Inflammation
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Random X chromosome (ChrX) inactivation and consequent cellular mosaicism for the active ChrXs in white blood cells (WBCs) is unique to females and may contribute to sex-biased modulation of the innate immune response. Polymorphic differences between the two parental ChrXs may result in ChrX skewing of circulating WBCs (ChrX inactivation-ratio (XCI) > 3) driven by differences in stem cell selection and activity in the bone marrow or WBC trafficking at the periphery. Independent of the mechanism, ChrX skewing may result in genotype-phenotype discrepancies. ⋯ Because injury was shown to induce de novo ChrX skewing of WBCs, we tested the directional XCI ratio changes in WBC in a sample of trauma patients heterozygous for the variant IRAK1 haplotype (n = 18). Using the allele-specific assay in combination with the DNA methylation status at the polymorphic HUMARA locus, we found that at admission, about 60% the patients presented XCI ratios skewed toward WBCs with active ChrXs carrying the variant-IRAK1 similar to healthy controls. De novo, trauma-induced XCI ratio changes showed increased extravasation of the more abundant mosaic WBC subset without reversal in the direction of ChrX skewing during the injury course.
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Salidroside, an active constituent of Rhodiola rosea, is neuroprotective after transient middle cerebral artery occlusion (tMCAO). However, its effects in other experimental stroke models are less understood. Here, we investigated the effect of daily intraperitoneal injections of salidroside in rats after permanent MCAO (pMCAO). ⋯ LY294002, a PI3K inhibitor, prevented all these effects of salidroside, including those on NeuN, p-PKB/PKB, Nrf2, HO-1, and pro-inflammatory mediators. In contrast, salidroside had no significant effect on the level of cerebral complement C3 after pMCAO, or on the activity of C3 as measured by the expression of cerebral Egr1. Our findings therefore suggest that salidroside reduces neuroinflammation and neural damage by regulating the PI3K/PKB/Nrf2/NFκB signaling pathway after pMCAO, and that this neuroprotective effect does not involve modulation of complement C3 activity.
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Sepsis is a life-threatening condition with a high rate of mortality. Unfortunately, very few therapies can improve outcomes in patients with sepsis. Butyrate, which is the most potent histone deacetylase (HDAC) inhibitor among short-chain fatty acids, exerts anti-inflammatory effects in a variety of inflammatory diseases. ⋯ FD-4 leakage from the intestinal tract was reduced, and the expression levels of the tight junction proteins claudin-1 and ZO-1 were also restored in rats that received sodium butyrate treatment. These effects were associated with less NF-κB p65 nuclear translocation, whereas the expression of Iκ-Bα was not affected or even increased. Sodium butyrate mitigates the inflammatory response and maintains intestinal barrier function in polymicrobial sepsis partly through inhibition of NF-κB activation and may serve as a novel therapy for sepsis.
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Cardiopulmonary bypass (CPB) can induce inflammatory lung injury, which is a common complication during cardiac surgery. Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation plays a crucial role in lung injury after CPB. Previous studies have shown that electroacupuncture (EA) has potential anti-inflammatory activity. ⋯ Our results showed that the expression of NLRP3 in the lung tissue increased significantly after CPB. The EA pretreatment suppressed NLRP3 inflammasome activation, reduced lung edema, and inhibited IL-1β release into the serum and BALF after CPB. Our findings suggest that EA pretreatment attenuates inflammatory lung injury after CPB by suppressing NLRP3 inflammasome activation.
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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) undergoes the process of pathological event including lung tissue dysfunction, pulmonary edema, and inflammation in sepsis. Autophagy is a cytoprotective process recognized as one of the major pathways for degradation and recycling of cellular constituents. Autophagy as a protective or maladaptive response was still confused in ALI during sepsis. ⋯ Compared with ALI group, Baf and CQ obviously elevated the level of LC3II and Beclin 1, and reduced the LAMP2 and Rab7 expressions in CLP + Baf group and ALI + CQ group. Compared with CLP group, autophagic inducer rapacymin improved the survival rate, histologic scores, lung wet/dry weight ratio, PaO2/FiO2, total cells, and PMNS in BALF and MPO activity and cytokines TNF-α, HMGB1, IL-6, IL-10, and MCP1 in CLP + RAP group, but there were exacerbated above indicators in CLP + 3-MA group, CLP + Baf group, and CLP + CQ group. Autophagy activation participated in the pathophysiologic process of sepsis, and alleviated the cytokine excessive release and lung injury in sepsis.