Exploring the potential mechanism of Xuebijing injection against sepsis based on metabolomics and network pharmacology.

Sepsis is a major contributor to the death of critically ill patients globally, in which metabolic disturbance is observed. Xuebijing injection (XBJ), a well-known traditional Chinese medicine, has received approval by the State Food and Drug Administration (SFDA) of China owing to its satisfactory clinical therapeutic effect. Nowadays, it has been applied clinically to the treatment of sepsis, but its effect on metabolic disorders remains unclear. In the present study, we sought to explore its underlying mechanism by employing a combination of network pharmacology and metabolomics. Initially, its protective effects were validated using a sepsis rat model created through cecal ligation puncture (CLP). Subsequently, the metabonomic strategy was utilized to discriminate the differential metabolic markers. Meanwhile, a comprehensive view of the potential ingredient-target-disease network was constructed based on a network pharmacology analysis. Next, the network diagram was constructed by integrating the results of network pharmacology and metabonomics. Finally, qRT-PCR together with Western blot was used to validate the expression levels of the associated genes. Based on our findings, we identified 34 differential metabolites in the sepsis group and 26 distinct metabolites in the XBJ group, with 8 common biological metabolites predominantly associated with arginine and proline metabolism. Through comprehensive analysis, we identified 21 genes that regulate metabolites, and qRT-PCR validation was conducted on six of these genes in both liver and kidney tissues. Additionally, XBJ demonstrated the capability to inhibit the activation of the NF-kB signaling pathway in both liver and kidney tissues, leading to a reduction in the occurrence of inflammatory responses. In summary, our study has validated the complexity of the natural compounds within XBJ and elucidated their potential mechanisms for addressing CLP-induced metabolic disturbances. This work contributes to our understanding of the bioactive compounds and their associated targets, providing insights into the potential molecular mechanisms involved.

[Corrigendum] Azurocidin 1 inhibits the aberrant proliferation of triple­negative breast cancer through the regulation of pyroptosis.

Following the publication of the above article, the authors drew to our attention that they had made a couple of inadvertent errors in assembling Figs. 4 and 5; first, for the BT­549 cell line, the data shown for the Pro­caspase­1/Cleaved caspase­1 in Fig. 5 and the GSDMD­F/GSDMD­N data in Fig. 4B were identical, and had been derived from the same original source; secondly, in Fig. 4A, the data shown correctly for the GSDMD BT­549 cell line had also inadvertently been included in this figure to represent the MDA­MB­231 cell line. The revised and corrected versions of Figs. 4 and 5, showing the correct western blotting data for the GSDMD experiment in Fig. 4A and the Pro­caspase­1/Cleaved caspase­1 data for the BT­549 cell line in Fig. 5, are shown in the next two pages. The authors regret that these errors in the assembly of Figs. 4 and 5 went unnoticed before the article was published, and thank the Editor of Oncology Reports for granting them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they apologize to the readership of the journal for any inconvenience caused.[Oncology Reports 50: 188, 2023; DOI: 10.3892/or.2023.8625].

Network-based pharmacology-based research on the effect and mechanism of the Hedyotis diffusa-Scutellaria Barbata pair in the treatment of hepatocellular carcinoma.

The Hedyotis diffusa-Scutellaria officinalis pair (HD-SB) has therapeutic effects on a variety of cancers. Our study was to explore the mechanism of HD-SB in the treatment of hepatocellular carcinoma (HCC). A total of 217 active ingredients of HD-SB and 1196 HCC-related targets were reserved from the TCMSP and the SwissTarget Prediction database, and we got 63 intersection targets from GeneCards. We used a Venn diagram, and Cytoscape found that the three core ingredients were quercetin, luteolin, and baicalein. The PPI analysis showed that the core targets were TP53, CDK2, XPO1, and APP. Molecular docking results showed that these core ingredients had good binding potential with the core targets. HD-SB acts simultaneously on various HCC-related signaling pathways, including proteoglycans in cancer and the P53 signaling pathway. In vitro experiments confirmed that HD-SB can inhibit HepG2 cell proliferation by increasing TP53 and APP levels and decreasing XPO1 and CDK2 levels. This study analyzed active ingredients, core targets, and central mechanisms of HD-SB in the treatment of HCC. It reveals the role of HD-SB in targeting the P53 signaling pathway in the treatment of HCC. We hope that our research could provide a new perspective to the therapy of HCC and find new anticancer drugs.

Metformin Mitigates Sepsis-Induced Acute Lung Injury and Inflammation in Young Mice by Suppressing the S100A8/A9-NLRP3-IL-1ß Signaling Pathway.

Background: Globally, the subsequent complications that accompany sepsis result in remarkable morbidity and mortality rates. The lung is among the vulnerable organs that incur the sepsis-linked inflammatory storm and frequently culminates into ARDS/ALI. The metformin-prescribed anti-diabetic drug has been revealed with anti-inflammatory effects in sepsis, but the underlying mechanisms remain unclear. This study aimed to ascertain metformin's effects and functions in a young mouse model of sepsis-induced ALI. Methods: Mice were randomly divided into 4 groups: sham, sham+ Met, CLP, and CLP+ Met. CLP was established as the sepsis-induced ALI model accompanied by intraperitoneal metformin treatment. At day 7, the survival state of mice was noted, including survival rate, weight, and M-CASS. Lung histological pathology and injury scores were determined by hematoxylin-eosin staining. The pulmonary coefficient was used to evaluate pulmonary edema. Furthermore, IL-1ß, CCL3, CXCL11, S100A8, S100A9 and NLRP3 expression in tissues collected from lungs were determined by qPCR, IL-1ß, IL-18, TNF-α by ELISA, caspase-1, ASC, NLRP3, P65, p-P65, GSDMD-F, GSDMD-N, IL-1ß and S100A8/A9 by Western blot. Results: The data affirmed that metformin enhanced the survival rate, lessened lung tissue injury, and diminished the expression of inflammatory factors in young mice with sepsis induced by CLP. In contrast to sham mice, the CLP mice were affirmed to manifest ALI-linked pathologies following CLP-induced sepsis. The expressions of pro-inflammatory factors, for instance, IL-1ß, IL-18, TNF-α, CXCL11, S100A8, and S100A9 are markedly enhanced by CLP, while metformin abolished this adverse effect. Western blot analyses indicated that metformin inhibited the sepsis-induced activation of GSDMD and the upregulation of S100A8/A9, NLRP3, and ASC. Conclusion: Metformin could improve the survival rate, lessen lung tissue injury, and minimize the expression of inflammatory factors in young mice with sepsis induced by CLP. Metformin reduced sepsis-induced ALI via inhibiting the NF-κB signaling pathway and inhibiting pyroptosis by the S100A8/A9-NLRP3-IL-1ß pathway.

Azurocidin 1 inhibits the aberrant proliferation of triple­negative breast cancer through the regulation of pyroptosis.

Azurocidin 1 (AZU1) is a heparin­binding protein which has been reported to be aberrantly expressed in various tumors, but its definite role in breast cancer (BC) has not been clarified. The aim of the present study was to explore the associations between AZU1 and BC. In the present study, bioinformatics and western blot analyses were applied to detect the expression level of AZU1 in BC tissues. The effect of AZU1 on cell proliferation and apoptosis was analyzed using Cell Counting Kit­8 assay, colony formation assay and flow cytometry. Based on bioinformatics analysis, AZU1 exhibited low expression in tissues and was negatively associated with the survival rate of patients with triple­negative BC (TNBC). Exogenous AZU1 stimuli significantly inhibited the proliferation and colony formation of TNBC cell lines. Furthermore, the data of flow cytometry revealed that exogenous AZU1 stimuli enhanced apoptosis in MDA­231 and BT­549 cells. As pyroptosis is a new type of cell death, the effects AZU1 played on the expression of gasdermin D (GSDMD), a specific biomarker of pyroptosis, were also investigated. The findings of the present study revealed that GSDMD, as well as its upstream regulators [NF­κB, NLR family pyrin domain containing 3 (NLRP3) and caspase­1], were significantly increased in TNBC cell lines when treated with exogenous AZU1, indicating that AZU1 contributed to the inhibition of pyroptosis of TNBC cell lines through the NF­κB/NLRP3/caspase­1 axis. Collectively, it was revealed for the first time, that AZU1 exposure promoted pyroptosis through the modulation of the pNF­κB/NLRP3/caspase­1/GSDMD axis in TNBC in vitro. The findings of the present study unveiled a novel mechanism of AZU1­induced pyroptosis in TNBC, which may aid in developing new strategies for therapeutic interventions in TNBC. breast cancer is the most commone form of cancer in women and is second only to lung cancer in terms of cancer­related mortality.

Shengjiang San alleviated sepsis-induced lung injury through its bidirectional regulatory effect.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection, for which effective therapeutic strategies are still absent. Shengjiang San (SJS), a well-known Traditional Chinese Medicine formula, has been widely used clinically. However, its role in sepsis-induced lung injury remains unclear. METHODS: To explore its specific mechanism, we firstly established a sepsis animal model using cecal ligation and puncture (CLP) and treated MH-S cells with LPS plus ATP. Then, UPLC/Q-TOF-MS/MS was utilized to identify its active ingredients. Network pharmacology analysis was performed to uncover the potential mechanism. HE staining and biochemical analysis were conducted to validate its therapeutic effect. ELISA was applied to detect the release of pro-inflammatory and anti-inflammatory cytokines. Western blot was utilized to detect the protein levels of GSDMD, NLRP3, P65, ASC and caspase-1. RESULTS: SJS could dramatically increase the survival rate of sepsis. In addition, it is able to inhibit the pro-inflammatory cytokines release at day 1 post CLP while promote their production at day 7, indicating SJS could attenuate uncontrolled inflammatory response in the early stage and improve immunosuppression in the late phase. Network pharmacology analysis showed that pyroptosis is the crucial action SJS exerted in the protection of sepsis-induced lung injury. Western blot data implicated SJS could attenuate pyroptosis in early sepsis while enhance in the late phase. CONCLUSIONS: SJS acted to alleviate sepsis-induced lung injury through its bidirectional regulatory effect.

Effectiveness and safety of different traditional Chinese medicines for Coronavirus disease 2019: A protocol for systematic review and network meta-analysis.

INTRODUCTION: The effectiveness of different Traditional Chinese Medicine in the treatment of COVID-19 is worthy of attention, but the efficacy and safety of different Traditional Chinese Medicine in the treatment of COVID-19 have not yet been compared, based on network meta-analysis. METHODS AND ANALYSIS: The 2 members independently searched 7 databases according to the retrieval strategy, and the retrieval time was from the beginning of the establishment of the database to June 19, 2021. Then the title was imported into the EndNote Software AQ8 (V.X9), and the duplicate literature was deleted successively, the nonconforming articles were deleted in the title reading, and finally the full text was read to determine the articles included in the study. The Cochrane Collaboration's Tool will be used to evaluate the article quality, and Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX) will be used for data analysis. Levels of evidence are evaluated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. RESULTS: The efficacy and safety of different Traditional Chinese Medicine in the treatment of COVID-19 were evaluated, and the order was determined according to the value of sucre. CONCLUSION: This study will provide evidence for the treatment of COVID-19 with TCM therapy, and provide ideas for the clinical treatment of COVID-19. INPLASY REGISTRATION NUMBER: No. INPLASY202160092.

Effectiveness and safety of different medicines for Uremia pruritus: A protocol for systematic review and network meta analysis.

INTRODUCTION: A large number of patients will experience pruritus after uremia. Medicine is the preferred treatment for many doctors, but the effectiveness and safety of different medicines for uremia pruritus has not yet been comprehensively compared, based on network meta-analysis. METHODS AND ANALYSIS: According to the retrieval strategy, two team members independently searched the literature in 7 databases, and imported the retrieval results into the EndNote Software AQ8 (V.X9). After deleting repeated articles, they read the abstract and the full text, selected the articles that met the inclusion criteria and extracted valid information. The main results were visual analogue scale (VAS) and the secondary results were verbal rating scale (VRS), Dirk R Kuypers score, and adverse event incidence. The methodological quality evaluation was conducted from 7 aspects, according to The Cochrane Collaborative Tool, Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX) was used for data analysis. The level of evidence will be assessed by the Grading of Recommendations, Development and Evaluation (GRADE) instrument). RESULTS: The results will rank the efficacy of drugs used to treat uremic pruritus and assess their safety. CONCLUSION: This study is the first to compare the efficacy and safety of medicines for uremic pruritus based on network analysis and will provide evidence and ideas for the treatment of uremic pruritus. INPLASY REGISTRATION NUMBER: No. INPLASY202090103.

Effectiveness and safety of different traditional Chinese medicine therapies for allergic rhinitis: A protocol for systematic review and network meta analysis.

INTRODUCTION: Traditional Chinese medicine has been widely used in the treatment of allergic rhinitis. However, currently randomized controlled trials (RCTs) and meta-analysis only compare 1 or 2 types of traditional Chinese medicine therapies, and the comprehensive ranking of efficacy and safety of multiple traditional Chinese medicine therapies for the treatment of allergic rhinitis has not been completed. Therefore, the purpose of this network meta-analysis is to evaluate the efficacy and safety of different traditional Chinese medicine therapies for the treatment of allergic rhinitis. METHODS AND ANALYSIS: Three English databases of PubMed, Embase, Cochrane Library, and 2 Chinese databases of CNKI and Wanfang were searched from their inceptions to September 1, 2020. At the same time, in order to prevent omissions, we also compared the previous meta-analysis to determine the final included trials. The main evaluation outcome was the total Clinical Score (total nasal symptom score [TNSS]), the secondary evaluation outcome was the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and adverse events. The Cochrane Collaboration's Tool was used to evaluate the methodological quality of articles, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument was used to evaluate the quality of evidence. Network meta-analysis was completed by using Stata Statistical Software (Version 14.0, Stata Corporation, College Station, TX). RESULTS: This study will compare and rank the different traditional Chinese medicine therapies for allergic rhinitis. CONCLUSION: This study is the first time to use network meta-analysis (NMA) to compare the efficacy and safety of traditional Chinese medicine for the treatment of allergic rhinitis, which will provide ideas and methods for the clinical treatment for allergic rhinitis. INPLASY REGISTRATION NUMBER: No. INPLASY202080119.

Comparative efficacy and safety of injection therapies for knee osteoarthritis: A protocol for systematic review and Bayesian network meta analysis.

INTRODUCTION: There are many injection methods for the treatment of knee osteoarthritis, but there is no comprehensive comparison, based on the fixed effect model. METHODS: According to the retrieval strategy, we searched randomized controlled trials (RCTs) randomly from PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), Wanfang Database from their inceptions to August 2020, and 2 members of us selected literatures and extracted data independently. Methodological quality was assessed by using the Cochrane bias risk tool, and meta-analysis was performed by using the Stat.14.0. RESULTS: This study will evaluate the effectiveness and safety of different injectable drugs for the treatment of knee osteoarthritis and rank the efficacies of drugs, then to determine the optimal treatment. CONCLUSION: This study will provide evidence for the choice of injection therapy for knee osteoarthritis. INPLASY REGISTRATION NUMBER: INPLASY202080099.