The serum soluble ASGR1 concentration is elevated in patients with coronary artery disease and is associated with inflammatory markers.

BACKGROUND AND AIMS: Current research has suggested that asialoglycoprotein receptor 1 (ASGR1) is involved in cholesterol metabolism and is also related to systemic inflammation. This study aimed to assess the correlation between the serum soluble ASGR1 (sASGR1) concentration and inflammatory marker levels. Moreover, the second objective of the study was to assess the association between sASGR1 levels and the presence of coronary artery disease (CAD). METHODS: The study subjects included 160 patients who underwent coronary angiography. Ninety patients were diagnosed with CAD, while seventy age- and sex-matched non-CAD patients served as controls. We measured the serum sASGR1 levels using an ELISA kit after collecting clinical baseline characteristics. RESULTS: Patients with CAD had higher serum sASGR1 levels than non-CAD patients did (P < 0.0001). sASGR1 was independently correlated with the risk of CAD after adjusting for confounding variables (OR = 1.522, P = 0.012). The receiver operating characteristic (ROC) curve showed that sASGR1 had a larger area under the curve (AUC) than did the conventional biomarkers apolipoprotein B (APO-B) and low-density lipoprotein cholesterol (LDL-C). In addition, multivariate linear regression models revealed that sASGR1 is independently and positively correlated with high-sensitivity C-reactive protein (CRP) (ß = 0.86, P < 0.001) and WBC (ß = 0.13, P = 0.004) counts even after adjusting for lipid parameters. According to our subgroup analysis, this relationship existed only for CAD patients. CONCLUSION: Our research demonstrated the link between CAD and sASGR1 levels, suggesting that sASGR1 may be an independent risk factor for CAD. In addition, this study provides a reference for revealing the potential role of sASGR1 in the inflammation of atherosclerosis.

A novel bioinformatics strategy to uncover the active ingredients and molecular mechanisms of Bai Shao in the treatment of non-alcoholic fatty liver disease.

Introduction: As a new discipline, network pharmacology has been widely used to disclose the material basis and mechanism of Traditional Chinese Medicine in recent years. However, numerous researches indicated that the material basis of TCMs identified based on network pharmacology was the mixtures of beneficial and harmful substances rather than the real material basis. In this work, taking the anti-NAFLD (non-alcoholic fatty liver disease) effect of Bai Shao (BS) as a case, we attempted to propose a novel bioinformatics strategy to uncover the material basis and mechanism of TCMs in a precise manner. Methods: In our previous studies, we have done a lot work to explore TCM-induced hepatoprotection. Here, by integrating our previous studies, we developed a novel computational pharmacology method to identify hepatoprotective ingredients from TCMs. Then the developed method was used to discover the material basis and mechanism of Bai Shao against Non-alcoholic fatty liver disease by combining with the techniques of molecular network, microarray data analysis, molecular docking, and molecular dynamics simulation. Finally, literature verification method was utilized to validate the findings. Results: A total of 12 ingredients were found to be associated with the anti-NAFLD effect of BS, including monoterpene glucosides, flavonoids, triterpenes, and phenolic acids. Further analysis found that IL1-ß, IL6, and JUN would be the key targets. Interestingly, molecular docking and molecular dynamics simulation analysis showed that there indeed existed strong and stable binding affinity between the active ingredients and the key targets. In addition, a total of 23 NAFLD-related KEGG pathways were enriched. The major biological processes involved by these pathways including inflammation, apoptosis, lipid metabolism, and glucose metabolism. Of note, there was a great deal of evidence available in the literature to support the findings mentioned above, indicating that our method was reliable. Discussion: In summary, the contributions of this work can be summarized as two aspects as follows. Firstly, we systematically elucidated the material basis and mechanism of BS against NAFLD from multiple perspectives. These findings further enhanced the theoretical foundation of BS on NAFLD. Secondly, a novel computational pharmacology research strategy was proposed, which would assist network pharmacology to uncover the scientific connotation TCMs in a more precise manner.

Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients.

Rheumatoid arthritis (RA) is marked by joint damage and inflammation, with B cells playing a key role by generating autoantibodies. This study shows that G protein-coupled receptor 40 (GPR40) deficiency in B cells leads to increased activation, proliferation, antibody production, germinal center formation, and class switch recombination. GPR40 regulates Plcγ2 phosphorylation and intracellular calcium flux downstream of the B cell receptor by binding to the Gαq protein. In GPR40-deficient mice, susceptibility to collagen-induced arthritis was higher. GPR40 agonists showed potential as therapeutic agents, and their reduced expression in patients with RA correlated with disease onset, suggesting GPR40 as a potential therapeutic target and diagnostic marker.

Identification of hepatoprotective traditional Chinese medicines based on the structure-activity relationship, molecular network, and machine learning techniques.

The efforts focused on discovering potential hepatoprotective drugs are critical for relieving the burdens caused by liver diseases. Traditional Chinese medicine (TCM) is an important resource for discovering hepatoprotective agents. Currently, there are hundreds of hepatoprotective products derived from TCM available in the literature, providing crucial clues to discover novel potential hepatoprotectants from TCMs based on predictive research. In the current study, a large-scale dataset focused on TCM-induced hepatoprotection was established, including 676 hepatoprotective ingredients and 205 hepatoprotective TCMs. Then, a comprehensive analysis based on the structure-activity relationship, molecular network, and machine learning techniques was performed at molecular and holistic TCM levels, respectively. As a result, we developed an in silico model for predicting the hepatoprotective activity of ingredients derived from TCMs, in which the accuracy exceeded 85%. In addition, we originally proposed a material basis and a drug property-based approach to identify potential hepatoprotective TCMs. Consequently, a total of 12 TCMs were predicted to hold potential hepatoprotective activity, nine of which have been proven to be beneficial to the liver in previous publications. The high rate of consistency between our predictive results and the literature reports demonstrated that our methods were technically sound and reliable. In summary, systematical predictive research focused on the hepatoprotection of TCM was conducted in this work, which would not only assist screening of potential hepatoprotectants from TCMs but also provide a novel research mode for discovering the potential activities of TCMs.

Identification of SLAMF1 as an immune-related key gene associated with rheumatoid arthritis and verified in mice collagen-induced arthritis model.

Background: Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. Immune dysregulation was implicated in the pathogenesis of RA. Thus, the aim of the research was to determine the immune related biomarkers in RA. Methods: We downloaded the gene expression data of RA in GSE89408 and GSE45291 from Gene Expression Omnibus public database (GEO). Differentially expressed genes (DEGs) were identified between RA and control groups. Infiltrating immune cells related genes were obtained by ssGSEA and weighted gene co-expression network analysis (WGCNA). We performed functional enrichment analysis of differentially expressed immunity-related genes (DEIRGs) by "clusterProfiler" R package, key genes screening by protein-protein interaction (PPI) network of DEIRGs. And mice collagen-induced arthritis (CIA) model was employed to verify these key genes. Results: A total of 1,885 up-regulated and 1,899 down-regulated DEGs were identified in RA samples. The ssGSEA analysis showed that the infiltration of 25 cells was significantly different. 603 immune related genes were obtained by WGCNA, and 270 DEIRGs were obtained by taking the intersection of DEGs and immune related genes. Enrichment analyses indicated that DEIRGs were associated with immunity related biological processes. 4 candidate biomarkers (CCR7, KLRK1, TIGIT and SLAMF1) were identified from the PPI network of DEIRGs and literature research.In mice CIA model, the immunohistochemical stain showed SLAMF1 has a significantly high expression in diseased joints. And flow cytometry analysis shows the expression of SLAMF1 on CIA mice-derived CTL cells, Th, NK cells, NKT cells, classical dendritic cell (cDCs) and monocytes/macrophages was also significantly higher than corresponding immune cells from HC mice. Conclusion: Our study identified SMLAF1 as a key biomarker in the development and progression of RA, which might provide new insight for exploring the pathogenesis of RA.

Lycopene mitigates ß-amyloid induced inflammatory response and inhibits NF-κB signaling at the choroid plexus in early stages of Alzheimer's disease rats.

The choroid plexus is able to modulate the cognitive function, through changes in the neuroinflammatory response and in brain immune surveillance. However, whether lycopene is involved in inflammatory responses at the choroid plexus in the early stages of Alzheimer's disease, and its molecular underpinnings are elusive. In this rat study, lycopene was used to investigate its protective effects on inflammation caused by ß-amyloid. We characterized the learning and memory abilities, cytokine profiles of circulating TNF-α, IL-1ß and IL-6ß in the serum and the expressions of Toll like receptor 4 and nuclear factor-κB p65 mRNA and protein at the choroid plexus. The results showed that functional deficits of learning and memory in lycopene treatment groups were significantly improved compared to the control group without lycopene treatment in water maze test. The levels of serum TNF-α, IL-1ß and IL-6ß were significantly increased, and the expressions of TLR4 and NF-κB p65 mRNA and protein at the choroid plexus were up-regulated, indicating inflammation response was initiated following administration of Aß1-42. After intragastric pretreatment with lycopene, inflammatory cytokines were significantly reduced and lycopene also reversed the Aß1-42 induced up-regulation of TLR4 and NF-κB p65 mRNA and protein expressions at the choroid plexus. These results provided a novel evidence that lycopene significantly improved cognitive deficits and were accompanied by the attenuation of inflammatory injury via blocking the activation of NF-κB p65 and TLR4 expressions and production of cytokines, thereby endorsing its usefulness for diminishing ß-amyloid deposition in the hippocampus tissues.