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      • KCI등재

        Loss of MicroRNA-137 Impairs the Homeostasis of Potassium in Neurons via KCC2

        Ting-Wei Mi,Xiao-Wen Sun,Zhi-Meng Wang,Ying-Ying Wang,Xuan-Cheng He,Cong Liu,Shuang-Feng Zhang,Hong-Zhen Du,Chang-Mei Liu,Zhao-Qian Teng 한국뇌신경과학회 2020 Experimental Neurobiology Vol.29 No.2

        Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.

      • KCI등재

        A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer

        Ting Liu,Qing Li,Zhen Lin,Chunhua Liu,Wei Pu,Shasha Zeng,Jun Lai,Xuebin Cai,Lisha Zhang,Shuyang Wang,Miao Chen,Wei Cao,Hongfeng Gou,Qing Zhu 대한암학회 2024 Cancer Research and Treatment Vol.56 No.2

        Purpose Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients.Materials and Methods Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m<sup>2</sup> nab-paclitaxel, 800 mg/m<sup>2</sup> gemcitabine, and 25 mg/m<sup>2</sup> cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy.Results After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients.Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

      • SCIESCOPUSKCI등재
      • Use of Lactobacillus Brevis LUC247 to Enrich Quinoa Sourdough with Γ-Aminobutyric Acid

        ( Ting Wei Liu ),( Chao Feng Yu ),( Syue Fong Lai ),( Ying Chen Lu ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

        γ-Aminobutyric acid is a neurotransmitter inhibitor with sedation, anti-depression, hypotensive and other physiological functions. This study aimed at investigating the effect of addition various amount of quinoa (Chenopodium quinoa) flours to sourdough in γ-aminobutyric acid production. Type I sourdough containing quinoa flours of different content (0%, 15%, 30%, 45%) were prepared in laboratory. Lactobacillus brevis LUC247 was used to ferment quinoa sourdough during different fermentation time (0, 2, 4, 6, 8, 12, 24, 36, 48 hours). Compared to control dough, without quinoa, the amount of GABA was representing about 3-fold increase, Cell count of Lactobacillus brevis LUC247 in quinoa sourdough fermented for 12 hours was the highest (1E+9 CFU/g). The higher the inoculated cell counts, the faster the pH decreased and total titratable acidity and organic acid (lactic acid and acetic acid) amounts increased in quinoa sourdough. The results indicated the potential of quinoa flour through sourdough fermentation by Lactobacillus brevis LUC247 to enrich γ-aminobutyric acid.

      • 5-Aza-2'-deoxycytidine Induces Hepatoma Cell Apoptosis via Enhancing Methionine Adenosyltransferase 1A Expression and Inducing S-Adenosylmethionine Production

        Liu, Wei-Jun,Ren, Jian-Guo,Li, Ting,Yu, Guo-Zheng,Zhang, Jin,Li, Chang-Sheng,Liu, Zhi-Su,Liu, Quan-Yan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

        In hepatocellular cancer (HCC), lack of response to chemotherapy and radiation treatment can be caused by a loss of epigenetic modifications of cancer cells. Methionine adenosyltransferase 1A is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation. Therefore, drugs releasing epigenetic repression have been proposed to reverse this process. We studied the effect of the demethylating reagent 5-aza-2'-deoxycitidine (5-Aza-CdR) on MAT1A gene expression, DNA methylation and S-adenosylmethionine (SAMe) production in the HCC cell line Huh7. We found that MAT1A mRNA and protein expression were activated in Huh7 cells with the treatment of 5-Aza-CdR; the status of promoter hypermethylation was reversed. At the same time, MAT2A mRNA and protein expression was significantly reduced in Huh7 cells treated with 5-Aza-CdR, while SAMe production was significantly induced. However, 5-Aza-CdR showed no effects on MAT2A methylation. Furthermore, 5-Aza-CdR inhibited the growth of Huh7 cells and induced apoptosis and through down-regulation of Bcl-2, up-regulation of Bax and caspase-3. Our observations suggest that 5-Aza-CdR exerts its anti-tumor effects in Huh7 cells through an epigenetic change involving increased expression of the methionine adenosyltransferase 1A gene and induction of S-adenosylmethionine production.

      • KCI등재

        Metabolic engineering of erythritol production from glycerol by Yarrowia lipolytica

        Ya-Ting Wang,Ling-Xuan Zhao,Liu-Jing Wei,Jun Chen,Zhijie Liu,Feng Liu,Qiang Hua 한국생물공학회 2024 Biotechnology and Bioprocess Engineering Vol.29 No.1

        Erythritol as a four-carbon polyol has been widely used in food, pharmaceutical and daily chemical industries with characteristics of low caloric value and high chemical stability. Here, a system metabolic engineering strategy was used to increase the yield of erythritol from glycerol in Yarrowia lipolytica by enhancing the substrate transformation and restricting the by-product synthesis. Specifi cally, we determined that over-expression of a newly identifi ed erythrose reductase YPR1 was able to improve the erythritol production as same as the well-known erythrose reductase ER27. Instead of its up-regulation, knockout of erythrose reductase ER10 was eff ective to improve erythritol synthesis. Moreover, both over-expression of YPR1 and deletion of ER10 signifi cantly accelerated the glycerol utilization in response to high osmotic stress. To further decrease the by-product accumulation, a restriction and recycling strategy was implemented by knockout of mannitol dehydrogenase MDH2 and enhancement of arabitol dehydrogenase ADH1 and fructokinase HXK1. The engineered strain YL13 produced a titer of 25 g/L erythritol and less than 0.5 g/L mannitol and arabitol. By over-expression of transketolase TKL1, the fi nal strain YL14 produced 28.5 g/L erythritol and none of mannitol and arabitol. This study provides a new idea for reducing the production of by-products and improving the glycerol conversion to erythritol.

      • SCIESCOPUSKCI등재
      • KCI등재

        Effect of qigong exercise and acupressure rehabilitation program on pulmonary function and respiratory symptoms in patients hospitalized with severe COVID-19: A randomized controlled trial

        Shu-ting Liu,Chao Zhan,Yun-jing Ma,Chao-yang Guo,Wei Chen,Xiao-ming Fang,Lei Fang 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.-

        Background There are several effective complementary and integrative therapies for patients with severe COVID-19. The trial aims to evaluate the efficacy and advantages of the qigong exercise and acupressure rehabilitation program (QARP) for treating patients with severe COVID-19. Methods A total of 128 patients with COVID-19 aged 20 to 80 years were recruited and randomly allocated in a 1:1 ratio to receive QARP plus standard therapies or standard therapies alone. QARP consisted of acupressure therapy and qigong exercise (Liu Zi Jue). The primary outcome was measured with the modified Medical Research Council (mMRC) dyspnea scale, and the secondary outcomes included the modified Borg dyspnea scale (MBS), fatigue Scale-14 (FS-14), patient health questionnaire-9 scale (PHQ-9), duration of respiratory symptoms, and vital signs. Results In total, 128 patients completed the clinical trial. The QARP group and standard therapies group showed significant improvements in vital signs (except blood pressure) and clinical scales compared with baseline (p<0.05). The QARP group also showed more significant improvement in the mMRC dyspnea scale (-1.8 [-2.1, -1.6], p=0.018) and modified Borg dyspnea scale (-3.7 [95% confidence intervals (CI) -4.3, -3.1], p=0.045). The duration of cough was 14.3 days (95% CI 12.6, 16.1, p=0.046), and the length of hospital stay was 18.5 days (95% CI 17.0, 20.0, p=0.042) in the QARP group, both of which were significantly reduced compared with the standard therapies group (p<0.05). Conclusion QARP plus standard therapies improved lung function and symptoms such as dyspnea and cough in patients with severe COVID-19 and shortened the length of hospital stay. Therefore, QARP may be considered an effective treatment option for patients with severe COVID-19. Trial registration Clinical Research Information Service Identifier: ChiCTR2000029994 Background There are several effective complementary and integrative therapies for patients with severe COVID-19. The trial aims to evaluate the efficacy and advantages of the qigong exercise and acupressure rehabilitation program (QARP) for treating patients with severe COVID-19. Methods A total of 128 patients with COVID-19 aged 20 to 80 years were recruited and randomly allocated in a 1:1 ratio to receive QARP plus standard therapies or standard therapies alone. QARP consisted of acupressure therapy and qigong exercise (Liu Zi Jue). The primary outcome was measured with the modified Medical Research Council (mMRC) dyspnea scale, and the secondary outcomes included the modified Borg dyspnea scale (MBS), fatigue Scale-14 (FS-14), patient health questionnaire-9 scale (PHQ-9), duration of respiratory symptoms, and vital signs. Results In total, 128 patients completed the clinical trial. The QARP group and standard therapies group showed significant improvements in vital signs (except blood pressure) and clinical scales compared with baseline (p<0.05). The QARP group also showed more significant improvement in the mMRC dyspnea scale (-1.8 [-2.1, -1.6], p=0.018) and modified Borg dyspnea scale (-3.7 [95% confidence intervals (CI) -4.3, -3.1], p=0.045). The duration of cough was 14.3 days (95% CI 12.6, 16.1, p=0.046), and the length of hospital stay was 18.5 days (95% CI 17.0, 20.0, p=0.042) in the QARP group, both of which were significantly reduced compared with the standard therapies group (p<0.05). Conclusion QARP plus standard therapies improved lung function and symptoms such as dyspnea and cough in patients with severe COVID-19 and shortened the length of hospital stay. Therefore, QARP may be considered an effective treatment option for patients with severe COVID-19. Trial registration Clinical Research Information Service Identifier: ChiCTR2000029994

      • RNAi-based Knockdown of Multidrug Resistance-associated Protein 1 is Sufficient to Reverse Multidrug Resistance of Human Lung Cells

        Shao, Shu-Li,Cui, Ting-Ting,Zhao, Wei,Zhang, Wei-Wei,Xie, Zhen-Li,Wang, Chang-He,Jia, Hong-Shuang,Liu, Qian Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

        Up-regulation of multidrug resistance-associated protein 1 (MRP1) is regarded as one of the main causes for multidrug resistance (MDR) of tumor cells, leading to failure of chemotherapy-based treatment for a multitude of cancers. However, whether silencing the overexpressed MRP1 is sufficient to reverse MDR has yet to be validated. This study demonstrated that RNAi-based knockdown of MRP1 reversed the increased efflux ability and MDR efficiently. Two different short haipin RNAs (shRNAs) targeting MRP1 were designed and inserted into pSilence-2.1-neo. The shRNA recombinant plasmids were transfected into cis-dichlorodiamineplatinum-resistant A549 lung (A549/DDP) cells, and then shRNA expressing cell clones were collected and maintained. Real time PCR and immunofluorescence staining for MRP1 revealed a high silent efficiency of these two shRNAs. Functionally, shRNA-expressing cells showed increased rhodamine 123 retention in A549/DDP cells, indicating reduced efflux ability of tumor cells in the absence of MRP1. Consistently, MRP1-silent cells exhibited decreased resistance to 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and DDP, suggesting reversal of MDR in these tumor cells. Specifically, MRP1 knockdown increased the DDP-induced apoptosis of A549/DDP cells by increased trapping of their cell cycling in the G2 stage. Taken together, this study demonstrated that RNAi-based silencing of MRP1 is sufficient to reverse MDR in tumor cells, shedding light on possible novel clinical treatment of cancers.

      • Prognostic Value of PLCE1 Expression in Upper Gastrointestinal Cancer: a Systematic Review and Meta-analysis

        Cui, Xiao-Bin,Peng, Hao,Li, Su,Li, Ting-Ting,Liu, Chun-Xia,Zhang, Shu-Mao,Jin, Ting-Ting,Hu, Jian-Ming,Jiang, Jin-Fang,Liang, Wei-Hua,Li, Na,Li, Li,Chen, Yun-Zhao,Li, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

        Background: A number of studies have identified a shared susceptibility locus in phospholipase C epsilon 1 (PLCE1) for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). However, the results of PLCE1 expression in esophageal and gastric cancer remain inconsistent and controversial. Moreover, the effects on clinicopathological features remain undetermined. This study aimed to provide a precise quantification of the association between PLCE1 expression and the risk of ESCC and GCA through meta-analysis. Materials and Methods: Eligible studies were identified from PubMed, Wanfang Data, ISI Web of Science, and the Chinese National Knowledge Infrastructure databases. Using RevMan5.2 software, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were employed to assess the association of PLCE1 expression with clinicopathological features relative to ESCC or GCA. Results: Seven articles were identified, including 761 esophageal and gastric cancer cases and 457 controls. Overall, we determined that PLCE1 expression was associated with tumor progression in both esophageal cancers (pooled OR=5.93; 95%CI=3.86 to 9.11) and gastric cancers (pooled OR=9.73; 95%CI=6.46 to 14.7). Moreover, invasion depth (pooled OR=3.62; 95%CI=2.30 to 5.70) and lymph node metastasis (pooled OR=4.21; 95%CI=2.69 to 6.59) were linked with PLCE1 expression in gastric cancer. However, no significant associations were determined between PLCE1 overexpression and the histologic grade, invasion depth, and lymph node metastasis in esophageal cancer. Conclusions: Our metaanalysis results indicated that upregulated PLCE1 is significantly associated with an increased risk of tumor progression in ESCC and GCA. Therefore, PLCE1 expression can be appropriately regarded as a promising biomarker for ESCC and GCA patients.

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