Yanping Zhuang

To investigate the association between single nucleotide polymorphism (SNP) at the rs3918188, rs1799983 and rs1007311 loci of the endothelial nitric oxide synthase (eNOS) gene and genetic susceptibility to systemic lupus erythematosus (SLE) in northeastern China. The base distribution of eNOS gene rs3918188, rs1799983 and rs1007311 in 1712 human peripheral blood samples from Northeast China was detected by SNaPshot sequencing technology. The correlation between genotype, allele and gene model of these loci of the eNOS gene and the genetic susceptibility to SLE was investigated by logistic regression analysis. The results of the differences in the frequency distribution of their gene models were visualised using R 4.3.2 software. Finally, HaploView 4.2 software was used to analyse the relationship between the haplotypes of the three loci mentioned above and the genetic susceptibility to SLE. A multifactor dimensionality reduction (MDR) analysis was used to determine the best SNP-SNP interaction model. The CC genotype and C allele at the rs3918188 locus may be a risk factor for SLE (CC vs AA: OR = 1.827, P < 0.05; C vs A: OR = 1.558, P < 0.001), and this locus increased the risk of SLE in the dominant model and the recessive model (AC + CC vs AA: OR = 1.542, P < 0.05; CC vs AA + AC: OR = 1.707, P < 0.001), while the risk of SLE was reduced in the overdominant model (AC vs AA + CC: OR = 0.628, P < 0.001). The GT genotype and T allele at locus rs1799983 may be a protective factor for SLE (GT vs GG: OR = 0.328, P < 0.001; T vs G: OR = 0.438, P < 0.001) and this locus reduced the risk of SLE in the overdominant model (GT vs GG + TT: OR = 0.385, P < 0.001). There is a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene. Among them, the formed haplotype AG increased the risk of SLE compared to GG. AT and GT decreased the risk of SLE compared to GG. In this study, the eNOS gene rs3918188 and rs1799983 loci were found to be associated with susceptibility to SLE. This helps to deeply explore the mechanism of eNOS gene and genetic susceptibility to SLE. It provides a certain research basis for the subsequent exploration of the molecular mechanism of these loci and SLE, as well as the early diagnosis, treatment and prognosis of SLE.

To investigate the correlation between susceptibility to systemic lupus erythematosus (SLE) and single nucleotide polymorphisms (SNPs) rs699, rs4762 and rs1926723 in the AGT gene in the population of Northeast China, while also introducing a new method for early detection of SLE. A total of 856 cases of SLE patients and healthy volunteers who attended the First Affiliated Hospital of Harbin Medical University from January 2020 to December 2022 were recruited. Clinical information and biood samples were collected from particpants in this study. SNaPshot sequencing technology was used to sequence the bases of the rs699, rs4762 and rs1926723 in the AGT gene. The genetic stability of SNPs was analysed by means of Hardy-Weinberg (HWE) genetic equilibrium. The study examined the correlation between genetically stable SNPs and susceptibility to SLE using logistic regression analysis. Rs699 did not adhere to the principles of the HWE genetic equilibrium (p < .01). Conversely, both rs4762 and rs1926723 conformed to the HWE genetic equilibrium (p > .05). However, no significant differences in genotypes and alleles frequencies of the rs4762 were observed between the two groups (p > .05). Furthermore, there was a significant difference in the distribution of AG, GG genotypes frequency and G allele frequency at the rs1926723 between the two groups (p < .001). Individuals with AG and GG genotypes and the G allele had a significantly lower frequency of SLE, indicating a potential genetic protective factor against susceptibility to the SLE. The SNPs rs1926723 may be linked to the susceptibility to SLE, and the AG, GG genotypes and the G allele may be important protective factors for the development of SLE in Northeast China.

Objective: To investigate the molecular mechanism and simulated validation of Zhi Bai Di Huang Pill (ZBDHP) for the treatment of systemic lupus erythematosus (SLE) using network pharmacology and molecular docking techniques. Methods: The active ingredients of ZBDHP were obtained through the TCMSP database and the Canonical SMILES of the active ingredients were queried through Pubchem. The targets of the active ingredients were predicted in the SwissTarget database based on the SMILES. The SLE-related disease targets were obtained through the GeneCards, OMIM and DisGenets databases, and the intersection targets of ZBDHP and SLE were obtained using the Venny 2.1.0 online platform. Intersection targets build a visual protein interaction network (PPI) through the STRING database, and the core targets were identified by network topology analysis. GO analysis and KEGG pathway enrichment analysis of the intersecting targets were performed using the DAVID database. Finally, the molecular docking of the first four active ingredients and the first four core target genes were verified by Pubchem, the PDB database and CB-Dock online molecular docking technology. Results: ZBDHP screened 91 potential active ingredients and 816 potential targets. Among them, 141 genes were intersected by ZBDHP and SLE. The network topology analysis showed that the main active ingredients were Hydroxygenkwanin, Alisol B, asperglaucide, Cerevisterol, etc., and the key target genes were TNF, AKT1, EGFR, STAT3, etc. GO and KEGG enrichment analysis showed that common targets interfere with biological processes or molecular functions such as signal transduction protein phosphorylation, inflammatory response, transmembrane receptor protein tyrosine kinase activity, etc., through multiple signaling pathways, such as pathways in cancer, Kaposi sarcoma-associated herpesvirus infection, the PI3K-Akt signaling pathway, lipid and atherosclerosis, hepatitis B, etc. Molecular docking results showed that the active components of ZBDHP have good binding activity to the core targets of SLE. Conclusions: This study reveals that the ZBDHP treatment of SLE is a complex mechanistic process with multi-components, multi-targets and multi-pathways, and it may play a therapeutic role in SLE by inhibiting the production, proliferation and apoptosis of inflammatory factors. In conclusion, the present study provides a theoretical basis for further research on ZBDHP.