• Title/Summary/Keyword: STAT-5a/b

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The Effects of Ionized Maifanite on Skin Damages of Nc/Nga Mice after Atopic Dermatitis Elicitation (이온화된 맥반석이 아토피 피부염 유발 Nc/Nga mice의 피부손상 및 염증 완화에 미치는 영향)

  • Kim, Jong-Chae;Hong, Seung-Ug
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.30 no.1
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    • pp.29-42
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    • 2017
  • Objectives : Atopic dermatitis accompanies with severe pruritus and collapse of skin barrier, inflammation. Maifanite could be used as an ointment for skin disease. However, there have been few studies about maifanite uses for atopic dermatitis. We report the anti-inflammatory and promoting skin recovery effects of ionized maifanite on damaged skin barrier with experimentally elicited atopic dermatitis. Methods : Nc/Nga mice were divided into 3 groups: control group(CON), atopic dermatitis elicited group(AE group), ionized maifanite treated group after atopic dermatitis elicitation(MT group). After 5% SDS was applied D. pteronyssinus crude extract also applied for 3 weeks to elicit atopic dermatitis-like skin disease. MT group was treated for 3 weeks with ionized maifanite. Ionized maifanite was applied once a day and voluntarily administrated. AE group and control group were treated with normal saline in the same way. Results : In MT group, skin lesions like eczema were more improved than AE group. p-ERK1/2 positive reaction was reduced in MT group. MMP-9 and substance P positive reaction at dermal papillae was also reduced in MT group. With skin angiogram, capillary vessel decreased in MT group. Also, IL-4 positive reaction cell and STAT-6 positive reaction cell reduced more in MT group than in AE group. $NF-{\kappa}B$ p65 positive reaction cell and iNOS positive reaction cell also declined more in MT group than in AE group. Conclusions : It is supposed that ionized maifanite has anti-inflammatory effects on NC/Nga mice's atopic dermatitis with suppressing IL-4 production and Th2 cell differentiation, and controlling $NF-{\kappa}B$ activation.

Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer

  • Zhu, Qing-Chao;Gao, Ren-Yuan;Wu, Wen;Qin, Huan-Long
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2689-2698
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    • 2013
  • Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

Novel Isoquinolinamine and Isoindoloquinazolinone Compounds Exhibit Antiproliferative Activity in Acute Lymphoblastic Leukemia Cells

  • Roolf, Catrin;Saleweski, Jan-Niklas;Stein, Arno;Richter, Anna;Maletzki, Claudia;Sekora, Anett;Escobar, Hugo Murua;Wu, Xiao-Feng;Beller, Matthias;Junghanss, Christian
    • Biomolecules & Therapeutics
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    • v.27 no.5
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    • pp.492-501
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    • 2019
  • Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

Optimization of Muffin with Dried Rhynchosia Molubilis Powder Using Response Surface Methodology (반응표면분석법을 이용한 쥐눈이콩가루 첨가 머핀 제조 조건의 최적화)

  • Lee, Sun-Mee;Joo, Na-Mi
    • Korean journal of food and cookery science
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    • v.24 no.5
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    • pp.626-635
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    • 2008
  • The purpose principal objective of this study was to develop a muffin with the addition of jinuni bean powder. The whole Our analysis was conducted by using using Design Expert 7(Stat - Easy Co. Minneapolis). The jinuni bean muffin was produced by varying the contents of jinuni bean powder(A), sugar(B), and butter(C). According to the Response Surface Methodology(RSM), it showed we delineated 16 experimental points, including two replicants. The optimization We attempted to optimize of the jinuni bean muffins was studied with regard to its analysis of rheology and sensory evaluations. As a result of the redness, hardness, and sensory evaluations, characteristics such as color, appearance, flavor, softness, and overall quality showed a varied in accordance with a quadratic model, whereas lightness, yellowness, and cohesiveness, and gumminess showed evidenced a linear model pattern. Lightness, and yellowness decreased with the increases in the of jinuni bean powder content(p<0.0001), while whereas redness increased with the increases of in the content of jinuni bean powder(p<0.001), in case of over 80g, the redness tended to increase decrease again. In addition, hardness(p<0.05), gumminess(p<0.05), and cohesiveness(p<0.01) showed differed significantly differences with the increases of in the jinuni bean powder content. The results of our sensory evaluation results showed demonstrated significant values in color, appearance, flavor, softness,and overall quality values(p<0.05). The optimal formulation, as assessed by numerical and graphical methods, were was determined to be 50.05 g of jinuni bean powder, 78.56 g of sugar, and 90.97 g of butter.

Bioinformatic Prediction of SNPs within miRNA Binding Sites of Inflammatory Genes Associated with Gastric Cancer

  • Song, Chuan-Qing;Zhang, Jun-Hui;Shi, Jia-Chen;Cao, Xiao-Qin;Song, Chun-Hua;Hassan, Adil;Wang, Peng;Dai, Li-Ping;Zhang, Jian-Ying;Wang, Kai-Juan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.937-943
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    • 2014
  • Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to target genes, resulting in differential mRNA and protein expression and susceptibility to common diseases. Our purpose was to predict SNPs (single nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0, miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were 99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72 inflammation-related genes associated with gastric cancer. NF-${\kappa}B$ and JAK-STAT are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa-miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA binding sites of inflammatory genes, and provide data and direction for subsequent functional verification research.

The Quality Characteristics of Beef Sausage with the Addition of Gynura procumbens (명월초 가루를 첨가한 우육 소시지의 최적화 연구)

  • Park, Young Il;Jeong, Hee Sun;Joo, Nami
    • Korean journal of food and cookery science
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    • v.31 no.4
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    • pp.395-404
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    • 2015
  • The aims of this study were to determine the optimal mixing condition for two different amounts of Gynura procumbens powder and olive oil for the preparation of beef sausage. The experiments were designed according to the central composite design of response surface methodology, which showed 10 experimental points including two replicates of Gynura procumbens powder and olive oil. The physicochemical and mechanical characteristics as well as the sensory properties were measured, and these values were applied to the mathematical optimization models. The results of the physiochemical and mechanical analysis of each sample, including chewiness, cohesiveness, color a, color b, moisture content, salinity and heating loss showed significant differences. The sensory measurements were significantly different in color, flavor, tenderness, texture and overall quality. The optimum formulation, which was calculated using the numerical and graphical method, was determined to be 2.1 g Gynura procumbens powder and 7.06 g of olive oil.

Interleukin-7 Receptor is Indispensable for Proliferation and Survival in Thymic ${\gamma}{\delta}$T Cell Development

  • Kim, Dong-Hyun;Yoon, Byung-Hak;Jung, Joo-Eun;Kim, Hoog-Sook;Ko, Seong-Hee;Choi, Eun-Young;Lee, Kwang-Ho;Kim, Kyung-Jae;Ye, Sang-Kyu;Chung, Myung-Hee
    • IMMUNE NETWORK
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    • v.5 no.1
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    • pp.23-29
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    • 2005
  • Background: Interleukin-7 receptor (IL-7R) ${\alpha}$-deficient mice have small numbers of B cells and ${\alpha}{\beta}$T cells in periphery, they totally lack ${\gamma}{\delta}$T cells. In addition, the V-J recombination and transcription of TCR ${\gamma}$ genes is also severely impaired in IL-7R ${\alpha}$-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCR ${\gamma}$ locus, and promotes V-J recombination and ${\gamma}{\delta}$T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic ${\gamma}{\delta}$T cell development are largely unknown. Methods: To clarify the role of the IL-7 receptor in proliferation and survival of ${\gamma}{\delta}$T cells, we introduced the TCR ${\gamma}{\delta}$ transgene, $V_{{\gamma}2}/V{\delta}_5$, into IL-7R ${\alpha}$-deficient mice, and investigated the development of ${\gamma}{\delta}$T cells. Results: We found that $V_{{\gamma}2}/V{\delta}_5$ transgene restored ${\gamma}{\delta}$T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of ${\gamma}{\delta}$T cells in the thymus and the spleen of these mice. Conclusion: Taken together, this study revealed that the IL-7R ${\alpha}$ is indispensable for proliferation and survival mainly in thymic ${\gamma}{\delta}$T cell development.

Chicken novel leukocyte immunoglobulin-like receptor subfamilies B1 and B3 are transcriptional regulators of major histocompatibility complex class I genes and signaling pathways

  • Truong, Anh Duc;Hong, Yeojin;Lee, Janggeun;Lee, Kyungbaek;Tran, Ha Thi Thanh;Dang, Hoang Vu;Nguyen, Viet Khong;Lillehoj, Hyun S.;Hong, Yeong Ho
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.5
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    • pp.614-628
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    • 2019
  • Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells

  • Xiong, Wei;Jiang, Yong-Xin;Ai, Yi-Qin;Liu, Shan;Wu, Xing-Rao;Cui, Jian-Guo;Qin, Ji-Yong;Liu, Yan;Xia, Yao-Xiong;Ju, Yun-He;He, Wen-Jie;Wang, Yong;Li, Yun-Fen;Hou, Yu;Wang, Li;Li, Wen-Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3395-3402
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    • 2015
  • Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.