Browsing by Author "Chuang, Wen-Han"

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Altered plasma acylcarnitine and amino acid profiles in type 2 diabetic kidney disease
(2016-06)
Chuang, Wen-Han
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Arundhathi, Arivajiagane
;
Lu, Ching
;
Chen, Chang-Chiang
;
Wu, Wan-Chen
Introduction Dysregulation of acylcarnitines (AcylCNs) and amino acids metabolism have implicated in abnormality of fatty acid oxidation in type 2 diabetes (T2D). However, it is not well known whether altered plasma AcylCN, and amino acid profiles are associated with albuminuria or diabetic nephropathy (DN) in T2D. Objective The aim of this study was to elucidate alterations in plasma levels of AcylCNs and amino acids with respect to the T2D patients with various stages of albuminuria. Methods We recruited 52 healthy subjects as control, and 156 T2D patients which were divided into 52 normoalbuminuria, 52 microalbuminuria, and 52 macroalbuminuria. Plasma 37 AcylCNs and 12 amino acids were analyzed by tandem mass spectrometry. Results We found that T2D with normoalbuminuria and microalbuminuria had lower shot-, medium-, and long-chain AcylCNs, whereas T2D with macroalbuminuria had higher short-and medium-chain AcylCNs and lower long-chain AcylCNs than healthy subjects. Moreover, estimated glomerular filtration rate (eGFR) was a negative, independent and significant predictor of albumin to creatinine ratio (ACR) levels (beta = -0.376, P < 0.001), whereas plasma Low-density lipoprotein cholesterol (LDL-C) was significantly and positively associated with ACR levels (beta = 0.169, P = 0.049). Furthermore, multivariate ordinal logistic regression analysis revealed that isobutyrylcarnitine (C4) was a positive, independent, and significant predictor of ACR levels with higher odds of having T2D patients with progression normoalbuminuria to microalbuminuria [OR = 9.93, 95 % CI (3.51-28.05), P < 0.001]. Conclusions The findings suggest that plasma C4 may serve as a potential biomarker for the early stages of DN.
Anthryl-1,2,4-oxadiazole-Substituted Calix[4]arenes as Highly Selective Fluorescent Chemodosimeters for Fe3+
(2015-04-01)
Chen, Ying-Jung
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Yang, Shun-Chieh
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Tsai, Chia-Chen
;
Chang, Kai-Chi
;
Chuang, Wen-Han
Fluorescent chemosensors 1 and 2, with 1,2,4-oxadiazoles as the binding ligands and anthracene as the fluorophore, were synthesized through sequential 1,3-dipolar cycloaddition reactions of 25,27-dioxyacetonitrilecalix[4]arenes 8 and 11. The fluorescence of 1 was severely quenched by both Fe3+ and Cu2+, whereas that of 2 was selectively quenched only by Fe3+. Control compound 4 was also selectively quenched by Fe3+, which implied the importance of anthryl-1,2,4-oxadiazole core; furthermore, it was shown to give various oxidation products such as oxanthrone 13, anthraquinone 14, and imidazolyl oxanthrone 15. In addition to product separation and identification, the fluorescent quenching mechanism of these 9-anthryl-1,2,4-oxadiazolyl derivatives by Fe3+ is also discussed. Furthermore, it should be noted that the oxadiazole-substituted anthracene 4 and calix[4]arene 2 are Fe3+-selective fluorescent chemodosimeters without the interference by Cu2+.
Comparative microarray analyses of mono(2-ethylhexyl)phthalate impacts on fat cell bioenergetics and adipokine network
(2017-12-01)
Chiang, Huai-Chih
;
Wang, Chih-Hong
;
Yeh, Szu-Ching
;
Lin, Yi-Hua
;
Kuo, Ya-Ting
Cellular accumulation of mono(2-ethylhexyl)phthalate (MEHP) has been recently demonstrated to disturb fat cell energy metabolism; however, the underlying mechanism remained unclear. The study aimed to determine how MEHP influenced fat cell transcriptome and how the changes might contribute to bioenergetics. Because of the pivotal role of PPAR gamma in energy metabolism of fat cells, comparative microarray analysis of gene expression in 3T3-L1 adipocytes treated with both MEHP and rosiglitazone was performed. Pathway enrichment analysis and gene ontology (GO) enrichment analysis revealed that both treatments caused up-regulation of genes involved in PPAR signaling/energy metabolism-related pathways and down-regulation of genes related to adipokine/inflammation signals. MEHP/rosiglitazone-treated adipocytes exhibited increased levels of lipolysis, glucose uptake, and glycolysis; the gene expression profiles provided molecular basis for the functional changes. Moreover, MEHP was shown to induce nuclear translocation and activation of PPAR gamma. The similarity in gene expression and functional changes in response to MEHP and rosiglitazone suggested that MEHP influenced bioenergetics and adipokine network mainly via PPAR gamma. Importantly, adipokine levels in C57BL/6J mice with di(2-ethylhexyl)phthalate (DEHP) treatments provided in vivo evidence for microarray results. On the basis of correlation between gene expression and functional assays, possible involvements of genes in bioenergetics of MEHP-treated adipocytes were proposed.
Higher serum betatrophin level in type 2 diabetes subjects is associated with urinary albumin excretion and renal function
(2016-01-07)
Chen, Chang-Chiang
;
Susanto, Hendra
;
Chuang, Wen-Han
;
Liu, Ta-Yu
;
Wang, Chih-Hong
Background: Betatrophin is a newly identified liver-derived hormone that is associated with glucose homeostasis and lipid metabolism. Although dysregulated lipid metabolism results in diabetic nephropathy (DN) development in patients with type 2 diabetes mellitus (T2DM), it is not understood whether betatrophin is associated with urinary albumin excretion and renal function. Methods: Based on albumin/creatinine ratio (ACR), 109 T2DM patients were divided into normoalbuminuria (ACR < 30 mg/g), microalbuminuria (ACR between 30 and 300 mg/g), and macroalbuminuria (ACR > 300 mg/g). Serum betatrophin levels of 109 T2DM patients and 32 healthy subjects were determined by enzyme-linked immunosorbent assay (ELISA). Results: Serum level of betatrophin was significantly increased in T2DM patients with normoalbuminuria, microalbuminuria, and macroalbuminuria as compared with healthy subjects (P < 0.001). Serum betatrophin level was positively correlated with sex, duration of diabetes, systolic blood pressure (SBP), body mass index (BMI), ACR, and triglyceride, whereas it was inversely correlated with estimated glomerular filtration rate (eGFR), total cholesterol, and high-density lipoprotein cholesterol (HDL-C) (P < 0.001). Furthermore, multivariate regression analysis showed the betatrophin was significantly and positively independent with triglyceride and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), whereas it was inversely independent with eGFR, total cholesterol, and low-density lipoprotein cholesterol (HDL-C) (P < 0.05). In addition, the betatrophin had higher odds of having DN [odds ratio (OR) = 5.65, 95 % confidence interval (CI) 2.17-14.57, P < 0.001]. Conclusion: Betatrophin is significantly increased in T2DM patients with different stages of albuminuria. Betatrophin may be a novel endocrine regulator involved in DN development.
Higher serum betatrophin level in type 2 diabetes subjects is associated with urinary albumin excretion and renal function (vol 15, pg 3, 2016)
(2017-04-26)
Chen, Chang-Chiang
;
Susanto, Hendra
;
Chuang, Wen-Han
;
Liu, Ta-Yu
;
Arundhathi, Arivajiagane
Prorenin receptor acts as a potential molecular target for pancreatic ductal adenocarcinoma diagnosis
(2016-08-23)
Arundhathi, Arivajiagane
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Chuang, Wen-Han
;
Chen, Jen-Kun
;
Wang, Shin-E
;
Shyr, Yi-Ming
Recent studies have implicated the prorenin receptor (PRR) is associated with pancreatic tumorigenesis. We therefore investigated the role of PRR in pancreatic tumorigenesis and assessed whether PRR can serve as a target for imaging diagnosis at early stages of PDAC. Here we show that aberrant expression of PRR in premalignant PanIN lesions, and human PDAC samples, and PDAC cell lines, particularly in Panc-1 cells. Interestingly, PRR expression was positively associated with PDAC progression. Moreover, overexpression of human PRR resulted in increased cell proliferation and decreased apoptosis, while knockdown of human PRR caused decreased cell proliferation and enhanced apoptosis in pancreatic cancer cells. We also observed that overexpression of human PRR enhanced MAPK and PI3K/Akt signaling pathways in PDAC cells, while knockdown of human PRR suppressed both of pathways. The confocal imaging analysis showed that human PRR was highly expressed in Panc-1, ASPC, and Miapaca cells, whereas BXPC-3, and HPAC cells had a significantly lower fluorescent signals. Consistently, the single-photon emission computed tomography (SPET/CT) showed that the uptake of anti-PRR labelled with I-125 was higher in Panc-1 and ASPC tumors-bearing mice after 96 hours injection. Importantly, tumors in pancreas of Pdx1-cre; LSL-Kras(G12D) mice had a significant increased PRR expression and accumulation of radioactivity at 96 h after injection. These data suggest that I-125-anti-PRR can detect the orthotopic tumors in Pdx1-cre; LSL-Kras(G12D) mice. Therefore, anti-PRR labelled with I-125 is a promising radiotracer for imaging diagnosis at early stages of pancreatic cancer.