Xiangshao Decoction alleviates gastric mucosal injury through NRF2 signaling pathway and reduces neuroinflammation in gastric ulcer rats.

BACKGROUND: A type of gastric mucosal injury disease known as gastric ulcer (GU) is clearly connected to the aberrant release of gastric acid. Traditional botanicals have the potential for anti-inflammation, anti-oxidation, and other multitarget therapies, as well as being safe. PURPOSE: The purpose of this study was to investigate the potential effects of Xiangshao Decoction (XST) on gastric mucosal injury in GU rats and to explore the possible molecular mechanisms. METHODS: After identifying XST and its components, we established GU rats and cell models by acetic acid and H2O2 induction, respectively. SOD and MDA indexes in gastric tissues and GES-1 cells, and the serum levels of BDNF, ALT, and AST were detected with relevant kits, changes of the gastric mucosa were observed and recorded, and gastric tissue pathology was observed by H&E staining. The production of ROS in GES-1 cells was detected by fluorescent probes. Cell transfection techniques were used to silence or overexpress NRF2. The mRNA or protein expressions of NRF2, KEAP1, NQO1, HO-1, SOD2, IL-1ß, IL-6, TNF-α, IBA1, GFAP, or γ-H2AX in the gastric tissue, hippocampus, or GES-1 cells were measured via qPCR, Western blot, immunofluorescence staining, or immunohistochemical staining. RESULTS: The pH of gastric acid, ulcer score, and pathological damage score in GU rats could be reversed by XST administration. Expressions of IL-1ß, IL-6, and TNF-α in the gastric mucosal tissues and the hippocampus of GU rats after administration of XST were down. Expressions of NRF2, NQO1, HO-1, SOD2, etc. in the gastric mucosal tissues and BDNF in the hippocampus were up-regulated. The production of ROS and MDA and the expressions of IL-1ß, IL-6, TNF-α, and KEAP1 in H2O2-induced GES-1 cells were significantly reduced after XST intervention, while the activities of SOD and the expression of NRF2, NQO1, HO-1, and SOD2 were significantly increased, and these could be blocked by silencing NRF2 expression. CONCLUSIONS: XST can improve oxidative stress injury and inflammatory response in GU rats and cell models, and its mechanism is mediated by the NRF2 signaling pathway.

Adverse events of vonoprazan in the treatments of acid-related diseases: a systematic review and meta-analysis.

BACKGROUND AND AIMS: vonoprazan, a novel potassium-competitive acid blocking agent, has better clinical outcomes in the treatment of acid-related diseases. However, some adverse events have been associated with vonoprazan for the treatment of acid-associated diseases. Therefore, this systematic review and meta-analysis aimed to explore the safety and tolerability of vonoprazan for acid-associated diseases. METHODS: electronic databases were retrieved to determine randomized controlled trials (RCTs) of vonoprazan for acid-associated diseases with any adverse effects and discontinuation. RESULTS: this systematic review and meta-analysis conforming to the selection criteria included 18 RCTs with a total of 7,932 participants. Compared with proton pump inhibitors, oral vonoprazan treatment showed no significant increase in the incidence of adverse effects (95 % CI = 0.987-1.095, p = 0.141). Diarrhea or loose stools analysis showed that there was a statistically significant difference between vonoprazan and proton pump inhibitors (PPIs) treatment (95 % CI = 0.661-0.966, p = 0.021). However, there was no significant difference in constipation, rash or eruption, nausea or vomiting, bloating or abdominal pain, dysgeusia, nasopharyngitis, neurological disorders, upper respiratory tract infection and abnormal investigations between vonoprazan and PPIs treatment. CONCLUSION: vonoprazan, which has better tolerability and safety, may significantly decrease diarrhea and loose stools in acid-related patients compared with PPIs. Our meta-analysis led to safer strategies for treating acid-related diseases. More high-quality studies with larger sample sizes are needed to further elucidate its efficacy and safety.

Atractylodes-I Overcomes the Oxidative Stress-induced Colonic Mucosal Epithelial Cells Dysfunction to Prevent Irritable Bowel Syndrome Via Modulating the miR-34a-5p-LDHA Signaling Pathway.

BACKGROUND: Irritable bowel syndrome (IBS) is a known brain-gut disorder. Currently, the molecular and cellular mechanisms of IBS remain unclear. Atractylenolide-I (ATL-I) is a majorly bioactive component extracted from Rhizoma Atractylodes Macrocephalae. METHODS: Studies have revealed that ATL-I functioned as an anti-tumor drug in various cancers. However, the effects and molecular mechanisms of ATL-I on the pathological processes of colonic mucosal epithelial cells (CMECs) during IBS remain unclear. This study reports ATL-I effectively alleviated the oxidative stress-induced colonic mucosal epithelial cell dysfunction. In colonic mucosal tissues from IBS patients, we detected upregulated miR-34a-5p and suppressed glucose metabolism enzyme expressions. Under H2O2 treatment which mimics in vitro oxidative stress, miR-34a-5p was induced and glucose metabolism was inhibited in the colon mucosal epithelial cell line, NCM460. Meanwhile, ATL-I treatment effectively overcame the oxidative stress-induced miR-34a- 5p expression and glucose metabolism in NCM460 cells. RESULT: By bioinformatics analysis, Western blot and luciferase assay, we illustrated that miR-34a-5p directly targeted the 3'UTR region of glucose metabolism key enzyme, lactate dehydrogenase-A (LDHA) in colonic mucosal epithelial cells. Rescue experiments validated that miR-34a-5p inhibited glucose metabolism by targeting LDHA. Finally, we demonstrated that ATL-I treatment reversed the miR-34a-5p-inhibited glucose metabolism and -exacerbated colonic mucosal epithelial cell dysfunction under oxidative stress by modulating the miR-34a-5p-LDHA pathway. CONCLUSION: Summarily, our study reports the roles and mechanisms of ATL-I in the oxidative stress-induced colonic mucosal epithelial cell dysfunction during IBS through regulating the miR-34a-5p-LDHA-glucose metabolism axis.

Adverse events of vonoprazan in the treatments of acid-related diseases: a systematic review and meta-analysis

Background and aims: vonoprazan, a novel potassium-competitive acid blocking agent, has better clinical outcomes in the treatment of acid-related diseases. However, some adverse events have been associated with vonoprazan for the treatment of acid-associated diseases. Therefore, this systematic review and meta-analysis aimed to explore the safety and tolerability of vonoprazan for acid-associated diseases. Methods: electronic databases were retrieved to determine randomized controlled trials (RCTs) of vonoprazan for acid-associated diseases with any adverse effects and discontinuation. Results: this systematic review and meta-analysis conforming to the selection criteria included 18 RCTs with a total of 7,932 participants. Compared with proton pump inhibitors, oral vonoprazan treatment showed no significant increase in the incidence of adverse effects (95 % CI = 0.987-1.095, p = 0.141). Diarrhea or loose stools analysis showed that there was a statistically significant difference between vonoprazan and proton pump inhibitors (PPIs) treatment (95 % CI = 0.661-0.966, p = 0.021). However, there was no significant difference in constipation, rash or eruption, nausea or vomiting, bloating or abdominal pain, dysgeusia, nasopharyngitis, neurological disorders, upper respiratory tract infection and abnormal investigations between vonoprazan and PPIs treatment. Conclusion: vonoprazan, which has better tolerability and safety, may significantly decrease diarrhea and loose stools in acid-related patients compared with PPIs. Our meta-analysis led to safer strategies for treating acid-related diseases. More high-quality studies with larger sample sizes are needed to further elucidate its efficacy and safety (AU)

Rhein Inhibits Autophagy in Rat Renal Tubular Cells by Regulation of AMPK/mTOR Signaling.

Rhubarb and its bioactive component rhein are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries. However, the potential therapeutic mechanism remains unclear. Autophagy plays an important role in CKD. However, there were some important related issues that remained unresolved in the role of autophagy in CKD and treatment by rhubarb and rhein. We designed a number of experiments to examine whether rhubarb may reduce renal fibrosis and autophagy in rats with adenine (Ade)-induced renal tubular injury, and whether rhein could affect autophagic pathways in rat renal tubular cells. We found that, autophagic activation accompanied with renal fibrosis in rats with Ade-induced renal tubular injury, and both autophagy and renal fibrosis were attenuated by rhubarb. In addition, we observed that rhein could inhibit autophagy through regulating the key molecules in the AMPK-dependent mTOR signaling pathways, as well as the Erk and p38 MAPKs signaling pathways. These findings may partly explain the therapeutic mechanisms of rhubarb and rhein in treating CKD patients in clinic, and further suggest that targeting autophagy and related signaling pathways may provide new strategies for the treatment of renal fibrosis in CKD.

[Molecular mechanisms of autophagy in regulating renal aging and interventional effects of Chinese herbal medicine].

Aging is the gradual functional recession of the living tissues or organs caused by a variety of genetic and environmental factors together. Autophagy is a process of degrading cytoplasmic components mediated by lysosomes in eukaryotic cells. Kidney is a typical target organ of aging. Autophagy regulates renal aging. Decrease in autophagy can accelerate renal aging,whereas,increase in autophagy can delay renal aging. During the process of regulating renal aging,the mammalian target of rapamycin (mTOR) and its related signaling pathways including the adenosine monophosphate activated protein kinase (AMPK)/mTOR,the phosphatidylinositol 3-kinase (PI3K)/ serine-threonine kinase(Akt)/mTOR,the AMPK/silent information regulation 1 (Sirt1) and transforming growth factor ß (TGF-ß) play the important roles in renal aging. Regulating the key signaling molecules in these pathways in vivo can control renal aging. Some Chinese herbal medicine (CHM) and their extracts with the effects of nourishing kidney or activating stasis, such as Cordyceps sinensis, curcumin and resveratrol have the beneficial effects on renal aging and/or autophagy. Therefore,revealing the pharmacological effects of CHM in anti-renal aging based on the molecular mechanisms of autophagy will become one of the development trends in the future study.

[Radionuclide scrotal imaging: an effective method for detecting varicocele].

OBJECTIVE: To evaluate radionuclide scrotal imaging (RSI) in the diagnosis of varicocele. METHODS: We performed physical examination (PE) and RSI for 126 patients with infertility for at least 12 months and seminal abnormality, obtained the scrotal blood-pool index (SBPI), observed the reflux in the spermatic vein during RSI, typed and graded varicocele by color Doppler flow imaging (CDFI) and compared the results of PE and RSI with those of CDFI. RESULTS: The rates of sensitivity and specificity of RSI in the diagnosis of varicocele (96.5% and 97.1%) were both higher than those of PE (71.7% and 69.1%). CONCLUSION: Simple, accurate and noninvasive, RSI is an effective method for the diagnosis of clinical and subclinical varicocele.