This study investigated whether high-normal thyrotropin (TSH) levels are associated with metabolic syndrome in euthyroid Chinese people≥40 years old. Clinical and metabolic factors were assessed in 2,356 subjects (40–77 years old) with TSH levels in the normal range (0.35–5.00 mU/L). Using 2.50 mU/L as the cut-off point of TSH level within the normal range, we divided subjects into the high-TSH (2.50–5.00 mU/L; n=1,064) and low-TSH (0.35–2.50 mU/L; n=11,292) group. The results showed that the mean levels of body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and fasting plasma glucose (FPG) were higher in the high-TSH group and TSH levels were significantly positively correlated with BMI, LDL-C, TC, and FPG. The prevalence of central obesity, hypertriglyceridemia, low high density lipoprotein cholesterol (HDL-C), and high FPG (>5.60 mmol/L) was significantly higher in females and subjects with high-TSH levels. Metabolic syndrome was also more prevalent in the high-TSH group. People over the age of 40 years with high-normal TSH levels had an approximately 1.2-fold increased risk of metabolic syndrome, compared with those with low-normal TSH levels, after adjusting for age and gender. In conclusion, high normal TSH is a risk factor for metabolic syndrome in people≥40 years old.
We sought to investigate variation of atrial electromechanical interval after catheter ablation procedure in patients with persistent atrial fibrillation using pulse Doppler (PW) and pulse tissue Doppler imaging (PW-TDI). A total of 25 consecutive in-patients with persistent atrial fibrillation, who restored sinus rhythm after ablation procedure, were recruited in our cardiac center. Echocardiography was performed on each patient at 2 hours, 1 day, 5 days, 1 month and 3 months after the ablation therapy, and atrial electromechanical delay was measured simultaneously by PW and PW-TDI. There was no significant difference between PW and TDI in measuring atrial electromechanical delay. However, at postoperative 2 hours, peak A detection rates were mathematically but nonsignificantly greater by PW-TDI than by PW. Second, there was a significant decreasing trend in atrial electromechanical interval from postoperative 2 hours to 3 months, but only postoperative 2-hour atrial electromechanical interval was significantly greater than atrial electromechanical interval at other time. Lastly, patients without postoperative 2-hour atrial electromechanical interval had a significantly longer duration of atrial fibrillation as compared to those with postoperative 2-hour atrial electromechanical interval, by the PW or by PW-TDI, respectively. In patients with persistent atrial fibrillation, atrial electromechanical interval may decrease significantly within the first 24 hours after ablation but remain consistent later, and was significantly related to patients' duration of atrial fibrillation. Atrial electromechanical interval, as a potential predicted factor, is recommended to be measured by either PW or TDI after 24 hours, when patients had recovered sinus rhythm by radiofrequency ablation.
Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis.
Excessive fibrogenesis disrupts normal liver structure, impairs liver function, and precipitates the development of cirrhosis, an irreversible end-stage liver disease. A host of factors including nutrition surplus contribute to liver fibrosis but the underlying mechanism is not fully understood. In the present study, we investigated the involvement of protein inhibitor for activated stat 4 (PIAS4) in liver fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH). We report that PIAS4 silencing using short hairpin RNA (shRNA) attenuated high-fat high-carbohydrate (HFHC) diet induced liver fibrosis in mice. Quantitative PCR and Western blotting analyses confirmed that PIAS4 knockdown downregulated a panel of pro-fibrogenic genes including type I and type III collagens, smooth muscle actin, and tissue inhibitors of metalloproteinase. Mechanistically, PIAS4 silencing blocked the recruitment of SMAD3, a potent pro-fibrogenic transcription factor, to the promoter regions of pro-fibrogenic genes and dampened SMAD3 acetylation likely by upregulating SIRT1 expression. In conclusion, PIAS4 may contribute to liver fibrosis by modulating SIRT1-dependent SMAD3 acetylation.
Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2 (VMAT2) contributes to the pathogenesis of Parkinson's disease. That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson's diseases. However, whether VMAT2 function is regulated by retrograde trafficking is unknown. By using biochemistry and cell biology approaches, we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells. The transporter also interacted with the key component of retromer, Vps35, biochemically and subcellularly. Using specific siRNA, we further showed that Vps35 depletion altered subcellular localization of VMAT2. Moreover, siRNA-mediated Vps35 knockdown also decreased the stability of VMAT2 as demonstrated by the reduced half-life. Thus, our work suggested that altered vesicular trafficking of VMAT2 may play a vital role in neuroprotection of the transporter as well as in the pathogenesis of Parkinson's disease.
Leucocytozoonosis was found in three layer farms in chickens with suspected fatty liver or fatty liver hemorrhagic syndrome in Korea between 2009 and 2011. These layer chicken flocks showed both mortality and decreased egg production for one or two weeks when they were between 59 and 82 weeks old. At the necropsy, the most prominent gross lesions were found in the liver, which was enlarged, had a fragile texture, exhibited yellowish discolorations, and had various hemorrhagic lesions. Tissue reactions associated with megaloschizonts specific for Leucocytozoon caulleryi were prominent upon microscopic examination of the liver without significant lipidosis. In addition, the ovaries and uterus were the most affected organs for Leucocytozoon caulleryi multiplication, which led to decreased egg productions. Molecular studies with formalin-fixed, paraffin-embedded tissues were performed in search of a partial region of the cytochrome b gene for hemosporidian parasites. Based on these results, the causal agent was determined to be closely related to Leucocytozoon caulleryi reported in Japan and Malaysia. In this study, we describe recently re-occurring leucocytozoonosis in layer chickens, which required histopathology for disease diagnosis. To prevent outbreaks and maintain chicken health and egg production, layer chickens need to be monitored for symptoms of leucocytozoonosis.