Exosomes and Melatonin: Where Their Destinies Intersect

Cell-to-cell communication is a broad and complex process associated with regular stimuli to maintain healthy cell interactions. One of the agents capable of cellular communication is known as an exosome, a subset of extracellular vesicles (EVs) released by the cell membrane. The exosome contains a wide range of functional proteins, mRNAs and miRNAs, which have the potential to interact with healthy or diseased cells in the body. On the other hand, melatonin also acts as a cellular communicator, produced and released by the pineal gland in a circadian way and also, non-circadian melatonin is derived from the mitochondria of all normal cells. In addition to exhibiting antioxidant, anti-inflammatory, anti-tumor and anti-aging activities, melatonin has recently been studied by its influence on exosomes. This review summarizes the relationship between exosomes and melatonin in various pathological processes. There is robust evidence that their combination ameliorates inflammation, ischemia-reperfusion injury, hepatic metabolic disturbance, cancer immunosuppression status, degenerative processes like chronic kidney disease, vascular calcification, ageing, ischemic brain injury, neurodegenerative diseases, obesity, colitis, wound healing and even embryonic development. Association of exosomes and melatonin represent a promising therapeutic tool, capable of interfering with basic molecular processes, such as oxidative stress and the inflammatory cascade, which support many pathophysiological aspects of diseases

Memory Networks in Tinnitus: A Functional Brain Image Study

Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. the network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. the objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. Methods: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). the severity of tinnitus was assessed using the Tinnitus Handicap Inventory (THI). the images were processed and analyzed using Statistical Parametric Mapping (SPM8). Results: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE<0.05) was observed in patients with tinnitus compared with healthy controls. the average total THI score was 50.8+18.24, classified as moderate tinnitus. Conclusion: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psiquiatria, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Radiol, Secao Med Nucl, São Paulo, BrazilHosp Israelita Albert Einstein, Inst Cerebro, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fonoaudiol, São Paulo, BrazilUniv Western Australia, Med Res Ctr, Western Australian Ctr Hlth & Ageing, Perth, WA 6009, AustraliaUniversidade Federal de São Paulo, Dept Psiquiatria, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Otorrinolaringol & Cirurgia Cabeca & Pescoco, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Radiol, Secao Med Nucl, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Fonoaudiol, São Paulo, BrazilFAPESP: FAPESP-2010/14804-6Web of Scienc

Agricultura orgânica em áreas urbanas e periurbanas com base na agroecologia.

A agricultura orgânica com base na agroecologia é o mote tecnológico adequado à realidade dos agroecossistemas urbanos. Este artigo ressalta a necessidade de se desenvolver tecnologias e insumos específicos. A partir de experiências com agricultura urbana em diferentes países em desenvolvimento, evidencia-se a necessidade de se buscar capacidades locais e apoio do poder público, especialmente nas iniciativas da sociedade organizada e mobilizada para a produção agrícola urbana

Nutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner

Acquisition and subsequent metabolism of different carbon and nitrogen sources have been shown to play an important role in virulence attributes of the fungal pathogen Aspergillus fumigatus, such as the secretion of host tissue-damaging proteases and fungal cell wall integrity. We examined the relationship between the metabolic processes of carbon catabolite repression (CCR), nitrogen catabolite repression (NCR) and virulence in a variety of A. fumigatus clinical isolates. A considerable amount of heterogeneity with respect to the degree of CCR and NCR was observed and a positive correlation between NCR and virulence in a neutropenic mouse model of pulmonary aspergillosis (PA) was found. Isolate Afs35 was selected for further analysis and compared to the reference strain A1163, with both strains presenting the same degree of virulence in a neutropenic mouse model of PA. Afs35 metabolome analysis in physiological-relevant carbon sources indicated an accumulation of intracellular sugars that also serve as cell wall polysaccharide precursors. Genome analysis showed an accumulation of missense substitutions in the regulator of protease secretion and in genes encoding enzymes required for cell wall sugar metabolism. Based on these results, the virulence of strains Afs35 and A1163 was assessed in a triamcinolone murine model of PA and found to be significantly different, confirming the known importance of using different mouse models to assess strain-specific pathogenicity. These results highlight the importance of nitrogen metabolism for virulence and provide a detailed example of the heterogeneity that exists between A. fumigatus isolates with consequences for virulence in a strain-specific and host-dependent manner

Study of reactions induced by 6He on 9Be

We present the results of experiments using a 6He beam on a 9Be target at\ud energies 7 − 9 times the Coulomb barrier. Angular distributions of the elastic, inelastic\ud scattering (target breakup) and the -particle production in the 6He+9Be collision have\ud been analysed. Total reaction cross sections were obtained from the elastic scattering\ud analyses and a considerable enhancement has been observed by comparing to stable systems.FAPESPFundação Araucári

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors