Melatonin-Loaded Nanocarriers: New Horizons for Therapeutic Applications

The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin (N-acetyl-5-methoxytriptamine) is a small indoleamine secreted essentially by the pineal gland during darkness, but also produced by most cells in a non-circadian manner from which it is not released into the blood. Although the therapeutic promise of melatonin is indisputable, aspects regarding optimal dosage, biotransformation and metabolism, route and time of administration, and targeted therapy remain to be examined for proper treatment results. Recently, prolonged release of melatonin has shown greater efficacy and safety when combined with a nanostructured formulation. This review summarizes the role of melatonin incorporated into different nanocarriers (e.g., lipid-based vesicles, polymeric vesicles, non-ionic surfactant-based vesicles, charge carriers in graphene, electro spun nanofibers, silica-based carriers, metallic and nonmetallic nanocomposites) as drug delivery system platforms or multilevel determinations in various in vivo and in vitro experimental conditions. Melatonin incorporated into nanosized materials exhibits superior effectiveness in multiple diseases and pathological processes than does free melatonin; thus, such information has functional significance for clinical intervention.Fil: Chuffa, Luiz Gustavo de Almeida. Universidade de Sao Paulo; BrasilFil: Seiva, Fábio Rodrigues Ferreira. Universidade Estadual do Norte do Paraná; BrasilFil: Novais, Adriana Alonso. Universidade Federal do Mato Grosso do Sul; BrasilFil: Simão, Vinícius Augusto. Universidade de Sao Paulo; BrasilFil: Martín Giménez, Virna Margarita. Universidad Católica de Cuyo. Facultad de Ciencias Químicas y Tecnológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Manucha, Walter Ariel Fernando. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Zuccari, Debora Aparecida Pires de Campos. Faculdade de Medicina de São José do Rio Preto; BrasilFil: Reiter, Russel. University of Texas at San Antonio; Estados Unido

Análise hormonal, imunolocalização e quantificação dos receptores de andrógenos (AR) e estrógenos (ER-α E ER-β) em ovário e útero de ratas submetidas a diferentes doses de decanoato de nandrolona: avaliação nos períodos pós-tratamento e pós-recuperação

Embora sejam extensas as opções de aplicação terapêutica dos esteroides anabólicos androgênicos (EAA), é crescente na sociedade o uso destas drogas por razões estéticas e este consumo tem aumentado principalmente entre as mulheres nas últimas décadas. É amplamente relatado que os EAA comprometem a saúde e promovem efeitos adversos na reprodução, no entanto, pouca atenção é dada a respeito dos efeitos promovidos pelos EAA no ciclo estral, na morfologia ovariana e uterina e na regulação da função ovariana após os períodos de tratamento e de recuperação. Nenhum relato foi obtido na literatura, quanto à administração de diferentes doses de EAA e a possibilidade de reversibilidade dos efeitos colaterais. Assim, o objetivo do projeto é avaliar o efeito de diferentes doses do esteroide decanoato de nandrolona (DN) no ciclo estral e nos ovários e útero de ratas albinas com ênfase no controle da imunoexpressão do AR, ERs, CYP450 aromatase e Inibina-A do tecido ovariano e nos níveis hormonais sexuais, e também se há recuperação dos prejuízos reprodutivos após a interrupção do tratamento esteroidal. Ratas Wistar foram tratadas com DN nas doses de 1,87, 3,75, 7,5 e 15 mg/kg ou óleo mineral (grupos controle) por 15 dias via subcutânea. Os animais foram divididos em três procedimentos: (a) tratamento durante 15 dias; (b) tratamento seguido por recuperação de 30 dias; (c) tratamento seguido por recuperação de 60 dias. O ciclo estral foi monitorado diariamente e no final de cada período os animais foram sacrificados. Durante o período de tratamento com DN e no pós-recuperação de 30 dias, os animais exibiram diestro persistente, que manteve-se somente no grupo de 15 mg DN/kg no período de recuperação de 60 dias. O peso ovariano foi reduzido e o uterino aumentado na comparação com o controle em função do tratamento com DN e somente foi recuperado no 60 dias pós-tratamento nos grupos que restabeleceram o ciclo estral. Houve uma redução (p<0,05) no número de corpos lúteos, folículos antrais e em crescimento e diminuição da camada endometrial uterina, em contraste com um aumento (p<0,05) nos folículos atrésicos e das camadas do miométrio e perimétrio nas ratas DN de maneira dose e período-dependente. Alterações histopatológicas notáveis ocorreram nos ovários e útero de todos os grupos tratados com DN em função do período avaliado e estiveram relacionados aos níveis dos hormônios sexuais e de expressão dos receptores ovarianos alterados de maneira dose-específica. Concluiu-se que o tratamento experimental com DN promoveu toxicidade ovariana e uterina em ratas de maneira dose-dependente e que o período de recuperação de 60 dias foi suficiente para a reversibilidade dos efeitos colaterais apenas no tratamento com as menores doses do esteroide, de forma que os níveis hormonais e de expressão dos receptores ovarianos puderam se recuperar após marcante desregulação promovida pelo tratamento androgênico.Although are extensive the options of therapeutic use of anabolic-androgenic steroids (AAS), the use of these drugs for aesthetic reasons is growing in society and this consumption has increased mainly among women in recent decades. It is widely reported that the AAS compromise the health and promote adverse effects on reproduction, however, little attention is given on the effects promoted by the AAS in the estrous cycle, in ovarian and uterine morphology and in the regulation of ovarian function after treatment periods and recovery. No report has been obtained from the literature regarding the administration of different doses of synthetic steroids and the possibility of reversibility of side effects. The objective of this project is to evaluate the effect of different doses of steroid nandrolone decanoate (ND) in the estrous cycle and ovaries and uterus of albino rats with emphasis on control of AR immunoexpression, ERs, CYP450 aromatase and inhibin-A in the ovarian tissue and sexual hormone levels, and evaluate if there is recovery of possible reproductive damages after cessation of steroid treatment. Female Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg or received mineral oil (control groups estrus and diestrus) for 15 days subcutaneously. The animals were divided into three procedures: (a) treatment for 15 days; (b) treatment followed by recovery to 30 days; (c) treatment followed by recovery for 60 days. The estrous cycle was monitored daily and at the end of each period the animals were sacrificed. During the ND treatment period and after recovery for 30 days, all animals exhibited persistent diestrus, which was maintained only in the group of 15 mg ND/kg after the recovery period of 60 days. The ovarian weight has been reduced and the uterine has increased (p<0.05) in comparison with the control due to the treatment with ND and it was only recovered at 60 days post-treatment in the groups that reestablished the estrous cycle. There was a reduction (p<0.05) in the number of corpora lutea, antral and growing follicles and decreased in uterine endometrial layer, in contrast with an increase (p<0.05) in atretic follicles, myometrium and perimetrium in the androgenized rats in a dose and time-dependent manner. Remarkable histopathological changes occurred in the ovaries and uterus of all groups treated with ND depending on the period assessed and were related to the levels of sex hormones and expression of altered ovarian receptors in a dose-specific manner. It was concluded that the experimental treatment with ND promoted ovarian and uterine toxicity in rats in a dose-dependent manner and the 60-day recovery period was sufficient for the reversibility of side effects only in treatment with lower steroid doses in a way that hormonal levels and expression of ovarian receptors could recover after remarkable dysregulation promoted by the androgenic treatment.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Epigenetic Mechanisms Involved in Inflammaging-Associated Hypertension

Purpose 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

Protective actions of vitamin D, anandamide and melatonin during vascular inflammation: epigenetic mechanisms involved

Vascular inflammation is one of the main activating stimuli of cardiovascular disease and its uncontrolled development may worsen the progression and prognosis of these pathologies. Therefore, the search for new therapeutic options to treat this condition is undoubtedly needed. In this regard, it may be better to repurpose endogenous anti-inflammatory compounds already known, in addition to synthesizing new compounds for therapeutic purposes. It is well known that vitamin D, anandamide, and melatonin are promising endogenous substances with powerful and wide-spread anti-inflammatory properties. Currently, the epigenetic mechanisms underlying these effects are often unknown. This review summarizes the potential epigenetic mechanisms by which vitamin D, anandamide, and melatonin attenuate vascular inflammation. This information could contribute to the improvement in the therapeutic management of multiple pathologies associated with blood vessel inflammation, through the pharmacological manipulation of new target sites that until now have not been addressed.Fil: Martín Giménez, Virna Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Chuffa, Luiz Gustavo A.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Simão, Vinícius Augusto. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Reiter, Russel. University Of Texas Health Science Center 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

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data