[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

[Human bone marrow mesenchymal stem cells improve steroid resistance of human airway epithelial BEAS-2B cells in vitro].

Objective: To explore the effect of human bone marrow mesenchymal stem cells(MSC) on the steroid resistance of human airway epithelial cells. Methods: Ovalbumin (OVA)/lipopolysaccharide (LPS) were used to construct steroid resistant BEAS-2B cells, which were then co-cultured with MSC. Groups were set as follows: blank group, model group, Glucocorticoid group, MSC group, MSC+Glucocorticoid group (MSC+bud group). The expression of interleukin (IL)-8 in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA); the expression of reactive oxygen species (ROS) in the cells was detected by flow cytometry; the expression of glucocorticoid receptor α (GRα) and histone deacetylase 2 (HDAC2) protein in the cell was detected by Western blotting; and the expression of GRα and HDAC2 mRNA was detected by reverse transcription-polymerase chain reaction (RTPCR). Results: The expression level of IL-8 in the MSC group was significantly lower than that in the Glucocorticoid group (31.7±0.7 vs. 49.8±3.6, P<0.01). The expression of ROS in the MSC group was significantly lower than that in the Glucocorticoid group (2754±154 vs.4624±228, P<0.05). The expression level of HDAC2 mRNA in the MSC group was significantly higher than that in the Glucocorticoid group(1.749±0.005 vs. 1.283±0.098, P<0.05). The expression level of GRα mRNA in the MSC group was significantly higher than that in the Glucocorticoid group (1.623±0.079 vs.1.047±0.220, P<0.01). The expression of HDAC2 protein in the MSC group was significantly higher than that in the Glucocorticoid group (1.067±0.100 vs. 0.620±0.083, P<0.01). The expression of GRα protein in the MSC group was significantly higher than that in the Glucocorticoid group (0.834±0.053 vs. 0.579±0.017, P<0.01). ROS was positively correlated with the IL-8 expression (r=0.796, P<0.01) and negatively correlated with the HDAC2 and GRα mRNA expression (r=-0.893 3, P<0.01; r=0.931 4, P<0.01, respectively), as well as the HDAC2 and GRα Protein expression (r=-0.929 5, P<0.01;r=-0.864 3, P<0.01, respectively). Conclusions: Human MSC can improve steroid resistance of airway epithelial cells in an exocrine manner. The mechanism may be related to the down-regulation of ROS and up-regulation of HDAC2, which lead to GRα overexpression. In addition, MSC may improve the steroid resistance by reducing the expression of IL-8.

Analysis of renal functions and proteinuria in young obese adults.

OBJECTIVE: To investigate the prevalence of obesity in young adults and to analyze the influencing factors on renal functions and proteinuria in this population. METHODS: This study comprised civil servants between 20 and 39 years old, who received physical examinations at the First Affiliated Hospital of Fujian Medical University. The subjects were categorized into four groups based on age (20-24, 25-29, 30-34 and 35-39 years) and the number of risk factors they had (hypertension, dyslipidemia, hyperglycemia and hyperuricemia). The relationships between obesity and the prevalence of proteinuria, between obesity and risk factors and between estimated glomerular filtration rate (eGFR) and proteinuria were analyzed. RESULTS: Among the 2293 young civil servants, in men the prevalence of obesity was 33.3 % and proteinuria was 2.5 %. However in women the prevalence of obesity and proteinuria was 7.5 % and 1.7 %, respectively. The levels of blood pressure, serum uric acid (UA), cholesterol (TC), triglyceride (TG), fasting glucose (FBG) and low-density lipoprotein cholesterol (LDL-C) were lower and the level of serum high-density lipoprotein cholesterol (HDL-C) was higher in nonobese groups compared with obese groups. There were no significant differences in eGFR between the two groups. The eGFR in male subjects was associated with age, UA, body mass index (BMI), FBG, TC, TG, LDL and HDL, and in female subjects associated with UA, age, BMI, diastolic blood pressure, FBG and LDL. BMI in both males and females increased with the higher number of risk factors. Multiple regression analysis revealed that hypertension, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with obesity. eGFR decreased with a higher number of risk factors. Obesity, blood pressure, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with proteinuria. CONCLUSION: Obesity can pose an independent risk factor for proteinuria in young adults. Hypertension, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with obesity. eGFR decreased with a higher number of risk factors.

Preparation and mechanical property of poly(ε-caprolactone)-matrix composites containing nano-apatite fillers modified by silane coupling agents.

This study aims to improve the tensile strength and elastic modulus of nano-apatite/poly(ε-caprolactone) composites by silane-modification of the nano-apatite fillers. Three silane coupling agents were used to modify the surfaces of nano-apatite particles and composites of silanized apatite and PCL were prepared by a technique incorporating solvent dispersion, melting-blend and hot-pressing. The results showed that the silane coupling agents successfully modified the surfaces of nano-apatite fillers, and the crystallization temperatures of the silanized apatite/PCL composites were the higher than that of the non-silanized control material, although the melting temperature of the composites remained almost unaffected by silanization. The ultimate tensile strength and elastic modulus of the silanized composites reached 22.60 MPa and 1.76 GPa, as a result of the improved interfacial bonding and uniform dispersion of nano-apatite fillers. This study shows that the processing technique and silanization of nano-apatite particles can effectively improve the tensile strength and elastic modulus of nano-apatite/PCL composites.

Genetic polymorphism of toxicant-metabolizing enzymes and prognosis of Chinese workers with chronic benzene poisoning.

Workers with chronic benzene poisoning (CBP) sometimes have a white blood cell count (WBC) below 4 x 10(9)/L even after cessation of workplace exposure to benzene for years. In order to explore this phenomenon, 120 workers with CBP were divided into two groups depending on the WBC, the mean diagnostic age of CBP, benzene exposure duration, and body mass index (BMI). The proportion of genotypes of cytochrome P450 2E1 (CYP2E1), glutathione-S-transferase mu-1 (GSTM1), glutathione-S-transferase theta-1 (GSTT1), myeloperoxidase (MPO), and NAD(P)H, quinone oxidoreductase 1 (NQO1) were compared between workers with WBC <4 x 10(9)/L and those with WBC > or =4 x 10(9)/L. With methods of logistic regression, a risk model was set up to predict the prognosis of CBP workers. The results indicated that the BMI of workers with WBC <4 x 10(9)/L was lower than that of workers with WBC of > or =4 x 10(9)/L (21.40 +/- 2.76 versus 23.09 +/- 3.36, P = 0.01), and the logistic regression model suggested there was a 4.5-fold increased risk among workers carrying GSTT1 null genotype (95% CI= 1.13- 17.54) compared with workers with GSTT1 non-null genotype. Our findings suggest that benzene exposure duration, BMI, and GSTT1 genotype may impact prognosis of the CBP workers.