Search

Feng Yu Kuo, 1, 2 Kai-Chun Cheng, 3 Yingxiao Li, 4 Juei-Tang Cheng, 5 Cheng-Chia Tsai 6, 7 1Cardiovascular Centre, Kaohsiung Veterans General Hospital, Kaohsiung Citty, Taiwan; 2Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung County, Taiwan; 3Pharmacological Department of Herbal Medicine and Department of Psychosomatic Internal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima Unuversity, Kagoshima, Japan; 4Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97005, Taiwan; 5Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; 6Department of Surgery, Mackay Memorial Hospital, Taipei City, Taiwan; 7Department of Medicine, Mackay Medical College, New Taipei, TaiwanCorrespondence: Juei-Tang ChengDepartment of Medical Research, Chi-Mei Medical Center, No. 901, Zhonghua Road Yongkang District, Tainan 71004, TaiwanTel +886-6-2517864Email jtcheng5503@gmail.comCheng-Chia TsaiDepartment of Surgery, Mackay Memorial Hospital, No. 92, Sec.2, Chung-Shan North Road, Taipei City 10449, TaiwanTel +886-2-25433535Email angle@ms1.mmh.org.twBackground: Adropin is a secreted polypeptide that has been demonstrated to play an important role in energy homeostasis and lipid metabolism. Signal transducer and activator of transcription 3 (STAT3) may promote the transcription of target genes including adropin. In the current study, we investigated the effect of adropin on glucose metabolism in diabetic rats and the mechanism that governs this effect was subsequently assessed.Materials and Methods: Rats received a single injection of streptozotocin to induce type 1 diabetes. The diabetic rats were treated with insulin or phloridzin, another antidiabetic agent through inhibition of glucose reabsorption, for 7 days. Plasma glucose levels and adropin levels were measured. The interaction between STAT3 and adropin was evaluated using the human hepatoma HepG2 cell line. HepG2 cells were pretreated with the specific antagonist Stattic or with STAT3-specific siRNAs to knockout STAT3. Changes in energy homeostasis-associated gene expression were measured using real-time PCR. The protein expression levels of pSTAT3 and STAT3 were measured using Western blotting.Results: In diabetic rats, the serum concentrations of adropin were increased in the vehicle-treated group and decreased in the insulin- or phloridzin-treated group. In liver tissues, the Enho expression level and the activity of STAT3 also showed similar tendencies. After HepG2 cells were treated with medium containing high glucose, the ratio of p-STAT3 to STAT3, Enho mRNA levels and reactive oxygen species expression levels in HepG2 cells were significantly increased in conjunction with increased glucose levels. The effect was inhibited after pretreatment with Stattic or knockdown with STAT3-specific siRNAs.Conclusion: STAT3 is involved in the genetic regulation of adropin, increasing the levels of circulating adropin and promoting Enho expression in the livers of diabetic rats.Keywords: adropin, Enho gene, STAT3, type 1 diabetes, reactive oxygen species

Shu Ping Lee,1 Feng Yu Kuo,1,2 Juei-Tang Cheng,3,4 Ming Chang Wu11Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan; 2Cardiovascular Center, Veterans General Hospital, Kaohsiung City 81362, Taiwan; 3Department of Medical Research, Chi-Mei Medical Center, Tainan City 71003, Taiwan; 4Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan City 71101, TaiwanBackground: Thymoquinone (TQ) is a safe nutrient isolated from the seeds or volatile oil extract of Nigella sativa. In addition to its benefits in glucose regulation, TQ improves feeding disorders in diabetic animals. Glucagon-like peptide-1 (GLP-1) analogs improve glycemic control and ameliorate obesity or hyperphagia. Therefore, the present study aimed to investigate the role of GLP-1 in TQ-induced anorexia.Method: Type 2 diabetes was induced in rats by nicotinamide and streptozotocin injection. TQ was orally administered to diabetic rats at different doses for 45 days. Following TQ treatment, changes in serum glucose levels, GLP-1 concentration, body weight, food intake, and water intake were determined. To further explore the interaction between GLP-1 and TQ, the inhibitor of dipeptidyl peptidase 4, sitagliptin and the GLP-1 receptor antagonist exendin 9–39 (Ex 9–39) were separately administered to TQ- or vehicle-treated diabetic rats.Results: TQ treatment attenuated hyperglycemia and reduced hyperphagy and water intake in streptozotocin-induced diabetic rats in a dose-dependent manner. Moreover, TQ treatment elevated plasma GLP-1 levels compared to those in control rats. The effects of TQ were enhanced by treatment with sitagliptin and reduced by the injection of Ex 9–39 into the brain. In contrast, similar treatment with another antioxidant (either ascorbic acid or N-acetylcysteine) produced the same anorexic effect as TQ without changing the plasma GLP-1 levels in diabetic rats. Therefore, TQ attenuated hyperphagy while increasing plasma GLP-1 levels and had antioxidant-like effects.Conclusion: TQ increased endogenous GLP-1 levels to reduce hyperphagy in diabetic rats.Keywords: thymoquinone, GLP-1, sitagliptin, body weight, food intake

Right ventricular dysfunction has been observed in uremic patients receiving percutaneous transluminal angioplasty (PTA). This prospective study focuses on the impact of tissue Doppler imaging echocardiographic parameters on assessing right ventricle function in uremic patients post PTA of dysfunctional hemodialysis access.Sixty uremic patients were divided into two groups by angiographic findings: an occlusive group (26 patients) and a stenotic group (34 patients). All uremic patients underwent routine echocardiography with tissue Doppler imaging both before and immediately following PTA to assess the right ventricular (RV) function and pulmonary artery systolic pressure (PASP). The right ventricular (RV) myocardial performance index (MPI) was obtained during tissue Doppler imaging over the lateral tricuspid annulus. The M index was measured and defined as the peak early diastolic mitral inflow velocity divided by the RV MPI. The RV MPI, RV isovolumic relaxation time (IVRT) and M-index were used to evaluate RV function post-PTA.Immediately following PTA, PASP (31.6 ± 11.3 mmHg versus 42.6 ± 12.0 mmHg, p = 0.001), RV MPI (0.46 ± 0.08 versus 0.62 ± 0.13, p0.001) and IVRT (75.1 ± 12.9 versus 98.4 ± 27.7 ms, p0.001) increased significantly in the occlusive group. However, PASP and RV function did not change significantly in the stenotic group. In 42.3% patients from the occlusive group, the M-index fell below 112 and RV MPI rose above 0.55 post-PTA; this occurred in only 8.8% of the stenotic group.This prospective study demonstrated that there was a higher incidence of RV dysfunction in uremic patients with elevated PASP with totally occluded hemodialysis access than those with stenotic access post-PTA.Myocardial performance index; Percutaneous transluminal angioplasty; Pulmonary hypertension; Tissue Doppler image; Uremic.

Lipid-lowering therapy plays an important role in preventing the recurrence of cardiovascular events in patients after acute myocardial infarction (AMI). This study aimed to assess the effect of intensified low density lipoprotein cholesterol (LDL-C) reduction on recurrent myocardial infarction and cardiovascular mortality in patients after AMI.The 562 enrolled AMI patients (84.2% male) were divided into two groups according to 3-month LDL-C decrease percentage equal to or more than 40% (n = 165) and less than 40% (n = 397). To evaluate the long-term efficacy of LDL-C reduction, the 5-year outcomes were collected, including time to the first occurrence of myocardial infarction and time to cardiovascular death.The baseline characteristics and complication rates were not different between the two study groups. The patients with 3-month LDL-C decrease ≥ 40% had higher baseline LDL-C and lower 3-month, 1-year, 2-year, 3-year, 4-year and 5-year LDL-C than the patients with 3-month LDL-C decrease40%. In Kaplan-Meier analyses, those patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction (p = 0.006) and survival rate (p = 0.02) at 5-year follow-up. The 3-month LDL-C40% parameter was significantly related to cardiovascular death (HR: 9.62, 95% CI 1.18-78.62, p0.04).After acute myocardial infarction, 3-month LDL-C decrease40% was identified to be a significant risk factor for predicting 5-year cardiovascular death. The patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction and lower cardiovascular mortality, even though these patients had higher baseline LDL-C value.Acute myocardial infarction; Cardiovascular death; Low-density lipoprotein cholesterol; Mortality; Statin.

In this paper, a new latch-up phenomenon, in which the positive trigger voltage V/sub trg+/ is smaller than the theoretical value, based on the two-step activation diode model, is found and analyzed by TCAD simulation. Based on the simulation result, an analytical model for the positive trigger point is developed and methodologies for evaluating the positive trigger point, varying with the geometry layout of the latch-up test patterns, are proposed. The calculated positive trigger current and trigger voltage fit the measurement results very well, so that the proposed method is efficient for evaluating the positive triggering point.