scholarly journals IL-13 Augments Histone Demethylase JMJD2B/KDM4B Expression Levels, Activity, and Nuclear Translocation in Airway Fibroblasts in Asthma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Khuloud Bajbouj ◽  
Mahmood Y. Hachim ◽  
Rakhee K. Ramakrishnan ◽  
Huwaida Fazel ◽  
Jumana Mustafa ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Immunohistochemical Analysis ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
Histone Demethylase ◽  
Lung Fibroblasts ◽  
Expression Levels ◽  
Downstream Target ◽  
Gene And Protein Expression ◽  
Bronchial Biopsies

Purpose. Asthma is one of the most common obstructive pulmonary diseases worldwide. Epigenetic alterations, including DNA methylation and histone modifications, have been reported to contribute to asthma pathogenesis. Since the inflammation mediator and remodeling trigger, IL-13, is known to play a central role in the pathophysiology of asthma, this study was aimed to identify novel IL-13-regulated epigenetic modifiers in asthma that may contribute to subepithelial fibrosis. Methods. Publicly available transcriptomic datasets from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes on an epigenetic level upon IL-13 exposure in lung fibroblasts. Bronchial fibroblasts isolated from healthy and asthmatic individuals were assessed for the gene and protein expression levels of the identified gene at baseline and upon IL-13 treatment using qRT-PCR and western blotting, respectively. Its subcellular localization and tissue distribution were examined in bronchial fibroblasts as well as bronchial biopsies by immunofluorescence and immunohistochemical analysis, respectively. Results. Bioinformatic analysis revealed the differential expression of the histone demethylase JMJD2B/KDM4B, a well-known epigenetic modulator that leads to the demethylation of different lysine residues on histones, in IL-13-treated lung fibroblasts. The baseline expression levels of JMJD2B were higher in asthmatic fibroblasts and in bronchial biopsies in comparison to healthy ones. There was also an increase in JMJD2B activity as evidenced by the demethylation of its downstream target, H3K36me3. Furthermore, IL-13 stimulation induced JMJD2B expression and further demethylation of H3K36me3 in asthmatic fibroblasts. This was accompanied by increased translocation of JMJD2B into the nucleus. Conclusion. This study highlights the novel pathological involvement of the histone demethylase JMJD2B/KDM4B in asthmatic airway fibroblasts that are regulated by IL-13. Clinical implications. Given that there is no single therapeutic medicine to effectively treat the various subtypes of asthma, this study provides promising insights into JMJD2B as a new therapeutic target that could potentially improve the treatment and management of asthma.

scholarly journals Identification of the Effects of Chondroitin Sulfate on Inhibiting CDKs in Colorectal Cancer Based on Bioinformatic Analysis and Experimental Validation

2021 ◽  
Vol 11 ◽  
Author(s):  
Yingyu Zhou ◽  
Xuyang Li ◽  
Yuki Morita ◽  
Satoshi Hachimura ◽  
Takuya Miyakawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Chondroitin Sulfate ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Occurrence Rate ◽  
Expression Levels ◽  
Gene And Protein Expression ◽  
Hct 116

With a high occurrence rate and high mortality, the treatment of colorectal cancer (CRC) is increasingly attracting the attention of scholars. Hub genes that determine the phenotypes of CRC become essential for targeted therapy. In the present study, the importance of cyclin-dependent kinases (CDKs) on the occurrence of CRC was identified by data mining of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The results showed that the gene expression levels of CDK1, CDK4, and CDK6 were obviously changed in different stages of CRC. Among the CDKs, CDK4 was suggested as an independent risk factor for CRC based on Cox analysis. Furthermore, chondroitin sulfate (CS), a kind of dietary supplement to treat osteoarthritis, was predicted to treat CRC based on its chemical structure and GEO datasets. Cell assay experiments with the human CRC cell line HCT-116 also verified this prediction. CS inhibited the gene and protein expression levels of CDKs and increased the ratios of apoptotic or dead HCT-116 cells by regulating mitogen-activated protein (MAP) kinase pathways. Our data highlight the essential roles of CDKs in CRC carcinogenesis and the effects of CS on treating CRC, both of which will contribute to the future CRC treatment.

scholarly journals Aberrant upregulation of TNFRSF21 enhances tumor aggressiveness in lung cancer via activation of the ERK/FOXM1 signaling cascade

2021 ◽  
Author(s):  
Chengwei Zhou ◽  
Zixuan Chen ◽  
Jiayan Liu ◽  
Shuai Fang
Keyword(s):  
Lung Cancer ◽  
Immunohistochemical Analysis ◽  
Gene Expression Omnibus ◽  
Nsclc Cell ◽  
Tissue Array ◽  
Cancer Tissue ◽  
Tumor Aggressiveness ◽  
Lung Cancers ◽  
Ncbi Gene Expression Omnibus ◽  
Downstream Target

Abstract Background Lung cancer is one of the leading causes of cancer-related death worldwide. Identifying alterations in oncogenic drivers are known to be an effective strategy to explore potential druggable targets in the treatment of this disease. Methods Integrative analysis of the NCBI Gene Expression Omnibus (GEO) datasets by R language identified TNFRSF21 is upregulated in lung cancers. Using overexpression or knockdown approach to demonstrate the gene effect and mechanisms on lung cancer cells. Immunohistochemical analysis of a commercial lung cancer tissue array showed clinic-pathological correlations. Results TNFRSF21 is frequently upregulated and associated with high-grade tumors and is highly correlated with advanced NSCLC. Biochemical studies confirmed that TNFRSF21 overexpression could markedly promote NSCLC cell growth and cell migration/invasion, while suppression of ERK and FOXM1 by U0126 and thiostrepton, respectively, could significantly counteract TNFRSF21-mediated NSCLC cell proliferation and aggressiveness. Mechanistic studies revealed that forced expression or ablation of TNFRSF21 could escalate or attenuate both the phosphorylation of ERK (p-ERK) and the expression of FOXM1, respectively, whereas the levels of TNFRSF21 and p-ERK were not altered when FOXM1 was inhibited by thiostrepton. On the contrary, inhibition of the intensity of p-ERK by U0126 could reduce FOXM1 expression in TNFRSF21-overexpressing NSCLC cells, which suggests that TNFRSF21 is the upstream effector of ERK signaling and that its downstream target is FOXM1. Conclusions This study highlights the significance of TNFRSF21 in promoting tumor aggressiveness in lung cancer by increasing ERK/FOXM1 signaling, which suggests that targeting TNFRSF21/MEK/ERK/FOXM1 may represent a potential therapy for lung cancer.

scholarly journals COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration

2021 ◽  
Vol 12 ◽  
Author(s):  
Shushan Li ◽  
Haitao Wang ◽  
Yi Zhang ◽  
Renqiu Qiao ◽  
Peige Xia ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blotting ◽  
Immune Cell ◽  
Gene Expression Omnibus ◽  
Pathological Process ◽  
Future Research ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Age Related ◽  
Gene And Protein Expression

BackgroundOsteoarthritis (OA) is one of the most common age-related degenerative diseases. In recent years, some studies have shown that pathological changes in the synovial membrane occur earlier than those in the cartilage in OA. However, the molecular mechanism of synovitis in the pathological process of OA has not been elucidated. This study aimed to identify novel biomarkers associated with OA and to emphasize the role of immune cells in the pathogenesis of OA.MethodsMicroarray datasets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases and were then analyzed using R software. To determine differential immune cell subtype infiltration, the CIBERSORT deconvolution algorithm was used. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expressions of selected genes. Besides, Western blotting was used to assess the protein expression levels in osteoarthritic chondrocytes.ResultsAfter analyzing the database profiles, two potential biomarkers, collagen type 3 alpha 1 chain (COL3A1), and matrix metalloproteinase 9 (MMP9), associated with OA were discovered, which were confirmed by qRT-PCR and Western blotting. Specifically, the results revealed that, as the concentration of IL-1β increased, so did the gene and protein expression levels of COL3A1 and MMP9.ConclusionThe findings provide valuable information and direction for future research into novel targets for OA immunotherapy and diagnosis and aids in the discovery of the underlying biological mechanisms of OA pathogenesis.

scholarly journals Bioinformatic analysis of the inner heterogeneity within MYCN non-amplified pediatric neuroblastoma sub-group

2020 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
Mycn Amplification ◽  
Expression Levels ◽  
Kaplan Meier

Abstract Background: Pediatric neuroblastoma is divided into MYCN amplified and MYCN non-amplified sub-groups. However, the extent of heterogeneity within MYCN amplified or non-amplified pediatric neuroblastoma is unclear.Methods: The prognostic significance of age and MYCN amplification was determined through multivariate cox regression and Kaplan-Meier survival analysis. MYCN non-amplified pediatric neuroblastoma patients were divided into different sub-consensuses using non-negative matrix factorization (NMF) based on the gene expression profiling. Genes particularly expressed in MYCN non-amplified younger neuroblastoma patients were identified using Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. The prognostic effects of ALCAM, CACNA2D3, DST, EPB41L4A and KIFIB in MYCN non-amplified pediatric neuroblastoma patients were determined by Kaplan-Meier survival.Results: Age and MYCN amplification were independent prognostic factors in pediatric neuroblastoma. Compared with MYCN non-amplified older neuroblastoma patients, MYCN non-amplified younger neuroblastoma patients had better clinical outcomes. MYCN non-amplified pediatric neuroblastoma was divided into three sub-consensuses through NMF assay and each sub-consensus was with significantly different clinical outcomes. However, MYCN amplified pediatric neuroblastoma could not divide into sub-groups with different clinical outcomes by age or by NMF assay. ALCAM, CACNA2D3, DST, EPB41L4A and KIFIB were highly expressed in MYCN non-amplified younger neuroblastoma patients. Moreover, the high expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIFIB were associated with the favorable prognosis of MYCN non-amplified neuroblastoma patients. We also found that DST was an independent prognostic factor in MYCN non-amplified neuroblastoma patients and MYCN non-amplified younger neuroblastoma patients with high DST expression levels had the best clinical overall survival.Conclusions: MYCN non-amplified neuroblastoma was a heterogeneous disease and could be divided into sub-groups based on age or the expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIFIB. MYCN non-amplified younger neuroblastoma patients with high DST expression levels had the best clinical overall survival.

scholarly journals IL-13 AUGMENTS HISTONE DEMETHYLASE JMJD2B/KDM4B EXPRESSION LEVELS, ACTIVITY AND NUCLEAR TRANSLOCATION IN AIRWAY FIBROBLASTS IN ASTHMA

CHEST Journal ◽  
2020 ◽  
Vol 158 (4) ◽  
pp. A42-A43
Author(s):  
Khuloud Bajbouj ◽  
Mahmood Hachim ◽  
Huwaida Fazel ◽  
Jumana Mustafa ◽  
Shahed Alzaghari ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Histone Demethylase ◽  
Expression Levels

scholarly journals Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues

2005 ◽  
Vol 187 (1) ◽  
pp. 89-101 ◽  
Author(s):  
M S Fernandes ◽  
V Pierron ◽  
D Michalovich ◽  
S Astle ◽  
S Thornton ◽  
...  
Keyword(s):  
Immunohistochemical Analysis ◽  
Bioinformatic Analysis ◽  
Tissue Expression ◽  
Female Reproduction ◽  
Expression Levels ◽  
Progestin Receptor ◽  
Reproductive Tissues ◽  
Human Reproductive ◽  
Cycle Dependent ◽  
Membrane Progestin Receptor

Rapid non-genomic actions of progesterone are implicated in many aspects of female reproduction. Recently, three human homologues of the fish membrane progestin receptor (mPR) have been identified. We combined bioinformatic analysis with expression profiling to define further the role of these mPRs in human reproductive tissues. Sequence analysis confirmed that the mPRs belong to a larger, highly conserved family of proteins, termed ‘progestin and adiponectin receptors’ (PAQRs). A comparison of the expression of mPR transcripts with that of two related PAQR family members, PAQRIII and PAQRIX, in cycling endometrium and pregnancy tissues revealed markedly divergent expression levels and profiles. For instance, endometrial expression of mPRα and γ and PAQRIX was cycle-dependent whereas the onset of parturition was associated with a marked reduction in myometrial mPRα and β transcripts. Interestingly, mPRα and PAQRIX were most highly expressed in the placenta, and the tissue expression levels of both genes correlated inversely with that of the nuclear PR. Phylogenetic analysis demonstrated that PAQRIX belongs to the mPR subgroup of proteins. We also validated a polyclonal antibody raised against the carboxy-terminus of human mPRα. Immunohistochemical analysis demonstrated more intense immunoreactivity in placental syncytiotrophoblasts than in endometrial glands or stroma. The data suggest important functional roles for mPRα, and possibly PAQRIX, in specific reproductive tissues, particularly those that express low levels of nuclear PR.

scholarly journals Different macrophages equally induce EMT in endometria of adenomyosis and normal

Reproduction ◽  
2017 ◽  
Vol 154 (1) ◽  
pp. 79-92 ◽  
Author(s):  
Min An ◽  
Dong Li ◽  
Ming Yuan ◽  
Qiuju Li ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Quantitative Polymerase Chain Reaction ◽  
Immunohistochemical Analysis ◽  
Secretory Phase ◽  
Normal Endometrium ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Endometrial Cells

Endometrial cells and microenvironment are two important factors in the pathogenesis of adenomyosis. Our previous study demonstrated that macrophages can induce eutopic epithelial cells of adenomyosis to suffer from epithelial–mesenchymal transition (EMT). The aim of this study is to detect whether macrophages interacting with epithelial cells equally induce the EMT process in normal and eutopic endometria of healthy and adenomyotic patients; and whether macrophages parallelly polarize to M2. We investigated the expression levels of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), cytokeratin7 (CK7), vimentin, transforming growth factor-β1 (TGFB1), SMAD3 and pSMAD3 using immunohistochemistry and western blot, and then estimated the genetic levels of CD163, IL10 and MMP12 using real-time quantitative polymerase chain reaction (RT-PCR) in macrophages. Eutopic and normal endometrial tissues were obtained from 20 patients with adenomyosis and 11 control patients without adenomyosis, respectively. The immunohistochemical analysis shows distinct EMT in eutopic endometria in secretory phase; the expression levels of TGFB1, SMAD3 and pSMAD3 that indicate signal pathway of EMT were also higher in secretory phase. Macrophages can induce EMT process in primary endometrial epithelial cells derived from normal and eutopic endometria. After co-culturing, THP-1-derived macrophages polarized to M2. Compared with the eutopic endometrium group, further polarization to M2 was observed in the normal endometrium group. These results indicate that adenomyosis may be promoted by the pathologic EMT of epithelial cells, which is induced by macrophages that incapably polarize to M2.

scholarly journals Antifungal Effect of Long Noncoding RNA 9708-1 in the Vulvovaginal Candidiasis Murine Model

2021 ◽  
Vol 186 (2) ◽  
pp. 177-188
Author(s):  
Ying Wu ◽  
Lisha Jiang ◽  
Lingling Zhang ◽  
Xia Liu ◽  
Lina Yan ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Basal Layer ◽  
Vulvovaginal Candidiasis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Blank Control Group ◽  
Candida Spp ◽  
Expression Levels ◽  
Gene And Protein Expression

AbstractVulvovaginal candidiasis (VVC) caused by Candida spp. affects 70–75% of women at least once during their lives. We aim to elucidate the potential mechanism of VVC and investigate the therapeutic effects of long noncoding RNA 9708-1. Female BALB/c mice were randomized to four treatment groups, including the blank control group, VVC control group, vehicle control group and lncRNA 9708-1-overexpressed group. Mice were euthanized on Day 4, Day 7 and Day 14 after treatment. Colony-forming unit (CFU) was measured, and the inflammation was detected by hematoxylin and eosin (H&E). Gene and protein expression levels of lncRNA 9708-1 and FAK were determined by real-time PCR, Western blot and immunohistochemistry. The overexpression of lncRNA 9708-1 significantly decreased the fungal load from Day 4 to 7. H&E staining indicated that the impaired histological profiles were improved in lncRNA 9708-1-overexpressed group. LncRNA 9708-1 led to a significant increase in FAK level of vagina tissue which is expressed mainly in epithelial basal layer. This study suggests that lncRNA 9708-1 played a protective role on murine experimental VVC by upregulating the expression levels of FAK.

scholarly journals Overexpression of CRABP2 inhibits dexamethasone-induced apoptosis in human osteoblast cells

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Haiping Zhang ◽  
Ziliang Yu ◽  
Farui Sun ◽  
Jin Jin
Keyword(s):  
Protein Expression ◽  
Underlying Mechanism ◽  
R Package ◽  
Treated Group ◽  
Gene Expression Omnibus ◽  
Human Osteoblast ◽  
Osteoblast Cells ◽  
Gene And Protein Expression ◽  
Osteoblast Apoptosis ◽  
Induced Apoptosis

Abstract Background The purpose of the current study was to explore the role and underlying mechanism of cellular retinoic acid binding protein 2 (CRABP2) in dexamethasone (DEX)-induced apoptosis in human osteoblast cells. Methods GSE10311 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. Primary human osteoblast was isolated and treated with different concentration of DEX (0, 10-8, 10-7, 10-6, 10-5, and 10-4 mol/L), and cell viability and flow cytometry were used to detect cell proliferation and apoptosis. A CRABP2 overexpression plasmid (oe-CRABP2) was used to overexpress CRABP2, and western blotting was conducted to detect protein expression. Results We found that CRABP2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated CRABP2 gene and protein expression, inhibited viability, and induced human osteoblast apoptosis. Overexpression of CRABP2 reversed DEX-induced apoptosis in human osteoblast. Moreover, overexpression of CRABP2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model. Conclusion In conclusion, CRABP2 is effective at inhibiting DEX-induced human osteoblast apoptosis and delayed ONFH progression.

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