Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct ro...Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is unknown.To date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.展开更多
As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The function...As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The functions of TNF-αin many species have been widely studied,particularly in mammals.However,little is known about the TNF-αfunctions in V.variegatus.We first cloned and sequenced the TNF-αgene in V.variegatus(VvTNF-α).The two conserved cysteine residues,transmembrane sequence,Thr-Leu motif,and TNF family signature,as well as the TA-rich motifs of its proteins related to inflammatory responses had high similarity to those of the other teleost and mammalian TNF-α.The phylogenetic analysis showed that VvTNF-αwas consistent with TNF-αgenes of other vertebrates.The VvTNF-αtranscripts were extensively distributed in the peripheral blood leukocytes(PBLs),spleen,and gill,indicating that the VvTNF-αhad a role in immune function.Furthermore,treatment with pathogen-associated molecular patterns(PAMPs)could induce a rapid and significant increase of VvTNF-αin the PBLs,which reveals that VvTNF-αdoes participate in the host immune responses against bacterial and viral pathogens.We found that VvTNF-αhad an interesting expression pattern during metamorphosis,showing that the flatfish TNF-αmay have some novel functions during specific developmental stages.In addition,the 3 D structure prediction of VvTNF-αprovided an indication of how it is likely to interact with other proteins.Therefore,VvTNF-αhas multiple functions,and provides valuable information to explore novel functions of TNF-α.展开更多
OBJECTIVE This study was to investigate the effects of CP-25 on the functions of activated human B cells through regulating BAFF and TNF-alpha signaling.METHODS B cells from peripheral blood mononuclear cells(PBMCs) o...OBJECTIVE This study was to investigate the effects of CP-25 on the functions of activated human B cells through regulating BAFF and TNF-alpha signaling.METHODS B cells from peripheral blood mononuclear cells(PBMCs) of normal human were isolated using magnetic cell separation(MACS) by a positive selection.B cells(107 cells·mL^(-1)) were stimulated by BAFF(100 ng·mL^(-1))or TNF-alpha(100 ng·mL^(-1)) for two hours,and then were treated with CP-25(10-5 mol·L^(-1)) or Rituximab(5 μg·mL^(-1)) or Etanercept(10 μg·mL^(-1)).B cell proliferation was detected by CCK-8.B cell subsets and BAFF receptors(BAFFR,BCMA and TACI) were analyzed by flow cytometry.The expression of TNFR1 and TNFR2 on B cells was analyzed by flow cytometry.The expression of MKK3,MKK6,P-p38,P-p65,TRAF2 and p100/52 was analyzed by Western blotting.RESULTS CP-25 inhibited B cells proliferation stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept reduced the percentage and numbers of CD19^+B cells,CD19^+CD20^+B cells,CD19^+CD27^+B cells and CD19^+CD20^+CD27^+B cells induced by BAFF or TNF-alpha.CP-25 down-regulated the high expression of BAFFR,BCMA and TACI stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated the expression of MKK3,P-p38,P-p65,TRAF2 and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha.CONCLUSION CP-25 regulated moderately activated B cells function by by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway.This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.展开更多
文摘Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is unknown.To date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(No.31101891)the Hitech Research and Development Program of China(No.2012AA10A408)
文摘As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The functions of TNF-αin many species have been widely studied,particularly in mammals.However,little is known about the TNF-αfunctions in V.variegatus.We first cloned and sequenced the TNF-αgene in V.variegatus(VvTNF-α).The two conserved cysteine residues,transmembrane sequence,Thr-Leu motif,and TNF family signature,as well as the TA-rich motifs of its proteins related to inflammatory responses had high similarity to those of the other teleost and mammalian TNF-α.The phylogenetic analysis showed that VvTNF-αwas consistent with TNF-αgenes of other vertebrates.The VvTNF-αtranscripts were extensively distributed in the peripheral blood leukocytes(PBLs),spleen,and gill,indicating that the VvTNF-αhad a role in immune function.Furthermore,treatment with pathogen-associated molecular patterns(PAMPs)could induce a rapid and significant increase of VvTNF-αin the PBLs,which reveals that VvTNF-αdoes participate in the host immune responses against bacterial and viral pathogens.We found that VvTNF-αhad an interesting expression pattern during metamorphosis,showing that the flatfish TNF-αmay have some novel functions during specific developmental stages.In addition,the 3 D structure prediction of VvTNF-αprovided an indication of how it is likely to interact with other proteins.Therefore,VvTNF-αhas multiple functions,and provides valuable information to explore novel functions of TNF-α.
基金supported by National Natural Science Foundation of China(81330081,81473223and 81673444)Anhui Province Postdoctoral Science Foundation(2016B134)
文摘OBJECTIVE This study was to investigate the effects of CP-25 on the functions of activated human B cells through regulating BAFF and TNF-alpha signaling.METHODS B cells from peripheral blood mononuclear cells(PBMCs) of normal human were isolated using magnetic cell separation(MACS) by a positive selection.B cells(107 cells·mL^(-1)) were stimulated by BAFF(100 ng·mL^(-1))or TNF-alpha(100 ng·mL^(-1)) for two hours,and then were treated with CP-25(10-5 mol·L^(-1)) or Rituximab(5 μg·mL^(-1)) or Etanercept(10 μg·mL^(-1)).B cell proliferation was detected by CCK-8.B cell subsets and BAFF receptors(BAFFR,BCMA and TACI) were analyzed by flow cytometry.The expression of TNFR1 and TNFR2 on B cells was analyzed by flow cytometry.The expression of MKK3,MKK6,P-p38,P-p65,TRAF2 and p100/52 was analyzed by Western blotting.RESULTS CP-25 inhibited B cells proliferation stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept reduced the percentage and numbers of CD19^+B cells,CD19^+CD20^+B cells,CD19^+CD27^+B cells and CD19^+CD20^+CD27^+B cells induced by BAFF or TNF-alpha.CP-25 down-regulated the high expression of BAFFR,BCMA and TACI stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha.CP-25,Rituximab and Etanercept down-regulated the expression of MKK3,P-p38,P-p65,TRAF2 and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha.CONCLUSION CP-25 regulated moderately activated B cells function by by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway.This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.
文摘胎儿生长受限(fetal growth restriction,FGR)是一种常见的产科疾病,其可导致新生儿低出生体质量和出生后肌肉量减少。这可能与肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)的调控密切相关。研究发现,这两种炎症因子在FGR胎儿中表达水平异常,可通过影响成肌细胞的增殖和分化,干扰正常骨骼肌的发育。此外,TNF-α与IL-6还可以激活特定的信号通路,如核因子κB(nuclear factor-κB,NF-κB)、Janus激酶/信号转导及转录活化因子(Janus kinase/signal transducer and activator of transcription,JAK/STAT)、丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)等信号通路,调节肌细胞的代谢和功能。如使用特定的抗炎药物或生物制剂来降低TNF-α和IL-6的活性,可能有助于改善FGR胎儿的骨骼肌发育。总的来说,TNF-α和IL-6在FGR胎儿骨骼肌发育中的作用是一个多层面、复杂的过程,需要进一步的深入研究来阐明其具体机制,帮助理解FGR的病理生理学,并为治疗FGR胎儿提供新的思路。
