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Assessment of Potential Drug-Drug Interactions for Novel Oral Melanocortin-1 Receptor Agonist Dersimelagon.
Pharmacol Res Perspect
February 2025
CareCeutics LLC, Berwyn, Pennsylvania, USA.
Dersimelagon is a novel investigational orally administered selective agonist of the melanocortin-1 receptor. The drug-drug interaction (DDI) potential of dersimelagon was investigated in both nonclinical (in vitro) and clinical studies. The in vitro inhibition of CYP/UGT isoforms and efflux/uptake transporters by dersimelagon was assessed.
View Article and Find Full Text PDFImmune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy.
Front Immunol
January 2025
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Biological sex is closely associated with the properties and extent of the immune response, with males and females showing different susceptibilities to diseases and variations in immunity. Androgens, predominantly in males, generally suppress immune responses, while estrogens, more abundant in females, tend to enhance immunity. It is also established that sex hormones at least partially explain sex biases in different diseases, particularly autoimmune diseases in females.
View Article and Find Full Text PDFHeterotropic allosteric modulation of CYP3A4 in vitro by progesterone: Evidence for improvement in prediction of time-dependent inhibition for macrolides.
Drug Metab Dispos
January 2025
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
Predictions of drug-drug interactions resulting from time-dependent inhibition (TDI) of CYP3A4 have consistently overestimated or mispredicted (ie, false positives) the interaction that is observed in vivo. Recent findings demonstrated that the presence of the allosteric modulator progesterone (PGS) in the in vitro assay could alter the in vitro kinetics of CYP3A4 TDI with inhibitors that interact with the heme moiety, such as metabolic-intermediate complex forming inhibitors. The impact of the presence of 100 μM PGS on the TDI of molecules in the class of macrolides typically associated with metabolic-intermediate complex formation was investigated.
View Article and Find Full Text PDFEndophytic strategies decoded by genome and transcriptome analysis of strain NQ8GII4.
Front Microbiol
January 2025
College of Forestry and Prataculture, Ningxia University, Yinchuan, China.
Introduction: strain NQ8GII4 is an endophytic fungus with significant potential for improving growth and disease resistance of alfalfa. However, the molecular mechanisms underlying the symbiotic relationship between NQ8GII4 and alfalfa roots remain poorly understood.
Methods: In this study, we conducted (1) a comparative genomic analysis of selected saprophytic, pathogenic, and endophytic fungi, including molecular phylogeny analysis, whole-genome alignment, and divergence date estimation positioning, and (2) transcriptomic profiling of alfalfa roots infected with NQ8GII4.
Sex reversal induced by 17β-estradiol may be achieved by regulating the neuroendocrine system of the Pacific white shrimp Penaeus vannamei.
BMC Genomics
January 2025
Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.
Background: Due to sexual dimorphism in growth of penaeid shrimp, all-female cultivation is desirable for the aquaculture industry. 17β-estradiol (E2) has the potential to induce the male-to-female sex reversal of decapod species. However, the mechanisms behind it remain poorly understood.
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