La Tomasa reduce parámetros metabólicos e inflamatorios asociados a síndrome metabólico en un modelo murino / Tomasa reduces metabolic and inflammatory parameters associated with metabolic syndrome in a murine model

In our country, cardiovascular diseases (CVD) are the main cause of death. Unhealthy eating habits and sedentary lifestyles, among other factors, have contributed to increase the risk for CDV in the population. An alternative to the commonly used pharmacological therapies is the use of validated natural products that can be incorporated in the development of functional foods or supplements. In particular, the tomato has been shown to have a protective role in CVD; its high content of antioxidants, particularly lycopene, provides it with extensively documented beneficial properties. Tomasa, a by-product of the agroindustry, maintains some of the beneficial characteristics of its fruit of origin. Mice fed with a high-fat (hypercaloric) diet increase their body weight and visceral adipose mass, and also display an increase in metabolic and inflammatory parameters. Our results allow us to conclude that the consumption of Tomasa in mice fed a hypercaloric diet reduces the blood levels of cholesterol, glycaemia and pro-inflammatory cytokines. These results support the rationale of using of this by-product in the generation of functional ingredients with proven beneficial effects.

Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells

BACKGROUND: Mast cells (MCs) have been found to play a critical role during development of inflammatory bowel disease (IBD) that characterized by dysregulation of inflammation and impaired intestinal barrier function. However, the function of MCs in IBD remains to be fully elucidated. RESULTS: In our study, we used exosomes isolated from human mast cells-1 (HMCs-1) to culture with NCM460, HT-29 or CaCO2 of intestinal epithelial cells (lECs) to investigate the communication between MCs and lECs. We found that MCs-derived exosomes significantly increased intestinal epithelial permeability and destroyed intestinal barrier function, which is attributed to exosome-mediated functional miRNAs were transferred from HMCs-1 into lECs, leading to inhibit tight junction-related proteins expression, including tight junction proteins 1 (TJP1, ZO-1), Occludin (OCLN), Claudin 8 (CLDN8). Microarray and bioinformatic analysis have further revealed that a panel of miRNAs target different tight junction-related proteins. Interestingly, miR-223 is enriched in mast cell-derived exosome, which inhibit CLDN8 expression in IECs, while treatment with miR-223 inhibitor in HT-29 cells significantly reversed the inhibitory effect of HMCs-1-derived exosomes on CLDN 8 expression. Most importantly, enrichment of MCs accumulation in intestinal mucosa of patients with IBD compared with those healthy control. CONCLUSIONS: These results indicated that enrichment of exosomal miR-223 from HMCs-1 inhibited CLDN8 expression, leading to destroy intestinal barrier function. These finding provided a novel insight of MCs as a new target for therapeutic treatment of IBD.

Hypertonic saline solution reduces the inflammatory response in endotoxemic rats

OBJECTIVE: Volume replacement in septic patients improves hemodynamic stability. This effect can reduce the inflammatory response. The objective of this study was to evaluate the effect of 7.5% hypertonic saline solution versus 0.9% normal saline solution for volume replacement during an inflammatory response in endotoxemic rats. METHODS: We measured cytokines (serum and gut), nitrite, and lipid peroxidation (TBARS) as indicators of oxidative stress in the gut. Rats were divided into four groups: control group (C) that did not receive lipopolysaccharide; lipopolysaccharide injection without treatment (LPS); lipopolysaccharide injection with saline treatment (LPS +S); and lipopolysaccharide injection with hypertonic saline treatment (LPS +H). Serum and intestine were collected. Measurements were taken at 1.5, 8, and 24 h after lipopolysaccharide administration. RESULTS: Of the four groups, the LPS +H group had the highest survival rate. Hypertonic saline solution treatment led to lower levels of IL-6, IL-10, nitric oxide, and thiobarbituric acid reactive substances compared to 0.9% normal saline. In addition, hypertonic saline treatment resulted in a lower mortality compared to 0.9% normal saline treatment in endotoxemic rats. Volume replacement reduced levels of inflammatory mediators in the plasma and gut. CONCLUSION: Hypertonic saline treatment reduced mortality and lowered levels of inflammatory mediators in endotoxemic rats. Hypertonic saline also has the advantage of requiring less volume replacement.

Inflammatory Bowel Diseases and Inflammasome / 대한소화기학회지

Inflammatory bowel disease (IBD), the most important entities being ulcerative colitis and Crohn's disease, are chronic, relapsing and remitting inflammatory conditions that result from chronic dysregulation of the mucosal immune system in the intestinal tract. Although the precise pathogenesis of IBD is still incompletely understood, increased levels of proinflammatory cytokines, including interleukin (IL)-1beta, IL-18 and tumor necrosis factor-alpha, are detected in active IBD and correlate with the severity of inflammation, indicating that these cytokines may play a key role in the development of IBD. Recently, the intracellular nucleotide-binding oligomerization domain-like receptor (NLR) family members, including NLRP1, NLRP3, NLRC4 and NLRP6, are emerging as important regulators of intestinal homeostasis. Together, one of those aforementioned molecules or the DNA sensor absent in melanoma 2 (AIM2), apoptosis-associated speck-like protein containing 'a caspase recruitment domain (CARD)' (ASC) and caspase-1 form a large (>700 kDa) multi-protein complex called the inflammasome. Stimulation with specific microbial and endogenous molecules triggers inflammasome assembly and caspase-1 activation. Activated caspase-1 leads to the secretion of proinflammatory cytokines, including IL-1beta and IL-18, and the promotion of pyroptosis, a form of phagocyte cell death induced by bacterial pathogens, in an inflamed tissue. Therefore, inflammasomes are assumed to mediate host defense against microbial pathogens and gut homeostasis, so that their dysregulation might contribute to IBD pathogenesis. This review focuses on recent advances of the role of NLRP3 inflammasome signaling in IBD pathogenesis. Improving knowledge of the inflammasome could provide insights into potential therapeutic targets for patients with IBD.

Doenças inflamatórias intestinais: o que há de novo em terapianutricional? / Intestinal inflammatory diseases: what is new in nutritional therapy? / Enfermedades inflamatorias intestinal: ¿qué hay de nuevo en terapia nutricional?

A doença inflamatória intestinal (DII) é uma denominação genérica que engloba várias entidades patológicas, sendo as mais comuns: retocolite ulcerativa inespecífica (RCUI) e doença de Crohn (DC), que acometem o trato gastrointestinal e são comumente associadas à desnutrição protéico-energética (DPE). As alterações nutricionais dependem da extensão e da gravidade com que se manifestam as moléstias, agravando o prognóstico tanto do paciente em tratamento clínico, quanto daqueles submetidos a cirurgias, deteriorando ainda a competência imune. A terapia nutricional tem se mostrado como recurso terapêutico auxiliar extremamente útil, atuando diretamente sobre o estado nutricional, mantendo-o e/ou recuperando-o, com conseqüente benefício na evolução e tratamento das DII. As indicações e as características básicas das dietas são motivos de discussão. O suporte nutricional oral, enteral e parenteral tem se mostrado bastante eficaz na indução e na manutenção da remissão da DII, pelo fornecimento de nutrientescom funções fisiológicas específicas. Estes nutrientes atuam modulando a resposta imunoinflamatória e mantendo a integridade da mucosa intestinal, melhorando o estado clínico e, conseqüentemente, o estado nutricional destes pacientes. O conhecimento do papel benéfico da flora intestinal estimulou as investigações com probióticos, sugerindo estratégias futuras detratamento.

Intestinal inflammatory disease (IID) is a generic denomination for various pathologic entities.The most common are non-specific ulcerative rectocolitis and Crohn’s disease (CD), which affect the gastrointestinal tract and are commonly associated with protein-energetic malnutrition(PEM). The nutritional alterations depend on the extent and gravity of the symptoms, aggravate the prognosis of patients receiving clinical treatment as well as surgical patients and worse nimmune competence. Nutritional therapy has revealed to be an extremely useful therapeutic resource, which exerts a direct influence, maintaining or recovering the nutritional state, andconsequently benefits the evolution and treatment of IID. The indications and basic characteristics of diets are a reason for discussion. Oral, enteral and parenteral nutritional support has revealed to be quite efficient to induce and maintain the remission of IID, as it supplies nutrients with specific physiological functions. The effect of these nutrients modulates the immuno-inflammatory response and maintains the integrity of the intestinal mucosa, improving these patients’ clinical and,consequently, nutritional condition. Knowledge about the beneficial role of the intestinal flora stimulated research on probiotics which has resulted in future treatment strategy suggestions.

La enfermedad inflamatoria intestinal (EII) es una denominación genérica que abarca varias entidades patológicas. Las más comunes son la rectocolitis ulcerativa inespecífica (RCUI) y enfermedad de Crohn (EC), que atacan al tracto gastrointestinal y son comúnmente asociadas a la desnutrición proteico-energética (DPE). Las alteraciones nutricionales dependen de la extensión y gravedad con que se muestran las molestias, agudizando el pronóstico tanto del paciente en tratamiento clínico como en aquellossometidos a cirugías y empeorando además la competencia inmune. La terapia nutricional se ha revelado como recurso terapéutico auxiliar extremamente útil, actuando directamente sobre el estado nutricional, manteniéndolo y/o recuperándolo, acarreando beneficios a la evolución y al tratamiento de las EII. Las indicaciones y características básicas de las dietas son motivo de discusión. El soporte nutricional oral, enteral y parenteral se hamostrado bastante eficaz en la inducción y el mantenimiento de la remisión de la EII,debido al suministro de nutrientes con funciones fisiológicas específicas. Estos nutrientes actúan modulando la respuesta inmunoinflamatoria y manteniendo la integridad de la mucosa intestinal, mejorando el estado clínico y, consecuentemente, el estado nutricional de estos pacientes. El conocimiento del papel benéfico de la flora intestinal estimuló las investigaciones con probióticos sugiriendo estrategias futuras de tratamiento.