Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Sepsis induces intestinal hyperpermeability, which is associated with higher mortality. Occludin is a tight junction protein that plays a critical role in regulating disease-associated intestinal barrier loss. This study examined the role of intestinal occludin on gut barrier function and survival in a pre-clinical model of sepsis. ⋯ Notably, 7-day mortality was significantly higher in occludin KOIEC mice following sepsis. Occludin thus plays a critical role in preserving gut barrier function and mediating survival during sepsis, associated with alterations in inflammation and bacteremia. Agents that preserve occludin function may represent a new therapeutic strategy in the treatment of sepsis.
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Background: Sepsis-induced cardiomyopathy (SIC), one of the most common complications of sepsis, seriously affects the prognosis of critically ill patients. Choline metabolism is an important biological process in the organism, and the mechanism of its interaction with SIC is unclear. The aim of this study was to reveal the choline metabolism genes (CMGs) associated with SIC and to provide effective targets for the treatment of SIC. ⋯ Subsequent differential analysis based on the high and low HIF-1α expression yielded 63 DEGs and then they were uploaded into Cytoscape software to construct a protein-protein interaction (PPI) network and 6 hub genes with the highest priority were obtained (CISH, THBS1, IMP1, MYC, SOCS3 and VCAN). Finally, a multifactorial COX analysis revealed a significant correlation between HIF-1α and survival in SIC patients, which was further validated by in vitro and in vivo experiments. Conclusion: Our findings will provide new insights into the pathogenesis of SIC, and HIF-1α may have important applications as a potential biomarker for early detection and therapeutic intervention in SIC.
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Background: Tumor necrosis factor receptor associated factor 3 (TRAF3) and deubiquitinating enzyme ubiquitin-specific protease 33 (USP33) have been identified to play important roles in inflammatory diseases, including acute pancreatitis (AP). Here, we aimed to explore whether USP33 affected AP progression by affecting TRAF3 expression through deubiquitination. Methods: Caerulein-treated HPDE6-C7 cells were used to mimic AP conditions in vitro. ⋯ Further analyses showed that USP33 knockdown reversed caerulein-induced apoptosis, oxidative stress and inflammation in HPDE6-C7 cells by TRAF3 (P < 0.05). Moreover, USP33-TRAF3 activated the NF-κB pathway (P < 0.05). Conclusion: USP33 promoted caerulein-induced apoptosis, oxidative stress and inflammation in pancreatic ductal cells by deubiquitinating TRAF3, indicating a novel insight into the pathogenesis of AP.
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Introduction: Hematopoiesis proceeds in a tiered pattern of differentiation, beginning with hematopoietic stem cells (HSC) and culminating in erythroid, myeloid, and lymphoid lineages. Pathologically altered lineage commitment can result in inadequate leukocyte production or dysfunctional cell lines. Drivers of emergency hematopoiesis after burn injury are inadequately defined. ⋯ Discussion: Full-thickness burn results in an emergency hematopoiesis via proportional increase of long-term HSC and short-term HSC/MPP1 subpopulations beginning in the early postinjury period. Subsequent lineage commitment displays a myeloid predominance with a shift toward myeloid progenitors with mRNA analysis corroborating this finding with associated upregulation of PU.1 and downregulation of GATA-1 and GATA-3. Further studies are needed to understand how burn-induced emergency hematopoiesis may predispose to infection by pathologic lineage selection.
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Background : Previous preclinical studies have demonstrated a pathobiome after traumatic injury; however, the impact of postinjury sepsis on gut epithelial permeability and bacterial translocation remains unknown. We hypothesized that polytrauma with postinjury pneumonia would result in impaired gut permeability leading to specific blood microbiome arrays. Methods : Male and proestrus female Sprague-Dawley rats were subjected to either polytrauma (PT), PT plus 2-hours daily chronic restraint stress (PT/CS), PT with postinjury day 1 inoculation with pseudomonas pneumonia (PT + PNA), PT/CS + PNA, or naive controls. ⋯ Females PT/CS + PNA had a significant abundance of Staphylococcus at day 2 and Streptococcus at day 7 in the blood biome compared to male counterparts ( P < 0.05). Conclusion : Multicompartmental trauma with postinjury pneumonia results in increased intestinal permeability and bacteremia with a unique blood biome, with sexual dimorphisms evident in the blood biome composition. These findings suggest that postinjury sepsis has clinical significance and could influence outcomes after severe trauma and critical illness.