S100A6经RAGE介导影响肥胖儿童血管内皮损伤的机制研究

目的 探讨钙结合蛋白A6(S100A6)经终末糖基化产物受体(RAGE)介导影响肥胖儿童血管内皮损伤的机制,为进一步提出有针对性的治疗方案提供依据。方法 选取十堰市妇幼保健院2015年7月-2018年7月收治的肥胖患儿91例,根据患儿是否存在血管内皮损伤分成损伤组(n=43)、无损伤组(n=48)。选取同期于本院体检的健康体检儿童45例作为对照组。三组受检者均于入院当日采血检测血清S100A6与游离RAGE(sRAGE)水平,并测定三组血管内皮损伤标志物,包括血管内皮黏附分子-1(sVCAM-1)、可溶性细胞黏附分子-1(sICAN-1)、血管性血友病因子(vWF)水平,检测方法为酶联免疫吸附法。经Pearson线性相关分析S100A6、sRAGE与血管内皮损伤标志物间的相关性。结果 损伤组血清S100A6、sRAGE水平高于无损伤组、对照组,差异有统计学意义(P<0.05)。损伤组血清sVCAM-1、vWF、sICAN-1水平高于无损伤组、对照组,差异有统计学意义(P<0.05)。经Pearson线性相关分析提示S100A6、sRAGE与sVCAM-1、vWF、sICAN-1均呈正相关(P<0.05)。结论 与正常儿童及无血管内皮损伤的肥胖儿童相比,有血管内皮损伤的肥胖儿童血清S100A6、sRAGE明显上调,这可能与sRAGE增高导致S100A6上调,而进一步致sVCAM-1、vWF、sICAN-1水平增高有关。     

Testing the nutritional relevance of food‐based dietary guidelines with mathematical optimisation of individual diets

Mathematical optimisation of diets is generally used to translate nutrient‐based recommendations into healthy food choices but can also be used to assess the possible impact of food‐based dietary guidelines (FBDG) on nutrient intakes. Optimisation of individual diets, which allows individual variability of food consumption to be taken into account, generates more robust results and more realistic diets than population diet optimisation. It was used to simulate the impact on nutrient intakes of complying with the new French FBDGs. For each observed diet of adults in the French INCA2 survey, a new isoenergetic diet was designed to meet all food consumption frequencies recommended by the new French FBDGs, as interpreted by the constraints included in a model called DP2. Because the dairy food group is the only one whose guideline has been reduced (from 3 to 2 portions/day) compared to the previous FBDGs, an alternative model, called DP3, imposing 3 daily portions of dairy products instead of 2 was also tested. Diets optimised with the DP2 model had lower energy density and higher nutrient density than the observed diets, and inadequate intakes decreased for most vitamins and minerals. With the alternative DP3 model, the decrease in saturates was less pronounced than with 2 portions/day of dairy products (13.8%, 11.9% and 12.8% energy in observed diets and in DP2 and DP3, respectively), but calcium adequacy was improved instead of being worsened (51%, 58% and 16% of inadequacy in observed diets and in diets modelled with 2 portions/day and 3 portions/day of dairy products, respectively). Individual diet optimisation is a powerful tool for assessing the nutritional relevance of existing FBDGs and to test possible alternatives.     

BrainAGE and regional volumetric analysis of a Buddhist monk: a longitudinal MRI case study

ABSTRACT

Yongey Mingyur Rinpoche (YMR) is a Tibetan Buddhist monk, and renowned meditation practitioner and teacher who has spent an extraordinary number of hours of his life meditating. The brain-aging profile of this expert meditator in comparison to a control population was examined using a machine learning framework, which estimates “brain-age” from brain imaging. YMR’s brain-aging rate appeared slower than that of controls suggesting early maturation and delayed aging. At 41 years, his brain resembled that of a 33-year-old. Specific regional changes did not differentiate YMR from controls, suggesting that the brain-aging differences may arise from coordinated changes spread throughout the gray matter.     

Biocompatibility and Bioactive Potential of New Calcium Silicate–based Endodontic Sealers: Bio-C Sealer and Sealer Plus BC

IntroductionBio-C Sealer (BC; Angelus, Londrina, PR, Brazil) and Sealer Plus BC (SPBC; MK Life, Porto Alegre, Brazil) are new ready-to-use bioceramic endodontic sealers. The aim of this study was to evaluate the biocompatibility and bioactive potential of BC and SPBC sealers in comparison with AH Plus (AHP; Dentsply DeTrey Gmbh, Konstanz, Germany) in subcutaneous tissue of rats.MethodsPolyethylene tubes filled with materials and empty tubes, serving as the control group, were implanted in the subcutaneous tissues of rats. After 7, 15, 30, and 60 days, the tubes with connective tissue were removed, and inflammatory cells (ICs)/mm² and immunolabeled cells for interleukin (IL)-6 were evaluated. Osteocalcin and von Kossa analysis were also performed. Data were submitted to analysis of variance and Tukey tests, with a significance level of 5%.ResultsAt 7 days, SPBC showed lower ICs than BC (P < .05). AHP exhibited greater immunolabeled cells for IL-6 (P < .05). After 15 days, BC showed lower ICs and IL-6 compared with other materials. At 30 days, SPBC and AHP showed higher values for ICs (P < .05). After 60 days, calcium silicate sealers did not show statistical difference (P > .05) for ICs and IL-6, with values lower than AHP (P < .05). The materials showed positive structures to von Kossa staining. BC exhibited osteocalcin labeling in all periods. SPBC showed osteocalcin labeling from 15–60 days. AHP and the control group did not exhibit osteocalcin labeling.ConclusionsBC and SPBC sealers are biocompatible and present bioactive potential.     

Slow-decaying presynaptic calcium dynamics gate long-lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse

Action potentials trigger two modes of neurotransmitter release, with a fast synchronous component and a temporally delayed asynchronous release. Asynchronous release contributes to information transfer at synapses, including at the hippocampal mossy fiber (MF) to CA3 pyramidal cell synapse where it controls the timing of postsynaptic CA3 pyramidal neuron firing. Here, we identified and characterized the main determinants of asynchronous release at the MF–CA3 synapse. We found that asynchronous release at MF–CA3 synapses can last on the order of seconds following repetitive MF stimulation. Elevating the stimulation frequency or the external Ca²⁺ concentration increased the rate of asynchronous release, thus, arguing that presynaptic Ca²⁺ dynamics is the major determinant of asynchronous release rate. Direct MF bouton Ca²⁺ imaging revealed slow Ca²⁺ decay kinetics of action potential (AP) burst-evoked Ca²⁺ transients. Finally, we observed that asynchronous release was preferentially mediated by Ca²⁺ influx through P/Q-type voltage-gated Ca²⁺ channels, while the contribution of N-type VGCCs was limited. Overall, our results uncover the determinants of long-lasting asynchronous release from MF terminals and suggest that asynchronous release could influence CA3 pyramidal cell firing up to seconds following termination of granule cell bursting.     

Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases

Introduction: Mitochondrial-derived peptides (MDPs) are encoded within the mitochondrial genome. They signal within the cell or are released to act as autocrine/paracrine/endocrine cytoprotective factors playing a key role in the cellular stress response. The first reported and better characterized MDP is humanin (HN), which exerts robust protective effects against a myriad of cytotoxic stimuli in many cell types. These effects have led to the evaluation of HN and its analogs as therapeutic targets for several chronic diseases.

Areas covered: We describe the latest findings on the mechanism of action of HN and discuss the role of HN as therapeutic target for neurodegenerative and cardiovascular diseases, diabetes, male infertility, and cancer. Since HN can be detected in circulation, we also depict its value as a biomarker for these diseases.

Expert opinion: HN analogs and peptide mimetics have been developed over the last decade and show promising results in preclinical models of degenerative diseases. Local administration of gene therapy vectors that overexpress or silence endogenous HN could also hold therapeutic potential. Controversy on the role of HN in cancer progression and chemoresistance should be addressed before the translation of these therapeutic approaches.