RESUMO
Cardiac transplantation of adipose-derived stem cells (ASC) modulates the post-myocardial infarction (post-MI) repair response. Biomolecules secreted or shuttled within extracellular vesicles, such as exosomes, may participate in the concerted response. We investigated the exosome's microRNAs due to their capacity to fine-tune gene expression, potentially affecting the multicellular repair response. We profiled and quantified rat ASC-exosome miRNAs and used bioinformatics to select uncharacterized miRNAs down-regulated in post-MI related to cardiac repair. We selected and validated miR-196a-5p and miR-425-5p as candidates for the concerted response in neonatal cardiomyocytes, cardiac fibroblasts, endothelial cells, and macrophages using a high-content screening platform. Both miRNAs prevented cardiomyocyte ischemia-induced mitochondrial dysfunction and reactive oxygen species production, increased angiogenesis, and polarized macrophages toward the anti-inflammatory M2 immunophenotype. Moreover, miR-196a-5p reduced and reversed myofibroblast activation and decreased collagen expression. Our data provide evidence that the exosome-derived miR-196a-5p and miR-425-5p influence biological processes critical to the concerted multicellular repair response post-MI.
Assuntos
Exossomos , MicroRNAs , Infarto do Miocárdio , Tecido Adiposo/metabolismo , Animais , Células Endoteliais/metabolismo , Exossomos/genética , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Ratos , Células-TroncoRESUMO
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) affects ~25% of world population and cases have increased in recent decades. These anomalies have several etiologies; however, obesity and metabolic dysfunctions are the most relevant causes. Despite being considered a public health problem, no effective therapeutic approach to treat NAFLD is available. For that, a deep understanding of metabolic routes that support hepatic diseases is needed. AREAS COVERED: This review covers aspects of the onset of NAFLD. Thereby, biochemistry routes as well as cellular and metabolic effects of the gut microbiota in body's homeostasis and epigenetics are contextualized. EXPERT OPINION: Recently, the development of biological sciences has generated innovative knowledge, bringing new insights and perspectives to clarify the systems biology of liver diseases. A detailed comprehension of epigenetics mechanisms will offer possibilities to develop new therapeutic and diagnostic strategies for NAFLD. Different epigenetic processes have been reported that are modulated by the environment such as gut microbiota, suggesting strong interplays between cellular behavior and pathology. Thus, a more complete description of such mechanisms in hepatic diseases will help to clarify how to control the establishment of fatty liver, and precisely describe molecular interplays that potentially control NAFLD.
Assuntos
Metabolismo dos Lipídeos/fisiologia , Fígado/fisiopatologia , Doenças Metabólicas/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Epigenômica , Microbioma Gastrointestinal/fisiologia , Humanos , Doenças Metabólicas/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Obesidade/complicações , Obesidade/fisiopatologiaRESUMO
Hepatic diseases leading to fibrosis affect millions of individuals worldwide and are a major public health challenge. Although, there have been many advances in understanding hepatic fibrogenesis, an effective therapy remains elusive. Studies focus primarily on activation of the hepatic stellate cells (HSCs), the principal fibrogenic cells in the liver; however, fewer numbers of studies have examined molecular mechanisms that deactivate HSC, controlling the profibrogenic phenotype. In the present study, we evaluated cellular and molecular actions of the chemical triclosan (TCS) in reverting activated HSCs to a quiesced phenotype. We demonstrated that the inhibition of the enzyme fatty acid synthase by TCS in activated HSCs promotes survival of the cells and triggers cellular and molecular changes that promote cellular phenotypic reversion, offering potentially new therapeutic directions.
Assuntos
Inibidores da Síntese de Ácidos Graxos/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Triclosan/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ácido Graxo Sintases/antagonistas & inibidores , Células Estreladas do Fígado/citologia , HumanosRESUMO
Oil spills are among the most significant threats to aquatic ecosystems. The present work describes the synthesis of different organic-inorganic hybrid matrices with magnetic properties, obtained in the forms of powders and membranes. The powders were synthesized using the following biomass wastes to form the organic phase: coconut mesocarp, sugarcane bagasse, sawdust, and water hyacinth. The resulting powders were denoted HMG-CO, HMG-CN, HMG-SE, and HMG-AP, respectively. Membranes (denoted MHMG-PES) were prepared using polyethersulfone polymer. In both cases, the inorganic phase was cobalt ferrite. The materials were evaluated in terms of their efficiencies in removing crude oil from water surfaces. The presence of organic matter, polyethersulfone, and cobalt ferrite in the structures of the materials was confirmed by XRD and FTIR analyses. The efficiencies of the materials were determined using the Standard Test Method for Sorbent Performance of Adsorbents (ASTM F726-99). Among the hybrids in powder form, the HMG-CN material presented the highest oil removal efficiency (85%, adsorptive capacity of 17â¯gâ¯g-1), which could be attributed to the fibrous nature of the sugarcane bagasse. The MHMG-PES membrane was able to remove 35 times its own mass of oil (adsorptive capacity of 35â¯gâ¯g-1). In addition to this high removal efficiency, an important advantage of MHMG-PES, compared to the HMG-CN hybrid powder, was that the oil could be mechanically removed from the membrane surface, eliminating the need for subsequent time-consuming extraction steps requiring large volumes of organic solvents and additional energy expenditure. When the two materials were used simultaneously, it was possible to remove 45 times their own mass of oil (adsorptive capacity of 45â¯gâ¯g-1), with the adsorptive capacity of HMG-CN increasing by 23%. This high adsorptive capacity was due to the retaining barrier formed by the HMG-CN hybrid powder, which prevented the oil patch from spreading and enabled its homogeneous removal, which was not possible using MHMG-PES alone. It could be concluded that use of the magnetic hybrids synthesized using biomass wastes, together with the hybrid magnetic membrane, provided an effective and inexpensive technological alternative for the removal of oil from water surfaces.
Assuntos
Petróleo , Poluentes Químicos da Água , Ecossistema , Pós , ÁguaRESUMO
A simple approach to exfoliate and functionalize MoS2 in a single-step is described, which combines the dispersion of MoS2 in polybutadiene solution and ultrasonication processes. The great advantage of this process is that a colloidal stability of MoS2 in nonpolar solvent is achieved by chemically bonding polybutadiene on the perimeter edge sites of MoS2 sheets. In addition, elastomeric nanocomposite has been prepared with singular mechanical properties using functionalized MoS2 as nanofiller in a polybutadiene matrix with a subsequent vulcanization reaction.