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      • KCI등재

        Phosphorylation of DYNLT1 at Serine 82 Regulates Microtubule Stability and Mitochondrial Permeabilization in Hypoxia

        Xue Xu,Yue-sheng Huang,Qiong Zhang,Jiong-yu Hu,Dong-xia Zhang2,Xu-pin Jiang,jie-zhi Jia,Jing-ci Zhu 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.4

        Hypoxia-induced microtubule disruption and mitochondrial permeability transition (mPT) are crucial events leading to fatal cell damage and recent studies showed that microtubules (MTs) are involved in the modulation of mitochondrial function. Dynein light chain Tctex-type 1 (DYNLT1) is thought to be associated with MTs and mitochondria. Previously we demonstrated that DYNLT1 knockdown aggravates hypoxia-induced mitochondrial permeabilization, which indicates a role of DYNLT1 in hypoxic cytoprotection. But the underlying regulatory mechanism of DYNLT1 remains illusive. Here we aimed to investigate the phosphorylation alteration of DYNLT1 at serine 82 (S82) in hypoxia (1% O2). We therefore constructed recombinant adenoviruses to generate S82E and S82A mutants, used to transfect H9c2 and HeLa cell lines. Development of hypoxia-induced mPT (MMP examining, Cyt c release and mPT pore opening assay), hypoxic energy metabolism (cellular viability and ATP quantification), and stability of MTs were examined. Our results showed that phosph-S82 (S82-P) expression was increased in early hypoxia; S82E mutation (phosphomimic) aggravated mitochondrial damage, ele-vated the free tubulin in cytoplasm and decreased the cellular viability; S82A mutation (dephosphomimic) seemed to diminish the hypoxia-induced injury. These data suggest that DYNLT1 phosphorylation at S82 is involved in MTs and mitochondria regulation, and their interaction and cooperation contribute to the cellular hypoxic tolerance. Thus, we provide new insights into a DYNLT1 mechanism in stabilizing MTs and mitochondria, and propose a potential therapeutic target for hypoxia cytoprotective studies.

      • SCIESCOPUSKCI등재

        The treatment effect of novel hGHRH homodimer to male infertility hamster

        Zhang, Xu-Dong,Guo, Xiao-Yuan,Tang, Jing-Xuan,Yue, Lin-Na,Zhang, Juan-Hui,Liu, Tao,Dong, Yu-Xia,Tang, Song-Shan The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.6

        Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.

      • Clinical Efficacy and Prognosis Factors for Advanced Hepatoblastoma in Children: A 6-year Retrospective Study

        Zhang, Yi,Zhang, Wei-Ling,Huang, Dong-Sheng,Hong, Liang,Wang, Yi-Zhuo,Zhu, Xia,Hu, Hui-Min,Zhang, Pin-Wei,Yi, You,Han, Tao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

        Objective: This study aimed to investigate the effect of multimodality treatment of advanced paediatric hepatoblastoma (HB) and the factors affecting prognosis. Methods: A total of 35 children underwent multimodality treatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stem cell transplantation. The patients were followed up every month. Results: Serum AFP levels in 33 out of 35 patients in this study were significantly increased (P = 0.0002). According to the statistical scatter plot, the values of serum AFP on the 25th, 50th, and 75th percentages were 1,210, 1,210 and 28,318 ng/dl, respectively. Of the 35 cases, 21 were stage IV. 18 cases were treated with systemic chemotherapy before surgery, and 3 cases with locally interventional chemotherapy before surgery. Statistical analysis showed that the preferred interventional treatment affected prognosis, and that there was a statistically significant difference (P = 0.024). Some 33 patients completed the follow-up, of which 17 were in complete remission (CR), 5 were in partial remission (PR), 1 became disease progressive (DP), and 10 died. The remission and overall survival rates were 66.7% (22/33) and 69.7% (23/33), respectively. Patients with the mixed HB phenotypes had worse prognoses than the epithelial phenotype (P < 0.001), and patients in stage IV had a lower survival rate than those in stage III (P < 0.001). Conclusion: Multimodality treatment can effectively improve remission rate and prolong the survival of children with advanced HB. In addition, alpha-fetoprotein (AFP), a tumor marker of liver malignant tumors, HB pathological classification, and staging are highly useful in predicting prognosis.

      • Quantitative Proteomic Analysis Reveals Up-Regulation of Type I Collagen During Tumorigenesis of Colorectal Cancer

        Xia Zou,Bo Feng,Taotao Dong,Binbin Tan,Hao Shen,Xiu Zhang,Menghui Zhang,Minhua Zheng,Yan Zhang 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1

        Colorectal cancer (CRC) is one of the most prevalent cancers in the world with high mortality and morbidity rates. In this study, we have performed comparative proteomic profiling of sera from CRC patients at stage I (n=17), stage II (n=40), stage III (n=24) and healthy subjects (n=25) to gain a global view of protein expression change during CRC tumorigenesis and provide potential targets for CRC diagnosis and treatment. As a result, a total of 93 proteins were found differentially expressed in CRC patients with a label-free quantitative APXE method. After GO and KEGG pathway analysis, those proteins most frequently involved in ECM-receptor interaction, complement and coagulation cascades. As important as components of ECM, we found several collagens in CRC serum had been changed from tumor stage I to IV. And the validation of collagen I (COL1) at RNA and protein expression level shown extremely comparable to pooled serum proteomic results using independent 26 paired tumor and matched normal colorectal tissues. Those findings indicated that the change of collagen I observed in serum were indeed from pathogenic lesion of colorectal tissue. Moreover, we further investigated serum levels of COL1, PICP (the synthesis indicator) and CTx (the breakdown indicator) in 77 CRC patients and 33 normal controls by ELISA. The results showed PICP and CTx were better for discriminating normal from cancer groups as well as non-metastatic from metastatic tumor than COL1. Finally, we evaluated the expression of MMPs in paired tumor and normal tissues from patients with different stages. Notably, the expression of MMP1, 7 and 14 were remarkably enhanced in carcinoma tissues and the trend were parallel with the progression of tumor stage. The expression of E-cadherin and CDX2, which had been considered as targets of COL1 in cell models, were also verified in tissues and displayed decrease in tumor. Overall, COL1 might be affected by MMP1, 7, 14 and had effects on cell adhesion and differentiation through E-cadherin and CDX2.

      • KCI등재

        C-type natriuretic peptide attenuates renal osteodystrophy through inhibition of FGF-23/MAPK signaling

        Dong Dong Zhang,Yang Fang Wu,Wei Xia Chen,Yao Xu,Si Yan Liu,Huang Huang Luo,Guang Mei Jiang,Yue Wu,Peng Hu 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

        Renal osteodystrophy (ROD) occurs as early as chronic kidney disease (CKD) stage 2 and seems ubiquitous in almost all pediatric patients with CKD stage 5. Fibroblast growth factor (FGF)-23, a bone-derived endocrine regulator of phosphate homeostasis, is overexpressed in CKD and disturbs osteoblast differentiation and matrix mineralization. In contrast, C-type natriuretic peptide (CNP) acts as a potent positive regulator of bone growth. In the present study, we infused CNP into uremic rats and observed whether CNP could attenuate ROD through the inhibition of FGF-23 cascades. In uremic rats, CNP administration significantly alleviated renal dysfunction, calcium phosphate metabolic disorders, hypovitaminosis D, secondary hyperparathyroidism, the decrease in bone turnover markers and retarded bone pathological progression. More importantly, within FGF-23/mitogen-activated protein kinase (MAPK) signaling, the fibroblast growth factor receptor-1, Klotho and alternative (STAT-1/phospho-STAT-1) elements were upregulated by CNP, whereas FGF-23, RAF-1/phospho-RAF-1, and downstream (ERK/phospho-ERK and P38/phospho-P38) elements were paradoxically underexpressed in bone tissue. Therefore, CNP exerts a therapeutic effect on ROD through inhibition of FGF-23/MAPK signaling at the RAF-1 level.

      • SCIESCOPUSKCI등재
      • KCI등재

        The treatment effect of novel hGHRH homodimer to male infertility hamster

        Xu-Dong Zhang,Xiao-Yuan Guo,Jing-Xuan Tang,Lin-Na Yue,Juan-Hui Zhang,Tao Liu,Yu-Xia Dong,Song-Shan Tang 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.6

        Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.

      • Antitumor Activity of Histone Deacetylase Inhibitor Trichostatin A in Osteosarcoma Cells

        Cheng, Dong-Dong,Yang, Qing-Cheng,Zhang, Zhi-Chang,Yang, Cui-Xia,Liu, Yi-Wen Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

        Background: Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation of tumor cells. The present study aimed to examine the effects of trichostatin A (TSA), one such inhibitor, on the cell cycle, apoptosis and invasiveness of osteosarcoma cells. Methods: MG-63 cells were treated with TSA at various concentrations. Then, cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively; cell cycling was assessed by flow cytometry; invasion assays were performed with the transwell Boyden Chamber system. Results: MTT assays revealed that TSA significantly inhibited the growth of MG-63 cells in a concentration and time dependent manner. TSA treated cells demonstrated morphological changes indicative of apoptosis and TUNEL assays revealed increased apoptosis of MG-63 cells after TSA treatment. Flow cytometry showed that TSA arrested the cell cycle in G1/G2 phase and annexin V positive apoptotic cells increased markedly. In addition, the invasiveness of MG-63 cells was inhibited by TSA in a concentration dependent manner. Conclusion: Our findings demonstrate that TSA inhibits the proliferation, induces apoptosis and inhibits invasiveness of osteosarcoma cells in vitro. HDAC inhibitors may thus have promise to become new therapeutic agents against osteosarcoma.

      • Fall Detection Algorithm for the Elderly Based on Human Characteristic Matrix and SVM

        WANG Rui-dong,ZHANG Yong-liang,DONG Ling-ping,LU Jia-wei,ZHANG Zhi-qin,HE Xia 제어로봇시스템학회 2015 제어로봇시스템학회 국제학술대회 논문집 Vol.2015 No.10

        Fall is one of the leading causes of injury and death for the elderly. Real-time fall detection is of great significance for the safety of the elderly. This paper proposes a coarse to fine fall detection algorithm based on Human characteristic matrix and Support Vector Machine (SVM). First, background subtraction and morphological processing are used to obtain more accurately human silhouette. Then, two human characteristic matrices are constructed based on Hu-moment invariant and the information of human body posture extracted from human silhouette and are used as features to train SVM classifier for fall detection. Experimental results indicate that the proposed algorithm can distinguish fall event from other movements such as squat, sitting down and back turning. Compared with other common methods, the proposed method can real-time and efficiently track the video with 18 frames per second.

      • Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

        Deng, Xiao-Dong,Gao, Qin,Zhang, Bo,Zhang, Li-Xia,Zhang, Wei,Er, Zhe-Er Mu,Xie, Ying,Ma, Ying,Liu, Yun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

        Background: Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. Method: To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. Results: When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk under different genetic models (heterozygote: OR=0.766, 95%CI=0.613-0.957, $P_{OR}$=0.019; homozygote: OR=0.51, 95%CI=0.303-0.858, $P_{OR}$=0.011; dominant: OR=0.733, 95%CI=0.593-0.905, $P_{OR}$=0.004; recessive: OR=0.565, 95%CI=0.337-0.947, $P_{OR}$=0.030). Subgroup analysis indicated that C2C2 genotype was significantly associated with decreased bladder cancer risk under the homozygote genetic model in Caucasians. There was no evidence of heterogeneity or publication bias. Conclusions: The current meta-analysis suggested that the CYP2E1 RsaI/PstI polymorphism might be associated with bladder cancer susceptibility, especially in Caucasians. Further studies are needed to validate the above conclusion.

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