The role and therapeutic potential of prohibitin in disease

AbstractProhibitin 1 (PHB1), a pleiotropic protein in the cell, has been implicated in the regulation of proliferation, apoptosis, transcription, mitochondrial protein folding, and as a cell-surface receptor. This diverse array of functions of PHB1 is attributed to the cell type studied and its subcellular localization. This review discusses recent data that indicate a diverse role of PHB1 in disease pathogenesis and suggest that targeting PHB1 may be a potential therapeutic option for treatment of diseases including cancer, inflammatory bowel disease, insulin resistance/type 2 diabetes, and obesity. These diseases are associated with increased oxidative stress and mitochondrial dysfunction and therefore, the role of PHB1 in both responses will also be discussed

Dimethyl Fumarate Alleviates Dextran Sulfate Sodium-Induced Colitis, through the Activation of Nrf2-Mediated Antioxidant and Anti-inflammatory Pathways.

Oxidative stress and chronic inflammation play critical roles in the pathogenesis of ulcerative colitis (UC) and inflammatory bowel diseases (IBD). A previous study has demonstrated that dimethyl fumarate (DMF) protects mice from dextran sulfate sodium (DSS)-induced colitis via its potential antioxidant capacity, and by inhibiting the activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. This study aims to clarify the nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrf2/ARE) pathway pharmacological activation and anti-inflammatory effect by DMF, through focusing on other crucial antioxidant enzymes and inflammatory mediator, including glutamate-cysteine ligase catalytic subunit (GCLC), glutathione peroxidase (GPX) and cyclooxygenase-2 (COX-2), in a DSS-induced colitis mouse model. The oral administration of DMF attenuated the shortening of colons and alleviated colonic inflammation. Furthermore, the expression of key antioxidant enzymes, including GCLC and GPX, in the colonic tissue were significantly increased by DMF administration. In addition, protein expression of the inflammatory mediator, COX-2, was reduced by DMF administration. Our results suggest that DMF alleviates DSS-induced colonic inflammatory damage, likely via up-regulating GCLC and GPX and down-regulating COX-2 protein expression in colonic tissue

Endogenous Antioxidants: A Review of their Role in Oxidative Stress

Oxidative stress (OxS) constitutes a disturbance caused by an imbalance between the generation of free radicals and antioxidant system, which causes damage to biomolecules. This, in turn, may lead the body to the occurrence of many chronic degenerative diseases. Therefore, it is very important to know the functioning of those endogenous (and exogenous) antioxidants systems to prevent such diseases. Due to evolutionary conditions in living beings, among other functions have been developed and selected defense systems against the deleterious action of free radicals. Such systems are intrinsic in cells (at level intracellular and extracellular) and act together with the dietary exogenous antioxidants. All these antioxidant systems have very important role in preserving the oxide/reduction equilibrium in the cell. To understand the role of the transcription factor Nrf2 in regulating the processes of antioxidant defense, it must also know the role of many of the endogenous antioxidants that occur because of its activation. Therefore, this chapter makes a literature review of the most important general aspects of endogenous antioxidant systems, which will provide another point of view from which to approach the study and treatment of many chronic degenerative diseases, such as diabetes, hypertension, and Parkinson

Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor γ activity

Colitis involves immune cell–mediated tissue injuries, but the contribution of epithelial cells remains largely unclear. Vanin-1 is an epithelial ectoenzyme with a pantetheinase activity that provides cysteamine/cystamine to tissue. Using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis model we show here that Vanin-1 deficiency protects from colitis. This protection is reversible by administration of cystamine or bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor (PPAR)γ antagonist. We further demonstrate that Vanin-1, by antagonizing PPARγ, licenses the production of inflammatory mediators by intestinal epithelial cells. We propose that Vanin-1 is an epithelial sensor of stress that exerts a dominant control over innate immune responses in tissue. Thus, the Vanin-1/pantetheinase activity might be a new target for therapeutic intervention in inflammatory bowel disease

Nutrition in Inflammatory Bowel Disease (IBD)

The purpose of this Special Issue “Nutrition in Inflammatory Bowel Disease (IBD)” is to increase knowledge regarding the role of dietary composition and effects in IBD, describing the prevalence of malnutrition in IBD and the effect on clinical outcomes, discussing methods of nutrition risk screening and assessment in IBD, and reviewing mechanisms through which diet and dietary components may affect disease severity. The articles focus on the following areas: Dietary Composition/Therapy Interventions in Ulcerative Colitis and effects on outcomes; Dietary Composition/Therapy Interventions in Crohn’s Disease and effects on outcomes; Nutrition Risk Screening and Assessment in IBD; Mechanisms of Diet in the pathogenesis of IBD

La Novela de Bolsillo (1914-1916). Una colección literaria «de transición»

Esta tesis se centra en una de las colecciones de novela breve de principios del siglo XX, La Novela de Bolsillo, que contribuyó al triunfo de este fenómeno editorial e incentivó el gusto del público español del primer tercio del siglo XX por la lectura. La Novela de Bolsillo, colección publicada entre los años 1914-1916, publicó cien números semanales, obra de setenta y nueve escritores, en cuyas colaboraciones se distinguen distintas tendencias estilísticas. Entre dichos autores se registran los nombres de algunos ya famosos en la época, como es el caso de Joaquín Dicenta, y otros que comenzaban su carrera literaria, como Ramón Gómez de la Serna, Wenceslao Fernández Flórez, Antonio de Hoyos y Vinent o Álvaro Retana. Uno de los valores más destacados de La Novela de Bolsillo es el nuevo modelo de edición que presenta para estas colecciones literarias, este nuevo formato reduce el tamaño de los ejemplares a 11,5×15,5 centímetros, dando lugar al formato de bolsillo, que en 1914 supuso una revolución, ya que permitió cambiar los hábitos de lectura, al poder llevar la literatura a cualquier lugar. En este sentido, el creador de la colección, Francisco de Torres, afirmaba que La Novela de Bolsillo, debido a su nuevo formato, “será la novela del ferrocarril, la novela del paseo, la novela de la misma calle”..