Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis

Wei-Chung Hsieh,Pei-Chen Hsu,Ya-Fan Liao,Shu-Ting Young,Zeng-Wei Wang,Chih-Li Lin,Gregory J. Tsay,Huei Lee,Hui-Chih Hung,Guang-Yaw Liu 한국분자세포생물학회 2010 Molecules and cells Vol.30 No.4

Ornithine decarboxylase (ODC), the key enzyme of poly-amine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC pre-vents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/en-doplasmic reticulum (ER) Ca2+ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpres-sion of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homolo-gous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC pre-served the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-medi-ated apoptotic pathway, induced by TG. Finally, overex-pression of ODC maintains the protein and mRNA expres-sion of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.

Transient Hiatal Separation During Straight Leg Raise Can Predict Reflux Burden in Gastroesophageal Reflux Disease Patients With Ineffective Esophageal Motility

Wei-Yi Lei,Shu-Wei Liang,Taher Omari,Wei-Chuan Chang,Ming-Wun Wong,Jui-Sheng Hung,Chih-Hsun Yi,Tso-Tsai Liu,Lin Lin,C Prakash Gyawali,Chien-Lin Chen 대한소화기 기능성질환∙운동학회 2022 Journal of Neurogastroenterology and Motility (JNM Vol.28 No.4

Background/Aims Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients. Methods Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR. Results Of 85 (56.3% female, mean age: 46.7 ± 12.3 years) completed SLR, esophagogastric junction morphology was normal in 31 (36.5%), transient hiatal separation in 19 (22.3%), and consistently hiatal hernia in 35 (41.2%). The values of total acid exposure time (P = 0.016), longest acid reflux episodes (P = 0.024), and DeMeester scores (P = 0.016) were higher in hiatal hernia compared to patients with non-transient hiatal separation, but there were no differences between those with and without transient hiatal separation. Within ineffective esophageal motility, the presence of transient hiatal separation during SLR significantly associated with a higher total acid exposure time (P = 0.014), higher DeMeester scores (P = 0.019), higher total acid reflux events (P = 0.037), and higher longest acid reflux episodes (P = 0.006). Conclusion Our work suggests that SLR may have value as a provocative test during HRM, and future outcome studies are warranted to elucidate the clinical relevance of motor abnormalities depicted from SLR.

Haloperidol and Other Antipsychotics Exposure before Endometrial Cancer Diagnosis: A Population-based Case-control Study

Wei-Ling Chen,Srinivasan Nithiyanantham,Yan-Chiao Mao,Chih-Hsin Muo,Chih-Pin Chuu,Shih-Ping Liu,Min-Wei Huang,Kuan-Pin Su 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.3

Objective: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and the associated relationship between endometrial cancer formation and various antipsychotics need to be confirmed. Methods: We conducted a case-control study by using data from Taiwan National Health Insurance Research Database to compare individual antipsychotic exposure between females with and without endometrial cancer. Among 14,079,089 females in the 12-year population-based national dataset, 9,502 females with endometrial cancer were identified. Their medical records of exposure to antipsychotics, including quetiapine, haloperidol, risperidone, olanzapine, amisulpride, clozapine, and aripiprazole, for up to 3 years before endometrial cancer diagnosis were reviewed. Daily dosage and cumulative exposure days were analyzed in the risky antipsychotic users. Additionally, the subsequent 5-year mortality rate of endometrial cancer among users of the risky antipsychotic were also analyzed. Results: Among endometrial cancer patients, the proportion of those who have used haloperidol before being diagnosed with endometrial cancer is significantly higher than other antipsychotic users. The significant odds ratio (OR) and a 95% confidence interval of 1.75 (1.31−2.34) were noted. Furthermore, haloperidol users were associated with a significantly higher 5-year mortality rate after getting endometrial cancer than non-users. Conclusion: There is a high correlation between the use of haloperidol and endometrial cancer formation. However, the underlying pathological biomechanisms require additional investigations.

2022 Taiwan clinical multicenter expert consensus and recommendations for thyroid radiofrequency ablation

Wei-Che Lin,Wen-Chieh Chen,Pei-Wen Wang,Yi-Chia Chan,Yen-Hsiang Chang,Harn-Shen Chen,Szu-Tah Chen,Wei-Chih Chen,Kai-Lun Cheng,Shun-Yu Chi,Pi-Ling Chiang,Chen-Kai Chou,Feng-Fu Chou,Shun-Chen Huang,Feng 대한초음파의학회 2023 ULTRASONOGRAPHY Vol.42 No.3

Radiofrequency ablation (RFA) is a minimally invasive management strategy that has been widely applied for benign and recurrent malignant thyroid lesions as an alternative to surgery in Taiwan. Members of academic societies for specialists in interventional radiology, endocrinology, and endocrine surgery collaborated to develop the first consensus regarding thyroid RFA in Taiwan. The modified Delphi method was used to reach a consensus. Based on a comprehensive review of recent and valuable literature and expert opinions, the recommendations included indications, pre-procedural evaluations, procedural techniques, post-procedural monitoring, efficacy, and safety, providing a comprehensive review of the application of RFA. The consensus effectively consolidates advice regarding thyroid RFA in clinical practice for local experts.

Smart monitoring system with multi-criteria decision using a feature based computer vision technique

Chih-Wei Lin,Wen-Ko Hsu,Dung-Jiang Chiou,Cheng-Wu Chen,Wei-Ling Chiang 국제구조공학회 2015 Smart Structures and Systems, An International Jou Vol.15 No.6

When natural disasters occur, including earthquakes, tsunamis, and debris flows, they are often accompanied by various types of damages such as the collapse of buildings, broken bridges and roads, and the destruction of natural scenery. Natural disaster detection and warning is an important issue which could help to reduce the incidence of serious damage to life and property as well as provide information for search and rescue afterwards. In this study, we propose a novel computer vision technique for debris flow detection which is feature-based that can be used to construct a debris flow event warning system. The landscape is composed of various elements, including trees, rocks, and buildings which are characterized by their features, shapes, positions, and colors. Unlike the traditional methods, our analysis relies on changes in the natural scenery which influence changes to the features. The “background module” and “monitoring module” procedures are designed and used to detect debris flows and construct an event warning system. The multi-criteria decision-making method used to construct an event warring system includes gradient information and the percentage of variation of the features. To prove the feasibility of the proposed method for detecting debris flows, some real cases of debris flows are analyzed. The natural environment is simulated and an event warning system is constructed to warn of debris flows. Debris flows are successfully detected using these two procedures, by analyzing the variation in the detected features and the matched feature. The feasibility of the event warning system is proven using the simulation method. Therefore, the feature based method is found to be useful for detecting debris flows and the event warning system is triggered when debris flows occur.

Effects of Codeine on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility: Studies Using High-resolution Manometry

Wei-Yi Lei,Tso-Tsai Liu,Wei-Chuan Chang,Chih-Hsun Yi,Jui-Sheng Hung,Ming-Wun Wong,Shu-Wei Liang,Lin Lin,Chien-Lin Chen 대한소화기 기능성질환∙운동학회 2024 Journal of Neurogastroenterology and Motility (JNM Vol.30 No.1

Background/AimsThis study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). MethodsEighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. ResultsCodeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, P = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P = 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P = 0.028) but did not change the 4-second integrated relaxation pressure (P = 0.794). Codeine significantly decreased the frequency of weak (P = 0.039) and failed contractions (P = 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. ConclusionsIn IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

( Chen-hua Liu ),( Chi-yi Chen ),( Wei-wen Su ),( Chun-jen Liu ),( Ching-chu Lo ),( Ke-jhang Huang ),( Jyh-jou Chen ),( Kuo-chih Tseng ),( Chi-yang Chang ),( Cheng-yuan Peng ),( Yu-lueng Shih ),( Chia 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.4

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR₁₂) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. The safety profiles were reported. Results: The SVR₁₂ rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR₁₂ were attributed to virologic failures. The SVR₁₂ rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR₁₂, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 ㎡/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 ㎡/month; P<0.001). Conclusions: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis. (Clin Mol Hepatol 2021;27:575-588)

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.

Taiwanese Female Vegetarians Have Lower Lipoprotein-Associated Phospholipase A2 Compared with Omnivores

Chih-Wei Chen,Chin-Lon Lin,Chih-Ta Lin,Ying-Lung Lin,Tin-Kwang Lin 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.1

Purpose: Many studies supported that vegetarians have a lower risk of cardiac diseases and mortality, partly due to better blood pressure and serum cholesterol profiles. However, the inflammatory markers, especially lipoprotein-associated phospholipase A2 (Lp-PLA2), have not been well-studied. This study aimed to compare inflammatory markers and conventional risk factors between vegetarians and omnivores. Materials and Methods: One hundred and seventy-three vegetarians and 190 omnivores were studied. Fasting blood samples were obtained to compare levels of glucose, total cholesterol, triacylglycerol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, homocysteine, Lp-PLA2 activity, and high-sensitivity C-reactive protein (hs-CRP). Results: Vegetarians had higher serum levels of the following markers: hs-CRP (1.8 ± 3.4 vs. 1.2 1.8 mg/L, respectively; p = 0.05), homocysteine (9.39 ± 3.22 vs. 7.62 ± 2.41 μmol/L, respectively; p < 0.01), and triacylglycerol (96.91 ± 59.56 vs. 84.66 ± 43.24 mg/dL, respectively; p < 0.05). Vegetarians also had lower levels of Lp-PLA2 (18.32 ± 7.19 10-3 μmol/min/mL vs. 20.22 8.13 10-3 μmol/min/mL; p < 0.05), total cholesterol (180.62 ± 36.55 mg/dL vs. 192.73 ± 36.57 mg/dL; p < 0.01), LDL cholesterol (118.15 ± 32.8 vs. 126.41 ± 34.28 mg/dL; p < 0.05), and HDL cholesterol (55.59 ± 13.30 vs. 62.09 ± 14.52 mg/dL, p < 0.01). Multivariate analyses demonstrated that a vegetarian diet increases the chances for high serum hs-CRP and low Lp-PLA2 activity. Conclusion: In addition to lower total cholesterol,LDL-cholesterol, and HDL-cholesterol, Taiwanese female vegetarians have lower serum Lp-PLA2 activity but higher levels of hs-CRP, homocysteine, and triacylglyerol. It might be due to geographic differences of vegetarian diets, and further studies are needed.

Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis

Hsieh, Wei-Chung,Hsu, Pei-Chen,Liao, Ya-Fan,Young, Shu-Ting,Wang, Zeng-Wei,Lin, Chih-Li,Tsay, Gregory J.,Lee, Huei,Hung, Hui-Chih,Liu, Guang-Yaw Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.4

Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC prevents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) $Ca^{2+}$ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpression of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homologous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC preserved the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-mediated apoptotic pathway, induced by TG. Finally, overexpression of ODC maintains the protein and mRNA expression of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.