MDA5 complements TLR3 in suppression of neuroblastoma

Toll-like receptor3 (TLR3) has been confirmed to be differentially expressed in neuroblastoma (NB), and predicts a favorable prognosis with a high expression in tumor tissues. Treatment with TLR3 agonist - polyinosinic-polycytidylic acid [poly(I:C)] could induce significant but limited apoptosis in TLR3-expressing NB cells, suggesting that other viral RNA sensors, including melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) in the cytosolic compartment might also be implicated in poly(I:C)-induced NB cell death. MDA5 and RIG-I were induced by poly(I:C) to express in two of six NB cell lines, SK-N-AS (AS) and SK-N-FI, which were associated with up-regulation of caspase9 and active caspase3. While knockdown of either MDA5 or RIG-I alone is ineffective to decrease caspase9 and active caspase3, simultaneously targeting MDA5 and TLR3 showed the best effect to rescue poly(I:C) induced up-regulation of mitochondrial antiviral signaling protein (MAVS), caspase9, active caspase3, and apoptosis in AS cells. Over-expression of MDA5 in FaDu cells resulted in significantly less colony formation and more poly(I:C)-induced cell death. Further studies in human NB tissue samples revealed that MDA5 expression in NB tissues predicted a favorable prognosis synergistically with TLR3. Our findings indicate that MDA5 may serve as a complementary role in the TLR3 activated suppression of NB.     

JAK2/STAT3信号通路介导灯盏花乙素抗人心脏微血管内皮细胞缺氧-复氧损伤

Objective: To investigate the antagonistic cell injury effect and molecular mechanism of scutellarin(SCU)in hypoxia reoxygenation(HR) treated human cardiac microvascular endothelial cells(HCMECs).Methods: The method of 12 h hypoxia following by 12 h reoxygenation was used to culture HCMECs in vitro to built cell injury model. The groups were divided into control group, model(HR) group, and HR + SCU(0.1 μmol/L, 1 μmol/L, and 10 μmol/L) group. The cell viability was determined by MTT, and oxidative stress was detected by malondialdehyde(MDA) levels by biochemical assay kit. Protein expression of JAK2/p-JAK2 and STAT3/p-STAT3 were evaluated by Western blot.Results: The results of MTT and MDA showed that HR decreased the cell viability(P 0.05) and increased MDA level significantly(P 0.05), SCU played a contrary role in these processes. Western blot analysis indicates that, the expression of JAK2 and p-JAK2, STAT3, and p-STAT3 were increased in model group when compared with control group(P 0.05); Compared with model group, their expression were reduced by SCU(P 0.05).Conclusion: SCU took a protective effect on HR-treated HCMECs, and the molecular mechanism may be associated with the inhibition of JAK2/STAT3 signal transduction pathway.     

Anti‐MDA‐5 antibody‐positive clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease treated with therapeutic plasma exchange: A case series

We present six cases of antimelanoma differentiation‐associated gene 5 antibody (anti‐MDA5‐Ab)‐positive clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP‐ILD), which is known to have a poor prognosis. The outcomes of these cases are described after treatment with therapeutic plasma exchange (TPE). Clinical and therapeutic data for patients with CADM with RP‐ILD were collected retrospectively from medical records. All six patients received early intensive care including high‐dose corticosteroids, intravenous cyclophosphamide, and a calcineurin inhibitor, but lung disease and hypoxia became more severe. TPE was performed over a median of 9.5 sessions (range 3‐14) per patient, and the median duration from admission to TPE was 23 days. Three patients received combined direct hemoperfusion using a polymyxin B‐immobilized fiber column (PMX‐DHP) therapy on successive days to manage acute respiratory failure. Four patients survived and two died due to respiratory failure. In the survival cases, ferritin decreased, and ferritin and KL‐6 were lower at diagnosis. The patients who died had a higher alveolar‐arterial oxygen difference and more severe lung lesions at the time of initiation of TPE. These findings indicate that a combination of conventional therapy and TPE may be useful for improvement of the prognosis of CADM with RP‐ILD at the early stage of onset.     

Adenosine-to-inosine editing of endogenous Z-form RNA by the deaminase ADAR1 prevents spontaneous MAVS-dependent type I interferon responses

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复元醒脑汤对大鼠局灶性脑缺血再灌注损伤的保护作用研究

目的 探讨复元醒脑汤对大鼠局灶性脑缺血再灌注损伤的保护作用及其机制。方法 将SPF级雄性SD大鼠随机分为假手术组、模型组、复元醒脑汤低、中、高（5.5、11、22 g/kg）剂量组。采用线栓法建立大鼠脑缺血再灌注损伤模型,缺血2 h再灌注24 h,对各组大鼠进行神经功能缺失评分,TTC染色测定脑梗死体积,HE染色观察脑组织病理变化,Nissl染色观察脑组织中尼氏小体的变化,Tunnel染色观察脑组织中神经细胞的凋亡情况。测定血清中的超氧化物歧化酶（SOD）及丙二醛（MDA）的水平。结果 与模型组相比,复元醒脑汤低、中、高剂量组均可明显改善大脑中动脉缺血再灌注损伤大鼠的神经行为障碍;TTC染色结果显示,复元醒脑汤低、中、高剂量组大鼠脑梗死体积明显减小;HE结果显示给药组改善脑组织病理结构,Nissl染色结果表明给药组尼氏小体形态数量得到改善,Tunnel染色阳性细胞数减少,细胞凋亡率下降;与模型组相比,复元醒脑汤可提高脑缺血再灌注大鼠血清中SOD的水平,降低MDA水平。结论 复元醒脑汤对大鼠大脑脑缺血再灌注损伤具有保护作用。     

地塞米松磷酸钠口服液的制备及其抗大鼠粘连性肠梗阻的初步研究

目的：制备地塞米松磷酸钠口服液并初步考察其抗大鼠粘连性肠梗阻作用。方法：采用高效液相色谱（HPLC）法测定地塞米松磷酸钠的含量、油水分配系数、考察地塞米松磷酸钠稳定性影响因素;采用裘法祖造模法和试剂盒考察其抗大鼠粘连性肠梗阻的作用。结果：在pH 1.0~8.0范围内,地塞米松磷酸钠的油水分配系数均小于零;pH为8.0时药物降解最慢,抗氧剂Na₂SO₃和稳定剂丙二醇联用可增加地塞米松磷酸钠的稳定性。与尾静脉注射给药相比,地塞米松磷酸钠口服液能显著降低粘连性肠梗阻（AIO）大鼠肠道丙二醛（MDA）含量（P<0.05）,显著提高超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）的活性（P<0.01,P<0.01）。结论：地塞米松磷酸钠口服液具有抗大鼠粘连性肠梗阻作用且其作用强于注射液。     

ApoA-1、MDA、Cys-C和血流动力学指标与帕金森病认知功能的相关性研究

目的探讨血浆载脂蛋白A-1(ApoA-1)、丙二醛(MDA)、胱抑素C(Cys-C)和血流动力学指标与帕金森病认知功能的相关性研究。方法 2016年1月至2017年12月本院收治120例帕金森病患者分为认知正常组(n=44)和认知障碍组(n=76)。选取同期健康体检50例老年人为对照组。采用简易智能状态量表(MMSE)和蒙特利尔认知评估(MoCA)评价患者的认知障碍情况;检测患者ApoA-1、MDA、Cys-C水平和血流动力学指标。结果认知正常组和认知障碍组患者UPDRS评分比对照组明显升高,MMSE和MoCA评分比对照组明显降低,PDD组表现更为明显(P <0.05)。认知正常组和认知障碍组患者MDA、Cys-C水平比对照组显著升高,ApoA-1比对照组显著降低(P<0. 05)。认知障碍组和认知正常组患者脑血流量(CBF)、脑血容量(CBV)和平均通过时间(MTT)显著下降,颅内压(ICP)显著上升,PDD组表现更为明显(P<0.05)。结论患者ApoA-1、MDA、Cys-C和血流动力学指标与帕金森病患者的认知功能明显相关,检验帕金森患者血清内ApoA-1、MDA、Cys-C和血流动力学指标变化对于临床判定患者是否具有认知障碍具有重要的意义。     

黄芪和山药配伍微粉对糖尿病肾病大鼠抗氧化能力的影响

目的:观察黄芪和山药配伍微粉对糖尿病肾病大鼠抗氧化能力的影响,探讨其保护大鼠肾功能的作用机制。方法:采用单侧肾脏切除合并腹腔注射链脲佐菌素的方法诱导建立糖尿病肾病大鼠模型,将造模成功的45只大鼠随机分为模型对照组12只、卡托普利组11只、微粉低剂量组11只和微粉高剂量组11只,另取10只作为假手术对照组。卡托普利组灌胃卡托普利溶液剂量为13.5 mg·kg-1,微粉低剂量组灌胃微粉溶液,剂量为5.4 g·kg-1,微粉高剂量组灌胃微粉溶液,剂量为10.8 g·kg-1,假手术对照组和模型对照组大鼠灌胃等容积蒸馏水,每日1次,连续给药6周。给药结束后,采用免疫浊度法于计算24 h尿微量白蛋白量,运用全自动生化仪测定血清血尿素氮(Blood urea nitrogen,BUN)、血肌酐(Serum creatinine,Scr)含量,采用黄嘌呤氧化酶法测定血清超氧化物歧化酶(Superoxide Dismutase,SOD)活性,硫代巴比妥酸法测定血清丙二醛(malonaldehyde,MDA)含量。结果:微粉高剂量组能明显改善糖尿病肾病大鼠的一般状况,体质量较模型对照组明显增加,肾脏肥大指数明显减小,差异具有统计学意义(P0.05)。与假手术组比较,模型对照组大鼠24 h尿蛋白定量、血清BUN、血清Scr均明显升高,微粉高剂量组和卡托普利组较模型对照组降低,差异具有统计学意义(P0.05)。与假手术组比较,模型对照组血清SOD活性明显降低,血清MDA含量明显升高,微粉高剂量组和卡托普利组与模型对照组比较,血清SOD活性升高,血清MDA含量降低,差异具有统计学意义(P0.05)。结论:黄芪和山药配伍微粉可明显降低糖尿病肾病大鼠尿蛋白的排泄,降低血清BUN和Scr水平,升高血清SOD活性,降低MDA含量,具有明显的肾脏保护作用,黄芪和山药微粉对糖尿病肾病大鼠肾脏的保护作用与提高抗氧化能力有关。