Indicios de fibrogénesis en hígado esteatósico no alcohólico de pacientes con componentes del síndrome metabólico

Non-alcoholic steatosis is generally associated with benign prognosis, however it can progress to fibrosis; the behavior of genes that contribute to their progression to fibrosis are not fully understood yet. The objective of this study was to analize the first signs of fibrogenesis in non-alcoholic steatosis in obese versus non-obese patients. A prospective descriptive study included patients with non-alcoholic steatosis was performed. The patients were divided in two groups, obese and non-obese. Sociodemographic, anthropometric and the suffering of the components of metabolic syndrome information were obtained. Biochemical parameters and expression leves of theTNF-α, NF-kβ, CYP2E1, TGF-β, OPN, COL4α5 and HGF genes were determined by RT-PCR. Our results showed significant differences in the levels of expression of the CYP2E1 gene, the level of expression being higher in obese patients suffering from complete metabolic syndrome. Furthermore, in non-obese patients with steatosis and without components of the metabolic syndrome, TGF-β is activated as a participant in fibrogen pathways and in obese patients with complete metabolic syndrome, the significant expression level of CYP2E1 could indicate an alarm signal for possible progress of the illness. Special attention and monitoring of steatosis should be paid in obese patients.La esteatosis no alcohólica es asociada con pronóstico benigno. Sin embargo, puede progresar a fibrosis, aunque no se comprende completamente el comportamiento de los genes que contribuyen a esta progresión. El objetivo de esta investigación fue analizar los indicios tempranos de fibrogénesis en la esteatosis no alcohólica en pacientes obesos frente a no obesos. Se realizó un estudio descriptivo prospectivo que incluyó a pacientes con esteatosis no alcohólica. Estos fueron divididos en dos grupos: obesos y no obesos. Se obtuvo información sociodemográfica, antropométrica y de padecimientos de componentes del síndrome metabólico. Se determinaron parámetros bioquímicos y niveles de expresión de los genes TNF-α, NF-kβ, CYP2E1, TGF-β, OPN, COL4α5 y HGF por RT-PCR. Los resultados muestran diferencias significativas en los niveles de expresión del gen CYP2E1, siendo mayor en pacientes obesos que padecían síndrome metabólico completo. Además, en pacientes no obesos sin componentes del síndrome metabólico se activa TGF-β como participante de vías fibrogénicas, y en pacientes obesos con síndrome metabólico completo el nivel de expresión significativo de CYP2E1 podría indicar una señal de alarma por un posible progreso de la enfermedad. Debe prestarse especial atención y seguimiento de la esteatosis en pacientes obesos

Attenuated mutants of Salmonella enterica Typhimurium mediate melanoma regression via an immune response

The lack of effective treatment options for an increasing number of cancer cases highlights the need for new anticancer therapeutic strategies. Immunotherapy mediated by Salmonella enterica Typhimurium is a promising anticancer treatment. Candidate strains for anticancer therapy must be attenuated while retaining their antitumor activity. Here, we investigated the attenuation and antitumor efficacy of two S. enterica Typhimurium mutants, ΔtolRA and ΔihfABpmi, in a murine melanoma model. Results showed high attenuation of ΔtolRA in the Galleria mellonella model, and invasion and survival in tumor cells. However, it showed weak antitumor effects in vitro and in vivo. Contrastingly, lower attenuation of the attenuated ΔihfABpmi strain resulted in regression of tumor mass in all mice, approximately 6 days after the first treatment. The therapeutic response induced by ΔihfABpmi was accompanied with macrophage accumulation of antitumor phenotype (M1) and significant increase in the mRNAs of proinflammatory mediators (TNF-α, IL-6, and iNOS) and an apoptosis inducer (Bax). Our findings indicate that the attenuated ΔihfABpmi exerts its antitumor activity by inducing macrophage infiltration or reprogramming the immunosuppressed tumor microenvironment to an activated state, suggesting that attenuated S. enterica Typhimurium strains based on nucleoid-associated protein genes deletion could be immunotherapeutic against cancer