20 results on '"Che, Yi"'
Search Results
2. A non-genetic engineering platform for rapidly generating and expanding cancer-specific armed T cells
- Author
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Chen, Yi-Jou, Chen, Michael, Cheng, Tian-Lu, Tsai, Yi-Shan, Wang, Chang-Hung, Chen, Che-Yi, Wu, Tung-Yun, Tzou, Shey-Cherng, Wang, Kai-Hung, Cheng, Jing-Jy, Kao, An-Pei, Lin, Shyr-Yi, and Chuang, Kuo-Hsiang
- Published
- 2023
- Full Text
- View/download PDF
3. SGLT-2 inhibitors may increase ultrafiltration in incident peritoneal dialysis patients: a case report
- Author
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Lai, Jia-Wen, Lin, Hsuan-Jen, and Chou, Che-Yi
- Published
- 2023
- Full Text
- View/download PDF
4. Repeated centrifuging and washing concentrates bacterial samples in peritoneal dialysis for optimal culture: an original article
- Author
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Tien, Ni, You, Bang-Jau, Lin, Hsuan-Jen, Chang, Chieh-Ying, Chou, Che-Yi, Lin, Hsiu-Shen, Chang, Chiz-Tzung, Wang, Charles C. N., and Chen, Hung-Chih
- Published
- 2020
- Full Text
- View/download PDF
5. Urinary tract infection is associated with hypokalemia: a case control study
- Author
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Shen, Ai-Ling, Lin, Hsiu-Li, Lin, Hsiu-Chen, Tseng, Yuan-Fu, Hsu, Chien-Yeh, and Chou, Che-Yi
- Published
- 2020
- Full Text
- View/download PDF
6. Text mining in a literature review of urothelial cancer using topic model
- Author
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Lin, Hsuan-Jen, Sheu, Phillip C.-Y., Tsai, Jeffrey J. P., Wang, Charles C. N., and Chou, Che-Yi
- Published
- 2020
- Full Text
- View/download PDF
7. Early prediction of acquiring acute kidney injury for older inpatients using most effective laboratory test results
- Author
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Chen, Yi-Shian, Chou, Che-Yi, and Chen, Arbee L.P.
- Published
- 2020
- Full Text
- View/download PDF
8. Abdominal aortic calcification score can predict future coronary artery disease in hemodialysis patients: a 5-year prospective cohort study
- Author
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Chen, Hung-Chih, Wang, Wei-Ting, Hsi, Chieh-Ning, Chou, Che-Yi, Lin, Hsuan-Jen, Huang, Chiu-Ching, and Chang, Chiz-Tzung
- Published
- 2018
- Full Text
- View/download PDF
9. Early prediction of acquiring acute kidney injury for older inpatients using most effective laboratory test results
- Author
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Che-Yi Chou, Arbee L. P. Chen, and Yi-Shian Chen
- Subjects
medicine.medical_specialty ,030232 urology & nephrology ,Renal function ,Health Informatics ,Health records ,lcsh:Computer applications to medicine. Medical informatics ,Early prediction ,03 medical and health sciences ,0302 clinical medicine ,Older patients ,medicine ,Electronic Health Records ,Humans ,030212 general & internal medicine ,K nearest neighbors ,Aged ,Inpatients ,Data collection ,Critically ill ,business.industry ,Clinical Laboratory Techniques ,Health Policy ,Acute kidney injury ,Laboratory tests ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Computer Science Applications ,Hospitalization ,Laboratory test ,Early Diagnosis ,Emergency medicine ,lcsh:R858-859.7 ,business ,Research Article ,Forecasting - Abstract
Background Acute Kidney Injury (AKI) is common among inpatients. Severe AKI increases all-cause mortality especially in critically ill patients. Older patients are more at risk of AKI because of the declined renal function, increased comorbidities, aggressive medical treatments, and nephrotoxic drugs. Early prediction of AKI for older inpatients is therefore crucial. Methods We use 80 different laboratory tests from the electronic health records and two types of representations for each laboratory test, that is, we consider 160 (laboratory test, type) pairs one by one to do the prediction. By proposing new similarity measures and employing the classification technique of the K nearest neighbors, we are able to identify the most effective (laboratory test, type) pairs for the prediction. Furthermore, in order to know how early and accurately can AKI be predicted to make our method clinically useful, we evaluate the prediction performance of up to 5 days prior to the AKI event. Results We compare our method with two existing works and it shows our method outperforms the others. In addition, we implemented an existing method using our dataset, which also shows our method has a better performance. The most effective (laboratory test, type) pairs found for different prediction times are slightly different. However, Blood Urea Nitrogen (BUN) is found the most effective (laboratory test, type) pair for most prediction times. Conclusion Our study is first to consider the last value and the trend of the sequence for each laboratory test. In addition, we define the exclusion criteria to identify the inpatients who develop AKI during hospitalization and we set the length of the data collection window to ensure the laboratory data we collect is close to the AKI time. Furthermore, we individually select the most effective (laboratory test, type) pairs to do the prediction for different days of early prediction. In the future, we will extend this approach and develop a system for early prediction of major diseases to help better disease management for inpatients.
- Published
- 2020
10. Severe hypertriglyceridemia secondary to venlafaxine use in an older adult on dialysis -case report.
- Author
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Hsiang-Wen Lin, Cory A. Simonavice, Chiung-Ray Lu, Wen-Ling Lin, Po-Lun Wu, Che-Yi Chou, Chun-Hui Liao, Hsieh-Yuan Lane, Lin, Hsiang-Wen, Simonavice, Cory A, Lu, Chiung-Ray, Lin, Wen-Ling, Wu, Po-Lun, Chou, Che-Yi, Liao, Chun-Hui, and Lane, Hsieh-Yuan
- Subjects
HYPERTRIGLYCERIDEMIA ,VENLAFAXINE ,NEUROTRANSMITTER uptake inhibitors ,HEMODIALYSIS ,OLDER people ,TREATMENT of chronic kidney failure ,CHRONIC kidney failure ,CHRONIC kidney failure complications ,ANTIDEPRESSANTS ,DRUG interactions ,HYPERLIPIDEMIA ,PSYCHOLOGY - Abstract
Background: Although the prescribing information for Venlafaxine extended release includes a discussion about possible increases in total cholesterol and triglycerides (TG) seen in healthier adult patients during premarketing clinical trials, no post-marketing studies or case reports, that discuss the effects of venlafaxine on TG in elderly patients with chronic kidney disease.Case Presentation: We report a 71 year-old male patient with end-stage renal disease on hemodialysis, with a history of coronary artery disease, mild hyperlipidemia, and hypertension. This patient twice demonstrated the severe rises in triglycerides while taking the antidepressant, i.e., venlafaxine, and discontinuing the long-term use of fenofirate. The adverse drug reaction sub-committee at the hospital rated the second event as a "probable reaction" using the Naranjo nomogram, accordingly.Conclusions: This case demonstrates the risk of changes in lipid profiles while taking venlafaxine and receiving on and off fenofibrate therapy in the older adult patient with chronic kidney disease and under hemodialysis. Regular monitoring for lipid changes after starting venlafaxine is strongly advised for patients with existing risk factors. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
11. Transformation of 5-D itch scale and numerical rating scale in chronic hemodialysis patients.
- Author
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Jia-Wen Lai, Hung-Chih Chen, Che-Yi Chou, Hung-Rong Yen, Tsai-Chung Li, Mao-Feng Sun, Hen-Hong Chang, Chiu-Ching Huang, Fuu-Jen Tsai, Tschen, Johannes, Chiz-Tzung Chang, Lai, Jia-Wen, Chen, Hung-Chih, Chou, Che-Yi, Yen, Hung-Rong, Li, Tsai-Chung, Sun, Mao-Feng, Chang, Hen-Hong, Huang, Chiu-Ching, and Tsai, Fuu-Jen
- Subjects
HEMODIALYSIS ,ITCHING ,MULTIDIMENSIONAL scaling ,QUALITY of life ,BIOINFORMATICS - Abstract
Background: Pruritus is a common and frustrating symptom in hemodialysis (HD) patients and 5-D itch scale is proposed as a reliable measurement of pruritus. However, information regarding 5-D itch scale categories is currently unavailable. We explored optimal cut-offs 5-D itching scale based on numerical rating scale (NRS) categories in HD patients.Methods: Four hundred and nine HD patients in China Medical University Hospital in December 2014 were included and severity of pruritus was estimated using NRS and 5-D itch scale. The association of NRS and 5-D itch scale was analyzed by linear regression. The optimal cut-offs for 5-D itch scale based on NRS categories were generated.Results: The average NRS was 3.4 ± 3.0 and the average 5-D itch scale was 10.9 ± 4.8. The 5-D score was strongly correlated with the NRS: r = 0.831 (p < 0.001). NRS = -2.31 + 0.52 × (5-D scale). The averages of 5-D scales were 6.4 ± 1.5, 9.6 ± 2.2, 13.1 ± 3.2, 15.7 ± 4.4, 19.5 ± 4.4 for no, mild, moderate, severe, and very severe pruritus based on categorized NRS. A 5-D itch scale categories were proposed, ≤ 8 for NRS = 0, 9-11 for mild pruritus, 12-17 for moderate pruritus, 18-21 for severe pruritus and ≥ 22 for very severe pruritus.Conclusions: Categories for the 5-D itch scale were proposed based on the measurements of pruritus severity in HD patients. This information provides a simple solution that enables transformation between the 5-D itch scale and the numerical rating scale. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
12. Klf8 regulates left-right asymmetric patterning through modulation of Kupffer's vesicle morphogenesis and spaw expression.
- Author
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Che-Yi Lin, Ming-Yuan Tsai, Yu-Hsiu Liu, Yu-Fen Lu, Yi-Chung Chen, Yun-Ren Lai, Hsin-Chi Liao, Huang-Wei Lien, Chung-Hsiang Yang, Chang-Jen Huang, and Hwang, Sheng-Ping L.
- Subjects
- *
HUMAN genetics , *MORPHOGENESIS , *VERTEBRATES , *MESODERM , *EMBRYOS - Abstract
Background: Although vertebrates are bilaterally symmetric organisms, their internal organs are distributed asymmetrically along a left-right axis. Disruption of left-right axis asymmetric patterning often occurs in human genetic disorders. In zebrafish embryos, Kupffer's vesicle, like the mouse node, breaks symmetry by inducing asymmetric expression of the Nodal-related gene, spaw, in the left lateral plate mesoderm (LPM). Spaw then stimulates transcription of itself and downstream genes, including lft1, lft2, and pitx2, specifically in the left side of the diencephalon, heart and LPM. This developmental step is essential to establish subsequent asymmetric organ positioning. In this study, we evaluated the role of krüppel-like factor 8 (klf8) in regulating left-right asymmetric patterning in zebrafish embryos. Methods: Zebrafish klf8 expression was disrupted by both morpholino antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. Whole-mount in situ hybridization was conducted to evaluate gene expression patterns of Nodal signalling components and the positions of heart and visceral organs. Dorsal forerunner cell number was evaluated in Tg(sox17:gfp) embryos and the length and number of cilia in Kupffer's vesicle were analyzed by immunocytochemistry using an acetylated tubulin antibody. Results: Heart jogging, looping and visceral organ positioning were all defective in zebrafish klf8 morphants. At the 18-22 s stages, klf8 morphants showed reduced expression of genes encoding Nodal signalling components (spaw, lft1, lft2, and pitx2) in the left LPM, diencephalon, and heart. Co-injection of klf8 mRNA with klf8 morpholino partially rescued spaw expression. Furthermore, klf8 but not klf8Δzf overexpressing embryos showed dysregulated bilateral expression of Nodal signalling components at late somite stages. At the 10s stage, klf8 morphants exhibited reductions in length and number of cilia in Kupffer's vesicle, while at 75% epiboly, fewer dorsal forerunner cells were observed. Interestingly, klf8 mutant embryos, generated by a CRISPR-Cas9 system, showed bilateral spaw expression in the LPM at late somite stages. This observation may be partly attributed to compensatory upregulation of klf12b, because klf12b knockdown reduced the percentage of klf8 mutants exhibiting bilateral spaw expression. Conclusions: Our results demonstrate that zebrafish Klf8 regulates left-right asymmetric patterning by modulating both Kupffer's vesicle morphogenesis and spaw expression in the left LPM. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
13. Fractionation and identification of 9 c, 11 t, 13 t-conjugated linolenic acid as an activator of PPARα in bitter gourd ( Momordica charantia L.).
- Author
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Chuang, Chia-Ying, Hsu, Chin, Chao, Che-Yi, Wein, Yung-Shung, Kuo, Yueh-Hsiung, and Huang, Ching-jang
- Subjects
MOMORDICA charantia ,PEROXISOMES ,TRADITIONAL medicine ,TREATMENT of diabetes ,STEROID receptors ,LIGANDS (Biochemistry) ,TRANSCRIPTION factors ,HOMEOSTASIS ,CHROMATOGRAPHIC analysis - Abstract
Bitter gourd ( Momordica charantia L.) is a common vegetable in Asia that has been used in traditional medicine for the treatment of Diabetes. PPARs are ligand-dependent transcription factors that belong to the steroid hormone nuclear receptor family and control lipid and glucose homeostasis in the body. We previously reported that the ethyl acetate (EA) extract of bitter gourd activated peroxisome proliferator receptors (PPARs) α and γ. To identify the active compound that activated PPARα, wild bitter gourd EA extract was partitioned between n-hexane and 90% methanol/10% H
2 O, and the n-hexane soluble fraction was further separated by silica gel column chromatography and finally by preparative HPLC. A transactivation assay employing a clone of CHOK1 cells stably transfected with a (UAS)4 -tk-alkaline phosphatase reporter and a chimeric receptor of GAL4-rPPARα LBD was used to track the active component. Based on Mass, NMR, and IR spectroscopy, 9 cis, 11 trans, 13 trans-conjugated linolenic acid (9 c, 11 t, 13 t-CLN) was identified as a PPARα activator in wild bitter gourd. The isolated 9 c, 11 t, 13 t-CLN rich fraction also significantly induced acyl CoA oxidase (ACO) activity in a peroxisome proliferator-responsive murine hepatoma cell line, H4IIEC3, implying that 9 c, 11 t, 13 t-CLN was able to act on a natural PPARα signaling pathway as well. The content of 9 c, 11 t, 13 t-CLN was estimated to be about 7.1 g/kg of our dried wild bitter gourd sample. The concentration of 9 c, 11 t, 13 t-CLN and activation activity in the hydrolyzed EA extract of the seeds was higher than that of the flesh. The potential health benefits of 9 c, 11 t, 13 t-CLN through the PPARα regulated mechanism are worthy to be further characterized in in vivo studies. [ABSTRACT FROM AUTHOR]- Published
- 2006
- Full Text
- View/download PDF
14. Bitter Gourd (Momordica charantia) Extract Activates Peroxisome Proliferator-Activated Receptors and Upregulates the Expression of the Acyl CoA Oxidase Gene in H4IIEC3 Hepatoma Cells.
- Author
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Che-Yi Chao and Ching-jang Huang
- Subjects
- *
PEROXISOMES , *MICROBODIES , *TRANSCRIPTION factors , *GENE transfection , *GOURDS , *HYPOLIPEMIA - Abstract
Peroxisome proliferator-activated receptor α (PPARα) is a ligand-dependent transcription factor that regulates the expression of genes involved in lipid metabolism and transport. Ligands/activators of PPARα, like fibrate-type drugs, may have hypolipidemic effects. To identify food that contains activators of PPARα, a transactivation assay employing a clone of CHO-K1 cells stably transfected with a (UAS)[sub4]-tk-alkaline phosphatase reporter and a chimeric receptor of Gal4-rPPARα LBD was used to screen ethyl acetate (EA) extracts of a large variety of food materials. It was found that the EA extract of bitter gourd (Momordica charantia), a common oriental vegetable, activated PPARα to an extent that was equivalent to or even higher than 10 µM Wy-14643, a known ligand of PPARα. This extract also activated PPARγ to a significant extent which was comparable to 0.5 µM BRL-49653. The activity toward PPARα was mainly in the soluble fraction of the organic solvent. The EA extract prepared from the whole fruit showed significantly higher activity than that from seeds or flesh alone. The bitter gourd EA extract was then incorporated into the medium for treatment of a peroxisome proliferator-responsive murine hepatoma cell line, H4IIEC3, for 72 h. Treated cells showed significantly higher activity of acyl CoA oxidase and higher expressions of mRNA of this enzyme and fatty acid-binding protein, indicating that the bitter gourd EA extract was able to act on a natural PPARα signaling pathway in this cell line. It is thus worth further investigating the PPAR-associated health benefits of bitter gourd. Copyright ? 2003 National Science Council, ROC and S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
15. Klf8 regulates left-right asymmetric patterning through modulation of Kupffer's vesicle morphogenesis and spaw expression.
- Author
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Lin CY, Tsai MY, Liu YH, Lu YF, Chen YC, Lai YR, Liao HC, Lien HW, Yang CH, Huang CJ, and Hwang SL
- Subjects
- Animals, Morphogenesis genetics, Transforming Growth Factor beta2 metabolism, Body Patterning genetics, Gene Expression Regulation, Developmental genetics, Kruppel-Like Transcription Factors genetics, Kruppel-Like Transcription Factors metabolism, Transforming Growth Factor beta2 genetics, Zebrafish embryology, Zebrafish genetics, Zebrafish Proteins genetics, Zebrafish Proteins metabolism
- Abstract
Background: Although vertebrates are bilaterally symmetric organisms, their internal organs are distributed asymmetrically along a left-right axis. Disruption of left-right axis asymmetric patterning often occurs in human genetic disorders. In zebrafish embryos, Kupffer's vesicle, like the mouse node, breaks symmetry by inducing asymmetric expression of the Nodal-related gene, spaw, in the left lateral plate mesoderm (LPM). Spaw then stimulates transcription of itself and downstream genes, including lft1, lft2, and pitx2, specifically in the left side of the diencephalon, heart and LPM. This developmental step is essential to establish subsequent asymmetric organ positioning. In this study, we evaluated the role of krüppel-like factor 8 (klf8) in regulating left-right asymmetric patterning in zebrafish embryos., Methods: Zebrafish klf8 expression was disrupted by both morpholino antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. Whole-mount in situ hybridization was conducted to evaluate gene expression patterns of Nodal signalling components and the positions of heart and visceral organs. Dorsal forerunner cell number was evaluated in Tg(sox17:gfp) embryos and the length and number of cilia in Kupffer's vesicle were analyzed by immunocytochemistry using an acetylated tubulin antibody., Results: Heart jogging, looping and visceral organ positioning were all defective in zebrafish klf8 morphants. At the 18-22 s stages, klf8 morphants showed reduced expression of genes encoding Nodal signalling components (spaw, lft1, lft2, and pitx2) in the left LPM, diencephalon, and heart. Co-injection of klf8 mRNA with klf8 morpholino partially rescued spaw expression. Furthermore, klf8 but not klf8△zf overexpressing embryos showed dysregulated bilateral expression of Nodal signalling components at late somite stages. At the 10s stage, klf8 morphants exhibited reductions in length and number of cilia in Kupffer's vesicle, while at 75% epiboly, fewer dorsal forerunner cells were observed. Interestingly, klf8 mutant embryos, generated by a CRISPR-Cas9 system, showed bilateral spaw expression in the LPM at late somite stages. This observation may be partly attributed to compensatory upregulation of klf12b, because klf12b knockdown reduced the percentage of klf8 mutants exhibiting bilateral spaw expression., Conclusions: Our results demonstrate that zebrafish Klf8 regulates left-right asymmetric patterning by modulating both Kupffer's vesicle morphogenesis and spaw expression in the left LPM.
- Published
- 2017
- Full Text
- View/download PDF
16. Severe hypertriglyceridemia secondary to venlafaxine use in an older adult on dialysis -case report.
- Author
-
Lin HW, Simonavice CA, Lu CR, Lin WL, Wu PL, Chou CY, Liao CH, and Lane HY
- Subjects
- Aged, Antidepressive Agents therapeutic use, Drug Interactions, Humans, Kidney Failure, Chronic complications, Kidney Failure, Chronic psychology, Male, Renal Dialysis, Risk Factors, Venlafaxine Hydrochloride therapeutic use, Antidepressive Agents adverse effects, Hypertriglyceridemia chemically induced, Kidney Failure, Chronic therapy, Venlafaxine Hydrochloride adverse effects
- Abstract
Background: Although the prescribing information for Venlafaxine extended release includes a discussion about possible increases in total cholesterol and triglycerides (TG) seen in healthier adult patients during premarketing clinical trials, no post-marketing studies or case reports, that discuss the effects of venlafaxine on TG in elderly patients with chronic kidney disease., Case Presentation: We report a 71 year-old male patient with end-stage renal disease on hemodialysis, with a history of coronary artery disease, mild hyperlipidemia, and hypertension. This patient twice demonstrated the severe rises in triglycerides while taking the antidepressant, i.e., venlafaxine, and discontinuing the long-term use of fenofirate. The adverse drug reaction sub-committee at the hospital rated the second event as a "probable reaction" using the Naranjo nomogram, accordingly., Conclusions: This case demonstrates the risk of changes in lipid profiles while taking venlafaxine and receiving on and off fenofibrate therapy in the older adult patient with chronic kidney disease and under hemodialysis. Regular monitoring for lipid changes after starting venlafaxine is strongly advised for patients with existing risk factors.
- Published
- 2017
- Full Text
- View/download PDF
17. Transformation of 5-D itch scale and numerical rating scale in chronic hemodialysis patients.
- Author
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Lai JW, Chen HC, Chou CY, Yen HR, Li TC, Sun MF, Chang HH, Huang CC, Tsai FJ, Tschen J, and Chang CT
- Subjects
- Aged, Female, Humans, Kidney Failure, Chronic complications, Male, Middle Aged, Pruritus complications, Severity of Illness Index, Surveys and Questionnaires, Kidney Failure, Chronic therapy, Pruritus diagnosis, Renal Dialysis
- Abstract
Background: Pruritus is a common and frustrating symptom in hemodialysis (HD) patients and 5-D itch scale is proposed as a reliable measurement of pruritus. However, information regarding 5-D itch scale categories is currently unavailable. We explored optimal cut-offs 5-D itching scale based on numerical rating scale (NRS) categories in HD patients., Methods: Four hundred and nine HD patients in China Medical University Hospital in December 2014 were included and severity of pruritus was estimated using NRS and 5-D itch scale. The association of NRS and 5-D itch scale was analyzed by linear regression. The optimal cut-offs for 5-D itch scale based on NRS categories were generated., Results: The average NRS was 3.4 ± 3.0 and the average 5-D itch scale was 10.9 ± 4.8. The 5-D score was strongly correlated with the NRS: r = 0.831 (p < 0.001). NRS = -2.31 + 0.52 × (5-D scale). The averages of 5-D scales were 6.4 ± 1.5, 9.6 ± 2.2, 13.1 ± 3.2, 15.7 ± 4.4, 19.5 ± 4.4 for no, mild, moderate, severe, and very severe pruritus based on categorized NRS. A 5-D itch scale categories were proposed, ≤ 8 for NRS = 0, 9-11 for mild pruritus, 12-17 for moderate pruritus, 18-21 for severe pruritus and ≥ 22 for very severe pruritus., Conclusions: Categories for the 5-D itch scale were proposed based on the measurements of pruritus severity in HD patients. This information provides a simple solution that enables transformation between the 5-D itch scale and the numerical rating scale.
- Published
- 2017
- Full Text
- View/download PDF
18. β-Lapachone induces heart morphogenetic and functional defects by promoting the death of erythrocytes and the endocardium in zebrafish embryos.
- Author
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Wu YT, Lin CY, Tsai MY, Chen YH, Lu YF, Huang CJ, Cheng CM, and Hwang SP
- Subjects
- Animals, Dicumarol pharmacology, Dimethyl Sulfoxide pharmacology, Embryonic Development, Endocardium physiopathology, Erythrocyte Count, Erythrocytes cytology, Gene Expression Regulation, Developmental, Heart drug effects, Heart embryology, Heart Defects, Congenital physiopathology, Microscopy, Fluorescence, Morphogenesis genetics, NAD(P)H Dehydrogenase (Quinone) antagonists & inhibitors, NAD(P)H Dehydrogenase (Quinone) genetics, NAD(P)H Dehydrogenase (Quinone) metabolism, Reactive Oxygen Species metabolism, Time-Lapse Imaging, Zebrafish embryology, Zebrafish growth & development, Apoptosis drug effects, Endocardium abnormalities, Erythrocytes drug effects, Heart Defects, Congenital chemically induced, Morphogenesis drug effects, Naphthoquinones pharmacology
- Abstract
Background: β-Lapachone has antitumor and wound healing-promoting activities. To address the potential influences of various chemicals on heart development of zebrafish embryos, we previously treated zebrafish embryos with chemicals from a Sigma LOPAC1280™ library and found several chemicals including β-lapachone that affected heart morphogenesis. In this study, we further evaluated the effects of β-lapachone on zebrafish embryonic heart development., Methods: Embryos were treated with β-lapachone or dimethyl sulfoxide (DMSO) at 24 or 48 hours post fertilization (hpf) for 4 h at 28°C. Heart looping and valve development was analyzed by whole-mount in situ hybridization and histological analysis. For fractional shortening and wall shear stress analyses, AB and Tg (gata1:DsRed) embryos were recorded for their heart pumping and blood cell circulations via time-lapse fluorescence microscopy. Dextran rhodamine dye injection into the tail reticular cells was used to analyze circulation. Reactive oxygen species (ROS) was analyzed by incubating embryos in 5-(and 6-)-chloromethyl-2',7'-dichloro-dihydrofluorescein diacetate (CM-H2DCFDA) and recorded using fluorescence microscopy. o-Dianisidine (ODA) staining and whole mount in situ hybridization were used to analyze erythrocytes. TUNEL assay was used to examine DNA fragmentation., Results: We observed a linear arrangement of the ventricle and atrium, bradycardia arrhythmia, reduced fractional shortening, circulation with a few or no erythrocytes, and pericardial edema in β-lapachone-treated 52-hpf embryos. Abnormal expression patterns of cmlc2, nppa, BMP4, versican, and nfatc1, and histological analyses showed defects in heart-looping and valve development of β-lapachone-treated embryos. ROS production was observed in erythrocytes and DNA fragmentation was detected in both erythrocytes and endocardium of β-lapachone-treated embryos. Reduction in wall shear stress was uncovered in β-lapachone-treated embryos. Co-treatment with the NQO1 inhibitor, dicoumarol, or the calcium chelator, BAPTA-AM, rescued the erythrocyte-deficiency in circulation and heart-looping defect phenotypes in β-lapachone-treated embryos. These results suggest that the induction of apoptosis of endocardium and erythrocytes by β-lapachone is mediated through an NQO1- and calcium-dependent pathway., Conclusions: The novel finding of this study is that β-lapachone affects heart morphogenesis and function through the induction of apoptosis of endocardium and erythrocytes. In addition, this study further demonstrates the importance of endocardium and hemodynamic forces on heart morphogenesis and contractile performance.
- Published
- 2011
- Full Text
- View/download PDF
19. Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARalpha in bitter gourd (Momordica charantia L.).
- Author
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Chuang CY, Hsu C, Chao CY, Wein YS, Kuo YH, and Huang CJ
- Subjects
- Animals, CHO Cells, Cricetinae, Cricetulus, Spectrophotometry, Ultraviolet, alpha-Linolenic Acid chemistry, Momordica charantia chemistry, PPAR alpha agonists, alpha-Linolenic Acid pharmacology
- Abstract
Bitter gourd (Momordica charantia L.) is a common vegetable in Asia that has been used in traditional medicine for the treatment of Diabetes. PPARs are ligand-dependent transcription factors that belong to the steroid hormone nuclear receptor family and control lipid and glucose homeostasis in the body. We previously reported that the ethyl acetate (EA) extract of bitter gourd activated peroxisome proliferator receptors (PPARs) alpha and gamma. To identify the active compound that activated PPARalpha, wild bitter gourd EA extract was partitioned between n-hexane and 90% methanol/10% H(2)O, and the n-hexane soluble fraction was further separated by silica gel column chromatography and finally by preparative HPLC. A transactivation assay employing a clone of CHOK1 cells stably transfected with a (UAS)(4)-tk-alkaline phosphatase reporter and a chimeric receptor of GAL4-rPPARalpha LBD was used to track the active component. Based on Mass, NMR, and IR spectroscopy, 9cis, 11trans, 13trans-conjugated linolenic acid (9c, 11t, 13t-CLN) was identified as a PPARalpha activator in wild bitter gourd. The isolated 9c, 11t, 13t-CLN rich fraction also significantly induced acyl CoA oxidase (ACO) activity in a peroxisome proliferator-responsive murine hepatoma cell line, H4IIEC3, implying that 9c, 11t, 13t-CLN was able to act on a natural PPARalpha signaling pathway as well. The content of 9c, 11t, 13t-CLN was estimated to be about 7.1 g/kg of our dried wild bitter gourd sample. The concentration of 9c, 11t, 13t-CLN and activation activity in the hydrolyzed EA extract of the seeds was higher than that of the flesh. The potential health benefits of 9c, 11t, 13t-CLN through the PPARalpha regulated mechanism are worthy to be further characterized in in vivo studies.
- Published
- 2006
- Full Text
- View/download PDF
20. Bitter gourd (Momordica charantia) extract activates peroxisome proliferator-activated receptors and upregulates the expression of the acyl CoA oxidase gene in H4IIEC3 hepatoma cells.
- Author
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Chao CY and Huang CJ
- Subjects
- Analysis of Variance, Animals, Blotting, Northern, Cell Line, Tumor, Genes, Reporter genetics, Mice, Plant Extracts pharmacology, Receptors, Cytoplasmic and Nuclear isolation & purification, Transcription Factors isolation & purification, Transcriptional Activation genetics, Transfection, Acyl-CoA Oxidase genetics, Gene Expression Regulation drug effects, Momordica charantia chemistry, Receptors, Cytoplasmic and Nuclear drug effects, Signal Transduction, Transcription Factors drug effects
- Abstract
Peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-dependent transcription factor that regulates the expression of genes involved in lipid metabolism and transport. Ligands/activators of PPARalpha, like fibrate-type drugs, may have hypolipidemic effects. To identify food that contains activators of PPARalpha, a transactivation assay employing a clone of CHO-K1 cells stably transfected with a (UAS)(4)-tk-alkaline phosphatase reporter and a chimeric receptor of Gal4-rPPARalpha LBD was used to screen ethyl acetate (EA) extracts of a large variety of food materials. It was found that the EA extract of bitter gourd (Momordica charantia), a common oriental vegetable, activated PPARalpha to an extent that was equivalent to or even higher than 10 microM Wy-14643, a known ligand of PPARalpha. This extract also activated PPARgamma to a significant extent which was comparable to 0.5 microM BRL-49653. The activity toward PPARalpha was mainly in the soluble fraction of the organic solvent. The EA extract prepared from the whole fruit showed significantly higher activity than that from seeds or flesh alone. The bitter gourd EA extract was then incorporated into the medium for treatment of a peroxisome proliferator-responsive murine hepatoma cell line, H4IIEC3, for 72 h. Treated cells showed significantly higher activity of acyl CoA oxidase and higher expressions of mRNA of this enzyme and fatty acid-binding protein, indicating that the bitter gourd EA extract was able to act on a natural PPARalpha signaling pathway in this cell line. It is thus worth further investigating the PPAR-associated health benefits of bitter gourd., (Copyright 2003 National Science Council, ROC and S. Karger AG, Basel)
- Published
- 2003
- Full Text
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