miR-200a attenuated oxidative stress, inflammation, and apoptosis in dextran sulfate sodium-induced colitis through activation of Nrf2

IntroductionOxidative stress and inflammatory responses are critical factors in ulcerative colitis disease pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) modulates oxidative stress and suppresses inflammatory responses, and the protective benefits of Nrf2 activation have been associated with the therapy of ulcerative colitis. MicroRNA-200a (miR-200a) could target Kelch-like ECH-associated protein 1 (Keap1) and activate the Nrf2-regulated antioxidant pathway. Nevertheless, whether miR-200a modulates the Keap1/Nrf2 pathway in dextran sulfate sodium (DSS)-induced colonic damage is unknown. Here, our research intends to examine the impact of miR-200a in the model of DSS-induced colitis.MethodsPrior to DSS intervention, we overexpressed miR-200a in mice for four weeks using an adeno-associated viral (AAV) vector to address this problem. ELISA detected the concentration of inflammation-related cytokines. The genes involved in inflammatory reactions and oxidative stress were identified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence. Moreover, we applied siRNAs to weakened Nrf2 expression to confirm the hypothesis that miR-200a provided protection via Nrf2.ResultsThe present study discovered miR-200a down-regulation, excessive inflammatory activation, enterocyte apoptosis, colonic dysfunction, and Keap1/Nrf2 antioxidant pathway inactivation in mouse colitis and NCM460 cells under DSS induction. However, our data demonstrated that miR-200a overexpression represses Keap1 and activates the Nrf2 antioxidant pathway, thereby alleviating these adverse alterations in animal and cellular models. Significantly, following Nrf2 deficiency, we failed to observe the protective benefits of miR-200a against colonic damage.DiscussionTaken together, through activating the Keap1/Nrf2 signaling pathway, miR-200a protected against DSS-induced colonic damage. These studies offer an innovative therapeutic approach for ulcerative colitis

The role of Nrf2 in the pathogenesis and treatment of ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease involving mainly the colorectal mucosa and submucosa, the incidence of which has been on the rise in recent years. Nuclear factor erythroid 2-related factor 2 (Nrf2), known for its key function as a transcription factor, is pivotal in inducing antioxidant stress and regulating inflammatory responses. Numerous investigations have demonstrated the involvement of the Nrf2 pathway in maintaining the development and normal function of the intestine, the development of UC, and UC-related intestinal fibrosis and carcinogenesis; meanwhile, therapeutic agents targeting the Nrf2 pathway have been widely investigated. This paper reviews the research progress of the Nrf2 signaling pathway in UC

Inhibition of IRAK 1/4 alleviates colitis by inhibiting TLR4/ NF-κB pathway and protecting the intestinal barrier

Interleukin-1 receptor-associated kinase 1/4 (IRAK1/4) is the main kinase of the Toll-like receptor (TLR)-mediated pathway, considered a new target for treating inflammatory diseases. Studies showed a significant correlation between TLRs and inflammatory responses in ulcerative colitis (UC). Therefore, in this study, after inducing experimental colitis in mice with 3% dextran sulfate sodium (DSS), different concentrations of IRAK1/4 inhibitors were administered intraperitoneally. Then, the disease activity index was assessed, including the degree of pathological damage, by HE staining. Subsequently, while western blotting detected the TLR4/NF-κB pathway and intestinal barrier protein expression (Zonula-1, Occludin, Claudin-1, JAM-A), real-time polymerase chain reaction (RT-PCR) detected the mRNA expression levels of IRAK1/4 and mucin1/2. Furthermore, the expression levels of Zonula-1 and occludin were detected by immunofluorescence, including the plasma FITC-dextran 4000 concentration, to evaluate intestinal barrier permeability. However, ELISA measured the expression of inflammatory factors to reflect intestinal inflammation in mice. Investigations showed that the IRAK 1/4 inhibitor significantly reduced clinical symptoms and pathological DSS-induced colitis damage in mice and then inhibited the cytoplasmic and nuclear translocation of NF-κB p65, including the phosphorylation of IκBα and reduction in downstream inflammatory factor production. Therefore, we established that the IRAK1/4 inhibitor effectively improves colitis induced by DSS, partly by inhibiting the TLR4/NF-κB pathway, reducing inflammation, and maintaining the integrity of the colonic barrier

Research on Defect Detection Technology of Composite Insulator Sheath

The composite insulator sheath plays an important role in protecting the core rod and insulation. The thickness of the sheath must meet the corresponding standard requirements. During the insulator manufacturing process, the core rod decentration leads to uneven thickness of the sheath, which is easy to cause the risk of composite insulators premature failure during operation. The phased array detection technology can accurately detect the thickness of the sheath, so that defects such as uneven thickness of the sheath (decentration of the core rod) can be detected, and the thickness of the sheath at the end of the composite insulator can also be effectively detected. DR detection technology can effectively identify the interface between the mandrel and the sheath, but there is a risk of the sheath thickness distortion due to inappropriate transillumination parameters

Corrosion Behaviors of Fe-22Cr-16Mn-0.55N High-Nitrogen Austenitic Stainless Steel in 3.5% NaCl Solution

In this study, the corrosion behavior of the high-nitrogen austenitic stainless steel (HNS) Fe-22Cr-16Mn-0.55N before and after solution treatment (ST) in 3.5% NaCl solution has been investigated. The effect of a solution temperature of 1100 °C and heat preservation for 30 min on the corrosion resistance and passive film protection of HNS steel was studied. Open-circuit potential, potentiodynamic polarization and electrochemical impedance tests were used to assess the corrosion resistance of treated and untreated steels. In addition, potentiostatic polarization and XPS techniques together with Mott–Schottky curves were applied to determine the composition and properties of the passive films. The results showed that after solution treatment, the grain size of HNS decreased and the grain became more uniform. Although corrosion occurred on HNSs both before and after treatment, solution treatment resulted in greater compactness in passive films, leading to lower carrier density, lower corrosion current density and better corrosion resistance