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Stress drives neuroendocrine signals with detrimental effects to the intestinal homeostasis. The aim of this study was to evaluate the effect of stress on intestinal hypoxia response elements, including G protein-coupled receptor 41 (GPR41), GPR43, and hypoxia inducible factor (HIF)-1α. Groups of five BALB/c mice were subjected to acute (2 h per day) and chronic (2 h per day for 4 days) stress induced by restraint, and the results were compared to those of an unstressed control group. Whole mucosal samples from the colon were collected to evaluate the expression of GPR41, GPR43 and HIF-1α using Western blot chemiluminescent analysis. Compared to the control group, in the chronic stress group the expression of GPR43 (P = 0.0092) and HIF-1α (P < 0.0001) were significantly lower and the expression of GPR41 was similar (P = 0.9184); acute stress significantly increased HIF-1α expression (P = 0.0030) and increased GPR41 expression (P = 0.0937), without affecting GPR43 (P = 0.9184). These findings offer insights into the modulation of hypoxia response elements under stress conditions and their pharmacological implications for developing drugs that mitigate the effects of stress on intestinal homeostasis. [ABSTRACT FROM AUTHOR]

Although the aetiology of inflammatory bowel diseases (IBDs) is still unknown, one of their main characteristics is that the immune system chronically affects the permeability of the intestinal lamina propria, in turn altering the composition of the microbiota. In this study, the TNBS rat model of colitis was used because it contains a complex inflammatory milieu of polymorphonuclear cells (PMN) and lymphocytes infiltrating the lamina propria. The aim of the present study was to investigate six dehydrogenases and their respective adaptations in the tissue microenvironment by quantifying enzymatic activities measured under substrate saturation conditions in epithelial cells and leukocytes from the lamina propria of rats exposed to TNBS. Our results show that in the TNBS group, an increased DAI score was observed due to the presence of haemorrhagic and necrotic areas in the colon. In addition, the activities of G6PDH and GADH enzymes were significantly decreased in the epithelium in contrast to the increased activity of these enzymes and increased lactate mediated by the LDH-A enzyme in leukocytes in the lamina propria of the colon. Over the past years, evidence has emerged illustrating how metabolism supports aspect of cellular function and how a metabolic reprogramming can drive cell differentiation and fate. Our findings show a metabolic reprogramming in colonic lamina propria leukocytes that could be supported by increased superoxide anion. [ABSTRACT FROM AUTHOR]

Host invasion by Entamoeba histolytica, the pathogenic agent of amebiasis, can lead to the development of amebic liver abscess (ALA). Due to the difficulty of exploring host and amebic factors involved in the pathogenesis of ALA in humans, most studies have been conducted with animal models (e.g., mice, gerbils, and hamsters). Histopathological findings reveal that the chronic phase of ALA in humans corresponds to lytic or liquefactive necrosis, whereas in rodent models there is granulomatous inflammation. However, the use of animal models has provided important information on molecules and mechanisms of the host/parasite interaction. Hence, the present review discusses the possible role of neutrophils in the effector immune response in ALA in rodents. Properly activated neutrophils are probably successful in eliminating amebas through oxidative and non-oxidative mechanisms, including neutrophil degranulation, the generation of free radicals (O2−, H2O2, HOCl) and peroxynitrite, the activation of NADPH-oxidase and myeloperoxidase (MPO) enzymes, and the formation of neutrophil extracellular traps (NETs). On the other hand, if amebas are not eliminated in the early stages of infection, they trigger a prolonged and exaggerated inflammatory response that apparently causes ALAs. Genetic differences in animals and humans are likely to be key to a successful host immune response.

Context: It has been reported that 17β-estradiol (E2) reduces the expression of inflammatory molecules, but there are no data that show the effect of E2 on the transcriptional regulation of innate immunity-related molecules and inflammasomes. Objective: To study the effect of 17β-estradiol (E2) on the transcriptional expression of the NLR family, pyrin domain containing 1 (Nlrp1) and (Nlrp3) inflammasomes, which are mediators of inflammation. Materials and methods: Inflammation was induced in adult female gonadectomized (Gdx) rats by intramuscular injection of complete Freund’s adjuvant (CFA). Measurements were taken at different times after the treatment. Gene expression determinations were done by quantitative real-time polymerase chain reaction (qRT-PCR). Results: CFA-induced inflammation increased the transcription ofNlrp3, IL-1β(p < 0.05), vascular cell adhesion molecule 1 (VCAM1),E-selectinand estrogen receptor 1 alpha (ERα) (p < 0.001) and decreased the transcription ofNlrp1, Caspase-1, IL-33, NFKB1, ICAM1, ICAM2, GCRα, GCRβ, UCP3andPGC1α(p < 0.001) compared to the control. The administration of E2 to the inflamed tissue significantly increased the expression ofNlrp1, NFKB1, ERα, UCP3, Caspase-1, E-selectin(p < 0.001),IL-18andERα(p < 0.05) and decreasedIL-1βandVCAM1(p < 0.005) compared to the control. Discussion and conclusion: CFA differentially modulates the transcription of inflammasome-related genes and the administration of E2 increases the expression ofERαandNlrp1together withNFKB1, a key molecule in the activation of the inflammasomes. Finally, an analysis using the web interface GeneMANIA revealed an interaction between several genes, indicating a functional correlation in this model. [ABSTRACT FROM PUBLISHER]

Life stress may influence symptom onset and severity in certain gastrointestinal disorders in association with a dysregulated intestinal barrier. It has been widely accepted that stress triggers the hypothalamus-pituitary-adrenal (HPA) axis, releasing corticosterone, which promotes intestinal permeability. In response, colonic inflammation alters mucosal immune homeostasis and destroys the colonic architecture, leading to severe intestinal diseases. Endogenous substance P (SP) does not inhibit the initial extent of the HPA axis response to restraint stress, but it reduces the duration of the stress, suggesting that SP plays an important role in the transition between acute and chronic stress. The present study aimed to investigate the effect of two groups of mice exposed to stress, including acute and chronic stress. The corticosterone was evaluated by ELISA, colon samples were obtained to detected polymorphonuclear cells by hematoxylin and eosin staining, goblet and mast cells were identified by immunocytochemistry and cytokine-producing CD4+ T cells were analyzed by flow cytometry assays, adhesion proteins in the colon epithelium by western blotting and serum SP levels by ELISA. The results demonstrated an increase in the number of polymorphonuclear, goblet and mast cells, a decrease in claudin-1 expression and an elevation in E-cadherin expression during acute stress. Increased E-cadherin expression was also detected during chronic stress. Moreover, it was found that acute stress caused a shift towards a predominantly anti-inflammatory immune response (T helper 2 cells), as shown by the increase in the percentage of CD4+/IL-6+ and CD4+/IL4+ lymphocytes in the lamina propria and the increase in serum SP. In conclusion, this response promoted colonic protection during acute stress. [ABSTRACT FROM AUTHOR]

Life stress may influence symptom onset and severity in certain gastrointestinal disorders in association with a dysregulated intestinal barrier. It has been widely accepted that stress triggers the hypothalamus‑pituitary‑adrenal (HPA) axis, releasing corticosterone, which promotes intestinal permeability. In response, colonic inflammation alters mucosal immune homeostasis and destroys the colonic architecture, leading to severe intestinal diseases. Endogenous substance P (SP) does not inhibit the initial extent of the HPA axis response to restraint stress, but it reduces the duration of the stress, suggesting that SP plays an important role in the transition between acute and chronic stress. The present study aimed to investigate the effect of two groups of mice exposed to stress, including acute and chronic stress. The corticosterone was evaluated by ELISA, colon samples were obtained to detected polymorphonuclear cells by hematoxylin and eosin staining, goblet and mast cells were identified by immunocytochemistry and cytokine‑producing CD4 + T cells were analyzed by flow cytometry assays, adhesion proteins in the colon epithelium by western blotting and serum SP levels by ELISA. The results demonstrated an increase in the number of polymorphonuclear, goblet and mast cells, a decrease in claudin‑1 expression and an elevation in E‑cadherin expression during acute stress. Increased E‑cadherin expression was also detected during chronic stress. Moreover, it was found that acute stress caused a shift towards a predominantly anti‑inflammatory immune response (T helper 2 cells), as shown by the increase in the percentage of CD4 + /IL‑6 + and CD4 + /IL4 + lymphocytes in the lamina propria and the increase in serum SP. In conclusion, this response promoted colonic protection during acute stress.