BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: inflammation

Vitamin D Points to Potential Life-saving Therapeutics for Severe Cases of SARS-CoV-2

A promising new joint study by Purdue University and the National Institutes of Health (NIH) suggests that active metabolites of vitamin D are linked to reducing lung inflammation after SARS-COV2 infection. And no, before you break out your vitamin D pills, the vitamins inside your capsules are quite different from the active metabolites studied. Because of this, these researchers are warning those infected with COVID-19 against taking excessive supplements of vitamin D in hopes of reducing lung inflammation.

The researchers identified an autocrine loop involving vitamin D which allows T-helper (Type 1) cells to activate and respond to the active metabolites of Vitamin D which represses the signaling protein, Interferon Gamma. Distinguishing features of Interferon Gamma is the central role it plays in promoting inflammation

Interferon Gamma

Structure of interferon gamma. The two chains are colored in red (chain A) and green (chain B).

Although interferon gamma sounds wildly unrecognizable at first, we have actually learned about these proteins more broadly in our AP Biology class. Interferon Gamma is actually a type of cytokine! Regarding this cytokine’s structure, the proteins that compose interferon gamma are dimerized (sounds familiar? This is because we have also previously learned about dimerization through the tyrosine kinase receptor pathway in class!). 

Along with the suppression of Interferon Gamma, Interleukin 10, a cytokine with potent anti-inflammatory properties, is amplified. This is significant because this cytokine prevents damage to the host and maintains normal tissue homeostasis by reducing inflammation.

IL10 Crystal Structure.rsh

Structure of interleukin 10 as published in the Protein Data Bank.

In the near future, these pathways could be exploited therapeutically to accelerate the shutdown program of hyper-inflammatory lung cells in patients with severe SARS-CoV-2 infections. But for now, before vitamin D is adopted to treat COVID-19, clinical trials are still needed. However, research findings like these are critical to creating effective treatment not just for those infected with SARS-CoV-2, but also other respiratory diseases as well.

What do you think about this new discovery? Do you think this could lead to scientific progress regarding the treatment of inflammation?

How Dandruff Can Lead to Crohn’s Cures

The Intro

Crohn’s disease is an inflammatory bowel disease (IBD) that causes inflammation of the digestive tract. Symptoms can include abdominal pain, malnutrition, stunted growth, and more on the gross side, diarrhea. There is no known cure for the condition, but a research team under David Underhill, “research chair for inflammatory bowel diseases at Cedars-Sinai Medical Center in Los Angeles,” has made a promising discovery in the gut microbiome. The researchers’ observations involve a microfungus present in and on our bodies, but before we unpack their findings, let’s figure out why the heck there are fungi inside our bodies and how all this relates back to dandruff!

The Mycobiome

There is a vast array of microbes that make their home in and around our person. This collection of organisms is known as the microbiome. While our microbiome consists of thousands of different microbial species, a whopping “99.9% of the total number of microbial cells belong to only a few species.” That other 0.1% of microbes is known as the “rare biosphere,” and within this diverse collection of organisms lies the mycobiome, the assortment of microscopic fungi that inhabit each and every one of us. While the microbiome has received lots of attention, especially in our gut area, research on the mycobiome’s effects on the human body is just beginning. Underhill’s team’s discovery gives us a glimpse into just how impactful these relatively rare organisms can be.

The Dandruff

So, what does dandruff from our scalp have to do with the fungi in our gut, and how does all this involve Crohn’s disease? Underhill and his researchers studied Malassezia, a fungus pretty much omnipresent in and around our bodies. It’s been known that a concentration of Malassezia on our scalps causes irritation that leads to dandruff. However, this fungus also inhabits our digestive tract. The research team found that “people with Crohn’s had high concentrations of Malassezia on their intestine walls, while healthy patients had almost none. The researchers then demonstrated that simply adding this type of fungi to the gut — at least, in mice — was enough to exacerbate the inflammation seen in Crohn’s.” Therefore, the same fungal substance that can cause minor dandruff may also be heavily responsible for a serious IBD that affects about 780,00 Americans. 

The Significance

Even though some patients may achieve permanent remission, as we noted before, there is not yet an established cure for Crohn’s disease. However, Underhill’s team’s study raises some questions that could help shape the future of IBD medical development. Could the current expensive, 60% effective anti-inflammatory medicine be replaced with simple antifungal drugs? If we prove that reducing fungus reduces intestinal inflammation, then antifungal Crohn’s cures could be accessible and affordable for thousands of people! In 5th grade, I was diagnosed with Crohn’s, and while my condition has improved, it’s far from cured. It’s exciting to hear about new discoveries that could lead to advances in treatment to help people like myself. Underhill’s team and another team of researchers in Montreal have already begun clinical trials with antifungal drugs, so depending on their results, we may be one big step closer to curing Crohn’s and other inflammatory bowel diseases alike!

I think these discoveries are important and worth talking about, so if you have anything to add, challenge, or discuss, feel free to comment below! Thanks for reading!

 

Using CRISPR to Prevent Chronic Pain & Inflammation

(https://commons.wikimedia.org/wiki/File:Rheumatoid_Arthritis_Hands.jpg)

Researchers at the University of Utah have recently figured out a way to use CRISPR gene-editing techniques to reduce chronic pain and inflammation.

Normally, inflammation around damaged tissue signals various cells to produce molecules that destroy the damaged tissue. However, this can quickly devolve into chronic pain when the tissue destruction does not stop.

The researchers have found a way to use CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) to relieve and prevent chronic pain. Unlike most popular CRISPR techniques, theirs does not involve altering the gene sequences– it instead relies upon epigenetics, and modifying the expression of the genes in the cytokine receptors in inflammatory areas, to prevent cells from producing the molecules that destroy tissue.

The treatment is delivered through a virus, which is injected into the inflammatory site. It is more potentially therapeutic than current treatments for chronic pain, in that it actually prevents tissue destruction and future pain, rather than just relieving present pain. The method is approximately ten years away from being used to treat human patients.

Dysbiosis: Does Imbalance Help?

The gut microbiome is a very large collection of mutualistic relationships between microorganisms and an animal. In our case, these microorganisms control very much of the digestive tract and have influences throughout the body. Crohn’s disease is something that can happen due to imbalance in this microbiome or “dysbiosis“. Usually marked by inflammation in the digestive tract, this disease is a result of an autoimmune response against possibly microbial antigens. Although there is no cure, scientists have determined the best course of action is to relieve the symptoms. This results in disruptions to the gut microbiome.

Inflammation of the colon due to Crohn’s disease

Scientists studying responses in the gut microbiome have found that treatment for Crohn’s disease have caused various responses in the people in the experiment. Antibiotics have been found to decrease bacterial growth in the tract while allowing fungus to grow more freely. Formula diets relieved inflammation and other symptoms but didn’t repair bacterial balance in the microbiome. Immunosuppressants decreased inflammation and bacterial dysbiosis at the expense of increasing fungal dysbiosis. All these methods don’t seem to work out.

But what if the microbiome does not need to be restored to remain healthy? Formula diets caused more dysbiosis but were able to alleviate symptoms. Suddenly, the microbiome does not seem to be as necessary as previous studies suggest. However, this experiment only measures a few variables. Results beneficial to treatments for Crohn’s disease may cause something bad to happen elsewhere in the microbiome. Replacing the gut microbiome would definitely have massive side effects.

Perhaps one day, we could find some way to substitute parts of our mutualistic relationship with the bacteria inhabiting our gut. However, that day seems far off. For now, we should probably stick with what we have.

Original Article

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