Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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This study aimed at expounding the synergistic effect of Bcl-2-associated athanogene 3 (BAG3) knockdown and poly ADP-ribose polymerase (PARP) inhibitor on ovarian cancer (OC) cells and the potential mechanism. Short hairpin RNA (shRNA) targeting BAG3 (sh-BAG3) was transfected into SK-OV-3 (SKOV-3 ;SKOV3) and A2780 cells, and western blot assay was used to detect transfection efficiency. Cell proliferation and apoptosis were detected by the cell counting kit-8 method, 5-Bromodeoxyuridine (BrdU) experiment and flow cytometry analysis, respectively. ⋯ Both sh-BAG3 and olaparib decreased the expression of Beclin-1 and the LC3-Ⅱ:LC3-I ratio, and their synergism further inhibited the process of autophagy. However, the aforementionede effects were reversed after the cells were treated with rapamycin. Based on these results, we concluded that BAG3 knockdown synergizes with olaparib to kill OC cells in vitro by repressing autophagy.
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This study compares the odds of being admitted for inflammatory bowel disease (IBD) in patients with psoriasis compared with those without psoriasis alone. We also compared hospital outcomes of patients admitted primarily for IBD with and without a secondary diagnosis of psoriasis. Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 database to search for hospitalizations of interest using International Classification of Diseases, 10th Revision codes. ⋯ IBD hospitalizations with coexisting psoriasis have similar lengths of stay, hospital charges, need for blood transfusion, and similar likelihood of having a secondary discharge diagnosis of deep venous thrombosis, gastrointestinal bleed, sepsis, and acute kidney injury compared with those without coexisting psoriasis. Patients with coexisting psoriasis have almost three times the odds of being admitted for IBD compared with patients without psoriasis. Hospitalizations for IBD with coexisting psoriasis have similar hospital outcomes compared with those without coexisting psoriasis.
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Disease-associated alterations of the intestinal microbiota composition, known as dysbiosis, have been well described in several functional gastrointestinal (GI) disorders. Several studies have described alterations in the gastric microbiota in functional dyspepsia, but very few have looked at the duodenum. Here, we explored the upper GI tract microbiota of inpatients with upper GI dyspeptic symptoms, and compared them to achalasia controls, as there is no indication for an esophagogastroduodenoscopy in healthy individuals. ⋯ Metabolic function prediction identified greater anaerobic metabolism in the stomach microbial community of patients with dyspepsia. Proton pump inhibitor use was not associated with any particular genus. Co-abundance analysis revealed Rothia as the main hub in the duodenum, a genus that significantly correlated with the relative abundance of Clostridium, Haemophilus, and ActinobacillusWe conclude that patients with upper GI symptoms consistent with dyspepsia have alterations in the microbiota of saliva, the stomach, and duodenum, which could contribute to symptoms of functional GI disorders.
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Hyperuricemia is more prevalent among people with obesity and metabolic syndrome, and is associated with adverse clinical outcomes. We hypothesized that increased renal reabsorption of uric acid (UA) in obesity and metabolic syndrome may be an adaptive response of the kidney when faced with fatty acid-induced oxidative stress. To test this hypothesis, we examined lipid accumulation, markers of oxidative stress, and renal UA handling in Zucker diabetic fatty (ZDF) rats, and in matched lean control animals. ⋯ We observed robust correlations between renal lipid content and oxidative stress markers in the pooled experimental groups, particularly in older animals after 20 weeks on the study diets. Dietary antioxidant supplementation did not prevent the gradual decline in renal function observed in older ZDF rats. These findings suggest that hyperuricemia in the ZDF rat model of obesity and the metabolic syndrome is not caused by renal oxidative stress, that there may be a pathophysiological link between lipid accumulation and oxidative stress in the kidney, and that antioxidant supplementation does not prevent age-related decline in renal function in ZDF rats.
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Growth differentiation factor 15 (GDF-15) has been suggested as a prognostic biomarker for bleeding and mortality in atrial fibrillation (AF). To date, serum and EDTA matrices are standardized for the GDF-15 assay but it is unclear if it can be measured also in citrate. In this study, we aim to investigate if the Elecsys GDF-15 assay (Roche Diagnostics, Mannheim, Germany) can be determined accurately in citrate samples in a cohort of 10 patients with AF and 10 healthy controls. ⋯ This was also observed in patients with AF: EDTA-serum (r=0.975; p<0.001), serum-citrate (r=0.835; p=0.003), and EDTA-citrate (r=0.768; p=0.009). Our results demonstrate that citrate samples may be used for the determination of GDF-15 in AF given the positive and good correlation with EDTA and serum matrices. Further studies should validate these observations.