BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,pe...BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,peripheral blood mononuclear cells(PBMCs)serve as a robust model for investigating intracellular alterations linked to SZ.AIM To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ.METHODS PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes(DEGs)and differentially expressed proteins while mapping putative disease-associated signaling pathways.Key findings were validated using western blot(WB)and real-time fluorescence quantitative PCR(RT-qPCR).RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro,with subsequent verification of target gene expression via RT-qPCR.The levels of neuronal conduction proteins,including calmodulin-dependent protein kinase II(caMKII),CREB,and BDNF,were assessed through WB.Apoptosis was quantified by flow cytometry,while cell proliferation and viability were evaluated using the Cell Counting Kit-8 assay.RESULTS The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes,among which 25 DEGs were significantly altered between the SZ group and healthy controls.Notably,haptoglobin(HP),lactotransferrin(LTF),and SERPING1 exhibited marked upregulation.KEGG pathway enrichment analysis implicated neuroactive ligand-receptor interaction pathways in disease pathogenesis.Clinical sample validation demonstrated elevated protein and mRNA levels of HP,LTF,and SERPING1 in the SZ group compared to controls.WB analysis of all clinical samples further corroborated the significant upregulation of SERPING1.In hippocampal CA1 neurons transfected with lentivirus,reduced SERPING1 expression was accompanied by increased levels of CaMKII,CREB,and BDNF,enhanced cell viability,and reduced apoptosis.CONCLUSION SERPING1 may suppress neural cell proliferation in SZ patients via modulation of the CaMKII-CREB-BDNF signaling pathway.展开更多
AIM: To investigate the association between SERPING1rs2511989(G】A) polymorphism and age-related macular degeneration(AMD).METHODS: A number of electronic databases(up to July 15, 2014) were searched independently by ...AIM: To investigate the association between SERPING1rs2511989(G】A) polymorphism and age-related macular degeneration(AMD).METHODS: A number of electronic databases(up to July 15, 2014) were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios(ORs) with 95% confidence intervals(CIs) were estimated.RESULTS: Eight studies with 16 cohorts consisting of9163 cases and 6813 controls were included in this Metaanalysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates(A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95% CI =0.719-1.056;AG vs GG: OR =0.944, 95% CI =0.845-1.054; AA +AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG +GG:OR =0.890, 95% CI =0.780-1.034). Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium(HWE) were excluded(overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95% CI =0.817-0.994, P =0.038). However, the results were notsufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction(with a significance level set at 0.05/25).CONCLUSION: This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future.展开更多
基金Supported by the Key R&D Projects of Hainan Province,No.ZDYF2022SHFZ295.
文摘BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,peripheral blood mononuclear cells(PBMCs)serve as a robust model for investigating intracellular alterations linked to SZ.AIM To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ.METHODS PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes(DEGs)and differentially expressed proteins while mapping putative disease-associated signaling pathways.Key findings were validated using western blot(WB)and real-time fluorescence quantitative PCR(RT-qPCR).RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro,with subsequent verification of target gene expression via RT-qPCR.The levels of neuronal conduction proteins,including calmodulin-dependent protein kinase II(caMKII),CREB,and BDNF,were assessed through WB.Apoptosis was quantified by flow cytometry,while cell proliferation and viability were evaluated using the Cell Counting Kit-8 assay.RESULTS The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes,among which 25 DEGs were significantly altered between the SZ group and healthy controls.Notably,haptoglobin(HP),lactotransferrin(LTF),and SERPING1 exhibited marked upregulation.KEGG pathway enrichment analysis implicated neuroactive ligand-receptor interaction pathways in disease pathogenesis.Clinical sample validation demonstrated elevated protein and mRNA levels of HP,LTF,and SERPING1 in the SZ group compared to controls.WB analysis of all clinical samples further corroborated the significant upregulation of SERPING1.In hippocampal CA1 neurons transfected with lentivirus,reduced SERPING1 expression was accompanied by increased levels of CaMKII,CREB,and BDNF,enhanced cell viability,and reduced apoptosis.CONCLUSION SERPING1 may suppress neural cell proliferation in SZ patients via modulation of the CaMKII-CREB-BDNF signaling pathway.
基金Supported by the Scientific and Technological Project of Tianjin Health Bureau(No.12KG123website URL)
文摘AIM: To investigate the association between SERPING1rs2511989(G】A) polymorphism and age-related macular degeneration(AMD).METHODS: A number of electronic databases(up to July 15, 2014) were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios(ORs) with 95% confidence intervals(CIs) were estimated.RESULTS: Eight studies with 16 cohorts consisting of9163 cases and 6813 controls were included in this Metaanalysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates(A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95% CI =0.719-1.056;AG vs GG: OR =0.944, 95% CI =0.845-1.054; AA +AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG +GG:OR =0.890, 95% CI =0.780-1.034). Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium(HWE) were excluded(overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95% CI =0.817-0.994, P =0.038). However, the results were notsufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction(with a significance level set at 0.05/25).CONCLUSION: This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future.
