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        The pivotal role of the NLRC4 inflammasome in neuroinflammation after intracerebral hemorrhage in rats

        Gan Hui,Zhang Li,Chen Hui,Xiao Han,Wang Lu,Zhai Xuan,Jiang Ning,Liang Ping,Zheng Shuyue,Zhao Jing 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

        The NLRC4 inflammasome, a member of the nucleotide-binding and oligomerization domain-like receptor (NLR) family, amplifies inflammation by facilitating the processing of caspase-1, interleukin (IL)–1β, and IL-18. We explored whether NLRC4 knockdown alleviated inflammatory injury following intracerebral hemorrhage (ICH). Furthermore, we investigated whether NLRC4 inflammasome activation can be adjusted by the regulator of G protein signaling 2/leucine-rich repeat kinase-2 pathway. Fifty microliters of arterial blood was drawn and injected into the basal ganglion to simulate the ICH model. NLRC4 small interfering RNAs (siRNAs) were utilized to knockdown NLRC4. An LRRK2 inhibitor (GNE7915) was injected into the abdominal cavity. Short hairpin (sh) RNA lentiviruses and lentiviruses containing RGS2 were designed and applied to knockdown and promote RGS2 expression. Neurological functions, brain edema, Western blot, enzyme-linked immunosorbent, hematoxylin and eosin staining, Nissl staining, immunoprecipitation, immunofluorescence assay and Evans blue dye extravasation and autofluorescence assay were evaluated. It was shown that the NLRC4 inflammasome was activated following ICH injury. NLRC4 knockdown extenuated neuronal death, damage to the blood-brain barrier, brain edema and neurological deficiency 3 days after ICH. NLRC4 knockdown reduced myeloperoxidase (MPO) cells as well as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-18 following ICH. GNE7915 reduced pNLRC4 and NLRC4 inflammasome activation. RGS2 suppressed the interaction of LRRK2 and NLRC4 and NLRC4 inflammasome activation by regulating pLRRK2. Our study demonstrated that the NLRC4 inflammasome may aggravate the inflammatory injury induced by ICH and that RGS2/LRRK2 may relieve inflammatory injury by restraining NLRC4 inflammasome activation.

      • Aberrant Methylation of RASSF1A gene Contribute to the Risk of Renal Cell Carcinoma: a Meta-Analysis

        Yu, Gan-Shen,Lai, Cai-Yong,Xu, Yin,Bu, Chen-Feng,Su, Ze-Xuan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.11

        The aim of this study was to assess the diagnostic value of RASSF1A methylation in renal cell carcinoma. Systematically search were performed using the Pubmed, ProQest and Web of Science for all articles on the association between RASSF1A methylation and renal cell carcinoma before 15 April 2015. After the filtration, 13 studies involving 677 cases and 497 controls met our criteria. Our meta-analysis suggested that hypermethylation of RASSF1A gene was associated with the increased risk of RCC(OR:4.14, 95%CI:1.06-16.1). Stratified analyses showed a similar risk in qualitative detection method(OR:28.4, 95%CI:10.2-79.6), body fluid sample(OR:12.8, 95%CI:5.35-30.8), and American(OR:10.5, 95%CI:1.97-55.9). Our result identified that RASSF1A methylation had a strong potential in prediction the risk of Renal cell carcinoma.

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        Induction of Apoptosis in Human Hepatoma SMMC-7721 Cells using 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone, a Chalcone from Buds of Cleistocalyx operculatus

        Chun-Lin Ye,Xuan-Gan Liu,Qi Huang,Xian-Liang Zhao 한국식품과학회 2013 Food Science and Biotechnology Vol.22 No.5

        The molecular mechanism to induce apoptosis in human hepatoma SMMC-7721 cells was investigated using 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from the buds of Cleistocalyx operculatus. Typical morphological changes in apoptotic body formation after DMC treatment were observed using acridine orange (AO)/ethidium bromide (EB) staining. After 48 h of incubation with 0, 6.25, 12.5, and 25 μM of DMC, the percentages of annexin V-FITC-positive/PI negative cells were 1.51, 9.33, 33.84, and 61.32%, respectively. Apoptosis induced by DMC was blocked by z-VAD-fmk, a caspase inhibitor. Analysis of fluorescence intensities of rhodamine 123 in cells showed that DMC induced a loss of mitochondrial membrane potential (ΔΨm). Western blot results showed that DMC decreased the Bcl-2/Bax ratio,suggesting that the Bcl-2 family is involved in control of apoptosis. All of these signal transduction pathways are involved in initiating apoptosis. DMC is a potential anticancer agent that deserves further exploration.

      • Prevalence and Age, Gender and Geographical Area Distribution of Esophageal Squamous Cell Carcinomas in North China from 1985 to 2006

        Feng, Xiao-Shan,Yang, Yan-Tong,Gao, She-Gan,Ru, Yi,Wang, Gong-Ping,Zhou, Bo,Wang, Yu-Feng,Zhang, Peng-Fei,Li, Pu-Yu,Liu, Yong-Xuan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

        Objective: To establish the prevalence and distribution profile of esophageal squamous cell carcinomas (ESCCs) over a 22-yr period in North China. Methods: Using endoscopy for primary diagnosis and histological analysis for the further confirmation, a total of 74,854 ESCC patients aged 20-89 between January 1985 and December 2006 were investigated to analyze the epidemiological profile including prevalence rates, distribution of age-of-onset, gender and geographical area of ESCC in Luoyang, the highest incidence area of North China. Results: A total of 4092 cases of ESCC were finally diagnosed among 74,854 patients who had their first endoscopies. The prevalence among males was higher than that among females (p<0.01), resulting in an overall male:female OR of 1.2 (95%CI, 1.2-1.3). The prevalence in rural areas was higher than in urban areas (p<0.01), resulting in an overall rural:urban OR of 2.6 (95%CI, 2.4-2.9). The rural:urban ORs and the 95% CI increased continuously from 2.6, 2.3-3.0 to 2.7, 2.2-3.3, respectively, for 4 consecutive periods during the 22-yr study period. Moreover, the median age of onset among females was higher than that among males (p<0.01). For both sexes and in both areas, the prevalence rates declined and the median age of onset rose for 4 consecutive periods in the 22-yrs time frame (p<0.01). Conculsions: These data reveal the epidemiological profile of ESCC in the area of North China, and suggest that urban areas and rural people account for a growing proportion of the ESCC patients although the prevalence of ESCC significantly declined and the median age-of-onset postponed over the 22-yrs period. Moreover, the prevalence status of ESCC in rural areas also underlines the need for public health initiatives aimed at reducing risk factors of this fatal disease.

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