• 제목/요약/키워드: Jak2

검색결과 163건 처리시간 0.025초

네트워크 약리학을 통한 당뇨병성 신병증에서의 황기와 산수유의 활성 성분 및 잠재 타겟 예측 (Network Pharmacology: Prediction of Astragalus Membranaceus' and Cornus Officinalis' Active Ingredients and Potential Targets to Diabetic Nephropathy)

  • 이근현;이하린;정한솔;신상우
    • 동의생리병리학회지
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    • 제31권6호
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    • pp.313-327
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    • 2017
  • The purpose of this study is to predict the effects of macroscopic and integrative therapies by finding active ingredients, potential targets of Astragalus membranaceus (Am) and Cornus officinalis (Co) for diabetic nephropathy. We have constructed network pharmacology-based systematic and network methodology by system biology, chemical structure, chemogenomics. We found several active ingredients of Astragalus membranaceus (Am) and Cornus officinalis (Co) that were speculated to bind to specific receptors which had been known to have a role in the progression of diabetic nephropathy. Four components of Am and eleven components of Co could bind to iNOS; two ingredients of Am and six ingredients of Co could docking to cGB-PDE; one component of Am and nine components of Co could bind to ACE; three ingredients of Co with neprilysin; three components of Co with ET-1 receptor; four ingredients of Am and fourteen ingredients of Co with mineralocorticoid receptor; one component of Am and seven components of Co with interstitial collagenase; one ingredient of Am and ten ingredients of Co with membrane primary amine oxidase; one component of Am and four components of Co with JAK2; two ingredients of Am and one ingredient of Co with MAPK 12; one component of Am and five components of Co could docking to TGF-beta receptor type-1. From this work we could speculate that the possible mechanisms of Am and Co for diabetic nephropathy are anti-inflammatory, antioxidant and antihypertensive effects.

Cross-talk between STAT6 and Ras/MAPK Pathway for the IL-4-mediated T Cell Survival

  • So, Eui-Young;Jang, Ji-Young;Lee, Choong-Eun
    • BMB Reports
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    • 제34권6호
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    • pp.578-583
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    • 2001
  • As a prototypic Thl vs Th2 cytokine, IFN-$\gamma$ and IL-4 activate distinct STAT proteins, STAT1 and STATE, respectively. In cytokine-producing Jurkat T cells, IL-4 is effectively rescued from cell death that is induced by dexamethasone, but IFN-$\gamma$ failed to do so. Since the Ras/MAPK pathway is known to play an important role in cytokine-induced cell survival, we investigated the mechanism of T cell survival through the analysis of functional cross-talk between Ras/MAPK and distinct STAT proteins that are activated by IL-4 and IFN-$\gamma$. Although IL-4 and IFN-$\gamma$ each induced the activation of STATE and STATI. in Jurkat T cells, respectively, only IL-4 was capable of inducing MAPK. Along with tyrosine kinase inhibitors, MEK/MAPK inhibitors also caused a significant suppression of the IL-4-induced STATE activity. This suggests a positive regulation of STATE by MAPK during IL-4 signal transduction. Furthermore, transfection studies with dominant active (da) vs dominant negative (dn) Ras revealed that daRas, but not dnRas, selectively up-regulated the expression and activity of STATE with a concomitant increase in MAPK activity. These results, therefore, suggest that there is a functional cross-talk between the Ras/MAPK and Jak/STAT6 pathways, which may have a role in the IL-4-induced T cell survival.

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Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development

  • Pietrzyk, Lukasz;Torres, Anna;Maciejewski, Ryszard;Torres, Kamil
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권10호
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    • pp.4161-4168
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    • 2015
  • Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).

방약합편(方藥合編) 하통(下統) 방제(方劑)의 병증(病症) 및 병리(病理) 활용(活用)에 대한 고찰(考察) (A Study On Symptom, Pathology In Prescription of Ha-Tong from Bangyakhappeun)

  • 염현식;김희수
    • 대한한의학방제학회지
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    • 제11권1호
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    • pp.45-55
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    • 2003
  • From the study of the symptom, pathology in prescription of Ha-Tong from The Bangyakhapeun. I have reserched 163 prescription. It can be concluded as follows. 1. Prescription about Fecal disease which was the most as 11.66% of the whole, following order Internal disease(6.75%), Uterus Disease(5.52%) Sick-by-Cold Disease(5.52%), Eye Disease(4.91%), Blood Disease(4.91%), Unbalanced humoral status Disease(4.91%), Gynecologic Disease(4.91%). 2. The Fecal Disease divide diarrhea and dysentery; The Internal Disease divides with Sik-sang(食傷) Chu-sang(酒傷), Sik-juck-yu-sang-han(食積類傷寒), Carbonic acid, Vomiting acid; The Uterus Disease divides with Urinnary Disadvantage, Urinary retention, Incontinence; The Sick-by-Cold Disease divides with yang-myung-byung(陽明病), sang-han-goi-jng(傷寒壞證), sang-han-bun-gal(傷寒煩渴), sang-han-sum-ou, sang-han-hyul-jng(傷寒血證), sang-han-ja-ri(傷寒自利), sang-han-bun-jo-jng(傷寒煩燥證). 3. The Diarrhea and Dysentery many used o-ryung-san, hwng-gum-jak-yak-tang(黃芩芍藥湯) hyang-ryun-hwan(香連丸) etc, and The Internal Disease many used pyung-we-san(平胃散) as a basic prescripton. 4. The organ problem use the Sil-yuol(實熱) of the liver, stomach, lung, uterus, small intestine; six natural factors problem used the Sil-jng(實證) of the wind, fire, heat, cold, dampness; And used Unbalanced humoral status, lntrnal hurt, qi and blood, seven extream feeling.

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The Immunomodulating Effects of the Supplementation of Paeonia Japonica Extracts in Mice

  • Kim, Jin;Kim, Hyun-Sook
    • Nutritional Sciences
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    • 제5권2호
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    • pp.60-67
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    • 2002
  • Paeonia japonica var. pilosa $N_{AKAI}$, (PJ; Baek-Jak-Yak) is a medicinal plant which has been widely used as a component or blood-building decoctions. This study was performed to investigate the immunomodulative effects of PJ in mice, using in vitro and in vivo experiments. The immunomodulative effects were studied in vitro by determining the proliferation or mice splenocytes and the production of three kinds of cytokines (IL-1$\beta$, IL-6, TNF-$\alpha$) by mire peritoneal macrophages which were cultured with sequential fractions of PJ methanol extract (methanol, hexane, chloroform, ethylacetate, butanol and water). In an in vivo experiment using mice, different concentrations of PJ water extract were orally administrated every other day for two weeks. The production of cytokines (IL-1$\beta$, IL-6, TNF-$\alpha$) secreted by activated macrophages, and the proliferation of mice splenocytes, were used as indices for immunocompetence. In vitro supplementation using a hexane fraction of PJ in the range of 1 to 100 $\mu$ g/ml enhanced splenocyte proliferation by 1.8 to 12%, and by 10-15% using an aqueous fraction, compared to the control. IL-l$\beta$ production was significantly increased with the supplementation of butanol, hexane and water extracts of PJ Higher levels of IL-6 production were detected with supplementation of chloroform or water extracts. However, there were no significant differences in the production of TNF-$\alpha$ among the treated groups and the control. From the in vivo study, the highest proliferation of splenocytes was seen in the mice orally administrated with the PJ water extract at the concentration of 500 mg/kg body weight. In the case of cytosine production, IL-1-$\beta$, IL-6, and TNF-$\alpha$ released by activated peritoneal macrophages were augmented by the oral administration of a PJ water extract. These results indicate that Pl may enhance the immune function by regulating splenocyte proliferation and cytokine production capacity in mice.

WD Repeat Domain 1 Deficiency Inhibits Neointima Formation in Mice Carotid Artery by Modulation of Smooth Muscle Cell Migration and Proliferation

  • Hu, JiSheng;Pi, ShangJing;Xiong, MingRui;Liu, ZhongYing;Huang, Xia;An, Ran;Zhang, TongCun;Yuan, BaiYin
    • Molecules and Cells
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    • 제43권8호
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    • pp.749-762
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    • 2020
  • The migration, dedifferentiation, and proliferation of vascular smooth muscle cells (VSMCs) are responsible for intimal hyperplasia, but the mechanism of this process has not been elucidated. WD repeat domain 1 (WDR1) promotes actin-depolymerizing factor (ADF)/cofilin-mediated depolymerization of actin filaments (F-actin). The role of WDR1 in neointima formation and progression is still unknown. A model of intimal thickening was constructed by ligating the left common carotid artery in Wdr1 deletion mice, and H&E staining showed that Wdr1 deficiency significantly inhibits neointima formation. We also report that STAT3 promotes the proliferation and migration of VSMCs by directly promoting WDR1 transcription. Mechanistically, we clarified that WDR1 promotes the proliferation and migration of VSMCs and neointima formation is regulated by the activation of the JAK2/STAT3/WDR1 axis.

사군자탕(四君子湯) 및 사물탕(四物湯)이 인체파동(人體波動)과 활성산소(活性酸素)에 미치는 영향(影響)에 관(關)한 실험적(實驗的) 연구(硏究) (Study on the effect of Sagunjatang(SGJT) and Samultang(SMT) extract on the Wave of Human body and Active Oxygen)

  • 조기용;유동열
    • 혜화의학회지
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    • 제9권1호
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    • pp.305-317
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    • 2000
  • To prove the effect of Sagunjatang(SGJT) and Samultang(SMT) extract on the wave of Human Body and Active Oxygen experimentally, QRS & Free Radical of extract and precipitate of SGJT and SMT was measured. The results were summarized as follows ; 1. SGJT extract and precipitate, as a result of measuring QRS and Free Radical, had a considerable effect on the function of immunity & pituitary gland. 2. BaekBokRung of SGJT, as a result of measuring QRS and Free Radical, had a considerable effect on the function of heart & spleen. 3. BaekChul and Gamcho of SGJT, as a result of measuring QRS and Free Radical, had a considerable effect on the function of stomach & duodenum. 4. YinSam of SGJT, as a result of measuring QRS and Free Radical, had a considerable effect on the function of immunity & spleen. 5. SMT extract and precipitate, as a result of measuring QRS and Free Radical, had a considerable effect on the function of immunity & uterus. 6. SukJiHwang of SMT, as a result of measuring QRS and Free Radical, had a considerable effect on the function of immunity & liver. 7. DangGui of SMT, as a result of measuring QRS and Free Radical, had a considerable effect on the function of heart & spleen. 8. ChunGung of SMT, as a result of measuring QRS and Free Radical, had a considerable effect on the function of spleen & pituitary gland. 9. BaekJakYak of SMT, as a result of measuring QRS and Free Radical, had a considerable effect on the function of stomach & duodenum. 10. SMT extract had an effect on the function of female Urogenital system, SGJT extract had an effect on the function of male Urogenital system. These results suggested that SGJT and SMT extract might be usefully applied for suppresing of Active Oxygen formation, preventing the aging, curing all the disease resulted from Active Oxygen.

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회화법으로 측정한 퇴비중 유기물 함량을 탄소 함량으로 변환하기 위한 환산계수 결정 (Conversion Factor for Determinating Carbon Contents from Organic Matter Contents in Composts by Ignition Method)

  • 남재작;조남준;정광용;이상학
    • 한국토양비료학회지
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    • 제31권4호
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    • pp.380-383
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    • 1998
  • 본 연구는 퇴비중의 유기물 함량으로부터 탄소함량을 구하기 위한 환산계수를 결정하기 위하여 수행하였다. 퇴비중의 유기물 함량은 회화법으로, 탄소함량은 원소 분석기를 사용하여 분석한 결과 유기물 함량과 탄소함량의 관계는 "탄소함량(%)=$1.995+0.484{\times}$유기물 함량(%)"의 직선 회귀식을 따랐고, 분산분석에 의한 회귀직선의 유의성 검정은 고도로 유의하게 나타났다(P < 0.001). 기존의 토양 유기물 환산계수 1.724나 1.8을 적용할 경우, 퇴비중의 유기물 함량으로부터 환산한 탄소함량은 실제보다 10% 이상 높게 평가되어 우리 나라에서 생산, 판매되는 퇴비의 탄소함량을 구할 때는 상기 회귀식을 적용하는 것이 타당하리라 생각된다.

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Tumour-Derived Reg3A Educates Dendritic Cells to Promote Pancreatic Cancer Progression

  • Guo, Jie;Liao, Mengfan;Hu, Xianmin;Wang, Jun
    • Molecules and Cells
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    • 제44권9호
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    • pp.647-657
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    • 2021
  • As a pancreatic inflammatory marker, regenerating islet-derived protein 3A (Reg3A) plays a key role in inflammation-associated pancreatic carcinogenesis by promoting cell proliferation, inhibiting apoptosis, and regulating cancer cell migration and invasion. This study aimed to reveal a novel immuno-regulatory mechanism by which Reg3A modulates tumour-promoting responses during pancreatic cancer (PC) progression. In an in vitro Transwell system that allowed the direct co-culture of human peripheral blood-derived dendritic cells (DCs) and Reg3A-overexpressing/ silenced human PC cells, PC cell-derived Reg3A was found to downregulate CD80, CD83 and CD86 expression on educated DCs, increase DC endocytic function, inhibit DC-induced T lymphocyte proliferation, reduce IL-12p70 production, and enhance IL-23 production by DCs. The positive effect of tumour-derived Reg3A-educated human DCs on PC progression was demonstrated in vivo by intraperitoneally transferring them into PC-implanted severe combined immunodeficiency (SCID) mice reconstituted with human T cells. A Reg3A-JAK2/STAT3 positive feedback loop was identified in DCs educated with Reg3A. In conclusion, as a tumour-derived factor, Reg3A acted to block the differentiation and maturation of the most important antigen-presenting cells, DCs, causing them to limit their potential anti-tumour responses, thus facilitating PC escape and progression.

Signaling Role of Adipocyte Leptin in Prostate Cell Proliferation Induced by Trichomonas vaginalis

  • Kim, Jung-Hyun;Han, Ik-Hwan;Shin, Su-Jin;Park, Sung-Yul;Chung, Hyo-Yeoung;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
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    • 제59권3호
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    • pp.235-249
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    • 2021
  • Leptin is a type of adipokine mainly produced by adipocytes and reported to be overproduced in prostate cancer. However, it is not known whether it stimulates the proliferation of prostate cells. In this study, we investigated whether benign prostatic hyperplasia epithelial cells (BPH-1 cells) infected with Trichomonas vaginalis induced the proliferation of prostate cells via a leptin signaling pathway. To investigate the effect of crosstalk between adipocyte leptin and inflamed epithelial cell in proliferation of prostate cells, adipocytes 3T3-L1 cells were incubated in conditioned medium of BPH-1 cells infected with T. vaginalis (T. vaginalis-conditioned medium, TCM), and then the adipocyte-conditioned medium (ATCM) was identified to cause proliferation of prostate cells. BPH-1 cells incubated with live T. vaginalis released pro-inflammatory cytokines, and conditioned medium of these cells caused migration of adipocytes. When prostate stromal cells and BPH-1 cells were incubated with adipocyte conditioned medium containing leptin, their growth rates increased as did expression of the leptin receptor (known as OBR) and signaling molecules such as JAK2/STAT3, Notch and survivin. Moreover, blocking the OBR reduced this proliferation and the expression of leptin signaling molecules in response to ATCM. In conclusion, our findings show that inflamed BPH-1 cells infected with T. vaginalis induce the proliferation of prostate cells through leptin-OBR signaling. Therefore, it is likely that T. vaginalis contributes to prostate enlargement in BPH via adipocyte leptin released as a result of inflammation of the prostate.