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AbstractBACKGROUNDMETHODSRESULTSCONCLUSIONSPrevious studies have shown that an increased number of immune cells is closely associated with the onset and course changes of intracerebral hemorrhage, but the exact causal relationship has not been clarified. The aim of this study was to investigate the causal relationship between immune cells and intracerebral hemorrhage by a two-way Mendelian randomization method.Two sets of SNPs were used as instrumental variables and two-way Mendelian randomization analyses were performed and leave-one-out method were used to assess the validity and heterogeneity of the included genetic variation instruments. The level of multiplicity and heterogeneity of the included genetic variance instruments was assessed.The results showed a clear causal relationship between three immune cells and intracerebral hemorrhage, and no heterogeneity between SNPs related to intracerebral hemorrhage, while scatterplot and funnel plot confirmed that the causality was less likely to be biased; MR-Egger results suggested that no genetic pleiotropy was found. Leave-one-out analysis was applied to suggest that the MR analysis results for a single SNP were robust; meanwhile, Meta-analysis was applied to combine the two intracerebral hemorrhage datasets, and the analysis results suggested that in the fixed-effects model and random-effects model, the immunocyte CD66b on Granulocytic Myeloid-Derived Suppressor Cells and other three immune cells were significantly causally associated with intracerebral hemorrhage, while the heterogeneity test suggested that there was no significant difference between the different datasets.The present study found a significant causal relationship between specific immune cell phenotypes and intracerebral hemorrhage by Mendelian randomization analysis. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) is a significant pathogen affecting swine, causing severe economic losses worldwide. This study explores the regulatory role of miRNA-328-3p to ZO-1 expression and its impact on PEDV proliferation via the PLC-β1-PKC pathway in IPEC-J2 cells. We found that miRNA-328-3p can target ZO-1, influencing its expression and subsequently affecting the integrity of tight junctions in the cells. Overexpression of PLC-β1, combined with miRNA-328-3p silencing, enhanced ZO-1 expression, while PLC-β1 knockdown combined with miRNA-328-3p overexpression inhibited ZO-1 expression. Furthermore, PLC-β1 overexpression increased both viral genome expression and PEDV titers, whereas its silencing had the opposite effect. Notably, our data indicated a negative correlation between PLC-β1 and PKC expression, and PKC silencing attenuated the upregulatory effect of PLC-β1 on ZO-1. These findings suggest that PLC-β1 modulates ZO-1 expression through the PKC pathway, providing new insights into the molecular mechanisms of PEDV infection and potential therapeutic targets. [ABSTRACT FROM AUTHOR]