• Title/Summary/Keyword: p-STAT3

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The role of p21/CIP1/WAF1 (p21) in the negative regulation of the growth hormone/growth hormone receptor and epidermal growth factor/epidermal growth factor receptor pathways, in growth hormone transduction defect

  • Kostopoulou, Eirini;Gil, Andrea Paola Rojas;Spiliotis, Bessie E.
    • Annals of Pediatric Endocrinology and Metabolism
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    • v.23 no.4
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    • pp.204-209
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    • 2018
  • Purpose: Growth hormone transduction defect (GHTD) is characterized by severe short stature, impaired STAT3 (signal transducer and activator of transcription-3) phosphorylation and overexpression of the cytokine inducible SH2 containing protein (CIS) and p21/CIP1/WAF1. To investigate the role of p21/CIP1/WAF1 in the negative regulation of the growth hormone (GH)/GH receptor and Epidermal Growth Factor (EGF)/EGF Receptor pathways in GHTD. Methods: Fibroblast cultures were developed from gingival biopsies of 1 GHTD patient and 1 control. The protein expression and the cellular localization of p21/CIP1/WAF1 was studied by Western immunoblotting and immunofluorescence, respectively: at the basal state and after induction with $200-{\mu}g/L$ human GH (hGH) (GH200), either with or without siRNA CIS (siCIS); at the basal state and after inductions with $200-{\mu}g/L$ hGH (GH200), $1,000-{\mu}g/L$ hGH (GH1000) or 50-ng/mL EGF. Results: After GH200/siCIS, the protein expression and nuclear localization of p21 were reduced in the patient. After successful induction of GH signaling (control, GH200; patient, GH1000), the protein expression and nuclear localization of p21 were reduced. After induction with EGF, p21 translocated to the cytoplasm in the control, whereas in the GHTD patient it remained located in the nucleus. Conclusion: In the GHTD fibroblasts, when CIS is reduced, either after siCIS or after a higher dose of hGH (GH1000), p21's antiproliferative effect (nuclear localization) is also reduced and GH signaling is activated. There also appears to be a positive relationship between the 2 inhibitors of GH signaling, CIS and p21. Finally, in GHTD, p21 seems to participate in the regulation of both the GH and EGF/EGFR pathways, depending upon its cellular location.

Molecular Characterization and Bitter Taste Formation of Tryptic Hydrolysis of 11S Glycinin

  • Kim, Mi-Ryung;Choi, Sang-Yun;Lee, Cherl-Ho
    • Journal of Microbiology and Biotechnology
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    • v.9 no.4
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    • pp.509-513
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    • 1999
  • The molecular size reduction and the formation of bitterness during a tryptic hydrolysis of soybean 11S glycinin were determined by using quantitative analysis and organoleptic evaluation. The 11S glycinin of 90% purity was prepared by cryoprecipitation and Con A Sepharose 4B affinity chromatography, and hydrolyzed with trypsin in a pH-stat reactor for 4 h. Bitterness was formed within 1 h of hydrolysis, and then slowly increased up to $3.5\times10^{-5}$ M quinine-HCl equivalent. The extent of hydrolysis (DH) was 7% at 1 h and increased up to 12% by the end of the reaction. The -amino nitrogen content increased from an initial 0.7 mM to 7 mM at the end of the period. The SDS-PAGE analysis showed that the acidic subunit of 11S glycinin was mostly hydrolyzed. The GP-HPLC analysis indicated that the bitterness was mainly contributed by the peptide fractions of molecular weights of 360-2,100 Da.

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A Study on the Effects of Topical Anesthesia to Pressure Pain Threshold of the Masticatory and Cervical Muscles (표면마취가 저작근 및 경부군의 압력통각역치에 끼치는 영향에 관한 연구)

  • Shin, Min
    • Journal of Oral Medicine and Pain
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    • v.22 no.1
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    • pp.183-192
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    • 1997
  • Pressure pain thresholds are routinely used in orofacial pain research to evaluate the response of deep orofacial tissues to mechanical stimulation. Like other psychophysical measurements, however, this technique must stimulate cutaneous tissues before stimulating deeper tissues. This study aimed at evaluating the influence of the cutaneous hypoesthesia on the pressure pain threshold in 30 healthy volunteers. PPTs were determined with electric pressure algometry over masseter, temporalis anterior, sternocleidomastoid, and trapezius muscle before and after skin hypoesthesia. A local anesthetic cream and a control cream were applied following a placebo-controlled double-blind design and PPTs were reassessed. Two examiners measured PPTs two times on each muscles, randomly. And the EMG activity of all muscles were measured to evaluate the relationship with PPTs. The collected data were processed by SAS/STAT program. The obtained results were as follows : 1. There were a tendency to increase PPTs after than before cutaneous hypoesthesia, but, there were no significant difference statistically. 2. PPTs were consistently higher in anterior temporalis than in masseter muscle. 3. In all occasions, PPTs were higher in males than in females(p<0.001). 4. A statistically significant correlation was obtained from values of intra-examiners and inter-examiners in all measured muscles. 5. A significantly positive correlation was not found between PPT and functional EMG activity.

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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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    • v.44 no.9
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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.

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.

Development of Biologically Active Compounds from Edible Plant Sources-XXIV. - Anti-cancer Activity of Alcohol Extracts from Edible Plants - (식용 식물자원으로부터 활성물질의 탐색-XXIV. - 식용 식물 추출물의 항암 활성 -)

  • Kwak, Ho-Young;Kwon, Byoung-Mog;Song, Myoung-Chong;Lee, Jin-Hee;Yang, Hye-Joung;Kim, Dae-Keun;Ahn, Eun-Mi;Baek, Nam-In
    • Korean Journal of Pharmacognosy
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    • v.38 no.4
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    • pp.312-320
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    • 2007
  • The screening of anti-cancer activity for the MeOH extracts of 163 natural sources, which were registered as edible plants by Korea Food & Drug Administration, exhibited 9 extracts to have significant inhibitory effects on farnesyl-protein transferase (FPTase) and phosphatase of regenerating liver-3 (PRL-3). In order to confirm the inhibitory activity of these active extracts, the activity assay was repeated for some fractions obtained from the active extracts using Medium Pressure Liquid Chromatography (MPLC). Some fractions of Carya illinoensis, Chlorella vulgaris, Panicum miliaceum, Perilla frutescens, Rosmarinus officinalis showed over 50% inhibitory activity on FPTase as well as those of Capsella bursa-pastoris, C. illinoensis, C. vulgaris, Coix lacrymajobi, Myristica fragrans, P. miliaceum, R. officinalis did over 50% inhibitory activity on PRL-3.

Transdermal Drug Release of Polymer Matrix of Unsaturated Poly(3-hydroxyalkanoate) (불포화 폴리(3-히드록시알칸오에이트)를 기질로 한 경피제제의 약물방출)

  • 이수홍;신병철;이영하;김형우;김영백;김승수
    • Polymer(Korea)
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    • v.27 no.6
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    • pp.536-541
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    • 2003
  • Unsaturated poly(3-hydroxyalkanoate) (UPHA) was biosynthesized and the properties of drug delivery using the polymer matrix were investigated. The biosynthesis of UPHA was carried out by pH-stat fed batch fermentation of Pseudomonas oleovorans (ATCC 29347) grown solely with 10-undecenoic acid as a carbon source. The physical and chemical properties of the biosynethesized UPHA were characterized using NMR, FT-IR, GPC and DSC. The drug release experiments were carried out using HPLC with a diffusion cell fur the release amount of ketoprofen as model drug. The effects of crosslinking degree, patch thickness, and enhancer on the drug release were studied. The drug release rate was linearly decreased and consistent with increased crosslinking degree of the polymer matrix. The duration of drug release was enhanced by the Increased patch thickness. The drug release rate was increased with increased amount of propylene gylcol as an enhancer.

Anti-tumor activities of Panax quinquefolius saponins and potential biomarkers in prostate cancer

  • He, Shan;Lyu, Fangqiao;Lou, Lixia;Liu, Lu;Li, Songlin;Jakowitsch, Johannes;Ma, Yan
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.273-286
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    • 2021
  • Background: Prostate carcinoma is the second most common cancer among men worldwide. Developing new therapeutic approaches and diagnostic biomarkers for prostate cancer (PC) is a significant need. The Chinese herbal medicine Panax quinquefolius saponins (PQS) have been reported to show anti-tumor effects. We hypothesized that PQS exhibits anti-cancer activity in human PC cells and we aimed to search for novel biomarkers allowing early diagnosis of PC. Methods: We used the human PC cell line DU145 and the prostate epithelial cell line PNT2 to perform cell viability assays, flow cytometric analysis of the cell cycle, and FACS-based apoptosis assays. Microarray-based gene expression analysis was used to display specific gene expression patterns and to search for novel biomarkers. Western blot and quantitative real-time PCR were performed to demonstrate the expression levels of multiple cancer-related genes. Results: Our data showed that PQS inhibited the viability of DU145 cells and induced cell cycle arrest at the G1 phase. A significant decrease in DU145 cell invasion and migration were observed after 24 h treatment by PQS. PQS up-regulated the expression levels of p21, p53, TMEM79, ACOXL, ETV5, and SPINT1 while it down-regulated the expression levels of bcl2, STAT3, FANCD2, DRD2, and TMPRSS2. Conclusion: PQS promoted cells apoptosis and inhibited the proliferation of DU145 cells, which suggests that PQS may be effective for treating PC. TMEM79 and ACOXL were expressed significantly higher in PNT2 than in DU145 cells and could be novel biomarker candidates for PC diagnosis.

[Retraction]Anti-inflammatory activity of a short peptide designed for anti-cancer: a beneficial off-target effect of tertomotide ([논문철회]항암백신 tertomotide의 항염활성 연구)

  • Lee, Hyosung
    • Journal of the Korea Convergence Society
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    • v.13 no.1
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    • pp.101-107
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    • 2022
  • Tertomotide is a peptide vaccine developed for anti-cancer therapy. Since it has been found to ameliorate inflammatory symptoms in animal studies and clinical test, we investigated anti-inflammation activity of the tertomotide and the mechanism of action in monocyte in order to assess if tertomotide may serve as an anti-inflammatory agent by checking inflammatory cytokines and related signaling pathway following tertomotide treatment. We found that tertomotide reduced the level of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-8 in LPS- or PMA-stimulated monocyte cell line and suppressed NF-κB signaling including the activation of ERK1/2 and P38 MAPK following TNF-α treatment. These results may correlate to the beneficial findings in animal studies, implicating that tertomotide may act as a potential anti-inflammatory agent. This study is an exemplary case for convergence that a computationally designed peptide for immunological purpose exerting unexpected biological activity may elicit novel anti-inflammatory drug.

Mouse neutrophils express functional umami taste receptor T1R1/T1R3

  • Lee, NaHye;Jung, Young Su;Lee, Ha Young;Kang, NaNa;Park, Yoo Jung;Hwang, Jae Sam;Bahk, Young Yil;Koo, JaeHyung;Bae, Yoe-Sik
    • BMB Reports
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    • v.47 no.11
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    • pp.649-654
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    • 2014
  • Neutrophils play an important role in the initiation of innate immunity against infection and injury. Although many different types of G-protein coupled receptors are functionally expressed in neutrophils, no reports have demonstrated functional expression of umami taste receptor in these cells. We observed that mouse neutrophils express the umami taste receptor T1R1/T1R3 through RNA sequencing and quantitative RT-PCR analysis. Stimulation of mouse neutrophils with L-alanine or L-serine, which are ligands for the umami taste receptor, elicited not only ERK or p38 MAPK phosphorylation but also chemotactic migration. Moreover, addition of L-alanine or L-serine markedly reduced the production of several cytokines including $TNF-{\alpha}$ induced by lipopoly-saccharide (LPS) through inhibition of $NF-{\kappa}B$ activity or STAT3 phosphorylation in neutrophils. Our findings demonstrate that neutrophils express the umami taste receptor, through which tastants stimulate neutrophils, resulting in chemotactic migration, and attenuation of LPS-induced inflammatory response.