Persistent Activation of the P2X7 Receptor Underlies Chronic Inflammation and Carcinogenic Changes in the Intestine.

Aberrant signaling through damage-associated molecular patterns (DAMPs) has been linked to several health disorders, attracting considerable research interest over the last decade. Adenosine triphosphate (ATP), a key extracellular DAMP, activates the purinergic receptor P2X7, which acts as a danger sensor in immune cells and is implicated in distinct biological functions, including cell death, production of pro-inflammatory cytokines, and defense against microorganisms. In addition to driving inflammation mediated by immune and non-immune cells, the persistent release of endogenous DAMPs, including ATP, has been shown to result in epigenetic modifications.

Gut-related molecules as potential biomarkers in patients with decompensated cirrhosis.

Introduction And Objectives: Microbial translocation contributes to cirrhosis progression and complications. This study aims to investigate whether molecules related to intestinal permeability or microbial translocation can serve as prognostic biomarkers in patients with decompensated cirrhosis.

Materials And Methods: We prospectively evaluated hospitalized patients with decompensated cirrhosis for liver function, complications during hospitalization, in-hospital mortality, composite outcomes of in-hospital mortality and complications, 12-month mortality, and survival rates.

P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of -Induced Ileitis.

In mice, oral infection induces severe ileitis. The aim of the present study was to investigate the impact of the P2X7 receptor (P2X7) on the inflammatory response to -induced ileitis. Cysts of the ME49 strain of were used to induce ileitis.

The P2X7 Receptor Promotes Colorectal Inflammation and Tumorigenesis by Modulating Gut Microbiota and the Inflammasome.

Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). CA-CRC was induced in P2X7R and P2X7R mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). In a therapeutic protocol, P2X7R mice were treated with a P2X7R-selective inhibitor (A740003).

Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets.

Microbe-host communication is essential to maintain vital functions of a healthy host, and its disruption has been associated with several diseases, including Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD). Although individual members of the intestinal microbiota have been associated with experimental IBD, identifying microorganisms that affect disease susceptibility and phenotypes in humans remains a considerable challenge. Currently, the lack of a definition between what is healthy and what is a dysbiotic gut microbiome limits research.

Sulforaphane and Albumin Attenuate Experimental Intestinal Ischemia-Reperfusion Injury.

Background: Intestinal ischemia-reperfusion (I/R) injury constitutes a severe disorder, in great part resulting from oxidative stress. Because sulforaphane and albumin were shown to increase antioxidant defenses, we evaluated the therapeutic potential of these agents in an experimental model of I/R injury.

Methods: Wistar rats were used to establish a model of intestinal I/R (35 min of ischemia, followed by 45 min of reperfusion) and were treated with albumin (5 mL/kg), sulforaphane (500 μg/kg), or saline intravenously before reperfusion.

Eating habits, sleep, and a proxy for circadian disruption are correlated with dyslipidemia in overweight night workers.

Objective: The aim of this study was to evaluate the relationship between proxy for circadian disruption, eating habits, sleep characteristics, and dyslipidemic parameters.

Methods: This was a randomized, double-blind, crossover controlled clinical trial, and for this study, only baseline data were used. The sample was composed of 36 overweight female nurses who worked on a fixed night shift (12 × 36 h).

P2Y Receptor Antagonist Clopidogrel Attenuates Lung Inflammation Triggered by Silica Particles.

Silicosis is an occupational lung disease caused by inhalation of silica particles. It is characterized by intense lung inflammation, with progressive and irreversible fibrosis, leading to impaired lung function. Purinergic signaling modulates silica-induced lung inflammation and fibrosis through P2X7 receptor.

MSU Crystals induce sterile IL-1β secretion via P2X7 receptor activation and HMGB1 release.

Backgroud: The mechanism by which monosodium urate (MSU) crystals induce inflammation is not completely understood. Few studies have shown that MSU is capable of stimulating the release of IL-1β in the absence of LPS treatment. The purinergic P2X7 receptor is involved in the release of IL-1β in inflammatory settings caused by crystals, as is the case in silicosis.

P2X7 Receptor Signaling Contributes to Sepsis-Associated Brain Dysfunction.

Sepsis results in unfettered inflammation, tissue damage, and multiple organ failure. Diffuse brain dysfunction and neurological manifestations secondary to sepsis are termed sepsis-associated encephalopathy (SAE). Extracellular nucleotides, proinflammatory cytokines, and oxidative stress reactions are associated with delirium and brain injury, and might be linked to the pathophysiology of SAE.

Silica-induced inflammasome activation in macrophages: role of ATP and P2X7 receptor.

Silicosis is a fibrotic lung disease caused by the inhalation of silica particles, and is considered an occupational disease, given that these particles are present in the working environment of many mining and civil construction industries. NLRP3 inflammasome activation is an important mechanism during the inflammatory process of silicosis, and it promotes the production of cytokines, such as IL-1β and IL-18. ATP also plays an important role in silicosis.

Lipopolysaccharide-induced lung injury: role of P2X7 receptor.

Rationale: P2X7 receptors have been involved in inflammatory and immunological responses, and their activation modulates pro-inflammatory cytokines production by LPS-challenged macrophages.

Objectives: To determine the role of P2X7R in LPS-induced acute lung injury in mice.

Methods: Wild-type (C57BL/6) and P2X7 knockout mice received intratracheal injection of saline or Escherichia coli LPS (60 μg).