Resiniferatoxin reduces cardiac sympathetic nerve activation to exert a cardioprotective effect during myocardial infarction

Background and objective: Myocardial infarction (MI) is a common critical disease of the cardiovascular system. The process of MI is often accompanied by the excessive activation of cardiac sympathetic nerves, which leads to arrhythmia. Resiniferatoxin (RTX) is a transient receptor potential vanilloid 1 (TRPV1), involved in the cardiac sympathetic afferent reflex. However, whether RTX can reduce the occurrence of arrhythmia and exert a cardioprotective effect by inhibiting the sympathetic reflex during MI is still unknown. Methods: The left anterior descending artery of cardiac was clamped to construct a model of MI. RTX (50 μg/ml) was used by epicardial application in MI rats. Ventricular electrophysiologic properties were continuously monitored by a body surface ECG. Yrosine hydroxylase (TH) and growth associated protein 43 (GAP43) were detected by Immunofluorescence staining. Connexin43 and transforming growth factor beta receptor 1 (TGF-β1) were detected by western blot. Norepinephrine (NE) and BNP levels in blood and tissue were determined by ELISA. Cardiac function was assessed by echocardiography. Results: The ERP, APD90, QRS, QT and the Tend-Tpeak intervals in MI rats were all prolonged, but decreased after RTX treatment (n = 3, P<0.05). In contrast, the RR interval was shortened in the MI group, but prolonged in the MI+RTX group (n = 3, P<0.05). RTX treatment significantly reduced ventricular arrhythmias after MI. TH- and GAP43-positive nerve densities and TGF-β1, and cx-43 protein expression were up-regulated in the MI group compared to the sham group, and they were decreased in the MI+RTX group compared to the MI group (n = 3, P<0.05). RTX can decrease serum and tissue NE and BNP levels (n = 3, P<0.05). RTX pretreatment significantly decreased heart rate, HW/BW ratio and LVIDS, and increased LVEF andLVFS values (n = 3, P<0.05). Conclusion: RTX improved cardiac dysfunction, ventricular electrophysiologic properties, and sympathetic nerve remodeling in rats with MI by inhibiting the excessive cardiac sympathetic drive.     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Demarcation of arteriopulmonary segments: a novel and effective method for the identification of pulmonary segments

ObjectiveEach pulmonary segment is an anatomical and functional unit. However, it is fundamentally difficult to precisely distinguish every pulmonary segment using the conventional pulmonary intersegmental planes from computed tomography images. Building arteriopulmonary segments is likely to be an effective way to identify pulmonary segments.MethodsThe thoracic computed tomography images of 40 patients were collected. The anatomic structures of interest were extracted in the transverse, sagittal, and coronal planes using the semi-automated segmentation tools provided by Amira software. The intrapulmonary vessels were subsequently segmented and reconstructed. The distributions of the pulmonary arteries, veins, and bronchi were observed. In patients with pulmonary masses, the mass was also reconstructed.ResultsThe three-dimensional reconstructed images showed the branches of the pulmonary artery ramified up to their eighth order covering the entire lung as well as evident intersegmental gaps without pulmonary arteries. The segmental artery was closely accompanied by the segmental bronchi in 486 pulmonary segments (90% of total number of segments). The size and spatial location of the pulmonary mass within a pulmonary segment were also clearly visible.ConclusionsDemarcation of arteriopulmonary segments can be used to precisely distinguish every pulmonary segment and provide its detailed anatomical structure before pulmonary segmentectomy.     

3-D Ultrasound Imaging Reliability of Measuring Dysplasia Metrics in Infants

Developmental dysplasia of the hip is a hip abnormality that ranges from mild acetabular dysplasia to irreducible femoral head dislocations. While 2-D B-mode ultrasound (US)-based dysplasia metrics or disease metrics are currently used clinically to diagnose developmental dysplasia of the hip, such estimates suffer from high inter-exam variability. In this work, we propose and evaluate 3-D US-derived dysplasia metrics that are automatically computed and demonstrate that these automatically derived dysplasia metrics are considerably more reproducible. The key features of our automatic method are (i) a random forest-based learning technique to remove regions across the coronal axis that do not contain bone structures necessary for dysplasia-metric extraction, thereby reducing outliers; (ii) a bone segmentation method that uses rotation-invariant and intensity-invariant filters, thus remaining robust to signal dropout and varying bone morphology; (iii) a novel slice-based learning and 3-D reconstruction strategy to estimate a probability map of the hypoechoic femoral head in the US volume; and (iv) formulae for calculating the 3-D US-derived dysplasia metrics. We validate our proposed method on real clinical data acquired from 40 infant hip examinations. Results show a considerable (around 70%) reduction in variability in two key 3-D US-derived dysplasia metrics compared with their 2-D counterparts.     

Aging attenuates the ovarian circadian rhythm

ObjectiveTo study the effect of aging on ovarian circadian rhythm.DesignHuman and animal study.SettingUniversity hospital and research laboratory.Patients/animalsHuman granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice.Intervention(s)None.Main outcome measure(s)Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice.Result(s)All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice.Conclusion(s)Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01943-y) contains supplementary material, which is available to authorized users.     

杜仲叶提取物所含四种主要成分体外抗非酒精性脂肪肝活性研究＊

目的 研究杜仲叶所含4种主要成分体外抗非酒精性脂肪肝（Non-alcoholic fatty liver disease，NAFLD）活性。方法 首先用UPLC-MS检测杜仲叶提取物中绿原酸、杜仲苷、京尼平苷酸、车叶草苷含量；以HepG2细胞为载体，建立NAFLD细胞模型，设正常组、模型组、绿原酸组、杜仲苷组、京尼平苷酸组、车叶草苷组；油红O染色检测细胞内脂质；微量法检测细胞内甘油三酯（Triglyceride，TG）、胆固醇（Total cholesterol，TC）、高密度脂蛋白（High-density lipoprotein cholesterol，HDL-C）、低密度脂蛋白（Low-density lipoprotein cholesterol，LDL-C）含量；微量法检测细胞培养液中谷草转氨酶（Aspartate aminotransferase，AST）、谷丙转氨酶（Alanine aminotransferase，ALT）含量。结果 杜仲叶提取物主要含绿原酸、杜仲苷、京尼平苷酸和车叶草苷，其中京尼平苷酸的含量最高；杜仲叶提取物所含四种主要成分可明显降低细胞内TG、TC、LDL-C含量，其中京尼平苷酸效果最为显著；绿原酸、杜仲苷，京尼平苷酸可显著降低细胞培养液中AST、ALT含量，其中京尼平苷酸效果最好。结论 杜仲叶提取物所含四种主要成分可不同程度降低HepG2细胞内脂质含量，其中京尼平苷酸效果较好。