Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy.

Diabetic nephropathy (DN) is a multifactorial disease characterized by hyperglycemia and close interaction of hemodynamic, metabolic and inflammatory factors. Nuclear factor-κB (NF-κB) is a principal matchmaker linking hyperglycemia and inflammation. The present work investigates the cell-permeable peptide containing the inhibitor of kappa B kinase γ (IKKγ)/NF-κB essential modulator (NEMO)-binding domain (NBD) as therapeutic option to modulate inflammation in a preclinical model of type 2 diabetes (T2D) with DN. Black and tan, brachyuric obese/obese mice were randomized into 4 interventions groups: Active NBD peptide (10 and 6 µg/g body weight); Inactive mutant peptide (10 µg/g); and vehicle control. In vivo/ex vivo fluorescence imaging revealed efficient delivery of NBD peptide, systemic biodistribution and selective renal metabolization. In vivo administration of active NBD peptide improved albuminuria (>40% reduction on average) and kidney damage, decreased podocyte loss and basement membrane thickness, and modulated the expression of proinflammatory and oxidative stress markers. In vitro, NBD blocked IKK-mediated NF-κB induction and target gene expression in mesangial cells exposed to diabetic-like milieu. These results constitute the first nephroprotective effect of NBD peptide in a T2D mouse model that recapitulates the kidney lesions observed in DN patients. Targeting IKK-dependent NF-κB activation could be a therapeutic strategy to combat kidney inflammation in DN.

Synthesis, Profiling, and in Vivo Evaluation of Cyclopeptides Containing N-Methyl Amino Acids as Antiplasmodial Agents.

Malaria is a major tropical disease where important needs are to mitigate symptoms and to prevent the establishment of infection. Cyclopeptides containing N-methyl amino acids with in vitro activity against erythrocytic forms as well as liver stage are presented. The synthesis, parasitological characterization, physicochemical properties, in vivo evaluation, and mice pharmacokinetics are described.

Inseguridad subjetiva y representaciones sociales de la delincuencia / Subjective Insecurity and Social Representations of Delinquency

Resumen El presente trabajo analiza las dinámicas de las representaciones sociales de la delincuencia en jóvenes universitarios de Venezuela (n = 305) y el País Vasco (n = 237) y la centralidad de la inseguridad subjetiva en sus principios organizadores. Siguiendo la metodología de Doise, Clèmence y Lorenzi-Cioldi (1993), se estudian los significados compartidos y diferenciales de la delincuencia, así como su anclaje en la percepción subjetiva del riesgo, experiencia de victimización y pertenencia a dos realidades nacionales. Los resultados muestran una representación más estereotipada de la delincuencia en los universitarios vascos asociando ciertos delitos a grupos y contextos criminógenos. Sin embargo, los venezolanos enfatizan las causas y consecuencias destructivas para la vida social y un estado de miedo e inseguridad, debido a una experiencia más cercana al delito. La percepción subjetiva del riesgo y la experiencia de victimización quedan asociadas a dichas representaciones, lo que permite la propuesta de nuevas prioridades y desafíos en los métodos utilizados para estudiar y combatir el miedo e inseguridad subjetiva.

Abstract This work analyses the dynamics of social representations with a sample of university students in Spain (n = 237) and Venezuela (n = 305) along with the centrality of subjective insecurity on their organizational principles. Following the methodology proposed by Doise, Clèmence, and Lorenzi-Cioldi (1993), the shared and differential meanings of delinquency are studied, as well as their anchoring in the subjective perception of risk, victimization experience and belonging to two national realities. Results show that Basque students represent delinquency stereotypically, associating some crime types to certain groups and criminogenic contexts related to young people, drugs, and immigration. Nevertheless Venezuelan students emphasise the causes of crime and its destructive consequences for social life, and a state of fear and insecurity due to a closer experience of crime. The subjective perception of risk and the victimization experiences are associated with these representations, allowing us to propose new priorities and challenges in the methods used for studying and facing fear and subjective insecurity.