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Objectives

Impaired intestinal barrier function has been demonstrated in the pathophysiology of diarrhea-predominant irritable bowel syndrome (IBS-D). This study aimed to describe the intestinal ultrastructural findings in the intestinal mucosal layer of IBS-D patients.

Methods

In total, 10 healthy controls and 10 IBS-D patients were analyzed in this study. The mucosa of each patient’s rectosigmoid colon was first assessed by confocal laser endomicroscopy (CLE); next, biopsied specimens of these sites were obtained. Intestinal tissues of IBS-D patients and healthy volunteers were examined to observe cellular changes by transmission electron microscopy (TEM).

Results

CLE showed no visible epithelial damage or inflammatory changes in the colonic mucosa of IBS-D compared with healthy volunteers. On transmission electron microscopic examination, patients with IBS-D displayed a larger apical intercellular distance with a higher proportion of dilated (>20 nm) intercellular junctional complexes, which was indicative of impaired mucosal integrity. In addition, microvillus exfoliation, extracellular vesicle as well as increased presence of multivesicular bodies were visible in IBS-D patients. Single epithelial cells appeared necrotic, as characterized by cytoplasmic vacuolization, cytoplasmic swelling, and presence of autolysosome. A significant association between bowel habit, frequency of abdominal pain, and enlarged intercellular distance was found.

Conclusion

This study showed ultrastructural alterations in the architecture of intestinal epithelial cells and intercellular junctional complexes in IBS-D patients, potentially representing a pathophysiological mechanism in IBS-D.

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Abstract

Renal injury is reported to have a high mortality rate. Additionally, there are several limitations to current conventional treatments that are used to manage it. This study evaluated the protective effect of hesperidin against ischemia/reperfusion (I/R)-induced kidney injury in rats. Renal injury was induced by generating I/R in kidney tissues. Rats were then treated with hesperidin at a dose of 10 or 20 mg/kg intravenously 1 day after surgery for a period of 14 days. The effect of hesperidin on renal function, serum mediators of inflammation, and levels of oxidative stress in renal tissues were observed in rat kidney tissues after I/R-induced kidney injury. Moreover, protein expression and mRNA expression in kidney tissues were determined using Western blotting and RT-PCR. Hematoxylin and eosin (H&E) staining was done for histopathological observation of kidney tissues. The data suggest that the levels of blood urea nitrogen (BUN) and creatinine in the serum of hesperidin-treated rats were lower than in the I/R group. Treatment with hesperidin also ameliorated the altered level of inflammatory mediators and oxidative stress in I/R-induced renal-injured rats. The expression of p-IκBα, caspase-3, NF-κB p65, Toll-like receptor 4 (TLR-4) protein, TLR-4 mRNA, and inducible nitric oxide synthase (iNOS) was significantly reduced in the renal tissues of hesperidin-treated rats. Histopathological findings also revealed that treatment with hesperidin attenuated the renal injury in I/R kidney-injured rats. In conclusion, our results suggest that hesperidin protects against renal injury induced by I/R by involving TLR-4/NF-κB/iNOS signaling.

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The aim of this study was to investigate postprandial effects of two Chinese liquors on s elected cardiovascular disease risk factors in humans. Sixteen healthy men were randomized into three groups in a three-way crossover study: tea-flavor liquor (TFL), traditional Chinese liquor (TCL) and water control (WC). Every subject consumed 60 mL of either liquor (45% (v/v) ethanol) or water together with a high-fat meal, respectively. Compared with baseline, serum uric acid was significantly increased in TFL group (0.5-hour: P = 0.012; 1-hour: P = 0.001; 2-hour: P = 0.008) and it was significantly decreased in WC group (1-hour: P = 0.001; 2-hour: P = 0.001; 4-hour: P < 0.001), while uric acid was non-significantly increased in the TCL group. High-sensitive C-reactive protein (hs-CRP) was significantly increased in the TCL (P = 0.014) and WC (P = 0.008) groups at postprandial 4 hours compared with baseline. There was no significant difference between groups during the postprandial period for these two parameters or other biochemical parameters. In conclusion, both liquors increased postprandial uric acid, and no significant difference was observed for the effects of TFL and TCL on the measured biochemical parameters.

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The aim of the present study was to investigate whether co-administration of nerve growth factor (NGF) and butyrate regulates vanilloid receptor 1 (VR1) and substance P (SP) levels in cultures of rat dorsal root ganglion (DRG) neurons. DRG was dissected out from embryonic 15-day-old Wistar rat and cultured as dissociated cells for 2 days then exposed to NGF (10 ng/ml), butyrate (1 mmol/L), NGF (10 ng/ml) plus butyrate (1 mmol/L) for another 4 days. The neurons cultured continuously in media served as normal control. After that, the cultures were processed for detecting expression of mRNA for VR1 and SP in DRG neurons by RT-PCR, and expression of VR1 protein by Western blot. SP basal release levels were measured by radioimmunoassay (RIA). Capsaicin-evoked SP release was measured by RIA after stimulation with capsaicin (100 nmol/L) for 10 minutes. The neurons exposed to vehicle solution served as vehicle control. Either NGF (10 ng/ml) or butyrate (1 mmol/L) promoted expression of SP mRNA, VR1 mRNA, and VR1 protein in DRG neurons and capsaicin-evoked SP release from DRG neurons. Co-administration of NGF and butyrate showed a synergistic effect on expression of VR1 mRNA, and VR1 protein in DRG neurons and capsaicin-evoked SP release from DRG neurons and a ceiling effect on SP mRNA expression. The elevation of SP mRNA, VR1 mRNA, and VR1 protein promoted by NGF and/or butyrate may be associated with increases of SP release evoked by capsaicin. The mechanisms of the effects of co-administration of NGF and butyrate should be clarified by further study.

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