A5029136629- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Dermatology and Skin Diseases
- Asthma and respiratory diseases
- Hair Growth and Disorders
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neuroscience of respiration and sleep
- Inhalation and Respiratory Drug Delivery
- Ion Transport and Channel Regulation
- IL-33, ST2, and ILC Pathways
- Protein Tyrosine Phosphatases
- Adenosine and Purinergic Signaling
- Regulation of Appetite and Obesity
- Receptor Mechanisms and Signaling
- Redox biology and oxidative stress
- Cytokine Signaling Pathways and Interactions
- Congenital heart defects research
- Tracheal and airway disorders
- T-cell and B-cell Immunology
- Pediatric health and respiratory diseases
- Ion channel regulation and function
- Histone Deacetylase Inhibitors Research
- Nosocomial Infections in ICU
AstraZeneca (Sweden)
2015-2024
AstraZeneca (Switzerland)
2022
AstraZeneca (Netherlands)
2020
University of Gothenburg
2010
Alopecia areata (AA) is a common autoimmune disease, causing patchy hair loss that can progress to involve the entire scalp (totalis) or body (universalis). CD8+ NKG2D+ T cells dominate follicle pathogenesis, but specific mechanisms driving are not fully understood.To provide detailed insight into systemic cytokine signature associated with AA, and assess association between cytokines depression.We conducted multiplex analysis of plasma from patients psoriatic arthritis (PsA) healthy...
Airway dehydration causes mucus stasis and bacterial overgrowth in cystic fibrosis chronic bronchitis (CB). Rehydration by hypertonic saline is efficacious but suffers from a short duration of action. We tested whether epithelial sodium channel (ENaC) inhibition would rehydrate normal dehydrated airways to increase mucociliary clearance (MCC) over significant time frame. For this, we used tool compound (Compound A), which displays nanomolar ENaC affinity retention the airway surface liquid...
Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1(-/-) mice). These confirmed previously reported lean phenotype characterized by increased expenditure and modestly caloric intake. Because is expressed lateral hypothalamic area, which also has regulation autonomic nervous system, heart rate blood pressure measured telemetric method to investigate whether these might...
Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family mainly targeting cytosolic nonhistone substrates, such as α-tubulin, cortactin, and heat shock protein 90 to regulate cell proliferation, metastasis, invasion, mitosis in tumors. We describe identification characterization series 2-(difluoromethyl)-1,3,4-oxadiazoles (DFMOs) selective nonhydroxamic acid HDAC6 inhibitors. By comparing structure-activity relationships performing quantum mechanical calculations catalytic...
The respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), accumulates instead. To address the mechanisms behind accumulation, proteome bronchoalveolar lavages from COPD patients collected an elastase-induced mouse model was analyzed, revealing similarities with each other protein content colonic mucus. Moreover, stratified laminated sheets were observed airways CF...
Alopecia areata (AA) is a hair loss disorder resulting from an autoimmune reaction against follicles. T-helper 1 cells are major contributor to this disorder, but little known about the role of T-regulatory (Tregs) in AA. Here, we analysed distribution circulating Treg subsets twenty AA patients with active and fifteen healthy subjects by flow cytometry. The suppressor HLA-DR+ subpopulation was significantly reduced (P<0.001) there were fewer expressing CD39 among CD4+CD25+Foxp3+ (P =...
Chronic autoimmune diseases are associated with mutations in PTPN22, a modifier of T cell receptor (TCR) signaling. As all protein tyrosine phosphatases, the activity PTPN22 is redox regulated, but if or how such regulation can modulate inflammatory pathways vivo not known. To determine this, we created mouse cysteine-to-serine mutation at position 129 (C129S), residue proposed to alter regulatory properties by forming disulfide catalytic C227 residue. The C129S mutant showed stronger...
Hyperglycaemia increases glucose concentrations in airway surface liquid and the risk of pulmonary Pseudomonas aeruginosa infection. We determined whether reduction blood by anti-diabetic drug dapagliflozin could reduce P. growth/survival lungs diabetic mice.The effect on concentration, inflammatory response infection were investigated C57BL/6J (wild type, WT) or leptin receptor-deficient (db/db) mice, treated orally with prior to intranasal dosing LPS inoculation aeruginosa. Pulmonary...
Abstract The receptors mediating the hemodynamic responses to cannabinoids are not clearly defined due multifarious pharmacology of many commonly used cannabinoid ligands. While both CB 1 and TRPV implicated, G protein‐coupled receptor 55 ( GPR 55) may also mediate some effects several atypical present studies attempted unravel underlying in vivo ACEA agonist), O‐1602 AM 251 antagonist), cannabidiol CBD ; antagonist). Agonist antagonist profiles each ligand were determined by ligand‐induced...
Janus Kinase (JAK) inhibition has recently demonstrated therapeutic efficacy in both restoring hair growth and resolving inflammation Alopecia Areata (AA). These effects are dose dependent mainly efficacious at ranges close to a questionable risk profile.
Bronchiectasis is a chronic, progressive disease of bronchial dilation, inflammation, and scarring leading to impaired mucociliary clearance increased susceptibility infection. Identified causes include previous severe respiratory infections. A small, single-center UK study demonstrated reduction in bronchiectasis exacerbations during the first year coronavirus (COVID-19) pandemic. No studies have been conducted U.S. (commercially insured) cohort date.
Background Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated a large Asian population asthma clinical trial. Objective To evaluate the efficacy and safety of benralizumab Asia. Methods MIRACLE (NCT03186209) was randomized, Phase 3 study China, South Korea, Philippines. Patients aged 12–75 years receiving medium-to-high-dose inhaled corticosteroid/long-acting β2-agonists, stratified (2:1) by baseline blood...
Epithelial sodium channel (ENaC) inhibitors may offer clinical benefit in cystic fibrosis (CF); however, data are limited. We report the outcomes of a Phase I (NCT02679729) and Ib (NCT02950805) study AZD5634, novel inhaled ENaC inhibitor.A I, first-in-human, single-blind, placebo-controlled, single ascending dose, sequential dose group assessed safety, tolerability, pharmacokinetics AZD5634 healthy subjects (n=53) part A following doses up to 1700 µg, and, B, administration (1700 µg)...
Abstract Although the anti‐inflammatory role of A 2a receptor is well established, controversy remains with regard to therapeutic value for agonists in treatment inflammatory lung diseases, also as a result unwanted ‐mediated cardiovascular effects. In this paper, we describe discovery and characterization new, potent selective agonist (compound 2) prolonged retention limited systemic exposure following local administration. To support lead optimization chemistry program compound selection...
Abstract Alopecia areata (AA) is an immune-mediated disease that causes non-scarring hair loss. Autoreactive CD8 T cells are key pathogenic effectors in the skin, and AA has been associated both with atopy perturbations intestinal homeostasis. This study aimed to investigate mechanisms driving by characterizing circulating immunophenotype faecal microbiome, stratifying understand how identified signatures heterogeneous clinical features of condition. Flow cytometric analyses alterations B...
Airway dehydration causes mucus stasis and bacterial overgrowth in cystic fibrosis (CF), resulting recurrent respiratory infections exacerbations. Strategies to rehydrate airway including inhibition of the epithelial sodium channel (ENaC) have potential improve mucosal defense by enhancing mucociliary clearance (MCC) reducing risk progressive decline lung function. In current work, we evaluated effects AZD5634, an ENaC inhibitor that shows extended retention safety profile as compared with...