Uncovering the molecular mechanism of Mume Fructus in treatment of Sjögren's syndrome.

BACKGROUND: Modern medicine has no cure for the xerostomia caused by the early onset of Sjögren's syndrome. Mume Fructus is a common Chinese herbal medicine used to relieve xerostomia. However, the molecular mechanisms of the effects of Mume Fructus are unknown. In this study, network pharmacology and molecular docking were used to investigate the mechanisms of action of Mume Fructus on Sjögren's syndrome. MATERIALS AND METHOD: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used to identify the active components and targets of Mume Fructus, and the UniProt database was used to identify the genes encoding these targets. SS-related targets were also identified from the GeneCards and OMIM databases. By finding the intersection of the targets of the compounds and the targets of Sjögren's syndrome, the predicted targets of Mume Fructus in the treatment of Sjögren's syndrome were obtained. Further investigation of the active compounds and their targets was carried out by constructing a network of "medicine-candidate compound-target-disease" using Cytoscape 3.7.2, the Protein-Protein Interaction network using the STRING database and Cytoscape 3.7.2, and key targets were identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on R software. Finally, molecular docking was used to verify the affinity of the candidate compounds to the key targets. RESULTS: Quercetin, beta-sitosterol, and kaempferol in Mume Fructus interact with AKT1, IL-6, IL-1B, JUN, CASP3, and MAPK8. These results suggest that Mume Fructus exerts its therapeutic effects on the peripheral gland injury of Sjögren's syndrome and its secondary cardiovascular disease and tumorigenesis through anti-inflammatory, anti-oxidant, and anti-tumor pathways. CONCLUSION: With network pharmacology, this study systematically identified the main active components, targets, and specific mechanisms of the therapeutic effects of Mume Fructus on Sjögren's syndrome, providing both a theoretical basis and research direction for further investigations on Mume Fructus.

Genetic prediction of the causal relationship between schizophrenia and tumors: a Mendelian randomized study.

Background: Patients with schizophrenia are at a higher risk of developing cancer. However, the causal relationship between schizophrenia and different tumor types remains unclear. Methods: Using a two-sample, two-way Mendelian randomization method, we used publicly available genome-wide association analysis (GWAS) aggregate data to study the causal relationship between schizophrenia and different cancer risk factors. These tumors included lung adenocarcinoma, lung squamous cell carcinoma, small-cell lung cancer, gastric cancer, alcohol-related hepatocellular cancer, tumors involving the lungs, breast, thyroid gland, pancreas, prostate, ovaries and cervix, endometrium, colon and colorectum, and bladder. We used the inverse variance weighting (IVW) method to determine the causal relationship between schizophrenia and different tumor risk factors. In addition, we conducted a sensitivity test to evaluate the effectiveness of the causality. Results: After adjusting for heterogeneity, evidence of a causal relationship between schizophrenia and lung cancer risk was observed (odds ratio [OR]=1.001, 95% confidence interval [CI], 1.000-1.001; P=0.0155). In the sensitivity analysis, the causal effect of schizophrenia on the risk of lung cancer was consistent in both direction and degree. However, no evidence of causality or reverse causality between schizophrenia and other tumors was found. Conclusion: This study elucidated a causal relationship between the genetic predictors of schizophrenia and the risk of lung cancer, thereby providing a basis for the prevention, pathogenesis, and treatment of schizophrenia in patients with lung cancer.

Protective Effect of Combined Metoprolol and Atractylenolide I in Rats with Acute Myocardial Infarction via Modulation of the SIRT3/ß-CATENIN/PPAR-γ Signaling Pathway

ABSTRACT Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/ß-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, ß-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, ß-catenin, and PPAR-γ

Efficacy and safety of traditional Chinese medicine decoction in the treatment of adolescent myopia: A protocol for systematic review and network meta-analysis.

BACKGROUND: Adolescent myopia has become a major public health problem in Asian countries and even the world. Due to its unstable prognosis and numerous complications, it has caused serious social and economic burden. As a common treatment in Asia, Chinese medicine has been shown to be effective in controlling the development of myopia, but its evidence-based medical evidence is not sufficient. Therefore, the purpose of this study is to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of adolescent myopia through network meta-analysis, and to provide evidence for clinical and scientific research. METHODS: We searched seven databases for randomized controlled trials of TCM decoction for adolescent myopia, including PubMed, the Cochrane Library, EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chinese Scientific Journals Database, and wan-fang databases, from the date of the establishment of each database to January 31, 2022. The network meta-analysis will be implemented through Aggregate Data Drug Information System 1.16.8 and Stata 13.0 software. Primary outcomes include distant vision, intraocular pressure, and diopter. Mean differences or odds ratios will be used for statistical analysis. We will ensure the reliability of the results through node-split model and heterogeneity analysis. In addition, the Cochrane Collaboration's tool and Grading of Recommendations Assessment, Development and Evaluation system will be used for the methodological quality and the evidence quality. RESULTS: This study will provide reliable evidence for the clinical selection of TCM decoction in the treatment of adolescent myopia. CONCLUSION: The results of this study will evaluate the efficacy and safety of TCM decoction in the treatment of adolescent myopia, and provide decision-making references for future clinical and scientific research. ETHICS AND DISSEMINATION: This study did not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/VXQUP.

Efficacy and safety of traditional Chinese medicine injections in the treatment of chronic obstructive pulmonary disease: A protocol for systematic review and network meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a widespread, heterogeneous disease characterized by chronic inflammation of the airway and the gradual blockage of air flow due to bronchial obstruction. At present, a large number of traditional Chinese medicine injections (TCMIs) has been applied in the clinical treatment of COPD. However, there is insufficient evidence of evidence-based medicine of the interaction between them. Therefore, the purpose of this study is through the network meta-analysis to evaluate the efficacy and safety of the different TCMIs treatment of COPD, offering reference and evidence for clinical application. METHODS: We will search 7 databases for randomized controlled trials of TCMI for the COPD, including PubMed, the Cochrane Library, EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chinese Scientific Journals Database, and Wan-fang databases, from the date of the establishment of each database to October 31, 2021. The network meta-analysis will be implemented through Aggregate Data Drug Information System 1.16.8 and Stata 13.0 software. Pulmonary function included forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC will be the primary outcomes, FEV1 as a percentage of the estimated value (FEV1%pred), maximal voluntary ventilation (MVV), MVV as a percentage of the estimated value (MVV%pred), 6 minutes walking distance, The St. George's Respiratory Questionnaire score, and safety/adverse event will be evaluated as secondary outcomes. Mean differences or odds ratios will be used for statistical analysis. We will ensure the reliability of the results through node-split model and heterogeneity analysis. In addition, methodological quality will be evaluated based on the Cochrane Collaboration's tool, and the quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: This study will provide reliable evidence for the clinical selection of TCMI in the treatment of COPD. CONCLUSION: The results of this study will evaluate the efficacy and safety of TCMI in the treatment of COPD, and provide decision-making references for future clinical and scientific research.

Neferine Inhibits 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumorigenesis by Suppression of Cell Proliferation and Induction of Apoptosis via Modulation of the PI3K/AKT/NF-κB Signaling Pathway.

AIM: To investigate the anticancer mechanism of neferine on DMBA-prompted mammary tumorigenesis in animals. METHODS: Mammary cancer was prompted by the subcutaneous injection of 25 mg DMBA mixed in 1 ml of the vehicle (sunflower oil [0.5 ml] and saline [0.5 ml]). We analyzed the biochemical and molecular expression of cell-proliferation and apoptotic markers in normal and DMBA-induced rats. RESULTS: We detected low body weight, elevated quantities of lipid peroxidation, and low antioxidant enzyme activities in mammary tissues of DMBA-induced animals. We also found an invasive ductal carcinoma in DMBA-induced animals by histopathological assessment. Furthermore, western blotting findings displayed an augmented expression of PI3K, AKT, NF-κB, PCNA, cyclin D1, Ki-67, and Bcl-2, while reducing expression of p53, Bax, caspase-3, and caspase-9 in DMBA-induced cancer-bearing animals. RT-PCR results found upregulation of cyclin D1, PCNA, and Ki-67, and reduced expression of p53 in DMBA-prompted animals. The oral administration of neferine effectually inhibited mammary tumors via improved antioxidants and prevented lipid peroxidation activities when compared with tumor-bearing rats. Furthermore, neferine also modulated PI3K/AKT/NF-κB signaling through inhibiting cell proliferation and induced apoptosis in tumor-bearing rats. CONCLUSION: In our findings, we concluded that neferine has an anti-proliferative and enhancing apoptotic property against DMBA-induced mammary cancer.