• Development and Reproduction
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• v.18 no.4
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• pp.197-212
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• 2014

Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-${\kappa}B$ appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-${\kappa}B$ pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, bio-physiological factors and their target pairs with NF-${\kappa}B$ to ameliorate oncogenesis with the "bridge between miRNAs and NF-${\kappa}B$". The application of NF-${\kappa}B$ inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.

• Gut and Liver
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• v.12 no.6
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• pp.682-693
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• 2018

Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

• Journal of Microbiology and Biotechnology
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• v.29 no.2
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• pp.297-303
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• 2019

Corticosteroids are commonly used for pain control in rotator cuff tear. Deregulated $NF-{\kappa}B$ activation is a hallmark of chronic inflammatory diseases and has been responsible for the pathogenesis of rotator cuff tear. The Dexamethasone(DEXA) is a synthetic corticosteroid. The purpose of this study was to examine the exact effect of dexamethasone on $NF-{\kappa}B$ signaling in rotator cuff tear. We measured $NF-{\kappa}B$ expression in four groups: control, $TNF-{\alpha}$-treated, DEXA-treated, and combined treatment with $TNF-{\alpha}$ and DEXA. Tenocytes were isolated from patients with rotator cuff tears and pre-incubated with $TNF-{\alpha}$ (10 ng/ml), DEXA ($1{\mu}M$), or both of them for 10 min, 1 h, and 2 h. Expression of p65, p50, and p52 in the nuclei and cytosol was analyzed by western blotting and immunofluorescence imaging using confocal microscopy. We also evaluated nucleus/cytosol (N/C) ratios of p65, p50, and p52. In our study, the combined treatment with DEXA and $TNF-{\alpha}$ showed increased N/C ratios of p65, p50, and p52 compared with those in the $TNF-{\alpha}$ group at all time points. Additionally, in the DEXA group, N/C ratios of p65, p50, and p52 gradually increased from 10 min to 2 h. In conclusion, DEXA promoted the nuclear localization of p65, p50, and p52, but was not effective in inhibiting the inflammatory response of $TNF-{\alpha}$-stimulated rotator cuff tear.