Browsing by Author "Arundhathi, Arivajiagane"

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Altered plasma acylcarnitine and amino acid profiles in type 2 diabetic kidney disease
(2016-06)
Chuang, Wen-Han
;
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.
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
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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
;
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.