No causal association between serum vitamin D levels and diabetes retinopathy: A Mendelian randomization analysis.

BACKGROUND AND AIM: Diabetes retinopathy (DR) is a common microvascular complication of diabetes, and it is the main cause of global vision loss. The current observational research results show that the causal relationship between Vitamin D and DR is still controversial. Therefore, we conducted a Mendelian randomization study to determine the potential causal relationship between serum 25-hydroxyvitamin D 25(OH)D and DR. METHODS AND RESULTS: In this study, we selected aggregated data on serum 25(OH)D levels (GWAS ID: ebi-a-GCST90000615) and DR (GWAS ID: finn-b-DM_RETINOPATHY) from a large-scale GWAS database. Then use MR analysis to evaluate the possible causal relationship between them. We mainly use inverse variance weighted (IVW), supplemented by MR Egger and weighted median methods. Sensitivity analysis is also used to ensure the stability of the results, such as Cochran's Q-test, MR-PRESSO, MR-Egger interception test, and retention method. The MR analysis results showed that there was no significant causal relationship between 25(OH)D and DR (OR = 1.0128, 95%CI=(0.9593,1.0693), P = 0.6447); Similarly, there was no significant causal relationship between DR and serum 25 (OH) D levels (OR = 0.9900, 95% CI=(0.9758,1.0045), P = 0.1771). CONCLUSION: Our study found no significant causal relationship between serum 25(OH)D levels and DR, and vice versa. A larger sample size randomized controlled trial is needed to further reveal its potential causal relationship.

Investigating the Mechanism of Rhizoma Coptidis-Eupatorium fortunei Medicine in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking.

Objective: This study systematically explored the mechanism of Rhizoma Coptidis-Eupatorium fortunei in treating type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking methods. Methods: The TCMSP database was used to screen out the active ingredients and related targets of Rhizoma Coptidis-Eupatorium fortunei (R-E) drug pair. GeneCards, OMIM, DrugBank, and other databases were used to screen the related targets of T2DM, and then, the UniProt database was used to standardize the relevant targets of T2DM. Then, the Venn analysis was performed on the active ingredient-related targets and disease-related targets of R-E drugs to find the intersection targets. Using the STRING database and Cytoscape software, the PPI network and "drug-active ingredient-target-disease" network are constructed by intersecting targets and corresponding active ingredients. Through the cluster profiler package in the R software, GO function enrichment analysis and KEGG pathway enrichment analysis were carried out on the intersection targets and the screened core targets, and the prediction results were verified by molecular docking. Results: Taking OB ≥ 30% and DL ≥ 0.18 as the standard, a total of 25 effective active ingredients of R-E drug pairs were screened, including berberine, palmatine, coptisine, and so on. After corresponding, 19 effective chemical components and 284 targets of the R-E drug pair were obtained. After searching multiple disease databases, 1289 T2DM-related targets were screened. After the summary, 159 common targets were obtained in this study. Finally, in the bioinformatics analysis, this study concluded that quercetin, luteolin, berberine, palmatine, and coptisine are the main chemical components of the R-E drug pair. ESR1, MAPK1, AKT1, TP53, IL6, and JUN are the important core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis-Eupatorium fortunei could improve T2DM by regulating multiple biological processes and pathways. Molecular docking results showed that berberine, palmatine, and coptisine had higher binding to the core target, and MAPK1, AKT1, and IL6 could stably bind to the active ingredients of Rhizoma Coptidis-Eupatorium fortunei. Conclusion: Rhizoma Coptidis-Eupatorium fortunei may have therapeutic effects on T2DM such as anti-inflammatory and regulating glucose and lipid metabolism through multiple components, multiple targets, and multiple signaling pathways, which provides a scientific basis for further research on the hypoglycemic effect of Rhizoma Coptidis-Eupatorium fortunei drug pair.

Insight into Shenqi Jiangtang Granule on the improved insulin sensitivity by integrating in silico and in vivo approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Presently, insulin resistance has been a growing concern that urgently needs to be addressed, because it not only places patients at risk of developing type 2 diabetes mellitus but also results in metabolic syndrome and different aspects of cardiovascular diseases. Shenqi Jiangtang Granule (SJG) is a classic traditional Chinese medicine (TCM) prescription that is widely used to treat diabetes mellitus and its complications in clinical practice. While studies have revealed that SJG with multi-ingredients and multi-targets characteristics possesses potential anti-insulin resistance pharmacological properties, its mechanisms of action and molecular targets for the treatment of insulin resistance are still obscure, which prompt us to conduct an in-depth research. AIM OF THE STUDY: This study was purposed to uncover the pharmacological mechanism of SJG against insulin resistance through integrating network pharmacology and experimental validation. MATERIALS AND METHODS: The putative ingredients of SJG and its related targets were discerned from the TCMSP database. Subsequently, insulin resistance-associated targets were retrieved from GeneCard, OMIM, and GEO database. Compound-target, protein-protein interaction (PPI), and compound-target-pathway networks were established using Cytoscape software. GO and KEGG pathway analyses were performed to identify possible enrichment of genes with specific biological themes. Molecular docking was used to verify the correlation between the main active ingredients and hub targets. Optimal docking conformation was further analyzed by molecular dynamics (MD) simulation. Finally, the potential molecular mechanisms of SJG acting on insulin resistance, as predicted by the network pharmacology analyses, were validated experimentally in insulin-resistant rat model. RESULTS: 136 active compounds, 211 corresponding targets in addition to 1463 disease-related targets were collected, of which 94 intersection targets were obtained. 29 key targets including AKT1, VEGFA, IL-6, CASP3, and PTGS2 were identified through PPI network analysis. Hub module of PPI network was closely associated with inflammation. GO and KEGG analyses also revealed that inflammation-related pathways may be a central factor for SJG to modulate insulin resistance. Molecular docking test showed a good binding potency between primary active ingredients and core targets, and the binding mode of optimal docking conformation was stable in MD simulation. A rat model of insulin resistance was successfully induced by chronic high-fat diet (HFD) consumption. Through a series of in vivo studies, including HEC, ITT, and HOMA-IR measurement, it was revealed that SJG exhibited a beneficial effect on ameliorating insulin resistance, as demonstrated by a significant increase of GIR and a significant decrease of AUCITT and HOMA-IR index value. Further molecular biological analysis showed that SJG can decrease the mRNA expression level and serum concentration of inflammatory cytokines (TNF-α, IL-6, and IL-1ß), along with suppressing the p-NFκB protein overexpression, indicating its anti-inflammatory activity. Also, it can contribute to the reversal of the impaired hepatic insulin signaling pathway, as evidenced by up-regulated protein expression of p-Akt and GLUT2. CONCLUSIONS: Through in silico and in vivo approaches, the present study not only provides a unique insight into the possible mechanism of SJG in insulin resistance after successfully filtering out associated key target genes and signaling pathways, but also suggests a novel promising therapeutic strategy for curing insulin resistance.

Efficacy of acupuncture based on acupoint combination theory for irritable bowel syndrome: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain, diarrhea or constipation, and changes in defecation patterns. No organic disease is found to explain these symptoms by routine clinical examination. This study aims to investigate the efficacy and safety of acupuncture therapy for IBS patients compared with those of conventional treatments. We also aim to identify the optimal acupoint combination recommended for IBS and to clarify the clinical advantage of the "multiacupoint co-effect and synergistic effect." METHODS AND ANALYSIS: A total of 204 eligible patients who meet the Rome IV criteria for IBS will be randomly stratified into acupuncture group A, acupuncture group B, or the control group in a 1:1:1 ratio with a central web-based randomization system. The prespecified acupoints used in the control group will include bilateral Tianshu (ST25), Shangjuxu (ST37), Neiguan (PC6), and Zusanli (ST36). The prespecified acupoints used in experimental group A will include bilateral Tianshu (ST25), Shangjuxu (ST37), and Neiguan (PC6). The prespecified acupoints used in experimental group B will include bilateral Tianshu (ST25), Shangjuxu (ST37), and Zusanli (ST36). Each patient will receive 12 acupuncture treatments over 4 weeks and will be followed up for 4 weeks. The primary outcome is the IBS-Symptom Severity Scale (IBS-SSS) score. The secondary outcomes include the Bristol Stool Form Scale (BSFS), Work and Social Adjustment Score (WSAS), IBS-Quality of Life (IBS-QOL), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) scores. Both the primary outcome and the secondary outcome measures will be collected at baseline, at 2 and 4 weeks during the intervention, and at 6 weeks and 8 weeks after the intervention. ETHICS AND DISSEMINATION: The entire project has been approved by the ethics committee of the Beijing University of Chinese Medicine (2020BZYLL0903). DISCUSSION: This is a multicenter randomized controlled trial for IBS in China. The findings may shed light on the efficacy of acupuncture as an alternative to conventional IBS treatment. The results of the trial will be disseminated in peer-reviewed publications. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2000041215 . First registered on 12 December 2020. http://www.chictr.org.cn/ .

Progress and trends of photodynamic therapy: From traditional photosensitizers to AIE-based photosensitizers.

Photodynamic therapy (PDT) is an established clinical treatment technology which utilizes excitation light of a specific wavelength to activate photosensitizers (PSs) to generate reactive oxygen species (ROS), which leads to cancer cell death. Over the past decades of PDT research, progress have been made in the development of PSs. However, many inherent characteristics of traditional PSs have caused various problems in PDT, such as low treatment efficiency at aggregation state and shallow treatment depth. In solution to these problems, aggregation-induced emission (AIE)-based PSs have been reported in recent years. Here, this article reviews the design strategy and the biomedical applications of AIE PSs in detail, which begins with a summary of traditional PSs for a comparison between traditional PSs and AIE PSs. Subsequently, the different functional AIE PSs in photodynamic cancer cells ablation and image-guided therapy are discussed in detail taking controllable excitation wavelength, stimulus response and PDT/photothermal therapy synergistic effect as examples. These studies have demonstrated the great potential of AIE PSs as effective theranostic agents. And the review provides references for the development of new PSs and hopefully spur research interest in AIE PSs for future clinical application.