Transforming human ES or IPS cells into functional lung epithelial cells
For the first time, scientists have succeeded in transforming human stem cells into functional lung and airway cells. The advance, reported by Columbia University Medical Center (CUMC) researchers, has significant potential for modeling lung disease, screening drugs, studying human lung development, and, ultimately, generating lung tissue for transplantation. The study was published in the journal Nature Biotechnology.
Pathological findings of atopic dermatitis (AD) include skin barrier abnormality, allergic inflammation, and dermal fibrotic remodeling. The canonicalWnt/ β-catenin signaling pathway is a fundamental mechanism involved in various biological activities. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic-AMP-response-element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, including cancer, organ fibrosis, acute lymphoblastic leukemia, and asthma.
Immunoglobulin E (IgE) plays a crucial role in immune functions produced mainly by plasma cells. IgE is related to Th2 cell-mediated allergic inflammatory diseases such as atopic dermatitis, asthma, and allergic rhinitis. Studies of twin and family samples ascertained through atopic disease have confirmed that genetic factors are important for affect total serum IgE levels, and account for from 45% to 78% heritability of total IgE levels are observed its levels from studies of twin and family of atopic diseases.
While atopic dermatitis (AD) is known to impact sleep among clinical populations, little is known about the association between AD disease activity and sleep over time among community-based populations. We aimed to determine whether children with active AD have impaired sleep duration and quality compared to children without AD throughout childhood using data from 11,432 individuals in the Avon Longitudinal Study of Parents and Children, a population-based prospective birth cohort in the UK. The annual period prevalence of active AD (assessed by maternal report of a typical itchy flexural rash in the past year, as defined ...
Autism spectrum disorders (ASD), which are characterized by deficits in sociability and communication, affect as many as 1 in 68 children worldwide. Recent epidemiological studies suggest a significant statistical correlation between ASD and atopic dermatitis (AD), asthma, eczema, and food intolerance. Currently, the diagnosis of ASD is based primarily on altered behavior, changes that become apparent only after 2 years. Because an early diagnosis could improve disease outcomes in ASD, significant efforts are underway to develop new diagnostic methods.
Interleukin-33 (IL-33) stimulates Th2 cells, basophils, and group 2 innate lymphoid cells (ILC2). We generated a transgenic mouse expressing IL-33 driven by a keratin-14 promoter (IL33Tg) and showed that IL-33 elicits atopic dermatitis (AD)-like inflammation with activation of ILC2 and basophils (Imai Y, PNAS, 2013; Imai Y, Sci Rep, 2017). Previously, we reported that basophils are a major source of IL-4 (Yoshimoto T, Nat immunol, 2009), and recently it was reported that basophils are necessary for the activation of ILC2 in asthma (Motomura Y, Immunity, 2014).
Dupilumab (DUP), a fully human IL-4R α mAb, inhibits signaling of IL-4/IL-13, key drivers of Type 2/Th2 immune diseases such as AD/asthma. CCL17 (TARC) and IgE production are enhanced by IL-4/IL-13 and correlate with AD severity. This pooled post hoc analysis reports the relationship between baseline (BL) serum CCL17 and total IgE lev els and DUP treatment effect in adults with moderate-to-severe AD in 2 identical double-blind, placebo (PBO)-controlled phase 3 trials (SOLO 1: NCT02277743 , N=671; SOLO 2: NCT02277769 , N=708).
Atopic dermatitis (AD) is characterized by type 2 cytokines in lesional skin. In AD, IgE-activated dermal mast cells may perpetuate type 2 dysregulation through the release of inflammatory granules and de novo transcribed cytokines. Current MC-therapies primarily target granule release and have limited success in AD treatment, necessitating exploration for improved MC-targeting agents. Immunoresolvins, such as lipoxin A4 (LXA4) are therapeutic in murine asthma models, and may be efficacious for treating allergic inflammation in the skin.
Cysteinyl leukotrienes (CysLTs; LTC4, LTD4, and LTE4) are inflammatory mediators known for their involvement in bronchoconstriction, asthma and allergy, and primarily signal through the receptors CysLT1 and CysLT2. Interestingly, recent studies have found that CysLT receptors are expressed in normal skin, and that CysLT signaling may interfere with wound healing. Furthermore, our preliminary data show that enzymes associated with CysLT synthesis are highly upregulated in burned murine skin compared to healthy skin, while a previous study showed that blister fluids from burn patients contain high LTC4 levels.
Inflammation plays an important role in cutaneous wounds. Disruption of the normal influx and resolution of inflammatory cells can lead to impaired wound healing in diabetes and other pathological conditions. Tumor necrosis factor stimulated gene-6 (TSG-6) is an enzyme that transfers heavy chains (HC) from inter-a-trypsin inhibitor (IaI) to hyaluronan (HA), forming HC-HA complexes (HC-HA) that are associated with various inflammatory conditions such as arthritis, asthma, and colitis. TSG-6 is thought to play important roles in neutrophil recruitment and macrophage polarization, two events critical to proper wound healing.
For patients needing improved asthma control, should a LABA/steroid combination be used or should the inhaled steroid dose be increased?American Family Physician