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Background/Aims: Overexpression of transforming growth factor β1-inducible gene h3 (βig-h3) is associated with renal scarring in several models of renal disease. We investigated the inhibitory effect of pravastatin on βig-h3 expression in a rat model of chronic cyclosporin A (CsA)-induced nephropathy. Methods: Adult Sprague Dawley rats kept on a low salt diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and pravastatin (20 mg/kg in drinking water). The effect of pravastatin on βig-h3 expression was evaluated using in situ hybridization, immunohistochemistry, and immunoblotting. Functional parameters, histopathology (tubulointerstitial fibrosis, TIF, and arteriolopathy), and levels of transforming growth factor β1 (TGF-β1) and endothelial nitric oxide synthase were compared for the different treatment groups. Results: Co-administration of pravastatin significantly inhibited βig-h3 mRNA production and gene expression within the tubulointerstitium of the CsA-treated kidneys, and this paralleled an attenuation of TIF (12.7 ± 2.2 vs. 35.9 ± 5.4%, p < 0.01 vs. CsA) and the expression of TGF-β1 mRNA (279 ± 40 vs. 719 ± 85%, p < 0.01 vs. CsA). Pravastatin treatment reduced endothelial nitric oxide synthase protein levels and reversed the renal dysfunction caused by CsA. Neither CsA nor pravastatin affected total serum cholesterol or triglyceride levels in the treatment groups. Conclusion: Pravastatin thus effectively abrogated the upregulation of βig-h3 gene expression and associated TGF-β1 production, and this was associated with attenuated TIF in this model of chronic CsA-induced nephropathy.

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TGF-beta-induced gene-h3 (beta ig-h3) is an adhesive molecule that interacts with integrins. Because TGF-beta plays an important role in diabetic complications and beta ig-h3 serves as a cell substrate, we hypothesized that diabetic conditions might increase beta ig-h3 synthesis in vascular smooth muscle cells (VSMCs), which may subsequently contribute to the pathogenesis of diabetic angiopathy. The concentrations of beta ig-h3 and TGF-beta were measured in conditioned media using an enzyme-linked immunosorbent assay. An immunohistochemical study showed that beta ig-h3 was expressed in the VSMCs and the matrix of rat aortas. TGF-beta stimulated beta ig-h3 production, and high glucose induced beta ig-h3 as well as TGF-beta production in the VSMCs. The high glucose-induced beta ig-h3 expression was almost entirely blocked by an anti-TGF-beta antibody. beta ig-h3 protein mediated the adhesion, spreading, migration, and proliferation of rat VSMCs. These results suggest that the high glucose-induced beta ig-h3 in VSMCs regulates VSMC functions and may play an important role in diabetic angiopathy.

Background: We recently demonstrated that upregulation of the transforming growth factor (TGF)-β1 inducible gene-h3 (βig-h3) is associated with tubulointerstitial fibrosis (TIF) in a rat model of chronic cyclosporine A (CsA) nephrotoxicity. This study investigated the association between βig-h3 expression and TIF during losartan treatment in this model. Methods: Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on βig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-β1 and intrarenal angiotensin II were compared across treatment groups. Results: Concurrent administration of losartan significantly attenuated βig-h3 mRNA and protein expression within the tubulointerstitium of CsA-treated kidneys. This was accompanied by the retardation of TIF (18 ± 5 vs. 39 ± 5%, p < 0.01 vs. CsA) and the expression of TGF-β1 mRNA (336 ± 49 vs. 685 ± 63%, p < 0.01 vs. CsA) and the number of angiotensin II-positive glomeruli (18 ± 5 vs. 38 ± 6, p < 0.05 vs. CsA). Conclusion: Losartan is capable of abrogating the upregulation of TGF-β1 and βig-h3 expression, and this is associated with attenuated tubulointerstitial fibrosis in chronic CsA nephrotoxicity.

ObjectiveThis study investigated the preventable death rate in Daegu, South Korea, and assessed affecting factors and preventable factors in order to improve the treatment of regional trauma patients.MethodsAll traumatic deaths between January 2012 and December 2012 in 5 hospitals in Daegu were analyzed by panel review, which were classified into preventable and non-preventable deaths. We determined the factors affecting trauma deaths and the preventable factors during trauma care.ResultsThere were overall 358 traumatic deaths during the study period. Two hundred thirty four patients were selected for the final analysis after excluding cases of death on arrival, delayed death, and unknown causes. The number of preventable death was 59 (25.2%), which was significantly associated with mode of arrival, presence of head injury, date, and time of injury. A multivariate analysis revealed that preventable death was more likely when patients were secondly transferred from another hospital, visited hospital during non-office hour, and did not have head injuries. The panel discovered 145 preventable factors, which showed that majority of factors occurred in emergency departments (49.0%), and were related with system process (76.6%).ConclusionThe preventable trauma death rate in Daegu was high, and mostly process-related.

Fructose-induced hepatic miR-33 suppression lead to fatty liver via upregulation of SREBP1. Additionally, fructose-induced hepatic ferroptosis may cause a spill-over of miR-33 into blood stream, which could be a potential serological biomarker for fructose-induced NAFLD.

Saccharomyces boulardii is the only probiotic yeast with US Food and Drug Administration approval. It is routinely used to prevent or treat acute diarrhea and other gastrointestinal disorders, including the antibiotic-associated diarrhea caused by Clostridium difficile infections. The formation of reactive oxygen species (ROS), specifically H 2 O 2 during normal aerobic metabolism, contributes to programmed cell death and represents a risk to the viability of the probiotic microbe. Moreover, a loss of viability reduces the efficacy of the probiotic treatment. Therefore, inhibiting the accumulation of ROS in the oxidant environment could improve the viability of the probiotic yeast and lead to more efficacious treatment. Here, we provide evidence that supplementation with a non-reducing disaccharide, namely trehalose, enhanced the viability of S. boulardii exposed to an oxidative environment by preventing metacaspase YCA1-mediated programmed cell death through inhibition of intracellular ROS production. Our results suggest that supplementation with S. boulardii together with trehalose could increase the viability of the organism, and thus improve its effectiveness as a probiotic and as a treatment for acute diarrhea and other gastrointestinal disorders.