Acute kidney injury (AKI), characterized by an increase of serum creatinine and urea, is a severe complication of severe acute pancreatitis (SAP) with high mortality. Endoplasmic reticulum (ER) stress has been considered as a key pathologic process in AKI. Chaiqin chengqi decoction (CQCQD) is an effective Chinese medicine formula for SAP treatment in China and has been used for many years. Our goal is to explore the role of CQCQD on ER stress of AKI in experimental SAP. SAP was induced in rats by retrograde duct injection of 5% sodium taurocholate (NaTC, 1 ml/kg), sham operation (SO) rats simultaneously received saline infusion. Intraperitoneal injection of 4-PBA (50 mg/kg, once a day for three days before the surgery) or intragastric gavage of CQCQD (1 g/kg, 2 hourly × 3 after disease induction) was used to treat SAP rats. All animals were humanely sacrificed 12 h after disease induction. Histopathology scores of kidney and pancreas; serum biochemical indices and kidney protein levels of ER stress and apoptosis markers were assessed. Tubular epithelial cell line (HK-2) was treated either with TNF-α (10 ng/ml) or IL-6 (10 ng/ml) for 12 h plus either 4-PBA (0.1 M) or CQCQD (1 mg/ml) for in vitro study. Cell viability and markers of ER stress and apoptosis were measured. Ductal perfusion of NaTC caused significant increases in serum lipase, amylase and pancreatic histopathology (inflammatory cell infiltration, interstitial edema, and acinar cell necrosis). Kidney histopathology (tubular dilation, brush border loss, little tubular necrosis, and cast formation), serum creatine and urea levels were raised when compared with the SO group. Moreover, apoptotic cell death markers (caspase-9, cleaved-caspase-3, and TUNEL) and kidney ER stress proteins (BIP, IRE1-α, XBP1s, and CHOP) were elevated after NaTC administration. 4-PBA and CQCQD significantly alleviated histopathological changes of kidney and pancreas, inflammatory cytokines, biochemical markers of AKI, ER stress proteins and apoptotic cell death markers. They also protected HK-2 cells from injury of TNF-α and IL-6, and alleviated both ER stress and apoptosis proteins in vitro. CQCQD may alleviate SAP-related AKI by inhibiting ER stress-related apoptosis.
14 March 2022 in Gastroenterology Research and Practice
Objectives. Gegen Qinlian decoction (GQD), a Chinese herbal compound, has been widely used in the treatment of ulcerative colitis (UC) in China. However, evidence from systematic reviews (SRs)/meta-analyses (MAs) of GQD in UC remains highly controversial. To collate, evaluate, and synthesize the current evidence, we carried out this study. Methods. SRs/MAs of GQD for UC were obtained from eight databases. Methodological Quality of Systematic Reviews 2 (AMSTAR-2) was utilized to appraise the methodological quality, Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) for reporting quality, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for evidence quality. Results. Four eligible SRs/MAs were obtained. According to AMSTAR 2, all SRs/MAs were graded as critically low quality. According to PRISMA checklist, all SRs/MAs failed to report the information of protocol and registration. With GRADE, no outcome measure with high-quality evidence was found, and the evidence quality for outcome measures was in the moderate to critically low levels. Conclusions. GQD with conventional medicine (CM) seems to be more effective in UC than CM alone. This finding provides a new alternative strategy for the treatment of UC. However, owing to the limitations of the evidence provided by the included SRs/MAs, this conclusion must be treated with caution.
Gastric cancer (GC) is with high mortality and morbidity. The GC morbidity of males is twice as high as that of females. G-protein estrogen receptor (GPER) bears on this phenomenon. Networks and experiments assessed the GPER expression in different validity and content. The evidence-based practice involved accessing the clinical relevance of GPER by UALCAN and Kaplan-Meier plotter. Enrichment analyses contributed to guide further experimental validations. Activation of the NF-κB/ROS/Apoptosis pathway was analyzed by WB, immunofluorescence (IF), microplate reader and flow cytometry. TISIDB and TIMER identified the immune infiltration investigations, with credibility boosted by the Kaplan-Meier plotter. The appraisers revealed that GPER significantly decreased in GC at both gene and protein levels with highly approved prognosis value (P < 0.05). GPER was a significant fate determinant governing the inner part of gastric glands. NF-κB pathway and the following ROS in gastric cells were activated after MNU stimulation (20 μM, 24 h), and the GPER antagonist G15 strengthened the effect of MNU. Furthermore, GPER expression positively correlated with immune cells and various immune markers in GC patients, with highly approved clinical relevance. For example, type-2 helper cells enriched GC patients had a lower survival rate in the GPER-high expression group (P < 0.05). We demonstrated that GPER governs the GC progression by activating the NF-κB/ROS/Apoptosis pathway in gastric cells and regulating the immune environment around them.
Objectives. Helicobacter pylori (H. pylori) immunoglobulin G (IgG) seropositivity is prevalent, but its correlation with homocysteine (Hcy), a biomarker of vascular risk events, is unclear. This study is aimed at exploring the correlation of H. pylori IgG seropositivity and plasma Hcy levels in adults. Methods. Data was obtained from the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Hcy was measured by the Abbott homocysteine assay, and H. pylori IgG was measured by enzyme-linked immunosorbent assays. The weighted multiple logistic regression analyses with adjustments for potential confounders were conducted. Subgroup analyses stratified by gender, age, and race were performed. Results. A total of 4029 subjects aged 20-85 years were included. Population prevalence of H. pylori IgG seropositivity was 44.7% in the overall population with higher prevalence found in those with older age, Mexican Americans, lower education, and lower household income. Levels of plasma Hcy were not elevated in those with H. pylori IgG seropositivity versus seronegativity (β -0.120 (-0.438, 0.199) ). This difference was not significant after stratifying by gender and age. However, in the subgroup analyses stratified by race, a negative correlation between H. pylori seropositivity and plasma Hcy levels was observed in Mexican Americans (β -0.802 (-1.253, -0.352) ). Conclusions. H. pylori IgG seropositivity was not associated with plasma Hcy levels in the general population, but there may be a negative correlation in Mexican Americans. These findings provide new insights to advance the research of the link between plasma Hcy levels and stomach health.