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Background: The prevalence of childhood asthma and obesity is increasing, while obesity increases the risk and severity of asthma. Lipid metabolism has been considered as an important factor in the pathogenesis of obesity-associated asthma. Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme that catalyzes the production of monounsaturated fatty acids (MUFA).Methods: In the present study, the microarray data retrieved from the Gene Expression Comprehensive Database (GEO) was analyzed to further clarify the impact of SCD1 on Mast cell activation related lipid mediators and the correlation between SCD1 and obesity asthma in the population.Results: SCD1 was highly expressed in IgE-activated bone marrow-derived mast cells (BMMCs). Meanwhile, SCD1 was also verified expressed highly in dinitrophenyl human serum albumin (DNP-HAS) stimulated RBL-2H3 cells. The expression of SCD1 was up-regulated in peripheral blood leukocytes of asthmatic children, and was positively correlated with skinfold thickness of upper arm, abdominal skinfold and body mass index (BMI). Inhibition of SCD1 expression significantly suppressed the degranulation, lipid mediator production, as well as the migration ability in DNP-HAS-stimulated RBL-2H3 cells.Conclusion: SCD1 is involved in obese-related asthma through regulating mast cells.
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Asma , Mastócitos , Estearoil-CoA Dessaturase , Estearoil-CoA Dessaturase/metabolismo , Estearoil-CoA Dessaturase/genética , Mastócitos/imunologia , Mastócitos/metabolismo , Humanos , Criança , Asma/imunologia , Asma/metabolismo , Masculino , Feminino , Animais , Camundongos , Obesidade/metabolismo , Ratos , Índice de Massa CorporalRESUMO
Introduction: Mycoplasma pneumoniae (MP) is a major pathogen of community-acquired pneumonia in children. However, the specific pathogenesis of the progression of Mycoplasma pneumoniae pneumonia (MPP) is unclear. We aimed to reveal the landscape of microbiota and the host immune response in MPP. Methods: This self-controlled study analyzed the microbiome and transcriptome of bronchoalveolar lavage fluid (BALF) from the severe side (SD) and opposite side (OD) of 41 children with MPP from January to December 2021 and revealed the differences of the peripheral blood neutrophil function among children with mild MPP, severe MPP, and healthy children through transcriptome sequencing. Results: The MP load or the pulmonary microbiota had no significant difference between the SD group and OD group, and the deterioration of MPP was related to the immune response, especially the intrinsic immune response. Discussion: The immune response plays a role in MPP, which may inform treatment strategies for MPP.
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Microbiota , Pneumonia por Mycoplasma , Criança , Humanos , Mycoplasma pneumoniae , Líquido da Lavagem Broncoalveolar , NeutrófilosRESUMO
Adenoviral pneumonia in children was an epidemic that greatly impacted children's health in China in 2019. Currently, no simple or systematic scale has been introduced for the early identification and diagnosis of adenoviral pneumonia. The early recognition scale of pediatric severe adenovirus pneumonia was established based on an analysis of the children's community-acquired pneumonia clinical cohort. This study analyzed the clinical data of 132 children with adenoviral pneumonia who were admitted to the Children's Hospital of Nanjing Medical University. The clinical parameters and imaging features were analyzed using univariate and multivariate logistic regression analyses. A nomogram was constructed to predict the risk of developing severe adenovirus pneumonia in children. There were statistically significant differences in age, respiratory rate, fever duration before admission, percentage of neutrophils and lymphocytes, CRP, ALT, and LDH between the two groups. Logistic regression analysis was conducted using the R language, and respiratory rate, percentage of neutrophils, percentage of lymphocytes, and LDH were used as scale indicators. Using the ROC curve, the sensitivity and specificity of the scale were 93.3% and 92.1%. This scale has good sensitivity and specificity through internal verification, which proves that screening for early recognition of severe adenovirus pneumonia can be realized by scales. This predictive scale helps determine whether a child will develop severe adenovirus pneumonia early in the disease course.
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OBJECTIVE: This study aimed to investigate the role of p50-associated cyclooxygenase- (COX-2) extragenic RNA (PACER) on the inflammation of airway epithelium caused by Mycoplasma pneumoniae (MP) infection. METHODS: A549 cells and MP strain were cultured respectively. The expressions of PACER, IL-8, TNF-α and COX-2 in MP-infected cells were detected by qRT-PCR, the concentration of IL-8 and TNF-α in the supernatant of the cells were detected by ELISA, and the expression of COX-2 protein in the cells was detected by western-blot. After knockdown of PACER, the expression of IL-8, TNF-α and COX-2 in MP infected cells were observed. The activity of NF-κB in cells was detected by fluorescence reporter assay, and the interaction between PACER and NF-κB was verified by RNA immunoprecipitation. RESULTS: First, we observed that PACER was upregulated in MP infected A549 cells. Knockdown of PACER suppressed the production of inflammatory cytokines as well as the expression of COX-2 in A549 cells after MP infection. By performing luciferase reporter assay, we found PACER knockdown inhibited NF-κB activation induced by MP. Furthermore, RNA immunoprecipitation showed that PACER could physically bind to NF-κB p50 in MP-treated A549 cells. CONCLUSION: Collectively, our data demonstrated that attenuation of PACER reduces the inflammatory response of MP-infected epithelial cells via regulating NF-κB.
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Mycoplasma pneumoniae , NF-kappa B , Pneumonia por Mycoplasma , RNA Longo não Codificante , Células A549 , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/microbiologia , NF-kappa B/metabolismo , Pneumonia por Mycoplasma/genética , Pneumonia por Mycoplasma/metabolismo , Pneumonia por Mycoplasma/microbiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To investigate the prevalence of mutations in domain V of Mycoplasma pneumoniae (MP) 23S ribosomal RNA (rRNA) and the clinical characteristics of pediatric MP pneumonia (MPP) in Nanjing, China. METHODS: Domain V of 23S rRNA was sequenced in MP strains collected from children diagnosed with MPP in Nanjing. Clinical and laboratory data were obtained. RESULTS: Among the 276 MP strains, 255 (92.39%) harbored mutations, primarily A2063G in domain V of MP 23S rRNA. When children were stratified according to the presence or absence of mutations, no significant differences were found in sex, age, the MP DNA load at enrollment, lymphocyte counts, pulmonary complications, immunomodulator levels, fever duration, the duration of fever after macrolide therapy, and hospital stay. The prevalence of refractory MPP in the two groups was similar. Children with refractory MPP exhibited higher MP DNA loads than those with non-refractory MPP. CONCLUSIONS: Despite the high prevalence of the A2063G mutation in domain V of MP 23S rRNA, mutations were not associated with the clinical characteristics of MPP. The MP DNA load significantly differed between refractory and non-refractory MPP.
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Pneumonia por Mycoplasma , RNA Ribossômico 23S , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , China/epidemiologia , Farmacorresistência Bacteriana/genética , Humanos , Mutação , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , RNA Ribossômico 23S/genéticaRESUMO
Bronchial asthma, a common chronic respiratory disease in children, is traditionally regarded as a noninfectious disease. Current hypotheses, however, argue that asthma can be caused by microbial infection. We, therefore, hypothesize that a variety of microbes are more commonly found in the sputum of children with asthma, and these microbes may contribute to the occurrence and development of asthma. The present study proposes to use metagenomic approach to explore microbial diversity and to identify the microbial community characteristics of sputum from children with asthma. We found that microbial communities in the sputum of children differed significantly between asthmatics and controls. Kruskal-Wallis testing showed that 16 phyla, 104 genera, and 159 species were significantly downregulated, whereas two phyla including Platyhelminthes phylum and Chordata phylum, two genera including Spirometra genus and Homo sapiens, and the Spirometra erinaceieuropaei species were significantly upregulated in asthma patients compared with controls (P < 0.05). Among them, H. sapiens and S. erinaceieuropaei exhibited 2.3- and 2.0-fold overabundance in asthmatics vs controls, respectively. Meanwhile, metastats assay demonstrated that 31 phyla, 400 genera, and 813 species were significantly downregulated, whereas two phyla, 10 genera, and 16 species were significantly upregulated in asthma patients compared with controls (P < 0.05). Among them, Tetrahymena thermophila and Candidatus Zinderia insecticola exhibited 4.7-fold overabundance in asthmatics vs controls. Our study establishes a link between microbial infection and the mechanisms leading to asthma development, which will be useful for developing novel diagnostic biomarkers and aiding in the prevention and control of asthma.
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Asma/epidemiologia , Asma/microbiologia , Bactérias/genética , Metagenômica , Adolescente , Biodiversidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
To improve diagnosis of asthma, we tend to confirm potential biomarkers by comparing sputum metabolome profiles between asthma patients and healthy controls, using ultra-high-performance liquid chromatography coupled to quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS). Thirty endogenous metabolites contributing to the separation of asthma patients and healthy controls were tentatively identified in positive mode, such as 1-hexadecanoyl-sn-glycerol, glycerol 1-stearate, sphingosine, Phe-Ser, Tyr-Ala and Phe-Gln, and 12 endogenous metabolites were identified in negative mode, such as cytidine 2',3'-cyclic phosphate, 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-rac-glycerol), 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoserine, thymidine, gamma-L-glutamyl-L-valine and adenine. Those differential metabolites were mainly participatedin glycerophospholipid metabolism, retrograde endocannabinoid signaling and metabolic pathways in positive mode and 2-oxocarboxylic acid metabolism, biosynthesis of amino acids, phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine degradation and metabolic pathways in negative mode. Importantly, several metabolic pathways including glycerophospholipid metabolism, inositol phosphate metabolism, and glycolysis or gluconeogenesis were found most important. These findings suggest sputum metabolomics can be used for the early diagnosis and risk prediction of asthma.