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412篇 您的检索式:作者名="Zhen Cao"
    题名 作者 年代 出处 被引量
1Upregulation of PTEN involved in rosiglitazone-induced apoptosis in human hepatocellular carcinoma cells显示文摘瞄准:调查 rosiglitazone 的效果, peroxisomeproliferator-ac-tivated 受体 gamma ( PPARy )收缩筋在在 hepatocellular carcinomacells 在染色体 10 基因( PTEN )和房间生长上删除的磷酸酶 andtensin 相当或相同事物的表示上,象这些 effects.Methods 的内在的机制一样: RT-PCR 和西方的 blottinganalyses 被执行在 Hep3B 房间 treatedwith rosiglitazone.3-( 4,5-Dimethylthiazol-2-yl )检测抄写和 PTEN 的表示 -2,5-diphenylLiang-qi CAO Xi-lin CHEN Qian WANG Xiao-hui HUANG Mao-chuan ZHEN Long-juan ZHANG Wen LI Jiong BI 2007Acta Pharmacologica Sinica2007,28,6:32
2IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A (HIN1) Virus显示文摘Chenggang Li Penghui Yang Yang Sun Taisheng Li Chen Wang Zhong Wang Zhen Zou Yiwu Yan Wei Wang Chen Wang Zhongwei Chen Li Xing Chong Tang Xiangwu Ju Feng Guo Jiejie Deng Yan Zhao Peng Yang Jun Tang Huanling Wang Zhongpeng Zhao Zhinan Yin Bin Cao Xiliang Wang Chengyu Jiang 2012Cell Research2012,22,3:22
3Transforming growth factor-β in stem cells and tissue homeostasis显示文摘TGF-β 1–3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix(ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-β is involved in the recruitment of stem/progenitor cell participation in tissue regeneration/remodeling process, whereas sustained abnormalities in TGF-β ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to pathobiology of major diseases. Modulation of TGF-β signaling with different approaches has proven effective pre-clinically in the treatment of multiple pathologies such as sclerosis/fibrosis, tumor metastasis, osteoarthritis, and immune disorders. Thus, further elucidation of the mechanisms by which TGF-β is activated in different tissues/organs and how targeted cells respond in a context-dependent way can likely be translated with clinical benefits in the management of a broad range of diseases with the involvement of TGF-β.Xin Xu Liwei Zheng Quan Yuan Gehua Zhen Janet L.Crane Xuedong Zhou Xu Cao 2018Bone Research2018,6,1:22
4Effects of Short-Term Forest Bathing on Human Health in a Broad-Leaved Evergreen Forest in Zhejiang Province,China显示文摘Objective To investigate the effects of short-term forest bathing on human health.Methods Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10.One group was sent on a two-night trip to a broad-leaved evergreen forest,and the other was sent to a city area.Serum cytokine levels reflecting inflammatory and stress response,indicators reflecting oxidative stress,the distribution of leukocyte subsets,and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments.A profile of mood states (POMS) evaluation was used to assess changes in mood states.Results No significant differences in the baseline values of the indicators were observed between the two groups before the experiment.Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level,as evidenced by decreased malondialdehyde,interleukin-6,and tumor necrosis factor α levels compared with the urban group.Serum cortisol levels were also lower than in the urban group.Notably,the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment.The POMS evaluation showed that after exposure to the forest environment,subjects had lower scores in the negative subscales,and the score for vigor was increased.Conclusion Forest bathing is beneficial to human health,perhaps through preventive effects related to several pathological factors.MAO Gen Xiang LAN Xiao Guang CAO Yong Bao CHEN Zhuo Mei HE Zhi Huat LV Yuan Dong WANG Ya Zhen HU Xi Lian WANG Guo Fu YAN Jing 2012Biomedical and Environmental Sciences2012,25,3:20
5The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals显示文摘Metabolic diseases are the most common and rapidly growing health issues worldwide.The massive population-based human genetics is crucial for the precise prevention and intervention of metabolic disorders.The China Metabolic Analytics Project(ChinaMAP)is based on cohort studies across diverse regions and ethnic groups with metabolic phenotypic data in China.Here,we describe the centralized analysis of the deep whole genome sequencing data and the genetic bases of metabolic traits in 10,588 individuals from the ChinaMAP.The frequency spectrum of variants,population structure,pathogenic variants and novel genomic characteristics were analyzed.The individual genetic evaluations of Mendelian diseases,nutrition and drug metabolism,and traits of blood glucose and BMI were integrated.Our study establishes a large-scale and deep resource for the genetics of East Asians and provides opportunities for novel genetic discoveries of metabolic characteristics and disorders.Yanan Cao Lin Li Min Xu Zhimin Feng Xiaohui Sun Jieli Lu Yu Xu Peina Du Tiange Wang Ruying Hu Zhen Ye Lixin Shi Xulei Tang Li Yan Zhengnan Gao Gang Chen Yinfei Zhang Lulu Chen Guang Ning Yufang Bi Weiqing Wang The ChinaMAP Consortium 2020Cell Research2020,30,9:20
6Effect of porosities of bilayered porous scaffolds on spontaneous osteochondral repair in cartilage tissue engineering显示文摘Poly(lactide-co-glycolide)-bilayered scaffolds with the same porosity or different ones on the two layers were fabricated,and the porosity effect on in vivo repairing of the osteochondral defect was examined in a comparative way for the first time.The constructs of scaffolds and bone marrow-derived mesenchymal stem cells were implanted into pre-created osteochondral defects in the femoral condyle of New Zealand white rabbits.After 12 weeks,all experimental groups exhibited good cartilage repairing according to macroscopic appearance,cross-section view,haematoxylin and eosin staining,toluidine blue staining,immunohistochemical staining and real-time polymerase chain reaction of characteristic genes.The group of 92%porosity in the cartilage layer and 77%porosity in the bone layer resulted in the best efficacy,which was understood by more biomechanical mimicking of the natural cartilage and subchondral bone.This study illustrates unambiguously that cartilage tissue engineering allows for a wide range of scaffold porosity,yet some porosity group is optimal.It is also revealed that the biomechanical matching with the natural composite tissue should be taken into consideration in the design of practical biomaterials,which is especially important for porosities of a multi-compartment scaffold concerning connected tissues.Zhen Pan Pingguo Duan Xiangnan Liu Huiren Wang Lu Cao Yao He Jian Dong Jiandong Ding 2015Regenerative Biomaterials2015,2,1:20
7shRNA targeting HDGF suppressed cell growth and invasion of squamous cell lung cancer显示文摘导出 Hepatoma 的生长因素(HDGF ) ,有 mitogenic 的原子蛋白质和 angiogenic 活动,被报导了主要涉及 tumorigenesis 和非小的房间肺癌症的前进。在这研究, HDGF 表示被 specific-shRNA 与在肺指向 HDGF 的 lentivirus 表示向量击倒有鳞的房间癌 520 房间。shRNA 击倒的 HDGF 在 vitro 并且在由 MTT,板克隆和移植肿瘤模型试金显示了的 vivo 显著地压制了房间增长。另外, HDGF 的组合式的表达式也禁止了出现在 transwell 和 Boyden 实验的房间移植和侵略。因为参予有鳞的房间肺癌症的致病的 oncogene,和 HDGF 可以是为非小的房间肺癌症的一个关键治疗学的目标,我们断定 HDGF 行动。Jie Meng Wei Xie Liming Cao Chengping Hu Zhiyuan Zhen 2010Acta Biochimica et Biophysica Sinica2010,42,1:19
8Dihydromyricetin protects neurons in an MPTPinduced model of Parkinson's disease by suppressing glycogen synthase kinase-3 beta activity显示文摘瞄准:它是相信的将军那个 mitochondrial 机能障碍和氧化应力在 Parkinsons 疾病(PD ) 的病理起关键作用。Dihydromyricetin (DHM ) ,从白蔹属 grossedentata 提取的自然 flavonoid,最近被发现得到有势力抗氧化效果。在现在的学习,我们在保护 dopaminergic neurons.Methods 探索了 DHM 的角色:男 C57BL/6 老鼠 intraperitoneally 与 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP ) 被注射让 7 d 导致 PD。另外,老鼠为 13 d 的一个总数与 5 或 10 mg/kg DHM 被对待(在 MPTP 的开始前的 3 d,在 MPTP 管理(7 d ) 和在 MPTP 的结束以后的 3 d 期间) 。为盐或 DHM 独自一个的处理组,老鼠被注射与盐或为 13 d 的 DHM。在 d 上 14,行为的测试(运动活动, rotarod 测试和杆测试) 被管理。在行为的测试以后,老鼠被牺牲,并且大脑织物为 immunofluorescence 染色并且西方的弄污是镇定的。另外, MES23.5 细胞与 MPP + 和 DHM 被对待,并且评估了使用细胞生存能力试金,反应的氧种(ROS ) 大小, apoptosis 分析和西方的 blotting.Results:DHM 显著地稀释了导致 MPTP 的老鼠行为的缺陷和 dopaminergic 神经原损失。在 MES23.5 房间, DHM 以一种剂量依赖者方式稀释了 MPP +-induced 房间损害和 ROS 生产。另外, DHM 在一个剂量依赖者和时间依赖者举止增加了肝糖 synthase kinase-3 贝它 phosphorylation,它可以与导致 DHM 的 dopaminergic neuronal protection.Conclusion 被联系:现在的学习证明 DHM 是为由 modulating 的 DA 神经原的一个有势力 neuroprotective 代理人 Akt/GSK-3β小径,它建议那 DHM 可以是 PD 的一个有希望的治疗学的候选人。Zhao-xiang REN Ya-fei ZHAO Ting CAO Xue-chu ZHEN 2016Acta Pharmacologica Sinica2016,37,10:19
9Green tea polyphenol epigallocatechin-3-gallate suppresses rat hepatic stellate cell invasion by inhibition of MMP-2 expression and its activation显示文摘瞄准:Epigallocatechin-3-gallate (EGCG ) 是绿茶多酚的主要部件,其生物性质的宽范围包括 anti-fibrogenic 活动。Matrixmetalloproteinases (MMP ) 参予细胞外的矩阵降级涉及肝的纤维变性的发展。现在的学习调查 EGCG 是否在老鼠禁止主要 gelatinase 矩阵 metalloproteinase-2 (MMP-2 ) 的激活肝的星形的房间(HSC ).METHODS:MMP-2 的表示, metalloproteinases-2 (TIMP-2 ) 的织物禁止者, andmembrane 类型 1-MMP (MT1-MMP ) 被 RT-PCR 和西方的污点分析估计。MMP-2 活动被 zymography 评估, MT1-MMP 活动被酶的试金估计。HSC 移植被弯屈的愈合的试金测量,房间侵略用 Transwell 房间文化房间被执行。结果:在 HSC 的 MMP-2 mRNA 和蛋白质的表示被 EGCGtreatment 实质地减少。EGCG 处理也减少了导致的 concanavalin A (ConA ) 分泌 MMP-2and 的激活以一种剂量依赖者方式减少了 MT1-MMP 活动。另外, EGCG 禁止了 HSCmigration 或侵略。结论:EGCG 的能力建议那 EGCG 可能在肝的纤维变性的处理和预防是有用的压制 MMP-2 激活和 HSCinvasiveness。Mao-chuan ZHEN Xiao-hui HUANG Qian WANG Kai SUN Yun-jian LIU Wen LI Long-juan ZHANG Liang-qi CAO Xi-ling CHEN 2006Acta Pharmacologica Sinica2006,27,12:17
10COVID-19 Outbreak Caused by Contaminated Packaging of Imported Cold-Chain Products—Liaoning Province,China,July 2020显示文摘Summary What is known about this topic?Few major outbreaks of coronavirus disease 2019(COVID-19)have occurred in China after major nonpharmaceutical interventions and vaccines have been deployed and implemented.However,sporadic outbreaks that had high possibility to be linked to cold chain products were reported in several cities of China..What is added by this report?In July 2020,a COVID-19 outbreak occurred in Dalian,China.The investigations of this outbreak strongly suggested that the infection source was from COVID-19 virus-contaminated packaging of frozen seafood during inbound unloading personnel contact.What are the implications for public health practice?Virus contaminated paper surfaces could maintain infectivity for at least 17–24 days at-25℃.Exposure to COVID-19 virus-contaminated surfaces is a potential route for introducing the virus to a susceptible population.Countries with no domestic transmission of COVID-19 should consider introducing prevention strategies for both inbound travellers and imported goods.Several measures to prevent the introduction of the virus via cold-chain goods can be implemented.Huilai Ma1 Jianqun Zhang Ji Wang Ying Qin Cao Chen Yang Song Liang Wang Jun Meng Lingling Mao Fengqin Li Ning Li Jian Cai Yong Zhang Dayan Wang Yunting Xia Hong Wang Shaofeng Jiang Xiang Zhao Peihua Niu Wenjie Tan Tao Ma Yecheng Yao Naiying Mao Zhen Zhu Tianjiao Ji Qian Yang Baoying Huang Li Zhao Jianxing Yu Li Bai Shuangli Zhu Dongyan Wang Yan Zhang Yingwei Sun Mingchun Luan Yanhai Wang Haibo Sun Shihong Yang Zhijian Bo Xiang Ren Zhongjie Li George Fu Gao Wei Yao Wenqing Yao Zijian Feng Wenbo Xu 2021China CDC weekly2021,3,21:16
11Investigation of the prevalence of patients co-colonized or infected with methiclllin-resistant Staphylococcus aureus and vancomycin- resistant enterococci in China: a hospital-based study显示文摘methicillin 抵抗的葡萄球菌 aureus (MRSA ) 和万古霉素抵抗的 enterococci (VRE ) 引起的背景医院的感染能导致增加的病态和死亡。在 2006,自从第一 VRE 医院的感染, VRE 医院的传播在 2003 在我们的医院里成为了现实。很少在病人与 VRE 和 MRSA 对共存的流行被知道。学习的主要目的是在2年的经期期间在一样的病人与 MRSA 和 VRE 在我们的医院和共存的流行里识别流行 MRSA 克隆的分子的特征, 2006-2007 .Methods 临床的特征,实验室测试结果,并且 129 个盒子的治疗学的结果从2006年1月孤立 MRSAcollected 到2007年12月的人,回顾地被分析。聚合酶链反应(PCR ) 被用来决定 mecA-femB 类型和 staphylococcal 盒子染色体 mec (SCCmec ) 打字。所有参加者被屏蔽为临床并且与 129 MRSA 孤立的 MRSA.Results 识别 VRE 紧张的共存的 microbiological 数据在学习被包括:71 (55%) 从特别护理联合起来, 35 (27.2%) 从外科的病房并且 23 (17.8%) 从医药病房。MRSA 的隔离的最经常的来源是唾沫(76.7%) 。从七个病人,我们孤立 MRSA 和 VRE (E。faecium ) 同时在他们的住院病人停留期间。127 (127/129, 98.4%) MRSA 孤立 harboured SCCmec 类型, 2 仅仅 MRSA 紧张包含了 SCCmec 类型。所有 129 MRSA 孤立对万古霉素, teicoplanin 和 linezolid 仍然保持敏感。更高的敏感率以氯霉素 99.2% 闻名(128/129 ) 。(26/129 ) 仅仅, 20.2% MRSA 孤立对 rifampin 敏感。所有与高最小的禁止的集中(MIC ) 孤立介绍抵抗到多重抗菌剂代理人,包括:酮(青霉素,新青霉素, cefoxitin,和 cefazolin )(ciprofloxacin, levofloxacin,和 moxifloxacin ) ,四圜素,抗生素的一种, gentamicin,和 quinolones .Conclusions 在从 2006 ~ 2007 的北京 Chaoyang 医院的占优势的 MRSA 克隆有类型 SCCmec 元素。所有 MRSA 孤立是到抗菌剂代理人的 multiresistant。在一样的病人的 MRSA 和 VRE 的共存的出现不是稀罕的。医生们应该对源于 MRSA 和 VRE 的感染给予更多的注意。好攻击的感染控制措施应该被采取阻止 multidrug 抵抗有机体的传播。WANG Zhen CAO Bin LIU Ying-mei GU Li WANG Chen 2009Chinese Medical Journal2009,,11:16
12Change of choline compounds in sodium selenite-induced apoptosis of rats used as quantitative analysis by in vitro 9.4T MR spectroscopy显示文摘AIM: To study liver cell apoptosis caused by the toxicity of selenium and observe the alteration of choline compounds using in vitro 9.4T high resolution magnetic resonance spectroscopy. METHODS: Twenty male Wistar rats were randomly divided into two groups. The rats in the treatment group were intraperitoneally injected with sodium selenite and the control group with distilled water. All rats were sacrifi ced and the livers were dissected. 1H-MRS data were collected using in vitro 9.4T high resolution magnetic resonance spectrometer. Spectra were processed using XWINNMR and MestRe-c 4.3. HE and TUNEL staining was employed to detect and confi rm the change of liver cells. RESULTS: Good 1H-MR spectra of perchloric acid extract from liver tissue of rats were obtained. The conventional metabolites were detected and assigned. Concentrations of different ingredient choline compounds in treatment group vs control group were as follows: total choline compounds,5.08 ± 0.97 mmol/L vs 3.81 ± 1.16 mmol/L (P = 0.05); and free choline,1.07 ± 0.23 mmol/L vs 0.65 ± 0.20 mmol/L (P = 0.00). However,there was no statistical signif icance between the two groups. The hepatic sinus and cellular structure of hepatic cells in treatmentgroup were abnormal. Apoptosis of hepatic cells was confi rmed by TUNEL assay. CONCLUSION: High dose selenium compounds can cause the rat liver lesion and induce cell apoptosis in vivo. High resolution 1H-MRS in vitro can detect diversified metabolism. The changing trend for different ingredient of choline compounds is not completely the same at early period of apoptosis.Zhen Cao Lin-Ping Wu Yun-Xia Li Yu-Bo Guo Yao-Wen Chen Ren-Hua Wu 2008World Journal of Gastroenterology2008,14,24:13
13Mechanically induced Ca^(2+) oscillations in osteocytes release extracellular vesicles and enhance bone formation显示文摘The vast osteocytic network is believed to orchestrate bone metabolic activity in response to mechanical stimuli through production of sclerostin, RANKL, and osteoprotegerin(OPG). However, the mechanisms of osteocyte mechanotransduction remain poorly understood. We've previously shown that osteocyte mechanosensitivity is encoded through unique intracellular calcium (Ca^(2+) ) dynamics. Here, by simultaneously monitoring Ca^(2+) and actin dynamics in single cells exposed to fluid shear flow, we detected actin network contractions immediately upon onset of flow-induced Ca^(2+) transients, which were facilitated by smooth muscle myosin and further confirmed in native osteocytes ex vivo. Actomyosin contractions have been linked to the secretion of extracellular vesicles(EVs), and our studies demonstrate that mechanical stimulation upregulates EV production in osteocytes through immunostaining for the secretory vesicle marker Lysosomal-associated membrane protein 1(LAMP1) and quantifying EV release in conditioned medium, both of which are blunted when Ca^(2+) signaling was inhibited by neomycin. Axial tibia compression was used to induce anabolic bone formation responses in mice, revealing upregulated LAMP1 and expected downregulation of sclerostin in vivo. This load-related increase in LAMP1 expression was inhibited in neomycin-injected mice compared to vehicle.Micro-computed tomography revealed significant load-related increases in both trabecular bone volume fraction and cortical thickness after two weeks of loading, which were blunted by neomycin treatment. In summary, we found mechanical stimulation of osteocytes activates Ca^(2+) -dependent contractions and enhances the production and release of EVs containing bone regulatory proteins. Further, blocking Ca^(2+) signaling significantly attenuates adaptation to mechanical loading in vivo, suggesting a critical role for Ca^(2+) -mediated signaling in bone adaptation.Andrea E.Morrell Genevieve N.Brown Samuel T.Robinson Rachel L.Sattler Andrew D.Baik Gehua Zhen Xu Cao Lynda F.Bonewald Weiyang Jin Lance C.Kam X.Edward Guo 2018Bone Research2018,6,1:13
14Long Distance Transmission of SARS-CoV-2 from Contaminated Cold Chain Products to Humans——Qingdao City,Shandong Province,China,September 2020显示文摘Summary What is already known about this topic?Though coronavirus disease 2019(COVID-19)has largely been controlled in China,several outbreaks of COVID-19 have occurred from importation of cases or of suspected virus-contaminated products.Though several outbreaks have been traced to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)isolated on the outer packaging of cold chain products,live virus has not been obtained.Huilai Ma Zhaoguo Wang Xiang Zhao Jun Han Yong Zhang Hong Wang Cao Chen Ji Wang Fachun Jiang Jie Lei Jingdong Song Shaofeng Jiang Shuangli Zhu Huihui Liu Dongyan Wang Yao Meng Naiying Mao Yanhai Wang Zhen Zhu Zhixiao Chen Bingling Wang Qinqin Song Haijun Du Qun Yuan Dong Xia Zhiqiang Xia Peipei Liu Yuchao Wu Zijian Feng Ruqin Gao George F.Gao Wenbo Xu 2021China CDC weekly2021,3,30:13
15Safety,tolerability,and pharmacokinetics of VV116,an oral nucleoside analog against SARS-CoV-2,in Chinese healthy subjects显示文摘VV116(JT001)is an oral drug candidate of nucleoside analog against SARS-CoV-2.The purpose of the three phase I studies was to evaluate the safety,tolerability,and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects,as well as the effect of food on the pharmacokinetics and safety of VV116.Three studies were launched sequentially:Study 1(single ascending-dose study,SAD),Study 2(multiple ascending-dose study,MAD),and Study 3(food-effect study,FE).A total of 86 healthy subjects were enrolled in the studies.VV116 tablets or placebo were administered per protocol requirements.Blood samples were collected at the scheduled time points for pharmacokinetic analysis.116-N1,the metabolite of VV116,was detected in plasma and calculated for the PK parameters.In SAD,AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25–800 mg.T_(1/2)was within 4.80–6.95 h.In MAD,the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116.In FE,the standard meal had no effect on Cmax and AUC of VV116.No serious adverse event occurred in the studies,and no subject withdrew from the studies due to adverse events.Thus,VV116 exhibited satisfactory safety and tolerability in healthy subjects,which supports the continued investigation of VV116 in patients with COVID-19.Hong-jie Qian Yu Wang Meng-qi Zhang Yuan-chao Xie Qing-qing Wu Li-yu Liang Ye Cao Hua-qing Duan Guang-hui Tian Juan Ma Zhuo-bing Zhang Ning Li Jing-ying Jia Jing Zhang Haji Akber Aisa Jing-shan Shen Chen Yu Hua-liang Jiang Wen-hong Zhang Zhen Wang Gang-yi Liu 2022Acta Pharmacologica Sinica2022,43,12:13
16Dapper1 promotes autophagy by enhancing the Beclinl -Vps34-Atg14L complex formation显示文摘Benvu Ma Weipeng Cao Wenxia Li Chan Gao Zhen Qi Yan Zhao Jun Du Hua Xue Junya Peng Jun Wen Hua Chen Yuanheng Ning Lei Huang Hong Zhang Xiang Gao Li Yu Ye-Guang Chen 2014Cell Research2014,24,8:12
17Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China显示文摘LAI Yue-yun HUANG Xiao-jun CAI Zhen CAO Xiang-shan CHEN Fang-ping CHEN Xie-qun CHEN Bao-an 2012Chinese Medical Journal2012,,15:12
18The oncometabolite 2-hydroxyglutarate inhibits microglial activation via the AMPK/mTOR/NF-kB pathway显示文摘Microglia,the brain-resident macrophage,is known as the innate immune cell type in the central nervous system.Microglia is also the major cellular component of tumor mass of gliomas that plays a key role in glioma development.Mutations of isocitrate dehydrogenases 1 and 2(IDH1/2)frequently occur in gliomas,which leads to accumulation of oncometabolic product 2-hydroxyglutarate(2HG).Moreover,IDH1/2 mutations were found to correlate with better prognosis in glioma patients.In thepresent study,we investigated the effects of the 2HG on microglial inflammatory activation.We showed that the conditioned media(CM)from GL261 glioma cells stimulated the activation of BV-2 microglia cells,evidenced by markedly increased expression of interleukin-6(IL-6),IL-1β,tumor necrosis factor-a(TNF-α),CCL2(C-C motif chemokine ligand 2)and CXCL10(C-X-C motif chemokine 10).CM-induced expression of proinflammatory genes was signifcantly suppressed by pretreatment with a synthetic cell-permeable 2HG(1 mM)or a nuclear factor-kB(NF-KB)inhibitor BAY11-7082(10μM).In lipopolysaccharide(LPS)-or TNF-a-stimulated BV-2 microglia cells and primary microglia,pretreatment with 2HG(0.25-1 mM)dose-dependently suppressed the expression of proinflammatory genes.We further demonstrated that 2HG significantly suppressed LPS-induced phosphorylation of IkB kinase a/β(IKKa/B),lkBa and p65,IkB degradation,and nuclear translocation of p65 subunit of NF-KB,as well as NF-KB transcriptional activity.Similarly,ectopic expression of mutant isocitrate dehydrogenase 1(IDH1)(R132H)significantly decreased TNF-a-induced activation of NF-KB signaling pathway,Finally,we revealed that activation of adenosine 5'-monophosphate-activated protein kinase(AMPK)and subsequent inhibition of mammalian target of rapamycin(mTOR)signaling contributed to theinhibitory effect of 2HG on NF-KB signaling pathway in BV-2 cells.Taken together,these results,for the frst time,show that oncometabolite 2HG inhibits microglial activation through affecting AMPK/mTOR/NF KB signaling pathway and provide evidence that oncometabolite 2HG may regulate glioma development via modulating microglial activation in tumor microenvironment.Chao-jun Han Ji-yue Zheng Lin Sun Hui-cui Yang Zhong-qiang Cao Xiao-hu Zhang Long-tai Zheng Xue-chu Zhen 2019Acta Pharmacologica Sinica2019,40,10:11
19Pressure balance and imbalance in the optic nerve chamber: The Beijing Intracranial and Intraocular Pressure (iCOP) Study显示文摘To determine the interdependence of intracranial pressure(ICP) and intraocular pressure(IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure(LCP), optic nerve subarachnoid space pressure(ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP(via shunting cerebrospinal fluid(CSF) from the ventricle) were recorded. At baseline, all examined pressures were different(ICP>LCP>ONSP), but correlated(P<0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient(TLPG) remained stable(ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined(ICP-IOP independent zone). The optic nerve pressure gradient(ONPG) and trans-optic nerve pressure gradient(TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.Ruowu Hou Zheng Zhang Diya Yang Huaizhou Wang Weiwei Chen Zhen Li Jinghong Sang Sumeng Liu Yiwen Cao Xiaobin Xie Ruojing Ren Yazhuo Zhang Bernhard A. Sabel Ningli Wang 2016Science China(Life Sciences)2016,59,5:11
20Texture analysis on gadoxetic acid enhanced-MRI for predicting Ki-67 status in hepatocellular carcinoma: A prospective study显示文摘Objective: To investigate the value of whole-lesion texture analysis on preoperative gadoxetic acid enhanced magnetic resonance imaging(MRI) for predicting tumor Ki-67 status after curative resection in patients with hepatocellular carcinoma(HCC).Methods: This study consisted of 89 consecutive patients with surgically confirmed HCC. Texture features were extracted from multiparametric MRI based on whole-lesion regions of interest. The Ki-67 status was immunohistochemical determined and classified into low Ki-67(labeling index ≤15%) and high Ki-67(labeling index >15%) groups. Least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression were applied for generating the texture signature, clinical nomogram and combined nomogram. The discrimination power, calibration and clinical usefulness of the three models were evaluated accordingly. Recurrence-free survival(RFS) rates after curative hepatectomy were also compared between groups.Results: A total of 13 texture features were selected to construct a texture signature for predicting Ki-67 status in HCC patients(C-index: 0.878, 95% confidence interval: 0.791-0.937). After incorporating texture signature to the clinical nomogram which included significant clinical variates(AFP, BCLC-stage, capsule integrity, tumor margin,enhancing capsule), the combined nomogram showed higher discrimination ability(C-index: 0.936 vs. 0.795,P<0.001), good calibration(P>0.05 in Hosmer-Lemeshow test) and higher clinical usefulness by decision curve analysis. RFS rate was significantly lower in the high Ki-67 group compared with the low Ki-67 group after curative surgery(63.27% vs. 85.00%, P<0.05).Conclusions: Texture analysis on gadoxetic acid enhanced MRI can serve as a noninvasive approach to preoperatively predict Ki-67 status of HCC after curative resection. The combination of texture signature and clinical factors demonstrated the potential to further improve the prediction performance.Zheng Ye Hanyu Jiang Jie Chen Xijiao Liu Yi Wei Chunchao Xia Ting Duan Likun Cao Zhen Zhang Bin Song 2019Chinese Journal of Cancer Research2019,31,5:11
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