Tainan Sinlau Hospital

Tainan, Taiwan

Tainan Sinlau Hospital

Tainan, Taiwan

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Cheng Y.-C.,Kaohsiung Medical University | Chen C.-A.,Tainan Sinlau Hospital | Chang J.-M.,Kaohsiung Municipal Hsiao Kang Hospital | Chen H.-C.,Kaohsiung Medical University
Journal of Biochemistry | Year: 2014

Proteinuria is a major hallmark of glomerular nephropathy and endoplasmic reticulum (ER) stress plays an important role in glomerular nephropathy. The protein levels of integrin-β1 in podocytes are found to be negative correlation with amount of proteinuria. This study investigated whether urinary protein, particularly albumin, induced ER stress that consequently reduced integrin-β1 expression. All experiments were performed using primary cultured rat podocyte. Protein and mRNA expression were measured by western blotting and semiquantified reverse transcriptase polymerase chain reaction. Albumin uptake was found at 1 h after albumin addition. Albumin reduced precursor and mature forms of integrin-β1, but did not change mRNA levels of integrinβ1. Albumin induced reactive oxygen species (ROS) generation and ER stress. Antioxidant (N-acetylcysteine) suppressed albumin-induced ER stress and decrements in precursor and mature forms of integrin-β1. Then, ER stress inhibitors (4-phenylbutyrate and salubrinal) also inhibited albumin-induced decrements in precursor and mature forms of integrin-β1. The potent ER stress inducers (thapsigargin and tunicamycin) directly decreased precursor and mature forms of integrin-β1 and led appearance of unglycosylated core protein of integrin-β1. Our results show that in proteinuric disease, albumin decreases precursor and mature forms of integrin-β1 through ROS-ER stress pathway in podocytes. © The Authors 2015.


PubMed | Tainan Sinlau Hospital, Kaohsiung Medical University and Kaohsiung Municipal Hsiao Kang Hospital
Type: Journal Article | Journal: Journal of biochemistry | Year: 2015

Proteinuria is a major hallmark of glomerular nephropathy and endoplasmic reticulum (ER) stress plays an important role in glomerular nephropathy. The protein levels of integrin-1 in podocytes are found to be negative correlation with amount of proteinuria. This study investigated whether urinary protein, particularly albumin, induced ER stress that consequently reduced integrin-1 expression. All experiments were performed using primary cultured rat podocyte. Protein and mRNA expression were measured by western blotting and semiquantified reverse transcriptase polymerase chain reaction. Albumin uptake was found at 1 h after albumin addition. Albumin reduced precursor and mature forms of integrin-1, but did not change mRNA levels of integrin-1. Albumin induced reactive oxygen species (ROS) generation and ER stress. Antioxidant (N-acetylcysteine) suppressed albumin-induced ER stress and decrements in precursor and mature forms of integrin-1. Then, ER stress inhibitors (4-phenylbutyrate and salubrinal) also inhibited albumin-induced decrements in precursor and mature forms of integrin-1. The potent ER stress inducers (thapsigargin and tunicamycin) directly decreased precursor and mature forms of integrin-1 and led appearance of unglycosylated core protein of integrin-1. Our results show that in proteinuric disease, albumin decreases precursor and mature forms of integrin-1 through ROS-ER stress pathway in podocytes.


Chen C.-A.,Tainan Sinlau Hospital | Chen T.-S.,Tainan Sinlau Hospital | Chen H.-C.,Kaohsiung Medical University
Experimental Biology and Medicine | Year: 2012

The effect of reactive oxygen species (ROS) and blocking integrin-extracellular matrix (ECM) interaction on apoptosis in podocytes, and the related signal transduction pathways remain unclear. Primary cultured rat podocytes were exposed to ROS. Integrin-ECM interaction was inhibited with anti-β1-integrin monoclonal antibody (mAb) or RGDS (Arg-Gly-Asp-Ser). Extracellular signal-regulated kinase (ERK) activation was evaluated with Western blotting. U0126 was used to inhibit ERK activation. Terminal deoxynucleotidyl transferase-mediated dUTP-peroxidase nick end-labeling of DNA (TUNEL) was used to evaluate apoptosis. We found that ROS-treated podocytes exhibited increased apoptosis, and both anti-β1- integrin mAb and RGDS induce apoptosis. Addition of ROS to either anti-β1-integrin mAb or RGDS enhanced apoptosis in both conditions. ERK activation was increased by either ROS or blocking integrin-ECM interaction. Preincubation with U0126 decreased apoptosis induced by ROS, anti-β1-integrin mAb or RGDS, respectively. Our study demonstrated that ROS and blocking integrin-ECM interaction induce podocyte apoptosis, which is mediated by ERK activation. © 2008 Society for Experimental Biology and Medicine.


PubMed | Tainan Sinlau Hospital and Kaohsiung Medical University
Type: Journal Article | Journal: Experimental biology and medicine (Maywood, N.J.) | Year: 2015

Endoplasmic reticulum stress occurs in a variety of patho-physiological mechanisms and there has been great interest in managing this pathway for the treatment of clinical diseases. Autophagy is closely interconnected with endoplasmic reticulum stress to counteract the possible injurious effects related with the impairment of protein folding. Studies have shown that glomerular podocytes exhibit high rate of autophagy to maintain as terminally differentiated cells. In this study, podocytes were exposed to tunicamycin and thapsigargin to induce endoplasmic reticulum stress. Thapsigargin/tunicamycin treatment induced a significant increase in endoplasmic reticulum stress and of cell death, represented by higher GADD153 and GRP78 expression and propidium iodide flow cytometry, respectively. However, thapsigargin/tunicamycin stimulation also enhanced autophagy development, demonstrated by monodansylcadaverine assay and LC3 conversion. To evaluate the regulatory effects of autophagy on endoplasmic reticulum stress-induced cell death, rapamycin (Rap) or 3-methyladenine (3-MA) was added to enhance or inhibit autophagosome formation. Endoplasmic reticulum stress-induced cell death was decreased at 6h, but was not reduced at 24h after Rap+TG or Rap+TM treatment. In contrast, endoplasmic reticulum stress-induced cell death increased at 6 and 24h after 3-MA+TG or 3-MA+TM treatment. Our study demonstrated that thapsigargin/tunicamycin treatment induced endoplasmic reticulum stress which resulted in podocytes death. Autophagy, which counteracted the induced endoplasmic reticulum stress, was simultaneously enhanced. The salvational role of autophagy was supported by adding Rap/3-MA to mechanistically regulate the expression of autophagy and autophagosome formation. In summary, autophagy helps the podocytes from cell death and may contribute to sustain the longevity as a highly differentiated cell lineage.


Chen J.-Y.,National Cheng Kung University | Chou C.-H.,Tainan Sinlau Hospital | Tsai W.-C.,National Cheng Kung University | Wang M.-C.,National Cheng Kung University | And 4 more authors.
Journal of the American Society of Hypertension | Year: 2012

Nonalcoholic fatty liver disease (NAFLD) is associated with increasing arterial stiffness. We studied the effects of inflammation on different measurements of arterial stiffness in NAFLD. We recruited 80 patients with NAFLD and 40 control subjects. Both compliance index (CI) and stiffness index (SI) were measured. Patients with NAFLD had significantly lower CI (3.8 ± 2.1 vs 4.9 ± 2.9 units; P <.05) and higher SI (8.5 ± 2.4 vs 7.1 ± 1.5 m/s; P <.05) than the controls. Patients with NAFLD were further divided into 2 groups according to the median level of high-sensitivity C-reactive protein (hs-CRP). The CI was significantly lower in patients with NAFLD with high hs-CRP than in those with low hs-CRP (3.2 ± 1.7 vs 4.4 ± 2.5 units; P <.05); however, SI was not statistically different. We further found that waist circumference (odds ratio, 1.06; 95% confidence interval, 1.01-1.13; P <.05) was the only independent factor that predicted low CI (


Chou C.-H.,Tainan Sinlau Hospital | Tsai W.-C.,National Cheng Kung University | Wang M.-C.,National Cheng Kung University | Ho C.-S.,National Taiwan Sport University | And 4 more authors.
International Heart Journal | Year: 2013

Premature arteriosclerosis may be one of the mechanisms linking pre-diabetes mellitus (pre-DM) and cardiovascular disease. We sought to characterize premature arteriosclerosis in pre-DM using different arterial stiffness indices and to find the independent contributors of this process. We recruited 33 patients without DM, 53 patients with pre-DM, and 34 subjects with DM. Both the compliance index (CI) and stiffness index (SI) were measured. Patients with pre-DM and DM had lower CI (3.8 ± 2.1 versus 5.2 ± 3.0 units; P < 0.05 and 3.6 ± 1.8 versus 5.2 ± 3.0 units; P < 0.05, respectively) and higher SI (8.0 ± 2.0 versus 6.7 ± 1.6 m/s; P < 0.01 and 9.4 ± 2.3 versus 6.7 ± 1.6 m/s; P < 0.001, respectively) than patients without DM. Using multivariate linear regression analysis, age, heart rate, and HOMA index were independent determinants for SI (whole model: R2 = 0.47, P < 0.001), whereas male gender, hsCRP, and HOMA index were independent determinants for CI (whole model: R2 = 0.34, P < 0.01). The HOMA index was an independent determinant for arterial stiffness. Increased insulin resistance may associate with increased arterial stiffness at peripheral arteries in pre-DM patients.


PubMed | National Cheng Kung University and Tainan Sinlau Hospital
Type: | Journal: The Journal of nutritional biochemistry | Year: 2016

Peripheral nervous injury (PNI) is a common form of trauma in modern society, especially in sport players. Despite the advance of therapy for PNI, the recovery of function can never reach the preinjury level after treatments. Recently, inhibiting neural oxidative stress shows a beneficial effect in improving functional recovery after PNI. In addition, sesame oil has been reported to possess the excellent antioxidative properties. However, whether sesame oil can improve the functional recovery after PNI by its antioxidative effect has never been investigated. Thirty mice were randomly divided into five groups of six: group I mice received sham operation; group II mice received sciatic nerve crush; and groups III-V mice daily ingested 0.5, 1 and 2 ml/kg of sesame oil for 6 days, respectively, after sciatic nerve crush. Oxidative stress, GAP43 and nuclear Nrf2 levels as well as spinal somatosensory evoked potentials were assessed on day 6, while paw withdrawal latency and sciatic function index were assessed on days 0, 3, and 6. Sesame oil significantly decreased lipid peroxidation and increased nuclear factor erythroid 2-related factor 2 and GAP43 expression in sciatic nerve. Furthermore, sesame oil improved electrophysiological and functional assessments in mice with sciatic nerve crush. In conclusion, sesame oil may improve nerve functional recovery by attenuating nerve oxidative stress in mouse acute peripheral nerve injury. Further, application of natural product sesame oil may be an alternative approach for improving nerve functional recovery in the clinical setting.


Tsai Y.-F.,Tainan Sinlau Hospital | Tsai Y.-F.,Southern Taiwan University of Science and Technology | Chen C.-A.,Tainan Sinlau Hospital | Kuo C.,Tainan Sinlau Hospital | Lin K.-C.,Chi Mei Medical Center
Clinical and Experimental Nephrology | Year: 2012

Aim Anti-platelet factor 4/heparin complex antibodies (anti-PF4/heparin Ab) have been found to cause heparininduced thrombocytopenia (HIT), a clinical syndrome thrombocytopenia and thrombosis. There is still controversy as to whether the presence of anti-PF4/heparin antibodies in hemodialysis patients augments clot formation in access fistula thrombosis, peripheral artery disease (PAD), and coronary heart disease (CHD). Methods We enrolled 111 non-diabetic hemodialysis patients without liver cirrhosis and without an ankle-brachial index (ABI) C1.3 (arterial calcification). ABI measurements were performed and patients with an ABI ≤0.9 were defined as having PAD and included in the PAD group. ELISA was used for determination of anti-PF4/ heparin Ab. Correlation factors include PAD, native arteriovenous fistula (AVF) thrombosis, platelet count, and CHD. Results Thirty-seven of 111 patients (33.3%) presented with anti-PF4/heparin Ab. Thirty-eight of 111 patients (34%) had PAD; fourteen of these patients (36.8%) and 23/73 of patients without PAD (31.5%) were anti-PF4/ heparin Ab-positive (P = 0.57). Fifty-Two of 111 patients (46.8%) had AVF thrombosis; twenty-Three of these patients (44.2%) and 14/59 of patients without AVF thrombosis (23.7%) were anti-PF4/heparin Ab-positive (P = 0.02). The odds ratio for AVF thrombosis was 2.55 (95% CI 1.14-5.71) for anti-PF4/heparin Ab-positive patients. Thirty-Two of 111 patients (28.8%) had thrombocytopenia (platelet count \140 × 103/μL); eleven of these patients (34.3%) and 26/79 patients without thrombocytopenia (32.9%) were anti-PF4/heparin Ab-positive (P = 0.88). Ten of 111 patients (9%) had CHD; two of these patients (20%) and 35/101 patients without CHD (34.6%) were anti-PF4/heparin Ab-positive (P = 0.49). Conclusions We found that anti-PF4/heparin Ab may contribute to an increased risk of AVF thrombosis in nondiabetic hemodialysis patients. © Japanese Society of Nephrology 2012.


PubMed | Tainan Sinlau Hospital and Southern Taiwan University of Science and Technology
Type: Journal Article | Journal: International urology and nephrology | Year: 2015

Iron may contribute to vascular injury through reactive oxygen species. Hemodialysis patients frequently receive iron supply for correction of anemia and are at a high risk of cardiovascular disease. We tested the relationship between iron status and change in arterial stiffness in hemodialysis patients.We measured iron status in 53 hemodialysis patients and studied the association with clinical, biochemical, and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) over 3 years. The blood pressure was controlled to below 140/90 mmHg by anti-hypertensive drugs.Median and interquartile range of baseline baPWV, baPWV at 3 years, and baPWV (difference between 3-year baPWV and baseline baPWV) were following: 17.6 (14.8-18.9), 16.9 (15.3-19.9), and 0.2 (-1.2 to 2.7) m/s. At baseline, baPWV was positively correlated with age, serum ferritin, and systolic blood pressure in univariate analysis. However, in multivariate analysis, only age and serum ferritin remained the significant determinants of baseline baPWV. After 3 years, baPWV was negatively correlated with age and positively with 3-year averaged serum ferritin in univariate analysis. Then, in multivariate analysis, only 3-year averaged serum ferritin was the important determinant of baPWV. baPWV was significantly increased in patients with 3-year averaged serum ferritin >500 ng/mL compared to patients with 3-year averaged serum ferritin 500 ng/mL.In hemodialysis patients, serum ferritin associates with the progressive arterial stiffness, especially when serum ferritin >500 ng/mL.


PubMed | Tainan Sinlau Hospital
Type: Journal Article | Journal: International journal of hematology | Year: 2016

Hemodialysis patients frequently receive intravenous iron for the treatment of anemia. Iron status has been found to be correlated with coronary artery disease. In the post hoc study reported here, we evaluate the association between iron status and coronary arterial stenosis (CAS) in a 3-year follow-up period. We enrolled 76 patients and collected iron status, and clinical/biochemical data over 3years. In this study, coronary arterial stenosis was considered significant when the narrowing of the coronary artery exceeded 50% of the luminal diameter on coronary angiography. The mean age was 61years old. The female/male ratio was 48/28, and the group included 16 diabetic patients and 23 smokers. Twenty-two of 76 patients had CAS. Mean intravenous iron dosage was 2167.111738.38 in a 3-year period. On the univariate regression analysis, 3-year-averaged serum ferritin was positively associated with CAS (r=0.288, P=0.012). The 3-year-averaged intravenous iron dosage, DM, age, smoking, and other biochemical parameters showed no association with CAS. When these factors were added to the multivariate-adjusted models, 3-year-averaged serum ferritin remained a determinant of CAS event (=0.290, P=0.029). The odds ratio for CAS was 6.93 (95% CI 2.41-19.94; P=0.001) for patients with 3-year-averaged serum ferritin 600ng/mL. In summary, serum ferritin was an independent risk factor for CAS among this group of hemodialysis patients, especially when serum ferritin was 600ng/mL.

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