β(2 → 1)-β(2 → 6) branched graminan-type fructans and β(2 → 1) linear fructans impact mucus-related and endoplasmic reticulum stress-related genes in goblet cells and attenuate inflammatory responses in a fructan dependent fashion

Dietary fibers such as fructans have beneficial effects on intestinal health but it is unknown whether they impact goblet cells (GCs). Here we studied the effects of inulin-type fructans (ITFs) and graminan- type fructans (GTFs) with different molecular weights on mucus- and endoplasmic reticulum (ER) stress-related genes in intestinal GCs. To that end, GCs were incubated in the presence of ITFs or GTFs, or ITFs and GTFs + TNFα or the N-glycosylation inhibitor tunicamycin (Tm). IL-8 production by GCs was studied as a marker of inflammation. Effects between ITFs and GTFs were compared. We found a beneficial impact of GTFs especially on the expression of RETNLB. GTF II protects from the TNFα-induced gene expression dysregulation of MUC2, TFF3, GAL3ST2, and CHST5. Also, all the studied fructans prevented Tm-induced dysregulation of GAL3ST2. Interestingly, only the short chain fructans ITF I and GTF I have anti-inflammatory properties on GCs. All the studied fructans except ITF I decreased the expression of the ER stress-related HSPA5 and XBP1. All these benefits were fructanstructure and chain length dependent. Our study contributes to a better understanding of chemical structure-dependent beneficial effects of ITFs and GTFs on gut barrier function, which could contribute to prevention of gut inflammatory disorders

β(2 → 1)-β(2 → 6) and β(2 → 1) fructans protect from impairment of intestinal tight junction's gene expression and attenuate human dendritic cell responses in a fructan-dependent fashion

β(2 → 1)-β(2 → 6) branched graminan-type fructans (GTFs) and β(2 → 1) linear fructans (ITFs) possess immunomodulatory properties and protect human intestinal barrier function, however the mechanisms underlying these effects are not well studied. Herein, GTFs and ITFs effects with different degree of polymerization (DP) values on tight junctions (TJs) genes CLDN-1, -2 and -3, CDH1, OCLN and TJP1 were studied in Caco-2 gut epithelial cells, under homeostatic and inflammatory conditions. Also, cytokine production in dendritic cells (DCs) was studied. Higher DP fructans decreased the expression of the pore forming CLDN-2. Higher DP GTFs enhanced CLDN-3, OCLN, and TJP-1. Fructans prevented mRNA dysregulation of CLDN-1, -2 and -3 induced by the barrier disruptors A23187 and deoxynivalenol in a fructan-type dependent fashion. The production of pro-inflammatory cytokines MCP-1/CCL2, MIP-1α/CCL3 and TNFα by DCs was also attenuated in a fructan-type dependent manner and was strongly attenuated by DCs cultured with medium of Caco-2 cells which were pre-exposed to fructans. Our data show that specific fructans have TJs and DCs modulating effects and contribute to gut homeostasis. This might serve to design effective dietary means to prevent intestinal inflammation.</p

RELACIÓN DE LA ORIENTACIÓN AL CLIENTE, DE VALOR AL CLIENTE Y LA INNOVACIÓN SOBRE EL DESEMPEÑO ORGANIZACIONAL. UN ESTUDIO EN MIPYMES DEL ESTADO DE HIDALGO, MÉXICO

El objetivo de la presente investigación fue validar la relación entre la orientación al cliente, las acciones de innovación, el valor al cliente y el desempeño organizacional en mipymes establecidas en el estado de Hidalgo, México, mediante la utilización del análisis de correlación. Utilizando el software Stata, se confirmó la relación positiva y significativa de la orientación al cliente y el valor al cliente con el desempeño organizacional. No se encontró apoyo que validara la relación entre la innovación y el desempeño. Estos resultados aportan evidencia empírica de la relación de estas variables en un país en desarrollo

TLR 2/1 interaction of pectin depends on its chemical structure and conformation

Citrus pectins have demonstrated health benefits through direct interaction with Toll-like receptor 2. Methyl-ester distribution patterns over the homogalacturonan were found to contribute to such immunomodulatory activity, therefore molecular interactions with TLR2 were studied. Molecular-docking analysis was performed using four GalA-heptamers, GalA7Me0, GalA7Me1,6, GalA7Me1,7 and GalA7Me2,5. The molecular relations were measured in various possible conformations. Furthermore, commercial citrus pectins were characterized by enzymatic fingerprinting using polygalacturonase and pectin-lyase to determine their methyl-ester distribution patterns. The response of 12 structurally different pectic polymers on TLR2 binding and the molecular docking with four pectic oligomers clearly demonstrated interactions with human-TLR2 in a structure-dependent way, where blocks of (non)methyl-esterified GalA were shown to inhibit TLR2/1 dimerization. Our results may be used to understand the immunomodulatory effects of certain pectins via TLR2. Knowledge of how pectins with certain methyl-ester distribution patterns bind to TLRs may lead to tailored pectins to prevent inflammation.</p

The Giardial Arginine Deiminase Participates in Giardia-Host Immunomodulation in a Structure-Dependent Fashion via Toll-like Receptors

Beyond the problem in public health that protist-generated diseases represent, understanding the variety of mechanisms used by these parasites to interact with the human immune system is of biological and medical relevance. Giardia lamblia is an early divergent eukaryotic microorganism showing remarkable pathogenic strategies for evading the immune system of vertebrates. Among various multifunctional proteins in Giardia, arginine deiminase is considered an enzyme that plays multiple regulatory roles during the life cycle of this parasite. One of its most important roles is the crosstalk between the parasite and host. Such a molecular “chat” is mediated in human cells by membrane receptors called Toll-like receptors (TLRs). Here, we studied the importance of the 3D structure of giardial arginine deiminase (GlADI) to immunomodulate the human immune response through TLRs. We demonstrated the direct effect of GlADI on human TLR signaling. We predicted its mode of interaction with TLRs two and four by using the AlphaFold-predicted structure of GlADI and molecular docking. Furthermore, we showed that the immunomodulatory capacity of this virulent factor of Giardia depends on the maintenance of its 3D structure. Finally, we also showed the influence of this enzyme to exert specific responses on infant-like dendritic cells

Gelatin–chitosan–PVA hydrogels and their application in agriculture

This work demonstrated the ability of a fabrication process in the preparation of gelatin-chitosan-PVA hydrogels for potential agricultural applications. The hydrogels showed a dense, tridimensional, interconnected and reticulated structure that was more evident in the hydrogel loaded with inulin. The hydrogels showed a water absorption capacity of ≤12 times its mass. FTIR and light microscopy demonstrated that the hydrogels were biodegradable. The percentage of degradation of hydrogels in inoculated soil was higher than in sterile soil using the soil burial test. Hydrogel loaded with inulin was found to be capable of inducing resistance in chili plants against Phytophthora capsici.ITESO, A.C

Multilevel Approach for the Treatment of Giardiasis by Targeting Arginine Deiminase

Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme’s structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman’s method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis

Naturally occurring deamidated triosephosphate isomerase is a promising target for cell-selective therapy in cancer

Human triosephosphate isomerase (HsTIM) is a central glycolytic enzyme and is overexpressed in cancer cells with accelerated glycolysis. Triple-negative breast cancer is highly dependent on glycolysis and is typically treated with a combination of surgery, radiation therapy, and chemotherapy. Deamidated HsTIM was recently proposed as a druggable target. Although thiol-reactive drugs affect cell growth in deamidated HsTIM-complemented cells, the role of this protein as a selective target has not been demonstrated. To delve into the usefulness of deamidated HsTIM as a selective target, we assessed its natural accumulation in breast cancer cells. We found that deamidated HsTIM accumulates in breast cancer cells but not in noncancerous cells. The cancer cells are selectively programmed to undergo cell death with thiol-reactive drugs that induced the production of methylglyoxal (MGO) and advanced glycation-end products (AGEs). In vivo, a thiol-reactive drug effectively inhibits the growth of xenograft tumors with an underlying mechanism involving deamidated HsTIM. Our findings demonstrate the usefulness of deamidated HsTIM as target to develop new therapeutic strategies for the treatment of cancers and other pathologies in which this post translationally modified protein accumulates