Research in revealing the effects on Cuscuta chinensis to diarrhea type irritable bowel syndrome based on network pharmacology and molecular docking potential mechanism.

To explore the potential mechanism in Cuscuta sinensis on diarrhea-type irritable bowel syndrome using network pharmacology and molecular docking techniques. First, the active components and related targets of Cuscuta were found setting oral utilization >30% and drug-like properties greater than or equal to 0.18 as filter information from TCMSP database. The targets of diarrheal irritable bowel syndrome were compiled by searching DrugBank, GeneCards, OMIM, PharmGkb, and TTD databases. The intersections of drugs and targets related to the disease were taken for gene ontology enrichment and Kyoto encyclopedia of genes and genomes enrichment analyses, to elucidate the potential molecular mechanisms and pathway information of Cuscuta sinensis for the treatment of diarrheal irritable bowel syndrome. The protein-protein interaction network was constructed by using the STRING database and visualized with Cytoscape_v3.10.0 software to find the protein-protein interaction network core At last, molecular docking was performed to validate the combination of active compounds with the core target. The target information of Cuscuta and diarrhea-type irritable bowel syndrome was compiled, which can be resulted in 11 active compounds such as quercetin, kaempferol, isorhamnetin, ß-sitosterol, and another 17 core targets such as TP53, IL6, AKT1, IL1B, TNF, EGFR, etc, whose Kyoto encyclopedia of genes and genomes was enriched in the pathways of lipids and atherosclerosis, chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, and fluid shear stress and atherosclerosis, etc. Docking demonstrated that the core targets and the active compounds were able to be better combined. Cuscuta chinensis may exert preventive effects on diarrhea-type irritable bowel syndrome by reducing intestinal inflammation, protecting intestinal mucosa, and playing an important role in antioxidant response through multi-targets and multi-pathways.

Utilising Network Pharmacology to Explore Underlying Mechanism of Astragalus membranaceus in Improving Sepsis-Induced Inflammatory Response by Regulating the Balance of IκBα and NF-κB in Rats.

Objective: The purpose of the present study was to explore the mechanism of Astragalus membranaceus in the treatment of sepsis. Methods: We searched the active components and targets of Astragalus membranaceus using the TCMSP and BATMAN databases. Then, the GeneCards, MalaCards, and OMIM databases were used to screen out relevant targets of sepsis. The common targets of the former two gene sets were uploaded to the STRING database to create an interaction network. DAVID was used to perform KEGG enrichment analysis of the core targets. Based on the results of KEGG and previous studies, key pathways for the development of sepsis were identified and experimentally validated. Result: We obtained 3,370 sepsis-related targets in databases and 59 active components in Astragalus membranaceus through data mining, corresponding to 1,130 targets. The intersection of the two types of targets led to a total of 318 common targets and 84 core targets were obtained after screening again. The KEGG and previous studies showed that these 84 core targets were involved in sepsis by regulating TNF, MAPK, and PI3K pathways. TNF, MAPK8, NF-κB, and IκBα are crucial in sepsis. Experimental validation demonstrated that some markers in sepsis model rats were improved after the intervention with Astragalus granules and their chemical components. Among them, IL-1ß, IL-6, and TNF-α in rat serum were reduced. The mRNA and protein expression of TNF-α, IL-6, MMP9, MAPK8, and NF-κB were reduced in rat blood. However, the mRNA and protein expression of IκBα and PI3K were increased in rat blood. Conclusion: The AST could affect the TNF, PI3K, and MAPK pathway cascade responses centred on IκBα and NF-κB, attenuate the expression of IL-6 and MMP9, and interfere with the inflammatory response during sepsis.

Bufei Decoction Improves Lung-Qi Deficiency Syndrome of Chronic Obstructive Pulmonary Disease in Rats by Regulating the Balance of Th17/Treg Cells.

Bufei decoction (BFD) has been applied to treat chronic obstructive pulmonary disease (COPD) for centuries as a recognized traditional Chinese herbal formula. However, mechanisms of BFD on COPD are unclear. This study conducts an inquiry into the underlying mechanisms of the therapeutic effect of BFD on COPD. A COPD rat model with qi deficiency in lungs was established through induction using cigarette and sawdust smoking combined with intratracheal instillation of lipopolysaccharide following BFD treatment for 28 days. Changes in Th17/Treg cells of COPD rats with the syndrome of lung qi deficiency after BFD administration were verified using pulmonary function, ELISA, flow cytometry, histopathology, and Western blotting assays. The findings showed that BFD protected COPD rats from decreased lung function and lung injury. BFD administration reduced proinflammatory cytokines IL-6 and IL-17 secretion, promoted inhibitory cytokines IL-10 and TGF-ß secretion, decreased Th17/Treg cell ratio, markedly downregulated the Th17 cell transcription factor ROR-γt expression, and upregulated transcription factor Foxp3 expression in Treg cells. We speculate that lung tonic soup improved pulmonary qi deficiency in rats with COPD by regulating the balance of Th17/Treg cells.

Exploration of the Danggui Buxue Decoction Mechanism Regulating the Balance of ESR and AR in the TP53-AKT Signaling Pathway in the Prevention and Treatment of POF.

OBJECTIVE: The purpose of this study was to explore the molecular mechanism of Danggui Buxue Decoction (DBD) intervening premature ovarian failure (POF). METHODS: The active compounds-targets network, active compounds-POF-targets network, and protein-protein interaction (PPI) network were constructed by a network pharmacology approach: Gene Ontology (GO) function and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis by DAVID 6.8 database. The molecular docking method was used to verify the interaction between core components of DBD and targets. Then, High-Performance Liquid Chromatography (HPLC) analysis was used to determine whether the DBD contained two key components including quercetin and kaempferol. Finally, the estrous cycle, organ index, ELISA, and western blot were used to verify that mechanism of DBD improved POF induced by cyclophosphamide (CTX) in rats. RESULTS: Based on the network database including TCMSP, Swiss Target Prediction, DisGeNET, DrugBank, OMIM, and Malacard, we built the active compounds-targets network and active compounds-POF-targets network. We found that 2 core compounds (quercetin and kaempferol) and 5 critical targets (TP53, IL6, ESR1, AKT1, and AR) play an important role in the treatment of POF with DBD. The GO and KEGG enrichment analysis showed that the common targets involved a variety of signaling pathways, including the reactive oxygen species metabolic process, release of Cytochrome C from mitochondria and apoptotic signaling pathway, p53 signaling pathway, the PI3K-Akt signaling pathway, and the estrogen signaling pathway. The molecular docking showed that quercetin, kaempferol, and 5 critical targets had good results regarding the binding energy. Chromatography showed that DBD contained quercetin and kaempferol compounds, which was consistent with the database prediction results. Based on the above results, we found that the process of DBD interfering POF is closely related to the balance of ESR and AR in TP53-AKT signaling pathway and verified animal experiments. In animal experiments, we have shown that DBD and its active compounds can effectively improve estrus cycle of POF rats, inhibit serum levels of FSH and LH, protein expression levels of Cytochrome C, BAX, p53, and IL6, and promote ovary index, uterine index, serum levels of E2 and AMH, and protein expression levels of AKT1, ESR1, AR, and BCL2. CONCLUSIONS: DBD and its active components could treat POF by regulating the balance of ESR and AR in TP53-AKT signaling pathway.

Efficacy and Safety of Aidi Injection as an Adjuvant Therapy on Advanced Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Aidi injection (ADI) is being used widely for breast cancer in China. However, the efficacy and safety of it need to be summarized. We conducted a systematic review and meta-analysis to compare ADI and non-ADI treatment for advanced breast cancer. METHODS: We searched PubMed, EMBASE, CNKI, SinoMed, and CENTRAL from inception to Jan 2020 for randomized controlled trials (RCTs) with diagnosis of advanced breast cancer that compared the efficacy of ADI with non-ADI treatment. Two researchers screened the literature, extracted data, and evaluated risk of bias separately. The primary outcomes were overall response rate (ORR) and disease control rate (DCR). The secondary outcomes included the QOL, immune cells, and adverse events. Review Manager software was used for estimating risks of bias of included studies, data analysis, and plotting. The sensitivity analysis and the publication bias test were performed using the R language. I 2 and chi-square tests were used to estimate heterogeneity. If P > 0.1 or I 2 < 40%, the fixed-effect model meta-analysis was performed. A random or fixed-effect analysis was used depending on the heterogeneity testing. Weighted mean difference (WMD) or standard mean difference (SMD) was used for analysis of continuous data, and the rate ratio (RR) was calculated for the dichotomous variable, respectively. RESULTS: We included 14 studies with 1006 patients diagnosed as advanced breast cancer in total. The pooled effect showed that ADI increased ORR in advanced BC patients as an add-on therapy with little heterogeneity (RR = 1.14, 95% CI 1.03-1.27). DCR in BC patients could not be improved by ADI. ADI improved the KPS score in BC patients compared with chemotherapy alone (MD = 3.26, 95% CI 1.74-4.78). There were no improvements on immune markers except CD4/CD8 and NK%. Serum tumor markers CEA and CA153 were decreased while treated with ADI, but only one trial was involved. ADI decreased the numbers of myelosuppression in advanced BC patients, and AST, ALT, γ-GT, and CK-MB were all decreased. The sensitivity evaluation indicated that the result of the pooled effect size had good stability. CONCLUSION: This meta-analysis suggested that based on the existing evidence, treatment with ADI significantly changed the ORR of patients with advanced BC and improved their quality of life with few side effects. However, more randomized trials involving larger samples should be considered, and detailed mechanisms are needed to be uncovered.

[Spatial phosphorus retention in an agricultural headwater stream].

The spatial dynamics of phosphorus and suspended solids were investigated for two years in a 1.8 km agricultural headwater stream, located by Chaohu Lake, southeastern China. The stream form was greatly modified by human activities. The stream could be divided into 4 channelized reaches (1.3 km), a pond reach (0.15 km) and 3 estuary reaches (0.36 km). It was found that the retention of total phosphorus (TP), phosphate and total suspended solids (TSS) predominantly occurred in the pond reach and estuary reaches. TP, phosphate and TSS retained in the pond and estuary reaches accounted for more than 50% of those retained in whole stream. The retention mostly happened in the precipitation-runoff events and it was 10 to 27 times than that in baseflow. The results showed that channelized reaches were the most important source for pollutant release under either runoff or baseflow conditions, and it accounted for more than 90% of whole stream release. There was a high spatial variation of nutrient dynamics in different channelized reaches. The channelized reach directly discharging into the pond did always retain nutrients and TSS under base flow and runoff, whereas the other channelized reaches performed differently in different hydrological conditions. Stream forms, hydrological conditions, and nutrients characteristics controlled the high spatial variation of the nutrients and TSS in the stream, while the human practices would accelerate these spatial patterns.