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Abstract Background High-altitude exposure can cause oxidative stress damage in the intestine, which leads to increased intestinal permeability and bacterial translocation, resulting in local and systemic inflammation. Control of infection is critically dependent on the host’s ability to kill pathogens with reactive oxygen species (ROS). Myeloperoxidase (MPO) targets ROS in pathogens. This study aimed to investigate the effects of hypoxia on the colonic mucosal barrier and myeloperoxidase (MPO)-mediated innate immune response in the colon. Methods and Results Genetically engineered mice were exposed to a hypobaric oxygen chamber for 3 days and an inflammation model was established using Salmonella Typhimurium infection. We found that hypoxic exposure caused the development of exacerbated bacterial colitis and enhanced bacterial dissemination in MPO-deficient mice. Infection and disease severity were associated with significantly increased Ly6G+ neutrophil and F4/80+ macrophage counts in infected tissues, which is consistent with elevated proinflammatory cytokines and chemoattractant molecules. Hypoxia restrained antioxidant ability and MPO deficiency aggravated the respiratory burst in the colon. Conclusion Hypoxia can damage the colonic mucosa. MPO mediates the innate immune response and regulates the mucosal and systemic inflammatory responses to Salmonella infection during hypoxia.

Ulcerative colitis (UC) is a prevalent disorder characterized by oxidative stress and the release of pro-inflammatory cytokines that disturb the colonic mucosa. Currently, available medicines for UC remain unsatisfactory. Diacerein (DIAC) has exhibited anti-oxidant and anti-inflammatory properties in wide inflammatory disorders. However, the limited understanding of DIAC's role in bowel inflammation has necessitated the investigation of its efficacy in dextran sodium sulfate (DSS)-induced UC in Balb/c mice in this study. Fifty mice were equally divided into five groups. Except for the control, all groups were given DSS for seven days to induce the colitis model. The model was treated with 25 and 50mg/kg/day of DIAC and 00mg/kg/day of 5-aminosalicylic acid (5-ASA) for ten days. Several clinical, molecular and biochemical parameters were evaluated. Following the exposure to DSS, there was a significant upregulation in the pro-inflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α) and oxidative stress index (MDA). Meanwhile, the concentration of anti-oxidative stress indices (SOD, GPx and CAT) and the levels of IL-10, mucin-1 and 2 and tight junction proteins (TJs) ZO-1 and occludin were markedly suppressed. The colon length and body weight were reduced while DAI and myeloperoxidase (MPO) were elevated. Conversely, DIAC 50mg and 5-ASA significantly reversed the altered pro-inflammatory cytokines, oxidative stress and MPO. Moreover, they significantly restored body weight, colon length, DAI, TJs, mucin-1 and 2 and IL-10. No significant results were found with DIAC 25mg. In conclusion, DIAC exhibited therapeutic effectiveness against colitis. This research may provide hope for testing its effectiveness against UC in humans

Abstract Purpose Myeloperoxidase (MPO) has been identified as a mediator in various inflammatory diseases. Bacterial infection of the intestine and hypoxia can both lead to inflammatory responses, but the role of MPO in these phenomena remains unclear. Methods By building the MPO‐/‐ mice, we evaluated relevant inflammatory factors and tissue damage in mice with intestinal Citrobacter rodentium infection and hypoxia. The body weight and excreted microorganisms were monitored. Intestinal tissues were collected 7 days after bacterial infection under hypoxia to undergo haematoxylin‐eosin staining and assess the degree of pathological damage. ELISA assays were performed to quantify the serum levels of TNF‐α, IFN‐γ, IL‐6, and IL‐1β inflammatory cytokines. PCR, WB, and IF assays were conducted to determine the expression of chemokines MCP1, MIP2, and KC in the colon and spleen. Results The C. rodentium infection and hypoxia caused weight loss, intestinal colitis, and splenic inflammatory cells active proliferation in wild‐type mice. MPO deficiency alleviated this phenomenon. MPO‐/‐ mice also displayed a significant decline in bacteria clearing ability. The level of TNF‐α in the serum and spleen was both lower in MPO‐/‐ hypoxia C. rodentium‐infected mice than that in wild‐type mice. The chemokines expression levels of MIP2, KC, and MCP1 in the spleen and colon of each bacterial infected group were significantly increased (p

ObjectiveTo explore the relationship between intestinal flora and obesity in Tibetan children at different altitudes.MethodsUsing16S rRNA gene sequencing results and blood lipid metabolism indexes to study the characteristics of the intestinal flora present in faeces and changes in blood lipid metabolism in obese children in Tibet who reside at different altitudes and to study correlations between blood lipid metabolism indicators and the intestinal flora composition.ResultsThe results showed the following. (a) The triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels in the obesity groups were higher than those in the normal-weight groups, and those in the high-altitude obesity groups were lower than those in the low-altitude obesity groups. (b) The 16S rRNA gene sequencing results showed that altitude affected the composition and relative abundance of the gut microbiota. These parameters were basically the same among the low-altitude groups, while they were significantly lower in the high-altitude groups than in the low-altitude groups. (c) Groups that lived at different altitudes and had different body weights had different dominant bacterial genera. Megamonas was closely related to obesity, and its relative abundance in the low-altitude groups was higher than that in the high-altitude groups. Prevotella was associated with altitude, and its relative abundance in the high-altitude groups was higher than that in the low-altitude groups. In addition, Prevotella elicited changes in the abundance of Escherichia-Shigella. The lower prevalence of obesity and incidence of intestinal inflammation in those living at high altitudes were related to the abundance of Prevotella. (d) There were correlations between the gut microbiota composition and lipid metabolism indicators. The abundance of Romboutsia was positively correlated with TG and LDL-C levels but negatively correlated with high-density lipoprotein cholesterol (HDL-C) levels. The abundance of Akkermansia was negatively correlated with LDL-C levels, and the abundance of Blautia was negatively correlated with body mass index (BMI) and LDL-C levels.ConclusionsThe intestinal flora diversity varied by body weight and altitude, with lower diversity in those at higher altitudes and with lower body weights. Prevotella likely plays a role in suppressing obesity at high altitudes.

With a large and increasing elderly population, neurodegenerative diseases such as Parkinson’s disease (PD), Huntington disease (HD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS) and Multiple sclerosis (MS) have become a major and growing health problem. During the past few decades, the elderly population has grown 2.5 % every year. Unfortunately, there are no specific therapeutic remedies available to slow the onset or development of these diseases. An aging brain causes many pathophysiological changes and is the major risk factor for most of the neurodegenerative disorders. Polyphenolic compounds such as flavonols have shown therapeutic potential and can contribute to the treatment of these diseases. In this review, evidence for the beneficial neuroprotective effect of multiple flavonols is discussed and their multifactorial cellular pathways for the progressions of age-associated brain changes are identified. Moreover, the animal models of these diseases support the neuroprotective effect and target the potential of flavonols in the treatment of neurodegenerative diseases.

Ulcerative colitis (UC) is a prevalent disorder characterized by oxidative stress and the release of pro-inflammatory cytokines that disturb the colonic mucosa. Currently, the available medicines for UC remain unsatisfactory. Diacerein (DIAC) has exhibited anti-oxidant and anti-inflammatory properties in a wide range of inflammatory disorders. However, limited understanding of DIAC's role in bowel inflammation has necessitated the investigation of its efficacy in dextran sodium sulfate (DSS)-induced UC in Balb/c mice in this study. Fifty mice were equally divided into five groups. Except for the control, all groups were given DSS for seven days to induce the colitis model. The model was treated with 25 and 50 mg/kg/day of DIAC and 100 mg/kg/day of 5-aminosalicylic acid (5-ASA) for ten days. Several clinical, molecular and biochemical parameters were evaluated. Following exposure to DSS, there was a significant upregulation in the pro-inflammatory cytokines (IL-1ß, IL-6, IL-17 and TNF-a) and oxidative stress index (MDA). Meanwhile, the concentration of antioxidative stress indices (SOD, GPx and CAT) and the levels of IL-10, mucin-1 and 2 and tight junction proteins (TJs) ZO-1 and occludin were markedly suppressed. The colon length and body weight were reduced while DAI and myeloperoxidase (MPO) were elevated. Conversely, DIAC 50 mg and 5-ASA significantly reversed the altered pro-inflammatory cytokines, oxidative stress, and MPO. Moreover, they significantly restored body weight, colon length, DAI, TJs, mucin-1 and 2, and IL-10. No significant results were found with DIAC 25 mg. In conclusion, DIAC exhibited therapeutic effectiveness against colitis. This research may provide hope for testing its effectiveness against UC in humans. [ABSTRACT FROM AUTHOR]