Vaccination and the risk of systemic lupus erythematosus: a meta-analysis of observational studies.

OBJECTIVE: This meta-analysis aims to explore the potential link between vaccines and systemic lupus erythematosus (SLE). METHODS: We systematically searched PubMed, Cochrane Library, and Embase for observational studies from inception to September 3, 2023, using medical subject headings (MeSH) and keywords. Study quality was assessed using the NOS scale. Statistical analyses were conducted using STATA software (version 14.0). Publication bias was evaluated using funnel plots and Egger's regression. RESULTS: The meta-analysis incorporated 17 studies, encompassing 45,067,349 individuals with follow-up periods ranging from 0.5 to 2 years. The pooled analysis revealed no significant association between vaccinations and an increased risk of SLE [OR = 1.14, 95% CI (0.86-1.52), I2 = 78.1%, P = 0.348]. Subgroup analyses indicated that HBV vaccination was significantly associated with an elevated risk of SLE [OR =2.11, 95% CI (1.11-4.00), I2 = 63.3%, P = 0.02], HPV vaccination was slightly associated with an increased risk of SLE [OR = 1.43, 95% CI (0.88-2.31), I2 = 72.4%, P = 0.148], influenza vaccination showed no association with an increased risk of SLE [OR = 0.96, 95% CI (0.82-1.12), I2 = 0.0%, P = 0.559], and COVID-19 vaccine was marginally associated with a decreased risk of SLE [OR = 0.44, 95% CI (0.18-1.21), I2 = 91.3%, P = 0.118]. CONCLUSIONS: This study suggests that vaccinations are not linked to an increased risk of SLE. Our meta-analysis results provide valuable insights, alleviating concerns about SLE risk post-vaccination and supporting further vaccine development efforts.

The mechanism of Langchuangding in treatment of systemic lupus erythematosus via modulating TLR7-IRF7-IFNα pathway.

Object: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by aberrant activity of the immune system. Plasmacytoid dendritic cells (pDCs) which the main producer of activated type I interferon, are related to SLE disease activity. To investigate the mechanism of Langchuangding (LCD) improving SLE based on TLR7-IRF7-IFNα pathway. Methods: SLE patients were randomly divided into Chinese medicine combined with western medicine (CWM) group and western medicine (WM) group, to observe the effect of LCD. The percent of pDCs in peripheral blood of SLE patients were detected by flow cytometry, and the influence of LCD on gene expression in SLE patients were detected by gene microarray. Mouse bone marrow cells were differentiated into dendritic like cells (DLC), then divided into Blank, immune complex (IC), LCD and dexamethasone (DXM) group. Employed RT-qPCR to detect MyD88, and IRF7 mRNA, and western blotting to determinate TLR7, MyD88, and p-IRF7 proteins. The IFNα in SLE patients were detected by enzyme-linked immunosorbent assay (ELISA). Employ dual luciferase to observe the interferon stimulated response element (ISRE) gene. Results: pDCs in WM group was higher than that of CWM group. The plasma IFNα in CWM group was significantly lower than that in WM group. The gene microarray showed that the gene expression of IFNα related signaling pathway in peripheral blood mononuclear cell (PBMC) and genes related to activation and proliferation of immune cells were down-regulated after LCD treatment. The DLCs MyD88, and IRF7 mRNA were down-regulated, TLR7, MyD88, and p-IRF7 proteins were significantly reduced, and the supernatant IFNα was significantly decreased in LCD group. LCD were mildly inhibited activation of ISRE in 293T cells. Conclusions: In certain degree, LCD is beneficial to SLE patients. LCD therapy SLE may be through TLR7 signaling pathway, and IRF7 may be a promising therapeutic target for the treatment of SLE.

Nuclear isoform of FGF13 regulates post-natal neurogenesis in the hippocampus through an epigenomic mechanism.

The hippocampus is one of two niches in the mammalian brain with persistent neurogenesis into adulthood. The neurogenic capacity of hippocampal neural stem cells (NSCs) declines with age, but the molecular mechanisms of this process remain unknown. In this study, we find that fibroblast growth factor 13 (FGF13) is essential for the post-natal neurogenesis in mouse hippocampus, and FGF13 deficiency impairs learning and memory. In particular, we find that FGF13A, the nuclear isoform of FGF13, is involved in the maintenance of NSCs and the suppression of neuronal differentiation during post-natal hippocampal development. Furthermore, we find that FGF13A interacts with ARID1B, a unit of Brahma-associated factor chromatin remodeling complex, and suppresses the expression of neuron differentiation-associated genes through chromatin modification. Our results suggest that FGF13A is an important regulator for maintaining the self-renewal and neurogenic capacity of NSCs in post-natal hippocampus, revealing an epigenomic regulatory function of FGFs in neurogenesis.

Metabolic inflammation exacerbates dopaminergic neuronal degeneration in response to acute MPTP challenge in type 2 diabetes mice.

Parkinson's disease (PD), one of the most common neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra. Increasing epidemiological evidence has indicated that type 2 diabetes (T2D) may be implicated in the pathogenesis of PD. However, the exact association and the underlying mechanism remain unclear. In the present study, ob/ob and db/db mice, the well accepted T2D models, were acutely treated with MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) to mimic PD-like neural injury. We found that insulin signaling impairment occurred not only in pancreas and livers, but also in the midbrain of ob/ob and db/db mice. Notably, the expressions of monomeric and oligomeric α-synuclein as well as endoplasmic reticulum stress markers (CHOP and GRP78) were significantly upregulated in both pancreas and midbrain of T2D mice, accompanied by the increased activation of NLRP3 inflammasomes to produce excess IL-1ß. Furthermore, we found that acute MPTP administration aggravated the loss of dopaminergic neurons and increased the activation of glial cells in the substantia nigra of db/db mice. Collectively, these findings demonstrate that α-synuclein accumulation and neuroinflammation are aggravated in the midbrain of T2D mice and T2D mice are more susceptible to the neurotoxicity induced by MPTP. Our study indicates that metabolic inflammation exacerbates DA neuronal degeneration in the progress of PD, which will provide a novel insight into the etiology of PD.