Background H. pylori infection induces reactive oxygen species- (ROS-) related DNA damage and activates the PI3K/Akt pathway in gastric epithelial cells. N-Acetylcysteine (NAC) is known as an inhibitor of ROS; the role of NAC in H. pylori-related diseases is unclear. Aim The aim of this study was to evaluate the role of ROS and the protective role of NAC in the pathogenesis of H. pylori-related diseases. Method An in vitro coculture system and an in vivo Balb/c mouse model of H. pylori-infected gastric epithelial cells were established. The effects of H. pylori infection on DNA damage and ROS were assessed by the comet assay and fluorescent dichlorofluorescein assay. The level of PI3K/Akt pathway-related proteins was evaluated by Western blotting. The protective role of N-acetylcysteine (NAC) was also evaluated with in vitro and in vivo H. pylori infection models. Results The results revealed that, in vitro and in vivo, H. pylori infection increased the ROS level and induced DNA damage in gastric epithelial cells. NAC treatment effectively reduced the ROS level and inhibited DNA damage in GES-1 cells and the gastric mucosa of Balb/c mice. H. pylori infection induced ROS-mediated PI3K/Akt pathway activation, and NAC treatment inhibited this effect. However, the gastric mucosa pathological score of the NAC-treated group was not significantly different from that of the untreated group. Furthermore, chronic H. pylori infection decreased APE-1 expression in the gastric mucosa of Balb/c mice. Conclusions An increased ROS level is a critical mechanism in H. pylori pathogenesis, and NAC may be beneficial for the treatment of H. pylori-related gastric diseases linked to oxidative DNA damage.
AIMTo explore the natural history of covert hepatic encephalopathy (CHE) in absence of medication intervention.METHODSConsecutive outpatient cirrhotic patients in a Chinese tertiary care hospital were enrolled and evaluated for CHE diagnosis. They were followed up for a mean of 11.2 ± 1.3 mo. Time to the first cirrhosis-related complications requiring hospitalization, including overt HE (OHE), resolution of CHE and death/transplantation, were compared between CHE and no-CHE patients. Predictors for complication(s) and death/transplantation were also analyzed.RESULTSA total of 366 patients (age: 47.2 ± 8.6 years, male: 73.0%) were enrolled. CHE was identified in 131 patients (35.8%). CHE patients had higher rates of death and incidence of complications requiring hospitalization, including OHE, compared to unimpaired patients. Moreover, 17.6% of CHE patients developed OHE, 42.0% suffered persistent CHE, and 19.8% of CHE spontaneously resolved. In CHE patients, serum albumin < 30 g/L (HR = 5.22, P = 0.03) was the sole predictor for developing OHE, and blood creatinine > 133 μmol/L (HR = 4.75, P = 0.036) predicted mortality. Child-Pugh B/C (HR = 0.084, P < 0.001) and OHE history (HR = 0.15, P = 0.014) were predictors of spontaneous resolution of CHE.CONCLUSIONCHE exacerbates, persists or resolves without medication intervention in clinically stable cirrhosis. Triage of patients based on these predictors will allow for more cost-effect management of CHE.
Liver fibrosis is a reversible wound‐healing response that occurs after liver injury. NADPH oxidases (NOXs) and reactive oxygen species (ROS) which are expressed in hepatocytes (HCs), hepatic stellate cells (HSCs), and Kupffer cells (KCs) play an important role in the development of hepatic fibrosis. In in vitro studies, we had shown that ursolic acid (UA) could reverse liver fibrosis by inhibiting the activation of NOX‐mediated fibrotic signaling networks in HSCs. In this study, we verified that UA could alleviate CCl4‐induced liver fibrosis by reducing the expression of NOXs/ROS in HCs, HSCs, KCs. Meanwhile, the phagocytic index α and clearance index K which represent phagocytosis of KCs were unchanged. Together, all our data demonstrated that UA induced the proliferation of HCs, promoted apoptosis in HSCs, and prevented activation of KCs in vivo by reducing the expression of NOXs/ROS in HCs, HSCs, KCs. Besides, UA had no effect on the host defense function.
between esophageal GISTs and LMs, 5/5 vs 0/24, 3/5 vs 0/24 (P < 0.005). All leiomyomas and leiomyosarcomas were positive for SMA, and desmin. Among 5 cases of esophageal GISTs, 2 cases were SMA positive, and 1 case was desmin positive. The differences in positive rates and expression intensity of SMA and desmin were significant between esophageal LMs and GISTs, 24/24 vs 2/5, 24/24 vs 1/5 (P < 0.005). C O N C L U S I O N :T h e m o s t c o m m o n e s o p h a g e a l mesenchymal tumors are leiomyomas, and esophageal GISTs are less common. Most of esophageal LMs and GISTs are benign. Endoscopy and EUS are the effective methods to diagnose esophageal mesenchymal tumors and they can provide useful information for the treatment of these tumors. However, they cannot exactly differentiate esophageal GISTs from LMs. Pathological, especially immunohistochemical features are useful to differentiate GISTs from leiomyomas.© 2007 The WJG Press. All rights reserved. Key words:Esophageal mesenchymal tumors; Gastrointestinal stromal tumors; Leiomyomas; Endoscopy; Pathology; Immunohistochemistry Z h u X , Z h a n g X Q, L i B M , Xu P, Z h a n g K H , C h e n J. INTRODUCTIONTraditionally, the gastrointestinal mesenchymal tumors (GIMTs) have been almost unifor mly classified as gastrointestinal leiomyomas (LMs). However, recent evidence indicates that most mesenchymal tumors of the gastrointestinal tract are gastrointestinal stromal tumors (GISTs) [1] . It is difficult to differentiate esophageal GISTs from LMs because of their similar appearance. Abstract AIM: To study the endoscopic, pathological and immunohistochemical features of esophageal mesenchymal tumors. METHODS:Tw e n ty-n i n e p a t i e n t s d i a g n o s e d a s e s o p h a g e a l m y s e n c h y m a l t u m o r s b y e l e c t r o n i c endoscopy and endoscopic ultrasound (EUS) were observed under light microscopes, and all tissues were stained by the immunohistochemical method. The expression of CD117, CD34, SMA and desmin were measured by staining intensity of cells and positive cell ratios. RESULTS:Endoscopically, esophageal gastrointestinal stromal tumors (GISTs) and leiomyomas (LMs) had similar appearances, showing submucosal protuberant lesions. They all showed low echo images originated from the muscularis propria or muscularis mucosa on EUS. Endoscopy and EUS could not exactly differentiate esophageal GISTs from LMs. Microscopically, there were two kinds of cells: spindle cell type and epitheloid cell type in esophageal GISTs. Leiomyomas and leiomyosarcomas were only of spindle cell type. One malignancy was found in five cases of esophageal GISTs, and one malignancy in 24 cases of leiomyomas and leiomyosarcomas. Using Fisher's exact method, the differences of malignant lesion proportion were not significant between esophageal LMs and GISTs, 1/5 vs 1/24 (P > 0.05). All cases of esophageal GISTs were positive for CD117, and 3 cases were also positive for CD34. The 24 cases of leiomyomas and leiomyosarcomas were all negative for CD117 and CD34. The differen...
Background Studies have shown that both NOX4 and RhoA play essential roles in fibrosis and that they regulate each other. In lung fibrosis, NOX4/ROS is located upstream of the RhoA/ROCK1 signaling pathway, and the two molecules are oppositely located in renal fibrosis. Currently, no reports have indicated whether the above mechanisms or other regulatory mechanisms exist in liver fibrosis. Objectives To investigate the effects of the NOX4/ROS and RhoA/ROCK1 signaling pathways on hepatic stellate cell (HSC)-T6 cells, the interaction mechanisms of the two pathways, and the impact of UA on the two pathways to elucidate the role of UA in the reduction of hepatic fibrosis and potential mechanisms of HSC-T6 cell proliferation, migration, and activation. Methods Stable cell lines were constructed using the lentiviral transduction technique. Cell proliferation, apoptosis, migration, and invasion were examined using the MTS, TdT-mediated dUTP nick-end labeling, cell scratch, and Transwell invasion assays, respectively. The DCFH-DA method was used to investigate the ROS levels in each group. RT-qPCR and western blotting techniques were utilized to assess the mRNA and protein expression in each group. CoIP and the Biacore protein interaction analysis systems were used to evaluate protein interactions. Results The NOX4/ROS and RhoA/ROCK1 signaling pathways promoted the proliferation, migration, and activation of HSCs. UA inhibited cell proliferation, migration, and activation by inhibiting the activation of the two signaling pathways, but the mechanism of apoptosis was independent of these two pathways. The NOX4/ROS pathway was upstream of and positively regulated the RhoA/ROCK1 pathway in HSCs. No direct interaction between the NOX4 and RhoA proteins was detected. Conclusion The NOX4/ROS and RhoA/ROCK1 signaling pathways are two critical signaling pathways in a series of behavioral processes in HSCs, and NOX4/ROS regulates RhoA/ROCK1 through an indirect pathway to control the activation of HSCs. Additionally, NOX4/ROS and RhoA/ROCK1 constitute a new target for UA antifibrosis treatment.
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