[Mechanism of Yuxuebi Tablets in treating synovial inflammation in rheumatoid arthritis based on transcriptomics].

This study investigated the mechanism of Yuxuebi Tablets(YXB) in the treatment of synovial inflammation in rheumatoid arthritis(RA) based on transcriptomic analysis. Transcriptome sequencing technology was employed to analyze the gene expression profiles of joint tissues from normal rats, collagen-induced arthritis(CIA) rats(an RA model), and YXB-treated rats. Common diffe-rentially expressed genes(DEGs) were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. RA synovial inflammation-related target genes were retrieved from the OMIM and GeneCards databases. Venny 2.1 software was used to identify the intersection of YXB target genes and RA synovial inflammation-related target genes, and GO and KEGG enrichment analyses were performed on the intersecting target genes. Immunohistochemistry was used to assess the protein expression levels of the inflammatory factors interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in rat joint tissues. Western blot analysis was employed to measure the expression levels of key proteins in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway. A total of 2 058 DEGs were identified by intersecting the genes from the normal group vs model group and the model group vs YXB treatment group. A search in OMIM and GeneCards databases yielded 1 102 RA synovial inflammation-related target genes. After intersecting with the DEGs in the YXB treatment group, 204 intersecting target genes were identified, primarily involving biological processes such as immune response, signal transduction, and inflammatory response; cellular components including plasma membrane, extracellular space, and extracellular region; molecular functions like protein binding, identical protein binding, and receptor binding. These target genes were mainly enriched in signaling pathways such as PI3K/Akt, cytokine-cytokine receptor interaction, and Janus kinase/signal transducer and activator of transcription(JAK/STAT). Western blot results showed that YXB at low, medium, and high doses could significantly inhibit the expression levels of key proteins in the PI3K/Akt signaling pathway in rat joint tissues in a dose-dependent manner. Immunohistochemistry further confirmed these findings, showing that YXB not only suppressed the protein expression levels of the inflammatory factors IL-1ß and TNF-α in the joint synovial tissues of CIA rats, but also inhibited p-Akt protein expression. In conclusion, this study used transcriptomic analysis to uncover the key mechanisms of YXB in inhibiting synovial inflammation and alleviating the progression of RA, with a focus on its role in suppressing the PI3K/Akt signaling pathway.

[Mechanism of artesunate on bone destruction in experimental rheumatoid arthritis based on transcriptomics and network pharmacology].

The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.

[Anti-rheumatoid arthritis mechanism of Sophorae Tonkinesis Radix et Rhizoma based on network pharmacology and experimental verification].

Based on the network pharmacology, molecular docking, and animal experiment, this study explored the anti-rheumatoid arthritis(RA) mechanism of Sophorae Tonkinesis Radix et Rhizoma(STRR). The active components of STRR were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicine Integrative Database(TCMID), and previous research, main targets of STRR from TCMSP and SwissTargetPrediction, and targets of RA from GeneCards, DrugBank, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). The common targets of the two were screened by Venny 2.1.0. Cytoscape 3.6.0 was used to generate the "component-target" network, and STRING and Cytoscape were used to construct the protein-protein interaction(PPI) network. DAVID 6.8 was employed for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and AutoDock Vina for molecular docking. Finally, collagen-induced rheumatoid arthritis(CIA) mouse model was constructed, and the expression of core target proteins was detected by Western blot. A total of 27 active components, including quercetin, genistein, kaempferol, subprogenin C, and daidzein, and 154 anti-RA targets, such as signal transducer and activator of transcription 3(STAT3), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), AP-1 transcription factor subunit(JUN), and interleukin 6(IL6), of STRR were screened out. It was preliminarily indicated that STRR may regulate phosphatidylinositol-3-kinase-protein kinase B(PI3 K-AKT) signaling pathway and TNF signaling pathway to modulate the positive regulation of RNA polymerase Ⅱ promoter transcription, inflammatory response, and other biological processes, thus exerting the anti-RA effect. The results of molecular docking showed that the main active components in STRR had high binding affinity to the core targets. Animal experiment suggested that the water extract of STRR can significantly reduce the levels of p-STAT3, p-MAPK1, and TNF. This study demonstrated the multi-component, multi-target and multi-pathway synergistic effect of STRR in the treatment of RA, laying an experimental basis for clinical application of this medicine.

Safety and Efficacy of Ginkgo-Damole and Nitroglycerin or Sodium Nitroprusside on Hypertensive Cerebropathies: A Meta-Analysis.

OBJECTIVE: To systematically evaluate the safety and efficacy of ginko-damole combined with nitroglycerin or unitary sodium nitroprusside on hypertensive cerebropathy. METHODS: Four Chinese databases (VIP, CBM, Wanfang database, and CNKI database) and three English databases (Cochrane, PubMed, and EMBASE) were used to screen randomised controlled trials (RCTs) on treatments of hypertensive cerebropathy using both ginko-damole and nitroglycerin or unitary sodium nitroprusside. Outcomes included clinical effect, blood pressure after treatment, and adverse effects. These indicators were then analysed statistically using the RevMan 5.3 and Stata 12.0 software. RESULTS: Altogether, 16 RCTs including 1507 patients with hypertensive cerebropathy were included in the present meta-analysis, of which, 755 patients treated with combined ginko-damole and nitroglycerin were included in the observation group and 752 patients treated with sodium nitroprusside were included in the control group. The curative effect of the observation group was significantly better than that of the control group (RR: 1.115 [1.077, 1.155], p < 0.05). DBPs of the observation and control groups were both lower after treatment, and no significant difference was observed between the observation and control groups (MD: -1.072 [-2.578, 0.434], p > 0.05). SBPs in the observation group were significantly lower than those in the control group (MD: -2.842 [-5.222, -0.462], p < 0.05). The probability of adverse response in both groups did not differ significantly (RR: 0.752 [0.412, 1.374], p > 0.05). CONCLUSION: Compared with sodium nitroprusside, the combined ginkgo-damole and nitroglycerin could better control blood pressure in patients with hypertensive cerebropathy and showed enhanced clinical effects and improved safety. However, due to poor quality of the included studies, results of the present meta-analysis should be confirmed by more stringent RCTs.