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Lin Chih-Hsin,Hsieh Yu-Shao,Sun Ying-Chieh,Huang Wun-Han,Chen Shu-Ling,Weng Zheng-Kui,Lin Te-Hsien,Wu Yih-Ru,Chang Kuo-Hsuan,Huang Hei-Jen,Lee Guan-Chiun,Hsieh-Li Hsiu Mei,Lee-Chen Guey-Jen 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.1
Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.
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.
Jeng, Jen-Eing,Tsai, Meng-Feng,Tsai, Hey-Ru,Chuang, Lea-Yea,Lin, Zu-Yau,Hsieh, Min-Yuh,Chen, Shinn-Chern,Chuang, Wan-Lung,Wang, Liang-Yen,Yu, Ming-Lung,Dai, Chia-Yen,Tsai, Jung-Fa Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2
The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.
Jeng, Jen-Eing,Wu, Hui-Fang,Tsai, Meng-Feng,Tsai, Huey-Ru,Chuang, Lea-Yea,Lin, Zu-Yau,Hsieh, Min-Yuh,Chen, Shinn-Chern,Chuang, Wan-Lung,Wang, Liang-Yen,Yu, Ming-Lung,Dai, Chia-Yen,Tsai, Jung-Fa Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23
To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.
Evaluating Green Supply Chain Management with Incomplete Information
Tseng, Ming-Lang,Lin, Ru-Jen,Chiu, Anthony Shun Fung Korean Institute of Industrial Engineers 2012 Industrial Engineeering & Management Systems Vol.11 No.2
There has been a growing interest in firms' environmental sustainability activities to improve environmental practices in their supply chain. This study aims to deal with supplier evaluation of firm's green supply chain management (GSCM) criteria with incomplete information. Nevertheless, the suitable supplier is a key strategic direction in eliminating environmental impact on supply chain management for manufacturing firms. The firm's GSCM criteria and supplier selection need to be unified as a system to improve the firm's performance.
IL-33/ST2 axis mediates hyperplasia of intrarenal urothelium in obstructive renal injury
Wei-Yu Chen,Jenq-Lin Yan,Yi-Hsiu Wu,Lung-Chih Li,Ru-Fang Li,Ya-Ting Chang,Lo-Hsin Dai,Wan-Chen Wang,Ya-Jen Chang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
The monolayered intrarenal urothelium covers the renal papilla and ureteropelvic junction (UPJ). In response to increased renal pressure during obstruction or ischemic injuries, intrarenal urothelial cells begin to proliferate and form a multilayered urothelium. Little is known regarding the mechanism and pathophysiological role of urothelium hyperplasia during renal obstruction. In this study, we investigated the expression of interleukin (IL)-33, an IL-1 family cytokine, in kidneys with unilateral ureteral obstruction (UUO)-induced obstructive injury. IL-33 levels in hydronephrotic urine and serum were upregulated 2 days after UUO. The number of ST2-expressing immune cells was increased in the UUO kidney. We found that IL-33 was upregulated in vimentin-positive cells in the cortical and medullar layers and the UPJ stroma. Moreover, IL-33 expression was predominantly induced in multilayered keratin 5- positive urothelial cells in the UPJ. IL-33 was not detected in terminally differentiated superficial umbrella cells expressing uroplakin 3a. In vivo, we confirmed that deficiency of IL33 or its receptor ST2 attenuated UUO-induced hyperplasia of the UPJ urothelium. Deficiency of IL33 attenuated the expression of UUO-induced type 2 inflammatory cytokines and upregulated uroplakins and urothelial differentiation signaling in UPJ tissues. Our results collectively suggest that the IL-33/ST2 axis mediates the activation of innate immune responses and contributes to urothelial hyperplasia by regulating urothelial differentiation in obstructive kidney injury.
Evaluating Green Supply Chain Management with Incomplete Information
Ming-Lang Tseng,Ru-Jen Lin,Anthony Shun Fung Chiu 대한산업공학회 2012 Industrial Engineeering & Management Systems Vol.11 No.2
There has been a growing interest in firms’ environmental sustainability activities to improve environmental practices in their supply chain. This study aims to deal with supplier evaluation of firm’s green supply chain management (GSCM) criteria with incomplete information. Nevertheless, the suitable supplier is a key strategic direction in eliminating environmental impact on supply chain management for manufacturing firms. The firm’s GSCM criteria and supplier selection need to be unified as a system to improve the firm’s performance.
Intense X-ray induced formation of silver nanoparticles stabilized by biocompatible polymers
Wang, Chang-Hai,Liu, Chi-Jen,Wang, Cheng-Liang,Chien, Chia-Chi,Hwu, Y.,Liu, Ru-Shi,Yang, Chung-Shi,Je, Jung-Ho,Lin, Hong-Ming,Margaritondo, G. Springer-Verlag 2009 Applied physics. A, Materials science & processing Vol.97 No.2
Development of an integrated Web-based system with a pile load test database and pre-analyzed data
Chen, Yit-Jin,Liao, Ming-Ru,Lin, Shiu-Shin,Huang, Jen-Kai,Marcos, Maria Cecilia M. Techno-Press 2014 Geomechanics & engineering Vol.7 No.1
A Web-based pile load test (WBPLT) system was developed and implemented in this study. Object-oriented and concept-based software design techniques were adopted to integrate the pile load test database into the system. A total of 673 case histories of pile load test were included in the database. The data consisted of drilled shaft and driven precast concrete pile axial load tests in drained, undrained, and gravel loading conditions as well as pre-analyzed data and back-calculated design parameters. Unified modeling language, a standard software design tool, was utilized to design the WBPLT system architecture with five major concept-based components. These components provide the static structure and dynamic behavior of system message flows in a visualized manner. The open-source Apache Web server is the building block of the WBPLT system, and PHP Web programming language implements the operation of the WBPLT components, particularly the automatic translation of user query into structured query language. A simple search and inexpensive query can be implemented through the Internet browser. The pile load test database is helpful, and data can be easily retrieved and utilized worldwide for research and advanced applications.