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( Jia Yi Yu ),( Xiao Fei Zhou ),( Mi Kyoung Chang ),( Mako Nakaya ),( Jae Hoon Chang ),( Yi Chuan Xiao ),( J. William Lindsey ),( Stephanie Dorta Estremera ),( Wei Cao ),( Anna Zal ),( Tomasz Zal ),( 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-
Development of an immune or autoimmune response involves T-cell activation in lymphoid organs and subsequent migration to peripheral tissues. Here we show that T-cell-specific ablation of the kinase TBK1 promotes T-cell activation but causes retention of effector T cells in the draininglumph node in a neuroinflammatory autoimmunity model,experimental autoimmune encephalomyelitis (EAE).Atolder ager,the T-cell-conditional TBK1-knockout mice also spontaneously accumulate T cells with activated phenotype.TBK1 contrlos the activation of AKT and its downsream kinase m TIORC1 by a mechanism involving TBK1-stimulated AKT ubiquitination and degradation. The deregulated AKT-mTORC1 signalling in turn contributes to enhanced T-cell activation and impaired effector T-cell egress from draining lymph nodes. Treatment of mice with a small-molecule inhibitor fo TBK1 inhibits EAE induction. These results suggest a role for TBK1 in regulating T-cell migration and establish TBK1 as a regulator of the AKT-mTORC1 signalling axis.
Jia-Jia Lin,Young-Hyun Han,Jung-Woo Kwon,Yong-Nan Xu,Yi-Bo Luo,Yu-Jin Jo,Chang-Eun Park,Jung-Kyu Baang,Suk Namgoong,Nam-Hyung Kim 한국동물생명공학회(구 한국동물번식학회) 2014 Reproductive & Developmental Biology(Supplement) Vol.38 No.2s
In meiosis, Emi2 plays important role as CSF (Cytostatic Factor) to make the oocyte arrested in mII stage by the inhibition of APC/C (anaphase promoting complex/cyclosome). Once the oocyte fertilized, Emi2 was destabilized and degraded. For the degradation of Emi2, calcium signaling activate calmodulin-dependent protein kinase (CaMK) and phosphorylate emi2. Phosphorylated emi2 is recognized by polo-box domain of polo-like kinase 1 (Plk1) and further degradated by ubiquitin-dependent proteolysis. But recognition of Plk1 and emi2 is unknown. In this works, we determined the high-resolution crystal structure of polo-box domain of Plk1 and phosphorylated emi2 peptide at 1.90Å. Determined structure revealed that several unique features, including binding of Phe169 in the tyrosin-rich hydrophobic pocket. This is the first report of crystallization that Plk1-emi2 complex. Based on the complex structure, we designed the peptide analogs which pontentially inhibits recognition of Emi2 by Plk1 and assessed its biological activity in oocyte maturation and pathernogenetic activation. Injection of AB103-8, the inhibitor of Plk1 Polo-box domain, in mouse oocytes, induced the maturation arrest in GV stage and the delay in mII parthenogenetic activation. Further investigations of the mechanism that Plk1 involved into the Emi2 mII arrest are underway.
Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1
Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.
Antimycobacterial Activity of Fusaric Acid from a Mangrove Endophyte and its Metal Complexes
Jia-Hui Pan,Yi Chen,Yu-Hong Huang,Yi-Wen Tao,Jun Wang,Yan Li,Yi Peng,Tao Dong,Xiao-Min Lai,Yong-Cheng Lin 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.7
Due to the increasing prevalence of multidrug-resistant Mycobacterium tuberculosis, there is an urgent need for new antituberculosis drugs that have novel mechanisms of action. As part of our ongoing search for antimycobacterial metabolites from mangrove endophytes, chemical analysis of the active extract of a strain of Fusarium sp. was performed, which led to the isolation of fusaric acid as the predominant constituent. A variety of metal complexes of fusaric acid were prepared. Antimycobacterial assays showed that Cadmium (II) and Copper (II) complexes exhibited potent inhibitory activity against the M. bovis BCG strain [minimum inhibitory concentration (MIC) = 4 μg/mL] and the M. tuberculosis H37Rv strain (MIC = 10 μg/mL), respectively. This is the first report of the antimycobacterial activity of the mangrove Fusarium metabolite and its coordinating metal complexes.
Yu-Jia Lin,Hsiao-Ting Chang,Ming-Hwai Lin,Ru-Yih Chen,Ping-Jen Chen,Wen-Yuan Lin,Jyh-Gang Hsieh,Ying-Wei Wang,Chung-Chieh Hu,Yi-Sheng Liou,Tai-Yuan Chiu,Chun-Yi Tu,Yi-Jen Wang,Bo-Ren Cheng,Tzeng-Ji Ch 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.2
Background: Medical staff may have difficulties in using conventional medicine to manage symptoms among terminally ill patients, including adverse effects of the treatment. Traditional Chinese medicine (TCM) is regarded as a complementary or alternative medicine, and has been increasingly used in the field of palliative medicine in recent years. This study aimed to investigate the experiences of and attitudes toward using TCM among palliative care professionals, and to provide preliminary information about its use in palliative care. Methods: This was a cross-sectional survey study conducted in eight inpatient hospice wards in Taiwan between December 2014 and February 2016. The questionnaire was self-administered, and was analyzed with descriptive statistics including Pearson’s Chi-square test and Fisher’s exact test. Results: A total of 251 palliative care professionals responded to the questionnaire, of whom 89.7% and 88.9% believed that the use of TCM could improve the physical symptoms and quality of life in terminally ill patients, respectively. Overall, 59.8%, of respondents suggested that TCM had rare side effects, and 58.2% were worried that TCM could affect the liver and kidney function of patients. In total, 89.7% and 88.0% of professionals agreed there were no suitable clinical practice guidelines and educational programs, respectively, for TCM use in palliative care. Conclusions: Most of the respondents agreed there was insufficient knowledge, skills-training, and continuing education on the use of TCM in terminally ill patients in Taiwan. These results show that to address patient safety considerations, guidelines about use of TCM in palliative care should be established.
Wang, Jia-Yi,Zhou, Yu-Qiao,Li, Xiao-Xu,Jin, Xin,Wang, Li-Li,Lei, Lei,Zhou, Yu,Lu, Jiang,Zeng, Xin,Dan, Hong-Xia,Liao, Ga,Chen, Qian-Ming Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12
Interleukin-4 receptor (IL-4R) gene single nucleotide polymorphisms (SNPs) are implicated in cancer development. However, results from the published reports have remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in IL-4R gene and cancer risk. Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched for case-control studies published up to October 30, 2012 that investigated IL-4R polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of any associations. Three IL-4R polymorphisms (Q576R, rs1801275; I75V, rs1805010; S503P, rs1805015) in 21 case-control studies were analyzed. Our meta-analysis indicated that these three polymorphisms are not associated with cancer risk when all studies were pooled together. In the subgroup analysis by tumor site, the results showed that Q576R G allele carriers were associated with a significantly decreased cervical cancer risk (recessive model: OR = 0.77, 95%CI = 0.60-0.98; homozygote comparison: OR = 0.76, 95%CI = 0.58-0.98). I75V G allele carriers were associated with a decreased risk of renal cancer (dominant model = 0.71, 95%CI = 0.57-0.89, heterozygote comparison: OR = 0.69, 95%CI = 0.55-0.87). When stratified by ethnicity, Q576R G allele carriers were associated with a decreased cancer risk in Caucasians (dominant model: OR = 0.90, 95%CI = 0.83-0.98; heterozygote comparison: OR = 0.89, 95%CI = 0.82-0.98). I75V G allele carriers were associated with a decreased cancer risk in Asians (heterozygote comparison: OR = 0.76, 95%CI = 0.62-0.94). S503P C allele carriers were also associated with a decreased cancer risk in Asians (CC VS TT: OR = 0.29, 95%CI = 0.08-0.99). Our results suggest that Q576R, I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specific ethnic groups. Future case-control studies with large sample size are needed to evaluate these associations in detail.
Yu, Changsong,Jia, Gang,Jiang, Yi,Deng, Qiuhong,Chen, Zhengli,Xu, Zhiwen,Chen, Xiaolin,Wang, Kangning Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.5
The glucagon-like peptide 2 (GLP-2) that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ) proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets' intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK) signaling pathway in piglets' intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco's modified Eagle's medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1), occludin and claudin-1 were increased (p<0.05). U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05). In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs' jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.