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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. [ABSTRACT FROM AUTHOR]

In response to vascular injury or alterations in the local environment, such as hypoxia and hypertension, contractile vascular smooth muscle cells (VSMCs) are able to switch to a synthetic phenotype characterized by increased extracellular matrix synthesis with decreased expression of contractile markers. miR‐182‐5p has recently been reported to play a regulatory role in VSMCs proliferation. However, little is known about its target genes and related pathways in VSMCs phenotypic switch. Here, we investigated the function of miR‐182‐5p in VSMCs phenotypic switch. The results showed that upregulation of miR‐182‐5p promoted the switching of VSMCs from a contractile to a synthetic phenotype under hypoxic conditions. Mechanistically, hypoxia elevated miR‐182‐5p, leading to a reduction in expression of contractile markers and weakened RhoA signaling. Using bioinformatics analysis, dual‐luciferase reporter assays and rescue assays, we demonstrated that miR‐182‐5p suppressed RhoA signaling by targeting RGS5. Collectively, the results from the present study indicated that miR‐182‐5p/RGS5/RhoA axis regulated hypoxia‐induced VSMCs phenotypic switch. [ABSTRACT FROM AUTHOR]

The molecular weight (MW) of a protein can be predicted based on its amino acids (AA) composition. However, in many cases a non-chemically modified protein shows an SDS PAGE-displayed MW larger than its predicted size. Some reports linked this fact to high content of acidic AA in the protein. However, the exact relationship between the acidic AA composition and the SDS PAGE-displayed MW is not established. Zebrafish nucleolar protein Def is composed of 753 AA and shows an SDS PAGE-displayed MW approximately 13 kDa larger than its predicted MW. The first 188 AA in Def is defined by a glutamate-rich region containing ~35.6% of acidic AA. In this report, we analyzed the relationship between the SDS PAGE-displayed MW of thirteen peptides derived from Def and the AA composition in each peptide. We found that the difference between the predicted and SDS PAGE-displayed MW showed a linear correlation with the percentage of acidic AA that fits the equation y = 276.5x − 31.33 (x represents the percentage of acidic AA, 11.4% ≤ x ≤ 51.1%; y represents the average ΔMW per AA). We demonstrated that this equation could be applied to predict the SDS PAGE-displayed MW for thirteen different natural acidic proteins. [ABSTRACT FROM AUTHOR]

[Display omitted] Atherosclerosis (AS) is the common pathophysiological basis of various cardiovascular diseases and the leading cause of death from cardiovascular disease worldwide. When the body is in a hypoxic environment, enhanced oxidative stress and significant accumulation of reactive oxygen species (ROS) in tissue cells exacerbate the inflammatory response, resulting in increased release of myeloperoxidase (MPO), catalyzing the formation of large quantities of hypochlorous acid (HOCl), further oxidative modification of low-density lipoprotein (LDL), and exacerbating the formation and progression of atherosclerotic plaques. The MAPK signaling pathway is important in oxidative stress-mediated promotion of atherogenesis. MPO -/- mice were used in this study to establish a hypoxia model simulating 5000 m altitude and a Western high-fat diet-induced atherosclerosis model for 12 weeks. Exploring the role of MPO in the atherosclerotic process in hypoxic mice by observing the MAPK signaling pathway to provide a therapeutic target for the prevention and treatment of hypoxic atherosclerotic disease in the plateau. We found that hypoxia promotes the formation of atherosclerosis in mice, and the mechanism may be that increased MPO in vivo promotes an inflammatory response, which plays a crucial role in the formation of atherosclerosis. In addition, hypoxia further exacerbates plaque instability by activating the MAPK signaling pathway to upregulate vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9), which in turn promotes angiogenesis within the plaque. Therefore, a potential target for preventing and treating hypoxic atherosclerotic disease is the inhibition of MPO. [ABSTRACT FROM AUTHOR]

[Display omitted] • Comprehensive review of flavonols in the treatment of neurodegenerative diseases. • Flavonols are the natural polyphenols abundant in fruits and traditional herbs. • Nano encapsulated and SNEDDS drugs delivery of flavonol improve cognitive function. 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. [ABSTRACT FROM AUTHOR]