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Parkinson’s disease (PD) is a complex disorder characterized by the impairment of the dopaminergic nigrostriatal system. PD has duplicated its global burden in the last few years, becoming the leading neurological disability worldwide. Therefore, there is an urgent need to develop innovative approaches that target multifactorial underlying causes to potentially prevent or limit disease progression. Accumulating evidence suggests that neuroinflammatory responses may play a pivotal role in the neurodegenerative processes that occur during the development of PD. Cortistatin is a neuropeptide that has shown potent anti-inflammatory and immunoregulatory effects in preclinical models of autoimmune and neuroinflammatory disorders. The goal of this study was to explore the therapeutic potential of cortistatin in a well-established preclinical mouse model of PD induced by acute exposure to the neurotoxin 1-methil-4-phenyl1-1,2,3,6-tetrahydropyridine (MPTP). We observed that treatment with cortistatin mitigated the MPTP-induced loss of dopaminergic neurons in the substantia nigra and their connections to the striatum. Consequently, cortistatin administration improved the locomotor activity of animals intoxicated with MPTP. In addition, cortistatin diminished the presence and activation of glial cells in the affected brain regions of MPTP-treated mice, reduced the production of immune mediators, and promoted the expression of neurotrophic factors in the striatum. In an in vitro model of PD, treatment with cortistatin also demonstrated a reduction in the cell death of dopaminergic neurons that were exposed to the neurotoxin. Taken together, these findings suggest that cortistatin could emerge as a promising new therapeutic agent that combines anti-inflammatory and neuroprotective properties to regulate the progression of PD at multiple levels.

Neurodegenerative disorders encompass a broad spectrum of profoundly disabling situations that impact millions of individuals globally. While their underlying causes and pathophysiology display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, is a common feature among them. Consequently, targeting the BBB has emerged as an innovative therapeutic strategy for addressing neurological disorders. Within this review, we not only explore the neuroprotective, neurotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will investigate the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological conditions like Alzheimer’s disease, Parkinson’s disease, and stroke, as well as immune-mediated diseases such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological contexts.

Este articulo presenta la implementación de un Prototipo para un Simulador Virtual con Inteligencia Artificial (IA) y Realidad Virtual (RV) que sea útil para presentar casos y se pueda implementar en la enseñanza-aprendizaje de Medios Alternos de Solución de Conflictos (MASC). El objetivo principal de esta técnica de prototipo de software es obtener un modelo funcional del sistema. Por lo tanto, permitirá al usuario tener una idea y enfoque de la aplicación. Además, de tener un mejor enfoque, se comprenderán y podrán refinar los requerimientos para disminuir los riesgos de estos. El modelo utilizado es Unified Modeling Language (UML), se eligió por ser un estándar en la industria de la Programación Orientada a Objetos, lo cual da mejores beneficios a nuestro proyecto. Cabe mencionar que al concluir el prototipo se ha encontrado que el proyecto es factible, novedoso y se puede experimentar con él y controlar los costos. En México, los MASC son un área del Derecho que encuentran su aplicabilidad en el área Penal, Civil, Familiar, Administrativa, Fiscal, Financiera, Deportiva, Escolar y Mercantil. La RV con el uso de la IA ha sido implementada con éxito para la enseñanza-aprendizaje en otras áreas como la Psicología, Ingeniería, Robótica, Física, Medicina (incluso Forense)., This paper presents the implementation of a Prototype for a Virtual Simulator with Artificial Intelligence (AI) and Virtual Reality (VR) that is useful to present cases and can be implemented in the teaching-learning of Alternative Dispute Resolution (ADR). The main objective of this software prototyping technique is to obtain a functional model of the system. Therefore, it will allow the user to have an idea and approach to the application. In addition, by having a better approach, the requirements will be understood and refined to reduce their risks. The model used is Unified Modeling Language (UML), it was chosen because it is a standard in the Object Oriented Programming industry, which gives better benefits to our project. It is worth mentioning that at the conclusion of our prototype it has been found that the project is feasible, innovative and can be experimented with it and costs can be controlled. In Mexico, ADR is an area of law that finds its applicability in the Criminal, Civil, Family, Administrative, Tax, Financial, Sports, School, or Commercial areas. VR with the use of AI has been successfully implemented for teaching-learning in other areas such as Psychology, Engineering, Robotics, Physics, Medicine (including Forensics), etc. where students can interact with real cases. Currently, the teacher in Law needs to improve and increase his knowledge to favor his educational practice using VR and its applicability in the educational process by means of Information and Communication Technologies or any other mechanical means., Este artigo apresenta a implementação de um Protótipo para um Simulador Virtual com Inteligência Artificial (IA) e Realidade Virtual (VR) que é útil para apresentar casos e pode ser implementado no ensino-aprendizagem da Resolução Alternativa de Disputas (ADR). O principal objetivo desta técnica de protótipo de software é a obtenção de um modelo funcional do sistema. Portanto, permitirá que o usuário tenha uma idéia e uma abordagem para a aplicação. Além disso, ao ter uma melhor abordagem, os requisitos serão compreendidos e refinados a fim de reduzir seus riscos. O modelo utilizado é a Unified Modeling Language (UML), foi escolhida por ser um padrão da indústria em Programação Orientada a Objetos, o que dá melhores benefícios ao nosso projeto. Vale mencionar que na conclusão do protótipo, o projeto foi considerado viável, inovador e pode ser experimentado e os custos podem ser controlados. No México, o ADR é uma área do direito que encontra sua aplicabilidade em direito penal, civil, familiar, administrativo, tributário, financeiro, esportivo, escolar e comercial. A RV com o uso da IA tem sido implementada com sucesso para o ensino-aprendizagem em outras áreas como Psicologia, Engenharia, Robótica, Física, Medicina (incluindo a Medicina Legal).

Neurodegenerative disorders encompass a broad spectrum of profoundly disabling situations that impact millions of individuals globally. While their underlying causes and pathophysiology display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, is a common feature among them. Consequently, targeting the BBB has emerged as an innovative therapeutic strategy for addressing neurological disorders. Within this review, we not only explore the neuroprotective, neurotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will investigate the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological conditions like Alzheimer’s disease, Parkinson’s disease, and stroke, as well as immune-mediated diseases such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological contexts.

Background and Purpose Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary fibrosis remain major causes of morbidity, mortality and healthcare burden in the critically ill patient. There is an urgent medical need for identifying factors of susceptibility and prognosis and for designing new therapeutic tools for treating these disorders. Here, we evaluate the capacity of the immunomodulatory neuropeptide cortistatin to regulate pulmonary inflammation and fibrosis in vivo. Experimental Approach ALI/ARDS and pulmonary fibrosis were induced experimentally in wild-type and cortistatin-deficient mice by pulmonary infusion of the bacterial endotoxin LPS or the chemotherapeutic drug bleomycin, and the histopathological signs, pulmonary leukocyte infiltration and cytokines and fibrotic markers were evaluated. Key Results Partially-deficient mice in cortistatin showed exacerbated pulmonary damage, pulmonary inflammation, alveolar oedema and fibrosis, and subsequent increased respiratory failure and mortality when challenged to LPS or bleomycin, even at low doses. Treatment with cortistatin reversed these aggravated phenotypes and protected from progression to severe ARDS and fibrosis after high-exposition to both injury agents. Moreover, cortistatin-deficient pulmonary macrophages and fibroblasts showed exaggerated ex vivo inflammatory and fibrotic responses, and treatment with cortistatin impaired their activation. Finally, the protective effects of cortistatin in ALI and pulmonary fibrosis were partially inhibited by specific antagonists for somatostatin- and ghrelin-receptors. Conclusion and Implications We identify to cortistatin as an endogenous break of pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of poor-prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin-based therapies emerge as attractive candidates to treat severe ALI/ARDS, including SARS-Cov-2-associated ARDS.