• Title/Summary/Keyword: p-STAT3

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Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

  • Chanthra, Nawin;Payungporn, Sunchai;Chuaypen, Natthaya;Pinjaroen, Nutcha;Poovorawan, Yong;Tangkijvanich, Pisit
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.5069-5073
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    • 2015
  • The single nucleotide polymorphism (SNP) rs1053004 in Signal transducer and activator of transcription 3 (STAT3) was recently reported to be associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) in a Chinese cohort. This study was aimed at investigating whether the SNP might also contribute to HCC susceptibility in the Thai population. Study subjects were enrolled and divided into 3 groups including CHB-related HCC (n=211), CHB without HCC (n=233) and healthy controls (n=206). The SNP was genotyped using allelic discrimination assays based on TaqMan real-time PCR. Data analysis revealed that the distribution of different genotypes was in Hardy-Weinberg equilibrium (P>0.05). The frequencies of allele T (major allele) in HCC patients, CHB patients and healthy controls were 51.4%, 58.6% and 61.4%, respectively, whereas the frequencies of C allele (minor allele) were 48.6%, 41.4% and 38.6%. The C allele frequency was higher in HCC when compared with CHB patients (odds ratio (OR)=1.34, 95% confidence interval (CI)=1.02-1.74, P=0.032). The genotype of SNP rs1053004 (CC versus TT+TC) was significantly associated with an increased risk when compared with CHB patients (OR=1.83, 95% CI=1.13-2.99, P=0.015). In addition, we observed a similar trend of association when comparing HCC patients with healthy controls (OR=1.77, 95% CI=1.07-2.93, P=0.025) and all controls (OR=1.81, 95% CI=1.19-2.74, P=0.005). These findings suggest that the SNP rs1053004 in STAT3 might contribute to HCC susceptibility and could be used as a genetic marker for HCC in the Thai population.

Astaxanthin Ameliorates Atopic Dermatitis by Inhibiting the Expression of Signal Molecule NF-kB and Inflammatory Genes in Mice

  • Donghwan, Kim;Yong-Suk, Kim;Ho Sueb, Song
    • Journal of Acupuncture Research
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    • v.39 no.4
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    • pp.304-309
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    • 2022
  • Background: This study was conducted to determine the anti-inflammatory effect of astaxanthin, on atopic dermatitis. Methods: Changes in mouse body weight, lymph node weight, and the degree of improvement in symptoms were measured to determine the inflammatory response. Real-time reverse transcription-polymerase chain reaction tests were performed to determine the degree of expression of inflammation-related cytokines (IL-31 and IL-33 and chemokines such as CCL17 and CCL22), and western blot analysis was performed to evaluate the expression of inflammation-related factors (iNOS, COX-2, and NF-kB signaling molecules p-IkBα, p50, p-65 and pSTAT3). Results: The degree of symptoms significantly improved in the PA+AX group. Lymph node weight in the PA+AX group was lower than the PA group. Inflammatory cytokines (IL-31, IL-33, and inflammatory chemokines such as CCL17 and CCL22) were significantly reduced in the PA+AX group compared with the PA group. The expression of inflammatory genes (iNOS, COX-2, NF-kB and signaling molecules (p-IkBα, p50, p65, and p-STAT 3) was lower in the PA+AX group compared with the PA group. Conclusion: Astaxanthin may modulate the inflammatory response in a mouse model of atopic dermatitis and has an anti-inflammatory effect.

MiR-30a-5p and miR-153-3p regulate LPS-induced neuroinflammatory response and neuronal apoptosis by targeting NeuroD1

  • Choi, Hye-Rim;Ha, Ji Sun;Kim, Eun-A;Cho, Sung-Woo;Yang, Seung-Ju
    • BMB Reports
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    • v.55 no.9
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    • pp.447-452
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    • 2022
  • Neurogenic differentiation 1 (NeuroD1) is an essential transcription factor for neuronal differentiation, maturation, and survival, and is associated with inflammation in lipopolysaccharide (LPS)-induced glial cells; however, the concrete mechanisms are still ambiguous. Therefore, we investigated whether NeuroD1-targeting miRNAs affect inflammation and neuronal apoptosis, as well as the underlying mechanism. First, we confirmed that miR-30a-5p and miR-153-3p, which target NeuroD1, reduced NeuroD1 expression in microglia and astrocytes. In LPS-induced microglia, miR-30a-5p and miR-153-3p suppressed pro-inflammatory cytokines, reactive oxygen species, the phosphorylation of c-Jun N-terminal kinase, extracellular-signal-regulated kinase (ERK), and p38, and the expression of cyclooxygenase and inducible nitric oxide synthase (iNOS) via the NF-κB pathway. Moreover, miR-30a-5p and miR-153-3p inhibited the expression of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, NLRP3, cleaved caspase-1, and IL-1β, which are involved in the innate immune response. In LPS-induced astrocytes, miR-30a-5p and miR-153-3p reduced ERK phosphorylation and iNOS expression via the STAT-3 pathway. Notably, miR-30a-5p exerted greater anti-inflammatory effects than miR-153-3p. Together, these results indicate that miR-30a-5p and miR-153-3p inhibit MAPK/NF-κB pathway in microglia as well as ERK/STAT-3 pathway in astrocytes to reduce LPS-induced neuronal apoptosis. This study highlights the importance of NeuroD1 in microglia and astrocytes neuroinflammation and suggests that it can be regulated by miR-30a-5p and miR-153-3p.

Synthesis of Poly[3-hydroxybutyrate-co-3-hydroxyvalerate] by Recombinant Escherichia coli from Whey (재조합 대장균에 의한 유청으로부터 Poly[3-hydroxybutyrate-co-3-hydroxyvalerate] 합성)

  • 김범수;이상엽
    • KSBB Journal
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    • v.18 no.5
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    • pp.404-407
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    • 2003
  • Two recombinant Escherichia coli strains, GCSC6576 harboring a plasmid pSYL107 containing the Ralstonia eutropha polyhydroxyalkanoate (PHA) biosynthesis genes and a fadR atoC mutant LS5218 harboring a plasmid pJC4 containing the Alcaligenes latus PHA biosynthesis genes were compared for their ability to synthesize poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV) from whey. The 3HV fraction could be increased by acetic acid induction and oleic acid supplementation in flask cultures of recombinant E. coli GCSC6576. With the pH-stat fed-batch culture of recombinant E. coli LS5218, we obtained a cell concentration, a P(3HB-co-3HV) concentration, a P(3HB-co-3HV) content, and a 3HV fraction of 31.8 g/L, 10.6 g/L, 33.4%, and 6.26 mol%, respectively in 39 h.

Immunoregulatory Effects of Water Extracts of Inonotus obliquus in Carbon Tetrachloride-Induced Liver Damage Animal Model (사염화탄소로 유도된 간 손상 동물모델에서 차가버섯 열수 추출물이 면역 조절 기능에 미치는 영향)

  • An, Chi-Sun;Jin, Hai-Lan;Jeon, Yun-Hui;Bak, Jong-Phil;Kim, Jong-Dai;Yoon, Jung-Han;Lim, Beong-Ou
    • Korean Journal of Medicinal Crop Science
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    • v.18 no.1
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    • pp.1-8
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    • 2010
  • Inonotus obliquus is one of the immune-regulatory substances and is recognized to play the role in the metabolic process of inflammation, allergy and immuntiy. The purpose of this study was to evaluate the effects of water extracts of Inonotus obliquus (IOW) on the liver lymphocyte immune function in the Sprague-Dawley male rats treated with carbon tetrachloride ($CCl_4$) to induce liver damage. Rats were fed with each experimental diet and water for 4 weeks. We found that effects of IOW on interferon-gamma (IFN-$\gamma$), signal transducer and activator of transcription 1 (STAT1), phospho-signal transducer and activator of transcription 1 (pSTAT1) and GATA-binding protein 3 (GATA-3) were decrease in vivo. Interleukin-4 (IL-4), STAT6, pSTAT6 and T-box expressed in T-cells (T-bet) decreased significantly lower in $CCl_4$+IOW group than the $CCl_4$ group. Our data indicated that cytokine protein production were increased in $CCl_4$ group and $CCl_4$+IOW group. As a result of this study, we assume that IOW fed could regulate the immuno-modulating functions through regulate the cytokine production capacity activated by liver damage.

Curcumin suppresses the production of interleukin-6 in Prevotella intermedia lipopolysaccharide-activated RAW 264.7 cells

  • Kim, Sung-Jo
    • Journal of Periodontal and Implant Science
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    • v.41 no.3
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    • pp.157-163
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    • 2011
  • Purpose: Curcumin is known to exert numerous biological effects including anti-inflammatory activity. In this study, we investigated the effects of curcumin on the production of interleukin-6 (IL-6) by murine macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory periodontal disease, and sought to determine the underlying mechanisms of action. Methods: LPS was prepared from lyophilized P. intermedia ATCC 25611 cells by the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time polymerase chain reaction to detect IL-6 mRNA expression. $I{\kappa}B-{\alpha}$ degradation, nuclear translocation of NF-${\kappa}B$ subunits, and STAT1 phosphorylation were characterized via immunoblotting. DNA-binding of NF-${\kappa}B$ was also analyzed. Results: Curcumin strongly suppressed the production of IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW 264.7 cells. Curcumin did not inhibit the degradation of $I{\kappa}B-{\alpha}$ induced by P. intermedia LPS. Curcumin blocked NF-${\kappa}B$ signaling through the inhibition of nuclear translocation of NF-${\kappa}B$ p50 subunit. Curcumin also attenuated DNA binding activity of p50 and p65 subunits and suppressed STAT1 phosphorylation. Conclusions: Although further study is required to explore the detailed mechanism of action, curcumin may contribute to blockade of the host-destructive processes mediated by IL-6 and appears to have potential therapeutic values in the treatment of inflammatory periodontal disease.

Immunomodulatory Effects of phellinus linteus Extracts on Liver Damage Induced by Carbon Tetrachloride in Rats. (상황버섯 추출물이 사염화탄소로 간 손상이 유발된 흰쥐에서의 면역조절 효과)

  • An, Chi-Sun;Choi, Se-Young;Jin, Hai-Lan;Jeon, Yun-Hui;Hur, Sun-Jin;Kim, Ick-Hee;Park, Geum-Duck;Jeoung, Young-Jun;Lim, Beong-Ou
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.3
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    • pp.217-222
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    • 2009
  • The purpose of this study evaluated the immunoregulatory effect of phellinus linteus ethanol (PLE) extracts on liver damage on carbon tetrachloride ($CCl_4$) induced in rats. Four-week old Male Sprague-Dawley rats were divided into the three experimental groups randomly; Control group, $CCl_4$ group, $CCl_4$ + PLE group. We found that effect of PLE on $IFN-\gamma$, STAT1 and pSTAT1 was decrease in vivo. Several genes were demonstrated to be IL-4 inducible prior to the discovery of STAT6. IL-4, STAT6 and pSTAT6 decreased significantly lower in $CCl_4$ + PLE than the $CCl_4$ group. Our data indicated that cytokine protein production were increased in $CCl_4$ group with $CCl_4$ + PLE group. In our data indicate that IgA levels in MLN lymphocytes were low, while IgE was high in $CCl_4$ + PLE group compared with $CCl_4$ group. Therefore, the results of this study show that PLE can be proposed to protect the liver against $CCl_4$-induced immunoregulatory activity in rats.

Methyl 9-Oxo-(10E,12E)-octadecadienoate Isolated from Fomes fomentarius Attenuates Lipopolysaccharide-Induced Inflammatory Response by Blocking Phosphorylation of STAT3 in Murine Macrophages

  • Choe, Ji-Hyun;Yi, Young-Joo;Lee, Myeong-Seok;Seo, Dong-Won;Yun, Bong-Sik;Lee, Sang-Myeong
    • Mycobiology
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    • v.43 no.3
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    • pp.319-326
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    • 2015
  • Fomes fomentarius is a fungus of the Polyporaceae family and is used in traditional oriental therapies. Although the anti-inflammatory activities of this species have been previously reported, the identity of the bioactive compounds responsible for this activity remains unknown. Here, we investigated whether methyl 9-oxo-(10E,12E)-octadecadienoate (FF-8) purified from F. fomentarius exerts anti-inflammatory activity in murine macrophages stimulated with lipopolysaccharide (LPS). FF-8 suppressed secretion of nitric oxide (NO) and prostaglandin $E_2$ through downregulation of inducible NO synthase and cyclooxygenase-2 expression induced by LPS. In addition, pretreatment of cells with FF-8 led to a reduction in levels of secreted inflammatory cytokines such as tumor necrosis factor-${\alpha}$ and interleukin-6 in macrophages stimulated with LPS. Conversely, FF-8 did not affect nuclear factor ${\kappa}B$, p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase pathways. Instead, FF-8 specifically interfered with signal transducer and activator of transcription 3 (STAT3) phosphorylation induced by LPS. Collectively, this study demonstrated that FF-8 purified from F. fomentarius suppresses inflammatory responses in macrophages stimulated with LPS by inhibiting STAT3 activation. Further studies will be required to elucidate the anti-inflammatory effect of FF-8 in vivo.

Pseudomonas oleovorans의 유가식 배양에 의한 medium chain length Polyhydroxyalkanoates (MCL-PHA) 생산

  • Kim, Beom-Su;Im, Hui-Yeon
    • 한국생물공학회:학술대회논문집
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    • 2000.04a
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    • pp.207-210
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    • 2000
  • Pseudomonas oleovorans was cultivated to produce medium chain length polyhydroxyalkanoates (MCL-PHA) fram octanoic acid and ammonium nitrate as carbon and nitrogen source, respectively, by a pH-stat fed-batch culture technique. The octanoate concentration of the culture broth was maintained below 4 g/L by feeding the mixture of octanoic acid and ammonium nitrate when the culture pH rose above high limit. The effect of the ratio of octanoic acid to ammonium nitrate (C/N ratio) in the feed on the PHA production was examined. The final cell concentrations of 62.5, 54.7, and 9.5 g/L, PHA contents of 62.9, 75.1, and 67.6% of dry cell weight, and productivities of 1.03, 0.632, and 0.161 g/L/h were obtained when the C/N ratio in the feed were 10, 20, and 100 g octanoic acid/g ammonium nitrate, respectively.

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Effect of acupuncture treatment on carrageenan-induced inflammation and NADPH-diaphorase reactivity in the hypothalamus of Stat4 knockout mice (Carrageenan 염증 유도된 Stat 4 유전자 제거생쥐의 시상하부에서 NADPH-diaphorase 반응에 대한 침의 영향)

  • Hong, Mee-Suk;Kim, Mi-Ja;Kim, Jin-Ju;Park, Hi-Joon;Chung, Joo-Ho
    • Korean Journal of Acupuncture
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    • v.24 no.4
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    • pp.221-231
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    • 2007
  • 목 적 : 본 연구의 목적은 시상하부에서 침처치에 대한 nitric oxide synthase (NOS)발현을 nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)를 이용한 조직화학 염색법으로 관찰하였다. 실험방법 : 동물은 Balb/c (wild type) 와 Stat 4 knockout (KO) 생쥐를 사용하였다. 염증유도는 1% carrageenan 용액 (20ul/마리)을 발 뒤꿈치 표피에 주사하였고, 침 처치는 족삼리 (ST36)에 시침하였다. 침 처치 후 5시간까지 부종율을 부종측정기로 측정하였으며, 마지막으로 부종을 측정한 후 동물을 희생하여 뇌를 적출하여 고정하였다. 침에 대한 효과를 확인하기 위하여 NADPH-d 반응의 조직염색을 실시하였다. 염증유도와 그룹간의 유의성 검증은 one-way ANOVA를 사용하였다. 결 과 : 대조군인 Balb/c와 실험군인 stat4 KO 생쥐를 carrageenan으로 염증을 유도시에 대조군은 90%이상 유도된 반면, Stat4 KO 그룹은 50% 정도의 염증만이 유도되었다. 염증을 유도한 생쥐의 족삼리에 침 처치시 대조군은 1시간에서 약 40%정도 감소하였고 (P<0.05), Stat4 KO 실험군은 유의한 염증 감소율을 보이지 않았다. 시상하부의 lateral hypothalamic area (LHA)와 paraventricular nucleus (PVN)부위의 침에 대한 효과를 NADPH-d 에 양성으로 반응하는 세포수로 비교하여 다음과 같은 결과를 얻었다. (1) 대조군에서 염증 유도시 시상하부의 PVN는 NADPH-d 양성세포수가 감소하였고, LHA에서는 증가하였다. (2) 염증을 유도한 대조군에 침을 처치시 PVN은 세포수가 증가하였고, LHA에서는 감소하는 경향을 보였다. (3) 염증을 유도한 Stat4 KO 군에서는 시상하부의 PVN과 LHA부위 모두에서 NADPH-d 양성세포수가 감소하였고, 염증유도그룹에 침을 처치시 PVN과 LHA부위 모두에서 세포수가 증가함을 관찰 할 수 있었다. (4) 대조군과 실험군 모두에 salicylic acid로 비교하였더니 염증유도 효과 및 NADPH-d 세포 수에서 침 처치와 비슷한 결과를 나타내었다. 결 론 : 침은 염증을 유도한 생쥐에서 염증 감소에 유의한 효과가 있다. 염증을 유도한 Balb/c 와 Stat4 KO 생쥐에 침을 처치 시 시상하부의 NADPH-d 발현이 LHA부위와 PVN에서 서로 다르게 나타나는 것으로 나타난다. 이러한 현상은 침 효과가 시상하부의 위치에 대한 작용이 다르기 때문이라고 생각된다.

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