Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

Statins for the Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become more common as a result of changes in dietary structure and lifestyle. It is now the most common chronic liver disease both in China and in the rest of the world (NAFLD is also of concern in European and American countries). STUDY QUESTION: NAFLD and nonalcoholic steatohepatitis (NASH) are different stages of fatty liver disease. There is currently a lack of consensus on the use of statin therapy. We conducted a meta-analysis to evaluate the efficacy of statins in the treatment of NAFLD and NASH. DATA SOURCES: PubMed, MEDLINE, and other literature databases, including the Cochrane Library, were searched. STUDY DESIGN: The primary inclusion criteria for studies included the use of different statins for the treatment of NAFLD and NASH. Two reviewers identified documents and extracted data based on predetermined inclusion and exclusion criteria. To examine heterogeneity and publication bias, all analyses were undertaken using the complete meta-analysis Review Manager 5.3 software. RESULTS: The meta-analysis includes 4 randomized controlled studies involving 169 participants with NAFLD and NASH. In comparison with the control group, statins dramatically lowered serum levels of aspartate transaminase, alanine aminotransferase (ALT), triglycerides, and cholesterol. CONCLUSIONS: The use of statins in the treatment of NAFLD and NASH has shown significant histological and biochemical benefits, especially in patients with hyperlipidemia. To assess the effects of statins on NAFLD and NASH, more large research and randomized placebo-controlled trials are needed.

SQSTM1/p62 is a prognostic molecular marker and potential therapeutic target for pancreatic neuroendocrine tumours.

BACKGROUND: There have been few studies on the role of autophagy in pancreatic neuroendocrine tumours (PNETs). SQSTM1/p62 (also called Sequestosome 1) is a potential autophagy regulator, and its biological roles and clinical significance in PNETs remain poorly understood. PURPOSE: The purpose of this study was to evaluate the clinical significance of SQSTM1/p62 in human PNET specimens and to evaluate its potential value as a therapeutic target by studying its biological function in PNET cell lines. METHODS: SQSTM1/p62 protein expression was assessed in 106 PNET patient specimens by immunohistochemistry, and the relationship between SQSTM1/p62 protein expression and the clinicopathological features of PNETs in patients was analysed. The proliferation, invasion and apoptosis of SQSTM1/p62-knockdown QGP-1 and INS-1 cells were assessed by the MTT assay, a Transwell assay and flow cytometry. Cell autophagy was assessed by western blotting and mCherry-GFP-LC3B. RESULTS: The protein expression of SQSTM1/p62 in PNET patient specimens was significantly correlated with tumour recurrence (p = 0.005) and worse prognosis (log rank p = 0.020). Downregulation of the SQSTM1/p62 gene inhibited tumour cell proliferation and migration and induced PNET cell death. Downregulation of SQSTM1/p62 activated autophagy in PNET cell lines but blocked autophagic flow. Knockdown of the SQSTM1/p62 gene inhibited mTOR phosphorylation. CONCLUSION: The SQSTM1/P62 protein could be an independent prognostic marker for PNET patients. Downregulating SQSTM1/P62 can inhibit PNET progression, inhibit mTOR phosphorylation and block autophagic flow.

Augmenter of liver regeneration ameliorates ischemia-reperfusion injury in steatotic liver via inhibition of the TLR4/NF-κB pathway.

Hepatocytes from donors with preexisting hepatic steatosis exhibited increased sensitivity to ischemia-reperfusion injury (IRI) during liver transplantation. Augmenter of liver regeneration (ALR) protected the liver against IRI, but the mechanism was not clarified. Therefore, the hypothesis that ALR attenuated IRI in steatotic liver by inhibition of inflammation and downregulation of the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway was examined. C57BL/6 mice were subjected to a methionine-choline-deficient (MCD) diet to induce liver steatosis. Mice were transfected with ALR-containing adenovirus 3 days prior to partial warm hepatic IRI. After 30 min of ischemia and 6 h of reperfusion injury, liver function, hepatic injury, the inflammatory response and TLR4/NF-κB signaling pathway activation were assessed. ALR maintained liver function and alleviated hepatic injury as indicated by the decreased levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), preserved hepatic structure and reduced apoptosis. ALR also reduced the IRI-induced inflammatory response by suppressing Kupffer cell activation, inhibiting neutrophil chemotaxis and reducing inflammatory cytokine production. Further investigation using reverse transcription-quantitative PCR, western blotting and immunohistochemistry revealed that ALR reduced TLR4/NF-κB signaling pathway activation, which led to a decreased synthesis of inflammatory cytokines. ALR functioned as a regulator of the IRI-induced inflammatory response by suppressing the TLR4/NF-κB pathway, which supports the use of ALR in therapeutic applications for fatty liver transplantation.

Alleviation of Ischemia-Reperfusion Injury in Liver Steatosis by Augmenter of Liver Regeneration Is Attributed to Antioxidation and Preservation of Mitochondria.

BACKGROUND: Fatty liver is one of the major impediments to liver surgery and liver transplantation because steatotic hepatocytes are more susceptible to ischemia-reperfusion injury (IRI). In this study, the effects of augmenter of liver regeneration (ALR) on hepatic IRI in steatotic mice were investigated. METHODS: In vivo, liver steatosis of mice was induced by feeding a methionine-choline-deficient diet for 2 weeks. Three days before hepatic partial warm IRI, mice were transfected with the ALR-containing adenovirus. In an in vitro study, the protective effect of ALR on steatotic HepG2 cells was analyzed after hypoxia/reoxygenation (HR) treatment. RESULTS: The transfection of the ALR gene into steatotic mice attenuated liver injury, inhibiting hepatic oxidative stress, increasing antioxidation capacities, promoting liver regeneration, and consequently suppressing cell apoptosis/death. Furthermore, resistance to HR injury was notably increased in ALR-transfected cells compared with the vector-transfected cells. The HR-induced rise in the mitochondrial reactive oxygen species was reduced, and cellular antioxidant activities were enhanced. The ALR transfection prevented cells from apoptosis, which can be attributed to the preservation of the mitochondrial membrane potential, enhancement of oxygen consumption rate and production of adenosine triphosphate. CONCLUSIONS: ALR protects steatotic hepatocytes from IRI by attenuating oxidative stress and mitochondrial dysfunction, as well as improving antioxidant effect. ALR may be used as a potential therapeutic agent when performing surgery and transplantation of steatotic liver.