Evaluation of Potential Furin Protease Inhibitory Properties of Pioglitazone, Rosiglitazone, and Pirfenidone: An In Silico Docking and Molecular Dynamics Simulation Approach.

Furin (Fur) is a member of the protease convertase family; its expression is crucial for cleaving and maturing many proteins. Fur also represents a therapeutic target in cancer, autoimmune diseases, and viral infections. Pioglitazone (PGZ) and rosiglitazone (RGZ) are thiazolidinediones prescribed to type 2 diabetes patients and are structurally similar to the known Fur inhibitors naphthofluorescein (NPF) and pirfenidone (PFD). Thus, this study used molecular docking and molecular dynamics to assess and compare the affinities and the molecular interactions of these four ligands with the Fur active site (FurAct) and the recently described Fur allosteric site (FurAll). The 7QXZ Fur structure was used for molecular dockings, and for the best pose complexes, molecular dynamics were run for 100 ns. The best affinities of the ligand/FurAct and ligand/FurAll complexes were with NPF, PGZ, and RGZ, while PFD presented the lowest affinity. Asp154 was the central residue involved in FurAct complex formation, while Glu488 and Asn310 were the central residues involved in FurAll complex formation. This study shows the potential of RGZ, PGZ, and PFD as Fur competitive (FurAct) and non-competitive (FurAll) inhibitors. Therefore, they are candidates for repurposing in response to future emerging diseases through the modulation of Fur activity.

Determination of Glyphosate in Water from a Rural Locality in México and Its Implications for the Population Based on Water Consumption and Use Habits.

Glyphosate is a broad-spectrum herbicide widely used worldwide. Indeed, it is the herbicide most applied to all Mexican crops. Due to the overuse and poor disposal of the waste, this herbicide can reach the aquatic environments such as groundwater and surface water. Thus, there is a clear need to implement monitoring and surveillance programs for evaluating and controlling the exposure to this herbicide in rural populations. The goal of this study was to quantify the presence of glyphosate in different water bodies (groundwater, surface and drinking water) as well as to identify the uses and managements of water resources by rural communities to evaluate the potential human exposure to glyphosate in the Tenampulco region of the Mexican state of Puebla. Measurements were performed by a rapid and cost-effective ELISA-based method in groundwater and surface water from various sampling sites of the Tenampulco region. Glyphosate was detected in all groundwater samples to be below the maximum limit for glyphosate in water in Mexico. Nevertheless, these results indicate an exposure of glyphosate in these agricultural communities and the need to establish a monitoring program.

Trends and Perspectives in Immunosensors for Determination of Currently-Used Pesticides: The Case of Glyphosate, Organophosphates, and Neonicotinoids.

Pesticides, due to their intensive use and their peculiar chemical features, can persist in the environment and enter the trophic chain, thus representing an environmental risk for the ecosystems and human health. Although there are several robust and reliable standard analytical techniques for their monitoring, the high frequency of contamination caused by pesticides requires methods for massive monitoring campaigns that are capable of rapidly detecting these compounds in many samples of different origin. Immunosensors represent a potential tool for simple, rapid, and sensitive monitoring of pesticides. Antibodies coupled to electrochemical or optical transducers have resulted in effective detection devices. In this review, the new trends in immunosensor development and the application of immunosensors for the detection of pesticides of environmental concern-such as glyphosate, organophosphates, and neonicotinoids-are described.

Primary B cell lymphoma of the rectum in a patient coinfected with HIV-1 and HTLV-I

Este artículo describe el caso clínico de un enfermo con SIDA coinfectado por HTLV-1 que desarrolló un linfoma B del recto, variedad sarcoma inmunoblástico con diferenciación plasmacitoide. Las células malignas mostraron arreglo clonal de los genes de las CP (Jh) y CLk. La infección por el VEB fue demostrada serológicamente y por hibridación de un monitor específico con el ADN genómico de las células cancerosas. No se detectaron secuencias de HTLV-1 en el seno del tumor. Una remisión clínica completa, pero temporal, se obtuvo con siete ciclos de VACO-B. El enfermo abandonó el tratamiento y la sobrevida se desconoce.