Network analysis of microbiome and metabolome to explore the mechanism of raw rhubarb in the protection against ischemic stroke via microbiota-gut-brain axis.

Ischemic stroke (IS) has attracted worldwide attention due to the high mortality and disability rate. Raw rhubarb (RR) is a traditional medicinal plant and whole-food that has been used in China for its various pharmacological activities, such as antioxidant and anti-inflammatory properties. Recent pharmacological research has shown the role of RR against IS, but its mechanism of action remains unclear, particularly in the context of the brain-gut axis. To address this gap in knowledge, the present study was conducted in the middle cerebral artery occlusion/reperfusion (MCAO/R) model with the aim of investigating the effects of RR on regulating the intestinal microbiota barrier and metabolism and thereby reducing inflammatory response so as to improve the IS. The results showed that pre-treatment of RR attenuated cerebral infarct area and inflammation response in MCAO rats. Furthermore, RR also improved intestinal barrier function, including the integrity and permeability of the intestinal barrier. Additionally, RR intervention significantly attenuated gut microbiota dysbiosis caused by ischemic stroke, especially the increased Firmicutes. Notably, the pseudo-germ-free (PGF) rats further demonstrated that the anti-stroke effect of RR might rely on intestinal microbiota. In addition, the UPLC/Q-Orbitrap-MS-Based metabolomics revealed the disrupted metabolic profiles caused by MCAO/R, and a total of 11 differential metabolites were modulated by RR administration, especially bile acids. Further correlation analysis and network pharmacology analysis also demonstrated a strong association between specific bacteria, such as Firmicutes and bile acids. In conclusion, our work demonstrated that RR could effectively ameliorate ischemic stroke by modulating the microbiota and metabolic disorders.

Targets and Potential Mechanism of Scutellaria baicalensis in Treatment of Primary Hepatocellular Carcinoma Based on Bioinformatics Analysis.

OBJECTIVE: To analyze the target and potential mechanism of Scutellaria baicalensis (SB) in the treatment of HCC based on bioinformatics, so as to provide suggestions for the diagnosis, treatment, and drug development of hepatocellular carcinoma (HCC). METHODS: The regulated gene targets of SB were screened by gene expression pattern clustering and differential analysis of gene expression data of HepG2 cells treated with SB at 0 h, 1 h, 3 h, 6 h, 12 h, and 24 h. The module genes related to HCC were identified by the weighted gene coexpression network analysis (WGCNA). KEGG and GO enrichment were used to analyze the molecular function and structure of the module, and GSEA was used to evaluate the different functional pathways between normal people and patients with HCC. Then, the module gene was used for univariate Cox proportional hazard analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to build a prognostic model. The protein-protein interaction network (PPI) was used to analyze the core genes regulated by SB (CGRSB) of the module, and the survival curve revealed the CGRSB impact on patient survival. The CIBERSORT algorithm combined with correlation analysis to explore the relationship between CGRSB and immune infiltration. Finally, the single-cell sequencing technique was used to analyze the distribution of CGRSB at the cellular level. RESULTS: SB could regulate 903 genes, of which 234 were related to the occurrence of HCC. The prognosis model constructed by these genes has a good effect in evaluating the survival of patients. KEGG and GO enrichment analysis showed that the regulation of SB on HCC mainly focused on some cell proliferation, apoptosis, and immune-related functions. GSEA enrichment analysis showed that these functions are related to the occurrence of HCC. A total of 24 CGRSB were obtained after screening, of which 13 were significantly related to survival, and most of them were unfavorable factors for patient survival. The correlation analysis of gene expression showed that most of CGRSB was significantly correlated with T cells, macrophages, and other functions. The results of single-cell analysis showed that the distribution of CGRSB in macrophages was the most. CONCLUSION: SB has high credibility in the treatment of HCC, such as CDK2, AURKB, RRM2, CENPE, ESR1, and PRIM2. These targets can be used as potential biomarkers for clinical diagnosis. The research also shows that the p53 signal pathway, MAPK signal pathway, apoptosis pathway, T cell receptor pathway, and macrophage-mediated tumor immunity play the most important role in the mechanism of SB in treating HCC.

A Data Mining-Based Analysis of Medication Rules in Treating Bone Marrow Suppression by Kidney-Tonifying Method.

OBJECTIVE: To investigate the rule of kidney-tonifying method in Chinese medicine for the treatment of bone marrow suppression (BMS), in order to provide evidence and references for the clinical application of herbs and formulae. DESIGN: Collecting and sorting the information about the treatment of BMS related to kidney-tonifying (Bushen) method in Chinese medicine literatures on databases including Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM), establishing a database of BMS treating formulae after radiotherapy and chemotherapy with traditional Chinese medicine (TCM) kidney-tonifying method, and finally applying the relevant theories and techniques of data mining to analyze the medication rules of it. RESULTS: A total of 239 formulae and 202 herbs were included in this database, in which the herbs occurred 2,602 times in general. The high frequency herbs included Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu), and Ligustri Lucidi Fructus (Nvzhenzi). The main herb categories were deficiency-tonifying herbs, blood-activating herbs, dampness-draining diuretic herbs, heat-clearing herbs, and digestant herbs. Deficiency-tonifying herbs accounted for 64.60% of the total number. A total of 8 clustering formulae are summarized according to cluster analysis and 26 herb suits association rules are identified by Apriori algorithm. CONCLUSION: The treatment of BMS is mainly based on the method of invigorating the spleen and tonifying the kidney and liver to strengthen healthy qi, supplementing with blood-activating herbs, and dampness-draining diuretic herbs to eliminate pathogenic factors.