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Mesenchymal stem cell-and extracellular vesicle-based therapies for Alzheimer's disease:progress,advantages,and challenges

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Neural Regeneration Research 2023年第8期18卷 1645-1651页

作者： Renata Guedes de Jesus Gonçalves Juliana Ferreira Vasques Almir Jordão da Silva-Junior Fernanda Gubert rosalia mendez-otero Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa Rio de JaneiroBrazil Plataformas Inovadoras em Terapias Avançadas Departamento de Ciência e Tecnologia-Ministério da Saúde(DECIT-MS)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Brazil Programa Redes de Pesquisa em Saúde no Estado do Rio de Janeiro Rio de JaneiroBrazil Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Programa Redes de Pesquisa em Nanotecnologia no Estado do Rio de Janeiro Rio de JaneiroBrazil

Alzheimer's disease is a severe, highly disabling neurodegenerative disease, clinically characterized by a progressive decline in cognitive functions, and is the most common form of dementia in the elderly. For decades, the search for disease-modifying therapies has focused on the two main Alzheimer's disease histopathological hallmarks, seeking to prevent, mitigate, or clear the formation of extracellular aggregates of β-amyloid peptide and intracellular neurofibrillary tangles of tau protein, although without clinical success. Mesenchymal stem cell-based therapy has emerged as a promising alternative for the treatment of Alzheimer's disease, especially because it also targets other crucial players in the pathogenesis of the disease, such as neuroinflammation, synaptic dysfunction/loss, oxidative stress, and impaired neurogenesis. Herein, we review current knowledge of the therapeutic potential of mesenchymal stem cells and their extracellular vesicles for Alzheimer's disease, discussing the most recent findings in both preclinical and clinical trials as well as how advanced technologies have helped to overcome some limitations and contributed to stimulate the development of more effective treatments.

关键词： Alzheimer's disease amyloid-β cell therapy cell transplantation exosomes extracellular vesicles mesenchymal stem cell micro vesicles neuroinflammation tau protein

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Gangliosides in nervous system development,regeneration,and pathologies

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Neural Regeneration Research 2023年第1期18卷 81-86页

作者： Juliana F.Vasques Renata Guedes de Jesus Gonçalves Almir Jordão da Silva-Junior Robertta Silva Martins Fernanda Gubert rosalia mendez-otero Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Programa Redes de Pesquisa em Saúde no Estado do Rio de Janeiro Rio de JaneiroBrazil Programa Rede NanoSaúde do Estado do Rio de Janeiro Rio de JaneiroBrazil Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa Rio de JaneiroBrazil

Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal *** to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different *** of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous *** GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous *** in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological *** in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’*** this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.

关键词： 9acGD3 gangliosides GD1a GD1b GD3 glycolipids GM1 GM2 GM3 GM4 GT1b

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Comment on retinal ganglion cell electrical activity,mammalian target of rapamycin signaling and optic nerve regeneration

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Eye Science 2016年第4期31卷 225-229页

作者： Louise A.Mesentier-Louro rosalia mendez-otero Universidade Federal do Rio de Janeiro Instituto de Biofísica Carlos Chagas Filho

Lim and coworkers have recently described impressive results on optic nerve regeneration in *** their paper published on Nature Neuroscience(1),the authors found that increasing electrical activity of adult retinal ga... 详细信息

关键词：视网膜神经节细胞神经再生雷帕霉素哺乳动物电活动靶蛋白神经科学论文发表

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Major regulatory mechanisms involved in sperm motility

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Asian Journal of Andrology 2017年第1期19卷 5-14页

作者： Rute Pereira rosalia Sa Alberto Barros Mario Sousa Department of Microscopy Laboratory of Cell Biology Institute of Biomedical Sciences Abel Salazar University of Porto (ICBAS-UP) Rua Jorge Viterbo Ferreira 2284050-313 Porto Portugal and Multidisciplinary Unit for Biomedical Research-UMIB ICBAS-UP Centre for Reproductive Genetics Alberto Barros Av. do Bessa 2401° Dto. Frente 4100-012 Porto Portugal Department of Genetics Faculty of Medicine University of Porto. Alameda Prof. Hernani Monteiro 4200-319 Porto Portugal and Institute of Health Research an Innovation (13S) University of Porto Portugal.

The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.

关键词： antioxidants calcium membrane channels protein kinases sperm genetic abnormalities sperm motility

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Splenic lymphangiomatosis showing rapid growth during lactation:A case report

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World Journal of Gastroenterology 2010年第9期16卷 1155-1157页

作者： rosalia Patti Emilio Iannitto Gaetano Di Vita General Surgery Unit Department of Surgical and Oncological SciencesUniversity of Palermo Haematological Division University of Palermo

Splenic lymphangiomatosis is a very rare condition that,from 1990 to date,has been described only nine *** the present report,we describe the first case of splenic lymphangiomatosis with rapid growth during lactation in a 35-year-old *** also underline the difficultly in making an accurate preoperative diagnosis,despite more modern imaging *** splenectomy was considered to be the treatment needed,both to make a definitive diagnosis and to exclude the presence of malignancy.

关键词： Lymphangiomatosis Spleen Lactation

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Optimization of the Outbound Logistic Flow of Bottled Water for Agua Planeta Azul

Optimization of the Outbound Logistic Flow of Bottled Water ...

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作者： rosalia Cabrera 东北大学

学位级别：硕士

物流系统无处不在,我们日常生活中经常出现的许多地方都是物流系统,从简单的系统到更复杂的系统。一个简单明了的例子就是餐馆。当你去餐馆时,服务员(运输渠道)会将食物从厨房(商店设施)带到你的餐桌(交付点)。所有这些在餐馆中进餐的... 详细信息

物流系统无处不在,我们日常生活中经常出现的许多地方都是物流系统,从简单的系统到更复杂的系统。一个简单明了的例子就是餐馆。当你去餐馆时,服务员(运输渠道)会将食物从厨房(商店设施)带到你的餐桌(交付点)。所有这些在餐馆中进餐的必要事件都与物流有着直接而密切的关系。Shapiro R.D评论说,“人类活动的几个方面最终并不取决于从起源点到消费点的货物流动”(Shapiro R.D.和 Heskett J.L.(1985)。根据供应链管理专业委员会的说法,物流管理负责有效地规划,实施和控制原产地和目的地之间的货物,服务或信息的所有方面,以满足客户的要求。从这个意义上说,它可以被视为一个综合功能,有助于在公司之间开发营销,财务,信息技术,会计和其他活动。根据这一定义,可以说任何需要移动货物,服务或信息的企业都应该将物流管理纳入其公司。鉴于其性质,物流通常仅被视为将货物从一个点移动到另一个点的方式,对于许多(通常是小公司)而言,物流管理并未考虑在内。Roberto Carro撰写的这本书评论说,从组织的角度来看,物流任务可以通过两种方式来考虑:一种是将产品放入市场的简单方法,或者是设计得很好的一部分业务。并计划,可以提供充足的竞争优势。对于多米尼加共和国的纯净水行业来说,纯净水是首要必需品,意味着顾客不愿意等待它。瓶装水需要在正确的地点,时间,客户和预期的条件下交付。据估计,25%的多米尼加人消费瓶装水和76.4%的顾客不愿意等待他们的偏好品牌无法获得(国家统计局,ONE,其缩写为西班牙语)这意味着纯化水行业物流不仅与客户满意度密切相关,而且与销售密切相关。Agua Planeta Azul是一家位于多米尼加共和国的公司,是纯净水和瓶装水行业的领导者。他们的瓶装水有七种不同的展示方式,分布在超市,便利店和其他商店。Planeta Azul因其高质量标准而受到国家健康基金会(NHF)和国际瓶装水协会(IBWA)的认可。公司,特别是像Agua Planeta Azul这样的市场领导者,应该一直在寻找新的方法来创新他们的流程。停止创新的公司注定要失败。与物流相关的活动往往会产生高成本,因此会降低公司的竞争力。在这方面,对于像Agua Planeta Azul这样的公司,其中一个流程是将其最终产品(瓶装水)运输到不同的交付点,拥有精心设计和规划的物流系统,以及正确的测量参数。保证流程的效率是其继续作为企业发展的关键部分.多米尼加共和国作为任何发展中国家仍然面临着工业,教育和卫生部门的许多挑战。多米尼加共和国的瓶装水是不是所有人都能负担的必需品,根据多米尼加国家饮用水和污水研究所的统计,只有25%的人口消费瓶装水,这意味着75%的人口无法负担负担得起,并且必须诉诸其他净化水的方法。由于无法杀死100%的现有细菌,这些方法通常效率低下,这是多米尼加共和国日益增加的胃肠道疾病的主要原因之一。使用与出境物流相关的方法,目前的工作目标是更好地了解多米尼加共和国的物流,通过分析和比较其发展和当前趋势与发达国家当前的物流发展和趋势。为了实现这一目标,将使用出站物流流程优化工具(如关键绩效指标和最佳路径理论)详细分析多米尼加市场领导者Agua Planeta Azul的瓶装水配送出境物流系统。所提到的工具将用于提供可以优化公司的出站物流过程的合适建议,并且这有助于公司降低与出站物流操作管理不善相关的高成本。在本节中,将首先从全球的角度解释所选主题的当前状态,解释其在发达国家的趋势,这些国家是出站物流中更先进的,然后是公司所在地。在多米尼加共和国。虽然如前所述,大多数活动都依赖于后勤,但这个领域并没有得到应有的重视。从历史上看,组织将所有精力投入到制作产品中,并且很少考虑相关的材料运动。1950年以前,物流的概念仅限于军事领域。直到两次世界大战,物流开始变得重要。事实上,第二次世界大战期间开发的许多后勤原则至今仍在使用。这些原则具有坚实的基础,因为对于企业而言,物流很重要,但对于军队来说,这是生死之别。在1950年之前,企业将生产和销售领域作为增加利润和客户满意度的唯一途径。1950年以后,由于第二次世界大战后发生的经济衰退,公司开始对物流产生兴趣,这种经济衰退迫使企业开始寻找降低工艺成本的创新方法。如今,物流越来越多地与公司内部的不同区域整合,被视为达到客户满意度的基本要素,现在比低产品成本更重要。物流专业人员现在被认为是公司面向客户的一部分,并被要求为他们的客户增加价值。改善客户服务是当前物流的主要趋势之一,公司致力于缩短交货时间(订购材料和使用材料之间的总时间),这一因素可以减少铅时间是物流过程中技术的实施。由于受技术革命影响的绝大多数领域,物流也受益于技术的整合,这主要是因为通信技术的进步使得供应链中的所有部分在每个阶段都能保持沟通和联系。每个过程,由于

关键词：企业集团境外物流流程优化关键绩效指标

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Three-year follow-up in advanced pediatric keratoconus:thin corneas may not have pachymetry properly assessed after crosslinking

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International Journal of Ophthalmology(English edition) 2020年第10期13卷 1561-1566页

作者： rosalia Antunes-Foschini Sidney Júlio Faria-e-Sousa Hospital das Clínicas Medical School of Ribeirao PretoUniversity of Sao PauloRibeirao Preto 14049-900Brazil Department of Ophthalmology OtorhinolaryngologyHead and Neck SurgeryMedical School of Ribeirao PretoUniversity of Sao PauloRibeirao Preto 14049-900Brazil

AIM:To analyze the crosslinking(CXL)effects in pediatric keratoconus,and to identify the patients’corneal characteristics whose pachymetry could not be adequately evaluated by Scheimpflug method after ***:Consecutive pediatric patients with progressive keratoconus underwent CXL were ***-corrected visual acuity(BCVA)and spheric equivalent(SE)were measured before and after *** CXL,groups 1 and 2 were divided based on the posterior surface Pentacam quality specifications(QS):"OK"(Group 1)and"not OK"(Group 2).The mean(RmF and RmB)and minimum(RminF and RminB)radius of curvatures of the anterior and posterior corneal surfaces,and the thinnest pachymetry(Pmin)were measured preoperatively at 3,6,12,24,and 36 *** was ***:Twenty-six patients(14 men,mean age 14±1.8 y)and median Kmax of 59.9 D initially and 61.4 D preoperatively were *** was not different before and 24 mo after *** 2 statistically differed to group 1 in that SE was more myopic before and with no difference 24 mo after CXL;RmF and RmB were steeper and Pmin was thinner *** 2,in which pachymetric changes could not be adequately evaluated after surgery,presented with significant RmF flattening,a shift to hyperopia,and more haze after ***:Patients whose pachymetry could not be adequately evaluated after CXL had steeper and thinner corneas before *** predictive factors for impaired QS after CXL are RmF,RmB,and *** advanced keratoconus,alternative methods to analyze pachymetry and the posterior surface should be considered.

关键词： keratoconus cross-linking corneal pachymetry corneal topography corneal opacity

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Complex Systems Theory: Some Considerations for Sociology

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Open Journal of Applied Sciences 2016年第7期6卷 422-448页

作者： rosalia Condorelli Department of Political and Social Sciences Catania University Via Vittorio Emanuele II 8 Catania Italy

This essay presents a reflection on the main implications of Complexity Theory for science in general, redefining and dispelling myths of traditional science, and Sociology in particular, suggesting a redefinition of Parsons’ classic concept of Social System, articulated around the property of self-maintenance of order rather than on its possible discontinuity and instability. It argues that Complexity Theory has established the limits of Classic Science, leading to a more realistic awareness of working and evolution mechanisms of Natural and Social Systems and showing the limits of our capacity to predict and control events. Dissipative structures have shown the creative role of time. Instability, emergence, surprise, unpredictability are the rule rather than the exception when systems move away from equilibrium (entropy), even if these processes are generated from a system’s deterministic working mechanisms. Therefore, we have come to realize how constructive the contribution of Complexity is, in regards to the long lasting problem of the relationship between order and disorder. Today, the terms of this relationship have been re-specified in its new configuration of inter-relationship link, according to a unicum which finds its synthesis in self-organization and deterministic chaos concepts. From this perspective, as Prigogine suggested, studies on Complex Systems are heading toward a historical, biological conception of Physics, and a new alliance between natural systems and living, social systems. Non-linearity, far from equilibrium self-organization, emergence and surprise meet at all levels, as this paper attempts to highlight. In Sociology, insights of Complexity Theory have contributed to a new way of thinking about social systems, by re-addressing some fundamental issues starting to social system, emergence and change concepts. The current social system conception as complex dynamical systems is supported by a profitable use of non-liner models (in particul

关键词： Complexity Theory Complex Adaptive and Autopoietic Systems Self-Organization Emergence Surprise Complex Social Systems Complexity Theory in Sociology

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Double-difference tomography of P- and S-wave velocity structure beneath the western part of Java, Indonesia

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Earthquake Science 2019年第1期32卷 12-25页

作者： Shindy rosalia Sri Widiyantoro Andri Dian Nugraha Pepen Supendi Faculty of Mining and Petroleum Engineerings Institute of Technology Bandung^Bandung 40132 Indonesia MeteorologicalClimatological and Geophysical Agency(BMKG)Bandung 40161Indonesia

West Java in the western part of the Sunda Arc has a relatively high seismicity due to subduction activity and *** this study,double-difference tomography was used to obtain the 3D velocity tomograms of P and S waves beneath the western part of *** infer the geometry of the structure beneath the study area,precise earthquake hypo・center determination was first performed before tomographic *** this,earthquake waveform data were extracted from the regional Meteorological,Climatological,Geophysical Agency(BMKG)network of Indonesia from South Sumatra to Central *** P and S arrival times for about 1,000 events in the period April 2009 to July 2016 were selected,the key features being events of magnitude>3,azimuthal gap8.A nonlinear method using the oct-tree sampling algorithm from the NonLinLoc program was employed to determine the earthquake *** hypocenter locations were then relocated using double-difference tomography(tomoDD).A significant reduction of travel-time(root mean square basis)and a better clustering of earthquakes were achieved which correlated well with the geological structure in West ***-difference tomography was found to give a clear velocity structure,especially beneath the volcanic arc area,i.e.,under Mt Anak Krakatau,Mt Salak and the mountains complex in the southern part of West *** velocity anomalies for the P and S waves as well as the vp/vs ratio below the volcanoes indicated possible partial melting of the upper mantle which ascended from the subducted slab beneath the volcanic arc.

关键词： West Java P-and S-wave velocity structures double-difference tomography

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Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells:Potential implications for their clinical use

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World Journal of Stem Cells 2023年第5期15卷 400-420页

作者： Vitale Miceli Giovanni Zito Matteo Bulati Alessia Gallo rosalia Busà Gioacchin Iannolo Pier Giulio Conaldi Department of Research IRCCS ISMETT(Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione)Palermo 90127Italy

Mesenchymal stromal/stem cells(MSCs)have shown significant therapeutic potential,and have therefore been extensively investigated in preclinical studies of regenerative ***,while MSCs have been shown to be safe as a cellular treatment,they have usually been therapeutically ineffective in human *** fact,in many clinical trials it has been shown that MSCs have moderate or poor *** inefficacy appears to be ascribable primarily to the heterogeneity of ***,specific priming strategies have been used to improve the therapeutic properties of *** this review,we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of *** found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological ***,while hypoxic priming can be used primarily for the treatment of acute diseases,inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related *** shift in approach from regeneration to inflammation implies,in MSCs,a shift in the production of functional factors that stimulate regenerative or anti-inflammatory *** opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.

关键词： Mesenchymal stromal/stem cells Mesenchymal stromal/stem cell therapeutic properties Mesenchymal stromal/stem cell paracrine effects Mesenchymal stromal/stem cell priming Pro-inflammatory priming Hypoxic priming,3D culture priming

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