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Category: biotech/medical – Page 33

Immunological Biomarkers in Autism Spectrum Disorder: The Role of TNF-Alpha and Dependent Trends in Serum IL-6 and CXCL8

Background: Autism spectrum disorder (ASD) has seen a rise in prevalence, and the immune system’s role in brain development is increasingly recognized. This study investigates the relationship between immune dysregulation and ASD by examining serum concentrations of interleukin 6 (IL-6), interleukin 8 (CXCL8), and tumor necrosis factor alpha (TNF-alpha) in children. Methods: Serum samples from 45 children with ASD and 30 controls, aged 2 to 12 years, were analyzed using electrochemiluminescence, chemiluminescent microparticle immunoassay, and chemiluminescent immunoassay. ASD symptoms were assessed using the Autism Spectrum Rating Scale (ASRS) and Social Communication Questionnaire (SCQ). Results: No significant correlation was observed between CXCL8 levels and ASD. IL-6 levels showed a trend toward elevation in boys with ASD.

Antibody evasion and receptor binding of SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and related subvariants

Mellis et al. show that the SARS-CoV-2 JN.1 sublineage has different virological features associated with its recently dominant subvariants. LP.8.1 has greater receptor-binding affinity than earlier strains but not increased antibody evasion, while the more recently dominant XFG and NB.1.8.1 have greater antibody evasion than LP.8.1.1.

Engineered immune cells target and destroy glioblastoma in animal models

With a five-year survival rate of less than 5%, glioblastoma is one of the most aggressive types of brain cancer. Until now, all available treatments, including immunotherapy—which involves strengthening the immune system to fight cancer—have proved disappointing. CAR-T cells are genetically modified immune cells manufactured in the laboratory and designed to identify and destroy cancer cells.

By targeting a protein present in the tumor environment, a team from the University of Geneva (UNIGE) and the Geneva University Hospital (HUG) has developed CAR-T cells capable of destroying glioblastoma cells. Their efficacy in an animal model of the disease paves the way for clinical trials in humans.

The results are published in the Journal for ImmunoTherapy of Cancer.

Free radicals in the brain that may fuel dementia

Researchers have discovered that free radicals generated at a specific site in non-neuronal brain cells called astrocytes, may promote dementia, according to a study. Their findings, published in Nature Metabolism, demonstrated that blocking this site lowered brain inflammation and protected neurons, suggesting a novel therapeutic approach for neurodegenerative disorders, including frontotemporal dementia and Alzheimer’s disease.

“I’m really excited about the translational potential of this work,” a co-lead of the research. “We can now target specific mechanisms and go after the exact sites that are relevant for disease.”

The researchers focused on mitochondria—metabolic structures inside cells that generate energy from food and, in the process, release molecules known as reactive oxygen species (ROS). At low levels, ROS play an important role in cell function, but they can be harmful when produced in excess or at the wrong time. “Decades of research implicate mitochondrial ROS in neurodegenerative diseases,” said the other co-lead.

Why some memories last a lifetime while others fade fast

Correlation alone could not answer the key questions, so co-lead Celine Chen created a CRISPR-based screening platform to alter gene activity in the thalamus and cortex. This approach showed that removing certain molecules changed how long memories lasted, and each molecule operated on its own timescale.

Timed Programs Guide Memory Stability

The results indicate that long-term memory relies not on a single on/off switch, but on a sequence of gene-regulating programs that unfold like molecular timers across the brain.

Astrocytic Sox9 overexpression in Alzheimer’s disease mouse models promotes Aβ plaque phagocytosis and preserves cognitive function

Researchers at Baylor College of Medicine have discovered a natural mechanism that clears existing amyloid plaques in the brains of mouse models of Alzheimer’s disease and preserves cognitive function. The mechanism involves recruiting brain cells known as astrocytes, star shaped cells in the brain, to remove the toxic amyloid plaques that build up in many Alzheimer’s disease brains. Increasing the production of Sox9, a key protein that regulates astrocyte functions during aging, triggered the astrocytes’ ability to remove amyloid plaques. The study, published in Nature Neuroscience, suggests a potential astrocyte-based therapeutic approach to ameliorate cognitive decline in neurodegenerative disease.

“Astrocytes perform diverse tasks that are essential for normal brain function, including facilitating brain communications and memory storage. As the brain ages, astrocytes show profound functional alterations; however, the role these alterations play in aging and neurodegeneration is not yet understood,” said first author Dr. Dong-Joo Choi, who was at the Center for Cell and Gene Therapy and the Department of Neurosurgery at Baylor while he was working on this project. Choi currently is an assistant professor at the Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine at the University of Texas Health Science Center at Houston.

Astrocytes are associated with Alzheimer’s disease pathogenesis. We found that the transcription factor Sox9 functions to enhance astrocytic phagocytosis of Aβ plaques via MEGF10, and this clearance of plaques is associated with the preservation of cognitive function in mouse models.

Mini lung organoids made in bulk could help test personalized cancer treatments

A team of scientists have developed a simple method for automated manufacturing of lung organoids which could revolutionize the development of treatments for lung disease. These organoids, miniature structures containing the cells that real lungs do, could be used to test early-stage experimental drugs more effectively, without needing to use animal material.

In the future, patients could even have personalized organoids grown from their own tissue to try out potential treatments in advance.

“The best result for now—quite simply—is that it works,” said Professor Diana Klein of University of Duisburg-Essen, first author of the article in Frontiers in Bioengineering and Biotechnology.

Opposite Effects of mRNA-Based and Adenovirus-Vectored SARS-CoV-2 Vaccines on Regulatory T Cells: A Pilot Study

New-generation mRNA and adenovirus vectored vaccines against SARS-CoV-2 spike protein are endowed with immunogenic, inflammatory and immunomodulatory properties. Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that induces in mice robust expansion of antigen-specific regulatory T (Treg) cells. The Pfizer/BioNTech BNT162b2 mRNA vaccine against SARS-CoV-2 is identical to MOGm1Ψ except for the lipid carrier, which differs for containing lipid nanoparticles rather than lipoplex. Here we report that vaccination with BNT162b2 led to an increase in the frequency and absolute count of CD4posCD25highCD127low putative Treg cells; in sharp contrast, vaccination with the adenovirus-vectored ChAdOx1 nCoV-19 vaccine led to a significant decrease of CD4posCD25high cells.

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