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| 1 | MicroRNAs as disease progression biomarkers and therapeutic targets in experimental autoimmune encephalomyelitis model of multiple sclerosis显示文摘Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice. | Bridget Martinez Philip V.Peplow | 2020 | Neural Regeneration Research2020，15，10： | 10 |
| 2 | Immunostimulatory effect of ethanol extract of Chondracanthus tenellus in RAW 264.7 macrophages in vitro显示文摘Objective:To investigate whether ethanol extracts of Chondracanthus tenellus(EECT)could improve immunomodulatory property of murine monocyte/macrophage RAW 264.7 cells.Methods:Cell viability,phagocytic ability,and nitric oxide were measured.The levels of prostaglandin E2 and cytokines were determined using enzyme-linked immunosorbent assay kits.Expression of immunoregulatory response protein was detected by Western blotting assay.Results:As the concentration of EECT increased,the morphology of the cells changed to a typical active macrophage shape,and the phagocytic activity increased significantly.EECT also effectively enhanced the production and secretion of immunomodulatory mediators,such as nitric oxide and prostaglandin E2,and cytokines.In addition,compared with the control group,EECT markedly stimulated the expression of Toll-like receptor 4(TLR4)and myeloid differentiation factor 88,one of the TLR4 adapter molecules.Furthermore,EECT promoted the nucleus translocation of nuclear factor-kappa B(NF-κB)by increasing the phosphorylation and degradation of the inhibitor of NF-κB-α,indicating activation of the NF-κB signaling pathway.Meanwhile,similar trends were found in cells treated with lipopolysaccharide as a positive control.Conclusions:Taken together,the results indicate that EECT has an immunomodulatory effect by increasing the production of immunomodulatory mediators and cytokines through activation of the TLR4/NF-κB signaling pathway.EECT could be used as a potential candidate for medication or dietary supplements to increase immune activity. | Cheol Park Da Hye Kwon Hyesook Lee Su Hyun Hong Gi-Young Kim Hee-Jae Cha Do-Hyung Kim Suhkmann Kim Heui-Soo Kim Hye-Jin Hwang Yung Hyun Choi | 2021 | Asian Pacific Journal of Tropical Biomedicine2021，11，6： | 1 |
| 3 | 牛蒡子苷元对大鼠实验性自身免疫性脑脊髓炎的治疗作用及其机制显示文摘目的观察牛蒡子苷元(ATG)对大鼠实验性自身免疫性脑脊髓炎(EAE)的治疗作用,并探讨其机制。方法将30只Wistar大鼠随机分为3组各10只,实验组和模型组均采用豚鼠全脊髓匀浆和完全弗氏佐剂混合而成的抗原乳剂诱导制备EAE模型,正常组皮下注射等量生理盐水与完全弗氏佐剂制备而成的空白乳剂。皮下注射后当日起,实验组大鼠每日腹腔注射3 mg/kg的ATG溶液,共14 d;正常组与模型组注射等量生理盐水。皮下注射后当日至第14 d,每日采用神经功能学评分法评价大鼠神经功能。皮下注射第14 d处死大鼠,HE染色观察脑和脊髓组织组织病理学,免疫荧光染色检测脊髓组织抗离子钙接头蛋白分子1(Iba1)相对荧光强度,RT-PCR法检测脊髓组织IL-1β、IL-6、TNF-α、单核细胞趋化蛋白-1(MCP-1)mRNA,Western blotting法检测脊髓组织Nod样受体蛋白3(NLRP3)、凋亡相关点样蛋白(ASC)、含半胱氨酸的天冬氨酸蛋白水解酶1(Caspase-1)、血红素氧合酶-1(HO-1)、核因子E2相关因子2(Nrf2)蛋白,分光光度法检测脊髓组织丙二醛(MDA)、还原型谷胱甘肽(GSH)。结果与模型组比较,实验组大鼠神经功能评分降低(P<0.05)。与模型组比较,实验组脑、脊髓组织中炎症细胞浸润明显减少,活化的小胶质细胞数量降低(P均<0.05)。与模型组比较,实验组脊髓组织中IL-1β、IL-6、TNF-α、MCP-1 mRNA相对表达量降低,NLRP3、ASC、Caspase-1蛋白相对表达量降低,MDA含量降低,GSH含量升高,Nrf2、HO-1相对表达量升高(P均<0.05)。结论ATG对大鼠EAE有治疗作用,机制可能与降低NLRP3/ASC/Caspase-1炎症体通路介导的神经炎症,活化Nrf2/HO-1信号通路介导的抗氧化作用有关。 | 黄蕾 袁玉印 李作孝 | 2020 | 山东医药2020，60，18： | 1 |
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