Analytical and Clinical Evaluation of a Chemiluminescent Immunoassay to Detect Serum Chitinase-3-like Protein 1 in HBV-Related Liver Diseases.

Serum chitinase-3-like protein 1 (CHI3L1) is a diagnostic marker for liver diseases, such as hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the analytical performance of a chemiluminescent immunoassay (CLIA) for the quantitative detection of CHI3L1 and its application in hepatitis B virus (HBV)-related liver diseases. The CLIA for CHI3L1 detection presented good analytical performance, with a linear range of 1.50-2000.00 ng/mL and a detection limit of 0.98 ng/mL. To evaluate its clinical application, serum CHI3L1 levels were detected in 82 patients with chronic hepatitis B (CHB) and in 21 healthy controls. The patients with CHB and HCC had higher CHI3L1 levels than the healthy controls and the patients with CHB without HCC. However, CHI3L1 levels did not change significantly with the increase in liver fibrosis stages. The area under the receiver operating characteristic curve for the diagnosis of HBV-related HCC was 0.808, representing a moderate diagnostic value. Correlation analysis revealed a significant association between CHI3L1 and alpha-fetoprotein (AFP) levels, the fibrosis-4 (FIB-4) index, and the aspartate aminotransferase-to-platelet ratio index (APRI). In conclusion, compared with currently reported methods for CHI3L1 detection, the CLIA has a high sensitivity, a wide linear range, and an acceptable accuracy, precision, and reference intervals, making it valuable in the diagnosis of HBV-related HCC.

Diagnostic Value of Serum Golgi Protein 73 for Liver Fibrosis: A Systematic Review and Meta-Analysis.

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 strictly searched studies according to inclusion and exclusion criteria, extracted data, and then 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 3,676 patients. Potential publication bias and threshold effect were not found. The pooled sensitivity, specificity, and area under the curve 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 the 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.

Diagnostic Value of Serum Chitinase-3-Like Protein 1 for Liver Fibrosis: A Meta-analysis.

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.

Amentoflavone prevents ox-LDL-induced lipid accumulation by suppressing the PPARγ/CD36 signal pathway.

The formation of fat-laden foam cells plays an important role in the initiation and progression of atherosclerosis (AS). Amentoflavone (AF) is found in various traditional Chinese medicines, such as ginkgo biloba, which are used to treat cardiovascular diseases (CVDs). We aimed to explore the potential effects and mechanisms of AF on lipid accumulation, and its possible application in atherosclerotic cardiovascular disease (ASCVD). Cellular models of lipid accumulation were established by treatment of HUASMCs and THP-1 cells with oxidized low-density lipoprotein (ox-LDL). Cell viability, lipid accumulation, and ox-LDL uptake were assessed. Small interfering RNAs (siRNAs) and overexpression plasmids were used to reveal the hierarchical correlations of regulatory pathways. AF reduced the lipid accumulation and ox-LDL uptake induced by ox-LDL, and reduced the expression levels of cluster of differentiation 36 (CD36) and peroxisome proliferator-activated receptor gamma (PPARγ) proteins, while the expression level of ATP binding cassette subfamily A member 1 (ABCA1) increased. Knockdown of PPARγ or CD36 with siRNAs prevented ox-LDL-induced lipid accumulation. Overexpression of CD36 or PPARγ promoted the lipid accumulation induced by ox-LDL and eliminated the effect of AF on ox-LDL-induced lipid accumulation. Overall, AF prevents ox-LDL-induced lipid accumulation by suppressing the PPARγ/CD36 signaling pathway.

Selenepezil, a Selenium-Containing Compound, Exerts Neuroprotective Effect via Modulation of the Keap1-Nrf2-ARE Pathway and Attenuates Aß-Induced Cognitive Impairment in Vivo.

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 H2O2-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 Aß-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.