Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Kim, Sokho,Oh, Myung-Hoon,Kim, Bum-Seok,Kim, Won-Il,Cho, Ho-Seong,Park, Byoung-Yong,Park, Chul,Shin, Gee-Wook,Kwon, Jungkee The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to $200{\mu}M$) for 1 h before treatment with 1 mg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Sokho Kim,Myung-Hoon Oh,Bum-Seok Kim,Won-Il Kim,Ho-Seong Cho,Byoung-Yong Park,Chul Park,Gee-Wook Shin,Jungkee Kwon 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been suffi- ciently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to 200mM) for 1 h before treatment with 1 mg/ mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

Genetic associations of body composition, flexibility and injury risk with ACE, ACTN3and COL5A1polymorphisms in Korean ballerinas

( Jun Ho Kim ),( Eun Sun Jung ),( Chul Hyun Kim ),( Hyeon Youn ),( Hwa Rye Kim ) 한국운동영양학회 2014 Physical Activity and Nutrition (Phys Act Nutr) Vol.18 No.2

Jun Ho Kim, Eun Sun Jung, Chul-Hyun Kim, Hyeon Youn and Hwa Rye Kim. Genetic associations of body composition, flexibilityand injury risk with ACE, ACTN3and COL5A1polymorphisms in Korean ballerinas. JENB., Vol. 18, No. 2, pp.205-214, 2014[Purpose] The purpose of this study was to exam the association of body composition, flexibility, and injury risk to genetic polymorphismsincluding ACEID, ACTN3RX, and COL5A1polymorphisms in ballet dancers in Korea. [Methods]For the purpose of this study,elite ballerinas (n = 97) and normal female adults (n = 203) aged 18 to 39 were recruited and these participants were tested forbody weight, height, body fat, fat free mass, flexibility, injury risks on the joints and gene polymorphisms (ACE, ACTN3, COL5A1polymorphism). [Results]As results, the ACEDD genotype in ballerinas was associated with higher body fat and percentageof body fat than the ACEII and ID genotypes (p< 0.05). In the study on the ACTN3polymorphism and ballerinas, the XXgenotype in ballerinas had lower body weight and lower fat-free mass than the RR and RX genotype (p < 0.005). Also, the meansof sit and reach test for flexibility was lower in the ACTN3XX genotype of ballerinas than the RR and RX genotype of ballerinas(p< 0.05). Among the sports injuries, the ankle injury of the XX-genotyped ballerinas was in significantly more prevalence thanthe RR and XX-genotyped ballerinas (p< 0.05). According to the odd ratio analysis, XX-genotyped ballerinas have the injuryrisk on the ankle about 4.7 (95% CI: 1.6~13.4, p< 0.05) times more than the RR and RX-genotyped ballerinas. Meanwhile, theCOL5A1polymorphism in ballerinas has no association with any factors including flexibility and injury risks. [Conclusion]Inconclusion, ACEpolymorphism and ACTN3polymorphism were associated with ballerinas` performance capacity; COL5A1wasnot associated with any factors of performance of Ballerinas. The results suggested that the ACEDD genotype is associated withhigh body fat, the ACTN3XX genotype is associated with low fat-free mass, low flexibility, and higher risk of ankle-joint injury. [Keyword]ballet, flexibility, body composition, injury risk, ACE, ACTN3, COL5A1

PGA2-induced HO-1 attenuates G2M arrest by modulating GADD45α expression

Yun-Jeong Choe,고경원,Hyein Lee,이선영,Byung-Chul Kim,Ho-Shik Kim,Ho-Shik Kim 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.4

Prostaglandin (PG) A2, a cyclopentenone PG, arrested the growth of U2OS cells in the G2M phase. While inducing G2M arrest, PGA2 increased the expression of heme oxygenase-1 (HO-1) at the level of transcription along with the accumulation of ROS and the activation of MAPKs including JNK, p38MAPK, and ERK1/2. Among the MAPKs, the inhibition of p38MAPK by a specific chemical inhibitor SB203580, or by RNA interference, but not JNK or ERK1/2, attenuated the PGA2-induced transcription of HO-1. Nacetylcysteine (NAC), a ROS scavenger, prevented PGA2-induced G2M arrest, p38MAPK activation and transcriptional induction of HO-1. PGA2 also stimulated GADD45α expression at the level of transcription, and the knockdown of GADD45α repressed PGA2- induced G2M arrest. Finally, the knockdown of the HO-1 protein elevated PGA2-induced GADD45α expression as well as G2M arrest. Collectively, these results suggest that PGA2 causes an increase in ROS accumulation which initiates both HO-1 transcription via p38MAPK, and G2M arrest via GADD45α transcription, and HO-1 attenuates G2M arrest by modulating the expression of GADD45α.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

임신 중 고혈압성 질환에 대한 임상적 고찰

김경철,정명철,김호성,조민형,고재환,김용봉 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Objective: The aim of this study was to investigate the clinical charact eristics of pregnancy induced hypertension(PIH). Methods: We retrospectively evaluated the clinical characteristics through the collected data of 176 PIH cases treated at Seoul Paik hospital from March 1995 to December 2002. Results: The proportions of severe PIH, mild PIH, and chronic hypertension were 70%, 24%, and 6% of the cases, respectively. According to maternal age, the highest rate of 45% was noted in the group of 26-30 years of age. The rate of cesarean(80%) was higher than the rate of vaginal delivery(20%). The blood pressure was controlled by hydralazine for 70% of the patients. The rate of single gestation was 90%. The birthweight of 20% of the newborn were 2500gm or more. The anemia, twin pregnancy, postpartum hemorrhage, pulmonary edema, and infection were found in 30%, 10%, 3%, 2%, and 1% of the PIH patients, respectively. In respect of the perinatal complications, the rates of low birth weight, stillbirth, and neonatal death were 80%, 3%, and 1%, respectively. Conclusion: We were able to decrease the mortality and morbidity of PIH patients and neonates with strict antenatal care and proper treatment.

단기간의 저용량 Cytosine arabinoside 치료에 반응하였던 Down 증후군에 병발한 급성골수성백혈병 1례

김현수,이정호,이정찬,강정현,곽상혁,김철희,배광봉,김종숙,조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

The incidence of hematologic disorders in patients with Down's syndrome is significantly increased, about 14∼30 - fold higher than in general population and includes neonatal transient abnormal myelopoieis and acute leukemias. The age of onset of leukemia in Down's syndrome is peaking first in the newborn period and then under 4 years of age. Down's syndrome with acute leukemia above the age of 20 is very rare and it's treatment oucome is unclear. The treatment of Down's syndrome with leukemia has been controversial because of toxicity and associated congenital cardiac and other abnormalities. But if treated adequately, children with Down's syndrome show a favorable response to anti-leukemia therapy. A 24-year-old man with Down's syndrome was first seen for the evaluation of anemia and thrombocytopenia. The peripheral blood morphology and bone marrow study revealed acute myelogenous leukemia, cytogenetic study of bone marrow showed trisomy 21. Beacuse of his sicioeconomic condition and medical abnormalities including deafness, visual loss, he was treated with low dose subcutaneous cytosine arabinoside(Ara-C) for 11 days. Complete remission was obtained after 37 days. The complete remission lasted for 5 months. He subsequently relapsed, and died 6 months later.

간 세포암에서 VEGF, TGF-β1, b-FGF 발현의 의의

김성용,남충현,주종우,채만규,백무준,이문수,김형철,안현철,김홍수,김창진,김창호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Purpose: Angiogenesis is important for the proliferation and the metastasis of solid tumors. The growth of a solid tumor is widely recognized to depend on the process of neovascularrozation. Without angiogenesis, tumors cease to grow beyond even a few milimeters in diameter. It has been shown that tumor vascular density is an independent prognostic marker in several types of human tumors and is known to correlate with poor prognosis. To date, many angiogenic factors have been identified, such as transforming growth factor-α(TGF-α), transforming growth factor-β(TGF-β), fibroblast growth factor family(FGF), vascular endothelial growth factor(VEGF), platelet derived endothelial cell growth factor(PD-ECGF), tumor necrosis factor-α(TNF-α), and angiogenin. Hepatocellular carcinoma(HCC) is the second most common tumor in Korean males and is known as a typical hypervascular tumor with frequent portal vein invastion. The authors identified the expreesion of VEGF, TGF-β1, and b-FGF in HCC specimens and evaluated the relationship between these growth factors and the clinicopathologic characteristics of HCC. Method: We reviewed the medical records of 30 patients who were diagnosed as hepatocellular carinoma treated with hepatic resection between January 1994 and December 1998 in Soonchunhyang University Chunan Hospital. The selection of the cases was decided according to the condition of paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum α-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus(HBV) infection, and Edmonson-Steiner(E-S) grade were investigated. Relationship between the prognostic factors and the immunopathologic expression of the TGF-β1, b-FGF, and VEGF was examined. Result: Thirty patients (24 males, 6 females) were included in the current study. The patient's mean age was 50.6 years and the age ranged from 36 to 65 years. The mean size of the tumor was found to be 5.2cm. All the patients were follewed up for 7 to 63 months. Child's classification A patients were 23(76.7%)cases, B patients were 7(23.3%)cases, and C was none. Immunohistochemical staining of HCC tumor mass in VEGF expression patients were 17(56.7%), b-FGF expression patients were 10(33.3%), and TGF-β1 expression patients were 10(33.3%). VEGF expression or more than one positive expression among the three factors correlated with tumor size and the stage of HCC but did not correlated with other clinicopathological characteristics. TGF-β1 and b-FGF did not correlate with any clinicopathological characteristics. Conclusion: The results suggest that the expression of VEGF or more than one positive expression among the three factors in HCC cells may be a significant prognostic factor of HCC.

중증 재생불량성 빈혈 환자에서 신우신염에 대한 광범위항생제치료 중에 속발한 Saccharomyces cerevisiae 진균감염 1예

김철희,이정호,이정찬,강정현,곽상혁,배광봉,김현수,김종숙,조덕연,김삼용 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.1

Most patients with aplastic anemia who do not respond to immunosuppressive treatment or are not candidates for bone marrow transplantation die of infection or bleeding. The neutropenia in acute leukemia, aplastic anemia, or occurring subsequently to chemotherapy and bone marrow transplantation increases susceptibility to infection. In general, the number of infectious episodes correlate with the degree and duration of neutropenia. Global immunosuppression produced by conditioning for bone marrow transplantation or graft-versus-host disease, is associated with unusual bacterial and fungal pathogens, or serious viral and protozoan infections. In addition, repeated treatment with broad-spectrum antibiotics is associated with the emergence of resistant organisms and fungal diseases because of the altered microbial microenvironment of the host. The incidence of invasive fungal infection caused by Saccharomycetes eerevisiae in immunosuppressed patients is very rare, compared with that of infection by candida or aspcrgillus species. Cases of Saccharomycetes cerevisiae fungemia occurring in the course of treatment with broad-spectrum antibiotics are reported in patients with extensive burn or with prosthetic valve endocarditis. We experienced a case of urinary tract infection by Saccharomycetes cerevisiae in a 27-year old female patient with severe aplastic anemia. We report the case with a review of relevant literatures.

Anti-Inflammatory and Cytoprotective Effects of TMC-256C1 from Marine-Derived Fungus <i>Aspergillus</i> sp. SF-6354 via up-Regulation of Heme Oxygenase-1 in Murine Hippocampal and Microglial Cell Lines

Kim, Dong-Cheol,Cho, Kwang-Ho,Ko, Wonmin,Yoon, Chi-Su,Sohn, Jae Hak,Yim, Joung Han,Kim, Youn-Chul,Oh, Hyuncheol MDPI AG 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.4

<P>In the course of searching for bioactive secondary metabolites from marine fungi, TMC-256C1 was isolated from an ethyl acetate extract of the marine-derived fungus <I>Aspergillus</I> sp. SF6354. TMC-256C1 displayed anti-neuroinflammatory effect in BV2 microglial cells induced by lipopolysaccharides (LPS) as well as neuroprotective effect against glutamate-stimulated neurotoxicity in mouse hippocampal HT22 cells. TMC-256C1 was shown to develop a cellular resistance to oxidative damage caused by glutamate-induced cytotoxicity and reactive oxygen species (ROS) generation in HT22 cells, and suppress the inflammation process in LPS-stimulated BV2 cells. Furthermore, the neuroprotective and anti-neuroinflammatory activities of TMC-256C1 were associated with upregulated expression of heme oxygenase (HO)-1 and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. We also found that TMC-256C1 activated p38 mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in HT22 and BV2 cells. These results demonstrated that TMC-256C1 activates HO-1 protein expression, probably by increasing nuclear Nrf2 levels via the activation of the p38 MAPK and PI3K/Akt pathways.</P>