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A trigger-inducible split-Csy4 architecture for programmable RNA modulation.
Nucleic Acids Res
January 2025
Research Center for Life Sciences Computing, Zhejiang Lab, Kechuang Avenue, Yuhang District, Hangzhou, Zhejiang, 311121, China.
The CRISPR-derived endoribonuclease Csy4 is a popular tool for controlling transgene expression in various therapeutically relevant settings, but adverse effects potentially arising from non-specific RNA cleavage remains largely unexplored. Here, we report a split-Csy4 architecture that was carefully optimized for in vivo usage. First, we separated Csy4 into two independent protein moieties whose full catalytic activity can be restored via various constitutive or conditional protein dimerization systems.
View Article and Find Full Text PDFThyromimetics and MASLD: Unveiling the Novel Molecules Beyond Resmetirom.
J Gastroenterol Hepatol
January 2025
Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India.
Background: Resmetirom, the first FDA-approved drug for nonalcoholic steatohepatitis (NASH) with fibrosis in obese patients, when combined with lifestyle modifications, improves NASH resolution and reduces fibrosis by at least one stage. Low thyroid hormone (T) levels are linked to a higher risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). Epidemiological studies have confirmed the positive correlation between hypothyroidism and MASLD.
View Article and Find Full Text PDFRecent clinical and mechanistic insights into vitiligo offer new treatment options for cell-specific autoimmunity.
J Clin Invest
January 2025
Department of Dermatology, UMass Chan Medical School, Worcester, Massachusetts, USA.
Vitiligo is an autoimmune disease that has been recognized, stigmatized, and treated for millennia. Recent translational research has revealed key mechanisms of disease, including cellular stress, innate immune activation, T cell-mediated elimination of melanocytes from the skin resulting in clinically apparent white spots, as well as stem cell regeneration that reverses established lesions. Many of these pathways have been targeted therapeutically, leading to the first FDA-approved medication to reverse the disease, with many more in clinical trials.
View Article and Find Full Text PDFExploring pathological targets and advancing pharmacotherapy in autism spectrum disorder: Contributions of glial cells and heavy metals.
Histol Histopathol
January 2025
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India.
Autism spectrum disorder (ASD) is a globally recognized neurodevelopmental condition characterized by repetitive and restrictive behavior, persistent deficits in social interaction and communication, mental disturbances, etc., affecting approximately 1 in 100 children worldwide. A combination of genetic and environmental factors is involved in the etiopathogenesis of the disease, but specific biomarkers have not yet been identified.
View Article and Find Full Text PDFThe Role of Intravenous Selexipag in Managing PAH and Bridging Gaps in Oral Treatment: A Narrative Review.
Ther Clin Risk Manag
January 2025
Departments of Medicine and Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY, USA.
Pulmonary arterial hypertension (PAH) is a rare and potentially fatal condition characterized by progressive increases in blood pressure in the arteries of the lungs. Oral selexipag, approved by the Food and Drug Administration (FDA) in 2015 for the treatment of PAH, targets prostacyclin receptors on pulmonary arterial vascular smooth muscle and endothelial cells to improve blood flow through the lungs and reduce pulmonary vascular resistance. Oral selexipag is effective, but may be discontinued due to factors like side effects, emergency conditions, or inability to take oral medication, potentially leading to severe adverse events, such as rebound pulmonary hypertension and right heart failure.
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