Influences of simulated gastrointestinal environment on physicochemical properties of gold nanoparticles and their implications on intestinal epithelial permeability

Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H₂O₂. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.     

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.     

Cellular mechanisms of hereditary photoreceptor degeneration – Focus on cGMP

The cellular mechanisms underlying hereditary photoreceptor degeneration are still poorly understood, a problem that is exacerbated by the enormous genetic heterogeneity of this disease group. However, the last decade has yielded a wealth of new knowledge on degenerative pathways and their diversity. Notably, a central role of cGMP-signalling has surfaced for photoreceptor cell death triggered by a subset of disease-causing mutations.In this review, we examine key aspects relevant for photoreceptor degeneration of hereditary origin. The topics covered include energy metabolism, epigenetics, protein quality control, as well as cGMP- and Ca²⁺-signalling, and how the related molecular and metabolic processes may trigger photoreceptor demise. We compare and integrate evidence on different cell death mechanisms that have been associated with photoreceptor degeneration, including apoptosis, necrosis, necroptosis, and PARthanatos. A special focus is then put on the mechanisms of cGMP-dependent cell death and how exceedingly high photoreceptor cGMP levels may cause activation of Ca²⁺-dependent calpain-type proteases, histone deacetylases and poly-ADP-ribose polymerase. An evaluation of the available literature reveals that a large group of patients suffering from hereditary photoreceptor degeneration carry mutations that are likely to trigger cGMP-dependent cell death, making this pathway a prime target for future therapy development.Finally, an outlook is given into technological and methodological developments that will with time likely contribute to a comprehensive overview over the entire metabolic complexity of photoreceptor cell death. Building on such developments, new imaging technology and novel biomarkers may be used to develop clinical test strategies, that fully consider the genetic heterogeneity of hereditary retinal degenerations, in order to facilitate clinical testing of novel treatment approaches.     

Cell integrity indicators assessed by bioelectrical impedance: A systematic review of studies involving athletes

IntroductionBioelectrical impedance analysis (BIA) has been used to evaluate cellular health and integrity through bioelectrical indicators. In the sporting context, monitoring these indicators can be useful to assess the quality and vitality of cells and body tissues.ObjectiveThe aim of this systematic review was to investigate indicators of cellular health and integrity evaluated by BIA in athletes.MethodsSearches were performed in December 2017 in the Lilacs, Medline, PubMed, Science Direct, Scielo, Scopus, SPORTDiscus, and Web of Science databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsThe searches retrieved 31 articles (30 involving professional athletes and one involving university athletes). In longitudinal studies (n = 15), the bioelectrical parameters directly associated with cellular health and integrity were extracellular water (ECW), phase angle (PA), BIA vector analysis (BIVA), crude reactance data (Xc), resistance (R), and ECW/BCM ratio. Regarding the findings of cross-sectional studies (n = 16), the investigated parameters (ECW, PA, BIVA, Z, BCM, and ECW/BCM) were directly associated with gender, age, sports performance level, modality, and game position.ConclusionsIn the included studies, the cellular health and integrity indicators were: Z, Xc, R, total water, intracellular water, ECW, PA, BIVA, BCM, and ECW/BCM.     

使用棱镜重新定位双侧中心暗点患者视网膜物像的预试验

目的 本研究使用激光扫描检眼镜(SLO)评价双侧中央暗点患者使用棱镜后的眼球运动反应.方法 本预试验共招募6例有双侧中央暗点的年龄相关性黄斑变性(AMD)患者以及6例正常视力的志愿者.首先用Nidek MP-1微视野仪确认患者的中央暗点和优选视网膜注视点(PRL),然后用Rodenstock SLO,在将视标投射在优选视网膜注视点时拍下实时视网膜像,接着在受检者眼前加入6～8 PD的棱镜,要求受检者保持注视视标,这时通过视网膜标记来测量视网膜像的移位量,以及随后发生的优选视网膜注视点的再次注视.过程中平均移位量和再次注视时间通过图像软件(ImageJ software)来计算.结果 实验组再次注视时的移位量在3个像素点或11.66个弧分之内(x轴:2.90±3.92,y轴:2.53±4.18).对照组再次注视时的移位会准确些(x轴:0.33±1.15,y轴:0.89±2.50),但与实验组差异无统计学意义(tx=1.32,Px＞0.05;ty=0.80,Py＞0.05).对照组再次注视时间(0.98±0.19)s较实验组(2.83±1.63)s要短,差距有统计学意义(t=5.03,P＜0.01).其中有1例实验组受检者没有发生再次注视,其结果被排除并单独分析.结论 研究发现,双眼中央暗点患者对棱镜物像转移后的再注视反应与正常人接近,但实验组再注视明显较对照组慢,并有1例受检者没有发生再注视.该数据说明双侧中央暗点患者无论眼前有没有棱镜,都会利用相同的视网膜位置视物,因此,通过棱镜物像再定位的意义不大.     

电子线照射对小鼠胰岛素生长因子相关蛋白表达的影响

目的：探讨电子线对胰岛素生长因子-1家族蛋白表达的影响，为研究辐射对肝脏的早期损伤提供依据。方法：采用电子线照射小鼠，照射剂量为1、2、4 Gy，用Western blot法检测照射后12、48和72 h小鼠肝脏中胰岛素生长因子1受体（IGF-1R）、胰岛素生长因子结合蛋白1（IGFBP1）、胰岛素生长因子结合蛋白4（IGFBP4）和胰岛素生长因子1（IGF-1）蛋白表达水平的改变。结果：照射剂量为1 Gy时，与对照组相比，IGF-1蛋白在照射后48 h时表达增加，IGFBP1、IGFBP4和IGF1R蛋白的表达在照射后12、48和72 h均表达减少。照射剂量为2 Gy时，IGF-1和IGFBP4蛋白在照射后48 h时表达增加，其余时间点表达减少。IGFBP1蛋白在照射后12 h时表达增加，48和72 h时表达减少。IGF1R蛋白在照射后3个时间点均呈现为表达减少。照射剂量4 Gy时，肝脏中IGF-1、IGFBP1和IGFBP4蛋白均表达减少，IGF1R蛋白在照射后12 h时表达增加，48、72 h时均表达减少（均为P < 0.05）。结论：电子线照射后小鼠肝脏中胰岛素生长因子-1家族蛋白多以下调表达为主，与前期基因表达的结果相一致，有可能作为反映放射性工作人员早期肝脏损伤的生物标志物之一。