RESUMO
Objective: Iguratimod (IGU) is a novel small disease-modifying compound widely used in Asia for the treatment of rheumatic diseases. IGU is a methane sulfonanilide. We applied network pharmacology to investigate the pharmacological mechanisms of IGU act on SLE. Methods: We used PharmMapper, UniProt, and OMIM databases to screen the potential targets of IGU, and the SLE-related disease targets were predicted. Hub target genes among the intersections of the potential targets (IGU) and related genes (SLE) were validated using the PPI network generated by the String database. GO and KEGG enrichment analyses were carried out using the David online platform. Finally, the molecular docking of hub targets and their corresponding compounds were completed through AutoDock Vina and PyMOL software for visualization. Result: A total of 292 potential targets of IGU, 6501 related disease targets of SLE, and 114 cross targets were screened from the aforementioned database. Network topology analysis identified 10 hub targets, such as CASP3, AKT1, EGFR, MMP9, and IGF1. GO enrichment analysis mainly focuses on the negative regulation of the apoptotic process and signal transduction. KEGG enrichment analysis illustrated that the PI3K-AKT signaling pathway, MAPK signaling pathway, and FoxO signaling pathway might play a significant role in the pharmacological mechanisms of IGU act on SLE. Molecular docking confirmed that the IGU ligand had strong binding activity to the hub targets. Conclusion: This study based on network pharmacology and molecular docking validation preliminarily revealed the protein targets affected by IGU acting on SLE through, and explored potential therapeutic mechanism role of IGU in SLE treatment by multi pathways.
RESUMO
Patients with rheumatic diseases (RD) are considered to be a high-risk population for infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The effectiveness of inactivated COVID-19 vaccinations (ICVs) was described as more effective than 95%. Despite this, no data on the immunogenicity and safety of the ICV in Han race stable RD patients in China. In this study, we sought to assess the safety and immunogenicity of the ICVs in RD patients in South China. A total of 80 adult stable RD patients were recruited. Following 14-35 days of immunization, cheiluminescence immunoassays (CLIA) were utilized to detect antibodies titers. An investigation into the relative parameters on the immunogenicity response to vaccination was carried out using logistic regression analysis. Compared to the HC group, the positive response of IgG and Nab in RD patients were lower than those in healthy control (HC) (P = .040 and P < .0001, respectively) after two doses of ICV were inoculated. The use of methotrexate (P = .016) and prednisolone (P = .018), and the level of red blood cell distribution width-C (RDW-C) (P = .035) and C-reactive protein (P = .015) were independently associated with lower rises in the magnitude of COVID-19 vaccine antibodies. No vaccine-related serious adverse reactions were observed in either group. After receiving two doses of ICVs, the production of protective antibodies in stable RD patients treated with immunosuppressive agents may decrease. It was discovered that ICVs were safe and well tolerated by RD patients.
What is the context?There are currently no accessible data on the efficacy and safety of inactivated COVID-19 vaccinations in South China RD patients who are receiving immunosuppressive medications.What is new?Inactivated COVID-19 vaccinations were immunogenic in stable RD patients in our investigation. No significant adverse reactions to the vaccination were seen in either group. No disease flares were observed in our study.What is the impact?Inactivated COVID-19 vaccinations are immunogenic and safe in stable RD patients in China, according to the findings of this study. The use of methotrexate or prednisolone, the RDW-C level, and the CRP level may all have an effect on the development of protective antibodies following vaccination.
