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Application of rapid genotyping of Warfarin individualized pharmacogenetic variants in Warfarin therapy.
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Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
Warfarin is the most widely used oral anticoagulant in clinical practice. The cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) genotypes are associated with warfarin dose requirements in China. Accurate genotyping is vital for obtaining reliable genotype-guided warfarin dosing information.
View Article and Find Full Text PDFA real-world pharmacovigilance analysis of potential ototoxicity associated with sacubitril/valsartan based on FDA Adverse Event Reporting System (FAERS).
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Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, is widely used to treat heart failure. Despite its efficacy, sacubitril/valsartan inevitably causes adverse events such as hypotension, renal dysfunction, hyperkalemia, and angioedema. Sacubitril/valsartan-associated ototoxicity is often underreported in clinical studies and real-world settings.
View Article and Find Full Text PDFTotal synthesis and target identification of marine cyclopiane diterpenes.
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Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Marine cyclopianes are a family of diterpenoid with novel carbon skeleton and diverse biological activities. Herein, we report our synthetic and chemical proteomics studies of cyclopiane diterpenes which culminate in the asymmetric total synthesis of conidiogenones C, K and 12β-hydroxy conidiogenone C, and identification of Immunity-related GTPase family M protein 1 (IRGM1) as a cellular target. Our asymmetric synthesis commences from Wieland-Miescher ketone and features a sequential intramolecular Pauson-Khand reaction and gold-catalyzed Nazarov cyclization to rapidly construct the 6-5-5-5 tetracyclic skeleton.
View Article and Find Full Text PDFImmune checkpoint inhibitor-induced severe epidermal necrolysis mediated by macrophage-derived CXCL10 and abated by TNF blockade.
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Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.
View Article and Find Full Text PDFPiperazine-based P2X4 receptor antagonists.
Arch Pharm (Weinheim)
January 2025
European Institute for Molecular Imaging (EIMI), University of Muenster, Muenster, Germany.
The P2X4 receptor (P2X4R), a ligand-gated ion channel activated by ATP, plays a critical role in neuroinflammation, chronic pain, and cancer progression, making it a promising therapeutic target. In this study, we explored the design and synthesis of piperazine-based P2X4R antagonists, building on the structural framework of paroxetine. A series of over 35 compounds were synthesized to investigate structure-activity relationships (SARs) in a Ca²⁺-flux assay for P2X4R antagonistic activity.
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