• Title/Summary/Keyword: Expression and secretion

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Protective Effect of Fermented Brassica Puree on HCl/Ethanol-Induced Acute Gastritis via Prevention of Gastric Mucosal Injury (염산/에탄올로 유도된 급성 위염 동물모델에서 십자화과 생즙 발효물의 위점막 보호 효과)

  • Park, Yang-Gyu;Cho, Jeong-Hwi;Choi, Jinyoung;Kim, Youngpil;Lee, Sang-yeob;Park, Ju-Hun;Oh, Hong-Geun
    • The Korean Journal of Food And Nutrition
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    • v.34 no.5
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    • pp.468-476
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    • 2021
  • In recent years, there has been an increase in the morbidity of gastritis in Korea due to lifestyle factors mostly changes in eating habits and stress. Gastritis is more likely to progress to gastric cancer, and therefore it is important to prevent and manage gastritis through lifestyle adjustment and treatment at an early stage. In this study, cabbage, which was found to be effective in gastritis, was mixed and fermented with other crucifer plants such as kale and broccoli to evaluate the overall efficacy of fermented brassica puree on alcoholic acute gastritis. Based on our results, fermented brassica puree alleviated gastric injury induced by 150 mM HCl/60% ethanol. In addition, it was confirmed that PGE2, a gastric mucosal protective factor, was increased, and other positive effects such as an increase of MUC1 and regulation of PKC were observed. The results of this study suggest that fermented brassica puree can relieve acute alcoholic gastritis by regulating PGE and the expression of MUC1, a gene related to mucus secretion, and activating PKC, which is related to mucosal cell activity.

p38-dependent c-Jun degradation contributes to reduced PGE2 production in sodium orthovanadate-treated macrophages

  • Aziz, Nur;Kim, Eunji;Yang, Yanyan;Kim, Han Gyung;Yu, Tao;Cho, Jae Youl
    • BMB Reports
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    • v.55 no.8
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    • pp.389-394
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    • 2022
  • In particular, the phenomenon of c-Jun degradation within the inflammatory response has not yet been fully analyzed. In order to verify this, we investigated LPS-stimulated murine macrophages pre-treated with sodium orthovanadate (SO) in order to uncover the regulatory mechanisms of the MAPKs which regulate c-Jun degradation within the inflammatory response. Through our study, we found that SO suppressed the production of prostaglandin E2 (PGE2) and the expression of COX-2 in LPS-stimulated RAW264.7 cells. Additionally, SO decreased total c-Jun levels, without altering the amount of mRNA, although the phospho-levels of p38, ERK, and JNK were strongly enhanced. Through the usage of selective MAPK inhibitors, and knockdown and overexpression strategies, p38 was revealed to be a major MAPK which regulates c-Jun degradation. Further analysis indicates that the phosphorylation of p38 is a determinant for c-Jun degradation, and is sufficient to induce ubiquitination-dependent c-Jun degradation, recovered through MG132 treatment. Therefore, our results suggest that the hyperphosphorylation of p38 by SO contributes to c-Jun degradation, which is linked to the suppression of PGE2 secretion in inflammatory responses; and thus, finding drugs to increase p38 activity could be a novel strategy for the development of anti-inflammatory drugs.

Effect of Hwanggeumjackyak-tang (HJT) on the DSS-induced ulcerative colitis mouse model : including changes in intestinal metabolites (황금작약탕이 DSS로 유발된 궤양성 대장염 생쥐 모델에 미치는 영향 : 장내 대사물질 변화를 포함하여)

  • Cha-Kyung Youn;Sang-Mi Kang;Seon-Ah Son;Yang-Hee You;Eun-Ju Kim;Hong-Seok Son;Jae-Uk Sul;Chang-Su Na
    • Herbal Formula Science
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    • v.31 no.4
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    • pp.341-360
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    • 2023
  • Background : To investigate the effect of Hwanggeumjackyak-tang (HJT) on Dextran sulfate sodium (DSS) induced ulcerative colitis. Methods : The experimental animals were divided into three groups; group 1, normal group(Normal); group 2, DSS-induced colitis and untreated group(UT+DSS); group 3, DSS-induced colitis and HJT 200 mg-treated group(HJT200+DSS). We evaluated cytotoxicity after HJT administration and confirmed the anti-inflammatory effect by histological changes in the intestine and genetic analysis of mucosal cells after HJT administration for each group. In addition, microbiological weapons and metabolites in faeces were examined, and the correlation between gut microbiome and metabolites was also investigated. Result : HJT was not observed to be cytotoxic, even at relatively high concentrations, and was effective in protecting the barrier and preventing intestinal inflammation by suppressing the increase in mucus secretion and the expression of inflammatory factors in mucosal cells. HJT treatment affected the increase in the amount and diversity of the gut microbiome in faeces and the increase in metabolites thought to be involved in alleviating inflammation in the gut. Conclusion : This study demonstrates the therapeutic potential of HJT in ulcerative colitis. Further studies should be carried out to confirm our findings.

Phloretin Protects Macrophages from E. coli-Induced Inflammation through the TLR4 Signaling Pathway

  • Chauhan, Anil Kumar;Jang, Mihee;Kim, Yangmee
    • Journal of Microbiology and Biotechnology
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    • v.30 no.3
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    • pp.333-340
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    • 2020
  • Macrophages are the cells of the first-line defense system, which protect the body from foreign invaders such as bacteria. However, Gram-negative bacteria have always been the major challenge for macrophages due to the presence of lipopolysaccharides on their outer cell membrane. In the present study, we evaluated the effect of phloretin, a flavonoid commonly found in apple, on the protection of macrophages from Escherichia coli infection. RAW 264.7 cells infected with standard E. coli, or virulent E. coli K1 strain were treated with phloretin in a dose-dependent manner to examine its efficacy in protection of macrophages. Our results revealed that phloretin treatment reduced the production of nitric oxide (NO) and generation of reactive oxygen species along with reducing the secretion of proinflammatory cytokines induced by the E. coli and E. coli K1 strains in a concentration-dependent manner. Additionally, treatment of phloretin downregulated the expression of E. coli-induced major inflammatory markers i.e. cyclooxygenase-2 (COX-2) and hemeoxygenase-1 (HO-1), in a concentration dependent manner. Moreover, the TLR4-mediated NF-κB pathway was activated in E. coli-infected macrophages but was potentially downregulated by phloretin at the transcriptional and translational levels. Collectively, our data suggest that phloretin treatment protects macrophages from infection of virulent E. coli K1 strain by downregulating the TLR4-mediated signaling pathway and inhibiting NO and cytokine production, eventually protecting macrophages from E. coli-induced inflammation.

Long-Duration Three-Dimensional Spheroid Culture Promotes Angiogenic Activities of Adipose-Derived Mesenchymal Stem Cells

  • Lee, Jun Hee;Han, Yong-Seok;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • v.24 no.3
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    • pp.260-267
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    • 2016
  • Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine.

Paromomycin Derived from Streptomyces sp. AG-P 1441 Induces Resistance against Two Major Pathogens of Chili Pepper

  • Balaraju, Kotnala;Kim, Chang-Jin;Park, Dong-Jin;Nam, Ki-Woong;Zhang, Kecheng;Sang, Mee Kyung;Park, Kyungseok
    • Journal of Microbiology and Biotechnology
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    • v.26 no.9
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    • pp.1542-1550
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    • 2016
  • This is the first report that paromomycin, an antibiotic derived from Streptomyces sp. AG-P 1441 (AG-P 1441), controlled Phytophthora blight and soft rot diseases caused by Phytophthora capsici and Pectobacterium carotovorum, respectively, in chili pepper (Capsicum annum L.). Chili pepper plants treated with paromomycin by foliar spray or soil drenching 7 days prior to inoculation with P. capsici zoospores showed significant (p < 0.05) reduction in disease severity (%) when compared with untreated control plants. The disease severity of Phytophthora blight was recorded as 8% and 50% for foliar spray and soil drench, respectively, at 1.0 ppm of paromomycin, compared with untreated control, where disease severity was 83% and 100% by foliar spray and soil drench, respectively. A greater reduction of soft rot lesion areas per leaf disk was observed in treated plants using paromomycin (1.0 μg/ml) by infiltration or soil drench in comparison with untreated control plants. Paromomycin treatment did not negatively affect the growth of chili pepper. Furthermore, the treatment slightly promoted growth; this growth was supported by increased chlorophyll content in paromomycin-treated chili pepper plants. Additionally, paromomycin likely induced resistance as confirmed by the expression of pathogenesis-related (PR) genes: PR-1, β-1,3-glucanase, chitinase, PR-4, peroxidase, and PR-10, which enhanced plant defense against P. capsici in chili pepper. This finding indicates that AG-P 1441 plays a role in pathogen resistance upon the activation of defense genes, by secretion of the plant resistance elicitor, paromomycin.

Effects of Korean Red Ginseng Extract for the Treatment of Atopic Dermatitis-Like Skin Lesions in Mice

  • Sohn, Eun-Hwa;Jang, Seon-A;Lee, Chul-Hoon;Jang, Ki-Hyo;Kang, Se-Chan;Park, Hye-Jin;Pyo, Suhk-Neung
    • Journal of Ginseng Research
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    • v.35 no.4
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    • pp.479-486
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    • 2011
  • Atopic dermatitis (AD) is an allergic, inflammatory skin disease characterized by chronic eczema and mechanical injury to the skin, caused by scratching. Korean red ginseng (RG) has diverse biological activities, but the molecular effects of RG on allergic diseases, like AD, are unclear. The present study was designed to investigate whether RG inhibits 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD in a mouse model. DNCB was applied topically on the dorsal surface of Balb/c mice to induce AD-like skin lesions. We observed the scratching behavior and examined the serum IgE level and interleukin (IL)-4 and IL-10 in splenocytes compared with dexamethasone. We also evaluated the DNCB-induced mitogen-activated protein kinases (MAPKs), NF-${\kappa}B$, and Ikaros activities after RG treatment using reverse transcriptase-polymerase chain reaction, Western blotting, and ELISA. Our data showed that the topical application of RG significantly improved the AD-like skin lesions and scratching behavior. RG decreased not only the mRNA expression of IL-4 and IL-10, but also the secretion of IL-4 protein and serum IgE in mice. Additionally, RG treatment decreased the DNCB-induced MAPKs activity and subsequent Ikaros translocation irrespective of NF-${\kappa}B$. We suggest that RG may be useful as a therapeutic nutrition for the treatment of AD.

Effects of Uncaria rhynchophylla Extracts on Differentiation and Bone Mineralized Formation in Human Osteoblast-like SaOS-2 cells

  • Huh, Jeong-Eun;Baek, Yong-Hyeon;Choi, Do-Young;Lee, Jae-Dong;Park, Dong-Suk
    • The Journal of Korean Medicine
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    • v.28 no.4
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    • pp.158-167
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    • 2007
  • Background & Objective : Uncaria rhynchophylla is traditional medicine herb used for enhancing body resistance against various diseases. The aim of this study was to identify if Uncaria rhynchophylla extracts induce osteogenic activity in human osteoblast-like SaOS-2 cells. Methods : The osteogenic activity of Uncaria rhynchophylla was evaluated on cell proliferation assay by WST-8, and osteoblast-specific genes, such as VEGF, type I collagen (Col I), osteocalcin (OCN), and osteopontin (OPN) by RT-PCR analysis and ELISA assay in osteoblasts-like SaOS-2 cells. Bone mineralization was stained with Alizalin red method. Results : Uncaria rhynchophylla had significantly increased cell proliferation at a dose dependent manner in human osteoblast-like SaOS-2 cells. Uncaria rhynchophylla markedly increased alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF) mRNA expression at 7 days and dose dependently increased ALP activity and VEGF secretion in human osteoblast-like SaOS-2 cells. Also, Uncaria rhynchophylla time-dependently increased type I collagen (Col I), osteopontin (OPN), and osteocalcin (OCN) mRNA in SaOS-2 cells. Extracellular accumulation of proteins such as Col I and OCN was maximal increased by Uncaria rhynchophylla at 10 ${\mu}g/ml$. Also, Uncaria rhynchophylla significantly induced mineralization in the culture of SaOS-2 cells. Conclusion : This study showed that Uncaria rhynchophylla had enhanced proliferation, ALP activity, VEGF, bone matrix proteins such as OCN, OPN, and Col I, and mineralization in SaOS-2 cells. These results propose that Uncaria rhynchophylla can play an important role in osteoblastic bone formation, osteogenesis, and may possibly lead to the development of bone-forming drugs.

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Effect of Feeding Time Shift on the Reproductive System in Male Rats

  • Kwak, Byung-Kook;Lee, Sung-Ho
    • Development and Reproduction
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    • v.16 no.1
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    • pp.53-58
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    • 2012
  • Circadian rhythmicity (e.g. secretory pattern of hormones) plays an important role in the control of reproductive function. We hypothesized that the alteration of feeding pattern via meal time shift/restriction might disrupt circadian rhythms in energy balance, and induce changes in reproductive activities. To test this hypothesis, we employed simple animal model that not allowing $ad$ $libitum$ feeding but daytime only feeding. The animals of $ad$ $libitum$ feeding group (Control) have free access to food for 4 weeks. The day feeding (=reverse feeding, RF) animals (RF group) have restricted access to food during daytime (0900-1800) for 4 weeks. After completing the feeding schedules, body weights, testis and epididymis weights of animals from both group were not significantly different. However, the weights of seminal vesicle (control : RF group = $0.233{\pm}0.014g$ : $0.188{\pm}0.009g$, $p$<0.01) and prostate (control : RF group = $0.358{\pm}0.015g$ : $0.259{\pm}0.015g$, $p$<0.001) were significantly lower in RF group animals. The mRNA levels of pituitary common alpha subunit ($C{\alpha}$; control : RF group = $1.0{\pm}0.0699$ AU : $0.1923{\pm}0.0270$ AU, $p$<0.001) and $FSH{\beta}$ (control : RF group = $1.0{\pm}0.1489$ AU : $0.5237{\pm}0.1088$ AU, $p$<0.05) were significantly decreased in RF group. The mRNA levels of ACTH were not significantly different. We were unable to find any prominent difference in the microstructures of epididymis, and there were slight alterations in those of seminal vesicles after 4 weeks of reversed feeding when compared to control samples. The present study demonstrates that the shift and/or restriction of feeding time could alter the pituitary gonadotropin expression and the weights of seminal vesicle and prostate in rats. These data suggest the lowered gonadotropin inputs may decrease androgen secretion form testis, and consequently results in poor response of androgen-dependent tissues such as seminal vesicle and prostate.

Anti-inflammatory Activity on LPS-stimulated in vitro RAW 264.7 Cells and in vivo Zebrafish of Heterosigma akshiwo

  • Kim, Junseong;Choi, Youn Kyung;Lee, Ji-Hyeok;Kim, Seo-Young;Kim, Hyun-Soo;Jeon, You-Jin;Heo, Soo-Jin
    • Journal of Chitin and Chitosan
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    • v.22 no.3
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    • pp.185-193
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    • 2017
  • Red tide Heterosigma akashiwo (H. akashiwo), a microscopic alga of the class Raphidophyceae, causes extensive damage to all marine ecosystems. It is essential to reduce the damage to marine ecosystems for them to be used as a resource. In this study, we used organic solvent fractionation to obtain an ethyl acetate-methanol extract from H. akashiwo (HAEM80) and then evaluated its anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and a zebrafish model. HAME80 markedly inhibited the production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). It also down-regulated the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreased the secretion of interleukin-$1{\beta}$ ($IL-1{\beta}$) in LPS-stimulated RAW 264.7 cells. HAME80 reduced yolk edema and improved the survival rate of LPS-stimulated zebrafish embryos; in addition, the extract significantly reduced the production of ROS and NO and attenuated cell death in this model. Gas chromatography-mass spectrometry (GC-MS) of the extract was used to confirm the identity of peaks 1-20. Taken together, our data suggest that H. akashiwo is a beneficial anti-inflammatory agent.