Oxidative stress is a major risk factor for neurodegenerative disease. The Kelch-like ECH-associated protein 1 (Keap1)−nuclear factor erythroid 2 related factor 2 (Nrf2)−antioxidant response element (ARE) pathway is one of the most potent defensive systems against oxidative stress. Selenepezil, a selenium-based compound, was previously found to exhibit excellent acetylcholinesterase (AChE) inhibition, to mimic endogenous glutathione peroxidase (GPx) activity, and to exhibit scavenging activity for hydrogen peroxide in vitro. However, none of these activities have been evaluated in a cellular model, and detailed molecular mechanisms are not elucidated. Moreover, whether selenepezil ameliorates memory deficits in vivo remains unknown. This study validated the cytoprotective effect of selenepezil against 6-hydroxydopamine (6-OHDA)-or H 2 O 2 -induced SH-SY5Y cell damage via alleviation or neutralization of intracellular microtubule disorder, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and cell apoptosis. Our study clearly demonstrated that selenepezil pretreatment exhibited remarkable cytoprotective effect in a Nrf2-dependent manner via activating the Keap1−Nrf2−ARE pathway and stimulating the transcription of Nrf2−ARE-regulated cytoprotective genes. Moreover, selenepezil•HCl exerts neuroprotective effect via attenuating Aβ-induced cognitive impairment in Alzheimer's disease (AD) rat and was more active than the reference drug donepezil. In summary, selenepezil deserves further consideration for AD therapy.

Background. Serum chitinase-3-like protein 1 (CHI3L1) is a promising marker for diagnosing liver fibrosis. This meta-analysis was carried out to assess the diagnostic performance of serum CHI3L1 for the estimation of liver fibrosis. Methods. Systematic searches were performed on PubMed, Embase, Web of Science, Scopus, the Cochrane Library, Google Scholar, Sinomed, the China National Knowledge Infrastructure (CNKI), the Chinese Medical Journal Database, and the Wanfang databases for available studies. The primary studies were screened strictly according to inclusion and exclusion criteria, and sensitivity, specificity, and other measures of accuracy of serum CHI3L1 for evaluating liver fibrosis were pooled with 95% confidence intervals. I 2 was calculated to assess heterogeneity, and sources of heterogeneity were explored by subgroup analysis. Deeks’ test was used to assess for publication bias, and likelihood ratio was used to determine posttest probability. Results. Our research integrated 11 articles, accounting for 1897 patients older than 18 years old. The pooled sensitivity and specificity for significant fibrosis, advanced fibrosis, and cirrhosis were 0.79 and 0.82 with an area under the receiver operating characteristic curve (AUC) of 0.85, 0.81 and 0.83 with an AUC of 0.91, and 0.72 and 0.74 with an AUC of 0.85, respectively. Random-effects models were used to assess for significant heterogeneity, and subgroup analysis showed that age and aetiology of included patients were likely sources of heterogeneity. No potential publication bias was found for serum CHI3L1 in the diagnosis of significant fibrosis, advanced fibrosis, or cirrhosis, and posttest probability was moderate. Conclusion. Measurement of serum CHI3L1 is a feasible diagnostic tool for liver fibrosis.

No abstract

Background: The assessment of liver fibrosis has been a critical component in the clinical management of liver diseases. We performed a meta-analysis to evaluate serum Golgi protein 73 (GP73) in the diagnosis of liver fibrosis. Methods: A literature search was performed in eight databases until July 13, 2022. We searched strictly studies according to inclusion and exclusion criteria, extracted data, and than assessed quality. We pooled the sensitivity, specificity and other diagnostic estimates of serum GP73 to assess liver fibrosis. Moreover, publication bias, threshold analysis, sensitivity analysis, meta-regression, subgroup analysis and post-test probability were evaluated. Results: Our research integrated 16 articles including 3676 patients. Potential publication bias and threshold effect were not found. The pooled sensitivity, specificity, and area under the curve (AUC) of the summary receiver operating characteristic curve were 0.63, 0.79 and 0.818 for significant fibrosis; 0.77, 0.76 and 0.852 for advanced fibrosis; and 0.80, 0.76 and 0.894 for cirrhosis, respectively. The aetiology was one of important sources of heterogeneity. Conclusion: Serum GP73 was a feasible diagnostic marker for liver fibrosis, which is of great significance for the clinical management of liver diseases.