- 作者列表："Zohar Y
:Driven by the broad diversity of species and physiologies and by reproduction-related bottlenecks in aquaculture, the field of fish reproductive biology has rapidly grown over the last five decades. This review provides my perspective on the field during this period, integrating fundamental and applied developments and milestones. Our basic understanding of the brain-pituitary-gonadal axis led to overcoming the failure of farmed fish to ovulate and spawn in captivity, allowing us to close the fish life cycle and establish a predictable, year-round production of eggs. Dissecting the molecular and hormonal mechanisms associated with sex determination and differentiation drove technologies for producing better performing mono-sex and reproductively-sterile fish. The growing contingent of passionate fish biologists, together with the availability of innovative platforms such as transgenesis and gene editing, as well as new models such as the zebrafish and medaka, have generated many discoveries, also leading to new insights of reproductive biology in higher vertebrates including humans. Consequently, fish have now been widely accepted as vertebrate reproductive models. Perhaps the best testament of the progress in our discipline is demonstrated at the International Symposia on Reproductive Physiology of Fish (ISRPF), at which our scientific family has convened every four years since the grandfather of the field, the late Ronald Billard, organized the inaugural 1977 meeting in Paimpont, France. As the one person who has been fortunate enough to attend all of these meetings since their inception, I have witnessed first-hand the astounding evolution of our field as we capitalized on the molecular and biotechnological revolutions in the life sciences, which enabled us to provide a higher resolution of fish reproductive and endocrine processes, answer more questions, and dive into deeper comprehension. Undoubtedly, the next (five) decades will be similarly exciting as we continue to integrate physiology with genomics, basic and translational research, and the small fish models with the aquacultured species.
: 在物种和生理的广泛多样性以及水产养殖中与繁殖相关的瓶颈的推动下，鱼类繁殖生物学领域在过去五十年中迅速发展。这次审查提供了我在此期间对该领域的看法，整合了基础和应用的发展和里程碑。我们对脑-垂体-性腺轴的基本认识，使我们克服了养殖鱼类在圈养中排卵和产卵的失败，使我们能够关闭鱼类的生命周期，并建立一个可预测的，全年生产的鸡蛋。解剖与性别决定和分化相关的分子和激素机制推动了生产更好的单性和生殖不育鱼的技术。越来越多的充满激情的鱼类生物学家，加上转基因和基因编辑等创新平台的可用性，以及斑马鱼和medaka等新模型，已经产生了许多发现，也带来了包括人类在内的高等脊椎动物生殖生物学的新见解。因此，鱼类现在已被广泛接受为脊椎动物生殖模型。也许我们学科进展的最好证明是在鱼类生殖生理学国际研讨会 (ISRPF) 上展示的，自该领域的祖父已故的罗纳德·比拉德在法国皮蒙特组织了1977首届会议以来，我们的科学家族每四年召开一次会议。作为一个有幸参加所有这些会议的人，我亲眼目睹了我们领域惊人的发展，我们利用了生命科学中的分子和生物技术革命，这使我们能够为鱼类生殖和内分泌过程提供更高的分辨率，回答更多的问题，并深入理解。毫无疑问，接下来的 (五十) 十年将同样令人兴奋，因为我们继续将生理学与基因组学、基础和转化研究以及小鱼模型与水产养殖物种相结合。
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.