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Category: biotech/medical – Page 13

New Breakthrough to Strengthen Bone Could Reverse Osteoporosis

A recent study points to a key bone-strengthening mechanism at work in the body, which could be targeted to treat the bone-weakening disease, osteoporosis.

Led by researchers from the University of Leipzig in Germany and Shandong University in China, the study identified the cell receptor GPR133 (also known as ADGRD1) as being crucial to bone density, via bone-building cells called osteoblasts.

Variations in the GPR133 gene had previously been linked to bone density, leading scientists to turn their attention to the protein it encoded.

Perfusion-Weighted Imaging: The Use of a Novel Perfusion Scoring Criteria to Improve the Assessment of Brain Tumor Recurrence versus Treatment Effects

Introduction: Imaging surveillance of contrast-enhancing lesions after the treatment of malignant brain tumors with radiation is plagued by an inability to reliably distinguish between tumor recurrence and treatment effects. Magnetic resonance perfusion-weighted imaging (PWI)—among other advanced brain tumor imaging modalities—is a useful adjunctive tool for distinguishing between these two entities but can be clinically unreliable, leading to the need for tissue sampling to confirm diagnosis. This may be partially because clinical PWI interpretation is non-standardized and no grading criteria are used for assessment, leading to interpretation discrepancies. This variance in the interpretation of PWI and its subsequent effect on the predictive value has not been studied. Our objective is to propose structured perfusion scoring criteria and determine their effect on the clinical value of PWI. Methods: Patients treated at a single institution between 2012 and 2022 who had prior irradiated malignant brain tumors and subsequent progression of contrast-enhancing lesions determined by PWI were retrospectively studied from CTORE (CNS Tumor Outcomes Registry at Emory). PWI was given two separate qualitative scores (high, intermediate, or low perfusion). The first (control) was assigned by a neuroradiologist in the radiology report in the course of interpretation with no additional instruction. The second (experimental) was assigned by a neuroradiologist with additional experience in brain tumor interpretation using a novel perfusion scoring rubric. The perfusion assessments were divided into three categories, each directly corresponding to the pathology-reported classification of residual tumor content. The interpretation accuracy in predicting the true tumor percentage, our primary outcome, was assessed through Chi-squared analysis, and inter-rater reliability was assessed using Cohen’s Kappa. Results: Our 55-patient cohort had a mean age of 53.5 ± 12.2 years. The percentage agreement between the two scores was 57.4% (κ: 0.271). Upon conducting the Chi-squared analysis, we found an association with the experimental group reads (p-value: 0.014) but no association with the control group reads (p-value: 0.734) in predicting tumor recurrence versus treatment effects. Conclusions: With our study, we showed that having an objective perfusion scoring rubric aids in improved PWI interpretation. Although PWI is a powerful tool for CNS lesion diagnosis, methodological radiology evaluation greatly improves the accurate assessment and characterization of tumor recurrence versus treatment effects by all neuroradiologists. Further work should focus on standardizing and validating scoring rubrics for PWI evaluation in tumor patients to improve diagnostic accuracy.

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.

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