PRESS-NEWS.org - Press Release Distribution
FREE PRESS RELEASES DISTRIBUTION

VUMC Team Develops Potential Treatment for Life-threatening Microbial Inflammation

VUMC Team Develops Potential Treatment for Life-threatening Microbial Inflammation
2021-06-09
(Press-News.org) A cell-penetrating peptide developed by researchers at Vanderbilt University Medical Center can prevent, in an animal model, the often-fatal septic shock that can result from bacterial and viral infections.

Their findings, published this week in Scientific Reports, could lead to a way to protect patients at highest risk for severe complications and death from out-of-control inflammatory responses to microbial infections, including COVID-19.

"Life-threatening microbial inflammation hits harder (in) patients with metabolic syndrome, a condition afflicting millions of people in the United States and worldwide," said the paper's corresponding author, Jacek Hawiger, MD, PhD, the Louise B. McGavock Chair in Medicine and Distinguished Professor of Medicine at VUMC.

An international authority on inflammation as the mechanism of multiple diseases, Hawiger also is professor of Molecular Physiology and Biophysics at Vanderbilt and a Health Research Scientist at the Nashville Veterans Affairs (VA) Medical Center.

"We explore the pathways to the cell's nucleus, the command center of inflammation," he said.

In response to bacterial infection, transcription factors are ferried to the nucleus of immune and vascular cells, where they reprogram gene expression to ramp up production of infection-fighting inflammatory molecules. Like a wildfire, however, the inflammatory response, if unchecked, can damage small blood vessels, leading to multiple organ failure and death.

Patients with pre-existing health conditions, including obesity and high blood levels of glucose (diabetes), triglycerides and cholesterol (hyperlipidemia) -- hallmarks of metabolic syndrome -- are at increased risk of developing a damaging inflammatory response to infection.

They also are more likely to die of complications of COVID-19, which include acute respiratory distress syndrome, septic cardiomyopathy (damage to heart muscle), microvascular thrombosis (tiny blood clots) and acute kidney injury. These complications result from infection-induced septic shock due to the collapse of small blood vessels. Pre-existing conditions, notably hyperlipidemia, already can cause inflammation in these small vessels. Infection, the researchers reasoned, may only make it worse.

In 2014 Hawiger and colleagues developed a cell-penetrating peptide, or protein fragment, that blocked signaling pathways leading to lethal shock in animals exposed to the endotoxin lipopolysaccharide (LPS), which is released during infection by Gram-negative bacteria.

This "parent" peptide, called cSN50.1, selectively suppressed the transport into the nucleus of transcription factors responsible for the out-of-control inflammatory response, and dramatically increased survival in mice exposed to high doses of LPS.

In a 2017 the Hawiger team used a polymicrobial sepsis model to show that the same treatment combined with an antibiotic increased survival in mice from 30% (using antibiotic alone) to 55%.

In 2019 the U.S. Food and Drug Administration designated the peptide as an "Investigational New Drug" and allowed a clinical trial in an inflammatory skin disease sponsored by Amytrx, a start-up company co-founded by Hawiger.

In the current study, the researchers tested whether, in a mouse model of hyperlipidemia, two novel, pathway-selective forms of this peptide could, as they put it, "stop pro-inflammatory and metabolic transcription factors in their tracks" at the nuclear transport checkpoint.

One peptide, which selectively targets the nuclear shuttle for proinflammatory transcription factors, protected against the acute stage of lethal microbial inflammation, while extended treatment with the other peptide, which targets the nuclear transport checkpoint for metabolic transcription factors, reduced production of cholesterol, triglycerides and fatty acids.

"Experimentally, by targeting the nuclear transport checkpoint, we suppressed the burst of inflammatory mediators while lowering elevated levels of blood glucose, triglycerides, and cholesterol and protecting small blood vessels from injury in the liver, lungs, heart and kidneys," Hawiger said.

"Our findings are of significant relevance to individuals displaying signs of metabolic syndrome that predisposes them to life-threatening microbial diseases, including recent outbreaks of COVID-19 as well as autoimmune and allergic disorders," the researchers concluded.

INFORMATION:

Yan Liu, MD, research assistant professor of Medicine, and Jozef Zienkiewicz, PhD, research associate professor of Medicine, are co-first authors of the paper. Other contributors were Kelli Boyd, DVM, PhD, currently at Gilead Sciences, Taylor Smith, MS, now attending Indiana University School of Medicine, and Zhi-Qi Xu.

The research was supported by grants from the U.S. Department of Veterans Affairs and the endowed McGavock Chair at Vanderbilt.


[Attachments] See images for this press release:
VUMC Team Develops Potential Treatment for Life-threatening Microbial Inflammation

ELSE PRESS RELEASES FROM THIS DATE:

CHIME telescope detects more than 500 mysterious fast radio bursts in its first year of operation

2021-06-09
BRIEFING NOTE: Researchers will announce these results at the 238th AAS meeting on Wednesday, June 9 at 12:15 p.m. E.D.T. Press registration details can be found here: https://aas.org/meetings/aas238/press. Interested journalists can also tune in to AAS briefings streamed live at: https://www.youtube.com/c/AASPressOffice. Please note that you will not be able to ask questions via YouTube; to ask questions, you'll need to register for the meeting and join the briefings via Zoom. Recordings will be archived on the AAS Press Office YouTube channel afterward. To catch sight of a fast radio burst is to be extremely lucky in where and when you point your radio dish. Fast radio bursts, or FRBs, are oddly bright flashes of light, registering ...

Emergency care for heart attacks and strokes rebounds

2021-06-09
OAKLAND, Calif. -- The significant declines in heart attack hospitalizations and emergency care for possible strokes seen in Northern California at the beginning of the COVID-19 pandemic were not seen in subsequent surges, new research from Kaiser Permanente shows. The study, published June 2 in JAMA, suggests public health campaigns that encouraged people to seek care if they were experiencing signs or symptoms of a stroke or heart attack were effective. "In May 2020, we reported that, in the early months of the pandemic, the weekly number of patients admitted to our hospitals for a heart attack fell to nearly half of what would be expected," said the study's lead author Matthew ...

Study shows adaptive brain response to stress, and its absence in people with depression

2021-06-09
A new study identifies a novel biomarker indicating resilience to chronic stress. This biomarker is largely absent in people suffering from major depressive disorder, and this absence is further associated with pessimism in daily life, the study finds. Nature Communications published the research by scientists at Emory University. The researchers used brain imaging to identify differences in the neurotransmitter glutamate within the medial prefrontal cortex before and after study participants underwent stressful tasks. They then followed the participants for four weeks, using a survey protocol to regularly assess how participants rated their expected and experienced outcomes for daily activities. "To our knowledge, this is the first work to show ...

Heart transplants: Age is no barrier to successful surgery

2021-06-09
A new study published in the Journal of the American Geriatrics Society suggests that survival rates after heart transplant surgery are similar in adults ages 18 to 69 and adults ages 70 and older. Researchers examined a large U.S. database of patients who were listed as candidates for surgery to replace their failing hearts with healthier donor hearts. The researchers found that: Only 1 in 50 people who are considered for heart transplant surgery and 1 in 50 people who receive a heart transplant are ages 70 or older. For older adults in the study, the likelihood of surviving one or five years after a heart transplant was about the same as for younger adults. Having a ...

A link between childhood stress and early molars

2021-06-09
Early in her career neuroscientist Allyson Mackey began thinking about molars. As a researcher who studies brain development, she wanted to know whether when these teeth arrived might indicate early maturation in children. "I've long been concerned that if kids grow up too fast, their brains will mature too fast and will lose plasticity at an earlier age. Then they'll go into school and have trouble learning at the same rate as their peers," says Mackey, an assistant professor in the Department of Psychology at Penn. "Of course, not every kid who experiences stress or [is] low income will show this pattern of accelerated development." What would help, she thought, was a scalable, objective way—a physical manifestation, ...

Better-fitting face masks greatly improve COVID-19 protection

Better-fitting face masks greatly improve COVID-19 protection
2021-06-09
Even the best face masks work only as well as their fit. And poorly fitting face masks greatly increase the risk of infection from airborne pathogens compared to custom-fitted masks, according to a new study by the University of Cincinnati. Researchers in UC's College of Engineering and Applied Science used computerized tomography or CT scans of three different-sized face masks attached to three different-sized dummy heads to measure the gaps between the face and the fabric. Then they calculated the leaks from these gaps to determine the infection risk.  They found that while N95 masks are effective barriers against airborne diseases like COVID-19, poorly ...

New adaptable nanoparticle platform enables enhanced delivery of gene therapies

New adaptable nanoparticle platform enables enhanced delivery of gene therapies
2021-06-09
Scientists have developed polypeptide-based materials that act as effective vectors for delivering gene therapies. The first-of-its-kind platform enables the vectors to be adapted to suit the specific gene therapy cargo. The work, led by researchers from RCSI University of Medicine and Health Sciences and funded by Science Foundation Ireland, is published in Biomaterials Science. A major challenge for gene therapies is preparing them in a way that can deliver the genetic information into the host cells. For the Covid-19 vaccines that use mRNA technology, the genetic information is delivered ...

Having trouble falling asleep predicts cognitive impairment in later life

2021-06-09
DARIEN, IL - A study of nearly 2,500 adults found that having trouble falling asleep, as compared to other patterns of insomnia, was the main insomnia symptom that predicted cognitive impairment 14 years later. Results show that having trouble falling asleep in 2002 was associated with cognitive impairment in 2016. Specifically, more frequent trouble falling asleep predicted poorer episodic memory, executive function, language, processing speed, and visuospatial performance. Further analysis found that associations between sleep initiation and later cognition were partially explained by both depressive symptoms and vascular ...

Persistent insomnia symptoms since childhood associated with mood, anxiety disorders

2021-06-09
DARIEN, IL - A 15-year longitudinal study shows that childhood insomnia symptoms that persist into adulthood are strong determinants of mood and anxiety disorders in young adults. Results show that insomnia symptoms persisting from childhood through adolescence and into adulthood were associated with a 2.8-fold increased risk of internalizing disorders. Insomnia symptoms that newly developed over the course of the study were associated with a 1.9-fold increased risk of internalizing disorders. No increased risk of internalizing disorders was found for those children in whom insomnia symptoms remitted during the study period. "We found that about ...

Measuring sound diversity of quietness

Measuring sound diversity of quietness
2021-06-09
MELVILLE, N.Y., June 9, 2021 -- The world is filled with myriad sounds that can overwhelm a person with relentless acoustics. Noise is so prevalent in everyday life that the concept and achievement of comfortable quiet is hard to define. During the 180th Meeting of the Acoustical Society of America, which will be held virtually June 8-10, Aggelos Tsaligopoulos, from the University of the Aegean, will describe how quiet could be measured in the hopes of better understanding its impact on people. The session, "Towards a new understanding of the concept of quietness," will take place Wednesday, ...

LAST 30 PRESS RELEASES:

Milk protein could help boost blueberries' healthfulness

Seeking a treatment for IBS pain in tarantula venom

Addressing inequity in air quality

Roughness of retinal layers, a new Alzheimer's biomarker

Study links sleep apnea in children to increased risk of high blood pressure in teen years

Black patients with cirrhosis more likely to die, less likely to get liver transplant

Researchers outline specific patterns in reading in Russian

These sea anemones have a diverse diet. And they eat ants

Viruses as communication molecules

Spirituality can promote the health of breast cancer survivors

Tiny ancient bird from China shares skull features with Tyrannosaurus rex

University of Minnesota Medical School report details the effects of COVID-19 on adolescent sexual health

Odd smell: flies sniff ammonia in a way new to science

Fracture setting method could replace metal plates, with fewer complications

Sneeze cam reveals best fabric combos for cloth masks (video)

'Lady luck' - Does anthropomorphized luck drive risky financial behavior?

People willing to pay more for coffee that's ethical and eco-friendly, meta-analysis finds

Low-cost imaging technique shows how smartphone batteries could charge in minutes

Pleistocene sediment DNA from Denisova Cave

Quantum birds

Antibody therapy rescues mice from lethal nerve-muscle disease

Life in these star-systems could have spotted Earth

Cutaneous reactions after mRNA COVID-19 vaccines

Skin reactions after COVID-19 vaccination: Rare, uncommonly recur after second dose

Mask mandates and COVID-19 case rates, hospitalizations, deaths in Kansas

Changes in physician work Hours, patterns during COVID-19

Voucher-based kidney donation, redemption for future transplant

Bird migration takes plants in wrong direction to cope with climate change

Scientists uncover new mechanism that enables development of cancer

Study reveals formation mechanism of first carbon-carbon bond in MTO process

[Press-News.org] VUMC Team Develops Potential Treatment for Life-threatening Microbial Inflammation