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Category: biotech/medical – Page 436

Protein discovery illuminates how the immune system switches between rest and action

Cells in the immune system don’t always fight; they often rest and wait for threats, like viruses or bacteria. When such threats emerge, the cells activate to defend the body. This delicate balance between rest and activation is crucial to our health—immune cells must be poised for activation to protect against threats, but if they’re overly active, autoimmune diseases can result.

But what controls this important balance?

In a new study published in Nature, scientists from Gladstone Institutes and UC San Francisco (UCSF) focused on T cells—which serve a vital role in the immune system—and pinpointed how a network of different proteins controls rest and activation.

A new class of antivirals could help prevent future pandemics

The arrival of Paxlovid in December 2021 marked another turning point in the COVID-19 pandemic—an effective antiviral that has since successfully treated millions. But like many antivirals before it, scientists know that at some point, Paxlovid is likely to lose some efficacy due to drug resistance. Researchers working to stay ahead of such emerging threats have now identified a wholly new way to treat SARS-CoV-2 infections—work that may have even broader implications.

In fact, a new study by the Tuschl laboratory introduces a proof-of-concept for a novel class of antivirals that would target a type of enzyme essential not just to SARS, but also many RNA viruses, including Ebola and dengue, as well as cytosolic-replicating DNA viruses, including Pox viruses. The findings may pave the way for a faster and more robust response to future pandemics.

“Nobody has found a way to inhibit this enzyme before,” says Thomas Tuschl, the F. M. Al Akl and Margaret Al Akl professor at Rockefeller. “Our work establishes cap methyl transferase enzymes as therapeutic targets and opens the door to many more antiviral developments against pathogens that until now we’ve had only limited tools to fight.”

First vaccine against blood-stage malaria is well-tolerated and offers effective protection in clinical trial

The results of a clinical trial into a new malaria vaccine candidate (RH5.1/Matrix-MTM) show it is well-tolerated and offers effective protection against the blood-stage of the disease—the first inoculation to do so.

Malaria, caused by Plasmodium falciparum parasites, is a leading cause of death in under five in many parts of Africa. Blood-stage —when the parasite infects —causes symptoms of the disease like fever and chills, and can lead to severe, life-threatening complications such as anemia and organ failure.

The study has been run by scientists at the University of Oxford in collaboration with the Clinical Research Unit of Nanoro (CRUN) at the Institut de Recherche en Sciences de la Santé (IRSS) in Burkina Faso, the London School of Hygiene and Tropical Medicine (LSHTM) in the U.K. and the National Institute of Health (NIH) in the U.S., with support from other partners including the Serum Institute of India Pvt. Ltd, Novavax and ExpreS2ion Biotechnologies ApS.

Early Cancer Detection Boosted by Molecular Fingerprint

Human fingerprints are detailed, unique, difficult to alter, and durable over the life of an individual, making them suitable as long-term markers of human identity. Could the same concept be used to help identify cancer? A new study by researchers at the Centre for Genomic Regulation (CRG) in Barcelona reveals different types of cancer have unique molecular “fingerprints” that are detectable in the early stages of the disease and can be picked up with near-perfect accuracy by small, portable scanners in a few hours. The discovery lays the groundwork for creating new, noninvasive diagnostic tests that detect different types of cancer faster and earlier than currently possible.

The findings are published in the journal Molecular Cell in an article entitled “Epitranscriptomic rRNA fingerprinting reveals tissue-of-origin and tumor-specific signatures.”

“Our ribosomes are not all the same. They are specialized in different tissues and carry unique signatures that reflect what’s happening inside our bodies,” explained ICREA research professor Eva Novoa, PhD, lead author of the study and researcher at the CRG. “These subtle differences can tell us a lot about health and disease.”

DNA sequencing test can predict prognosis for advanced prostate cancer patients

Published in Nature Communications, a new study led by the University of Minnesota Medical School and Duke University found that a DNA sequencing test for advanced prostate cancer patients can distinguish between patients with poor and favorable prognoses.

The new blood-based —called AR-ctDETECT—is designed to detect and analyze small fragments of tumor-derived DNA in the blood of certain with advanced, .

In this new study, the AR-ctDETECT test was used to analyze DNA from more than 770 from a phase 3 clinical trial of advanced prostate cancer patients. The test identified circulating tumor DNA (ctDNA) in 59% of patients with metastatic prostate cancer. Patients with detectable circulating tumor DNA had significantly worse overall survival compared to those without. These results demonstrate the potential of the AR-ctDETECT test to provide key genetic information to tailor treatments based on similar characteristics among patients.

Longevity Breakthrough: New Protein Discovery Could Be the Key to Healthier Aging

New research found that the protein MANF helps cells manage toxic protein clumps, improving cellular health and potentially aiding treatments for age-related diseases like Alzheimer’s and Parkinson’s.

Researchers at McMaster University have uncovered a previously unidentified cell-protective role of a protein, potentially paving the way for new treatments for age-related diseases and promoting healthier aging.

The team has found that a class of protective proteins known as MANF plays a role in the process that keep cells efficient and working well.

Protein NLRP12 Protects Against Colon Cancer

A newly published research study from the UNC Lineberger Comprehensive Cancer Center describes how the absence of the protein NLRP12 significantly increases susceptibility to colitis-associated colon cancer in pre-clinical models.

A family of proteins is yielding new information about how it contributes to the development of gastrointestinal disease and cancer. A team of UNC scientists reports that in pre-clinical models, the absence of a protein called NLRP12 significantly increases susceptibility to colitis-associated colon cancer.

The NLR family of proteins is very complex and scientists have determined that the majority of them act as activators of inflammation. However, scientists at UNC and elsewhere have recently reported that one NLR protein, NLRP12, actually functions to reduce disease by inhibiting a major inflammatory pathway mediated by a protein called NF-Kappa B activation has been long associated with inflammation and cancer promotion. But NF-Kappa B has an alternate signaling pathway that is not as well understood. This alternative pathway was the focus of the UNC team’s study. Their study was published in the April 12, 2012 online issue of the journal Immunity.

Estimation of physiological aging based on routine clinical biomarkers: a prospective cohort study in elderly Chinese and the UK Biobank

Chronological age (CA) does not reflect individual variation in the aging process. However, existing biological age predictors are mostly based on European populations and overlook the widespread nonlinear effects of clinical biomarkers.

Using data from the prospective Dongfeng-Tongji (DFTJ) cohort of elderly Chinese, we propose a physiological aging index (PAI) based on 36 routine clinical biomarkers to measure aging progress. We first determined the optimal level of each biomarker by restricted cubic spline Cox models. For biomarkers with a U-shaped relationship with mortality, we derived new variables to model their distinct effects below and above the optimal levels. We defined PAI as a weighted sum of variables predictive of mortality selected by a LASSO Cox model. To measure aging acceleration, we defined ΔPAI as the residual of PAI after regressing on CA. We evaluated the predictive value of ΔPAI on cardiovascular diseases (CVD) in the DFTJ cohort, as well as nine major chronic diseases in the UK Biobank (UKB).

In the DFTJ training set (n = 12,769, median follow-up: 10.38 years), we identified 25 biomarkers with significant nonlinear associations with mortality, of which 11 showed insignificant linear associations. By incorporating nonlinear effects, we selected CA and 17 clinical biomarkers to calculate PAI. In the DFTJ testing set (n = 15,904, 5.87 years), PAI predict mortality with a concordance index (C-index) of 0.816 (95% confidence interval, [0.796, 0.837]), better than CA (C-index = 0.771 [0.755, 0.788]) and PhenoAge (0.799 [0.784, 0.814]). ΔPAI was predictive of incident CVD and its subtypes, independent of traditional risk factors. In the external validation set of UKB (n = 296,931, 12.80 years), PAI achieved a C-index of 0.749 (0.746, 0.752) to predict mortality, remaining better than CA (0.706 [0.702, 0.709]) and PhenoAge (0.743 [0.739, 0.746]).

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