Anticholinergic agent, ipratropium bromide (IB) ameliorates symptoms of allergic rhinitis (AR) using neuroimmunologic mechanisms. However, the underlying molecular mechanism remains largely unclear. In the present study, 27 mice with AR induced by ovalbumin were randomly allocated to one of three groups: Model group, model group with IB treatment for 2 weeks, and model group with IB treatment for 4 weeks. Allergic symptoms were evaluated according to symptoms scores. Differentially expressed genes [microRNAs (miRNAs) and messenger RNAs (mRNAs)] of nasal mucosa were identified by microarray analysis. The expression levels of candidate genes were measured by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The data indicates that the symptoms scores in allergic mice were significantly reduced by IB treatment. In the nasal mucosa of allergic mice with IB treatment, 207 mRNAs and 87 miRNAs were differentially expressed, when compared with the sham group. IB treatment significantly downregulated the expression levels of interleukin‑4Rα and prostaglandin D2 synthase, whereas the leukemia inhibitory factor, A20 and nuclear receptor subfamily 4, group A, member 1 expression levels were upregulated. Similarly, the expression levels of mmu‑miR‑124‑3p/5p, ‑133b‑5p, ‑133a‑3p/5p, ‑384‑3p, ‑181a‑5p, ‑378a‑5p and ‑3071‑5p were significantly increased. RT‑qPCR data further validated these mRNA and miRNA expression levels. Thus, IB treatment regulated expression of allergic immune‑associated mRNAs and miRNAs of the nasal mucosa in allergic mice, which may be associated with ameliorated nasal allergic symptoms.

In Parkinson's disease (PD), microglial activation-mediated neuroinflammation is associated with dopaminergic neurons degeneration in the substantia nigra pars compacta. Previous studies that have investigated this neurodegenerative disease have reported that the Sonic hedgehog (SHH) signaling pathway, through inhibiting the inflammatory processes, exerts a beneficial neuroprotective effect. However, the mechanisms underlying the anti‑inflammatory and neuroprotective effects of this signaling pathway remain poorly understood. The present study aimed to further investigate these mechanisms in vitro and in vivo. At first, BV2 microglial cells treated with lipopolysaccharide (LPS) were used to induce an inflammatory response. It was observed that the activation of SHH signaling by Purmorphamine attenuated the LPS‑induced inflammatory response, increased the expression of transforming growth factor‑β1 through the phosphatidylinositol 3‑kinase (PI3K)/AKT serine/threonine kinase (Akt) intracellular signaling pathway and inhibited nuclear receptor subfamily 4 group A member 2, independently of the PI3K/Akt signaling pathway. Furthermore, the blockade of the PI3K/Akt signaling pathway by intranasal administration of LY294002, significantly reduced the SHH‑associated neuroprotective effects on dopaminergic neurons, improved motor functions, and increased the microglial activation and inflammatory response in a mouse model of PD induced using 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine. In conclusion, the data of the present study reported that anti‑inflammatory and neuroprotective effects can be obtained in BV2 microglial cells and in a mouse model of PD by successive activation of the SHH and PI3K/Akt signaling pathways.

In order to further elucidate the potential correlations and treatments of IgA nephropathy (IgAN) and hypertensive nephropathy (HT), bioinformatics analysis of IgAN and HT was performed. The mRNA expression profiles of human renal biopsy samples from patients with IgAN, patients with HT and pre‑transplant healthy living controls (LD) were downloaded from the Gene Expression Omnibus database. Then, the differentially expressed genes (DEGs) were identified and functions of DEGs were analyzed. Finally, the regulatory networks containing DEGs and related‑transcription factors (TFs) were constructed using Cytoscape software. When compared with the LD group, 134 and 188 DEGs were obtained in the IgAN and HT groups, respectively. A total of 39 genes were altered in the HT group when compared with the IgAN group. In addition, 66 genes were shared in the IgAN and HT groups when compared with the LD group, 6 of which [early growth response 1, activating transcription factor 3, nuclear receptor subfamily 4 group A member 2 (NR4A2), NR4A1, v‑maf avian musculoaponeurotic fibrosarcoma oncogene homolog F and Kruppel like factor 6] were identified as TFs. In addition, DEGs including interleukin (IL) 1 receptor antagonist, collagen type 4 α2 chain, IL8, FBJ murine osteosarcoma viral oncogene homolog and somatostatin were enriched in a number of inflammation‑associated biological processes, and DEGs including structural maintenance of chromosomes protein 3, v‑crk avian sarcoma virus CT10 oncogene homolog and myosin 6 were enriched in non‑inflammation‑associated biological processes. Therefore, the differentially expressed TF genes and the genes associated with inflammation may be effective as potential therapeutic targets for IgAN and HT.

Increasing evidence has indicated that circular (circ)RNAs participate in carcinogenesis; however, the specific regulatory mechanisms underlying the effects of circRNAs, microRNAs (miRNAs/miRs) and genes on the development of clear cell renal cell carcinoma (CCRCC) remain unclear. In the present study, RNA microarray data from CCRCC tissues and control samples were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas, in order to identify significantly dysregulated circRNAs, miRNAs and genes. The Cancer‑Specific circRNA Database was used to explore the interactions between miRNAs and circRNAs, whereas TargetScan and miRDB were employed to predict the mRNA targets of miRNAs. Functional enrichment and prognostic analyses were conducted in R. The results revealed that 324 circRNAs were downregulated, whereas 218 circRNAs were upregulated in cancer. In addition, a circRNA‑miRNA‑mRNA interaction network was constructed. Gene Ontology analysis of the upregulated genes revealed that these genes were enriched in biological processes, including 'flavonoid metabolic process', 'cellular glucuronidation' and 'T cell activation'. The downregulated genes were mainly enriched in biological processes, such as 'nephron development', 'kidney development' and 'renal system development'. The hub genes, including membrane palmitoylated protein 7, aldehyde dehydrogenase 6 family member A1, transcription factor AP‑2α, collagen type IV α 4 chain, nuclear receptor subfamily 3 group C member 2, plasminogen, Holliday junction recognition protein, claudin 10, kinesin family member 18B and thyroid hormone receptor β, and the hub miRNAs, including miR‑21‑3p, miR‑155‑3p, miR‑144‑3p, miR‑142‑5p, miR‑875‑3p, miR‑885‑3p, miR‑3941, miR‑224‑3p, miR‑584‑3p and miR‑138‑1‑3p, were significantly associated with CCRCC survival. In conclusion, these results suggested that the significantly dysregulated circRNAs, miRNAs and genes identified in this study may be considered potential biomarkers of the carcinogenesis of CCRCC and the survival of patients with this disease.

The current study aimed to identify therapeutic gene and microRNA (miRNA) biomarkers for diabetic kidney disease (DKD). The public expression profile GSE30122 was used. Following data preprocessing, the limma package was used to select differentially-expressed genes (DEGs) in DKD glomeruli samples and tubuli samples and they were compared with corresponding controls. Then overlapping DEGs in glomeruli and tubuli were identified and enriched analysis was performed. In addition, protein‑protein interaction (PPI) network analysis as well as sub‑network analysis was conducted. miRNAs of the overlapping DEGs were investigated using WebGestal. A total of 139 upregulated and 28 downregulated overlapping DEGs were selected, which were primarily associated with pathways involved in extracellular matrix (ECM)‑receptor interactions and cytokine‑cytokine receptor interactions. CD44, fibronectin 1, C‑C motif chemokine ligand 5 and C‑X‑C motif chemokine receptor 4 were four primary nodes in the PPI network. miRNA (miR)‑17‑5p, miR‑20a and miR‑106a were important and nuclear receptor subfamily 4 group A member 3 (NR4A3), protein tyrosine phosphatase, receptor type O (PTPRO) and Kruppel like factor 9 (KLF9) were all predicted as target genes of the three miRNAs in the integrated miRNA‑target network. Several genes were identified in DKD, which may be involved in pathways such as ECM‑receptor interaction and cytokine‑cytokine receptor interaction. Three miRNAs may also be used as biomarkers for therapy of DKD, including miR‑17‑5p, miR‑20a and miR‑106a, with the predicted targets of NR4A3, PTPRO and KLF9.

Nuclear receptor subfamily 3, group C, member 2 (NR3C2) serves an antitumorigenic role in several types of cancer; however, its role and mechanisms of action in colon cancer remains to be elucidated. The aim of the present study was to explore the effects of NR3C2 on the proliferation, migration, invasion and angiogenesis of colon cancer cells. The expression levels of NR3C2 in human colon epithelial NCM460 cells (spontaneously immortalized cell line) and colon cancer cell lines was detected using reverse transcription‑quantitative PCR and western blotting. Cell Counting Kit‑8 (CCK‑8) and colony formation assays were used to assess cell viability and wound healing and Transwell assays were used to detect cell invasion and migration. ELISA was used to detect the expression levels of VEGF and tube formation assays were used to assess angiogenesis. The expression levels of angiogenesis‑related proteins and AKT/ERK signaling pathway‑related proteins were detected by western blotting. NR3C2 expression was downregulated in colon cancer cells and overexpression of NR3C2 inhibited proliferation, colony formation, migration and invasion of colon cancer cells. Overexpression of NR3C2 inhibited angiogenesis and activity of the AKT/ERK signaling pathway in colon cancer cells. Thus, it was demonstrated that NR3C2 inhibited the proliferation, colony formation, migration, invasion and angiogenesis of colon cancer cells through the AKT/ERK signaling pathway. These results may highlight novel targets for the treatment of colon cancer.

Anesthetic agents are used in surgical operations to reversibly reduce consciousness and pain. Sevoflurane is an inhalational anesthetic. Propofol is a short‑acting intravenous general anesthetic. The mechanism of anesthetic agents at pathway level on individual patients has not been reported to date. In the present study, pathway aberrance in the human atrial tissue in response to anesthetics was examined. Microarray data of anesthesia‑treated samples were downloaded from the Array Express database. Pathway information was obtained from the Reactome Pathway Database. The individual pathway aberrance score (iPAS) was introduced to identify dysregulated pathways in individual patients. The present data demonstrated 157 dysregulated pathways in the sevoflurane group, and 44 pathways were identified with the least P‑values. A subset of 49 differentially expressed genes (DEGs) that were shared between the expression profiling results and the dysregulated pathways results were constructed into a co‑expression network. The top 5 ranked DEGs, nuclear receptor subfamily 4 group A member 3 (NR4A3), JUNB proto‑oncogene, MYC proto‑oncogene, tachykinin precursor 1 and nicotinamide phosphoribosyltransferase, were identified as important in the topology analysis. In the propofol group, 87 dysregulated pathways were identified and 44 pathways had the least P‑values. In total 28 DEGs were constructed into a co‑expression network, of which 5 DEGs were important in the topology analysis, NR4A3, suppressor of cytokine signaling 3, cyclin dependent kinase inhibitor 1A, C‑C motif chemokine ligand 2 and C‑X‑C motif chemokine ligand 1. A total of 72 dysregulated pathways were identified in common in the two groups. In conclusion, the two types of anesthetics induced partially similar mechanisms. The pathways enriched by DEGs, particularly those that were unique to sevoflurane and propofol, may affect surgical outcomes and aid the prevention of complications from anesthetics.

Chronic rhinosinusitis (CRS) is a highly prevalent disease characterized by mucosal inflammation of the nose and paranasal sinuses. CRS can be divided into two main categories, CRS with nasal polyps (NPs; CRSwNP) and CRS without NPs (CRSsNP). Although the pathophysiology of CRS remains unclear, DNA methylation has been implicated in the etiology of CRSwNP. The aim of the present study was to elucidate whether DNA methylation of specific genes is involved in the development of NPs. In total, 18 individuals were included in the present study, and were divided into three groups: CRSwNP (n=7), CRSsNP (n=7) and healthy controls (n=4). NP tissues were obtained from the seven patients with CRSwNP and biopsies of the inferior turbinate mucosa from all three groups were used as controls. Methylated genes detected by methyl‑CpG‑binding domain sequencing were validated by methylation‑specific polymerase chain reaction (PCR), bisulfite sequencing, and reverse transcription‑quantitative PCR (RT‑qPCR). Methyl‑CpG‑binding domain sequencing identified 43,674 CpG islands in 518 genes. The promotor regions of 10 and 30 genes were hypermethylated and hypomethylated, respectively, in NP samples compared with controls. The top four genes with altered hypomethylation in NP tissues were, Keratin 19 (KRT19), nuclear receptor subfamily 2 group F member 2 (NR2F2), A Disintegrin‑like And Metallopeptidase (Reprolysin Type) with Thrombospondin type 1 motif 1 (ADAMTS1) and zinc finger protein 222 (ZNF222). RT‑qPCR demonstrated that the expression levels of KRT19, NR2F2 and ADAMTS1 were significantly increased in NP tissues; however, there was no difference in the levels of ZNF222 between NP and control tissues. Further studies are required to confirm the relevance of these epigenetic modifications in the mechanisms underlying NP formation.