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Mechanism of RNA-binding protein Lin28 in neuronal ferroptosis after intracerebral haemorrhage. rna结合蛋白Lin28在脑出血后神经元铁下垂中的作用机制。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.114101
Luqian Feng, Likun Wang, Guofeng Wu
Intracerebral haemorrhage (ICH) is a highly risky cerebrovascular disease with poor prognosis. Lin-28 homolog A (Lin28) has been identified as a crucial regulator in ICH. This study aims to analyse the mechanism of Lin28 in neuronal ferroptosis after ICH and provide theoretical basis for ICH treatment. An ICH mouse model was established via injection of collagenase VII, followed by neurological impairment assessment, and haematoxylin-eosin staining. An in vitro ICH model was established using hemin treatment. Next, cell viability and ferroptosis parameters were detected via cell counting kit-8, assay kits, enzyme-linked immunosorbent assay and western blot. Lin28 expression and tripartite motif-containing 37 (Trim37) mRNA level were detected via western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The binding relationship of Lin28 and Trim37 was verified. ICH mice exhibited neuronal ferroptosis and upregulation of Lin28. Lin28 inhibition alleviated neurological impairment, manifested by decreased hematoma, oedema, neuronal necrosis, glial cell swelling, intracellular vacuoles and inflammatory cell infiltration, reduced Fe2+ concentration and reactive oxygen species content, and increased glutathione and glutathione peroxidase 4 activity. In the hemin-induced HT-22 cells, Lin28 inhibition promoted cell viability and alleviated neuronal ferroptosis. Lin28 bound to Trim37 mRNA to stabilize the mRNA level of Trim37. Overexpression of Trim37 reversed the alleviating role of silencing Lin28 in neuronal ferroptosis after ICH. Overall, Lin28 stabilized the mRNA level of Trim37 to aggravate neuronal ferroptosis after ICH.
脑出血(ICH)是一种预后不良的高危脑血管疾病。Lin-28同源物A (Lin28)已被确定为ICH的重要调节因子。本研究旨在分析Lin28在脑出血后神经元铁下垂中的作用机制,为脑出血治疗提供理论依据。通过注射胶原酶VII建立脑出血小鼠模型,随后进行神经损伤评估,并进行血红素-伊红染色。采用血红素处理建立体外脑出血模型。接下来,通过细胞计数试剂盒-8、测定试剂盒、酶联免疫吸附法和western blot检测细胞活力和铁下垂参数。western blot和定量实时聚合酶链反应(qRT-PCR)检测Lin28表达和Trim37 mRNA表达水平。验证了Lin28和Trim37的结合关系。脑出血小鼠表现出神经元铁下垂和Lin28表达上调。抑制Lin28可减轻神经功能损害,表现为血肿、水肿、神经元坏死、胶质细胞肿胀、细胞内空泡和炎症细胞浸润减少,Fe2+浓度和活性氧含量降低,谷胱甘肽和谷胱甘肽过氧化物酶4活性升高。在hemin诱导的HT-22细胞中,抑制Lin28可提高细胞活力,减轻神经元铁下垂。Lin28结合Trim37 mRNA稳定Trim37 mRNA水平。Trim37的过表达逆转了沉默Lin28在脑出血后神经元铁下垂中的缓解作用。总的来说,Lin28稳定了Trim37的mRNA水平,加重了脑出血后神经元铁下垂。
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引用次数: 3
Exercise improves the body function and protects the neuronal injury in Parkinson's disease rats by activating calpain 1 and kallikrein 6. 运动通过激活钙蛋白酶1和钾激肽6,改善帕金森病大鼠机体功能,保护神经元损伤。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.118794
Jing Guo, Jinsuo Yang, Jiang Fu, Alok Tripathi

Parkinson's disease (PD) is a neurodegenerative disease, which alters body and cognitive functions. The present study evaluates the effect of exercise on body function and neuronal injury against a 6-hydroxydopamine hydrobromide (6-OHDA) induced PD rat model and postulates a possible molecular mechanism of its action. Parkinson's disease was induced by administration of (20 µg/5 µl at the rate of 1 µl/min) 6-OHDA and exercise training was given to mice by motorized rodent treadmill for a period of 14 days after the confirmation of PD. Behavioural changes were observed by apomorphine-induced rotation and motor function was assessed using the rotarod apparatus. The effect of exercise was observed on the levelof neurochemicals and the expression of calpain-1 (CAPN1) and kallikrein 6 (KLK6) was estimated in brain tissue of PD rats using western blot assay. A more significant improvement in the motor and cognitive function was observed in the PD + exercise group than in the PD group of rats. Exercise attenuates the altered level of g-aminobutyric acid (GABA), dopamine (DA) and glutamate in brain tissue of PD rats. Intracellular concentration of Ca+ ion was reduced significantly in brain tissue of the PD + exercise group compared to PD rats. Moreover, exercise activates the expression of KLK6 and CAPN1 protein in brain tissue of PD rats. In conclusion, data of the study reveal that exercise protects neuronal injury by reducing intracellular concentration Ca+ ion and activates KLK6 and CAPN1 in brain tissue of PD rats and thereby improves motor and cognitive functions.

帕金森病(PD)是一种神经退行性疾病,它会改变身体和认知功能。本研究在6-羟多巴胺氢溴化物(6-OHDA)诱导的PD大鼠模型上评估了运动对机体功能和神经元损伤的影响,并推测了其作用的可能分子机制。以(20µg/5µl,速率1µl/min) 6-OHDA诱导小鼠帕金森病,确认帕金森病后,在啮齿类动物电动踏车上进行运动训练,为期14天。通过阿吗啡诱导的旋转观察行为改变,并使用旋转棒仪评估运动功能。采用western blot法观察运动对PD大鼠脑组织神经化学物质水平的影响,并检测脑组织中calpain-1 (CAPN1)和kallikrein 6 (KLK6)的表达。与PD组相比,PD +运动组大鼠的运动和认知功能改善更为显著。运动可减轻PD大鼠脑组织中g-氨基丁酸(GABA)、多巴胺(DA)和谷氨酸的变化。与PD大鼠相比,PD +运动组脑组织细胞内钙离子浓度明显降低。运动可激活PD大鼠脑组织中KLK6和CAPN1蛋白的表达。综上所述,本研究数据表明,运动通过降低细胞内Ca+离子浓度,激活PD大鼠脑组织中的KLK6和CAPN1,保护神经元损伤,从而改善运动和认知功能。
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引用次数: 0
Study on the relationship between 25-hydroxyvitamin D level and rehabilitation of stroke patients. 25-羟基维生素D水平与脑卒中患者康复关系的研究。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.114347
Meixin Li, Chao-Jin-Zi Li, Jin He, Xin Zheng
AIM OF THE STUDY To analyse the relationship between 25-hydroxyvitamin D (25(OH)D) level and rehabilitation in stroke patients. MATERIAL AND METHODS 100 stroke patients hospitalized in the Neurorehabilitation Department of China Rehabilitation Research Center from November 2019 to April 2020 were selected as the research subjects. And set up a case group. 50 subjects who underwent outpatient physical examination in China Rehabilitation Research Center in the same period were selected as the control group. The differences of biochemical and bone metabolism indexes such as serum 25(OH)D, blood lipid, liver and kidney function between the two groups were analysed. We took rehabilitation efficacy as the dependent variable, Pearson correlation analysis and multivariate logistic regression analysis were performed to analyse the indicators affecting rehabilitation efficacy. RESULTS The average level of 25(OH)D in the case group was significantly lower than that in the control group ( p < 0.05). The rehabilitation efficacy was significantly positively correlated with 25(OH)D level ( p < 0.003) and significantly negatively correlated with duration of disease ( p < 0.01) and NIHSS score ( p < 0.05). CONCLUSIONS The increase in 25(OH)D is a protective factor for non-occurrence of cerebral infarction, and the increase in the 25(OH)D level is conducive to the prognosis of cerebral infarction.
目的分析25-羟基维生素D (25(OH)D)水平与脑卒中患者康复的关系。材料与方法选择2019年11月至2020年4月在中国康复研究中心神经康复科住院的脑卒中患者100例作为研究对象。成立一个案件小组。选取同期在中国康复研究中心门诊体检的50名受试者作为对照组。分析两组患者血清25(OH)D、血脂、肝肾功能等生化指标及骨代谢指标的差异。以康复疗效为因变量,采用Pearson相关分析和多因素logistic回归分析对影响康复疗效的指标进行分析。结果病例组25(OH)D平均水平显著低于对照组(p < 0.05)。康复疗效与25(OH)D水平显著正相关(p < 0.003),与病程显著负相关(p < 0.01),与NIHSS评分显著负相关(p < 0.05)。结论25(OH)D水平升高是脑梗死不发生的保护因素,25(OH)D水平升高有利于脑梗死预后。
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引用次数: 2
The effects of home exercise program on limb-girdle disease: a cohort study. 家庭运动项目对四肢束带疾病的影响:一项队列研究。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.114149
Askeri Turken, Maria Luckas, Vatan Kavak, Ö. Satıcı, D. Kavak
This study aims to demonstrate the effectiveness of rehabilitation in patients with limb-girdle disease, who were given a home exercise program and called for follow-up in certain periods by observing the functional areas of the shoulder and pelvic groups every six months. Suitable statistical methods were conducted. Descriptive findings and continuous variables regarding the patients were presented. As a result of the analyses, no statistically significant difference was found only in pre-treatment and post-treatment wrist strength and trunk extension variables, but a statistically significant difference was found between the pre-treatment and post-treatment scores of all other types of strength. Significant differences were found between the pre-treatment and post-treatment cervical flexion strength in terms of general weakness and inability to walk, joint limitation and walking status. It is believed that the rehabilitation method to be applied to patients with limb-girdle muscular dystrophy (LGMD) detected in the early period will provide effective results and may form the basis for referring them to physicians and health professionals. It has been concluded that rehabilitation will help them lead a comfortable life.
本研究旨在证明康复治疗对肢带疾病患者的有效性,对肢带疾病患者进行了家庭锻炼计划,并要求每六个月进行一次肩部和骨盆群功能区域的随访。采用合适的统计方法。介绍了有关患者的描述性发现和连续变量。分析结果显示,仅治疗前与治疗后腕部力量和躯干伸展变量的得分差异无统计学意义,而其他所有类型的力量得分在治疗前与治疗后均有统计学意义。治疗前和治疗后的颈椎屈曲强度在一般无力和无法行走、关节受限和行走状态方面存在显著差异。我们认为,将康复方法应用于早期发现的肢体带状肌营养不良(LGMD)患者将会获得有效的结果,并可能成为转诊给医生和卫生专业人员的依据。已经得出结论,康复将帮助他们过上舒适的生活。
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引用次数: 0
The application of pre-hospital first aid mode in patients with acute stroke: meta-analysis. 院前急救模式在急性脑卒中患者中的应用:meta分析。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.117614
Xiaoting Zhu, Rong Niu, Fangfang Bai, Zhufeng Zhang

To systematically evaluate the application effect of pre-hospital and in-hospital emergency mode in patients with acute stroke. The study was conducted by systematic search of Chinese (CNKI, Wanfang and VIP) and English (PubMed, EMBASE and Cochrane Library) databases. The case-control studies comparing the role of pre-hospital and in-hospital emergency mode for patients with acute stroke were included in this study. Outcome indicators included the time from admission to thrombolytic therapy (DNT), the time from calling for help to receiving professional treatment, the first aid effect (effective rate, disability rate and mortality), complications and prognosis. Meta-analysis was performed using RevMan 5.3. Seventeen studies were included in the final analysis. Compared with traditional emergency measures, pre-hospital and in-hospital emergency measures can significantly reduce DNT (mean difference [MD] = -22.63, p < 0.00001), time from call to professional treatment (MD: -13.22, p < 0.00001), disability rate (RR = 0.88, p = 0.004), fatality rate (RR = 0.58, p < 0.00001), central cerebral fever (RR = 0.44, p = 0.0009), and gastrointestinal bleeding (RR = 0.44, p = 0.002). In addition, daily living ability (MD = 16.56, p < 0.00001) and emergency response rate (RR = 1.50, p < 0.00001) were significantly improved. The pre-hospital and in-hospital emergency mode has a significant emergency effect in patients with acute stroke, which is a protective factor. This emergency mode can be widely used in clinical practice.

目的:系统评价院前、院内急救模式在急性脑卒中患者中的应用效果。本研究通过系统检索中文(CNKI、万方和VIP)和英文(PubMed、EMBASE和Cochrane Library)数据库进行。本研究纳入了比较院前和院内急救模式在急性脑卒中患者中的作用的病例对照研究。结局指标包括入院至溶栓治疗时间(DNT)、报警至专业治疗时间、急救效果(有效率、致残率、死亡率)、并发症及预后。采用RevMan 5.3进行meta分析。17项研究被纳入最终分析。与传统急救措施相比,院前与院内急救措施可显著降低患者DNT(平均差值[MD] = -22.63, p < 0.00001)、呼叫至专业治疗时间(MD: -13.22, p < 0.00001)、致残率(RR = 0.88, p = 0.004)、病死率(RR = 0.58, p < 0.00001)、中脑发热(RR = 0.44, p = 0.0009)、胃肠道出血(RR = 0.44, p = 0.002)。此外,日常生活能力(MD = 16.56, p < 0.00001)和应急反应率(RR = 1.50, p < 0.00001)均显著提高。院前院内急救模式对急性脑卒中患者的急救效果显著,是一个保护因素。这种应急模式可广泛应用于临床。
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引用次数: 0
Comparative study of two integrated traditional Chinese and Western medicine treatment methods on treatment compliance of patients with diabetic peripheral neuropathy. 两种中西医结合治疗方法对糖尿病周围神经病变患者治疗依从性的比较研究。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.117523
Yongli Qiao, Guiying Guo, Jianhua Zhao

Introduction: This study aims to compare the treatment satisfaction and compliance of two integrated traditional Chinese and Western medicine methods for diabetic peripheral neuropathy (DPN) patients with cold coagulation and blood stasis.

Material and methods: A total of 120 patients with cold coagulation and blood stasis type of distal symmetric polyneuropathy (DSPN), the most common form of diabetic neuropathy, were selected from the urology department of a hospital and randomly divided into a control group (60 patients), who were given external medicinal liquid application with Tangbiling(Magic Diabetic Arthralgia Treating Paste) herbs, and an observation group (60 patients), who were treated with modified Tangbiling herbs (Tangbiling herbs mixed with mud moxibustion substrate) for external medicinal liquid application. Both groups were treated with a TDP therapeutic apparatus at the same time as the external medicinal liquid application. After three courses of treatment (14 days/course of treatment), the efficacy was evaluated by the score of traditional Chinese medicine (TCM), and the questionnaires were used to compare the treatment compliance of the two groups.

Results: After the external medicinal liquid application with modified traditional Chinese medicine, the moulding and cleaning degree of TCM and the symptoms of the two groups were improved. The effective rate of the observation group was 91.7%, which was higher than the control group (86.7%). The compliance of the observation group was higher than the control group, and the differences were statistically significant (p < 0.05).

Conclusions: The external medicinal liquid application with modified Tangbiling herbs improved the treatment compliance and satisfaction of DPN patients and effectively improved the symptoms of pain and numbness in the lower limbs of patients, which is worth promoting.

前言:本研究旨在比较两种中西医结合方法对寒凝血瘀型糖尿病周围神经病变(DPN)患者的治疗满意度和依从性。材料和方法:选择某医院泌尿外科最常见的糖尿病神经病变形式远端对称型多神经病变(DSPN)患者120例,随机分为对照组(60例)和观察组(60例),对照组给予糖必灵外敷药液治疗糖尿病关节炎。经改良的糖必灵(糖必灵与泥灸底物混合)外用药液治疗。两组均采用TDP治疗仪治疗,同时外敷药液。治疗3个疗程(14天/疗程)后,采用中医评分法评价疗效,并采用问卷法比较两组患者的治疗依从性。结果:加味中药外用药液后,两组患者中药的塑形、清洁程度及症状均有改善。观察组有效率为91.7%,高于对照组(86.7%)。观察组患者治疗依从性高于对照组,差异有统计学意义(p < 0.05)。结论:加味汤必灵外敷提高了DPN患者的治疗依从性和满意度,有效改善了患者下肢疼痛、麻木的症状,值得推广。
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引用次数: 1
Abstracts from the Conference. 会议摘要。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.124409
s from the Conference NeuropAtologiA NeurosCieNCe
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引用次数: 2
Effects of miR-211-3p/RHBDD1 axis on cell proliferation, cell cycle progression, and epithelial-mesenchymal transition in glioma. miR-211-3p/RHBDD1轴对胶质瘤细胞增殖、细胞周期进展和上皮-间质转化的影响。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.118186
Lei Chen, Xiangyi Wang, Yude Zhu, Fuquan Liu, Laixing Liu, Ning Jiang

This study was designed to elucidate the relationship of miR-211-3p and rhomboid domain containing 1 (RHBDD1) in glioma. Here, we first observed that miR-211-3p directly targets the 3˘-UTR of RHBDD1 in glioma cells using dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot analysis. Pearson's correlation analysis showed that miR-211-3p expression was negatively correlated with RHBDD1 expression in glioma tissues. CCK-8 assay, flow cytometry, and transwell assay were applied to assess cell proliferation, cell cycle distribution, migration, and invasion. The results showed that RHBDD1 knockdown inhibited cell proliferation, cell cycle G1/S transition, migration, and invasion in two glioma cell lines (U87 and LN-229). Knockdown of miR-211-3p obtained opposite results. Moreover, overexpression of RHBDD1 counteracted suppressive effects of miR-211-3p on glioma cells. Furthermore, decreased expression of CDK4, cyclin D1, N-cadherin, and vimentin as well as increased E-cadherin expression induced by miR-211-3p was reversed by RHBDD1 overexpression. Our results suggested that targeting miR-211-3p/RHBDD1 axis might be a novel effective therapeutic target for glioma treatment.

本研究旨在阐明miR-211-3p与胶质瘤中rhomboid domain containing 1 (RHBDD1)的关系。在这里,我们首先通过双荧光素酶报告基因检测、RNA免疫沉淀(RIP)检测、逆转录-定量聚合酶链反应(RT-qPCR)和Western blot分析,观察到miR-211-3p直接靶向胶质瘤细胞中RHBDD1的3 × × -UTR。Pearson相关分析显示,在胶质瘤组织中miR-211-3p的表达与RHBDD1的表达呈负相关。CCK-8法、流式细胞术和transwell法评估细胞增殖、细胞周期分布、迁移和侵袭。结果表明,RHBDD1敲低抑制了两种胶质瘤细胞系(U87和LN-229)的细胞增殖、细胞周期G1/S转换、迁移和侵袭。敲低miR-211-3p得到相反的结果。此外,RHBDD1的过表达抵消了miR-211-3p对胶质瘤细胞的抑制作用。此外,mir - 311 -3p诱导的CDK4、cyclin D1、N-cadherin和vimentin的表达降低以及E-cadherin的表达升高被RHBDD1过表达逆转。我们的研究结果表明,靶向miR-211-3p/RHBDD1轴可能是治疗胶质瘤的一个新的有效的治疗靶点。
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引用次数: 0
Vanillin attenuates the ethanol withdrawal syndrome and ethanol withdrawal induced anxiety by regulating the neurochemical balance. 香兰素通过调节神经化学平衡减轻乙醇戒断综合征和乙醇戒断引起的焦虑。
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.118546
Lihui Du, Liping Xiao, Chenglin Zou, Jinrong Huang

Ethanol abuse is a major public issue globally and withdrawal of ethanol after chronic exposure contributes to the development of behavioural changes. The present study evaluates vanillin effect against the ethanol withdrawal syndrome (EWS) and the associated anxiety. Rats were exposed to ethanol for 21 days at 7.2% concentration maximum with drinking water in a modified liquid diet. Vanillin at doses of 100 and 200 mg/kg were administered 30 min prior to ethanol withdrawal, and behavioural changes were observed at 1st, 2nd, 4th, 6th and 12th h of ethanol withdrawal. Moreover, the locomotor activity was assessed using the astrophotometer and level of anxiety by the elevated plus maze. The level of neurotransmitters and mRNA expression of corticotropin-releasing factor (CRF) and corticotropin releasing factor receptor 1 (CRFR1) were estimated in brain tissue of vanillin treated EWS rats. There was a significant improvement in the ethanol withdrawal behaviour in the vanillin treated group compared to EWS rats. The locomotor activity and level of anxiety was observed to be reduced significantly (p < 0.01) in the vanillin treated group compared to EWS rats. Treatment with vanillin ameliorates the altered level of g-aminobutyric acid (GABA), dopamine and glutamate and level of corticosterone in ethanol withdrawal rats. mRNA expression of CRF and CRFR1 was reduced significantly (p < 0.01) in brain tissue of the vanillin treated group compared to the EWS group of rats. In conclusion, data reveal that treatment with vanillin shows a beneficial effect against EWS and ethanol withdrawal associated anxiety by regulating CRF/CRFR1 expression.

乙醇滥用是全球的一个重大公共问题,长期接触乙醇后戒断乙醇有助于行为改变的发展。本研究评估香兰素对乙醇戒断综合征(EWS)和相关焦虑的作用。大鼠以最高浓度7.2%的乙醇与改良液体饮食中的饮用水接触21天。在乙醇戒断前30分钟给予100和200 mg/kg剂量的香兰素,并在乙醇戒断后的第1、2、4、6和12小时观察行为变化。此外,用天文光度计评估运动活动,用高架正迷宫评估焦虑水平。测定香兰素处理后EWS大鼠脑组织神经递质水平及促肾上腺皮质激素释放因子(CRF)和促肾上腺皮质激素释放因子受体1 (CRFR1) mRNA表达量。与EWS大鼠相比,香草醛治疗组的乙醇戒断行为有显著改善。与EWS大鼠相比,香兰素治疗组的运动活性和焦虑水平显著降低(p < 0.01)。香兰素治疗可改善乙醇戒断大鼠体内g-氨基丁酸(GABA)、多巴胺和谷氨酸以及皮质酮水平的变化。与EWS组相比,香兰素处理组大鼠脑组织中CRF和CRFR1 mRNA表达量显著降低(p < 0.01)。总之,数据显示香兰素治疗通过调节CRF/CRFR1表达对EWS和乙醇戒断相关焦虑有有益作用。
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引用次数: 0
microRNA-146a as a biomarker for transmissible spongiform encephalopathy. microRNA-146a作为传染性海绵状脑病的生物标志物
IF 2 4区 医学 Q2 Medicine Pub Date : 2022-01-01 DOI: 10.5114/fn.2022.113561
A. Pogue, Yuhai Zhao, W. Lukiw
The pro-inflammatory, innate-immune system ribonucleic acid mediator microRNA-146a, constitutively expressed in the brain and central nervous system (CNS) of both the mouse and the human, is pathologically up-regulated in multiple transmissible spongiform encephalopathies (TSEs) to several times its basal level. miRNA-146a: (i) exists as a ~22-ribonucleotide (nt) single-stranded non-coding RNA (sncRNA) whose sequence is unique and highly selected over evolution; (ii) is brain-, CNS- and lymphoid-tissue enriched and exhibits a 100% RNA sequence homology between the mouse and the human; (iii) has been repeatedly shown to play critical immunological and pro-inflammatory roles in the onset and propagation of several human CNS disorders including progressive, incapacitating, and lethal neurological syndromes that include prion disease (PrD) and Alzheimer's disease (AD); (iv) is a fascinating molecular entity because it is representative of the smallest class of soluble, information-carrying, amphipathic sncRNA yet described; (v) has capability to be induced by cellular stressors and the pro-inflammatory transcription factor NF-kB (p50/p65); (vi) has capability to post-transcriptionally regulate multiple mRNAs and cellular processes in neurological health and disease; (vii) is upregulated in human host cells after viral invasion by single-stranded RNA (ssRNA) or double-stranded DNA (dsDNA) neurotropic viruses; and (viii) has an immense potential in neuro-degenerative disease therapeutics via anti-NF-kB and/or anti-miRNA-146a treatment strategies. In this short communication we provide for the first time evidence that miRNA-146a is a prominent sncRNA species in experimental murine prion disease, progressively increasing in the pre-symptomatic stages in C57BL/6J, SJL/J or Swiss Albino murine scrapie prion models. The highest miRNA-146a levels were quantified in these three different murine scrapie models exhibiting full symptomology of prion infection. The results suggest that miRNA-146a levels in the brain may be useful as an accessory diagnostic, prognostic or response-to-treatment biomarker to monitor the onset and development of PrD in experimental murine models that may also be extrapolated to be a relevant adjunct biomarker in human TSEs.
促炎、先天免疫系统核糖核酸介质microRNA-146a在小鼠和人的大脑和中枢神经系统(CNS)中组成性表达,在多种传染性海绵状脑病(ses)中病理上调至其基础水平的数倍。miRNA-146a:(i)作为一种~22核糖核苷酸(nt)单链非编码RNA (sncRNA)存在,其序列是独特的,并且在进化过程中被高度选择;(ii)富含大脑、中枢神经系统和淋巴组织,并且小鼠和人类之间的RNA序列具有100%的同源性;(iii)已被反复证明在几种人类中枢神经系统疾病(包括朊病毒病(PrD)和阿尔茨海默病(AD)等进行性、失能性和致死性神经系统综合征)的发病和传播中发挥关键的免疫学和促炎作用;(iv)是一个令人着迷的分子实体,因为它代表了迄今为止描述的最小的可溶性、携带信息的两亲sncRNA;(v)能够被细胞应激源和促炎转录因子NF-kB (p50/p65)诱导;(vi)在神经健康和疾病中具有转录后调节多种mrna和细胞过程的能力;(vii)在嗜神经病毒单链RNA (ssRNA)或双链DNA (dsDNA)入侵后在人宿主细胞中表达上调;(viii)通过抗nf - kb和/或抗mirna -146a治疗策略在神经退行性疾病治疗中具有巨大潜力。在这篇简短的文章中,我们首次提供了证据,证明miRNA-146a在实验性小鼠朊病毒疾病中是一个重要的sncRNA物种,在C57BL/6J、SJL/J或Swiss Albino小鼠痒病朊病毒模型的症状前阶段逐渐增加。在这三种不同的小鼠痒病模型中,miRNA-146a水平被量化为最高,表现出朊病毒感染的全部症状。研究结果表明,大脑中的miRNA-146a水平可能是一种辅助诊断、预后或治疗反应的生物标志物,可用于监测实验性小鼠模型中PrD的发生和发展,也可能被推断为人类tse的相关辅助生物标志物。
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引用次数: 5
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Folia neuropathologica
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