Connect with us

Economics

Adipose tissue may be the source of inflammatory factors that aggravate COVID-19

Adipose tissue may be the source of inflammatory factors that aggravate COVID-19

Published

on

Preliminary results of patient tissue analysis show that the virus infects adipocytes and alters the quantity of signaling molecules released by these cells into the bloodstream

IMAGE

Credit: Rodolfo Marinho

There is growing evidence that adipose tissue plays a key role in the aggravation of COVID-19. One of the theories under investigation is that fat cells (adipocytes) act as a reservoir for SARS-CoV-2 and increase viral load in obese or overweight individuals. Scientists also suspect that during infection fat cells release into the bloodstream substances that boost the inflammatory reaction triggered by the virus in the organism.

These hypotheses are being investigated by researchers at the University of São Paulo’s Medical School (FM-USP) in Brazil under the coordination of Marilia Cerqueira Leite Seelaender, a professor in the Department of Clinical Surgery. Peter Ratcliffe, a professor at the University of Oxford in the UK and one of the winners of the 2019 Nobel Prize for Medicine, is collaborating.

“A cytokine storm resulting in systemic inflammation similar to sepsis occurs in some severe COVID-19 patients. We believe these inflammatory factors come from adipose tissue. It’s been shown that when adipocytes expand too much, they can cause inflammation throughout the body, even in the brain,” Seelaender told Agência FAPESP.

The FM-USP group analyzed samples of adipose tissue obtained from autopsies of people who died from COVID-19, and also from patients infected with SARS-CoV-2 who had to be submitted to emergency surgery at the university’s hospital for appendicitis or other reasons not related to the viral infection. Preliminary results confirmed that the virus can be found in fat cells, whose membranes are rich in ACE-2, the main receptor used by the virus to invade human cells. The researchers have yet to confirm that once it has invaded adipocytes, it can remain there long enough to replicate inside them.

“It’s worth noting that visceral adipocytes [located deep in the abdomen and around internal organs] have much more ACE2 than subcutaneous adipose tissue,” Seelaender said. “In addition, they’re much more inflammatory. As a result, visceral obesity tends to be even more harmful as far as COVID-19 is concerned.”

The preliminary findings also brought to light a change in the pattern of exosome secretion in the adipose tissue of infected people. Exosomes are extracellular vesicles, comparable to tiny bubbles, released by cells into the bloodstream with proteins and other types of signaling molecules. This is one of the mechanisms whereby information is exchanged between different tissues as the body adapts to changes in its environment.

The aims of the research conducted by the FM-USP group include investigating whether infection by SARS-CoV-2 makes adipocytes release more exosomes containing inflammatory factors. So far it has shown that the number of vesicles released into the bloodstream does indeed increase. The researchers will now analyze the contents of these circulating vesicles, as well as those remaining inside cells. They also plan to investigate the inflammatory pathways presumably activated by these molecules.

“We first assumed that as a person gets fat, their adipose tissue becomes hypoxic, meaning the person has less oxygen available. Hypoxia is itself a cause of inflammation, so one of the things we want to investigate is whether COVID-19 causes hypoxia in adipocytes,” Seelaender said.

Research on how human cells adapt to hypoxia won Ratcliffe the Nobel with William G. Kaelin (Harvard University) and Gregg Semenza (Johns Hopkins School of Medicine). Currently, his work focuses on analyzing autopsy samples to find out how SARS-CoV-2 affects the carotid body, a cluster of chemoreceptors and supporting cells in the carotid artery that function as an oxygen sensor. When it senses that blood oxygen levels are too low, the carotid body activates responses that raise heart and respiratory rates.

Ratcliffe believes the virus infects the carotid body and impairs its functioning, which explains why many COVID-19 patients are slow to recognize they are hypoxic, not least because they do not feel short of breath (“silent hypoxia”).

The FM-USP group, meanwhile, is concentrating on an effort to understand the effect of infection on adipose tissue. “We’re analyzing everything secreted by fat cells: proteins, saturated fatty acids, prostaglandins [lipids with diverse hormone-like effects], microRNAs [small non-coding RNA molecules that regulate gene expression] and exosomes,” Seelaender said.

Inflammatory factors released by adipose tissue in COVID-19 patients may be the cause of damage to the heart, lungs, and nervous system described in such patients, she added. “Our hypothesis is that obese COVID-19 patients undergo a similar process to that observed in the adipose tissue of patients with cachexia [significant rapid weight loss and muscle wasting associated with AIDS, heart failure and cancer, among other diseases],” she said. “Adipocytes in cachexic individuals release more exosomes, and their contents are altered so that they have a pro-inflammatory profile. We know there’s inflammation in both cachexia and obesity. The difference lies in the type of inflammatory mediator released and the signaling pathways activated.”

Seelaender and her group have been researching the links between cachexia and inflammation since 2013 with FAPESP’s support.

Opposite but similar

In an article published in the journal Advances in Nutrition, Seelaender and her group discuss how nutritional status can influence a patient’s response to COVID-19. According to the authors, both obesity and malnutrition – including cachexia and sarcopenia (loss of skeletal muscle mass associated with aging) – can impair the immune response and prevent the organism from combating viral infection.

“Immune cells require more energy during an infectious process, especially if the body takes a long time to overcome it. Their metabolism needs to change so that they can multiply rapidly, but in an undernourished organism, this isn’t possible. During an infection the number of T-lymphocytes in a malnourished individual is much smaller than in a eutrophic [well-nourished] individual,” Seelaender said.

Moreover, she continued, undernourished organisms suffer from atrophy of the lymphoid organs (especially bone marrow, thymus and lymph nodes), in which the lymphocytes are produced and reach maturity. As a result, the number of circulating defense cells declines. Experiments with animals have also shown that an organism suffering from malnutrition takes longer to eliminate viruses.

“Fat can be a problem when it’s excessive or insufficient. However paradoxical it may seem, both extremes are dangerous,” she explained. “Adipose tissue secretes leptin, a hormone that regulates T-lymphocyte metabolism. Leptin signaling falls in a body with very low fat. Excessively high fat makes cells less sensitive to leptin, so the amount of leptin released rises sharply.”

Aging affects several of the factors mentioned by Seelaender. The immune system becomes less responsive. Skeletal muscle mass dwindles, visceral fat increases, and the proportion between lean and fat mass worsens.

“Loss of lean mass can worsen the outcome of chronic and acute diseases in older people. Muscle is a reservoir of energy substrate [amino acids] that can be mobilized at times of need, such as during an infection,” she said. “That’s why it’s important to stress that not just adiposity but also the lean-to-fat mass ratio is a problem in COVID-19 patients. If a person has a lot of fat and little muscle, it’s worse than if they have a lot of fat but a good muscular condition.”

###

About São Paulo Research Foundation (FAPESP)

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

Media Contact
Heloisa Reinert
hreinert@fapesp.br

Original Source

https://agencia.fapesp.br/34625/

Related Journal Article

http://dx.doi.org/10.1093/advances/nmaa125

Read More

Continue Reading

Spread & Containment

No sign of major crude oil price decline any time soon

Bullish pressure on crude oil markets doesn’t seem to be easing Crude oil prices fell last week, notching their second weekly decline in the face of…

Published

on

By

Bullish pressure on crude oil markets doesn’t seem to be easing

Crude oil prices fell last week, notching their second weekly decline in the face of concern that rising interest rates could push the global economy into recession.

Yet the future of crude oil still seems bullish to many. Spare capacity, or lack of it, is just one of the reasons.

The global surplus of crude production capacity in May was less than half the 2021 average, the U.S. Energy Information Administration (EIA) reported on Friday.

The EIA estimated that as of May, producers in nations not members of the Organization of Petroleum Exporting Countries (OPEC) had about 280,000 barrels per day (bpd) of surplus capacity, down sharply from 1.4 million bpd in 2021. It said 60 per cent of the May 2021 figure was from Russia, which is increasingly under sanctions related to its invasion of Ukraine.

The OPEC+ alliance of oil producers is running out of capacity to pump crude, and that includes its most significant member, Saudi Arabia, Nigerian Minister of State for Petroleum Resources Timipre Sylva told Bloomberg last week.

“Some people believe the prices to be a little bit on the high side and expect us to pump a little bit more, but at this moment there is really little additional capacity,” Sylva said in a briefing with reporters on Friday. “Even Saudi Arabia, Russia, of course, Russia, is out of the market now more or less.” Nigeria was also unable to fulfil its output obligations, added Sylva.

Recent COVID-19-related lockdowns in parts of China – the world’s largest crude importer – also played a significant role in the global oil dynamics. The lack of Chinese oil consumption due to the lockdowns helped keep the markets in a check – somewhat.

Oil prices haven’t peaked yet because Chinese demand has yet to return to normal, a United Arab Emirates official told a conference in Jordan early this month. “If we continue consuming, with the pace of consumption we have, we are nowhere near the peak because China is not back yet,” UAE Energy Minister Suhail Al-Mazrouei said. “China will come with more consumption.”

Al-Mazrouei warned that without more investment across the globe, OPEC and its allies can’t guarantee sufficient supplies of oil as demand fully recovers from the pandemic.

But the check on the Chinese crude consumption seems to be easing.

On Saturday, Beijing, a city of 21 million-plus people, announced that primary and secondary schools would resume in-person classes. And as life seemed to return to normal, the Universal Beijing Resort, which was closed for nearly two months, reopened on Saturday.

Chinese economic hub Shanghai, with a population of 28 million-plus people, also declared victory over COVID after reporting zero new local cases for the first time in two months.

The two major cities were among several places in China that implemented curbs to stop the spread of the omicron wave from March to May.

But the easing of sanctions should mean oil’s price trajectory will resume its upward march.

In the meantime, in the U.S., the Biden administration is eying tougher anti-smog requirements. According to Bloomberg, that could negatively impact drilling across parts of the Permian Basin, which straddles Texas and New Mexico and is the world’s biggest oil field.

While the world is looking for clues about what the loss of supply from Russia will mean, reports are pouring in that the ongoing political turmoil in Libya could plague its oil output throughout the year.

The return of blockades on oilfields and export terminals amid renewed political tension is depriving the market of some of Libya’s oil at a time of tight global supply, said Tsvetana Paraskova in a piece for Oilrpice.com.

And in the ongoing political push to strangle Russian energy output, the G7 was reportedly discussing a price cap on oil imports from Russia. Western countries are increasingly frustrated that their efforts to squeeze out Russian energy supplies from the markets have had the counterproductive effect of driving up the global crude price, which is leading to Russia earning more money for its war chest.

To tackle the issue, and increase pressure on Russia, U.S. Treasury Secretary Janet Yellen is proposing a price cap on Russian crude oil sales. The idea is to lift the sanction on insurance for Russian crude cargo for countries that accept buying Russian oil at an agreed maximum price. Her proposal is aimed at squeezing Russian crude out of the market as much as possible.

So the bullish pressure on crude oil markets doesn’t seem to be easing.

By Rashid Husain Syed

Toronto-based Rashid Husain Syed is a respected energy and political analyst. The Middle East is his area of focus. As well as writing for major local and global newspapers, Rashid is also a regular speaker at major international conferences. He has provided his perspective on global energy issues to the Department of Energy in Washington and the International Energy Agency in Paris.

Courtesy of Troy Media

Read More

Continue Reading

Spread & Containment

University of Cincinnati enrolling patients for PTSD clinical trials

About 8% of Americans will experience post-traumatic stress disorder at some point in their lives, but there are still few effective options to treat the…

Published

on

About 8% of Americans will experience post-traumatic stress disorder at some point in their lives, but there are still few effective options to treat the condition.

Credit: Photo/University of Cincinnati

About 8% of Americans will experience post-traumatic stress disorder at some point in their lives, but there are still few effective options to treat the condition.

“There are some medical treatments for PTSD and psychotherapies for PTSD, but patients continue to suffer with symptoms that aren’t responsive to the currently available treatments,” said Lesley Arnold, MD.

June is PTSD Awareness Month, and the University of Cincinnati is currently enrolling patients for clinical trials examining the effectiveness of different medications to better treat PTSD symptoms.

The basics

Arnold said PTSD is a common and often chronic disorder that develops after a traumatic event that is either personally experienced or witnessed by a person.

“People with PTSD often re-experience aspects of the original trauma and can develop symptoms such as avoidance of trauma reminders, negative thoughts and feelings and increased alertness to their surroundings,” said Arnold, director of the Women’s Health Research Program and professor in the Department of Psychiatry and Behavioral Neuroscience in the UC College of Medicine.

Most people who are exposed to a trauma will have an acute stress response in the moment, Arnold said, but about 30% of those who experience a trauma develop PTSD. Symptoms can last for months or years and also include disrupted sleep or nightmares, issues with memory or focus and depression and anxiety. 

In people who are at higher risk for exposure to trauma, such as war veterans, PTSD occurs in even higher proportions, Arnold said. The COVID-19 pandemic has also exacerbated symptoms of PTSD for some individuals.

“It led to some isolation and made it difficult for individuals to seek treatment or to continue to engage in treatment,” Arnold said. 

New trials

Arnold and her team are focused on testing medication-based treatments that could help alleviate the symptoms of PTSD that have not responded to currently available medications, including sleeplessness and nightmares among others.

“The problem that we have is that there are two FDA medications approved for the treatment of PTSD, but these medications aren’t effective for everybody, and they take a long time to work,” Arnold said. 

Each of the clinical trials will test different novel drugs that take new approaches to treat unregulated neurotransmitters in the brain that are involved in PTSD. The randomized trials will measure the effectiveness of the medications compared to a placebo control group.

“We are in urgent need of treatments for PTSD,” Arnold said. “That’s why these trials are so important because they offer a novel approach that we hope to be effective in helping patients overcome the problems associated with PTSD and return to full function.”

Adults, both women and men, over the age of 18 with PTSD are eligible to participate in the trials, with patients with a variety of different trauma experiences being recruited. The trials will involve about three months of participation from patients.

“We’re asking for volunteers to help us with our trials, those individuals who continue to have symptoms of PTSD,” Arnold said. “We are conducting these trials actively, and I would encourage individuals to come forward to help.”

Arnold said there has been an increased interest in finding drug treatments for PTSD in about the last five years.

“This is an exciting time and a hopeful time for people with PTSD because we are actively seeking out better treatments,” she said. “There’s been a growing interest and a recognition of the unmet need in this population, so I’m really gratified to be able to have these trials going on now and to be able to offer some hope to individuals with PTSD.”

For more information on the PTSD trials at UC, call 513-558-6612.


Read More

Continue Reading

Economics

Why REV Stock is Trending After Filing Chapter 11 Bankruptcy

Will Revlon end up getting bought out after filing for bankruptcy? And if so, how will it affect investors holding REV stock?
The post Why REV Stock is…

Published

on

Revlon (NYSE: REV), the iconic beauty brand, has filed for chapter 11 bankruptcy. Meanwhile, REV stock rallied on the news as traders promoted the idea of a buyout on social media.

After implementing a new strategy to drive growth, Revlon did see business pick up last year. But it wasn’t enough to overcome the massive debt Revlon piled on throughout the years. Nonetheless, the company has been losing money since 2015.

The bankruptcy filing will help the company “reorganize its capital structure” and “improve its long-term outlook.”

Will it be enough to turn the company around? Revlon still faces intense competition and rising costs. Not to mention an uphill battle with its supply chain.

Yet the company has a strong portfolio of brands. On top of this, Revlon already has a buyout offer, according to reports. Will Revlon end up getting bought out? And if so, how will it affect investors holding REV stock?

Keep reading to learn why Revlon stock is trending and what you can expect next.

Why Is REV Stock Trending

The news of Revlon’s bankruptcy broke about two weeks ago. As a result, retail traders piled into REV stock, promoting it as a short squeeze candidate.

The announcement caused REV shares to first crater. And then, after hitting an all-time low of $1.08, Revlon shares rallied on heavy volume. Revlon stock soared over 800% within a week, gaining meme stock status.

Traders on social media sites such as Reddit and StockTwits compared the situation to rental car company Hertz (NASDAQ: HTZ).

After the initial fallout, Hertz stock soared after announcing bankruptcy in 2020. As a result, HTZ stock gained over 900% as retail traders bid the price up.

Doesn’t bankruptcy mean the company is going out of business? Why would someone want to own a bankrupt company?

For one thing, Chapter 11 bankruptcy doesn’t mean the company is going out of business. To illustrate, in Hertz’s case, the company sold over 200,000 vehicles. Not only that, but investors bet on the company’s turnaround.

An investment group gave Hertz $5.9B while the company managed debt. As a result, Hertz is back in business, with demand for rentals heating up.

At the same time, it may be a different situation with Revlon than Hertz.

How Did This Happen

Revlon has been losing market share for years. Newcomers enter the industry with attractive marketing campaigns, drawing in the younger crowd.

For example, a longtime rival, Coty Inc (NYSE: COTY), teamed up with Kim Kardashian and Kylie Jenner. Coty has a 20% stake in Kim’s beauty business and an over 50% in Kylie’s. With this in mind, the deals are part of Coty’s transition to an online, DTC business model.

Meanwhile, Revlon has failed to keep up in the digital age. That said, the company was started 90 years ago and has built strong ties with leading retailers.

But, as shoppers move online, especially younger crowds, Revlon has been slower to catch trends. Coty’s partnerships expand their reach online, particularly on social media. Celebrity influencers push products to their millions of followers.

Then, the pandemic hit. Revlon saw sales crater as a result. For one thing, with lockdowns in place, people wore less makeup. And on top of this, if they did buy makeup, it was online.

So, Revlon lost even more market share. And then higher raw material costs, shortages, and rising labor put the company over the edge. Below is a look at Revlon’s debt by year since 2012.

Revlon started missing payments as a result, and vendors had enough. The past due accounts piled up, and the company couldn’t keep up. So, Revlon filed for voluntary chapter 11 bankruptcy on June 16, 2022.

What’s Next for Revlon

As shown, chapter 11 doesn’t mean Revlon is going out of business. In fact, it will give the company a chance to restructure its debt, like Hertz. Here’s what we know so far.

  • Revlon expects to receive $575M in financing to support day-to-day operations.
  • The pre-trial hearings are ongoing, with another one today.
  • Revlon will have the chance to work with creditors to write off some debt.
  • Another option is the company gets bought out.

We could also see a potential sale of Revlon’s assets. Revlon’s CEO says demand remains solid, and “people love our brands” while adding the company’s strong market position.

But she added that the company’s debt situation has made it challenging to do business. In particular, rising costs and shortages.

Revlon will continue doing business for now while working with those they owe money to. If they come to a resolution, the company may reduce its debt to better position itself in the long term.

At the same time, investors holding REV stock may not get anything.

Is It Worth Buying REV Stock

The first thing to know about buying REV stock right now is that you can lose everything. If Revlon fails to turn a profit, it will continue losing money.

The bankruptcy filing will give the company a second chance to restructure its debt. But Revlon will still be operating with the challenging conditions from before.

Though raw material costs have dropped slightly in the past month, they are still well above pre-pandemic levels. Revlon will need to make significant changes behind the scenes to overcome the difficulties.

Can REV stock become the next GameStop (NYSE: GME) or Hertz? That’s what traders on social media are hoping for. But, with competition gaining market share, the situation seems different.

At the same time, Revlon is a massive brand in makeup. For instance, Revlon is the #3 global cosmetics brand. Not only that, but they are also the #1 for mass fragrance and nail brand for professionals.

Yet these facts don’t mean Revlon stock is worth buying. The company still faces rising costs. Furthermore, Revlon has a long list of creditors they will pay before investors. For this reason, it may be best to stay on the sidelines for this one.

The post Why REV Stock is Trending After Filing Chapter 11 Bankruptcy appeared first on Investment U.

Read More

Continue Reading

Trending