bay-11-7082 and Inflammatory-Bowel-Diseases

Social anxiety (SA) and depression are prevalent, often comorbid disorders, associated with poor psychosocial functioning. Experimental psychopathology approaches can clarify the transdiagnostic mechanisms underlying these disorders, but most laboratory tasks are limited. We developed and validated the Audio-Dialogue Inductions of Social Stress (A-DISS) experimental task to model real-time rejection sensitivity in a realistic and developmentally relevant context. Participants are asked to imagine overhearing peers at a party talking badly about them (Rejection) or a teacher at their school (Neutral).. The Rejection condition elicited higher negative affect/lower positive affect while the Neutral condition sustained stable affect. Findings were consistent across gender and race/ethnicity. Moderation analyses were statistically significant; participants with elevated SA or depression reported feeling more rejected, insecure, and anxious after Rejection than those with below average symptoms.. Findings provide preliminary validation of a novel peer rejection task for research on understanding the affective experience of real-time rejection overall, especially for those with elevated SA and depression. SA and depression symptoms each uniquely moderating the effects of Rejection exposure on similar affective states, suggests individuals with SA or depression may benefit from interventions targeting specific reactions to rejection/stress and transdiagnostic risk factors.. Our results suggest that T lymphocyte immune dysfunction does exist in adult ITP patients and plays an important role in the pathogenesis of ITP.. ClinicalTrials.gov, identifier NCT03575988.. Brown/beige adipocyte-specific h

Topics: A549 Cells; Acute Lung Injury; Adipose Tissue, Brown; Adipose Tissue, White; Adolescent; Adult; Aged; Animals; Anthropometry; Anti-Inflammatory Agents; Antiviral Agents; Arachidonic Acid; Archaeoglobus fulgidus; Australia; Blood Glucose; Blotting, Western; Carcinoma, Hepatocellular; Cathartics; Cell Differentiation; Chemokine CCL2; Child; China; Colonoscopy; Crosses, Genetic; Cyclin B1; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Endothelin-1; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Finland; Follow-Up Studies; Genes, Dominant; Glycated Hemoglobin; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Homeodomain Proteins; Humans; Hypothalamus; Incidence; Inflammatory Bowel Diseases; Interleukin-1beta; Interleukin-6; Italy; Lipopolysaccharides; Liver Cirrhosis; Liver Neoplasms; Lung; Male; Mice; MicroRNAs; Middle Aged; Motivational Interviewing; NAD; Neuroendocrine Tumors; NF-kappa B; Nitric Oxide; Nitriles; Outpatients; Oxidoreductases; Phenotype; Pilot Projects; Polyethylene Glycols; Polymorphism, Genetic; Prospective Studies; Protein Interaction Maps; Quality of Life; Reproducibility of Results; Shewanella; Signal Transduction; Spain; Sulfides; Sulfones; Thermogenesis; Transcription Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Uncoupling Protein 1; United Kingdom

Pharmacological inhibition of NLRP3 inflammasome activation may offer a new option in the treatment of inflammatory bowel disease. In this work, we report the design, synthesis, and biological screening of a series of acrylate derivatives as NLRP3 inhibitors. The in vitro determination of reactivity, cytotoxicity, NLRP3 ATPase inhibition, and antipyroptotic properties allowed the selection of 11 (INF39), a nontoxic, irreversible NLRP3 inhibitor able to decrease interleukin-1β release from macrophages. Bioluminescence resonance energy transfer experiments proved that this compound was able to directly interfere with NLRP3 activation in cells. In vivo studies confirmed the ability of the selected lead to alleviate the effects of colitis induced by 2,4-dinitrobenzenesulfonic acid in rats after oral administration.

Topics: Acrylates; Animals; Energy Transfer; Inflammasomes; Inflammatory Bowel Diseases; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley