JAM-A regulates permeability and inflammation in the intestine in vivo

Recent evidence has linked intestinal permeability to mucosal inflammation, but molecular studies are lacking. Candidate regulatory molecules localized within the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of barrier function and leukocyte migration. Thus, we analyzed the intestinal mucosa of JAM-A–deficient (JAM-A−/−) mice for evidence of enhanced permeability and inflammation. Colonic mucosa from JAM-A−/− mice had normal epithelial architecture but increased polymorphonuclear leukocyte infiltration and large lymphoid aggregates not seen in wild-type controls. Barrier function experiments revealed increased mucosal permeability, as indicated by enhanced dextran flux, and decreased transepithelial electrical resistance in JAM-A−/− mice. The in vivo observations were epithelial specific, because monolayers of JAM-A−/− epithelial cells also demonstrated increased permeability. Analyses of other TJ components revealed increased expression of claudin-10 and -15 in the colonic mucosa of JAM-A−/− mice and in JAM-A small interfering RNA–treated epithelial cells. Given the observed increase in colonic inflammation and permeability, we assessed the susceptibility of JAM-A−/− mice to the induction of colitis with dextran sulfate sodium (DSS). Although DSS-treated JAM-A−/− animals had increased clinical disease compared with controls, colonic mucosa showed less injury and increased epithelial proliferation. These findings demonstrate a complex role of JAM-A in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation

Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages

Intestinal macrophages are highly mobile cells with extraordinary plasticity and actively contribute to cytokine-mediated epithelial cell damage. The mechanisms triggering macrophage polarization into a proinflammatory phenotype are unknown. Here, we report that during inflammation macrophages enhance its intercellular adhesion properties in order to acquire a M1-phenotype. Using in vitro and in vivo models we demonstrate that intercellular adhesion is mediated by integrin-αVβ3 and relies in the presence of the unconventional class I myosin 1F (Myo1F). Intercellular adhesion mediated by αVβ3 stimulates M1-like phenotype in macrophages through hyperactivation of STAT1 and STAT3 downstream of ILK/Akt/mTOR signaling. Inhibition of integrin-αVβ3, Akt/mTOR, or lack of Myo1F attenuated the commitment of macrophages into a pro-inflammatory phenotype. In a model of colitis, Myo1F deficiency strongly reduces the secretion of proinflammatory cytokines, decreases epithelial damage, ameliorates disease activity, and enhances tissue repair. Together our findings uncover an unknown role for Myo1F as part of the machinery that regulates intercellular adhesion and polarization in macrophages

Role of the intestinal barrier in inflammatory bowel disease

A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the interstitium. The single layer of intestinal epithelial cells (IECs) serves as a dynamic interface between the host and its environment. Cell polarity and structural properties of the epithelium is complex and is important in the development of epithelial barrier function. Epithelial cells associate with each other via a series of intercellular junctions. The apical most intercellular junctional complex referred to as the Apical Junction Complex (AJC) is important in not only cell-cell recognition, but also in the regulation of paracellular movement of fluid and solutes. Defects in the intestinal epithelial barrier function have been observed in a number of intestinal disorders such as inflammatory bowel disease (IBD). It is now becoming evident that an aberrant epithelial barrier function plays a central role in the pathophysiology of IBD. Thus, a better understanding of the intestinal epithelial barrier structure and function in healthy and disease states such as IBD will foster new ideas for the development of therapies for such chronic disorders

SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells

B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1β. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism’s mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection

Rendimiento y calidad del chile habanero ("Capsicum chinense" Jacq.) por efecto del régimen nutrimental

With the purpose of evaluating the effect of ten nutritional regimes in habanero chili cultivated in a hydroponic system under plastic cover, in 2015 a study was carried out from April to September in the experimental field of the Faculty of Agricultural Sciences of the Autonomous University of the State of Morelos. The treatments consisted of three nitrate concentrations in the vegetative stage (10, 12 and 14 me L -1 ), each with three nitrate:phosphate:sulfate ratios in the flowering stage (14:1.25:4.75, 12:1:7 and 14:1.25:4.75 me L -1 ) and with three nitrate/potassium ratios in the fruiting stage (14:5, 14:5 and 12:7 me L -1 ). The treatments were distributed in a completely randomized design with ten replicates each. The supply of the nutritive solutions was by drip irrigation, with a flow rate of 8 Lh -1 . Eight irrigations were applied daily, with a time of 1 min irrigation -1 at the beginning of the crop development and up to 4 min irrigation -1 at the fruiting stage. The experimental unit was a black polyethylene container with a capacity of 15.14 L, with red tezontle gravel as a substrate and a plant. The results indicated that, due to the nutritive regime of 14 m L -1 of NO 3 - (vegetative stage), 14: 1.25:4.75 m L -1 of NO 3 - :H 2 PO 4 - :SO 4 2- (flowering stage) and 14:5 me L -1 de NO 3 - :K + (fruiting stage), there was an increase in the number of flowers/plant, number of fruits/plant and yield, which was 1054 g plant -1 in six fruit sections, 33% higher than the yield obtained from the plants they are fed with Steiner solution during the whole crop cycle, while the accumulation of dry matter was also higher by 20.3%. Palabras clave: Flowering, fructification, phenology, nutrient solution, vegetative stage.Con la finalidad de evaluar el efecto de diez regímenes nutrimentales en chile habanero cultivado en un sistema hidropónico bajo cubierta plástica, en 2015 se realizó un estudio de abril a septiembre en el campo experimental de la Facultad de Ciencias Agropecuarias de la Universidad Autónoma del estado de Morelos. Los tratamientos consistieron en tres concentraciones de nitrato en la etapa vegetativa (10, 12 y 14 me L -1 ), combinadas cada una con tres relaciones de nitrato:fosfato:sulfato en la etapa de floración (14:1.25:4.75, 12:1:7 y 14:1.25:4.75 me L -1 ) y con tres relaciones nitrato/potasio en la etapa de fructificación (14:5, 14:5 y 12:7 me L -1 ). Los tratamientos se distribuyeron en un diseño completamente al azar con diez repeticiones cada uno. El suministro de las soluciones nutritivas fue mediante riego por goteo, con caudal de 8 L h -1 . Se aplicaron 8 riegos diarios, con un tiempo de 1 min riego -1 al inicio del desarrollo del cultivo y hasta 4 min riego -1 en la etapa de fructificación. La unidad experimental fue un contenedor de polietileno negro con capacidad para 15.14 L, con grava de tezontle rojo como sustrato y una planta. Los resultados indicaron que por efecto del régimen nutrimental de 14 me L -1 de NO 3 - (etapa vegetativa), 14:1.25:4.75 me L -1 de NO 3 - :H 2 PO 4 - :SO 4 2- (etapa de floración) y 14:5 me L -1 de NO 3 - :K + (etapa de fructificación), hubo un incremento en el número de flores/planta, número de frutos/planta y rendimiento, el cual fue de 1054 g planta -1 en seis cortes de fruto, 33% superior al rendimiento obtenido de las plantas que se nutren con solución Steiner durante todo el ciclo de cultivo, mientras que la acumulación de materia seca también fue superior 20.3%. Palabras clave: Etapa vegetativa, fenología, floración, fructi ficación, solución nutritiva

Occurrence of scorpion sting and associated factors in a highly marginalized municipality in Guerrero, Mexico: A cross-sectional study.

BackgroundScorpion sting is a neglected public health problem, despite a global estimate of 1.2 million scorpion stings and some 3,250 deaths annually.MethodsThis cross-sectional study estimates the occurrence of scorpion stings and identifies associated factors in seven communities in the highly marginalized municipality of Chilapa, in the Mexican state of Guerrero. After informed consent, 1,144 households provided information on 4,985 residents. The questionnaire collated sociodemographic data, characteristics of the dwelling, efforts to avoid scorpion stings, and individual information of scorpion stings suffered in the last year. Cluster-adjusted (acl), bivariate and multivariate analysis relied on the Mantel-Haenszel procedure.ResultsThe overall period prevalence of scorpion stings in the year prior to the study was 4.4% (218/4985), 5.4% in men (126/2320), and 3.5% in women (92/2665), pConclusionThis study confirms scorpion bites are a public health problem in these marginalized communities in Guerrero State, with risk factors related to living conditions and the work process at home and in the fields. Almost all risk factors identified could be reduced with low-cost interventions implemented by the communities themselves

Experimental Colitis Is Attenuated by Cardioprotective Diet Supplementation That Reduces Oxidative Stress, Inflammation, and Mucosal Damage

Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD) are multifactorial, relapsing disorders of the gastrointestinal tract. However, the etiology is still poorly understood but involves altered immune responses, epithelial dysfunction, environmental factors, and nutrition. Recently, we have shown that the diet supplement corabion has cardioprotective effects due to reduction of oxidative stress and inflammation. Since oxidative stress and inflammation are also prominent risk factors in IBD, we speculated that corabion also has beneficial effects on experimental colitis. Colitis was induced in male mice by administration of 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for a period of 3 or 7 days with or without daily gavage feeding of corabion consisting of vitamin C, vitamin E, L-arginine, and eicosapentaenoic and docosahexaenoic acid. We found that corabion administration attenuated DSS-induced colon shortening, tissue damage, and disease activity index during the onset of colitis. Mechanistically, these effects could be explained by reduced neutrophil recruitment, oxidative stress, production of proinflammatory cytokines, and internalization of the junctional proteins ZO-1 and E-cadherin leading to less edema formation. Thus, corabion may be a useful diet supplement for the management of chronic inflammatory intestinal disorders such as IBD