• 제목/요약/키워드: STAT2

검색결과 376건 처리시간 0.027초

선방활명음(仙方活命飮)이 알레르기 비염을 동반한 급성 비부비동염 마우스에 미치는 영향 (The Effects of Sunbanghwalmyung-eum Extract on Acute Sinusitis-induced Mouse)

  • 박민철;홍승욱
    • 대한한의학회지
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    • 제30권2호
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    • pp.133-144
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    • 2009
  • Background and Objectives: Sinusitis, referring to an inflammatory disease that occurs on the mucus membrane inside the sinus, is one of the most common diseases in the otorhinolaryngology area. In oriental clinic, Sunbanghwalmyungeum (SHE) has been used as a primary prescription to treat inflammatory diseases and intumescence and to treat sinusitis. The aim of this study was to investigate the anti-inflammatory and anti-allergic effects of SHE on acute sinusitis induced mice. Materials and Methods: BALB/c mice were divided into three groups: the normal group, the group inoculated with S. pneumoniae which caused them allergic rhinitis (control group), and the group treated with the SHE extract after it was treated the same as the control group (sample group). We investigated the inhibition of Th 2 cell differentiation by SHE and the suppression of NF-${\kappa}B$ activation. Results: NF-${\kappa}B$ activation was suppressed, and iNOS & COX-2 production were inhibited by SHE in acute sinusitis. IL-4 and STAT 6 also appeared to be suppressed. The number of eosinophils in the sample group noticeably decreased when compared to the control group. In the general morphologic change, the increase of damaged respiratory ciliated epithelium & eosinophil's infiltration were decreased in the sample group. Goblet cells were maintained in the sample group. MIP-2 and HSP-70 decreased in the sample group. Apocrine secretion decreased in the sample group. Conclusion: The results suggest that SHE is significantly effective in the treatment of inflammation caused by acute sinusitis through the suppression of NF-${\kappa}B$ activation and the inhibition of Th 2 cell differentiation.

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Combined Treatment with Stattic and Docetaxel Alters the Bax/Bcl-2 Gene Expression Ratio in Human Prostate Cancer Cells

  • Mohammadian, Jamal;Sabzichi, Mehdi;Molavi, Ommoleila;Shanehbandi, Dariush;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권11호
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    • pp.5031-5035
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    • 2016
  • Docetaxel, recognized as a stabilizing microtubule agent, is frequently administrated as a first line treatment for prostate cancers. Due to high side effects of monotherapy, however, combinations with novel adjuvants have emerged as an alternative strategy in cancer therapy protocols. Here, we investigated the combined effects of stattic and docetaxel on the DU145 prostate cancer cell line. Cytotoxicity was evaluated by MTT assay. To understand molecular mechanisms of stattic action, apoptotic related genes including Bcl-2, Mcl-1, Survivin and Bax were evaluated by real-time RT-PCR. Alteration in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 genes and Bax/Bcl-2 ratio were investigated via the $2^{{\Delta}{\Delta}CT}$ method. The $IC_{50}$ values for docetaxel and stattic were $3.7{\pm}0.9nM$ and $4.6{\pm}0.8{\mu}M$, respectively. Evaluation of key gene expression levels revealed a noticeable decrease in antiapoptotic Bcl-2 and Mcl-1 along with an increase in pro-apoptotic Bax mRNA levels (p<0.05). Our results suggest that combination of a STAT3 inhibitor with doctaxel can be considered as a potent strategy for induction of apoptosis via increasing Bax mRNA expression.

Inflammatory Responses in a Benign Prostatic Hyperplasia Epithelial Cell Line (BPH-1) Infected with Trichomonas vaginalis

  • Kim, Sang-Su;Kim, Jung-Hyun;Han, Ik-Hwan;Ahn, Myoung-Hee;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
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    • 제54권2호
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    • pp.123-132
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    • 2016
  • Trichomonas vaginalis causes the most prevalent sexually transmitted infection worldwide. Trichomonads have been detected in prostatic tissues from prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic prostatic inflammation is known as a risk factor for prostate enlargement, benign prostatic hyperplasia symptoms, and acute urinary retention. Our aim was to investigate whether T. vaginalis could induce inflammatory responses in cells of a benign prostatic hyperplasia epithelial cell line (BPH-1). When BPH-1 cells were infected with T. vaginalis, the protein and mRNA of inflammatory cytokines, such as CXCL8, CCL2, IL-$1{\beta}$, and IL-6, were increased. The activities of TLR4, ROS, MAPK, JAK2/STAT3, and NF-${\kappa}B$ were also increased, whereas inhibitors of ROS, MAPK, PI3K, NF-${\kappa}B$, and anti-TLR4 antibody decreased the production of the 4 cytokines although the extent of inhibition differed. However, a JAK2 inhibitor inhibited only IL-6 production. Culture supernatants of the BPH-1 cells that had been incubated with live T. vaginalis (trichomonad-conditioned medium, TCM) contained the 4 cytokines and induced the migration of human monocytes (THP-1 cells) and mast cells (HMC-1 cells). TCM conditioned by BPH-1 cells pretreated with NF-${\kappa}B$ inhibitor showed decreased levels of cytokines and induced less migration. Therefore, it is suggested that these cytokines are involved in migration of inflammatory cells. These results suggest that T. vaginalis infection of BPH patients may cause inflammation, which may induce lower urinary tract symptoms (LUTS).

수종의 Engine driven NiTi file과 stainless steel K-file을 이용한 근관형성 후 근관의 조직형태학적 변화에 관한 연구 (A STUDY OF HISTOMORPHOLOGICAL CHANGE OF CURVED ROOT CANAL PREPARATION USING GT ROTARY FILE, PROFILE AND STAINLESS STEEL K-FILE)

  • 고현정;백승호
    • Restorative Dentistry and Endodontics
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    • 제27권6호
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    • pp.612-621
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    • 2002
  • The purpose of this study was to compare the histomorphological change of curved root canal preparation using GT rotary File, Profile .04 taper and stainless steel K-file. 45 mesial canals(over 20 degree) of extracted human mandibular first molars were mounted in resin using a modified Bramante muffle system and divided into three groups. The roots were cross-sectioned at 2.5mm 5mm and 8mm levels from apical foramen. Tracings of the canals were made from preinstrumentation pictures of the cross section. The canals were prepared using a step-back technique with stainless steel K file(group 1), Profile .04 taper rotary file(group 2) and GT rotary file(group 3). Tracings of the prepared canals were made from postinstrumentation picture. Canal centring ratio. amount of transportation, area of dentin removed and shape of canal were measured and statistically were evaluated with Student-Newman-Keuls test using Sigma Stat(Jandel Scientific Software, USA). The results were as followings : 1 Amount of transportation of group 2 was the lowest at apical part, but there was no statistical difference. The direction of transportation was the outside of curvature at apical part. 2. Centering ratio at the apical part of group 1 was the highest, and there was statistical differences between apical and middle part, apical and coronal part(p<0.05). Centering ratio at the middle part of group 3 was the lowest, and there was statistical difference between apical and middle part(p<0.05). Centering ratio of group 2 was the lowest at apical part, but there was no statistical difference. 3. Amount of dentin removed of group 1 was the highest at coronal, middle and apical part among three groups, and there was statistical difference(p<0.05). 4. The majority of the cross-sectioned canal shape after instrumentation were irregular at coronal, middle and apical part. But there are more number of round shaped canals at group 3 than other group.

Th2 skewed condition 조절을 통한 대장점막 내 염증개선효과에 대한 두시 하태독법과 오메가3 비교 연구 (A Comparative Study of Douchi Hataedock versus Omega-3 on the Effect of Anti-inflammation in the Colonic Muscle through Th2 Skewed Condition Control)

  • 안상현;김기봉
    • 대한한방소아과학회지
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    • 제31권3호
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    • pp.37-45
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    • 2017
  • Objectives Hataedock is an orally-administered herbal extract that used to treat toxic heat and help excrete meconium accumulates in the fetus from pregnancy. This study compared the effects of Hataedock using the extract of Douchi and omega-3 to control inflammation in the colonic mucosa. Methods NC/Nga mice were divided into three groups; Control group (no treatment), FGT group (given the extract of Douchi), and O3T group (given omega-3). The 3-week-old mouse from each group were given the extract of Douchi and omega-3. After 2 weeks, the colonic mucosa tissues of the mice were observed via Immunohistochemical staining for IL-4, IL-13, CD40, $Fc{\varepsilon}RI$, $p-I{\kappa}B$, EGF in the intestinal mucosa. Results In both FGT and O3T group, IL-4, IL-13, STAT-6 levels and CD40-positive reactions were decreased. However, EGF-positive responses were increased. FGT group showed 35% decrease in IL-4, 45% decrease in IL-13, 48% decrease in CD40, 50% decrease in $Fc{\varepsilon}RI$, 54% decrease in $p-I{\kappa}B$, 52% increase in EGF compared to the control group. O3T group also showed 14% decrease in IL-4, 23% decrease in IL-13, 22% decrease in CD40, 29% decrease in $Fc{\varepsilon}RI$, 41% decrease in $p-I{\kappa}B$, 39% increase in EGF compared to the control group. Conclusions Both early administration of Douchi extract and omega-3 were effective in regulating Th2, relieving inflammation and developing colonic mucosal tissues. Hataedock with Douchi extract may be more effective in modulating immune system in colonic mucosa than omega-3.

Nitric Oxide Dependency in Inflammatory Response-related Gene Transcripts Expressed in Lipopolysaccharide-treated RAW 264.7 Cells

  • Pie, Jae-Eun;Yi, Hyeon-Gyu
    • Molecular & Cellular Toxicology
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    • 제5권4호
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    • pp.354-363
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    • 2009
  • Cytotoxic Nitric oxide (NO) overproduced by inducible NO Synthase (iNOS or NOS2), which was induced in inflammatory reactions and immune responses directly or indirectly affects the functions as host defense and can cause normal tissue damage. Microarray analysis was performed to identify gene profiles of both NO-dependent and -independent transcripts in RAW 264.7 macrophages that use selective NOS2 inhibitors aminoguanidine ($100\;{\mu}M$) and L-canavanine (1 mM). A total of 3,297 genes were identified that were up- or down-regulated significantly over 2-fold in lipopolysaccharide (LPS)-treated macrophages. NO-dependency was determined in the expressed total gene profiles and also within inflammatory conditions-related functional categories. Out of all the gene profiles, 1711 genes affected NO-dependently and -independently in 567 genes. In the categories of inflammatory conditions, transcripts of 16 genes (Pomp, C8a, Ifih1, Irak1, Txnrd1, Ptafr, Scube1, Cd8a, Gpx4, Ltb, Fasl, Igk-V21-9, Vac14, Mbl1, C1r and Tlr6) and 29 geneas (IL-1beta, Mpa2l, IFN activated genes and Chemokine ligands) affected NO-dependently and -independently, respectively. This NO dependency can be applied to inflammatory reaction-related functional classifications, such as cell migration, chemotaxis, cytokine, Jak/STAT signaling pathway, and MAPK signaling pathway. Our results suggest that LPS-induced gene transcripts in inflammation or infection can be classified into physiological and toxic effects by their dependency on the NOS2-mediated NO release.

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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    • 제15권2호
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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 increasing hematopoietic effect of the combined treatment of Korean Red Ginseng and Colla corii asini on cyclophosphamide-induced immunosuppression in mice

  • Lee, Yuan Yee;Irfan, Muhammad;Quah, Yixian;Saba, Evelyn;Kim, Sung-Dae;Park, Seung-Chun;Jeong, Myung-Gyun;Kwak, Yi-Seong;Rhee, Man Hee
    • Journal of Ginseng Research
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    • 제45권5호
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    • pp.591-598
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    • 2021
  • Background: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. Methods: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. Results: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8+ T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. Conclusion: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.

Efficacy of Hataedock Treatments for Maintenance and Formation of Lipid Barrier in Obese NC/Nga Mice with Dermatophagoides Farinae-Induced Atopic Dermatitis

  • Kim, Hee-Yeon;Ahn, Sang-Hyun;Yang, In-Jun;Cheon, Jin-Hong;Kim, Kibong
    • 대한한의학회지
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    • 제39권4호
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    • pp.74-85
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    • 2018
  • Objectives: HTD treatment is a traditional preventive therapy for neonatal inflammatory diseases such as AD. The aim of this study was to investigate the efficacy of HTD treatments for the maintenance and formation of lipid barrier in Dermatophagoides farina-induced obese NC/Nga mice. Methods: 20 mg/kg of CRGR extracts as HTD treatments were orally administered to NC/Nga mice. To induce obesity, high fat diet was served. Dermatophagoides farina extracts was applied on the 4th-6th and 8th-10th weeks to induce AD-like skin lesions in NC/Nga mice. Changes of skin conditions in mice were observed by histochemistry and immunohistochemistry. Results: The results showed that HTD treatments effectively maintained and formed the lipid barrier. In the experimental groups, restorations of Lass2 expression and distributions of filaggrin, involucrin, loricrin, ASM, and LXR means that HTD treatments maintained and generated the lipid barrier. In the dermal papillae, HTD treatments reduced PKC production accompanied by epidermis damage. Furthermore, levels of IL-4, and STAT6 was low. HTD treatment may be effective for preventing inflammation induced by Th2-skewed condition by suppressing the main pathway of Th2 differentiation. Conclusions: HTD treatment alleviated the inflammatory damage in the skin tissues of the NC/Nga mice by maintaining the lipid barrier and suppressing Th2 differentiation.

8-Methoxypsoralen Induces Apoptosis by Upregulating p53 and Inhibits Metastasis by Downregulating MMP-2 and MMP-9 in Human Gastric Cancer Cells

  • Eun Kyoung, Choi;Hae Dong, Kim;Eun Jung, Park;Seuk Young, Song;Tien Thuy, Phan;Miyoung, Nam;Minjung, Kim;Dong-Uk, Kim;Kwang-Lae, Hoe
    • Biomolecules & Therapeutics
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    • 제31권2호
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    • pp.219-226
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    • 2023
  • Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOP-induced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.