RESUMO
Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)-Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.
RESUMO
Gene therapy has evolved due to the development of a number of biotechnology weapons, i.e., vectors that achieve for a longer expression and safer administration. Among viral vectors developed adeno-associated virus have shown promising advantages. These DNA viruses transduce a wide cell range, can integrate in host's genome and achieve for a long-period expression, besides avoiding a cellular immune response. The new technologies applied to the production and purification of these vectors had resulted in notable increases in quantity and quality of the infectious particles obtained. Actually, due to biotechnological advances, gene therapy is a potential therapeutic option.
Assuntos
Adenoviridae , Terapia Genética/métodos , Vetores Genéticos , Animais , Humanos , Lentivirus , Hepatopatias/terapia , RetroviridaeRESUMO
Transforming growth factor-beta (TGF-beta) family members include TGF-beta, activins, and bone morphogenetic proteins (BMP). These proteins are structurally related cytokines secreted in diverse Metazoans. TGF-beta family members regulate cellular functions such as proliferation, apoptosis, differentiation, and migration, and play an important role in organism development. Deregulated TGF-beta family signaling participates in various human pathologies including autoimmune diseases, vascular disorders, fibrotic disease, and cancer. Ligand-induced activation of TGF-beta family receptors with intrinsic serine/threonine kinase activity, triggers phosphorylation of the intracellular effectors of TGF-beta signaling, the Smads proteins. Once these proteins are activated they translocate into the nucleus, where they induce transcription of target genes and regulate cellular processes and functions. Novel therapeutic strategies are currently being developed to correct alterations in pathologies that involve TGF-beta as the main mediator. The English version of this paper is available at: http://www.insp.mx/salud/index.html.
Assuntos
Fator de Crescimento Transformador beta/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Humanos , FosforilaçãoRESUMO
El factor de crecimiento transformante beta (TGF-beta) es una familia de proteínas que incluye al TGF-beta, activinas y a la proteína morfogénica de hueso (BMP, por sus siglas en inglés), citocinas que son secretadas y se relacionan estructuralmente en diferentes especies de metazoarios. Los miembros de la familia del TGF-beta regulan diferentes funciones celulares como proliferación, apoptosis, diferenciación, migración, y tienen un papel clave en el desarrollo del organismo. El TGF-beta está implicado en varias patologías humanas, incluyendo desórdenes autoinmunes y vasculares, así como enfermedades fibróticas y cáncer. La activación del receptor del TGF-beta propicia su fosforilación en residuos de serina/treonina y dispara la fosforilación de proteínas efectoras intracelulares (smad), que una vez activas se translocan al núcleo para inducir la transcripción de genes blanco, y así regular procesos y funciones celulares. Se están desarrollando novedosas estrategias terapéuticas encaminadas a corregir las alteraciones presentes en patologías que involucran al TGF-beta como actor principal.