Correction to: Vedolizumab Concentrations Are Associated with Long-Term Endoscopic Remission in Patients with Inflammatory Bowel Diseases.

The original version of the article unfortunately contained a couple of errors. In 'methods' section, in 'Outcomes' subsection, the sentence 'Endoscopic remission was defined as an SESCD ≤ 2 in patients with CD and an EMS ≤ 2 in UC patients while off corticosteroids.'

Higher Trough Vedolizumab Concentrations During Maintenance Therapy are Associated With Corticosteroid-Free Remission in Inflammatory Bowel Disease.

Background And Aims: Vedolizumab is an anti-α4β7 biologic approved for ulcerative colitis [UC] and Crohn's disease [CD]. We aimed to examine the association of maintenance vedolizumab concentrations with remission.

Methods: We performed a cross-sectional multi-centre study of inflammatory bowel disease [IBD] patients on maintenance vedolizumab.

Vedolizumab Concentrations Are Associated with Long-Term Endoscopic Remission in Patients with Inflammatory Bowel Diseases.

Background: The aim of this study was to assess the relationship of serum vedolizumab concentrations (SVC) during induction and endoscopic remission in patients with inflammatory bowel diseases (IBD) after 52 weeks of therapy with vedolizumab. We also sought to assess the incidence of antibody to vedolizumab (ATV) formation, the effect of ATV on drug pharmacokinetics and efficacy, and identify variables associated with SVC through the first 30 weeks of treatment.

Methods: This is a prospective cohort study of patients with active IBD initiating standard therapy with vedolizumab.

The Impact of Combination Therapy on Infliximab Levels and Antibodies in Children and Young Adults With Inflammatory Bowel Disease.

Goal: The aim of this study was to evaluate the effect of combination therapy with methotrexate or 6-mercaptopurine on infliximab levels (IFXL) and antibodies to infliximab (ATI).

Background: Infliximab (IFX) is a highly effective therapy for inflammatory bowel disease (IBD). Unfortunately, 25%-50% of patients will lose response to IFX.

Detection of adalimumab and antibodies to adalimumab using a homogeneous mobility shift assay.

Objective: In 2013 a novel commercial test was launched (Anser ADA test) for the assay of serum adalimumab (ADL) and antibodies to adalimumab (ATA). This study aims to understand clinical practice patterns used with ADL in a real-world cross-sectional population.

Methods: Wilcoxon rank sum test, and linear and logistic regression methods were applied in the statistical analysis to test hypotheses.

The functional repertoire of rabbit antibodies and antibody discovery via next-generation sequencing.

To gain insight into the functional antibody repertoire of rabbits, the VH and VL repertoires of bone marrow (BM) and spleen (SP) of a naïve New Zealand White rabbit (NZW; Oryctolagus cuniculus) and that of lymphocytes collected from a NZW rabbit immunized (IM) with a 16-mer peptide were deep-sequenced. Two closely related genes, IGHV1S40 (VH1a3) and IGHV1S45 (VH4), were found to dominate (~90%) the VH repertoire of BM and SP, whereas, IGHV1S69 (VH1a1) contributed significantly (~40%) to IM. BM and SP antibodies recombined predominantly with IGHJ4.

Establishment of paternal allele-specific DNA methylation at the imprinted mouse Gtl2 locus.

The monoallelic expression of imprinted genes is controlled by epigenetic factors including DNA methylation and histone modifications. In mouse, the imprinted gene Gtl2 is associated with two differentially methylated regions: the IG-DMR, which serves as a gametic imprinting mark at which paternal allele-specific DNA methylation is inherited from sperm, and the Gtl2-DMR, which acquires DNA methylation on the paternal allele after fertilization. The timeframe during which DNA methylation is acquired at secondary DMRs during post-fertilization development and the relationship between secondary DMRs and imprinted expression have not been well established.

Peroxisome proliferator-activated receptor-α activation promotes macrophage reverse cholesterol transport through a liver X receptor-dependent pathway.

Objective: Peroxisome proliferator-activated receptor-α (PPARα) activation has been shown in vitro to increase macrophage cholesterol efflux, the initial step in reverse cholesterol transport (RCT). However, it remains unclear whether PPARα activation promotes macrophage RCT in vivo.

Methods And Results: We demonstrated that a specific potent PPARα agonist GW7647 inhibited atherosclerosis and promoted macrophage RCT in hypercholesterolemic mice expressing the human apolipoprotein A-I (apoA-I) gene.

PPARγ activation redirects macrophage cholesterol from fecal excretion to adipose tissue uptake in mice via SR-BI.

PPARγ agonists, used in the treatment of Type 2 diabetes, can raise HDL-cholesterol, therefore could potentially stimulate macrophage-to-feces reverse cholesterol transport (RCT). We aimed to test whether PPARγ activation promotes macrophage RCT in vivo. Macrophage RCT was assessed in mice using cholesterol loaded/(3)H-cholesterol labeled macrophages.

Both the peroxisome proliferator-activated receptor delta agonist, GW0742, and ezetimibe promote reverse cholesterol transport in mice by reducing intestinal reabsorption of HDL-derived cholesterol.

Peroxisome proliferator-activated receptor delta (PPARdelta) agonism increases HDL cholesterol and has therefore the potential to stimulate macrophage-to-feces reverse cholesterol transport (RCT). To test whether PPARdelta activation promotes RCT in mice, in vivo macrophage RCT was assessed using cholesterol-loaded/3H-cholesterol-labeled macrophages injected intraperitoneally. PPARdelta agonist GW0742 (10 mg/kg per day) did not change 3H-tracer plasma appearance, but increased fecal 3H-free sterols excretion by 103% ( p < 0.

Vascular Endothelial Growth Factor Receptor-1 Is Synthetic Lethal to Aberrant {beta}-Catenin Activation in Colon Cancer.

PURPOSE: The Wnt/beta-catenin (beta-cat) signaling cascade is a key regulator of development, and dysregulation of Wnt/beta-cat contributes to selected cancers, such as colorectal, breast, and hepatocellular carcinoma, through abnormal activation of Wnt target genes. To identify novel modulators of the Wnt/beta-cat pathway that may emerge as therapeutic targets, we did an unbiased high-throughput RNA interference screen. EXPERIMENTAL DESIGN: A synthetic oligonucleotide small interfering RNA library targeting 691 known and predicted human kinases was screened in Wnt3a-stimulated human cells in a live cell luciferase assay for modulation of Wnt/beta-cat-dependent transcription.

Detection of protein-protein interactions in live cells and animals with split firefly luciferase protein fragment complementation.

Protein fragment complementation has emerged as a powerful tool for measuring protein-protein interactions in the context of live cells. The adaptation of this strategy for use with firefly luciferase now allows for the non-invasive, quantitative, real-time readout of protein interactions in lysates, live cells, and whole animals. Bioluminescence provides a robust imaging modality due to its extremely low background signal and large dynamic range.

Real-time imaging of beta-catenin dynamics in cells and living mice.

beta-Catenin (beta-cat) is a key signaling component of the canonical Wnt pathway as well as an increasingly studied contributor to various pathways that regulate cell adhesion, proliferation, and differentiation. For its best known function, posttranslational stabilization of beta-cat is required for T cell factor-dependent transcription of numerous downstream targets of Wnt, and this process is aberrantly active in a wide array of cancers. To enable direct monitoring of posttranslational stabilization of beta-cat in cells and living animals, we constructed and characterized the bioluminescent fusion reporters beta-cat firefly luciferase (beta-cat-FLuc) and beta-cat click beetle green luciferase (beta-cat-CBG).

Current state of imaging protein-protein interactions in vivo with genetically encoded reporters.

Signaling pathways regulating proliferation, differentiation, and inflammation are commonly mediated through protein-protein interactions as well as reversible modification (e.g., phosphorylation) of proteins.

Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivo.

Background: Liver X receptors (LXRs) are ligand-activated transcription factors involved in the control of lipid metabolism and inflammation. Synthetic LXR agonists have been shown to inhibit the progression of atherosclerosis in mice, but the mechanism is uncertain. LXR agonism upregulates the genes encoding ATP binding cassette transporters A1 (ABCA1) and G1 (ABCG1) in macrophages, thus promoting efflux of cholesterol; it also upregulates liver and intestinal ABCG5 and ABCG8, helping to promote biliary and fecal excretion of cholesterol.

Regulation of cysteinyl leukotriene type 1 receptor internalization and signaling.

Cysteinyl leukotrienes activate the cysteinyl leukotriene type 1 receptor (CysLT1R) to regulate numerous cell functions important in inflammatory processes and diseases such as asthma. Despite its physiologic importance, no studies to date have examined the regulation of CysLT1R signaling or trafficking. We have established model systems for analyzing recombinant human CysLT1R and found regulation of internalization and signaling of the CysLT1R to be unique among G protein-coupled receptors.