A Genome-Wide Association Study of Serum Metabolite Profiles in Septic Shock Patients.

Objectives: We sought to assess whether genetic associations with metabolite concentrations in septic shock patients could be used to identify pathways of potential importance for understanding sepsis pathophysiology.

Design: Retrospective multicenter cohort studies of septic shock patients.

Setting: All participants who were admitted to 27 participating hospital sites in three countries (Australia, New Zealand, and the United Kingdom) were eligible for inclusion.

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.

Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain.

Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), and sacroiliac MRI.

Septic Shock: A Genomewide Association Study and Polygenic Risk Score Analysis.

Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits.

Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci.

Purpose: Acute anterior uveitis (AAU) is a common intraocular inflammatory disease. AAU occurs in 30% to 50% of patients with ankylosing spondylitis (AS), and both conditions are strongly associated with human leukocyte antigen (HLA)-B27, implying a shared etiology. This study aims to apply genomewide association study (GWAS) to characterize the genetic associations of AAU and their relationship to the genetics of AS.

Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS.

JAK2 and AMP-kinase inhibition in vitro by food extracts, fractions and purified phytochemicals.

We have identified a range of food phytochemicals that inhibit Janus Kinase 2 (JAK2) and Adenosine Monophosphate Kinase (AMPK). A mutated and dysregulated form of JAK2, a tyrosine kinase, is associated with several diseases including Crohn's disease. Using an in vitro, time-resolved fluorescence (TR-FRET) assay, we tested 49 different types of food extracts, plus 10 concentrated fractions of increasing hydrophobicity from each extract, to find foods containing JAK2 inhibitors.

Inconsistent hepatic antifibrotic effects with the iron chelator deferasirox.

Background And Aim: Development of effective antifibrotic treatments that can be translated to clinical practice is an important challenge in contemporary hepatology. A recent report on β-thalassemia patients demonstrated that deferasirox treatment reversed or stabilized liver fibrosis independent of its iron-chelating properties. In this study, we investigated deferasirox in cell and animal models to better understand its potential antifibrotic effects.

Lack of efficacy of mTOR inhibitors and ACE pathway inhibitors as antifibrotic agents in evolving and established fibrosis in Mdr2⁻/⁻ mice.

Background & Aims: Mammalian target of rapamycin and angiotensin-converting enzyme inhibition has been shown to have antifibrotic activity in models of liver fibrosis. The aim of our study was to determine the efficacy of rapamycin, everolimus, irbesartan and captopril, alone and in combination, as antifibrotic agents in the Mdr2(-/-) model of cholestasis both in early injury and established disease.

Methods: Mdr2(-/-) mice were treated for 4 weeks with vehicle, rapamycin (1 mg/kg) or everolimus (5 mg/kg) every second day or with captopril (30 mg/kg/day), irbesartan (10 mg/kg/day) or vehicle.

Alterations in deoxyribonucleic acid (DNA) methylation patterns of Calca, Timp3, Mmp2, and Igf2r are associated with chronic cystitis in a cyclophosphamide-induced mouse model.

Objective: To determine whether epigenetic changes occur during cyclophosphamide-induced chronic bladder inflammation in mice.

Materials And Methods: Epigenetic changes play a role in the regulation of inflammatory genes in noncancer diseases such as asthma and chronic obstructive pulmonary disease. However, epigenetic (deoxyribonucleic acid [DNA] methylation) changes during chronic bladder inflammation have not been previously described.