Sialyltransferase7A promotes angiotensin II-induced cardiomyocyte hypertrophy via HIF-1α-TAK1 signalling pathway.

AIMS: Sialylation is up-regulated during the development of cardiac hypertrophy. Sialyltransferase7A (Siat7A) mRNA is consistently over-expressed in the hypertrophic left ventricle of hypertensive rats independently of genetic background. The aims of this study were: (i) to detect the Siat7A protein levels and its roles in the pathological cardiomyocyte hypertrophy; (ii) to elucidate the effect of sialylation mediated by Siat7A on the transforming-growth-factor-ß-activated kinase (TAK1) expression and activity in cardiomyocyte hypertrophy; and (iii) to clarify hypoxia-inducible factor 1 (HIF-1) expression was regulated by Siat7A and transactivated TAK1 expression in cardiomyocyte hypertrophy. METHODS AND RESULTS: Siat7A protein level was increased in hypertrophic cardiomyocytes of human and rats subjected to chronic infusion of angiotensin II (ANG II). Delivery of adeno-associated viral (AAV9) bearing shRNA against rat Siat7A into the left ventricular wall inhibited ventricular hypertrophy. Cardiac-specific Siat7A overexpression via intravenous injection of an AAV9 vector encoding Siat7A under the cardiac troponin T (cTNT) promoter aggravated cardiac hypertrophy in ANG II-treated rats. In vitro, Siat7A knockdown inhibited the induction of Sialyl-Tn (sTn) antigen and cardiomyocyte hypertrophy stimulated by ANG II. Mechanistically, ANG II induced the activation of TAK1-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling in parallel to up-regulation of Siat7A in hypertrophic cardiomyocytes. Siat7A knockdown inhibited activation of TAK1-NF-κB pathway. Interestingly, HIF-1α expression was increased in cardiomyocytes stimulated by ANG II but decreased after Siat7A knockdown. HIF-1α knockdown efficiently decreased TAK1 expression. ChIP and luciferase assays showed that HIF-1α transactivated the TAK1 promoter region (nt -1285 to -1274 bp) in the cardiomyocytes following ANG II stimulus. CONCLUSION: Siat7A was up-regulated in hypertrophic myocardium and promoted cardiomyocyte hypertrophy via activation of the HIF-1α-TAK1-NF-κB pathway.

Complete atrioventricular block due to timolol eye drops: a case report and literature review.

BACKGROUND: Timolol Maleate is a non-selective beta-adrenergic blocker that is commonly used to treat open-angle glaucoma. Despite its topical administration, ophthalmic timolol enters systemic circulation and produces a systemic beta-adrenergic blockade. We report a case of long-term timolol use that uncovered and worsened an underlying cardiac conduction defect demonstrated as a third degree atrioventricular (AV) block. CASE PRESENTATION: A 62-year old male with a 13-year history of glaucoma was hospitalized due to shortness of breath, dizziness, and amaurosis. Electrocardiography indicated a heart rate (HR) of 29 bpm with complete atrioventricular (AV) block, and the HR was significantly increased with the treatment of isoprenaline. However, the patient experienced bradycardic episodes (- 20 Δbpm) immediately after self-administration of timolol eye drops. The AV block and bradycardia resolved 48-h after timolol cessation. The man was discharged 1 week later with an asymptomatic first-degree A-V block. However, he presented with a worsened A-V block at his one-year checkup. CONCLUSION: We conclude that chronic topical timolol administration may aggravate a cardiac conduction defect leading to an AV block that is only temporarily resolved by timolol cessation. Patients taking timolol should be routinely monitored for cardiovascular aberrations and if any detected, immediately discontinue timolol therapy. Individuals experiencing timolol induced cardiovascular side effects should receive long term follow-up even if symptoms resolve, as they may be indicative of an underlying conduction defect.

Optimization of b-values in diffusion-weighted imaging for esophageal cancer: Measuring the longitudinal length of gross tumor volume and evaluating chemoradiotherapeutic efficacy.

PURPOSE: To study the optimization of b-values of magnetic resonance-diffusion-weighted (MR-DWI) in evaluating the chemoradiotherapeutic efficacy for esophageal squamous cell carcinoma (ESCC) and measuring the longitudinal length of gross tumor volume (GTV) of ESCC. MATERIALS AND METHODS: Eighteen patients with biopsy-proven ESCC were undergoing concurrent chemoradiotherapy (CCRT). Conventional magnetic resonance imaging (MRI) combined with DWI using b-values of 600 s/mm2, 800 s/mm2, and 1000 s/mm2 was performed before CCRT and after the 1st, 3rd, 5th, and 10th weeks. The apparent diffusion coefficient (ADC) values of ESCC were derived from DWI using multiple b-values. The correlations between ADC values and apoptosis positive rates of ESCC cells obtained from the endoscope biopsy were statistically analyzed. Thirty-eight patients with confirmed ESCC who underwent radical surgery were analyzed. Longitudinal length of GTV of ESCC was measured using endoscopy, esophageal barium fluoroscopy, computed tomography (CT), and T2-weighted MRI and DWI using different b-values (b = 400, 600, and 800 s/mm2) before surgery and were compared with pathologic lesion length. RESULTS: The ADC values of DWI images with different b-values are positively correlated with ESCC cell apoptosis positive ratios, the relation is significant, especially in the group of b = 1000 s/mm2 (P < 0.01). The measured length of esophageal lesions from short to long was MR-DWI b = 800 s/mm2, endoscopy, real tumor, MR-DWI b = 600 s/mm2, esophageal barium fluoroscopy, CT, and MR-DWI b = 400 s/mm2. CONCLUSION: MR-DWI b = 800 s/mm2 and b = 1000 s/mm2 are in favor of observing the chemoradiotherapeutic efficacy with time variation and evaluating the chemoradiotherapeutic efficacy, respectively. MR-DWI b = 600 s/mm2 could be used as a supplementary means in measuring the length of ESCC.

Information Extraction of High Resolution Remote Sensing Images Based on the Calculation of Optimal Segmentation Parameters.

Multi-scale image segmentation and the selection of optimal segmentation parameters are the key processes in the object-oriented information extraction of high-resolution remote sensing images. The accuracy of remote sensing special subject information depends on this extraction. On the basis of WorldView-2 high-resolution data, the optimal segmentation parameters methodof object-oriented image segmentation and high-resolution image information extraction, the following processes were conducted in this study. Firstly, the best combination of the bands and weights was determined for the information extraction of high-resolution remote sensing image. An improved weighted mean-variance method was proposed andused to calculatethe optimal segmentation scale. Thereafter, the best shape factor parameter and compact factor parameters were computed with the use of the control variables and the combination of the heterogeneity and homogeneity indexes. Different types of image segmentation parameters were obtained according to the surface features. The high-resolution remote sensing images were multi-scale segmented with the optimal segmentation parameters. Ahierarchical network structure was established by setting the information extraction rules to achieve object-oriented information extraction. This study presents an effective and practical method that can explain expert input judgment by reproducible quantitative measurements. Furthermore the results of this procedure may be incorporated into a classification scheme.