Immune system protein may defend against deadly necrotizing enterocolitis in infants

Immune system protein may defend against deadly necrotizing enterocolitis in infants

  • June 17, 2021

Necrotizing enterocolitis, or NEC, is the most common and serious intestinal disease among premature babies. In this condition, bacteria invade the wall of the intestine. Inflammation sets in.

The disease causes tissue decay in the bowels. Once entered into the bloodstream, it can be more infectious and deadly.

Despite years of research, effective treatments remain elusive, and mortality rates remain unchanged.

A study by the Washington University School of Medicine in St. Louis has revealed a protein that may protect babies from necrotizing enterocolitis (NEC) and lead to the development of new treatments.

Interleukin-22 (IL-22) protein plays a vital role in regulating immune responses and maintaining a healthy gut microbiome in adults.

Scientists focused on Interleukin-22 (IL-22) protein in mice models. They studied signaling and production of the protein in healthy intestines and intestines damaged by NEC. They analyzed IL-22 levels before and after birth and into adulthood, which for mice begins when they are weaned, at about 28 days.

They analyzed IL-22 levels before and after birth and into adulthood, which for mice begins when they are weaned, at about 28 days. In both healthy and diseased intestines, there was low postnatal IL-22 production IL-22 production up until day 21.

Scientists also studied tissue samples from preemies who did and did not develop NEC. They found low levels of IL-22 in all of the intestinal samples. And in the babies who had developed NEC, an appropriate immune response had not been mounted in the intestines.

Misty Good, MD, assistant professor of pediatrics in the Division of Newborn Medicine, said, “Immune cells in the neonatal intestine have shown an inability to produce adequate amounts of IL-22 to control the progression of NEC. Immature intestines are associated with a lack of IL-22 production, a theory strengthened by the fact that premature infants weighing less than 3 pounds 5 ounces are most at risk for NEC.”

“Typically, the more premature a baby is the lower the baby’s weight and the more undeveloped a baby’s gastrointestinal immune system is. Harmful bacteria can get cross the gut barrier and activate the immune system. And because the immune system of preemies isn’t fully developed, it leads to an exaggerated inflammatory response that can lead to tissue death.”

Later, scientists injected the mice with IL-22. Doing so controlled the inflammation while promoting the regeneration of tightly packed cells lining the intestine.

 IL-22 can help strengthen the intestinal walls, creating a barrier in the gut that allows for nutrient absorption while preventing toxic or otherwise hostile microorganisms from seeping into the bloodstream.

Good said“Interestingly, our work demonstrated that treatment with IL-22, in mice, protects the newborn intestine against damage caused by NEC. Our study represents a substantial advance in understanding the role of IL-22 in early life and sets the stage for new ways to treat NEC in the future.”

Journal Reference:
  1. Belgacem Mihi et al. Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration. DOI: 10.1016/j.xcrm.2021.100320
Plant Immune Proteins Trigger Cell Death

Plant Immune Proteins Trigger Cell Death

  • June 17, 2021

Summary

Researchers have pieced together the mechanism by which key plant immune proteins kill their cells to defend against pathogens.

Researchers engineered this human cell to express plant defense proteins called NLRs. Though the human cell doesn’t contain any other components of the plant immune system, NLRs alone can still trigger cell death. Credit: Pierre Jacob

Plant cells self-destruct to survive. After detecting a pathogen, they set off a chain reaction that ultimately destroys them, preventing disease from spreading.

Now, scientists have discovered the mechanism behind this self-destruction. Plant defense proteins cluster together to pierce the cell membrane, opening a channel into the infected cell. Calcium then floods in, ultimately killing the cell, Howard Hughes Medical Institute Investigator Jeffery Dangl and his team report June 17, 2021, in the journal Science.

Scientists have long known such pathogen-induced cell death occurs in plants. And the defense proteins were first identified in the mid 1990s. “But nobody knew how they worked to control cell death and immune responses,” says Dangl, a plant biologist at the University of North Carolina at Chapel Hill. “Now, we know they all work through a never-before-seen kind of channel.”

The findings align with a recent study in Cell, which reported a similar result in a different category of plant immune proteins. Because this family of proteins is found in most land plants, the mechanism probably holds true across the plant kingdom, Dangl suggests.

“This is a profoundly important advance,” says Jonathan Jones, a plant immunologist at The Sainsbury Laboratory in Norwich, England, who wasn’t involved in the work. “We get two parallel stories with complementary results that show the same thing.”

Activated plant immune proteins (pink) move to the cell membrane (left panel). When inactive, these proteins spread throughout the cell (right). The overlay (green and blue ribbons) shows the protein structure that pierces the cell membrane to form a channel. Credit: Dr. Farid El Kasmi

The proteins Dangl’s team studied, called NLRs, detect specific pathogen molecules. Most plants carry genes for hundreds of NLRs. A few years ago, Dangl came across a paper reporting an interesting phenomenon in one kind of these proteins. They clumped together and moved towards the cell membrane ­– a behavior often seen in proteins that make membrane channels. Dangl and his team wondered whether something similar might occur with the NLR proteins his lab studied, and whether it could be related to the cell death pathway.

The researchers used a technique called x-ray crystallography to take detailed pictures of this NLR protein’s structure. Then, they made targeted mutations to the protein, to see how changes in various places affected its function.

By testing how different versions of the protein behaved in cells and in lab dishes, the researchers pieced together a picture of its mode of action. That picture looks something like this: In the presence of a pathogen, NLR proteins merge into a mega-protein. Then, part of the protein forms a funnel-like structure that pokes into the membrane of an infected cell. That creates a channel that lets calcium into the cell. Because high levels of calcium are toxic, an influx can mean death for the cell.

In another experiment, the team engineered human cells to contain an NLR protein. Human cells don’t have any other parts of the plant immune system. But just having an active NLR protein was enough to let calcium in and kill the cells, the researchers showed. That suggests the protein is the driving force behind the calcium surge.

Next, the team is exploring whether calcium kills the plant cells directly, or whether it turns on other defense pathways that lead to cell death. Hammering out these pathways gives scientists a better understanding of how plants protect themselves, Dangl says, and that could help improve the design of disease-resistant crops.

###

Citation

P. Jacob et al. “Plant ‘helper’ immune receptors are Ca2+-permeable non-selective cation channels.” Science. Published online June 17, 2021. doi: 10.1126/science.abg7917

Immune system protein may defend against deadly intestinal disease in babies

Immune system protein may defend against deadly intestinal disease in babies

  • June 17, 2021

IMAGE

IMAGE: A study led by researchers at Washington University School of Medicine in St. Louis has identified a protein in the immune system that may protect babies from necrotizing enterocolitis, a…
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Credit: Matt Miller/Washington University

The intestinal disease necrotizing enterocolitis is a leading cause of death among premature infants born in the U.S. and across the globe. Characterized by excessive inflammation that can cause tissue decay in the bowels, the disease provides a pathway for infectious and deadly bacteria to enter the bloodstream.

Despite four decades of research, effective treatments remain elusive, and mortality rates in babies who develop the disease have remained essentially unchanged, hovering at about 30%.

Now, a study led by researchers at Washington University School of Medicine in St. Louis has identified, in mice, a protein in the immune system that may protect babies from necrotizing enterocolitis (NEC) and lead to the development of new treatments.

The findings are published online June 15 in Cell Reports Medicine.

“Necrotizing enterocolitis is a serious, fast-acting condition that can lead to death within hours,” said the study’s senior author, Misty Good, MD, an assistant professor of pediatrics in the Division of Newborn Medicine. “We don’t know why NEC happens, and we can try to treat it with antibiotics and surgical removal of the dead tissue; however, in severe cases, many babies will still die. No treatments stop the disease from progressing, but our hope is that the protein we’ve identified will change that.”

The scientists focused on Interleukin-22 (IL-22), a protein that regulates immune responses and helps maintain a healthy gut microbiome in adults.

Over the years, research has suggested that IL-22 has a critical role in adult gastrointestinal diseases. Consequently, potential treatments involving IL-22 are being studied in COVID-19 illness, alcohol-induced liver disease, and graft-versus-host disease that develops after organ or bone marrow transplants. However, IL-22’s role in newborns’ intestines has been unclear.

To better understand the protein’s role, the researchers created a mouse model to examine IL-22 signaling and production in healthy intestines and in intestines damaged by NEC. They analyzed IL-22 levels before and after birth and into adulthood, which for mice begins when they are weaned, at about 28 days old. In both the healthy and diseased intestines, the researchers documented low postnatal IL-22 production up until day 21, when production skyrocketed for the mice and continued into adulthood.

The researchers also studied tissue samples from preemies who did and did not develop NEC. The scientists found low levels of IL-22 in all of the intestinal samples. And in the babies who had developed NEC, an appropriate immune response had not been mounted in the intestines.

“Immune cells in the neonatal intestine have shown an inability to produce adequate amounts of IL-22 to control the progression of NEC,” said Good, who treats patients at St. Louis Children’s Hospital and is also co-program director of the university’s Neonatal-Perinatal Medicine Fellowship. As a member of the scientific advisory council of the Necrotizing Enterocolitis Society, Good has led an effort involving seven medical centers that have developed a large biorepository of samples from infants affected by NEC.

Good surmised that immature intestines are associated with a lack of IL-22 production, a theory strengthened by the fact that premature infants weighing less than 3 pounds 5 ounces are most at risk for NEC. Typically, the more premature a baby is, the lower the baby’s weight and the more undeveloped a baby’s gastrointestinal immune system is. Harmful bacteria can get cross the gut barrier and activate the immune system. And because the immune system of preemies isn’t fully developed, it leads to an exaggerated inflammatory response that can lead to tissue death.

The researchers’ findings of low levels of IL-22 in neonatal tissues led to their next step: injecting the mice with IL-22. The protein aids in controlling inflammation while promoting regeneration of tightly packed cells lining the intestine. IL-22 can help strengthen the intestinal walls, creating a barrier in the gut that allows for nutrient absorption while preventing toxic or otherwise hostile microorganisms from seeping into the bloodstream.

“Interestingly, our work demonstrated that treatment with IL-22, in mice, protects the newborn intestine against damage caused by NEC,” Good said. “Our study represents a substantial advance in understanding the role of IL-22 in early life and sets the stage for new ways to treat NEC in the future.”

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Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

New therapy extends breast cancer survival rate, prevents reoccurrence

New research is first to show how key gut bacterium trains infant immune system

  • June 17, 2021

DAVIS, CA, June 17, 2021 — Research published today in the journal Cell is the first to establish how a specific gut bacterium, activated Bifidobacterium infantis EVC001 (B. infantis), influences immune system development in infants, and could thereby reduce the risk of allergic and autoimmune conditions later in life.

While prior studies have shown a correlation between a lack of beneficial bacteria in the infant gut and the development of allergies and autoimmune diseases, this groundbreaking research, Bifidobacteria-mediated immune system imprinting in early life, found the presence of bifidobacteria, specifically the B. infantis EVC001 bacterial strain, early in a breastfed infant’s life, programs naïve immune cells away from responses associated with immune-related conditions while producing regulatory cells that improve the body’s ability to control inflammation.

The study also confirms the critical window of opportunity for impacting immune system development and reducing systemic inflammation is within the first 100 days of infancy.

The immune system normally guards against bacteria and viruses by marshalling specific immune T-cells to recognize and attack the foreign invaders in the body. The adaptive immune system at birth is naturally a blank slate; it has had very little exposure to viruses or dangerous bacteria, so immune cells, called naïve T-cells, have yet to be programmed accordingly. In immune disorders and allergies, these cells are misprogrammed early on, by harmful bacteria or inflammation, to attack normal healthy cells in the body. Researchers have been working to determine how this misprogramming happens, to enable clinicians with solutions to reduce the risk of childhood allergic and autoimmune conditions.

Study Details


For the study, researchers found that infants who lacked beneficial microbes able to metabolize complex sugars in breast milk, human milk oligosaccharides (HMOs), had disordered development of immune cell networks and significantly increased systemic inflammation.

Furthermore, in vitro experiments showed that gut bacterial metabolites and host factors from breastfed infants that lacked B. infantis EVC001 in their gut microbiome programmed naïve immune cells toward Th2 and Th17, two immune cell types associated with the development of autoimmune and allergic diseases.

In contrast, breastfed infants fed B. infantis EVC001 skewed those naïve immune cells toward Th1, an immune cell type that allows the body to properly react and rid itself of dangerous pathogens. Researchers also found far greater levels of interferon Beta (IFNβ) in the B. infantis EVC001 isolates, which is an important regulatory mediator that improves the body’s ability to control inflammation and viral infections.

Additionally, the research shows that the unique genetic capacity of B. infantis EVC001 to fully metabolize human milk oligosaccharides (HMOs) produced the bacterial metabolite indolelactate (ILA). ILA, in turn, amplifies a broadly immunoregulatory factor, Galactin-1, effectively silencing Th2 and Th17.

“More than 90 percent of newborns have a severe deficiency of B. infantis; this study is an exciting step forward in our understanding of the role of B. infantis EVC001 in the positive programming of immune cells and how it actually changes the trajectory of immune system development to protect against inflammation,” said Dr. Bethany Henrick, PhD, first and corresponding author of the study and Director of Immunology and Diagnostics at Evolve BioSystems. “For the first time we’ve been able to demonstrate that the unique ability of B. infantis EVC001 to fully break down HMOs and the abundance of HMO utilization genes in the microbiome is directly correlated with decreased enteric and systemic inflammation.”

The study examined the development of immune system changes in 208 infants born at the Karolinska University Hospital in Sweden between April 2014 and December 2019, evaluating bifidobacterial species and other microbes expressing HMO utilization genes. To further assess the beneficial effects of HMO utilization gene expressing microbes, a second cohort of the study involved 40 breastfed infants in California, with half receiving B. infantis EVC001, a strain of Bifidobacterium possessing all HMO utilization genes, and the other half given no supplementation.

“These are important findings because, while they point to the disturbing fact that infants lacking B. infantis – unfortunately, now the norm in developed countries – can’t properly metabolize HMOs and are missing the critical window to develop a healthy immune system, it also shows that there’s a simple fix; feeding breastfed babies B. infantis EVC001 early in infancy can shut down inflammatory processes and reduce the life-time risk of developing immune-mediated diseases,” said Dr. Petter Brodin, MD, PhD, consultant pediatrician and lead author of the study and Professor of Pediatric Immunology at the Karolinska Institute in Sweden.

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About Evolve BioSystems, Inc.

Evolve BioSystems, Inc. is a privately-held leading microbiome company dedicated to discovering and implementing solutions that improve the short and long-term health of infants worldwide. Launched at the University of California, Davis, following more than a decade of pioneering research at the Food for Health Institute, Evolve is a portfolio company of Horizons Ventures, Cargill, Manna Tree Partners, The Bill & Melinda Gates Foundation, and Johnson &Johnson Development Corporation. Since 2014, Evolve has built substantial science and technology assets, focused on the nutrition, biochemistry, physiology of the developing infant gut microbiome. The company’s breakthrough research shows that nine out of ten U.S. infants are suffering from Newborn Gut Deficiency, a dramatic shortage of key good bacteria in the infant gut microbiome. Together with clinical research partners all over the world, Evolve is on a mission to establish B. infantis EVC001 as standard-of-care for all infants – for a better life-long health trajectory.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Next-Generation COVID-19 Vaccines Could Stimulate Another Arm of the Immune System

Next-Generation COVID-19 Vaccines Could Stimulate Another Arm of the Immune System

  • June 17, 2021

A new study looking at the way human cells activate the immune system in response to SARS-CoV-2 infection could open the door to even more effective and powerful vaccines against the coronavirus and its rapidly emerging variants keeping the global pandemic smoldering.

Researchers from Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and the Broad Institute of MIT and Harvard say it’s the first real look at exactly what types of “red flags” the human body uses to enlist the help of T cells—killers sent out by the immune system to destroy infected cells. Until now, COVID vaccines have been focused on activating a different type of immune cell, B cells, which are responsible for creating antibodies. Developing vaccines to activate the other arm of the immune system—the T cells—could dramatically increase immunity against coronavirus, and importantly, its variants.

In their findings, published in Cell, the researchers say current vaccines might lack some important bits of viral material capable of triggering a holistic immune response in the human body. Based on the new information, “companies should reevaluate their vaccine designs,” says Mohsan Saeed, a NEIDL virologist and the co-corresponding author of the paper.

Saeed, a BU School of Medicine assistant professor of biochemistry, performed experiments on human cells infected with coronavirus. He isolated and identified those missing pieces of SARS-CoV-2 proteins inside one of the NEIDL’s Biosafety Level 3 (BSL-3) labs. “This was a big undertaking because many research techniques are difficult to adapt for high containment levels [such as BSL-3],” Saeed says. “The overall coronavirus research pipeline we’ve created at the NEIDL, and the support of our entire NEIDL team, has helped us along the way.”

Saeed got involved after he was contacted by genetic sequencing experts at the Broad Institute, computational geneticists Pardis Sabeti and Shira Weingarten-Gabbay. They hoped to identify fragments of SARS-CoV-2 that activate the immune system’s T cells.

“The emergence of viral variants, an active area of research in my lab, is a major concern for vaccine development,” says Sabeti, a leader in the Broad Institute’s Infectious Disease and Microbiome Program. She is also a Harvard University professor of systems biology, organismic and evolutionary biology, and immunology and infectious disease, as well as a Howard Hughes Medical Institute investigator.

“We swung into full action right away because my laboratory had [already] generated human cell lines that could be readily infected with SARS-CoV-2,” Saeed says. The group’s efforts were spearheaded by two members of the Saeed lab: Da-Yuan Chen, a postdoctoral associate, and Hasahn Conway, a lab technician.

From the outset of COVID pandemic in early 2020, scientists around the world knew the identity of 29 proteins produced by SARS-CoV-2 virus in infected cells—viral fragments that now make up the spike protein in some coronavirus vaccines, such as the Moderna, Pfizer-BioNTech, and Johnson & Johnson vaccines. Later, scientists discovered another 23 proteins hidden inside the virus’ genetic sequence; however, the function of these additional proteins was a mystery until now. The new findings of Saeed and his collaborators reveal—unexpectedly and critically—that 25 percent of the viral protein fragments that trigger the human immune system to attack a virus come from these hidden viral proteins.

How exactly does the immune system detect these fragments? Human cells contain molecular “scissors”—called proteases—that, when the cells are invaded, hack off bits of viral proteins produced during infection. Those bits, containing internal proteins exposed by the chopping-up process—like the way the core of an apple is exposed when the fruit is segmented—are then transported to the cell membrane and pushed through special doorways. There, they stick outside the cell acting almost like a hitchhiker, waving down the help of passing T cells. Once T cells notice these viral flags poking through infected cells, they launch an attack and try to eliminate those cells from the body. And this T cell response isn’t insignificant—Saeed says there are links between the strength of this response and whether or not people infected with coronavirus go on to develop serious disease.

“It’s quite remarkable that such a strong immune signature of the virus is coming from regions [of the virus’ genetic sequence] that we were blind to,” says Weingarten-Gabby, the paper’s lead author and postdoctoral fellow in the Sabeti lab. “This is a striking reminder that curiosity-driven research stands at the basis of discoveries that can transform the development of vaccines and therapies.”

“Our discovery … can assist in the development of new vaccines that will mimic more accurately the response of our immune system to the virus,” Sabeti says.

T cells not only destroy infected cells but also memorize the virus’ flags so that they can launch an attack, stronger and faster, the next time the same or a different variant of the virus appears. That’s a crucial advantage, because Saeed and his collaborators say the coronavirus appears to delay the cell’s ability to call in immune help.

“This virus wants to go undetected by the immune system for as long as possible,” Saeed says. “Once it’s noticed by the immune system, it’s going to be eliminated, and it doesn’t want that.”

Based on their findings, Saeed says, a new vaccine recipe, incorporating some of the newly discovered internal proteins making up the SARS-CoV-2 virus, would be effective in stimulating an immune response capable of tackling a wide swath of newly emerging coronavirus variants. And given the speed with which these variants continue to appear around the world, a vaccine that can provide protection against all of them would be a game changer. 

Reference:
 Weingarten-Gabbay S, Klaeger S, Sarkizova S, et al. Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs. Cell. doi: 10.1016/j.cell.2021.05.046.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Best vitamin D supplements UK to boost your immune system

Best vitamin D supplements UK to boost your immune system

  • June 17, 2021
D

idn’t your parents always tell you when you were young to go outside in the sun and soak up some all-important vitamin D? Well, it turns out they might have a point.

Research by the British Nutrition Foundation suggests that across the UK, approximately one in five people have low vitamin D levels. And this has only been worsened by Covid, as people have tended to stay indoors more over the past year.

But why is vitamin D so important? And should we all be supplementing it?

Vitamin D is needed to help regulate the amount of phosphate and calcium in the body in order to keep bones, teeth and muscles healthy, as well as maintaining your immune system. Lack of it can lead to bone deformities such as rickets in children or bone pain due to osteomalacia in adults.

The two most important forms of vitamin D for humans are D2 and D3. Vitamin D2 is made by plants, while D3 (the more important one) is made by the skin when exposed to sunlight.

According to the NHS, from about April to September, most people should be able to get all the vitamin D they need from sunlight. But that doesn’t help for the remaining dark and gloomy half of the year.

Although vitamin D can be found in a small number of foods – including oily fish, red meat and eggs – it is difficult to get sufficient quantities from food alone which is why it is recommended that, for anyone over the age of one, 10 micrograms a day should be supplemented – up to a maximum of 100 micrograms for adults.

Shop the best vitamin D supplements below.

BetterYou D3000 Vitamin D Daily Oral Spray

BetterYou is a product that appears time and time again in health shops, and for good reason.

Their pill-free daily oral spray is extremely easy to use and can by shoved in a bag and taken on the go, without the need for water to wash it down. Its liquid formula is a great option for those who struggle to swallow pills and its subtle minty taste means no bitter flavour is left behind in your mouth. The sprays come in a variety of potencies and include ones specially formulated for vegans, juniors and infants.

If all that wasn’t enough, half of BetterYou’s product range now uses plastic for their packaging that has been collected from the Jakarta and Java Seas – a win on all fronts.

BetterYou

Nature’s Way Alive! Women’s Energy

If you find it a struggle to get your children to eat anything healthy, let alone vitamins, these Alive! vitamin D gummies will be your new best friend.

The bright purple easy-to-chew tablet with a berry citrus flavour means there’s no nasty “medicinal” taste and so makes ensuring children are getting all they goodness they need without a fuss.

Not only that, but these vitamins are stuffed full of 26 fruits and veggies, including cherry and cauliflower, and they are also vegetarian friendly – a double win!

For adults, Nature’s Way also offer high strength vitamin D capsules, which are available in various strengths and flavours.

Nature’s Way

Nourished 3D Printed Vitamins

Want to avoid the faff of having to take multiple vitamins for every aspect of your health? Opt for Nourished. Their 3D-printed vitamins are vegan-friendly and designed by you, to your specification, so you can be sure to get all the nutrients you need.

Whether you’re looking to have more energy, be more focused or get better heart health, build your own custom seven-ingredient stack from 28 nourishments (including ashwagandha, lycopene and vita-algae D3) or take Nourished’s quiz to determine exactly the right combination to help optimise your lifestyle.

You can sign up for just a one-off box of vitamins or they offer a fab subscription service where you can get the box sent directly to your door, so you’ll never need to worry about running out.

As far as vitamins go, they are also the tastiest ones on the market by a long shot. What’s not to love?

Nourished

Voost Vitamin D 25ug

Struggle to swallow pills? Voost takes all the stress out of getting a nutritional boost with their effervescent tablets – just add water.

The sugar-free dissolvable pills offer your daily dose of vitamin D and come in a tasty berry flavour – it’s almost like drinking a soft drink. Voost has a range of different vitamins in 10 and 20-tablet packs, the smaller of which is perfect for taking on the go.

Still not convinced? Research suggests that unlike conventional pills that sometimes only partially dissolve and so can lead to irritation, effervescent tablets dissolve completely so you can be sure you’ll get the maximum benefit.

Voost

Botanycl Vegan Vitamin D3

For those who are looking for the most natural supplement possible, opt for Botanycl. Their plant-based botanical range, which is manufactured in the UK, extends to three products: the skincare elixir, vitamin C and vitamin D3.

Their vegan vitamin D3 comes from lichen, which is the only known plant-based source of vitamin D3 as many others derive from sheep’s wool, and is in a base of high-oleic sunflower oil and coconut oil to allow for superior absorption.

The four-month supply of capsules come in a glass bottle, eliminating plastic waste and meaning the pot is recyclable so you can feel good about the environment while doing good to yourself.

Botanycl

MyVitamins Vitamin D3 Spray

Sports nutrition specialists MyProtein offer a whole range of vitamin D supplements under their sister brand MyVitamins, with products that are uniquely tailored to give an extra boost to active people.

As well as the standard vitamin D3 softgel capsules (in both vegan and regular formulas) and spray, they also have a vitamin D3 and K2 supplement which helps support the immune system and bone health.

For serious sportspeople, the vitamin D3 elite supplement has been tested by Informed-Sport in line with the World Anti-Doping Agency guidelines and declared safe for professional athletes of all levels.

Lastly, their vegetarian curcumin and vitamin D capsules contain all the benefits of vitamin D, along with curcumin – the active ingredient in turmeric which is known for its anti-inflammatory nature – making it perfect for anyone wishing to prevent injuries through sports training.

Myvitamins

Solgar Vitamin D3

Solgar is a great, high-quality product that does exactly what it says on the tin. With 13 vitamin D products alone and a variety of different strengths, formulas and sizes, there’s something for everyone.

For those that need a little extra boost, their “introduction” dose starts at 10 micrograms and is the perfect pick-me-up. Otherwise, if you’re looking for a full-on sunshine soaking, opt for the 100 micrograms.

The range includes softgel, chewable and regular tables, vegetable capsules, as well as a natural orange flavour liquid supplement, so you’re guaranteed to find one that works for you, however you like to take it. All of the above, except the softgels, are also suitable for vegetarians.

Solgar

Cytoplan Vitamin D3 & K2

Cytoplan offers fantastic wholefood, organic and vegan supplements that are both ethically and sustainably sourced. It is worth considering that they are charity-owned, meaning ethical decisions over profit are at the heart of the company, and also every product bought contributes to social change, all of which garners them serious plus points.

Their vegan vitamin D3 pills also contain K2, as the vitamins work synergistically so taking both helps to ensure optimum biological activity. Or, if tablets aren’t for you, they also do vegan vitamin D3 drops, as well as supplements tailored to juniors.

With Cytoplan, feeling good and doing good has never been so simple.

Cytoplan

Vitabiotics Vitamin D

Chances are you’ve already heard of Britain’s number one vitamin company, so I’ll save the introduction.

All you need to know is that their British Pharmacopoeia-quality (that’s the quality standards for UK medicinal products, to you and me) vitamin D tablets are free from artificial preservatives, colours, yeast and lactose and are also suitable for vegetarians.

Their tablets are very small and so easy to for even those that struggle to swallow, and they come in a variety of different strengths, from everyday to maximum. However, if tablets really aren’t an option for you, they also do vitamin D gummies, drops for babies and jellies for children.

Vitabiotics

Verdict

For their fret-free application and ease of portability, BetterYou’s daily oral vitamin D spray ticks all of the boxes when it comes to simple supplementing. The large range of strengths, as well as both adult and children formulas, also means there is something suitable for everyone.

Immune system dysfunction can alter the link between cannabis use and psychosis

Immune system dysfunction can alter the link between cannabis use and psychosis

  • June 17, 2021

The presence of pro-inflammatory cytokines in the blood can boost the effects of daily cannabis use and heighten the risk of developing psychosis in adulthood. Similar results have been observed, also in the presence of cytokines, when cannabis is used during adolescence. Psychotic disorders have symptoms such as delirium, loss of a sense of reality, hallucinations, hearing voices, and cognitive and social impairments.

A study by researchers at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) in Brazil, reported in an article in the journal Psychological Medicine, finds for the first time that individuals exposed to a combination of these two factors – the presence of pro-inflammatory cytokines in the blood and cannabis use (either daily or during adolescence) – are more likely to suffer from psychosis than those who are exposed to neither or to only one. According to the authors, the study provides “the first clinical evidence that immune dysregulation modifies the cannabis-psychosis association”.

The study was part of a project conducted by the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI), a consortium of research centers in 13 countries, including Brazil. An article published in The Lancet Psychiatry by the consortium in 2019 showed that daily cannabis use increased the likelihood of suffering from a psychotic disorder threefold.

In the more recent study, the researchers analyzed data for 409 people aged 16-64, including patients experiencing their first psychotic episode and community-based controls. The sample was drawn from the populations of Ribeirão Preto and 25 other cities in the region. The variables analyzed included cannabis use frequency (daily, not daily or never), duration (five years or less), and onset age (in adolescence or later).

In addition to the questionnaire on cannabis use, the researchers measured various cytokines in plasma donated by the volunteers and calculated scores representing their systemic inflammatory profiles. They also collected clinical and socio-demographic data, especially variables known as confounders, such as age, gender, schooling, ethnicity, body mass index, smoking, and use of psychoactive substances. The results obtained were independent of confounding factors.

Not everyone who uses cannabis develops psychosis. This suggests that the association may be modified by other factors, which may be biological, genetic or environmental. In a previous study conducted as part of my master’s research, we identified a correlation between plasma cytokines and the first psychotic episode. Following up on this discovery, and the consortium’s recent publication showing a higher incidence of psychosis among subjects who used cannabis on a daily basis, our next step was to see if the biological factor [inflammatory profile] affected the link between cannabis use and psychosis.”


Fabiana Corsi-Zuelli, First Author of the Article

The main conclusion was that such a link did indeed exist. “We found a statistically significant correlation between inflammatory profile and cannabis use on a daily basis or during adolescence. In sum, the results showed that immune system dysfunction can modify the association between cannabis use and psychosis and that a combination of these two factors increases the odds of suffering from a psychotic disorder,” she said.

Corsi-Zuelli is currently a PhD candidate in FMRP-USP’s graduate program in neurology and neurosciences, with support from São Paulo Research Foundation – FAPESP.

The principal investigator for the project is Cristina Marta Del-Ben, a professor at FMRP-USP’s Department of Neurosciences and Behavioral Sciences. According to Del-Ben, risk factors for psychosis may be biological, including genetic predisposition and problems during pregnancy, as well as environmental, including traumatic experiences during childhood and adolescence, and exposure to psychoactive substances, especially cannabis.

“The mechanisms of the disorder are poorly understood,” she said. “Our findings show that frequent current use of cannabis or use of the drug in adolescence is a risk factor for psychosis. We didn’t detect the same correlation with occasional or recreational use. In the multicenter study, which included European cities with varying levels and types of cannabis availability, we also found that the risk of psychosis is greater in users of stronger cannabis strains with a THC content or 10% of higher.” THC (delta-9-tetrahydrocannabinol) is the primary psychoactive constituent of cannabis or marijuana.

The medical explanation of psychosis is that it is a neuropsychiatric syndrome associated with anatomical and functional alterations in the brain, possibly linked to changes in the action of dopamine, a key neurotransmitter for communication among neurons. Excessive dopamine or direct damage to certain brain regions can lead to hallucinations, delusions, delirium and disorganized behavior.

Other neurotransmitters, such as glutamate, have also been implicated in the neurobiology of psychosis. Specialists are currently discussing what they call the neuroimmune link, and how immune system dysregulation may trigger neurochemical, morphological and behavioral alterations that heighten the risk of developing psychiatric disorders.

Psychotic symptoms may be present in several psychiatric disorders, which may or may not be affective. Recent research has taken note of cases of psychosis in patients infected by SARS-CoV-2. Treatment of psychosis involves a combination of medication, psychotherapy and family support.

Next steps

According to Corsi-Zuelli, the origin of the inflammatory alterations involved in psychosis is still obscure, but it may arise from a combination of genetic and environmental factors. “The inflammation seen in psychiatric disorders is considered low-level and isn’t as severe as in patients with autoimmune diseases or sepsis,” she said. “Nevertheless, experimental studies suggest it entails sufficient dysregulation to produce neurochemical and behavioral alterations.”

The researchers plan next to study genetic variants associated with the immune system and use neuroimaging data to explore the link with environmental risk factors. “Focusing in this way on the interactions between genetics and the environment will help us understand the neurobiology of psychosis, especially the role played by the immune system,” she said.

The association between inflammation and psychiatric disorders is highly relevant to clinical practice and has received growing attention. “It’s important to the search for alternative treatments for these disorders, and also to answering often neglected questions relating to the physical health of psychiatric patients,” Corsi-Zuelli said.

According to Del-Ben, in the pipeline for next steps is a partnership with Geraldo Busatto Filho, a professor at the Medical School (FM) in USP’s main campus, to investigate whether inflammatory markers in blood are linked to brain alterations in some of the patients studied.

The research has twice received international recognition. The Society of Biological Psychiatry selected the study for its Predoctoral Scholars Award, which was to have been formalized at SOBP’s 2020 annual meeting in New York, but the pandemic forced a postponement until April 2021, when the meeting was held online. And the study was selected by the Schizophrenia International Research Society (SIRS) for presentation at its 2020 Congress, also held online.urce:

Eat jackfruit to strengthen immune system 

Eat jackfruit to strengthen immune system 

  • June 17, 2021

Amid the ongoing Covid-19 crisis, people are making several efforts to improve their immunity. There is no better way to strengthen the immune system than through a healthy diet. Eating nutritious food daily is the easiest way to build immunity naturally. There are many types of food rich in essential micronutrients. You can easily include them in diet and one of them is jackfruit and jackfruit nuts.

Benefits of delicious summer fruit 

Sweet-smelling, succulent summer fruit can be eaten either raw or cooked. Most people prefer the fleshy fruit and discard the hard nut-like seeds. Perhaps they do not know that nutrients can also be found in seeds which can help in increasing immunity. Eating a variety of food and leading a disciplined lifestyle is the foundation of immunity building. The powerful seeds of jackfruit can be cooked or you can roast it with a little salt and chilli. Using it as a snack will prove beneficial for you. Rich in a variety of nutrients, this fruit can help you in many ways. This will add variety to your diet while strengthening your immunity.

Immunity 

Jackfruit is not only rich in protein but a small amount of fat can also be found. In addition to the antioxidants present in the yellow fruit, vitamins A and C can prevent many diseases. Eating this fruit regularly can also reduce the risk of viral infection. Vitamin C can help in prevention of inflammation and may reduce the risk of chronic diseases such as heart disease and cancer. Carotenoids and flavonoids, two major antioxidants, may help reduce the risk of inflammation, type 2 diabetes, heart disease and high blood pressure.

Other benefits of jackfruit 

The yellow fruit of summer can also work to improve skin and wrinkles. The antioxidants present in it can protect you from inflammation and oxidative stress. Jackfruit is also used in many places in the treatment of asthma, diarrhoea and stomach ulcers.

Immune system dysfunction can modify the association between cannabis use and psychosis

Immune system dysfunction can modify the association between cannabis use and psychosis

  • June 16, 2021

The presence of pro-inflammatory cytokines in the blood can boost the effects of daily cannabis use and heighten the risk of developing psychosis in adulthood. Similar results have been observed, also in the presence of cytokines, when cannabis is used during adolescence. Psychotic disorders have symptoms such as delirium, loss of a sense of reality, hallucinations, hearing voices, and cognitive and social impairments.

A study by researchers at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) in Brazil, reported in an article in the journal Psychological Medicine, finds for the first time that individuals exposed to a combination of these two factors – the presence of pro-inflammatory cytokines in the blood and cannabis use (either daily or during adolescence) – are more likely to suffer from psychosis than those who are exposed to neither or to only one. According to the authors, the study provides “the first clinical evidence that immune dysregulation modifies the cannabis-psychosis association”.

The study was part of a project conducted by the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI), a consortium of research centers in 13 countries, including Brazil. An article published in The Lancet Psychiatry by the consortium in 2019 showed that daily cannabis use increased the likelihood of suffering from a psychotic disorder threefold.

In the more recent study, the researchers analyzed data for 409 people aged 16-64, including patients experiencing their first psychotic episode and community-based controls. The sample was drawn from the populations of Ribeirão Preto and 25 other cities in the region. The variables analyzed included cannabis use frequency (daily, not daily or never), duration (five years or less), and onset age (in adolescence or later).

In addition to the questionnaire on cannabis use, the researchers measured various cytokines in plasma donated by the volunteers and calculated scores representing their systemic inflammatory profiles. They also collected clinical and socio-demographic data, especially variables known as confounders, such as age, gender, schooling, ethnicity, body mass index, smoking, and use of psychoactive substances. The results obtained were independent of confounding factors.

“Not everyone who uses cannabis develops psychosis. This suggests that the association may be modified by other factors, which may be biological, genetic or environmental,” said Fabiana Corsi-Zuelli, first author of the article. “In a previous study conducted as part of my master’s research, we identified a correlation between plasma cytokines and the first psychotic episode. Following up on this discovery, and the consortium’s recent publication showing a higher incidence of psychosis among subjects who used cannabis on a daily basis, our next step was to see if the biological factor [inflammatory profile] affected the link between cannabis use and psychosis.”

The main conclusion was that such a link did indeed exist. “We found a statistically significant correlation between inflammatory profile and cannabis use on a daily basis or during adolescence. In sum, the results showed that immune system dysfunction can modify the association between cannabis use and psychosis and that a combination of these two factors increases the odds of suffering from a psychotic disorder,” she said.

Corsi-Zuelli is currently a PhD candidate in FMRP-USP’s graduate program in neurology and neurosciences, with support from São Paulo Research Foundation – FAPESP.

The principal investigator for the project is Cristina Marta Del-Ben, a professor at FMRP-USP’s Department of Neurosciences and Behavioral Sciences. According to Del-Ben, risk factors for psychosis may be biological, including genetic predisposition and problems during pregnancy, as well as environmental, including traumatic experiences during childhood and adolescence, and exposure to psychoactive substances, especially cannabis.

“The mechanisms of the disorder are poorly understood,” she said. “Our findings show that frequent current use of cannabis or use of the drug in adolescence is a risk factor for psychosis. We didn’t detect the same correlation with occasional or recreational use. In the multicenter study, which included European cities with varying levels and types of cannabis availability, we also found that the risk of psychosis is greater in users of stronger cannabis strains with a THC content or 10% of higher.” THC (delta-9-tetrahydrocannabinol) is the primary psychoactive constituent of cannabis or marijuana.

The medical explanation of psychosis is that it is a neuropsychiatric syndrome associated with anatomical and functional alterations in the brain, possibly linked to changes in the action of dopamine, a key neurotransmitter for communication among neurons. Excessive dopamine or direct damage to certain brain regions can lead to hallucinations, delusions, delirium and disorganized behavior.

Other neurotransmitters, such as glutamate, have also been implicated in the neurobiology of psychosis. Specialists are currently discussing what they call the neuroimmune link, and how immune system dysregulation may trigger neurochemical, morphological and behavioral alterations that heighten the risk of developing psychiatric disorders.

Psychotic symptoms may be present in several psychiatric disorders, which may or may not be affective. Recent research has taken note of cases of psychosis in patients infected by SARS-CoV-2. Treatment of psychosis involves a combination of medication, psychotherapy and family support.

Next steps

According to Corsi-Zuelli, the origin of the inflammatory alterations involved in psychosis is still obscure, but it may arise from a combination of genetic and environmental factors. “The inflammation seen in psychiatric disorders is considered low-level and isn’t as severe as in patients with autoimmune diseases or sepsis,” she said. “Nevertheless, experimental studies suggest it entails sufficient dysregulation to produce neurochemical and behavioral alterations.”

The researchers plan next to study genetic variants associated with the immune system and use neuroimaging data to explore the link with environmental risk factors. “Focusing in this way on the interactions between genetics and the environment will help us understand the neurobiology of psychosis, especially the role played by the immune system,” she said.

The association between inflammation and psychiatric disorders is highly relevant to clinical practice and has received growing attention. “It’s important to the search for alternative treatments for these disorders, and also to answering often neglected questions relating to the physical health of psychiatric patients,” Corsi-Zuelli said.

According to Del-Ben, in the pipeline for next steps is a partnership with Geraldo Busatto Filho, a professor at the Medical School (FM) in USP’s main campus, to investigate whether inflammatory markers in blood are linked to brain alterations in some of the patients studied.

The research has twice received international recognition. The Society of Biological Psychiatry selected the study for its Predoctoral Scholars Award, which was to have been formalized at SOBP’s 2020 annual meeting in New York, but the pandemic forced a postponement until April 2021, when the meeting was held online. And the study was selected by the Schizophrenia International Research Society (SIRS) for presentation at its 2020 Congress, also held online.

Besides the scholarship awarded to Corsi-Zuelli, FAPESP also supported the research via four other grants: 2012/05178-0, 2013/11167-3, 2017/13353-0, and 2018/07581-2.

###

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.

Immune system protein may defend against deadly intestinal disease in babies – Washington University School of Medicine in St. Louis

Immune system protein may defend against deadly intestinal disease in babies – Washington University School of Medicine in St. Louis

  • June 16, 2021

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Findings may lead to new therapies for necrotizing enterocolitis

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The intestinal disease necrotizing enterocolitis is a leading cause of death among premature infants born in the U.S. and across the globe. Characterized by excessive inflammation that can cause tissue decay in the bowels, the disease provides a pathway for infectious and deadly bacteria to enter the bloodstream.

Despite four decades of research, effective treatments remain elusive, and mortality rates in babies who develop the disease have remained essentially unchanged, hovering at about 30%.

Now, a study led by researchers at Washington University School of Medicine in St. Louis has identified, in mice, a protein in the immune system that may protect babies from necrotizing enterocolitis (NEC) and lead to the development of new treatments.

The findings are published online June 15 in Cell Reports Medicine.

“Necrotizing enterocolitis is a serious, fast-acting condition that can lead to death within hours,” said the study’s senior author, Misty Good, MD, an assistant professor of pediatrics in the Division of Newborn Medicine. “We don’t know why NEC happens, and we can try to treat it with antibiotics and surgical removal of the dead tissue; however, in severe cases, many babies will still die. No treatments stop the disease from progressing, but our hope is that the protein we’ve identified will change that.”

The scientists focused on Interleukin-22 (IL-22), a protein that regulates immune responses and helps maintain a healthy gut microbiome in adults.

Over the years, research has suggested that IL-22 has a critical role in adult gastrointestinal diseases. Consequently, potential treatments involving IL-22 are being studied in COVID-19 illness, alcohol-induced liver disease, and graft-versus-host disease that develops after organ or bone marrow transplants. However, IL-22’s role in newborns’ intestines has been unclear.

To better understand the protein’s role, the researchers created a mouse model to examine IL-22 signaling and production in healthy intestines and in intestines damaged by NEC. They analyzed IL-22 levels before and after birth and into adulthood, which for mice begins when they are weaned, at about 28 days old. In both the healthy and diseased intestines, the researchers documented low postnatal IL-22 production up until day 21, when production skyrocketed for the mice and continued into adulthood.

The researchers also studied tissue samples from preemies who did and did not develop NEC. The scientists found low levels of IL-22 in all of the intestinal samples. And in the babies who had developed NEC, an appropriate immune response had not been mounted in the intestines.

“Immune cells in the neonatal intestine have shown an inability to produce adequate amounts of IL-22 to control the progression of NEC,” said Good, who treats patients at St. Louis Children’s Hospital and is also co-program director of the university’s Neonatal-Perinatal Medicine Fellowship. As a member of the scientific advisory council of the Necrotizing Enterocolitis Society, Good has led an effort involving seven medical centers that have developed a large biorepository of samples from infants affected by NEC.

Good surmised that immature intestines are associated with a lack of IL-22 production, a theory strengthened by the fact that premature infants weighing less than 3 pounds 5 ounces are most at risk for NEC. Typically, the more premature a baby is, the lower the baby’s weight and the more undeveloped a baby’s gastrointestinal immune system is. Harmful bacteria can get cross the gut barrier and activate the immune system. And because the immune system of preemies isn’t fully developed, it leads to an exaggerated inflammatory response that can lead to tissue death.

The researchers’ findings of low levels of IL-22 in neonatal tissues led to their next step: injecting the mice with IL-22. The protein aids in controlling inflammation while promoting regeneration of tightly packed cells lining the intestine. IL-22 can help strengthen the intestinal walls, creating a barrier in the gut that allows for nutrient absorption while preventing toxic or otherwise hostile microorganisms from seeping into the bloodstream.

“Interestingly, our work demonstrated that treatment with IL-22, in mice, protects the newborn intestine against damage caused by NEC,” Good said. “Our study represents a substantial advance in understanding the role of IL-22 in early life and sets the stage for new ways to treat NEC in the future.”

Matt Miller

Misty Good, MD, an assistant professor of pediatrics in the Division of Newborn Medicine at Washington University School of Medicine in St. Louis, led research involving a protein in the immune system that may protect babies from necrotizing enterocolitis (NEC).

Mihi B, Gong Q, Nolan LS, Gale SE, Goree M, Hu E, Lanik WE, Rimer JM, LiuV, Parks OB, Lewis AN, Agrawal P, Laury ML, Kumar P, Huang E, Bidani SS, Luke CJ, Kolls JK, Good M. Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration. Cell Reports Medicine. June 15, 2021. DOI: 10.1016/j.xcrm.2021.100320.

This research was funded by National Institutes of Health (NIH) grants R01DK118568, R03DK111473, K08DK101608, and 5T32HD043010; the March of Dimes Foundation, grant 5-FY17-79; the American Academy of Pediatrics Marshall Klaus Award, the St. Louis Children’s Hospital Foundation, the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital, and the Department of Pediatrics at Washington University School of Medicine.

Declaration of interests: Misty Good and Jay Kolls have a patent pending on the use of interleukin-22 to prevent or treat necrotizing enterocolitis. Good has received sponsored research agreement funding from Astarte Medical, Evive Biotech and Takeda Pharmaceuticals. Good serves on the Scientific Advisory Council of the NEC Society, and the Clinical and Technology Advisory Board of Astarte Medical. She participated in a neonatal microbiome advisory board for Abbott Laboratories in 2019. None of these sources had any role in this study.

Washington University School of Medicine’s 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is a leader in medical research, teaching and patient care, consistently ranking among the top medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.


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