysfunction and neurodegeneration," says senior author Yingfei Wang, Ph.D., assistant professor of pathology and neurology and a member of the O'Donnell Brain Institute. "Our study provides a valuable tool to understand the role of AIF3 splicing in the brain and a potential therapeutic target to prevent or delay the progress of neurodegenerative diseases."

The findings are important for understanding the aftereffects of stroke, which strikes nearly 800,000 U.S. residents annually. Stroke kills one person every four minutes, according to the Centers for Disease Control and Prevention (CDC), and about one in every six deaths from cardiovascular disease is attributed to stroke - with ischemic strokes accounting for about 87 percent of all cases. Leading causes of stroke include high blood pressure, high cholesterol, smoking, obesity, and diabetes. Stroke also disproportionately affects certain populations and occurs more often in men, though more women than men die from stroke. CDC figures show Black people have twice the risk of first-time stroke than white people and a higher risk of death. Hispanic populations have seen an increase in death rates since 2013, while other populations have not.

Des Plaines, IL - In a randomized, double-blind trial of patients with acute undifferentiated agitation in the emergency department, droperidol was more effective for sedation and was associated with fewer episodes of respiratory depression than lorazepam or either dose of ziprasidone. This is the conclusion of Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department, to be published in the April 2021 issue of Academic Emergency Medicine (AEM), a journal of the Society for Academic Emergency Medicine (SAEM).

Agitation is a common presentation in emergency medicine, ranging from a state of restlessness to overtly violent behavior and can result in injury to both patients and their caregivers. The purpose of this study was to compare intramuscular droperidol, ziprasidone, and lorazepam in patients with acute agitation in the emergency department, using the proportion of patients adequately sedated at 15 minutes as the primary outcome measure. Secondary outcomes included rates of rescue medication, respiratory depression, adverse medication effects, and emergency department length of stay. The authors suggest that larger studies are needed to confirm these findings, particularly to address safety outcomes.

The lead author of the study is Marc L. Martel, MD, of the Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.

The findings of the study are discussed with Dr. Martel in a recent AEM podcast titled, I Can't Fight This Med Any Longer - Droperidol for Acute Agitation.

COLUMBIA, Mo. -- Having grown up poor in a rural village in Zimbabwe, Wilson Majee saw firsthand as a child the lack of educational opportunities that were easily accessible and how that impacted the youth in his village.

Now an associate professor in the University of Missouri School of Health Professions, Majee researches the challenges facing disadvantaged, rural youth. He found in a recent study that young people who are disengaged from their communities are much more likely to participate in risky behaviors such as substance abuse, particularly in rural areas that lack educational opportunities.

For the study, Majee spoke with youth in rural South Africa about the factors contributing to drug abuse for the NEET population, which stands for young people around the world "Not in Employment, Education or Training." He found that a lack of educational opportunities, combined with other factors - such as a lack of motivation, absent adult role models and few recreational activities - compound to create feelings of hopelessness and despair in young people. These feelings can influence drug use and other risky behaviors.

"All of these factors the young people mentioned, in addition to poverty, unemployment and a lack of basic resources such as health facilities, libraries, available drinking water and internet access, compound together to limit opportunities for rural youth," Majee said. "Toward the end of Apartheid in South Africa, there was a mass migration of young people to urban cities, and since then, the necessary infrastructure has not been put in place in rural areas to help struggling youth successfully advance in life."

The number of young people around the world in the NEET population, currently an estimated 273 million worldwide and 10 million in the United States, has been steadily increasing since 2017, according to the International Labor Organization. Majee explained that, as it was for him almost 35 years ago, access to higher education has remained a major challenge for rural youth, particularly those who have never traveled to larger cities where more resources and universities are typically located.

"At the time I was pursuing higher education, there was only one university in all of Zimbabwe, and it was very far from my village, so I was overwhelmed at first when I attended because I had never been to a big city before," Majee said. "I also knew I had to be among the best students in the nation to earn a spot at the university."

According to Majee, in rural South Africa, as in rural Zimbabwe, primary and secondary schools often lack the infrastructure and resources necessary to prepare students for diverse fields.

"Rural schools not only lack qualified teachers, but they also often lack a variety of subject choices for students to take, as many rural schools do not offer classes in science, information technology, engineering or math," Majee said. "Yet we live in a technology-driven world that is fueled by these STEM subjects; so rural youth see no value in going to school if they can't learn the subjects that will help them get a job."

When Majee asked the rural South African youth who participated in the study for possible solutions to their challenges, the most common suggestion was creating smaller, community college-style satellite campuses for major universities that would be located in rural areas to increase access to those resources. Others emphasized the need for agriculture training programs, educating parents and community members on the power of role models and mentors, and the establishment of internet cafés to provide youth with a safe environment to explore topics that interest them.

"These complex solutions will require collaboration from community members, families, youth, private organizations, universities, researchers and government," Majee said. "These are multi-level issues the youth are facing, which calls for diverse stakeholders to come together to address them."

The goal of Majee's research is to empower youth by exploring strategies that help them become engaged members of their communities so they are less likely to participate in risky behaviors like drug abuse and crime.

"Young people today are the future community leaders of tomorrow," Majee said. "We need to invest in them to make sure they have the skills and knowledge they need to save their communities in the future, which will ultimately benefit society at large."

Neurons result from a highly complex and unique series of cell divisions. For example, in fruit flies, the process starts with stem cells that divide into mother cells (progenitor cells), that then divide into precursor cells that eventually become neurons.

A team of the University of Michigan (U-M), spearheaded by Nigel Michki, a graduate student, and Assistant Professor Dawen Cai in the departments of Biophysics (LS&A) and Cell and Developmental Biology at the Medical School, identified many genes that are important in fruit flies' neuron development, and that had never been described before in that context.

Since many genes are conserved across species such as between fruit flies (Drosophila), mice, and humans, what is learnt in flies can also serve as a model to better understand other species, including humans. "Now that we know which genes are involved in this form of neurogenesis in flies, we can look for them in other species and test for them. We work on a multitude of organisms at U-M and we've the potential to interrogate across organisms," explains Michki. "In my opinion, the work we did is one of the many pieces that will inform other work that will inform disease," adds Michki. "This is why we do foundational research like this one."

Flies are also commonly used in many different types of research that might benefit from having a more comprehensive list of the fly genes with their associated roles in neuron cell development.

The discovery

Neurons are made from stem cells that massively multiply before becoming neurons. In the human brain, the process is extremely complex, involving billions of cells. In the fly brain, the process is much simpler, with around 200 stem cells for the entire brain. The smaller scale allows for a fine analysis of the neuronal cell division process from start to finish.

In flies, when the stem cell divides, it yields another stem cell and a progenitor cell. When this last one divides, it makes a so-called precursor cell that divides only once and gives rise to two neurons. Genes control this production process by telling the cells either to divide --and which particular type of cell to produce-- or to stop dividing.

To this day, only a few of the genes that control this neuron development process have been identified and in this publication in Cell Reports, the scientists have characterized many more genes involved. Along the timeline of the neuron development process, the U-M team could precisely record which genes were involved and for how long.

In particular, at the progenitors' stage, the scientists identified three genes that are important at this stage for defining what 'kind' of neuron each progenitor will make; these particular genes had never been described before in this context. They also validated previously known marker genes that are known to regulate the cell reproduction process.

When they applied their analysis technique to the other phases of the neuron development process, they also recorded the expression of additional genes. However, it is still unknown why these genes go up in expression at different steps of the neuron development process and what role they actually play in these different steps. "Now that many candidate genes are identified, we are investigating the roles they play in the neuron maturation and fate determination process," says Cai. "We are also excited to explore other developmental timepoints to illustrate the dynamic changes of the molecular landscape in the fly brain."

"This work provides rich information on how to program stem cell progeny into distinct neuron types as well as how to trans-differentiate non-neuronal cell types into neurons. These findings will have significant impact on the understanding of the normal brain development as well as on neuron regeneration medicine," adds Cheng-Yu Lee, a Professor from the U-M Life Sciences Institute who collaborated with the Cai Lab.

The techniques

This study is mostly based on high-throughput single-cell RNA-sequencing techniques. The scientists took single cells from fruit flies' brains and sequenced the RNA, generating hundreds of gigabytes of data in only one day. From the RNA sequences, they could determine the developmental stage of each neuron. "We now have a very good understanding of how this process goes at the RNA level," says Michki.

The team also used traditional microscope observations to localize where these different RNAs are being expressed in the brain. "Combining in silico analysis and in situ exploration not only validates the quality of our sequencing results, but also restores the spatial and temporal relationship of the candidate genes, which is lost in the single cell dissociation process," says Cai.

At the beginning of their study, the scientists analyzed the large data set with open-source software. Later, they developed a portal (MiCV) that eases the use of existing computer services and allows to test for repeatability. This portal can be utilized for cell and gene data analysis from a variety of organs and does not require computer programming experience. "Tools like MiCV can be very powerful for researchers who are doing this type of research for the first time and who want to quickly generate new hypotheses from their data," says Michki. "It saves a lot of time for data analysis, as well as expenses on consultant fees. The ultimate goal is to allow scientists to focus more on their research rather than on sometimes daunting data analysis tools." The MiCV tool is currently being commercialized.

Rockville, Md. (April 27, 2021)--Researchers from Wake Forest School of Medicine in North Carolina have demonstrated that a common diabetes drug inhibits the spread of Clostridioides difficile, or C. diff--a potentially life-threatening infection commonly acquired during hospital stays. The team will present their work virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

C. diff is the most common hospital-acquired infection in the U.S. It starts in the intestines, often after a course of antibiotics. The Centers for Disease Control and Prevention categorizes the bacteria C. diff as a public health threat that "require[s] urgent and aggressive action." In 2017, nearly 223,900 people required hospitalization for its treatment, and at least 12,800 died from it. Of those who recover, 1 in 6 people experience reinfection within eight weeks. Antibiotic-resistant strains are also a growing concern.

Metformin, approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes, is the fourth most prescribed drug in the U.S. Earlier studies have shown that metformin beneficially alters the microbiomes of people with diabetes and of the elderly. Inspired by these findings, Shaohua Wang, PhD, a researcher in the lab of Hariom Yadav, PhD, evaluated the effect of metformin on C. diff infection in three different models. She tested the treatment in cell cultures, mice and an ex vivo model of the human microbiota developed by the lab.

In all three systems, metformin had the desired effect. It reduced C. diff proliferation in the cell culture. In the ex vivo model, it both reduced the population of the pathogen and increased the growth of closely related nonpathogenic bacteria. Lastly, in the mouse model, it reduced C. diff in the colon a hundredfold and limited the pathogen's spread to organs outside the intestine.

Yadav, who now heads the University of South Florida Center for Microbiome Research, plans to move forward with future studies that "determine the mechanisms by which metformin inhibits C. difficile infections and clinical efficacy in patients with [C. difficile infection]."

Rockville, Md. (April 27, 2021)--Fatty acid supplements may protect children with high cholesterol from heart disease later in life by increasing their blood levels of healthy omega-3 fatty acids, according to a new study. Researchers from the Uniformed Services University of the Health Sciences in Bethesda, Maryland, will present their work virtually this week at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

Previous research has shown that high blood levels of beneficial fatty acids, including omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) found in seafood, are associated with a lower risk of coronary artery disease and a higher likelihood of healthy aging. "Since coronary artery disease develops early in life in children with high cholesterol, there needs to be lifelong treatment started in childhood," said Marguerite M. Engler, PhD, first author of the new study. This is especially important as global obesity rates in young people are rising and the long-term safety of cholesterol-lowering statin drugs in children is not known.

The researchers of the current study examined children ages nine to 16 who had a history of high blood cholesterol levels. The children followed a Mediterranean diet--known for being rich in lean proteins, vegetables, whole grains and "healthy" fats such as olive oil and fish--for six weeks, followed by the continuation of the diet plus an EPA supplement for another six weeks. The research team measured the children's fatty acid levels before beginning and after the Mediterranean diet for six weeks, and again after the combination of the diet and EPA supplement for six weeks. Taking the EPA supplement for six weeks raised the blood levels of both EPA and DPA. DPA is anti-inflammatory in nature and keeps platelets from sticking together, which gives the fatty acid cardioprotective properties.

"The good news is that our findings show that we can change the lipid profile in the blood of children at high risk for heart disease with an omega-3 fatty acid supplement to a more favorable anti-inflammatory [lipid profile] that has been associated with decreased risk of heart disease and [with] healthy aging," Engler said.

Rockville, Md. (April 27, 2021)--Exposure to extreme heat (95 degrees Fahrenheit and above) and humidity for eight hours raises the core body temperature and causes dehydration, resulting in an increased risk of acute kidney injury, according to a new study. The researchers, from the Indiana University School of Public Health-Bloomington and University at Buffalo Center for Research and Education in Special Environments in New York, will present their findings virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

Acute kidney injury, which is defined as a sudden decline in kidney function, is a major cause of hospitalization during heat waves, especially in vulnerable populations such as older adults and obese individuals. This disorder is expected to worsen as the frequency, intensity and duration of heat waves expand in the U.S. due to climate change, according to study co-author Hayden Hess, PhD. As a result, there is concern the public health burden during these extreme hot weather events will be exacerbated.

The study was conducted in a group of adult men who were subjected to a heat- and humidity-controlled environmental chamber. The findings also indicate the risk of acute kidney injury was only evident when environmental conditions outpaced the ability of study participants to maintain core body temperature when cooling and hydrating were not permitted.

Researchers say this information will help lay a foundation for additional studies that improve understanding of the causal mechanisms that lead to a higher risk of acute kidney injury induced by extreme heat exposure. The findings will also be used to develop treatment and prevention measures-- such as cooling strategies and hydration recommendations--to reduce the risk of acute kidney injury in vulnerable populations.

Rockville, Md. (April 27, 2021)--New research to be presented this week virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021 explores the positive and negative effects of lifespan-extending drugs on mitochondrial function and age-related osteoarthritis (OA).

Decreased function of mitochondria--the energy centers of the cells--is a hallmark characteristic of aging. Maintaining mitochondrial function during the aging process while delaying age-related diseases, such as OA, could be a key to extending lifespan. Previous research has found that metformin, primarily used to treat type 2 diabetes, and rapamycin, a drug used to prevent organ transplant rejection, can extend lifespan and maintain physiological function in many animal models.

In a new study, researchers from the University of Wisconsin-Madison explored the effects of rapamycin, metformin or a regimen of both medications on a guinea pig model of OA. These drugs were chosen because they have been shown to expand lifespan and healthspan through positive change in the mitochondria. The research team found that the animals treated with rapamycin and the two-drug combination had lower mitochondrial content in their muscles and the function of the mitochondria was impaired. In addition to changes in mitochondrial function, rapamycin treatment also led to a rise in blood glucose levels and worsened OA scores, a measure of disease severity.

These results suggest "there may be an indirect connection between impaired skeletal muscle mitochondrial function to exacerbated OA after rapamycin treatment," said Christian Elliehausen, first author of the study. More research is needed to examine if it is possible to "harness the positive effects of rapamycin while minimizing the negative effects," Elliehausen explained.

Rockville, Md. (April 27, 2021)--People who self-report daytime sleepiness were found to have shorter telomeres regardless of whether they had obstructive sleep apnea, according to a new study from researchers at the Mayo Clinic in Rochester, Minnesota. The findings will be presented virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

Telomeres protect DNA from biological stressors, and shortened telomeres are associated with multiple cardiovascular diseases, according to the research team. This study found people reporting daytime sleepiness had similar telomere length compared to those without sleepiness; however, obstructive sleep apnea influences telomere length and was more prevalent in the sleepy group. When the researchers matched individuals between groups for the presence of sleep apnea, among other variables (e.g., age, weight), they found sleepy people without sleep apnea had shorter telomeres compared to those without sleepiness. In addition, there were no differences in telomere length between sleepy and non-sleepy individuals with sleep apnea. In essence, the study concluded daytime sleepiness was found to be linked to telomere shortening in the absence of sleep apnea.

Researchers are hopeful additional study will lead to reducing the rate of telomere shortening or reversing it altogether, which will could lower cardiovascular risk in people who report daytime sleepiness.

Rockville, Md. (April 27, 2021)--Urine analysis of COVID-19 patients revealed elevated levels of specific biomarkers of the immune system compared to those who were not infected with the coronavirus. In addition, levels of these inflammatory markers were higher in patients with comorbidities such as high blood pressure and diabetes, according to researchers from Wayne State University in Detroit. The findings will be presented virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

Researchers said they undertook this study in hopes of determining whether biomarkers of COVID-19 could predict which individuals will develop "overly exuberant immune responses," also called a cytokine storm. They chose to screen the urine of COVID-19 patients because of its non-invasive nature that doesn't require the use of needles or blood samples.

Scientists said they hope the results of this study will translate to a regular screening process for COVID-19 patients to predict who is more likely to develop severe disease and to aid in a successful treatment strategy.

Rockville, Md. (April 27, 2021)--Although bronchopulmonary dysplasia (BPD)--a chronic lung disease affecting newborns--is the most common complication of preterm birth, it remains difficult to diagnose and treat. Researchers from Fundación INFANT in Buenos Aires, Argentina, and The University of Oklahoma Health Sciences Center, hope to address these difficulties using machine learning to inform the clinical care of preemies with BPD. The team will present their work virtually at the American Physiological Society's (APS) annual meeting at Experimental Biology 2021.

BPD affects between 20% and 40% of all infants with birthweight below 3 pounds, 4 ounces (1,500 grams). It usually subsides by age five but can extend into adulthood. Infants with BPD face prolonged hospitalization and are at risk of developmental delays and heart failure.

The research team presented an algorithm with a large data set of longitudinal clinical information for preterm infants, which the computer divided into three clusters. They then presented the trained algorithm with a second data set with comparable demographic characteristics. In this set, the computer was able to anticipate comorbidities and rehospitalizations better than the application of standard BPD diagnostic categories.

By more accurately aligning which biometrics correspond to different degrees of disease severity, these findings could enable better understanding of the underlying causes of BPD. They could also help clinicians diagnose BPD earlier and more precisely, allowing for personalized treatments.

Corresponding author Gaston Ofman, MD, says the next step is "to implement our analysis in real time and guide health care workers in their day-to-day care of preterm babies."

A new study found that non-pungent synthetic analog of capsaicin -- the compound that makes chili peppers hot -- made small cell lung cancer cells more responsive to treatment. Small cell lung cancer is a very aggressive form of cancer with a low survival rate.

Cisplatin-based combination chemotherapy is typically the first-line treatment for small cell lung cancer patients. Although patients initially respond very well to this chemotherapy, the tumor usually comes back within a year in a form that doesn't respond to treatments. Patients with relapsed small cell lung cancer have very few treatment options.

"Irinotecan is the only FDA approved second-line drug for small cell lung cancer, but less than 3% of patients respond to it," said research team leader Piyali Dasgupta, PhD, from Marshall University. "Therefore, agents that improve the anti-cancer activity of irinotecan would be of great value to these patients."

Jamie Friedman, a former doctoral student in Dasgupta's lab will present the new findings at the American Society for Investigative Pathology annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

The natural compound capsaicin has been shown to have anti-cancer effects, but its heat can also cause a burning sensation, stomach cramps, gut pain and nausea. In the new work, the researchers studied arvanil, a synthetic capsaicin analog without capsaicin's undesirable side effects.

When the researchers exposed two cisplatin-resistant lung cancer cell lines to a low concentration of arvanil, they saw no growth-inhibitory activity. However, when they treated the cells with varying concentrations of SN38 -- the active ingredient irinotecan -- they observed that the presence of arvanil greatly enhanced the ability of SN38 to slow cancer cell growth. Statistical analysis showed that the interaction between arvanil and SN38 was synergistic in nature.

"Because arvanil enhanced the anti-cancer activity of SN38 in human small cell lung cancer cells, arvanil-based combination therapies may be useful for patients with relapsed small cell lung cancer cells," said Friedman. "We hope that this work will pave the way for novel therapies for relapsed and cisplatin-resistant small cell lung cancer."

Jamie Friedman will present the findings in poster R361 (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

Scientists from around the world are gathering to share the latest research at the forefront of biology during the Experimental Biology (EB) 2021 meeting. Many sessions focus on the year's most pressing priorities in bioscience: COVID-19 and the virus that causes it, SARS-CoV-2. Here are five highlights:

Legacy of COVID-19 in blood vessels may raise risk of heart disease

A study from the Medical College of Wisconsin suggests COVID-19 could cause long-term problems with the functioning of blood vessels, potentially increasing the risk of heart disease. Scientists examined arterioles, small branches of the cardiovascular system, in tissue samples from 14 people who had recovered from COVID-19 and 19 who had never had COVID-19. Arterioles regulate the flow of oxygen-rich blood to tissues by widening (dilating) and narrowing according to the body's needs at each moment. When exposed to stimuli (like chemicals or flow) that cause blood vessels to dilate, the arterioles from COVID-19 patients did not widen nearly as much as those from people without COVID-19. This effect was attributed to impaired functioning of the endothelium, the lining of the blood vessels. The effect was most pronounced in samples from people who had COVID-19 less than three months earlier; endothelium functioning was still impaired but closer to normal by eight months after infection. Over time, endothelial dysfunction in the blood vessels can lead to several forms of heart disease.

Yoshinori Nishijima will present this research online from 11:15-11:30 a.m. Thursday, April 29 (abstract). Images available.

Promising leads in the search for COVID-19 treatments

While vaccines are critical to curbing the COVID-19 pandemic, there is still a need for better treatments to improve the outlook for those who become infected. Research from the University of Oklahoma Health Sciences Center suggests drugs that inhibit a key enzyme in the SARS-CoV-2 virus could offer promising leads for an antiviral treatment. In experiments using cell cultures, the researchers found that three naturally occurring compounds significantly reduced the activity of the SARS-CoV-2 main protease, an enzyme the virus uses to replicate. The research team was able to trace how two of the compounds, phebestin and probestin, inhibit the main protease at the molecular level. They also found that these compounds did not harm mouse cells from the lining of the lungs, a test used to screen for safety concerns associated with delivering medicines through the nose. Based on these findings, the researchers say the compounds, which are members of a class of molecules called peptidic ?-hydroxy amides, warrant further study as potential antiviral drugs for COVID-19.

Nagendra Yarla will present this research online on-demand from April 27-30 (abstract). Images available.

Molecules found in stem cells could calm COVID-19 cytokine storm

Treatment options are currently limited for patients with COVID-19 who suffer an excessive immune response known as a cytokine storm, which causes life-threatening damage to organs and tissues. Research led by the Houston Methodist Research Institute demonstrates that stem cells isolated from amniotic fluid contain several molecules that might be able to help counter a cytokine storm. Unlike embryonic stem cells, these cells are routinely collected to test amniotic fluid during prenatal diagnosis, without harm to the mother or fetus. Researchers found that the amniotic stem cells contained molecules involved in communicating with immune cells, regulating immunity and inflammation, protecting and repairing the lining of the lungs and maintaining a healthy heart. The study suggests mesenchymal stem cells from amniotic fluid, which have previously been explored as a therapy for other conditions, could offer a new option for treating the severe and chronic inflammation resulting from COVID-19 infection.

Salvatore Vaiasicca will present this research online from 2:45-3 p.m. Wednesday, April 28 (abstract).

Expert roundtable: Toward understanding and containing the COVID-19 pandemic

Researchers will present a series of lightning talks on the mechanisms underlying COVID-19 infections along with updates on current and emerging treatments and vaccines. Topics include SARS-CoV-2 variants and genomic analysis; autopsy-derived insights into the pathobiology of COVID-19; the race for a vaccine; and mitigating COVID-19 in meat and poultry processing plants.

The session will be held online from 2-5 p.m. on Friday, April 30, and include a live Q&A with experts (more information).

How COVID-19 changed practices for science education

How did science educators and students adjust to constraints on in-person learning during the COVID-19 pandemic? A survey of educators in anatomy -- a field with a strong emphasis on in-person, hands-on learning -- sheds light on changing practices. Researchers from 10 universities across the U.S. and Canada conducted two surveys of anatomy educators in 2020. The first survey collected 67 responses from May through August, and the second collected 191 responses from August to December, reflecting the summer and fall terms, respectively. Respondents reported a drastic reduction of in-person lectures while remote instruction increased; they also reduced the use of cadavers and increased the use of other laboratory teaching materials, such as digital and virtual anatomical technology. These changes were most pronounced early in the pandemic. During the final months of 2020, respondents reported greater use of in-person teaching and use of cadavers, though these practices were still diminished and varied by institution compared with prepandemic levels. The researchers suggest further study can help elucidate whether these trends may represent long-term changes for anatomy education.

Derek Harmon will present this research online in poster R2047 (abstract). Images available.

EB 2021 is the premiere annual meeting of five scientific societies to be held online April 27-30, 2021. Contact the media team for more information or to obtain a free press pass to attend the virtual meeting.

Recent years have brought increased attention to the lasting effects of chemicals we unwittingly inhale, touch and ingest while going about our daily lives. The Experimental Biology (EB) 2021 meeting features the latest research on how environmental exposures affect health. Here are five highlights:

Study sheds light on health hazards of hog farms

People who work at or live near concentrated animal feeding operations, especially hog farms, commonly face an increased risk of respiratory problems and gastrointestinal diseases. New research from the University of California, Riverside, investigates the mechanisms through which exposure to hog farms may harm health. In studies using mice and cell cultures, scientists found evidence that breathing dust from hog farms leads to inflammation in the airways. The research also suggests that compounds from hog dust increase the permeability of the intestine, possibly by damaging the intestinal lining, which may help explain why farm workers are more susceptible to gastrointestinal disease. The research could help inform interventions to better protect the health of farm workers and people living near large farming operations.

Meli'sa Crawford will present this research online from 2-2:15 p.m. Friday, April 30 (abstract).

Common ingredient in antimicrobial soap and toothpaste linked with inflammation

Inflammation is a natural process our bodies use to heal and fight infections, but chronic or unwarranted inflammation can lead to diseases including arthritis and cancer. Researchers at Tennessee State University report new evidence that triclosan, an antimicrobial compound used in personal hygiene products such as soap, toothpaste and mouthwash, may cause inflammation and potentially increase the risk of associated health problems. The researchers exposed cell cultures to triclosan and measured interleukin-6 (IL-6), a biomarker used to assess inflammation. They found that triclosan exposure caused a substantial increase in IL-6 production over a 24-hour period, with levels peaking at six hours after exposure. The study adds to a growing body of evidence suggesting potential detrimental effects of triclosan, which can be ingested or absorbed through the skin when using products that contain it, according to researchers.

Wendy Wilburn will present this research online in poster R318 (abstract).

Cigarettes may pose risk even after they're extinguished

Health problems associated with smoking and being near someone who is smoking (secondhand smoke) are well established. A new study from Texas A&M University suggests the residual smoke that remains even after a cigarette is put out -- called thirdhand smoke -- could affect the health of fetuses. The researchers exposed pregnant mice to smoke contaminants from extinguished cigarettes and traced health markers in their offspring. They found that mice exposed to thirdhand smoke in utero showed a significant increase in aggregation of platelets, a component of blood involved in clotting. In other tests, these mice showed markers indicating a predisposition toward cardiovascular problems related to blood clots. Researchers say the study draws attention to the need to further investigate the potential consequences of thirdhand smoke exposure.

Ahmed Alarabi will present this research online in poster R4465 (abstract). Images available.

Gulf War veterans may be more susceptible to alcohol-induced liver damage

Some veterans of the 1990-1991 Persian Gulf War suffer Gulf War illness, a syndrome with a wide range of symptoms thought to be caused by chemical exposures encountered during combat. A new study from Central Texas Veterans Health Care System suggests these veterans may be more prone to liver damage from heavy alcohol consumption. Researchers exposed mice to chemicals similar to those thought to cause Gulf War illness and assessed the effects of ethanol on liver health in these mice, comparing them with mice that had not been exposed to the chemicals. They found that exposure to chemicals caused long-term changes to the liver, including low-level inflammation, suggesting a greater susceptibility to alcohol-induced liver disease. This type of liver disease is associated with heavy alcohol use, but researchers have struggled to understand why some people who drink heavily develop liver problems while others do not. The study bolsters the evidence that environmental exposures may play a role.

Suyeon An will present this research online in poster R4162 (abstract).

New evidence suggests role of epigenetic factors in determining anatomy

With the same genetic makeup, identical twins share many similarities. But new research suggests twins show subtle differences beneath the surface, possibly as a result of epigenetics (changes in gene expression) or environmental factors such as nutrition and chemical exposures. Scientists at the University of Colorado Anschutz Medical Campus examined cadavers donated by a pair of identical twins. Comparing the structures of nerves, veins and arteries in the neck, trunk, pelvis and limbs, they found significant differences in these structures between twins. In addition, some paired structures showed asymmetric differences within a single individual. While the researchers were not able to attribute the differences to specific causes, the study, which is the first to demonstrate unique anatomic variations in identical twins, suggests further research could help elucidate how epigenetic factors may alter our bodies over the course of a lifetime.

Chelsea Lohman Bonfiglio will present this research online in poster R2536 (abstract).

EB 2021 is the premiere annual meeting of five scientific societies to be held online April 27-30, 2021. Contact the media team for more information or to obtain a free press pass to attend the virtual meeting.

Results from a new cell study suggest that the SARS-CoV-2 spike protein can bring about long-term gene expression changes. The findings could help explain why some COVID-19 patients -- referred to as COVID long-haulers -- experience symptoms such as shortness of breath and dizziness long after clearing the infection.

SARS-CoV-2, the virus that causes COVID-19, is covered in tiny spike proteins. During infection, the spike proteins bind with receptors on cells in our body, starting a process that allows the virus to release its genetic material into the inside of the healthy cell.

"We found that exposure to the SARS-CoV-2 spike protein alone was enough to change baseline gene expression in airway cells," said Nicholas Evans, a master's student in the laboratory of Sharilyn Almodovar, PhD, at the Texas Tech University Health Sciences Center. "This suggests that symptoms seen in patients may initially result from the spike protein interacting with the cells directly."

Evans will present the research at the American Society for Biochemistry and Molecular Biology annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.

Culturing human airway cells requires specific conditions that allow cells to mature into the differentiated cells that would be found in the airway. The researchers optimized a previously developed culturing approach known as the air-liquid interface technique so that it would more closely simulate the physiological conditions found in the lung airway. This involved exposing cells to air and then giving them time to mature into airway cells.

The researchers found that cultured human airway cells exposed to both low and high concentrations of purified spike protein showed differences in gene expression that remained even after the cells recovered from the exposure. The top genes included ones related to inflammatory response.

"Our work helps to elucidate changes occurring in patients on the genetic level, which could eventually provide insight into which treatments would work best for specific patients," said Evans.

The researchers also compared their cultured human airway cells to studies from others where cells were collected from patients with COVID-19 infection. They were able to confirm that the optimized cell culture approach reflected what occurs in patients, making it useful for future translational studies. They plan to use the new approach to better understand how long the genetic changes last and the potential long-term consequences of these changes in relation to long-haul COVID-19 cases.

Nicholas Evans will present the findings from 12:00-12:15 p.m. Friday, April 30 (abstract). Contact the media team for more information or to obtain a free press pass to access the meeting.

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