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Deciphering the dual role and prognostic potential of PINK1 across cancer types 认领
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作者 Katherine Dai Daniel P.Radin Donna Leonardi 《中国神经再生研究:英文版》 SCIE CAS 2021年第4期659-665,共7页
Metabolic rewiring and deregulation of the cell cycle are hallmarks shared by many cancers.Concerted mutations in key tumor suppressor genes,such as PTEN,and oncogenes predispose cancer cells for marked utilization of... Metabolic rewiring and deregulation of the cell cycle are hallmarks shared by many cancers.Concerted mutations in key tumor suppressor genes,such as PTEN,and oncogenes predispose cancer cells for marked utilization of resources to fuel accelerated cell proliferation and chemotherapeutic resistance.Mounting research has demonstrated that PTEN-induced putative kinase 1(PINK1)acts as a pivotal regulator of mitochondrial homeostasis in several cancer types,a function that also extends to the regulation of tumor cell proliferative capacity.In addition,involvement of PINK1 in modulating inflammatory responses has been highlighted by recent studies,further expounding PINK1’s multifunctional nature.This review discusses the oncogenic roles of PINK1 in multiple tumor cell types,with an emphasis on maintenance of mitochondrial homeostasis,while also evaluating literature suggesting a dual oncolytic mechanism based on PINK1’s modulation of the Warburg effect.From a clinical standpoint,its expression may also dictate the response to genotoxic stressors commonly used to treat multiple malignancies.By detailing the evidence suggesting that PINK1 possesses distinct prognostic value in the clinical setting and reviewing the duality of PINK1 function in a context-dependent manner,we present avenues for future studies of this dynamic protein. 展开更多
关键词 apoptosis CANCER cell cycle inflammation metabolic stress mitochondral quality control MITOPHAGY PINK1 tumor Warburg effect
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Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide dual receptor agonist DA-CH5 is superior to exendin-4 in protecting neurons in the 6-hydroxydopamine rat Parkinson model 认领
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作者 Ling-Yu Zhang Qian-Qian Jin +1 位作者 Christian Hölscher Lin Li 《中国神经再生研究:英文版》 SCIE CAS 2021年第8期1660-1670,共11页
Patients with Parkinson's disease(PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), can re-sensiti... Patients with Parkinson's disease(PD) have impaired insulin signaling in the brain. Incretin hormones, including glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), can re-sensitize insulin signaling. In a recent phase II clinical trial, the first GLP-1 mimic, exendin-4, has shown reliable curative effect in patients with PD. DA-CH5 is a novel GLP-1/GIP receptor unimolecular coagonist with a novel peptide sequence added to cross the blood-brain barrier. Here we showed that both exendin-4 and DA-CH5 protected against 6-hydroxydopamine(6-OHDA) cytotoxicity, inhibited apoptosis, improved mitogenesis and induced autophagy flux in SH-SY5Y cells via activation of the insulin receptor substrate-1(IRS-1)/alpha serine/threonine-protein kinase(Akt)/c AMP response element-binding protein(CREB) pathway. We also found that DA-CH5(10 nmol/kg) daily intraperitoneal administration for 30 days post-lesion alleviated motor dysfunction in rats and prevented stereotactic unilateral administration of 6-OHDA induced dopaminergic neurons loss in the substantia nigra pars compacta. However, DA-CH5 showed curative effects in reducing the levels of α-synuclein and the levels of pro-inflammatory cytokines(tumor necrosis factor-α, interleukin-1β). It was also more effective than exendin-4 in inhibiting apoptotic process and protecting mitochondrial functions. In addition, insulin resistance was largely alleviated and the expression of autophagy-related proteins was upregulated in PD model rats after DA-CH5 treatment. These results in this study indicate DA-CH5 plays a therapeutic role in the 6-OHDAunilaterally lesioned PD rat model and is superior to GLP-1 analogue exendin-4. The study was approved by the Animal Ethics Committee of Shanxi Medical University of China. 展开更多
关键词 neurodegenerative disease Parkinson's disease insulin resistance inflammation GLP-1/GIP receptor unimolecular co-agonist
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猪骨髓间充质干细胞抑制脂多糖诱导炎症反应改善猪胰岛细胞功能损伤 认领
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作者 袁宝红 赵维山 +3 位作者 王若天 管傲然 王珏 李汝红 《中国组织工程研究》 CAS 北大核心 2021年第13期1969-1975,共7页
背景:猪胰岛移植是治疗糖尿病的常用手段,但炎症反应和氧化应激会导致猪胰岛移植的远期效果欠佳。猪骨髓间充质干细胞已被证实与胰岛联合移植可改善移植物的功能。但关于猪骨髓间充质干细胞通过调节胰岛细胞中miR-299-5p的表达来调控胰... 背景:猪胰岛移植是治疗糖尿病的常用手段,但炎症反应和氧化应激会导致猪胰岛移植的远期效果欠佳。猪骨髓间充质干细胞已被证实与胰岛联合移植可改善移植物的功能。但关于猪骨髓间充质干细胞通过调节胰岛细胞中miR-299-5p的表达来调控胰岛β细胞功能和存活率还尚未被报道。目的:探讨猪骨髓间充质干细胞通过miR-299-5p/SIAH1分子轴调控JNK/C-Jun信号通路对猪胰岛细胞功能损伤的影响。方法:用脂多糖诱导猪胰岛细胞功能损伤,然后与骨髓间充质干细胞共培养24 h,采用ELISA检测猪胰岛细胞中白细胞介素6、白细胞介素1β、肿瘤坏死因子α、活性氧、超氧化物歧化酶及胰岛素水平,Hoechst 33258染色观察猪胰岛细胞凋亡情况,Annexin V-FITC/PI检测猪胰岛细胞凋亡率,Western blot检测SIAH1和JNK/C-Jun信号通路相关蛋白表达;qPCR检测猪胰岛细胞中与胰岛细胞功能损伤有关的miRNAs表达;双荧光素酶报告基因验证miR-299-5p和SIAH1的靶向关系。结果与结论:①猪骨髓间充质干细胞抑制脂多糖引起的白细胞介素6、白细胞介素1β、肿瘤坏死因子α、活性氧上调和促凋亡作用,同时也抑制脂多糖引起的超氧化物歧化酶、胰岛素分泌量下调作用;②猪骨髓间充质干细胞显著上调miR-299-5p表达,miR-299-5p可通过靶向下调SIAH1表达抑制JNK/C-Jun信号通路激活;③结果表明,猪骨髓间充质干细胞通过调控miR-299-5p/SIAH1分子轴抑制JNK/C-Jun信号通路激活,抑制脂多糖诱导的炎症反应、氧化应激和猪胰岛细胞凋亡,并促进胰岛素分泌,从而改善猪胰岛细胞功能。 展开更多
关键词 干细胞 骨髓间充质干细胞 胰岛细胞 脂多糖 炎症 氧化应激 猪 实验
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Peritoneal macrophages attenuate retinal ganglion cell survival and neurite outgrowth 认领
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作者 Jia-Jian Liang Yu-Fen Liu +4 位作者 Tsz Kin Ng Ci-Yan Xu Mingzhi Zhang Chi Pui Pang Ling-Ping Cen 《中国神经再生研究:英文版》 SCIE CAS 2021年第6期1121-1126,共6页
Inflammation is a critical pathophysiological process that modulates neuronal survival in the central nervous system after disease or injury.However,the effects and mechanisms of macrophage activation on neuronal surv... Inflammation is a critical pathophysiological process that modulates neuronal survival in the central nervous system after disease or injury.However,the effects and mechanisms of macrophage activation on neuronal survival remain unclear.In the present study,we co-cultured adult Fischer rat retinas with primary peritoneal macrophages or zymosan-treated peritoneal macrophages for 7 days.Immunofluorescence analysis revealed that peritoneal macrophages reduced retinal ganglion cell survival and neurite outgrowth in the retinal explant compared with the control group.The addition of zymosan to peritoneal macrophages attenuated the survival and neurite outgrowth of retinal ganglion cells.Conditioned media from peritoneal macrophages also reduced retinal ganglion cell survival and neurite outgrowth.This result suggests that secretions from peritoneal macrophages mediate the inhibitory effects of these macrophages.In addition,increased inflammationand oxidation-related gene expression may be related to the enhanced retinal ganglion cell degeneration caused by zymosan activation.In summary,this study revealed that primary rat peritoneal macrophages attenuated retinal ganglion cell survival and neurite outgrowth,and that macrophage activation further aggravated retinal ganglion cell degeneration.This study was approved by the Animal Ethics Committee of the Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong,Shantou,Guangdong Province,China,on March 11,2014(approval no.EC20140311(2)-P01). 展开更多
关键词 in vitro INFLAMMATION MACROPHAGES MODEL neurite outgrowth optic nerve retinal ganglion cells SURVIVAL
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Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke 认领
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作者 Wan Zhang Tian Tian +4 位作者 Shao-Xin Gong Wen-Qian Huang Qin-Yi Zhou Ai-Ping Wang Ying Tian 《中国神经再生研究:英文版》 SCIE CAS 2021年第1期6-11,共6页
Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke.Microglial activation and polarization,and the inflammatory response mediated by these cells play important role... Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke.Microglial activation and polarization,and the inflammatory response mediated by these cells play important roles in the development,progression and outcome of brain injury after ischemic stroke.Currently,there is no effective strategy for treating ischemic stroke in clinical practice.Therefore,it is clinically important to study the role and regulation of microglia in stroke.In this review,we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke,with the aim of providing a better understanding of the relationship between ischemic stroke and microglia. 展开更多
关键词 brain cells central nervous system inflammation injury MACROPHAGES repair review STROKE
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人牙周膜干细胞条件培养液对炎症组织来源牙周膜干细胞增殖及成骨分化的影响 认领
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作者 刘焱 高翔 +2 位作者 赵晓霞 陈青宇 高俊武 《中国组织工程研究》 CAS 北大核心 2021年第13期2005-2010,共6页
背景:富含生物活性物质的条件培养液可以维持干细胞增殖活性和生物学特性的稳定。健康组织来源的人牙周膜干细胞条件培养液能否影响炎症组织来源人牙周膜干细胞的增殖和成骨分化对于牙周组织再生重建意义重大。目的:探讨健康组织来源的... 背景:富含生物活性物质的条件培养液可以维持干细胞增殖活性和生物学特性的稳定。健康组织来源的人牙周膜干细胞条件培养液能否影响炎症组织来源人牙周膜干细胞的增殖和成骨分化对于牙周组织再生重建意义重大。目的:探讨健康组织来源的人牙周膜干细胞条件培养液对炎症组织来源人牙周膜干细胞增殖及成骨分化的影响。方法:由健康成人的正常牙周韧带中分离、纯化人牙周膜干细胞并传代培养,对融合达80%的第3代人牙周膜干细胞进行无血清培养基连续培养24 h,收集上清液即得到人牙周膜干细胞条件培养液。采取有限稀释克隆法培养来源于慢性牙周炎患者牙周韧带中的人牙周膜干细胞,分别在含50%人牙周膜干细胞条件培养液+50%常规培养液(条件培养液处理组)及常规培养液(对照组)2种条件下培养。免疫荧光染色法检测两组细胞中波形丝蛋白、角蛋白和间充质干细胞标志物STRO-1的表达;MTT比色法结合流式细胞术分析细胞增殖活性;经体外成骨诱导后,碱性磷酸酶试剂盒和RT-PCR检测两组细胞碱性磷酸酶活性和成骨相关基因(Runx2,OPN,OCN)的表达水平。结果与结论:①两组细胞均符合成体干细胞的形态特征,呈现长梭形或多角形,倒置相差显微镜下观察其形态无明显差异;②经免疫荧光染色可见两组细胞均呈现波形丝蛋白阳性表达,角蛋白阴性表达,且间充质干细胞标志物STRO-1阳性表达;③MTT结果显示:培养第3,5,7天时,条件培养液处理组的细胞增殖活性均显著高于对照组(P<0.01);④细胞周期分析显示:与对照组相比,条件培养液处理组细胞处于G2/M期及S期的数量明显增多(P<0.05);⑤体外成骨诱导第5,7天时,条件培养液处理组碱性磷酸酶活性高于对照组(P<0.05);⑥成骨诱导21 d后,成骨相关基因Runx2、OPN、OCN在条件培养液处理组的表达量均显著高于对照组(P<0.01,P<0.05);⑦ 展开更多
关键词 干细胞 人牙周膜干细胞 条件培养液 炎症 增殖 成骨分化 基因 实验
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通络止痛凝胶干预膝关节骨性关节炎模型兔的软骨炎症及退变 认领
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作者 陈谱 阮安民 +4 位作者 周俊 张晓哲 马玉峰 宗晨钟 王庆普 《中国组织工程研究》 CAS 北大核心 2021年第17期2670-2675,共6页
背景:软骨损伤是膝关节骨性关节炎的重要病理表现之一。通络止痛凝胶是在通络止痛方的基础上,以卡波姆、明胶等具有良好生物相容性的化合物作为载体制备而成的,可直接外敷于患处,更加方便患者携带与使用。目的:观察通络止痛凝胶对于不... 背景:软骨损伤是膝关节骨性关节炎的重要病理表现之一。通络止痛凝胶是在通络止痛方的基础上,以卡波姆、明胶等具有良好生物相容性的化合物作为载体制备而成的,可直接外敷于患处,更加方便患者携带与使用。目的:观察通络止痛凝胶对于不同程度家兔膝关节骨性关节炎软骨炎症和退变的影响,初步探讨通络止痛凝胶治疗膝关节骨性关节炎的作用机制。方法:随机将56只家兔等分为8组,即空白对照组,假手术组,轻、中、重度膝关节骨性关节炎模型组,通络止痛凝胶干预轻、中、重度膝关节骨性关节炎组。除空白对照组及假手术组外,其余各组均予以改良Hulth法建立膝关节骨性关节炎模型,轻、中、重度膝关节骨性关节炎模型组分别于造模后4,8,16周处死,通络止痛凝胶干预轻、中、重度膝关节骨性关节炎组分别在造模4,8,16周予以通络止痛凝胶外敷3周治疗,每周3次,每次1 mL。观察各组造模前后右膝关节直径变化,苏木精-伊红染色观察各组软骨形态学变化;RT-qPCR和Western blot法检测软骨组织白细胞介素1β、肿瘤坏死因子α、基质金属蛋白酶13及解聚蛋白样金属蛋白酶5的表达水平。结果与结论:①改良Hulth法造模后的家兔右膝关节直径较空白对照组及假手术组显著增加,且随时间延长而变化(P<0.05,P<0.01);予以通络止痛凝胶治疗后各组右膝关节直径均有下降,差异有显著性意义,轻、中度组变化更为显著(P<0.01);②苏木精-伊红染色结果显示假手术组软骨形态学变化与空白对照组无明显区别,轻、中、重度膝关节骨性关节炎模型组软骨表面凹凸不平,层次紊乱,出现分层、剥脱;予以通络止痛凝胶干预后软骨表面稍光滑、平整;③与空白对照组相比,轻、中、重度膝关节骨性关节炎模型组白细胞介素1β、肿瘤坏死因子α、基质金属蛋白酶13及解聚蛋白样金属蛋白酶5表达水� 展开更多
关键词 骨 关节炎 膝关节 软骨退变 凝胶 炎症 因子 家兔 实验
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Total flavonoids of hawthorn leaves promote motor function recovery via inhibition of apoptosis after spinal cord injury 认领
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作者 Qiong Zhang Yin Xiong +5 位作者 Bo Li Gui-Ying Deng Wen-Wen Fu Bai-Chuan Cao Shao-Hui Zong Gao-Feng Zeng 《中国神经再生研究:英文版》 SCIE CAS 2021年第2期350-356,共7页
Flavonoids have been reported to have therapeutic potential for spinal cord injury.Hawthorn leaves have abundant content and species of total flavonoids,and studies of the effects of the total flavonoids of hawthorn l... Flavonoids have been reported to have therapeutic potential for spinal cord injury.Hawthorn leaves have abundant content and species of total flavonoids,and studies of the effects of the total flavonoids of hawthorn leaves on spinal cord injury have not been published in or outside China.Therefore,Sprague-Dawley rats were used to establish a spinal cord injury model by Allen's method.Rats were intraperitoneally injected with 0.2 m L of different concentrations of total flavonoids of hawthorn leaves(5,10,and 20 mg/kg)after spinal cord injury.Injections were administered once every 6 hours,three times a day,for 14 days.After treatment with various concentrations of total flavonoids of hawthorn leaves,the Basso,Beattie,and Bresnahan scores and histological staining indicated decreases in the lesion cavity and number of apoptotic cells of the injured spinal cord tissue;the morphological arrangement of the myelin sheath and nerve cells tended to be regular;and the Nissl bodies in neurons increased.The Basso,Beattie,and Bresnahan scores of treated spinal cord injury rats were increased.Western blot assays showed that the expression levels of pro-apoptotic Bax and cleaved caspase-3 were decreased,but the expression level of the anti-apoptotic Bcl-2 protein was increased.The improvement of the above physiological indicators showed a dose-dependent relationship with the concentration of total flavonoids of hawthorn leaves.The above findings confirm that total flavonoids of hawthorn leaves can reduce apoptosis and exert neuroprotective effects to promote the recovery of the motor function of rats with spinal cord injury.This study was approved by the Ethics Committee of the Guangxi Medical University of China(approval No.201810042)in October 2018. 展开更多
关键词 APOPTOSIS Bax protein Bcl-2 protein cleaved caspase-3 INFLAMMATION motor function recovery NEUROPROTECTION Nissl bodies spinal cord injury total flavonoids of hawthorn leaves
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Co-nanoencapsulated meloxicam and curcumin improves cognitive impairment induced by amyloid-beta through modulation of cyclooxygenase-2 in mice 认领
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作者 Maria Eduarda Ziani Gutierrez Anne Suély Pinto Savall +8 位作者 Edina da Luz Abreu Kelly Ayumi Nakama Renata Bem Dos Santos Marina Costa Monteiro Guedes Daiana SilvaÁvila Cristiane Luchese Sandra Elisa Haas Caroline Brandão Quines Simone Pinton 《中国神经再生研究:英文版》 SCIE CAS 2021年第4期780-786,共7页
Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s disease.However,there is data suggesting that inflammation plays a role in its developmen... Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s disease.However,there is data suggesting that inflammation plays a role in its development and progression.Indeed,some non-steroidal antiinflammatory drugs,such as meloxicam,which act by inhibiting cyclooxygenase-2 have been used as neuroprotective agents in different neurodegenerative disease models.The purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules(LCN)on cognitive impairment induced by amyloid-beta peptide injection in mice.LCN were prepared by the nanoprecipitation method.Male Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates(fragment 25–35,3 nmol/3μL)or vehicle and were subsequently treated with curcumin-loaded LCN(10 mg/kg)or meloxicam-loaded LCN(5 mg/kg)or meloxicam+curcumin-co-loaded LCN(5 and 10 mg/kg,respectively).Treatments were given on alternate days for 12 days(i.e.,six doses,once every 48 hours,by intragastric gavage).Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in mice.In the inhibitory avoidance test,both meloxicam and curcumin formulations(oil or co-loaded LCN)improved amyloid-beta-induced memory impairment in mice.However,only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition test.Moreover,the beneficial effects of meloxicam and curcuminco-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical cyclooxygenase-2 downregulation.Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical cyclooxygenase-2 modulation.This study was approved by the Committee on Care and Use of Experimental Animal Resources,the Federal University of Pampa,Brazil(approval No.02-2015)on April 16,2015. 展开更多
关键词 Alzheimer’s disease CURCUMIN CYCLOOXYGENASE-2 lipid core nanocapsules MELOXICAM memory rats inflammation
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低氧诱导因子1α与低氧相关疾病信号通路的关系 认领
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作者 顾霞 赵敏 +2 位作者 王平义 李一梅 李文华 《中国组织工程研究》 CAS 北大核心 2021年第8期1284-1289,共6页
背景:众所周知,PI3K/Akt/mTOR、MAPK、Jak/Stat、NF-κB、Notch等信号通路在细胞增殖分化、基因转录、免疫炎症介导等过程中扮演着重要角色,而低氧诱导因子1α作为低氧反应过程中的核心因子,在介导低氧信号通路中发挥着至关重要的作用... 背景:众所周知,PI3K/Akt/mTOR、MAPK、Jak/Stat、NF-κB、Notch等信号通路在细胞增殖分化、基因转录、免疫炎症介导等过程中扮演着重要角色,而低氧诱导因子1α作为低氧反应过程中的核心因子,在介导低氧信号通路中发挥着至关重要的作用。目的:总结了低氧诱导因子1α与低氧相关疾病信号通路的关系,以期为高原病的研究和治疗提供新思路。方法:应用计算机检索2000至2019年PubMed、Medline数据库,以及2011至2019年中国知网、万方数据库发表的相关文献,检索关键词为“hypoxia inducible factor 1α,signal pathway”“低氧诱导因子1α,信号通路”。结果与结论:在低氧相关疾病(炎症、肿瘤、心脑血管疾病)及高原病发生过程中,低氧诱导因子1α和相关信号通路中的关键因子的表达水平会发生不同程度变化。低氧诱导因子1α与低氧条件下所激活的信号通路关系密切,在经典的PHDs/HIF-1α/pVHL通路的基础上,调控这些信号通路的分子表达水平,或者受到这些信号通路的调控导致自身表达水平升高或降低,以应对低氧环境给机体带来的变化。 展开更多
关键词 低氧诱导因子1Α 通路 低氧 低氧疾病 高原病 炎症 肿瘤 心脑血管疾病
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黑骨藤醇提取物调控急性痛风性关节炎模型大鼠血清炎性因子及滑膜功能 认领
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作者 党荣敏 李宁怡 +3 位作者 谢洪书 蒋催蓉 罗康华 姚文琴 《中国组织工程研究》 CAS 北大核心 2021年第17期2681-2686,共6页
背景:研究发现,阻断滑膜分泌炎症递质的药物治疗急性痛风性关节炎有较好的应用前景。近年来,中药治疗急性痛风性关节炎的研究取得了很大成就。目的:探讨黑骨藤醇提取物对急性痛风性关节炎血清炎性因子及滑膜功能的影响。方法:将60只健... 背景:研究发现,阻断滑膜分泌炎症递质的药物治疗急性痛风性关节炎有较好的应用前景。近年来,中药治疗急性痛风性关节炎的研究取得了很大成就。目的:探讨黑骨藤醇提取物对急性痛风性关节炎血清炎性因子及滑膜功能的影响。方法:将60只健康SD大鼠随机分为6组,分别为空白对照组、模型对照组、秋水仙碱治疗组、黑骨藤醇提取物高、中、低剂量治疗组,每组10只。除空白对照组外,其他各组均在关节腔内注入尿酸钠溶液制备急性痛风性关节炎模型,然后予以秋水仙碱、高、中、低剂量黑骨藤醇提取物治疗。造模后1-7 d观察关节肿胀度;造模后7 d采用ELISA检测血清和滑膜组织中白细胞介素1β、肿瘤坏死因子α、白细胞介素17水平,苏木精-伊红染色观察滑膜病理改变,Western blot检测滑膜组织中NF-κB、ERK1/2和JNK蛋白表达。结果与结论:①模型对照组大鼠关节肿胀,血清和滑膜组织中白细胞介素1β、肿瘤坏死因子α、白细胞介素17水平升高,滑膜组织具有明显炎性细胞浸润和滑膜细胞增生,NF-κB、ERK1/2和p-JNK蛋白表达水平明显升高;②给予秋水仙碱、黑骨藤醇提取物治疗后,上述指标明显改善,高剂量黑骨藤醇提取物组与秋水仙碱组无显著差异,且黑骨藤醇提取物具有剂量依赖性;③结果表明,黑骨藤醇提取物能明显改善急性痛风性关节炎大鼠关节症状,下调炎症因子表达水平,改善滑膜功能,该作用可能与其下调NF-κB、ERK1/2和p-JNK蛋白表达有关。 展开更多
关键词 骨 痛风性关节炎 黑骨藤醇提取物 炎症 因子 滑膜 大鼠 实验
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复方中药圣愈汤治疗股骨头坏死机制的网络药理学分析 认领
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作者 周毅 陈跃平 +3 位作者 章晓云 赖渝 廖建钊 李时斌 《中国组织工程研究》 CAS 北大核心 2021年第17期2687-2696,共10页
背景:圣愈汤可用于治疗股骨头坏死,但其机制不明。目的:基于网络药理学和分子对接探讨圣愈汤治疗股骨头坏死的潜在分子机制研究。方法:利用TCMSP数据库筛选圣愈汤的活性成分及对应靶点,整合GEO芯片数据库、Gene Cards、OMIM数据库的查... 背景:圣愈汤可用于治疗股骨头坏死,但其机制不明。目的:基于网络药理学和分子对接探讨圣愈汤治疗股骨头坏死的潜在分子机制研究。方法:利用TCMSP数据库筛选圣愈汤的活性成分及对应靶点,整合GEO芯片数据库、Gene Cards、OMIM数据库的查询结果获取股骨头坏死相关靶点,然后利用Venny平台进行映射取交集得到圣愈汤治疗股骨头坏死的潜在作用靶点。利用Cytoscape软件构建圣愈汤治疗股骨头坏死的"单味药-活性成分-作用靶点"网络和PPI网络,并使用David数据库对圣愈汤治疗股骨头坏死的作用靶点进行GO功能富集分析和KEGG通路富集分析。使用Autodock vina软件将关键有效成分和重要靶标进行分子对接,评估其结合活性。结果与结论:①筛选出圣愈汤有效活性成分66个和靶点196个,股骨头坏死的相关靶点6045个,取交集获得圣愈汤治疗股骨头坏死靶点73个;②"单味药-活性成分-作用靶点"网络提示主要活性成分有山柰酚、槲皮素、β-谷甾醇、豆甾醇和异鼠李素等;③蛋白互作分析提示主要核心靶点有炎性细胞因子白细胞介素6、血管内皮生长因子A和基质金属肽酶9等;④GO功能富集分析得到804个条目(P<0.01),主要涉及氧化应激反应、血管生成调节、细胞周期调控、免疫反应和炎症因子等方面;⑤KEGG通路富集分析获得120条通路,主要通路涉及缺氧诱导因子1α、白细胞介素17、肿瘤坏死因子、核转录因子κB和Toll样受体等与炎症反应、血管生成和免疫调节相关的通路;⑥分子对接表明5个核心靶标蛋白与5种主要活性成分结合能均远小于参考值,表明主要活性成分与核心靶点受体蛋白稳定结合;⑦结果证实,圣愈汤可能通过山柰酚、槲皮素、β-谷甾醇、豆甾醇和异鼠李素等活性成分,参与调节免疫炎症反应、骨代谢、调节血管生成和氧化应激等相关相关通路,从而起到治疗股骨头坏死� 展开更多
关键词 骨 股骨头坏死 中医药 分子靶点 炎症 骨代谢 氧化应激 网络药理学
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The NLRP3 inflammasome: a potential therapeutic target for traumatic brain injury 认领
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作者 Saifudeen Ismael Heba A.Ahmed +3 位作者 Tusita Adris Kehkashan Parveen Parth Thakor Tauheed Ishrat 《中国神经再生研究:英文版》 SCIE CAS 2021年第1期49-57,共9页
Although the precise mechanisms contributing to secondary brain injury following traumatic brain injury are complex and obscure,a number of studies have demonstrated that inflammatory responses are an obvious and earl... Although the precise mechanisms contributing to secondary brain injury following traumatic brain injury are complex and obscure,a number of studies have demonstrated that inflammatory responses are an obvious and early feature in the pathogenesis of traumatic brain injury.Inflammasomes are multiprotein complexes that prompt the stimulation of caspase-1 and subsequently induce the maturation and secretion of proinflammatory cytokines,such as interleukin-1β and interleukin-18.These cytokines play a pivotal role in facilitating innate immune responses and inflammation.Among various inflammasome complexes,the NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is the best characterized,a crucial role for NLRP3 has been demonstrated in various brain diseases,including traumatic brain injury.Several recent studies have revealed the contribution of NLRP3 inflammasome in identifying cellular damage and stimulating inflammatory responses to aseptic tissue injury after traumatic brain injury.Even more important,blocking or inhibiting the activation of the NLRP3 inflammasome may have substantial potential to salvage tissue damage during traumatic brain injury.In this review,we summarize recently described mechanisms that are involved in the activation and regulation of the NLRP3 inflammasome.Moreover,we review the recent investigations on the contribution of the NLRP3 inflammasome in the pathophysiology of TBI,and current advances and challenges in potential NLRP3-targeted therapies.A significant contribution of NLRP3 inflammasome activation to traumatic brain injury implies that therapeutic approaches focused on targeting specific inflammasome components could significantly improve the traumatic brain injury outcomes. 展开更多
关键词 INFLAMMATION INTERLEUKIN-1Β NLRP3-inflammasome CASPASE-1 MCC950 traumatic brain injury
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Dynamic changes in the systemic immune responses of spinal cord injury model mice 认领
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作者 Tian-Yun Gao Fei-Fei Huang +5 位作者 Yuan-Yuan Xie Wen-Qing Wang Liu-Di Wang Dan Mu Yi Cui Bin Wang 《中国神经再生研究:英文版》 SCIE CAS 2021年第2期382-387,共6页
Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated... Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019. 展开更多
关键词 C-reactive protein immune dysfunction INFLAMMATION inflammatory cytokines regulatory T-cells spinal cord injury systemic immune response T-helper cells
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Effect of Shexiang Baoxin Pill(麝香保心丸) in Alleviating Early Hypertensive Renal Injury in Rats 认领
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作者 ZHAO Jia-hui ZHANG Lei +1 位作者 LIU Yang CHENG Qing-li 《中国结合医学杂志:英文版》 SCIE CAS 2021年第1期47-53,共7页
Objective:To investigate the effect of Shexiang Baoxin Pill(麝香保心丸,SBP)on early hypertensive renal injury in rats and to explore the possible mechanism.Methods:Twelve-week-old spontaneous hypertensive rats(SHRs)wi... Objective:To investigate the effect of Shexiang Baoxin Pill(麝香保心丸,SBP)on early hypertensive renal injury in rats and to explore the possible mechanism.Methods:Twelve-week-old spontaneous hypertensive rats(SHRs)with high-salt diet(dietary containing 8%NaCl)were randomized into the SBP group[40 mg/(kg·d)],losartan potassium group[20 mg/(kg·d)]and saline group by stratified random sampling method,12 in each group.Blood pressure and urea albumin creatinine ratio were measured.After 10 weeks,the expression levels of serum creatinine(Scr),hypersensitive C-reactive protein(hs-CRP),interleukin(IL)-1β,IL-6,tumor necrosis factorα(TNF-α),and transforming growth factorβ(TGF-β)in serum were assessed.Kidney pathology periodate-schiff staining was performed.Semi-quantitative count of macrophage infiltration was determined by immunochemistry of CD68 staining.Real-time quantitative polymerase chain reaction and Western blot were performed to examine the mRNA and protein expressions of Toll-like receptor 4(TLR4),nuclear factorκB(NF-κB),monocyte chemokine peptide(MCP-1),inducible nitric oxide synthase(iNOS),and arginase-1(Arg-1).Results:SBP did not affect the mortality of SHR(P<0.05).SBP significantly reduced the level of elevated blood pressure of SHRs,but the effect was less significantly than that of losartan potassium.SBP decreased urine protein(P<0.01)and the expression levels of IL-1β,IL-6,TNF-α,and TGF-βin serum.The 22-week-old SHRs showed mild proliferation of glomerular endothelial cells,glomerular ischemic lesions,inflammatory cell infiltration in renal tubular interstitium and arteriosclerosis.Both SBP and losartan potassium had alleviated renal pathological change,and significantly reduced the infiltration of macrophage(P<0.05,P<0.01).SBP and losartan potassium decreased the expressions of TLR4,NF-κB,MCP-1,iNOS,and Arg-1.Conclusion:SBP significantly modified the early hypertensive renal injury by reducing inflammation,and the effect was similar to losartan potassium. 展开更多
关键词 HYPERTENSION kidney injury Shexiang Baoxin Pill Chinese medicine INFLAMMATION
振荡电场刺激脊髓损伤模型大鼠抑制神经炎症反应促进功能恢复 认领
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作者 方超 孙健 +2 位作者 魏来福 高飞 钱军 《中国组织工程研究》 CAS 北大核心 2021年第11期1717-1722,共6页
背景:振荡场刺激是一种新兴的脊髓损伤治疗技术,在受伤的脊髓上施加电流可以促进愈合和组织再生。然而,振荡电场刺激导致脊髓损伤恢复的机制尚不完全清楚。目的:探讨振荡电场能否通过减轻大鼠脊髓损伤后神经炎症反应促进神经功能恢复。... 背景:振荡场刺激是一种新兴的脊髓损伤治疗技术,在受伤的脊髓上施加电流可以促进愈合和组织再生。然而,振荡电场刺激导致脊髓损伤恢复的机制尚不完全清楚。目的:探讨振荡电场能否通过减轻大鼠脊髓损伤后神经炎症反应促进神经功能恢复。方法:雌性SD大鼠63只,随机被分为3组:实验组、脊髓损伤组和假手术组。假手术组大鼠仅行椎板切除术而不损伤脊髓;实验组和脊髓损伤组大鼠建立大鼠脊髓损伤模型,并在大鼠胸部(T9-T10)植入振荡电场刺激器装置,实验组在术后接受持续电刺激,脊髓损伤组不进行电刺激。用Basso-bettie-Bresnahan(BBB)评分法评价大鼠术后运动功能恢复情况;苏木精-伊红染色检测损伤部位组织修复和炎性细胞的募集;免疫荧光染色检测损伤部位星形胶质细胞和小胶质细胞的数量。动物实验方案由安徽医科大学实验动物伦理委员会批准,编号为LLSC20190736。结果与结论:①BBB评分,实验组的BBB评分较脊髓损伤组显著增加;②苏木精-伊红染色结果表明,实验组损伤局部炎性细胞的数量较脊髓损伤组显著减少;③免疫荧光结果显示,实验组术后各时间点的神经胶质纤维酸性蛋白阳性细胞和小胶质细胞数量均明显少于脊髓损伤组;④结果说明,振荡电场刺激能改善大鼠脊髓损伤后的下肢运动功能,促进脊髓损伤后的组织修复,减轻炎性细胞募集,有效抑制星形胶质细胞和小胶质细胞的激活;提示振荡电场可以通过抑制脊髓损伤后炎症反应促进神经功能恢复。 展开更多
关键词 振荡电场 脊髓 脊髓损伤 炎症 功能恢复 再生 星形胶质细胞
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Comparative transcriptomic analysis of rat versus mouse cerebral cortex after traumatic brain injury 认领
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作者 Meng-Shi Yang Xiao-Jian Xu +2 位作者 Bin Zhang Fei Niu Bai-Yun Liu 《中国神经再生研究:英文版》 SCIE CAS 2021年第7期1235-1243,共9页
The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative st... The heterogeneity of traumatic brain injury(TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients.Targeting common processes across species may be an innovative strategy to combat debilitating TBI.In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact.The RNA sequencing data from the mouse model of TBI were downloaded from the Gene Expression Omnibus(ID: GSE79441) at the National Center for Biotechnology Information.For the rat data, peri-injury cerebral cortex samples were collected for transcriptomic analysis 24 hours after TBI.Differentially expressed gene-based functional analysis revealed that common features between the two species were mainly involved in the regulation and activation of the innate immune response, including complement cascades as well as Toll-like and nucleotide oligomerization domain-like receptor pathways.These findings were further corroborated by gene set enrichment analysis.Moreover, transcription factor analysis revealed that the families of signal transducers and activators of transcription(STAT), basic leucine zipper(BZIP), Rel homology domain(RHD), and interferon regulatory factor(IRF) transcription factors play vital regulatory roles in the pathophysiological processes of TBI, and are also largely associated with inflammation.These findings suggest that targeting the common innate immune response might be a promising therapeutic approach for TBI.The animal experimental procedures were approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No.201802001) on June 6, 2018. 展开更多
关键词 cognitive impairment cross-species comparison gene set enrichment analysis INFLAMMATION innate immune neurodegenerative disease secondary injury transcription factor TRANSCRIPTOME traumatic brain injury
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Klotho and neurons: mutual crosstalk between autophagy, endoplasmic reticulum, and inflammatory response 认领
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作者 Jennifer Mytych 《中国神经再生研究:英文版》 SCIE CAS 2021年第8期1542-1543,共2页
Klotho is one of a number of well-known longevity-associated genes.Its depletion in aging or disease may promote several neuropathologies associated with the central nervous system,including hypomyelination and phosph... Klotho is one of a number of well-known longevity-associated genes.Its depletion in aging or disease may promote several neuropathologies associated with the central nervous system,including hypomyelination and phosphorylation of neurofilaments,synaptic loss and modulation of their plasticity,behavioral impairments,neuroinflammation。 展开更多
关键词 KLOTHO INFLAMMATION reticulum
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Glial-derived transforming growth factor β1(TGF-β1):a key factor in multiple sclerosis neuroinflammation 认领
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作者 Coram Guevara Fernando C.Ortiz 《中国神经再生研究:英文版》 SCIE CAS 2021年第3期510-511,共2页
Glial cell activation and neuroinflammation in multiple sclerosis(MS):MS is an irreversible and progressive central nervous system(CNS)disease which originates in the autoimmune attack of lymphocytes against CNS myeli... Glial cell activation and neuroinflammation in multiple sclerosis(MS):MS is an irreversible and progressive central nervous system(CNS)disease which originates in the autoimmune attack of lymphocytes against CNS myelin.This specialized membrane,synthesized by oligodendrocytes(OL)in the CNS,provides metabolic support to axons and allows for saltatory conduction in neurons.The lack of myelin(i.e.,demyelination)leads to axonal degeneration,neuronal death,and the consequent neurological disabilities(Franklin and Ffrench-Constant,2017). 展开更多
关键词 INFLAMMATION DEGENERATION SCLEROSIS
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Psychosis symptoms following aberrant immunity in the brain 认领
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作者 Akitoshi Ozaki Yuki Yamawaki Gen Ohtsuki 《中国神经再生研究:英文版》 SCIE CAS 2021年第3期512-513,共2页
Neuroinflammation in the brain is thought related to the emergence of various psychoses,although the identifying regional significance,the involvement of immune-cells and lymphocytic activity,and ways for the therapeu... Neuroinflammation in the brain is thought related to the emergence of various psychoses,although the identifying regional significance,the involvement of immune-cells and lymphocytic activity,and ways for the therapeutic recovery are under the effort of researchers.We recently revealed that the cerebellar acute inflammation causes the symptoms manifested in mood disorders or developmental disorders,which were associated with hyperexcitability due to immune-triggered plasticity and the overconnectivity between the inflamed cerebellum and prefrontal cortex(Yamamoto et al.,2019). 展开更多
关键词 INFLAMMATION IMMUNITY INVOLVEMENT
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