The Journal of clinical investigation
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Our group recently discovered that certain dietary nutrients possessing a trimethylamine (TMA) moiety, namely choline/phosphatidylcholine and L-carnitine, participate in the development of atherosclerotic heart disease. A meta-organismal pathway was elucidated involving gut microbiota-dependent formation of TMA and host hepatic flavin monooxygenase 3-dependent (FMO3-dependent) formation of TMA-N-oxide (TMAO), a metabolite shown to be both mechanistically linked to atherosclerosis and whose levels are strongly linked to cardiovascular disease (CVD) risks. Collectively, these studies reveal that nutrient precursors, gut microbiota, and host participants along the meta-organismal pathway elucidated may serve as new targets for the prevention and treatment of CVD.
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Clostridium difficile infection (CDI) is the leading health care-associated illness. Both human and animal models have demonstrated the importance of the gut microbiota's capability of providing colonization resistance against C. difficile. ⋯ Future studies directed at how microbial communities influence the metabolic environment may help elucidate the role of the microbiota in disease development. These findings will improve current biotherapeutics for patients with CDI, particularly those with recurrent disease.
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Anemia, or low blood hemoglobin (Hgb) levels, afflicts 2 billion people worldwide. Currently, Hgb levels are typically measured from blood samples using hematology analyzers, which are housed in hospitals, clinics, or commercial laboratories and require skilled technicians to operate. A reliable, inexpensive point-of-care (POC) Hgb test would enable cost-effective anemia screening and chronically anemic patients to self-monitor their disease. We present a rapid, stand-alone, and disposable POC anemia test that, via a single drop of blood, outputs color-based visual results that correlate with Hgb levels. ⋯ These results demonstrate the feasibility of this POC color-based diagnostic test for self-screening/self-monitoring of anemia.
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In humans, vWF levels predict the risk of myocardial infarction and thrombosis; however, the factors that influence vWF levels are not completely understood. Recent genome-wide association studies (GWAS) have identified syntaxin-binding protein 5 (STXBP5) as a candidate gene linked to changes in vWF plasma levels, though the functional relationship between STXBP5 and vWF is unknown. We hypothesized that STXBP5 inhibits endothelial cell exocytosis. ⋯ However, Stxbp5 KO mice also displayed hemostasis defects, including prolonged tail bleeding times and impaired mesenteric arteriole and carotid artery thrombosis. Furthermore, platelets from Stxbp5 KO mice had defects in platelet secretion and activation; thus, STXBP5 inhibits endothelial exocytosis but promotes platelet secretion. Our study reveals a vascular function for STXBP5, validates the functional relevance of a candidate gene identified by GWAS, and suggests that variation within STXBP5 is a genetic risk for venous thromboembolic disease.