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Safety, Tolerability, and Pharmacokinetics of a Novel Anti-obesity Agent, S-309309, in Healthy Adults with or Without Obesity.
Clin Drug Investig
January 2025
Medical Science Department, Shionogi & Co., Ltd., Osaka, Japan.
Background: Anti-obesity medications are recommended for patients who do not achieve and maintain weight loss despite lifestyle interventions. S-309309 is a novel oral inhibitor of monoacylglycerol O-acyltransferase 2 being developed as a treatment for obesity.
Objective: The objective of the study was to investigate the safety, clinical pharmacology, pharmacokinetics and pharmacodynamic biomarker of S-309309.
Background: Electroconvulsive therapy (ECT) is a well-established and effective treatment for severe depression and other conditions. Though ECT induces a generalized seizure, it is unclear why seizures are therapeutic. This study analyzed relationships between pre-treatment brain morphology, stimulation dose, and seizure duration to better understand ECT-induced seizures.
View Article and Find Full Text PDFEvaluating the association between lipidome and female reproductive diseases through comprehensive Mendelian randomization analyses.
Sci Rep
January 2025
Department of Anesthesiology, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China.
This study aimed to assess the causal relationship between lipidome and female reproductive diseases (FRDs) using an advanced series of Mendelian randomization (MR) methods. This study utilized genome-wide association study (GWAS) summary statistics encompassing 179 lipidomes and six prevalent FRDs, namely polycystic ovary syndrome (PCOS), endometriosis, uterine fibroid, female infertility, uterine endometrial cancer, and ovarian cancer. The two-sample MR (TSMR) approach was employed to investigate the causal relationships, with further validation using false discovery rate (FDR) and multivariable MR (MVMR) methods.
View Article and Find Full Text PDFStructural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.
Nat Commun
January 2025
Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
IFNλ4 has posed a conundrum in human immunology since its discovery in 2013, with its expression linked to complications with viral clearance. While genetic and cellular studies revealed the detrimental effects of IFNλ4 expression, extensive structural and functional characterization has been limited by the inability to express and purify the protein, complicating explanations of its paradoxical behavior. In this work, we report a method for robust production of IFNλ4.
View Article and Find Full Text PDFCurrent approaches in CRISPR-Cas system for metabolic disorder.
Prog Mol Biol Transl Sci
January 2025
School of Health Sciences & Technology, UPES, Dehradun, Uttarakhand, India. Electronic address:
A new era in genomic medicine has been brought by the development of CRISPR-Cas technology, which presents hitherto unheard-of possibilities for the treatment of metabolic illnesses. The treatment approaches used in CRISPR/Cas9-mediated gene therapy, emphasize distribution techniques such as viral vectors and their use in preclinical models of metabolic diseases like hypercholesterolemia, glycogen storage diseases, and phenylketonuria. The relevance of high-throughput CRISPR screens for target identification in discovering new genes and pathways associated with metabolic dysfunctions is an important aspect of the discovery of new approaches.
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