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Vipin M. Vashishtha

@vipintukur

Aug 14

A ‘universal’ antiviral for everyone!

🔥 A fascinating tale that reinforces the power of research driven by curiosity without preconceived notions.

➡️ For a few dozen people in the world, the downside of living with a rare immune condition comes with a surprising superpower—the ability to fight off all viruses.

➡️ An immunologist from Columbia discovered the individuals' antiviral powers about 15 years ago, soon after he identified the genetic mutation that causes the condition. 1/

At first, the condition only seemed to increase vulnerability to some bacterial infections. But as more patients were identified, its unexpected antiviral benefits became apparent.

The researcher soon learned that everyone with the mutation, which causes a deficiency in an immune regulator called IFN-I–stimulated gene 15 (ISG15), has mild but persistent systemic inflammation. 2/

The type I interferon (IFN-I) response is a conserved cascade of signaling and gene expression that, among other functions, confers protection of cells from viral infection.

After resolution of infection, the response is tamped down by regulators such as IFN-I–stimulated gene 15 (ISG15).

Cells from individuals lacking ISG15 are able to control viral infections in vitro as a consequence of maintaining a low-grade IFN-I response. 3/

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Vipin M. Vashishtha

@vipintukur

Jul 31

In a small trial, researchers have found that a drug designed to treat celiac disease supported a more rapid return to normal activities for patients following COVID. The researchers found the oral drug #larazotide—an experimental drug originally designed to treat celiac disease—was both safe and effective in treating children with MIS-C. 1/

Current MIS-C treatments are limited. Some patients receive general anti-inflammatory drugs, but many experience a rebound of symptoms after completing a course. Such drugs are not designed to target the sticky SARS-CoV-2 viral particles that may persist in the gut. 2/

Enter larazotide, an orally administered drug that does target the gut. Larazotide strengthens intestinal barriers to limit the number of materials—like SARS-CoV-2 viral particles—that exit the intestines and enter circulation. 3/

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Vipin M. Vashishtha

@vipintukur

Jul 25

Researchers have discovered that gut bacteria produce a molecule that not only induces but also causes atherosclerosis, the accumulation of fat and cholesterol in the arteries that can lead to heart attacks and strokes.

This unexpected link between microbes and cardiovascular disease — the leading cause of death in humanity — is a paradigm shift. 1/

The new results show that some gut bacteria, in certain states, produce imidazole propionate, a simple molecule with six carbon atoms, eight hydrogen atoms, two nitrogen atoms, and two oxygen atoms (C₆H₈N₂O₂). This compound enters the blood, interacts with immature white blood cells, and triggers an inflammatory reaction in the arteries, which promotes the buildup of fatty plaques. Imidazole propionate induces atherosclerosis on its own. There’s a causal relationship. 2/

Furthermore, scientists observed elevated levels of imidazole propionate in one out of every five volunteers with active atherosclerosis, the type in which fatty plaques are more likely to rupture and form the blood clots that cause heart attacks and strokes. The new results demonstrate that atherosclerosis is not only a disease caused by fat, but that it also has an inflammatory and autoimmune component. 3/

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Vipin M. Vashishtha

@vipintukur

Jul 20

An exceptional study from Stanford found that lymphocytes from ME/CFS & #LongCOVID patients show elevated oxidative stress, disrupted redox balance, and mitochondrial damage.

These abnormalities lead to excess energy use by immune cells, which may contribute to severe fatigue and other symptoms. 1/

The researchers identified increased lipid peroxidation and glutathione metabolism changes, indicating shared metabolic dysfunction in ME/CFS and LongCOVID.

Females show higher mitochondrial ROS levels and insufficient antioxidant levels (GSH), while males show mitochondrial lipid oxidative damage. These findings suggest that the pathophysiology for ME/CFS and LC are distinct between sexes. 2/

The group also tested ROS-targeting therapies. Metforminshowed some benefit on CD4 T cell proliferation in vitro, and the findings suggest oxidative stress could be a target for diagnosis and therapy. 3/

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Vipin M. Vashishtha

@vipintukur

Jul 19

New gene discovery may change cancer and autoimmune treatment!

Researchers have identified the #SDR42E1 gene as crucial for absorbing vitamin D from the gut and metabolizing it into the active hormone calcitriol, which is essential for bone health, immune function, and cellular processes.

They used CRISPR/Cas9 gene editing to disable SDR42E1 in HCT116 colorectal cancer cells, resulting in a dramatic 53% reduction in cancer cell viability while leaving healthy cells unharmed. 1/

The gene disruption triggered widespread molecular changes affecting over 4,600 downstream genes involved in sterol metabolism and cancer-related signaling pathways.

A specific mutation in #SDR42E1 on chromosome 16 has been linked to vitamin D deficiency, causing the protein to be cut short and rendered inactive. 2/

This discovery opens potential new avenues for precision medicine, including targeted cancer therapies and treatments for autoimmune diseases where vitamin D plays a regulatory role. 3/

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Vipin M. Vashishtha

@vipintukur

Jul 18

A promising new COVID-19 vaccine candidate developed by researchers at the Centenary Institute and the University of Sydney has shown strong potential to protect against both current and emerging coronavirus variants.

By targeting features shared by a range of coronaviruses, the vaccine is designed to offer broader and longer-lasting protection as the virus continues to evolve. 1/

The new study shows that the vaccine candidate, named #CoVEXS5, protected mice from multiple coronaviruses, including the highly immune-evasive omicron XBB.1.5 variant and SARS-CoV-1, a relative of SARS-CoV-2 that was responsible for the 2002–2004 SARS outbreak. 2/

In laboratory tests, CoVEXS5 reduced virus levels in the lungs of infected mice by approximately 99.9% compared to unvaccinated controls, demonstrating a dramatic protective effect. 3/

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