Project description:In order to better understand the systemic immunological responses in a clinical cohort of obese and non-obese asthmatics and healthy subjects, we sought to analyze gene expression from whole blood. We collected whole blood samples from 156 donors and performed gene expression analysis of these samples and identified differentially expressed genes (DEGs) in each obese and/or asthma group relative to healthy volunteers.
Project description:Obese asthma is a chronic disease that poses a serious threat to children's health, resulting in more severe wheezing, earlier airway remodelling, and insensitivity to hormone therapy. Despite its clinical importance, knowledge on the underlying mechanisms of this disease remains limited. This study aimed to elucidate the pathogenesis of obese asthmatic utilizing a murine model. The present study randomly divided thirty female BALB/c mice into three groups: normal mice, asthmatic mice, and obese asthmatic mice. The mice were fed a with high-fat diet (HFD) to induce obesity. Asthmatic mice were subjected to ovalbumin (OVA) sensitization and challenge. Mice with obesity were then subjected to OVA sensitization and challenge to develop obese asthmatic. Airway remodelling was observed in obese asthmatic mice. Proteomic and bioinformatics analyses were conducted on lung tissues from obese asthmatic and normal mice. A total of 200 proteins were differentially expressed in obese asthmatic compared to normal mice; of these, 53% were upregulated and 47% were downregulated. Pathway analysis revealed that obese asthmatic primarily affected the lysosome, phagosome, and sphingolipid metabolism pathways. In addition, pyroptosis was observed in obese asthmatic, along with significant increases in pyroptosis-related factors. Orosomucoid like 3 (ORMDL3), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and Gasdermin-D (GSDMD) expression was examined, with particularly high expression levels observed in obese asthmatic mice. In vitro experiments demonstrated that overexpression of ORMDL3 in human bronchial epithelial (HBE) cells led to increased expression of NLRP3, GSDMD, and cathepsin D (CTSD). These findings suggest that ORMDL3 may regulate pyroptosis and subsequent airway remodelling in obese asthmatic, possibly via CTSD/NLRP3/GSDMD pathway.
Project description:Asthma is a very frequent airway disease that affects 6 to 20% of the population. Severe asthma, represents 3 to 5% of all asthmatic patients and is histologically characterized by an increased bronchial smooth muscle (BSM) mass and clinically by viral exacerbations. Functionally, BSM remodeling had a poor prognostic value in asthma, since higher BSM mass was associated with lower lung function and increased exacerbation rate. However, the role of BSM as a potential actor of asthma exacerbation has only been sparsely suggested. We thus hypothesis that asthmatic BSM cells could act on bronchial epithelium and modified its response to rhinovirus infection.
Project description:BACKGROUND: 50% to 80% of asthma exacerbations are precipitated by viral upper respiratory tract infections (RTI), yet the influence of viral pathogen diversity on asthma outcomes is poorly understood due to the limited scope and throughput of conventional viral detection methods. METHODS: We investigated the capability of the Virochip, a DNA microarray-based viral detection platform, to characterize the viral diversity in RTIs in asthmatic and non-asthmatic adults. RESULTS: The Virochip detected viruses in a higher proportion of samples (65%) than culture isolation (17%), while exhibiting high concordance (98%), sensitivity (97%) and specificity (98%) with pathogen-specific PCR. A similar spectrum of viruses was identified in the RTIs from each patient subgroup; however, unexpected diversity among the coronaviruses (HCoVs) and HRVs was revealed. All but one of the HCoVs corresponded to the newly-recognized HCoV-NL63 and HCoV-HKU1 viruses, and over 20 different serotypes of HRVs were detected, including a set of 5 divergent isolates that form a distinct genetic subgroup. CONCLUSIONS: The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger scale studies will be necessary to determine if particular substrains of viruses confer an elevated risk of asthma exacerbation This SuperSeries is composed of the SubSeries listed below.
Project description:RNA-seq comparison of coding RNA expression in blood eosinophils from patients with severe allergic eosinophilic asthma treated with mepolizumab with those of healthy controls and matched severe asthmatic patients receiving omalizumab.
Project description:Although the rate of fatty acid release from adipose tissue into the systemic circulation is very high in most obese adults, some obese adults maintain relatively low rates of fatty acid release, which helps protect them against the development of systemic insulin resistance. The primary aim of this study was to identify factors in adipose tissue that may underlie low vs. high rates of fatty acid mobilization in a relatively homogeneous cohort of obese adults. We obtained subcutaneous abdominal adipose tissue samples from 30 obese adults (BMI: 38±1 kg/m2, age: 30±2 yr) after an overnight fast. We performed microarray analysis on the adiose tissue samples.
Project description:Asthma is a very frequent airway disease that affects 6 to 20% of the population. Severe asthma, represents 3 to 5% of all asthmatic patients and is histologically characterized by an increased bronchial smooth muscle (BSM) mass and clinically by viral exacerbations. Functionally, BSM remodeling had a poor prognostic value in asthma, since higher BSM mass was associated with lower lung function and increased exacerbation rate. However, the role of BSM as a potential actor of asthma exacerbation has only been sparsely suggested. Thus, we hypothesis that asthmatic BSM cell metabolism is modified compare to that of non-asthmatic and that could be a potential target to reduce asthmatic BSM cell proliferation and remodeling in asthma.
Project description:OBJECTIVE Diet intervention in obese adults is the first strategy to induce weight loss and to improve insulin sensitivity. We hypothesized that improvements in insulin sensitivity after weight loss from a short-term dietary intervention tracks with alterations in expression of metabolic genes and abundance of specific lipid species. RESEARCH DESIGN AND METHODS Eight obese, insulin resistant, non-diabetic adults were recruited to participate in a three-week low calorie diet intervention study (1000 kcal/day). Fasting blood samples and vastus lateralis skeletal muscle biopsies were obtained before and after the dietary intervention. Clinical chemistry and measures of insulin sensitivity were determined. Unbiased microarray gene expression and targeted lipidomic analysis of skeletal muscle was performed. RESULTS Body weight was reduced, insulin sensitivity (HOMA-IR) was enhanced, and serum insulin concentration and blood lipid (triglyceride, cholesterol, LDL and HDL) levels were improved after dietary intervention. Gene set enrichment analysis of skeletal muscle revealed that oxidative phosphorylation and inflammatory processes were among the most enriched KEGG-pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD decreased in skeletal muscle after dietary intervention. Dietary intervention altered the intramuscular lipid profile of skeletal muscle, with changes in content of phosphatidylcholine and triglyceride species among the pronounced. CONCLUSIONS Short-term diet intervention and weight loss in obese adults alters metabolic gene expression and reduces specific phosphatidylcholine and triglyceride species in skeletal muscle, concomitant with improvements in clinical outcomes and enhanced insulin sensitivity.