1,720,965 research outputs found
¿Qué otras acciones sobre vías celulares y mitocondriales contribuyen a la protección tisular de los iSGLT2? Datos experimentales e información clínica en distintos órganos
No full textLos efectos pleiotrópicos de los iSGLT2 sobre las distintas vías de señalización celular y mitocondriales en diferentes órganos y tejidos se evidencian en estudios de metabolómica, y estos podrían acompañarse de cambios epigenéticos que requieren aún mayor evidencia. Conceptualmente, se destaca que –sumados a los efectos protectores descriptos en otras secciones– los iSLGT2 actuarían en distintos órganos blanco previniendo su lesión a través de la mejora en el balance entre el consumo de oxígeno y la energía producida. Los efectos a nivel mitocondrial, el menor estrés oxidativo así como la protección celular resultan determinantes clave de esta estrategia.Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ferder, Leon Fernando. Universidad de Maimónides; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Choi, Marcelo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; Argentin
Epigenetic Mechanisms Involved in Inflammaging-Associated Hypertension
No full textPurpose of Review: This review summarizes the involvement of inflammaging in vascular damage with focus on the epigenetic mechanisms by which inflammaging-induced hypertension is triggered. Recent Findings: Inflammaging in hypertension is a complex condition associated with the production of inflammatory mediators by the immune cells, enhancement of oxidative stress, and tissue remodeling in vascular smooth muscle cells and endothelial cells. Cellular processes are numerous, including inflammasome assembly and cell senescence which may involve mitochondrial dysfunction, autophagy, DNA damage response, dysbiosis, and many others. More recently, a series of noncoding RNAs, mainly microRNAs, have been described as possessing epigenetic actions on the regulation of inflammasome-related hypertension, emerging as a promising therapeutic strategy. Summary: Although there are a variety of pharmacological agents that effectively regulate inflammaging-related hypertension, a deeper understanding of the epigenetic events behind the control of vessel deterioration is needed for the treatment or even to prevent the disease onset.Fil: Simão, Vinícius Augusto. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Ferder, Leon Fernando. Universidad Maimónides; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Aconcagua. Facultad de Ciencias Médicas; ArgentinaFil: Chuffa, Luiz Gustavo. Universidade Estadual Paulista Julio de Mesquita Filho; Brasi
Daily and seasonal mitochondrial protection: Unraveling common possible mechanisms involving vitamin D and melatonin
No full textFrom an evolutionary point of view, vitamin D and melatonin appeared very early and share functions related to defense mechanisms. In the current clinical setting, vitamin D is exclusively associated with phosphocalcic metabolism. Meanwhile, melatonin has chronobiological effects and influences the sleep-wake cycle. Scientific evidence, however, has identified new actions of both molecules in different physiological and pathological settings. The biosynthetic pathways of vitamin D and melatonin are inversely related relative to sun exposure. A deficiency of these molecules has been associated with the pathogenesis of cardiovascular diseases, including arterial hypertension, neurodegenerative diseases, sleep disorders, kidney diseases, cancer, psychiatric disorders, bone diseases, metabolic syndrome, and diabetes, among others. During aging, the intake and cutaneous synthesis of vitamin D, as well as the endogenous synthesis of melatonin are remarkably depleted, therefore, producing a state characterized by an increase of oxidative stress, inflammation, and mitochondrial dysfunction. Both molecules are involved in the homeostatic functioning of the mitochondria. Given the presence of specific receptors in the organelle, the antagonism of the renin-angiotensin-aldosterone system (RAAS), the decrease of reactive species of oxygen (ROS), in conjunction with modifications in autophagy and apoptosis, anti-inflammatory properties inter alia, mitochondria emerge as the final common target for melatonin and vitamin D. The primary purpose of this review is to elucidate the common molecular mechanisms by which vitamin D and melatonin might share a synergistic effect in the protection of proper mitochondrial functioning.Fil: Mocayar Maron, Feres Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ferder, Leon Fernando. University of Miami; Estados UnidosFil: Reiter, Russel. University of Texas at San Antonio; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
Vitamin D deficiency in African Americans is associated with a high risk of severe disease and mortality by SARS-CoV-2
Get PDFCOVID-19 is said to be a pandemic that does not distinguish skin color or ethnic origin, but data in many parts of the world, especially in the United States, begins to show that there is a sector of society that is suffering a more significant impact from this pandemic. The black population is being more vulnerable than the white population to infection and death by COVID-19, and hypertension and diabetes mellitus seems to predispose to this vulnerability. Over time, multiple disparities have been observed between the health of blacks and whites, mainly associated with inequalities in the socio-economic scope. However, little by little, some mechanisms and pathophysiological susceptibilities that are directly related to the higher prevalence of multiple diseases in the black population, including infection and death by COVID-19, begin to be elucidated.Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system in black people are considerably different between this and other races, and it is well established their role in the development and progression of hypertension and multiple lung diseases, among them, COVID-19 infection.This letter to discuss and proposes whether or not vitamin D and renin-angiotensin-aldosterone system ethnical disparities influence susceptibility to infection and death by COVID-19 in black people and suggests possible mechanisms for this susceptibility.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inserra, Felipe. Universidad Maimónides; ArgentinaFil: Ferder, Leon Fernando. Universidad Maimónides; ArgentinaFil: García, Joxel. Ambitious Solutions for Health Cures; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
Hypertension linked to allostatic load: From psychosocial stress to inflammation and mitochondrial dysfunction
No full textAlthough a large number of available treatments and strategies, the prevalence of cardiovascular diseases continues to grow worldwide.émergingévidence supports the notion of counteracting stress as a critical component of a comprehensive therapeutic strategy for cardiovascular disease. Indeed, an unhealthy lifestyle is a burden to biological variables such as plasma glucose, lipid profile, and blood pressure control. Recent findings identify allostatic load as a new paradigm for an integrated understanding of the importance of psychosocial stress and its impact on the development and maintenance of cardiovascular disease. Allostasis complement homeostasis and integrates behavioral and physiological mechanisms by which genes,éarlyéxperiences,énvironment, lifestyle, diet, sleep, and physicaléxercise can modulate and adapt biological responses at the cellular level. Foréxample, variability is a physiological characteristic of blood pressure necessary for survival and the allostatic load in hypertension can contribute to its related cardiovascular morbidity and mortality. Therefore, the current review will focus on the mechanisms that link hypertension to allostatic load, which includes psychosocial stress, inflammation, and mitochondrial dysfunction. We will describe and discuss new insights on neuroendocrine-immuneéffects linked to allostatic load and its impact on the cellular and molecular responses; the links between allostatic load, inflammation, andéndothelial dysfunction; theépidemiologicalévidence supporting the pathophysiological origins of hypertension; and the biologicalémbedding of allostatic load and hypertension with anémphasis on mitochondrial dysfunction.Fil: Mocayar Maron, Feres Jose. Universidad Nacional de Cuyo; ArgentinaFil: Ferder, Leon Fernando. University of Miami; Estados UnidosFil: Saraví, Fernando Daniel. University of Miami; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
Lungs as Target of COVID-19 Infection: Protective Common Molecular Mechanisms of Vitamin D and Melatonin as a New Potential Synergistic Treatment
Get PDFCOVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level. Until now, there is not a specific and definitive treatment for this pathology that worries the world population, especially the older adults who constitute the main risk group. In this context, it results in a particular interest in the evaluation of the efficacy of existing pharmacological agents that may be used for overcoming or attenuating the severity of this pulmonary complication that has ended the lives of many people worldwide. Vitamin D and melatonin could be good options for achieving this aim, taking into account that they have many shared underlying mechanisms that are able to modulate and control the immune adequately and oxidative response against COVID-19 infection, possibly even through a synergistic interaction. The renin-angiotensin system exaltation with consequent inflammatory response has a leading role in the physiopathology of COVID-19 infection; and it may be down-regulated by vitamin D and melatonin in many organs. Therefore, it is also essential to analyze this potential therapeutic association and their relation with RAS as part of this new approach.Fil: Martín Giménez, Virna Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Catolica de Cuyo. Facultad de Ciencias Quimicas y Tecnologicas; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Universidad de Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tajer, Carlos Daniel. Hospital El Cruce Néstor Kirchner; ArgentinaFil: Mariani, Javier. Hospital El Cruce Néstor Kirchner; ArgentinaFil: Ferder, Leon Fernando. Universidad de Maimónides; ArgentinaFil: Reiter, Russel. University Of Texas At San Antonio.; Estados UnidosFil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
Vitamin D supplementation as a rational pharmacological approach in the COVID-19 pandemic
Get PDFCOVID-19 pandemic reached most of the countries of the world causing death as a result of the inflammatory storm, oxidative imbalance from the severe acute respiratory syndrome. Many laboratories fight against the clock in search of a specific and definitive treatment. Additionally, it is interesting the evaluation -preventive and therapeutic- of the existing pharmacological agents that could be used to avoid or attenuate the severity at the pulmonary level as well as in other organs of the body is of interest. In this regard, there is evidence of vitamin D that -in high doses- could be a promising preventive and therapeutic option, especially if it is considered that this hormone modulates the same inflammatory and oxidative signaling pathways triggered during COVID-19 infection. Similarly, it is useful to highlight that vitamin D is opposed to the actions of the renin-angiotensin system, which has a determining role in the pathophysiology of the inflammatory response by COVID-19. Finally, the purpose of this review is to call for reflection and to discuss the suggestion to implement vitamin D for preventive/therapeutic purposes in groups at risk or infected with COVID-19. This proposal could be extended to the entire community as a preventive measure. Also, our objective points to the debate and critical reflection of health professionals and health policymakers in a way that contributes to the development of consistent clinical designs to evaluate the possible benefits of using high doses of vitamin D for the benefit of public health in pandemic time.Fil: Ferder, Leon Fernando. Universidad Maimónides; ArgentinaFil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inserra, Felipe. Universidad Maimónides; ArgentinaFil: Tajer, Carlos Daniel. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Antonietti, Laura. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina. Universidad Nacional Arturo Jauretche; ArgentinaFil: Mariani, Javier. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad del Aconcagua. Facultad de Ciencias Médicas; Argentin
Key Aspects to Consider about Beneficial and Harmful Effects on the Central Nervous System by the Endocannabinoid Modulation Linked to New Cardiovascular Therapies
Get PDFThe endocannabinoid system (ECS) is closely related to the central nervous system (CNS) and exerts a promising therapeutic potential on the cardiovascular system, mainly through its neuromodulatory, neuroprotective, and neuroinflammatory effects. For this reason, when designing new treatments for different cardiovascular pathologies, it is necessary to consider the side effects that such therapies can cause at the neurological level. ObjectiveTo deepens the knowledge of each cannabinoid (CB) and the molecular mechanisms that can lead to undesired results to analyze its possible use in cardiovascular therapy.MethodsThe present review analyzes the psychoactive consequences of anandamide and other similar substances such as other endocannabinoids, phytocannabinoids, and synthetic cannabinoids, to assess their little-explored therapeutic potential in clinical investigations. Finally, the major behavioral tests most used until the moment to predict possible changes in the conduct of animals treated with various substances of cannabinoid nature are summarized. It has been observed that endocannabinoids have few adverse central nervous effects, unlike the phytocannabinoids, synthetic cannabinoids and antagonists of CB receptors. These molecules act on typical receptors due to a similar spatial configuration; however, their structure is not identical between them. For this reason, the competition and displacement of endogenous ligands of the ECS by exogenous cannabinoids provokes an alteration in the CNS normal functioning, leading to the associated side effects. An exhaustive analysis of each cannabinoid and the molecular mechanisms that can lead to undesired results is necessary at the time of proposing them as news cardiovascular therapeutic alternatives.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Mocayar Maron, Feres Jose. Universidad Nacional de Cuyo.Facultad de Ciencias Médicas; ArgentinaFil: Kassuha, Diego Enrique. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Ferder, Leon Fernando. Universidad de Miami; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentin
COVID-19 pandemic and vitamin D deficiency: a different approach with an analysis of the findings and a complimentary proposal
Get PDFVitamin D is an essential immune-modulator with receptors widely distributed throughout the body, and its serum levels fluctuate significantly among individuals between winter and summer months (from 30 to 50%). This study examines the association between low vitamin D status and prevalence of COVID-19 cases around the world and proposes a relationship between the seasonal character of the human immune system strength rather than to the seasonal infectivity of viruses. Also, this review suggests the observed geographical disparities in COVID-19 infections were due to differences in vitamin D levels. On the international scale, serum vitamin D levels are reportedly lowest in China, the Middle East, and South Europe; these populations also had the largest outbreaks of COVID-19 cases. In addition to the geographical differences in vitamin D status, there are known risk groups (ethnic, age-related, pregnancies). On the contrary, some countries including Canada, Finland, and North Europe incorporate increased amounts of vitamin D through fortified foods, vitamin D supplements, and sunbathing. These countries show the lowest morbidity and mortality rates by COVID-19 infection and demonstrate that lower ambient temperatures do not contribute to a higher number of COVID-19 cases. COVID-19 has spread around the globe almost simultaneously in both warm and cold areas. Given this information, vitamin D measurement should become an essential component of public health monitoring as a biomarker of immunity status. Clinical trials should be conducted to confirm this hypothesis. COVID-19 tests should be performed together with vitamin D status tests to verify this proposed relationship.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo. Facultad de Ciencias Quimicas y Tecnologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bergam, Ivana. Croatia Osiguranje Pension Company; CroaciaFil: Inserra, Felipe. Universidad Maimónides; ArgentinaFil: Ferder, Leon Fernando. Universidad Maimónides; ArgentinaFil: Reiter, Russel. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentin
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