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Health proteins disulfide isomerase prevents endoplasmic reticulum strain result and also apoptosis through the oxidoreductase exercise inside intestines cancer.
BACKGROUND & AIMS Intestinal short-chain fatty acids have been demonstrated to modulate host energy metabolism and are elevated in overweight and obese individuals. We hypothesized that other intestinal energy products especially tricarboxylic acid (TCA) cycle intermediates might also related to overweight status. In addition, little information is available regarding to the potential relationship between gut microbiota and underweight status. Therefore, the aim of this study was to investigate whether gut microbiota and intestinal energy metabolites differ in underweight, normal weight, and overweight individuals, and their correlations with host cardiometabolic risk factors. SUBJECTS/METHODS Gut microbiome, intestinal energy metabolites, circulating cardiometabolic risk factors, and proinflammatory markers were determined in 29 underweight, 67 normal weight, and 67 overweight adults. RESULTS The fecal concentrations of succinic acid, fumaric acid, malic acid, propionic acid, and adipic acid were significantly increased in the overweight individuals in parallel with a higher relative abundance of Veillonellacea after adjusting for multiple comparisons (all p 0.25, p less then 0.05). Compared with the normal weight individuals, the gut microbial α-diversity was lower in the overweight (p = 0.007 for Shannon index and p = 0.009 for Ace index) and underweight (p = 0.05 for Shannon index and p = 0.08 for Ace index) groups. However, no significant differences in the overall gut microbiota composition were observed among the three groups. CONCLUSIONS Our findings revealed that low gut microbiota diversity was associated with both overweight and underweight status. Intestinal TCA cycle intermediates were associated with overweight development and might be potential markers for future studies related to gut microbiota and host cardiometabolic health. BACKGROUND Angelman syndrome (AS) is a neurodegenerative disorder caused by functional loss of the maternal ubiquitin-protein ligase 3A gene. Nonepileptic myoclonus, also described as tremulous movement, often occurs during puberty and increases in adulthood. The involuntary movement in AS has not been defined patho-physiologically and the drugs used such as levetiracetam and piracetam are not always effective. Recently, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist, perampanel (PER), was used to alleviate myoclonus in progressive myoclonus epilepsy. Herein, we tested the efficacy of PER for nonepileptic myoclonus. METHODS AND RESULTS Four patients with AS, aged from 20 to 40 years at the beginning of treatment, were enrolled in our study. All patients reported disruption to their daily lives from the myoclonus movement. They experienced mild to moderate improvement with the starting dose of 2 mg. The dose was increased to 4 mg in one patient to achieve sufficient efficacy, while two had their dose reduced to 1 mg due to dizziness or possible exacerbation of myoclonus. The last patient continued to take the starting dose. Follow-up over 16-20 months revealed a significant reduction in the severity of nonepileptic myoclonus in all patients. CONCLUSION Our study suggests that PER could be one of the promising drugs for nonepileptic myoclonus in AS. BACKGROUND Although echocardiography is widely used to measure left ventricular ejection fraction (LVEF), its prognostic value has not been demonstrated in a broad range of patients including those acutely hospitalized for cardiac or noncardiac causes. We determined whether greater degrees of left ventricular systolic dysfunction were associated with progressively increasing risks of death or cardiovascular hospitalizations among patients in hospital or outpatient settings. METHODS A total of 27,323 patients with LVEF measured and 19,445 matched controls were followed for 223,034 person-years. Outcomes of total mortality, cardiovascular death, cardiovascular hospitalizations, and heart failure hospitalizations were examined using cause-specific hazard competing-risks analysis. selleck chemicals RESULTS In the study cohort (median age, 68 [interquartile range, 58-77], 14,828 women [31.7%]), the hazard ratios (95% CI) for all-cause death were 1.67 (1.57-1.77), 1.30 (1.24-1.36), and 1.17 (1.11-1.23) when LVEF was less then 25%, 25%-35%, or 36%-45% compared with LVEF 46%-55% (all P less then .001). Rates of cardiovascular death were similarly higher with lower LVEF. The hazard ratios for cardiovascular hospitalization were 1.35 (1.27-1.42), 1.21 (1.16-1.27), and 1.13 (1.07-1.18) for LVEFs less then 25%, 25%-35%, and 36%-45%, respectively (all P less then .001). The rate of heart failure hospitalizations was amplified, with hazard ratios of 1.71 (1.59-1.85), 1.39 (1.31-1.48), and 1.21 (1.13-1.29) for LVEFs less then 25%, 25%-35%, or 36%-45% (all P less then .001). The rate of mortality and hospitalizations increased comparably with greater reductions in LVEF during both inpatient cardiac or noncardiac admissions (P less then .001). CONCLUSIONS Quantitative echocardiographic LVEF stratified the risk of death and hospitalization in a wide range of clinical settings, including during noncardiac admissions. While more than 7000 rare diseases have been identified, only about 5 percent benefit from a licensed treatment. As the majority of these diseases is life threatening, these facts underscore the need for new drugs. Drug repositioning is an alternative strategy in drug development, which represents an attractive opportunity for rare diseases. Drug repositioning (also called drug repurposing, drug reprofiling or drug re-tasking) consists in identifying for an already approved or investigational drug a new use outside the scope of the original medical indication. Drug repositioning is considered in the field of orphan drugs as being a faster and somehow less costly strategy than traditional new drug development for pharmaceutical companies. While several successful repositioning cases have been discovered by serendipity, most successes straightly derive from the molecular characterization of the concerned disease. This short commentary is mainly dedicated to these rationally-based success stories.
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