An interspecies translation model implicates integrin signaling in infliximab-resistant inflammatory bowel disease.

Anti-tumor necrosis factor (anti-TNF) therapy resistance is a major clinical challenge in inflammatory bowel disease (IBD), due, in part, to insufficient understanding of disease-site, protein-level mechanisms. Although proteomics data from IBD mouse models exist, data and phenotype discrepancies contribute to confounding translation from preclinical animal models of disease to clinical cohorts. We developed an approach called translatable components regression (TransComp-R) to overcome interspecies and trans-omic discrepancies between mouse models and human subjects.

Development and Application of the Metalloprotease Activity Multiplexed Bead-Based Immunoassay (MAMBI).

Metalloproteinases (MMPs) are zinc-dependent endopeptidases that cleave various proteins to regulate normal and diseased cellular functions, and as such, they play significant roles in human tissue development, homeostasis, and the pathogenesis of many diseases, including cancers, endometriosis, arthritis, etc. Most MMPs are produced as zymogenic latent enzymes that must be cleaved to activate their catalytic regions, and localized endogenous protein inhibitors further regulate activity. Accordingly, they operate within recursive networks to degrade extracellular matrix proteins and regulate cell signaling by cleaving growth factors and receptors at the cell surface and in the local pericellular environment.

Peritoneal fluid cytokines related to endometriosis in patients evaluated for infertility.

Objective: Our aim was to characterize peritoneal cytokine profiles in patients with infertility, with and without endometriosis, to illuminate potential differences in immune profiles that may reflect mechanistic differences between these two patient populations.

Design: Cross-sectional study.

Setting: University hospital and research center.

The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury Models.

Neural input to the immune system can alter its ability to clear pathogens effectively. Patients suffering mild traumatic brain injury (mTBI) have shown reduced rates of pneumonia and a murine model replicated these findings, with better overall survival of TBI mice compared with sham-injured mice. To further investigate the mechanism of improved host response in TBI mice, this study developed and characterized a mild tail trauma model of similar severity to mild TBI.

Antagonism of the Neurokinin-1 Receptor Improves Survival in a Mouse Model of Sepsis by Decreasing Inflammation and Increasing Early Cardiovascular Function.

Objectives: Sepsis remains a serious clinical problem despite intensive research efforts and numerous attempts to improve outcome by modifying the inflammatory response. Substance P, the principal ligand for the neurokinin-1 receptor, is a potent proinflammatory mediator that exacerbates inflammatory responses and cardiovascular variables in sepsis.

Design: The current study examined whether inhibition of the neurokinin-1 receptor with a specific antagonist (CJ-12,255) would improve survival in the cecal ligation and puncture model of sepsis in adult female outbred mice.

Acute-Phase Deaths from Murine Polymicrobial Sepsis Are Characterized by Innate Immune Suppression Rather Than Exhaustion.

Sepsis, a leading cause of death in the United States, has poorly understood mechanisms of mortality. To address this, our model of cecal ligation and puncture (CLP) induced sepsis stratifies mice as predicted to Live (Live-P) or Die (Die-P) based on plasma IL-6. Six hours post-CLP, both Live-P and Die-P groups have equivalent peritoneal bacterial colony forming units and recruitment of phagocytes.

Location, location, location: cytokine concentrations are dependent on blood sampling site.

Objective: Considerable breakthroughs in the field of sepsis have been made using animal models. Sepsis exhibits a wide array of derangements that may be evaluated in the blood, including the release of proinflammatory and anti-inflammatory cytokines. The Shock journal adheres to the ARRIVE guidelines regarding reporting in vivo results to allow reproducibility of data findings.

Early murine polymicrobial sepsis predominantly causes renal injury.

Multiple organ failure in sepsis substantially increases mortality. This study examined if there was greater hepatic, pancreatic, splenic, or renal injury in mice that would die during sepsis induced by cecal ligation and puncture (CLP) compared with that of those that would survive. Mice were stratified into groups predicted to die (Die-P) or predicted to live (Live-P) in the first 5 days after CLP based on plasma interleukin 6 levels.