A Safety Study of the Effects of 2-Dimensional Shear Wave Elastography on Synaptic Morphologic Characteristics and Function in the Hippocampus of Neonatal Mice.
- 作者列表："Zhang C","Li N","Li C","Li J
OBJECTIVES:The aim of this study was to determine the effects of 2-dimensional (2D) shear wave elastography (SWE) on synaptic morphologic characteristics and function in the neonatal mouse hippocampus and whether it affects the capacity for learning and memory later in life. METHODS:We divided neonatal mice into a control group and a 2D SWE group scanned for 10, 20, or 30 minutes. Hippocampal morphologic characteristics were assessed by hematoxylin-eosin and Nissl staining. Ultrastructures of hippocampal neurons were visualized by electron microscopy. Protein and messenger RNA expression levels of synaptophysin, N-methyl-d-aspartate receptor 1 (NMDAR1), NMDAR2A, and NMDAR2B were quantified by a western blot and polymerase chain reaction, respectively. Learning and memory of adult mice were evaluated by the Morris water maze and the novel object recognition task. RESULTS:Compared with the control group, the hippocampal morphologic characteristics of the experimental groups did not differ under light microscopy, and the synaptic structures assessed by electron microscopy appeared normal. Western blot and polymerase chain reaction results showed that expression of synaptophysin, NMDAR1, NMDAR2A, and NMDAR2B were downregulated after exposure to 2D SWE, but there were no statistical differences between the experimental groups. This downregulation disappeared within 24 hours. The results of the Morris water maze and novel object recognition suggested that the 2D SWE scanning on neonatal mice had no effect on learning and memory in adulthood. CONCLUSIONS:This study demonstrated that when the mice were exposed to neonatal cranial ultrasound by 2D SWE lasting for longer than 10 minutes, the expression of genes involved in synaptic function was affected, but this effect lasted no longer than 24 hours and did not affect learning and memory in adulthood.
目的: 本研究的目的是确定二维 (2D) 剪切波弹性成像 (SWE) 对新生小鼠海马突触形态特征和功能的影响，以及它是否影响以后的学习和记忆能力。 方法: 我们将新生小鼠分为对照组和2D SWE组，扫描10、20或30分钟。通过苏木精-伊红和尼氏染色评估海马形态特征。通过电子显微镜观察海马神经元的超微结构。通过蛋白质印迹和聚合酶链反应分别定量突触素、N-甲基-d-天冬氨酸受体1 (NMDAR1) 、NMDAR2A和NMDAR2B的蛋白质和信使RNA表达水平。通过Morris水迷宫和新物体识别任务评价成年小鼠的学习和记忆。 结果: 与对照组相比，光镜下实验组大鼠海马形态特征无差异，电镜下突触结构表现正常。Western blot和聚合酶链反应结果显示，暴露于2D SWE后，突触素、NMDAR1、NMDAR2A和NMDAR2B的表达下调，但各实验组之间无统计学差异。这种下调在24小时内消失。Morris水迷宫和新物体识别结果表明，新生小鼠2D SWE扫描对成年后学习记忆无影响。 结论: 本研究表明，当小鼠暴露于新生儿颅脑超声持续超过10分钟时，突触功能相关基因的表达受到影响，但这种影响持续时间不超过24小时，并且不影响成年后的学习和记忆。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.