Integrating Untargeted and Targeted Metabolomics Coupled with Pathway Analysis Reveals Muscle Disorder in Osteoporosis on Orchiectomized Mice.

Most osteoporosis (OP) fracture accidents in men are due not only to a low BMD but also because of unhealthy muscle support. However, there has been a limited number of reports about how muscle metabolism is disturbed by OP in males. In this work, a pathway analysis based on metabolomic research was carried out to fill this gap. A classical orchiectomy procedure was adapted to create an OP animal model. A micro-CT and pathological section were applied for a bone and muscle phenotype assessment and a pathology analysis. UPLC-Q-TOF/MS and UPLC-QQQ-MS/MS were applied to measure metabolites in skeletal muscle samples among groups. In total, 31 significantly differential metabolites were detected by comparing healthy models and OP animals, and 7 representative metabolites among the 31 significantly differential metabolites were identified and validated experimentally by UPLC-QQQ-MS/MS (xanthine, L-phenylalanine, choline, hypoxanthine, L-tryptophan, succinic acid, and L-tyrosine). An ingenuity pathway analysis (IPA) analysis revealed significantly enriched pathways involved in inflammation, oxidative stress, and necrosis. To our best knowledge, this is the first study to investigate early muscle disorder processes in Cases of OP at a metabolic level, facilitating early intervention and protection from OP fractures for aged men.

Multiple genetic mutations increase the risk of thrombosis associated with clopidogrel after percutaneous coronary intervention.

Background: The effect of multiple mutations in CYP2C19, PON1 and ABCB1 genes on the effectiveness and safety of dual antiplatelet therapy after percutaneous coronary intervention remains unclear. Methods: In total, 263 Chinese Han patients were enrolled in this study. Platelet aggregation rates and thrombosis risk were used to compare clopidogrel responses and outcomes in patients with different numbers of genetic mutations. Results: Our study demonstrated that 74% of the patients carried more than two genetic mutations. High platelet aggregation rates were associated with genetic mutations in patients receiving clopidogrel and aspirin after percutaneous coronary intervention. Genetic mutations were closely related to the recurrence of thrombotic events, but not bleeding. The number of genes that become dysfunctional in patients is directly correlated with the risk of recurrent thrombosis. Conclusion: Compared with CYP2C19 alone or the platelet aggregation rate, it is more helpful to predict clinical outcomes by considering the polymorphisms of all three genes.

The effects of different combinations of mutations in the genes CYP2C19, PON1 and ABCB1 on the effectiveness and safety of dual antiplatelet therapy in patients who undergo percutaneous coronary intervention (PCI) are unclear. In total, 263 Chinese Han patients receiving 75 mg clopidogrel and 100 mg aspirin daily for 12 months after PCI were enrolled in this study. ADP-induced platelet aggregation rates, thrombosis and bleeding risk were used to compare clopidogrel responses among the patients. Only 3.4% of patients had no mutations in CYP2C19, PON1 or ABCB1, and 74% of patients who chose to be genetically tested carried more than two mutations in these genes. High ADP-induced platelet aggregation rates in patients receiving clopidogrel and aspirin after PCI were associated with mutations in CYP2C19, PON1 and ABCB1. Patients with double or triple genetic mutations in CYP2C19, PON1 or ABCB1 had a higher risk of thrombosis within 18 months of follow-up. We conclude that multiple genetic polymorphisms influence platelet reactivity, bleeding and thrombosis risk during dual antiplatelet therapy after PCI.