Integrated network pharmacology analysis and in vitro validation revealed the underlying mechanism of Xiyanping injection in treating coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, leading to a pandemic. In China, Xiyanping injection (XYP) has been recommended as a drug for COVID-19 treatment in the Guideline on Diagnosis and Treatment of COVID-19 by the National Health Commission of the People Republic of China and National Administration of Traditional Chinese Medicine (Trial eighth Edition). However, the relevant mechanisms at the molecular-level need to be further elucidated. METHODS: In this study, XYP related active ingredients, potential targets and COVID-19 related genes were searched in public databases. Protein-protein interaction network and module analyzes were used to screen for key targets. gene ontology and Kyoto encyclopedia of genes and genomes were performed to investigate the potentially relevant signaling pathways. Molecular docking was performed using Autodock Tools and Vina. For the validation of potential mechanism, PolyI:C was used to induce human lung epithelial cells for an inflammation model. Subsequently, CCK-8 assays, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blot were employed to determine the effect of XYP on the expression of key genes. RESULTS: Seven effective active ingredients in XYP were searched for 123 targets in the relevant databases. Furthermore, 6446 COVID-19 disease targets were identified. Sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate was identified as the vital active compounds, and IL-6, TNF, IL-1ß, CXCL8, STAT3, MAPK1, MAPK14, and MAPK8 were considered as the key targets. In addition, molecular docking revealed that the active compound and the targets showed good binding affinities. The enrichment analysis predicted that the XYP could regulate the IL-17, Toll-like receptor, PI3K-Akt and JAK-STAT signaling pathways. Consistently, further in vitro experiments demonstrated that XYP could slow down the cytokine storm in the lung tissue of COVID-19 patients by down-regulating IL-6, TNF-α, IL-1ß, CXCL8, and p-STAT3. CONCLUSION: Through effective network pharmacology analysis and molecular docking, this study suggests that XYP contains many effective compounds that may target COVID-19 related signaling pathways. Moreover, the in vitro experiment confirmed that XYP could inhibit the cytokine storm by regulating genes or proteins related to immune and inflammatory responses.

Construction of an evaluation index system of core competencies for critical care blood purification nurses in China: A Delphi study.

AIM: The purpose of this study was to construct a core competencies evaluation index system for critical care blood purification nurses in China. BACKGROUND: While nursing is an integral part of critical care blood purification treatment, there are no established indicators to evaluate the core competencies of critical care blood purification nurses. DESIGN: A Delphi study. METHODS: An initial draft of the competencies evaluation index system for critical care blood purification nurses was developed through a literature review and semi-structured interviews. From February 2023 to March 2023, a two-round Delphi survey was conducted to consult with 18 experts in the field of critical care blood purification from eight provinces in China to rate the importance of each item and propose modifications to the evaluation index system. RESULTS: The effective questionnaire recovery rates in two rounds of expert consultation were 94.4 % and 94.1 % and the average expert authority coefficients were 0.88 in both rounds. The core competencies evaluation index system of critical care blood purification nurses consisted of 39 items in five domains, namely theoretical knowledge, practical skills, professional development capability, critical thinking ability and personal qualities and attributes. The Kendall's W coefficients for the first- and second-level indicators were.21 and.20 in the first round and.23 and.25, respectively, in the second round of consultations (p < .01). CONCLUSION: The core competencies evaluation index system of critical care blood purification nurses is scientific and reliable and can provide references for the recruitment, training and management of critical care blood purification nurses.

Corrigendum: Revealing the mechanism of Huazhi Rougan granule in the treatment of nonalcoholic fatty liver through intestinal flora based on 16S rRNA, metagenomic sequencing and network pharmacology.

[This corrects the article DOI: 10.3389/fphar.2022.875700.].

Identification of an immune-related 6-lncRNA panel with a good performance for prognostic prediction in hepatocellular carcinoma by integrated bioinformatics analysis.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors with a poor prognosis. The long non-coding RNA (lncRNA) has been found to have great potential as a prognostic biomarker or therapeutic target for cancer patients. However, the prognostic value and tumor immune infiltration of lncRNAs in HCC has yet to be fully elucidated. To identify prognostic biomarkers of lncRNA in HCC by integrated bioinformatics analysis and explore their functions and relationship with tumor immune infiltration. The prognostic risk assessment model for HCC was constructed by comprehensively using univariate/multivariate Cox regression analysis, Kaplan-Meier survival analysis, and the least absolute shrinkage and selection operator regression analysis. Subsequently, the accuracy, independence, and sensitivity of our model were evaluated, and a nomogram for individual prediction in the clinic was constructed. Tumor immune microenvironment (TIME), immune checkpoints, and human leukocyte antigen alleles were compared in high- and low-risk patients. Finally, the functions of our lncRNA signature were examined using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and gene set enrichment analysis. A 6-lncRNA panel of HCC consisting of RHPN1-AS1, LINC01224, CTD-2510F5.4, RP1-228H13.5, LINC01011, and RP11-324I22.4 was eventually identified, and show good performance in predicting the survivals of patients with HCC and distinguishing the immunomodulation of TIME of high- and low-risk patients. Functional analysis also suggested that this 6-lncRNA panel may play an essential role in promoting tumor progression and immune regulation of TIME. In this study, 6 potential lncRNAs were identified as the prognostic biomarkers in HCC, and the regulatory mechanisms involved in HCC were initially explored.

Compound Kushen Injection inhibits epithelial-mesenchymal transition of gastric carcinoma by regulating VCAM1 induced by the TNF signaling pathway.

BACKGROUND: Gastric carcinoma (GC) treatment needs to be developed rapidly. Compound Kushen Injection (CKI), a formula from traditional Chinese medicine, has been used clinically in combination with chemotherapy to treat GC with satisfactory results. However, the molecular mechanism by which CKI acts to cure GC is still unclear. METHODS: In the present study, in vivo and in vitro experiments were used to assess the efficacy of CKI. Using ceRNA microarray and TMT technologies, the molecular mechanism of CKI was further investigated at the transcriptional and protein levels, and a bioinformatics approach was employed to investigate and functionally validate key CKI targets in GC. RESULTS: When combined with cisplatin (DDP), CKI significantly increased its efficacy in preventing the proliferation and metastasis of GC cells and malignant-looking tumors in mice. High-throughput sequencing data and bioinformatics analysis showed that CKI regulated the TNF signaling pathway, epithelial-mesenchymal transition (EMT), with VCAM1 as a key target. The transcription factors CEBPB, JUN, RELA, NFKB1, the EMT mesenchymal-like cell markers N-cadherin and vimentin, as well as the expression of VCAM1 and its upstream signaling driver TNF, were all downregulated by CKI. In contrast, the expression of the EMT epithelial-like cell marker E-cadherin was upregulated. CONCLUSION: CKI can effectively inhibit GC growth and metastasis, improve body's immunity, and protect normal tissues from damage. The molecular mechanism by which CKI inhibits metastasis of GC is by regulating VCAM1 induced by the TNF signaling pathway to inhibit EMT of GC. Our results provide an important clue to clarify precisely the multi-scale molecular mechanism of CKI in the treatment of GC.

Elucidating the pharmacological effects of Compound Kushen injection on MYC-P15-CCND1 signaling pathway in nasopharyngeal carcinoma - An in vitro study.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Kushen injection (CKI) is a representative medication of Chinese herbal injection and is often used in the adjuvant treatment of nasopharyngeal carcinoma (NPC), but its antitumor mechanism is poorly understood. AIM OF THE STUDY: To preliminarily elucidate the effects and possible mechanisms of CKI on NPC. METHODS: In this work, we explored the possible molecular mechanisms of CKI against NPC by using network pharmacology and molecular docking. In addition, proteomics was used to explore the localization and quantitative information of protein in NPC C666-1 cells after the intervention of CKI, and enrichment analysis was used to obtain the potential targets and pathways. Finally, the effect and the core targets of CKI in the intervention of NPC were explored in vitro experiments. RESULTS: Network pharmacology analysis identified three active components of CKI and 13 key targets. Molecular docking analysis showed that TNF, PTEN, CCND1, MAPK3, IL6, HIF1A, MYC had high affinity with corresponding components. Then the key pathway, cell cycle and the core targets MYC, CCND1, and P15 related to the key pathway were obtained. The results of in vitro experiments showed that CKI could inhibit the proliferation, migration, and invasion of NPC 5-8F cells and C666-1 cells, induce apoptosis of C666-1 cells, and arrest cell cycle G0/G1 phase. In addition, RT-qPCR and western blot showed that the expression of P15 was up-regulated and E2F4, E2F5, c-Myc, CCND1, and P107 was down-regulated in 5-8F cells and C666-1 cells intervened by CKI. CONCLUSION: The key pathway, cell cycle and the corresponding core targets MYC, CCND1, and P15 were obtained from network pharmacology, molecular docking, and proteomics. CKI could inhibit the proliferation, migration, and invasion of NPC cells, induce apoptosis of C666-1 cells. Especially CKI may arrest cell cycle G0/G1 phase through regulating targets MYC/P15/CCND1 of cell cycle pathway.

Exploring the effect of Yinzhihuang granules on alcoholic liver disease based on pharmacodynamics, network pharmacology and molecular docking.

BACKGROUND: Yinzhihuang granules (YZHG) is a commonly used Chinese patent medicine for the treatment of liver disease. However, the mechanism of YZHG in alcoholic liver disease (ALD) is still unclear. METHODS: This study combined liquid chromatography-mass spectrometry technology, pharmacodynamics, network pharmacology and molecular docking methods to evaluate the potential mechanism of YZHG in the treatment of ALD. RESULTS: A total of 25 compounds including 4-hydroxyacetophenone, scoparone, geniposide, quercetin, baicalin, baicalein, chlorogenic acid and caffeic acid in YZHG were identified by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The pharmacodynamic investigations indicated that YZHG could improve liver function and the degree of liver tissue lesions, and reduce liver inflammation and oxidative stress in ALD mice. Network pharmacology analysis showed that YZHG treated ALD mainly by regulating inflammation-related signaling pathways such as the PI3K-Akt signaling pathway. The results of the PPI network and molecular docking showed that the targets of SRC, HSP90AA1, STAT3, EGFR and AKT1 could be the key targets of YZHG in the treatment of ALD. CONCLUSION: This study explored the potential compounds, potential targets and signaling pathways of YZHG in the treatment of ALD, which is helpful to clarify the efficacy and mechanism of YZHG and provide new insights for the clinical application of YZHG.

Integrated serum pharmacochemistry, 16S rRNA sequencing and metabolomics to reveal the material basis and mechanism of Yinzhihuang granule against non-alcoholic fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Yinzhihuang granule (YZHG) has liver protective effect and can be used for clinical treatment of non-alcoholic fatty liver disease (NAFLD), but its material basis and mechanism need to be further clarified. AIM OF THE STUDY: This study aims to reveal the material basis and mechanism of YZHG treating NAFLD. MATERIALS AND METHODS: Serum pharmacochemistry were employed to identify the components from YZHG. The potential targets of YZHG against NAFLD were predicted by system biology and then preliminarily verified by molecular docking. Furthermore, the functional mechanism of YZHG in NAFLD mice was elucidated by 16S rRNA sequencing and untargeted metabolomics. RESULTS: From YZHG, 52 compounds were identified, of which 42 were absorbed into the blood. Network pharmacology and molecular docking showed that YZHG treats NAFLD with multi-components and multi-targets. YZHG can improve the levels of blood lipids, liver enzymes, lipopolysaccharide (LPS), and inflammatory factors in NAFLD mice. YZHG can also significantly improve the diversity and richness of intestinal flora and regulate glycerophospholipid and sphingolipid metabolism. Moreover, Western Blot experiment showed that YZHG can regulate liver lipid metabolism and enhance intestinal barrier function. CONCLUSIONS: YZHG may treat NAFLD by improving the disruption of intestinal flora and enhancing the intestinal barrier. This will reduce the invasion of LPS into the liver subsequently regulate liver lipid metabolism and reduce liver inflammation.

Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is a type of cancer which often at itsadvanced stage apon diagnosis and mortality in clinical practice. Several factors influencethe prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment. We here investigated the biomarkers related to the diagnosis and prognosis of gastric cancer, hoping to provide insights for the diagnosis and treatment of gastric cancer in the future. STAD and normal patient RNA sequencing data sets were accessed from the cancer genome atlas (TCGA database). Differential genes were determined and obtained by using the R package DESeq2. The stromal, immune, and ESTIMATE scores are calculated by the ESTIMATE algorithm, followed by the modular genes screening using the R package WGCNA. Subsequently, the intersection between the modular gene and the differential gene was taken and the STRING database was used for PPI network module analysis. The R packages clusterProfiler, enrichplot, and ggplot2 were used for GO and KEGG enrichment analysis. Cox regression analysis was used to screen survival-related genes, and finally, the R package Venn Diagram was used to take the intersection and obtain 7 hub genes. The time-dependent ROC curve and Kaplan-Meier survival curve were used to find the SERPINE1 gene, which plays a critical role in prognosis. Finally, the expression pattern, clinical characteristics, and regulatory mechanism of SERPINE1 were analyzed in STAD. We revealed that the expression of SERPINE1 was significantly increased in the samples from STAD compared with normal samples. Cox regression, time-dependent ROC, and Kaplan-Meier survival analyses demonstrated that SERPINE1 was significantly related to the adverse prognosis of STAD patients. The expression of SERPINE1 increased with the progression of T, N, and M classification of the tumor. In addition, the results of immune infiltration analysis indicated that the immune cells' expression were higher in high SERPINE1 expression group than that in low SERPINE1 expression group, including CD4+ T cells, B cells, CD8+ T cells, macrophages, neutrophils and other immune cells. SERPINE1 was closely related to immune cells in the STAD immune microenvironment and had a synergistic effect with the immune checkpoints PD1 and PD-L1. In conclusion, we proved that SERPINE1 is a promising prognostic and diagnostic biomarker for STAD and a potential target for immunotherapy.

Identification of key pharmacological components and targets for Aidi injection in the treatment of pancreatic cancer by UPLC-MS, network pharmacology, and in vivo experiments.

BACKGROUND: Pancreatic cancer is one of the most lethal cancers worldwide. Aidi injection (ADI) is a representative antitumor medication based on Chinese herbal injection, but its antitumor mechanisms are still poorly understood. MATERIALS AND METHODS: In this work, the subcutaneous xenograft model of human pancreatic cancer cell line Panc-1 was established in nude mice to investigate the anticancer effect of ADI in vivo. We then determined the components of ADI using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) and explored the possible molecular mechanisms against pancreatic cancer using network pharmacology. RESULTS: In vivo experiments, the volume, weight, and degree of histological abnormalities of implanted tumors were significantly lower in the medium and high concentration ADI injection groups than in the control group. Network pharmacology analysis identified four active components of ADI and seven key targets, TNF, VEGFA, HSP90AA1, MAPK14, CASP3, P53 and JUN. Molecular docking also revealed high affinity between the active components and the target proteins, including Astragaloside IV to P53 and VEGFA, Ginsenoside Rb1 to CASP3 and Formononetin to JUN. CONCLUSION: ADI could reduce the growth rate of tumor tissue and alleviate the structural abnormalities in tumor tissue. ADI is predicted to act on VEGFA, P53, CASP3, and JUN in ADI-mediated treatment of pancreatic cancer.

Investigation on the efficiency of Brucea javanica oil emulsion injection with chemotherapy for treating malignant pleural effusion: A meta-analysis of randomized controlled trials.

Introduction: Systematic evaluation of the clinical efficacy and safety of Brucea javanica oil emulsion injection (BJOEI) in combination with chemotherapy in the treatment of malignant pleural effusion (MPE). Methods: The study searched CNKI, Wanfang database, VIP database, SinoMed, PubMed, Embase, the Cochrane Library, and the Web of Science database and retrieved randomized controlled trials (RCTs) on the treatment of MPE with BJOEI in combination with chemotherapy from seven electronic databases from inception to 31 March 2022. Meta-analysis and sensitivity analysis were performed using Revman 5.4 and Stata 13.0 software. Results: Ultimately, 30 RCTs with 2035 patients were included, including 1002 cases in the control group and 1033 cases in the treatment group. The results of the meta-analysis showed that the overall efficacy rate of BJOEI combined with chemotherapy was higher in the treatment of MPE compared with chemotherapy alone (RR = 1.45, 95%CI: 1.36-1.54, p < 0.00001). And it could improve the Karnofsky (KPS) score (RR = 1.54, 95%CI: 1.41-1.68, p < 0.00001), reduce adverse reactions such as fever (RR = 0.82, 95%CI:0.60-1.12), chest pain (RR = 0.90, 95%CI: 0.67-1.21), gastrointestinal reactions (RR = 0.70, 95%CI: 0.57-0.87, p < 0.005), and leukopenia (RR = 0.51, 95%CI: 0.43-0.61, p < 0.00001). Conclusion: BJOEI combined with chemotherapy has better clinical efficacy than chemotherapy alone in the treatment of MPE. It can further improve KPS score, improve patients' quality of life, and reduce the occurrence of adverse reactions. However, the conclusions of this study need to be confirmed by further randomized, double-blind, controlled trials with large sample size, reasonable design, and strict implementation.

Single-Cell and Bulk RNA Sequencing Reveal Malignant Epithelial Cell Heterogeneity and Prognosis Signatures in Gastric Carcinoma.

Gastric carcinoma (GC) heterogeneity represents a major barrier to accurate diagnosis and treatment. Here, we established a comprehensive single-cell transcriptional atlas to identify the cellular heterogeneity in malignant epithelial cells of GC using single-cell RNA sequencing (scRNA-seq). A total of 49,994 cells from nine patients with paired primary tumor and normal tissues were analyzed by multiple strategies. This study focused on the malignant epithelial cells, which were divided into three subtypes, including pit mucous cells, chief cells, and gastric and intestinal cells. The trajectory analysis results suggest that the differentiation of the three subtypes could be from the pit mucous cells to the chief cells and then to the gastric and intestinal cells. Lauren's histopathology of GC might originate from various subtypes of malignant epithelial cells. The functional enrichment analysis results show that the three subtypes focused on different biological processes (BP) and pathways related to tumor development. In addition, we generated and validated the prognostic signatures for predicting the OS in GC patients by combining the scRNA-seq and bulk RNA sequencing (bulk RNA-seq) datasets. Overall, our study provides a resource for understanding the heterogeneity of GC that will contribute to accurate diagnosis and prognosis.

Identification of molecular mechanisms underlying the therapeutic effects of Xintong granule in coronary artery disease by a network pharmacology and molecular docking approach.

Coronary artery disease (CAD) is a cardiovascular disease characterized by atherosclerosis, angiogenesis, thrombogenesis, inflammation, etc. Xintong granule (XTG) is considered a practical therapeutic strategy in China for CAD. Although its therapeutic role in CAD has been reported, the molecular mechanisms of XTG in CAD have not yet been explored. A network pharmacology approach including drug-likeness (DL) evaluation, oral bioavailability (OB) prediction, protein-protein interaction (PPI) network construction and analysis, and Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses was used to predict the active ingredients, potential targets, and molecular mechanisms of XTG associated with the treatment of CAD. Molecular docking analysis was performed to investigate the interactions between the active compounds and the underlying targets. Fifty-one active ingredients of XTG and 294 CAD-related targets were screened for analysis. Gene Ontology enrichment analysis showed that the therapeutic targets of XTG in CAD are mainly involved in blood circulation and vascular regulation. KEGG pathway analysis indicated that XTG intervenes in CAD mainly through the regulation of fluid shear stress and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, and the relaxin signaling pathway. Molecular docking analysis showed that each key active ingredient (quercetin, luteolin, kaempferol, stigmasterol, resveratrol, fisetin, gamma-sitosterol, and beta-sitosterol) of XTG can bind to the core targets of CAD (AKT1, JUN, RELA, MAPK8, NFKB1, EDN1, and NOS3). The present study revealed the CAD treatment-related active ingredients, underlying targets, and potential molecular mechanisms of XTG acting by regulating fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and relaxin signaling pathway.

Revealing the Mechanism of Huazhi Rougan Granule in the Treatment of Nonalcoholic Fatty Liver Through Intestinal Flora Based on 16S rRNA, Metagenomic Sequencing and Network Pharmacology.

Background: The incidence of Nonalcoholic Fatty Liver (NAFL) is increasing year by year, growing evidence suggests that the intestinal flora plays a causative role in NAFL. Huazhi Rougan Granule (HRG) is commonly used in the clinical treatment of NAFL. It is reported that it can reduce lipids and protect the liver, but no research has confirmed whether the drug's effect is related to the intestinal flora. Therefore, we investigated whether the effect of HRG is related to the regulation of intestinal flora to further explore the mechanism of HRG in the treatment of NAFL through intestinal flora. Methods: In this study, C57BL/6J mice were fed a high-fat diet for 8 weeks, and the high-fat diet plus HRG or polyene phosphatidylcholine capsules were each administered by gavage for 4 weeks. High-throughput sequencing, network pharmacology, and molecular docking were used to explore the mechanism of HRG in the treatment of NAFL through intestinal flora. Results: HRG treatment can reduce body weight gain, lipid accumulation in liver and lipogenesis and reduce serum biochemical indexes in high-fat-fed mice. Analysis of intestinal flora showed that HRG changed the composition of intestinal flora, which was characterized by a decrease in the Firmicutes/Bacteroidetes ratio. Moreover, the species distribution was significantly correlated with AKP, HDL-C, and TG. Metagenetic analysis showed that HRG altered the functional composition and functional diversity of microorganisms, which was mainly characterized by an increase in the abundance of metabolic pathways. The network pharmacology results show that the mechanism of HRG in the treatment of NAFL through intestinal flora is mainly reflected in the biological process of gene function and related to infectious diseases, immune systems, and signal transduction pathways, such as cytokine-cytokine receptor interaction, Chagas disease, IL-17 signaling pathway and other signaling pathways. Conclusion: These results strongly suggest that HRG may alleviate NAFL by preventing IFD.

Exploring the Multicomponent Synergy Mechanism of Yinzhihuang Granule in Inhibiting Inflammation-Cancer Transformation of Hepar Based on Integrated Bioinformatics and Network Pharmacology.

Background: The Chinese patent drug Yinzhihuang granule (YZHG) is used to treat hepatitis B. This research is aimed at exploring the multicomponent synergistic mechanism of YZHG in the treatment of inflammation-cancer transformation of hepar and at providing new evidence and insights for its clinical application. Methods: To retrieve the components and targets of Yinzhihuang granules. The differentially expressed genes (DEGs) of hepar inflammation-cancer transformation were obtained from TTD, PharmGKB, and GEO databases. Construct the compound-prediction target network and the key module network using Cytoscape 3.7.1. Results: The results show that hepatitis B and hepatitis C shared a common target, MMP2. CDK1 and TOP2A may play an important role in the treatment with YZHG in hepatitis B inflammatory cancer transformation. KEGG pathway enrichment showed that key genes of modules 1, 2, and 4 were mainly enriched in the progesterone-mediated oocyte maturation signaling pathway and oocyte meiosis signaling pathway. Conclusion: The multicomponent, multitarget, and multichannel pharmacological benefits of YZHG in the therapy of inflammation-cancer transition of hepar are directly demonstrated by network pharmacology, providing a scientific basis for its mechanism.

Revealing Calcium Signaling Pathway as Novel Mechanism of Danhong Injection for Treating Acute Myocardial Infarction by Systems Pharmacology and Experiment Validation.

Introduction: Danhong injection (DHI) is a traditional Chinese medicine preparation commonly used in the clinical treatment of acute myocardial infarction (AMI). In this study, the active components of DHI and its mechanism in the treatment of AMI were investigated. Methods: The chemical components of DHI were detected by the ultra-high-performance liquid chromatography-linear trap quadrupole-orbitrap-tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS), and the targets and pathways of DHI in the treatment of AMI were analyzed by systems pharmacology, which was verified by molecular docking and animal experiments. Results: A total of 12 active components of DHI were obtained, and 158 common targets of component and disease were identified by systems pharmacology. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results showed that DHI is closely related to the calcium signaling pathway in the treatment of AMI. Molecular docking showed that the key target protein has good binding affinity to related compounds. The experimental results showed that compared with the model group, LVAWs, EF, and FS significantly (p < 0.05) increased in the DHI group. The percentage of myocardial infarction significantly (p < 0.01) decreased, both in the ventricular and total cardiac regions, and the pathological damage of myocardial tissue also decreased. In addition, the expression of the protein CaMK II decreased (p < 0.01) and the expression of SERCA significantly increased (p < 0.01). Conclusion: This study revealed that ferulic acid, caffeic acid and rosmarinic acid could inhibit AMI by regulating PLB, CaMK II, SERCA, etc. And mechanistically, calcium signaling pathway was critically involved. Combination of systems pharmacology prediction with experimental validation may provide a scientific basis for in-depth clinical investigation of the material basis of DHI.

A novel strategy to reveal clinical advantages and molecular mechanism of aidi injection in the treatment of pancreatic cancer based on network meta-analysis and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pancreatic cancer is a common malignancy worldwide due to its poor prognosis and high mortality rate. It is clinically proven that the combination of chemotherapeutic drugs and Traditional Chinese Medicine injections (TCMIs) significantly improves the therapeutic effect. AIM OF THE STUDY: To evaluate the efficacy and clinical benefits of TCMIs in combination with chemotherapy in the treatment of pancreatic cancer and to explore the mechanism of clinical advantage of Aidi injection. METHODS: Randomized controlled trials (RCTs) were searched in databases by NMA before December 29, 2020. WinBUGS 1.4, Stata 14.0, and R 4.0.4 software were used for calculations. All results were expressed as odds ratios and 95% credible intervals. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed. And then, biological experiments were integrated to verify the results of network pharmacology analysis. (PROSPERO ID: CRD42021283559). RESULTS: A total of 33 RCTs with 8 TCMIs and 2011 patients were included. The results of NMA showed that Aidi injection can significantly improve the clinical efficacy (OR = 0.34, 95%CI: 0.16-0.74), and the clinical advantage was that it can significantly alleviate the leukopenia and thrombocytopenia caused by chemotherapy (OR = 5.65, 95%CI: 1.18-28.13). A total of 23 chemical compounds and 280 potential targets for Aidi injection were obtained from the online databases. Among them, there were 22 compounds, 50 targets and 211 signaling pathways closely related to leukopenia. Five genes were predicted to be core targets of ADI in alleviating leukopenia, and 2 of them (TP53 and VEGFA) were confirmed by biological experiments as regulatory targets of ADI in the treatment of PC. CONCLUSIONS: In conclusion, TCMIs in combination with chemotherapy, can improve clinical efficacy and safety in the treatment of pancreatic cancer. However, the overall evidence base is low, and large samples with multi-center RCTs are still needed to support further research findings. Aidi injection can alleviate leukopenia mainly by intervening in oxidative stress, regulating cell proliferation and apoptosis, and regulating the inflammatory response. The combined application of NMA, network pharmacology, and biological experiments provides a reference for clinical evaluation and mechanism of action exploration of other drugs.

Exploring potential mechanisms of Suhexiang Pill against COVID-19 based on network pharmacology and molecular docking.

BACKGROUND: The traditional Chinese medicine prescription Suhexiang Pill (SHXP), a classic prescription for the treatment of plague, has been recommended in the 2019 Guideline for coronavirus disease 2019 (COVID-19) diagnosis and treatment of a severe type of COVID-19. However, the bioactive compounds and underlying mechanisms of SHXP for COVID-19 prevention and treatment have not yet been elucidated. This study investigates the mechanisms of SHXP in the treatment of COVID-19 based on network pharmacology and molecular docking. METHODS: First, the bioactive ingredients and corresponding target genes of the SHXP were screened from the traditional Chinese medicine systems pharmacology database and analysis platform database. Then, we compiled COVID-19 disease targets from the GeneCards gene database and literature search. Subsequently, we constructed the core compound-target network, the protein-protein interaction network of the intersection of compound targets and disease targets, the drug-core compound-hub gene-pathway network, module analysis, and hub gene search by the Cytoscape software. The Metascape database and R language software were applied to analyze gene ontology biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, AutoDock software was used for molecular docking of hub genes and core compounds. RESULTS: A total of 326 compounds, 2450 target genes of SHXP, and 251 genes related to COVID-19 were collected, among which there were 6 hub genes of SHXP associated with the treatment of COVID-19, namely interleukin 6, interleukin 10, vascular endothelial growth factor A, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and epidermal growth factor. Functional enrichment analysis suggested that the effect of SHXP against COVID-19 is mediated by synergistic regulation of several biological signaling pathways, including Janus kinase/ STAT3, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), T cell receptor, TNF, Nuclear factor kappa-B, Toll-like receptor, interleukin 17, Chemokine, and hypoxia-inducible factor 1 signaling pathways. SHXP may play a vital role in the treatment of COVID-19 by suppressing the inflammatory storm, regulating immune function, and resisting viral invasion. Furthermore, the molecular docking results showed an excellent binding affinity between the core compounds and the hub genes. CONCLUSION: This study preliminarily predicted the potential therapeutic targets, signaling pathways, and molecular mechanisms of SHXP in the treatment of severe COVID-19, which include the moderate immune system, relieves the "cytokine storm," and anti-viral entry into cells.

A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation.

BACKGROUND: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. METHODS: Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis. RESULTS: The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis. CONCLUSIONS: Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI.