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The Anti-Inflammatory Effect of Trichilia martiana C. DC. in the Lipopolysaccharide-Stimulated Inflammatory Response in Macrophages and Airway Epithelial Cells and in LPS-Challenged Mice

  • Park, Ji-Won;Ryu, Hyung Won;Ahn, Hye In;Min, Jae-Hong;Kim, Seong-Man;Kim, Min-Gu;Kwon, Ok-Kyoung;Hwang, Daseul;Kim, Soo-Yong;Choi, Sangho;Zamora, Nelson;Rosales, Kattia;Oh, Sei-Ryang;Lee, Jae-Won;Ahn, Kyung-Seop
    • Journal of Microbiology and Biotechnology
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    • v.30 no.11
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    • pp.1614-1625
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    • 2020
  • A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1β, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

Anti-Inflammatory Effects of 1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose in LPS-Stimulated Macrophages (LPS로 자극한 대식세포에서 1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose의 염증 억제 효과)

  • Lee, Hee Won;Kang, Ye Rim;Bae, Min Seo;Kim, Yoon Hee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.409-416
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    • 2017
  • 1,2,3,4,6-Penta-O-galloyl-${\beta}$-D-glucose (PGG) is a gallotannin isolated from Galla Rhois. In a previous study, PGG was shown to suppress the allergic response by attenuating immunoglobulin E production both in vitro and in vivo. However, the effect of PGG on bacteria-induced inflammation at physiological concentration remains unclear. Therefore, the aim of this study was to investigate the effect of PGG on lipopolysaccharide (LPS)-stimulated macrophages. PGG inhibited release of nitric oxide (NO) and prostaglandin $E_2$ by alleviating protein expression of inducible NO synthase and cyclooxygenase-2 in LPS-treated RAW264.7 cells. Furthermore, PGG suppressed the release of interleukin-6 and tumor necrosis factor-${\alpha}$ induced by LPS. Further study indicated that PGG blocked translocation of the p65 subunit of nuclear factor-${\kappa}B$ from the cytosol into the nucleus, which is one of the underlying mechanisms of the anti-inflammatory action of PGG. Collectively, these data suggest that PGG might be useful for the treatment of inflammatory disease.

Prognostic Significance of Lymphatic and Perineural Invasions in Patients with Gastric Cancer Who Have No Lymph Node and Serosal Involvement (장막 침윤과 림프절 전이가 없는 위암에서 림프관 및 신경초 침윤의 의의)

  • Kim Wook;Park Cho Hyun;Park Seung Man;Park Woo Bai;Lim Keun Woo;Kim Seung Nam
    • Journal of Gastric Cancer
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    • v.1 no.2
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    • pp.77-82
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    • 2001
  • Purpose: The most important prognostic factors in gastric cancer are depth of invasion and lymph node metastasis. Therefore, the prognosis for serosa and lymph node negative gastric cancer is favorable. However, there is no general agreement on the prognostic factors in this subset of patients. This study was undertaken to evaluate the prognostic significances of venous invasion (VI), lymphatic invasion (LI), and perineural invasion (NI) in T1 and T2 gastric cancer without lymph node involvement. Materials and Methods: We retrospectively evaluated 206 patients with T1 and T2, lymph node negative gastric cancer who underwent a curative resection from 1989 to 1993 at Kangnam St. Mary's Hospital, Seoul, Korea. The Chi-square test was used to determine the statistical significance of differences, and the Kaplan-Meier method was used to calculate survival rates. Significant differences in the survival rates were assessed using the log-rank test, and the Cox regression method was used to evaluate independent prognostic significance. Results: The rate of VI, LI and NI correlated well with the depth of tumor invasion. The rates of VI (+) for T1 vs T2 was $0\%\;vs\;5.1\%$, of LI (+) was $5.6\%\;vs\;26.8\%$, and of NI (+) was $1.6\%\;vs\;26.8\%$ in NI (+). There were 13 recurrent cases, 10 cases out of the 13 were T2 gastric cancers, and the recurrence rate was higher in LI (+) and NI (+) cases than in LI (-) and NI (-) cases. The 5-year survival rates were $93.4\%$ in LI (-) cases, $77.4\%$ in LI (+) cases, $92.5\%$ in NI (-) cases, $74\%$ in NI(+) cases, $95.9\%$ in LI (-) NI (-) cases, and $73.9\%$ in LI (+) NI (+) cases. Multivariate analysis demonstrated that simultaneous LI and NI was the only significant factor influencing the prognosis. Conclusion: These results suggest that simultaneous lymphatic and perineural invasion may be an independent prognostic factor in patients with T1 and T2 gastric cancer without lymph node metastasis.

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Anti-inflammatory Effects of the Fruits of Foeniculum vulgare in Lipopolysaccharide-stimulated Macrophages (대식세포에서 LPS로 유도된 염증에 대한 회향 열매의 항염 효과)

  • Yang, In Jun;Yu, Hak Yin;Lee, Dong-Ung;Shin, Heung Mook
    • Journal of Life Science
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    • v.24 no.9
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    • pp.981-987
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    • 2014
  • Foeniculum vulgare has long been prescribed in traditional medicine for the treatment of inflammation diseases. In this study, we aimed to investigate the inhibitory effects of the fruits of F. vulgare on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells under non-cytotoxic ($100{\mu}g/ml$) conditions. The 80% methanol extract was subsequently partitioned successively with hexane, methylene chloride, ethyl acetate, and n-butanol, and the fractions so obtained were also examined for their anti-inflammatory effects. Among them, the hexane, methylene chloride, and ethyl acetate fractions inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in LPS stimulated macrophages. The methylene chloride and ethyl acetate fractions also suppressed the productions of interleukin $(IL)-1{\beta}$ and IL-6 by down-regulating their mRNA levels in LPS stimulated RAW 264.7 cells. Furthermore, the ethyl acetate fraction strongly suppressed tumor necrosis factor (TNF)-${\alpha}$ at the protein and mRNA levels in LPS stimulated RAW 264.7 cells. These observations suggest that the anti-inflammatory actions of F. vulgare are due to inhibitions of the productions of NO, PGE2, and pro-inflammatory cytokines.

Effects of Mole Crickets (Gryllotalpa orientalis) Extracts on Anti-oxidant and Anti-inflammatory Activities. (땅강아지(Gryllotalpa orientalis) 추출물의 항산화 및 항염증 활성)

  • Heo, Jin-Chul;Lee, Dong-Yeob;Son, Min-Sik;Yun, Chi-Young;Hwang, Jae-Sam;Kang, Seok-Woo;Kim, Tae-Ho;Lee, Sang-Han
    • Journal of Life Science
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    • v.18 no.4
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    • pp.509-514
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    • 2008
  • Tremendous natural product extracts were used as a herb medicine remedy or therapy for centuries. Because these extracts have various biological activities, we examined the effects of Gryllotalpa orientalis extract for anti-oxidant and anti-inflammation activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP), hydroxy radical scarvenging and cyclooxygenase-2 promoter assays. Gryllotalpa orientalis extracts were prepared from solvents such as distilled water (DW), dimethyl sulfoxide (DMSO), ethanol and methanol. The results showed that Gryllotalpa orientalis extracts have potent DPPH (methanol extract), FRAP (DW extract) and hydroxy radical scavenging (DW and methanol extracts) activity than any other extracts used. A significant inhibition of cyclooxygenase-2 (Cox-2) promoter activity was detected in the presence of DMSO extract or ethanol extract. Collectively, the present results suggested that Gryllotalpa orientalis extract could be used for anti-oxidant and/or anti-inflammation agent for human or agricultural purposes.

Sex-specific Associations Between Serum Hemoglobin Levels and the Risk of Cause-specific Death in Korea Using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS)

  • An, Yoonsuk;Jang, Jieun;Lee, Sangjun;Moon, Sungji;Park, Sue K.
    • Journal of Preventive Medicine and Public Health
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    • v.52 no.6
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    • pp.393-404
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    • 2019
  • Objectives: The purpose of this study was to determine the associations between blood hemoglobin (Hgb) levels and the risk of death by specific causes. Methods: Using the National Health Insurance Services-National Health Screening Cohort (n=487 643), we classified serum Hgb levels into 6 sex-specific groups. Cox regression analysis was used to analyze the associations between Hgb levels and the risk of cause-specific death. Results: Hgb levels in male population showed a U-shaped, J-shaped, or inverse J-shaped association with the risk of death from ischemic heart disease, acute myocardial infarction, liver cancer, cirrhosis and chronic obstructive pulmonary disease (COPD) (all non-linear p<0.05; hazard ratio [HR]; 95% confidence interval [CI]) for the lowest and the highest Hgb levels for the risk of each cause of death in male population: HR, 1.14; 95% CI, 0.98 to 1.34; HR, 2.87; 95% CI, 1.48 to 5.57; HR, 1.16; 95% CI, 0.96 to 1.40; HR, 3.05; 95% CI, 1.44 to 6.48; HR, 1.36; 95% CI, 1.18 to 1.56; HR, 2.11; 95% CI, 1.05 to 4.26; HR, 3.64; 95% CI, 2.49 to 5.33; HR, 5.97; 95% CI, 1.44 to 24.82; HR, 1.62; 95% CI, 1.14 to 2.30; HR, 3.84; 95% CI, 1.22 to 12.13, respectively), while in female population, high Hgb levels were associated with a lower risk of death from hypertension and a higher risk of death from COPD (overall p<0.05; HR, 1.86; 95% CI, 1.29 to 2.67 for the lowest Hgb levels for hypertension; overall p<0.01, HR, 6.60; 95% CI, 2.37 to 18.14 for the highest Hgb levels for COPD). For the risk of lung cancer death by Hgb levels, a linear negative association was found in male population (overall p<0.01; the lowest Hgb levels, HR, 1.17; 95% CI, 1.05 to 1.33) but an inverse J-shaped association was found in female population (non-linear p=0.01; HR, 1.25; 95% CI, 0.96 to 1.63; HR, 2.58; 95% CI, 1.21 to 5.50). Conclusions: Both low and high Hgb levels were associated with an increased risk of death from various causes, and some diseases showed different patterns according to sex.

Anti-inflammatory activity of indigenous Tuber himalayense in Korea (자생 Tuber himalayense 자실체 추출물의 항염증 활성)

  • Kim, Minkyeong;Hong, Hyehyun;Kim, Jung-Hwan;Kim, Seung-Young;Kim, Changmu
    • Journal of Mushroom
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    • v.19 no.3
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    • pp.176-183
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    • 2021
  • In this study, the anti-inflammatory activity of an extract of the fruiting body of the Tuber himalayense (TH) truffle collected from oak growing areas in Korea was investigated. The extract was not cytotoxic at concentrations below 100 ㎍/mL in an experiment evaluating inflammation inhibitory effect in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production was inhibited by the extract in a concentration-dependent manner. Western blot assay results indicated that the anti-inflammatory activity of TH extract was likely caused by the reduced production of NO and PGE2 via suppression of induced NO synthase and cyclooxygenase-2 gene expression. In addition, TH extract effectively inhibited the production of interleukin (IL)-1β and IL-6 by macrophages. Thus, TH extract effectively inhibits the overexpression of various inflammatory mediators and could be valuable in formulating anti-inflammatory foods and medicines that target these components.

Preoperative Risk Factors for Pathologic N2 Metastasis in Positron Emission Tomography-Computed Tomography-Diagnosed N0-1 Non-Small Cell Lung Cancer

  • Yoon, Tae-hong;Lee, Chul-ho;Park, Ki-sung;Bae, Chi-hoon;Cho, Jun-Woo;Jang, Jae-seok
    • Journal of Chest Surgery
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    • v.52 no.4
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    • pp.221-226
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    • 2019
  • Background: Accurate mediastinal lymph node staging is vital for the optimal therapy and prognostication of patients with lung cancer. This study aimed to determine the preoperative risk factors for pN2 disease, as well as its incidence and long-term outcomes, in patients with clinical N0-1 non-small cell lung cancer. Methods: We retrospectively analyzed patients who were treated surgically for primary non-small cell lung cancer from November 2005 to December 2014. Patients staged as clinical N0-1 via chest computed tomography (CT) and positron emission tomography (PET)-CT were divided into two groups (pN0-1 and pN2) and compared. Results: In a univariate analysis, the significant preoperative risk factors for pN2 included a large tumor size (p=0.083), high maximum standard uptake value on PET (p<0.001), and central location of the tumor (p<0.001). In a multivariate analysis, central location of the tumor (p<0.001) remained a significant preoperative risk factor for pN2 status. The 5-year overall survival rates were 75% and 22.9% in the pN0-1 and pN2 groups, respectively, and 50% and 78.2% in the patients with centrally located and peripherally located tumors, respectively. In a Cox proportional hazard model, central location of the tumor increased the risk of death by 3.4-fold (p<0.001). Conclusion: More invasive procedures should be considered when preoperative risk factors are identified in order to improve the efficacy of diagnostic and therapeutic plans and, consequently, the patient's prognosis.

Anti-inflammatory effect of soil blue-green algae Nostoc commune isolated from Daejeon National Cemetery (국립대전현충원에서 분리한 남조류 구슬말(Nostoc commune)의 항염증 효과)

  • Hong, Hyehyun;Bae, Eun Hee;Park, Tae-Jin;Kang, Min-Sung;Kang, Jae Shin;Chi, Won-Jae;Kim, Seung-Young
    • Journal of Applied Biological Chemistry
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    • v.65 no.2
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    • pp.113-120
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    • 2022
  • We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E2 and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

The protective effect of Areca Semen and Toosendan Fructus mixture in a chronic model of reflux esophagitis (빈랑자와 천련자 복합물의 만성 역류성 식도염에서 보호 효과)

  • Shin, Mi-Rae;Lee, Jin A;Kim, Min Ju;An, Hyo-Jin;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.35 no.1
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    • pp.57-68
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    • 2020
  • Objective : The aim of present study was to clarify the effect of Areca Semen and Toosendan Fructus Mixture (AT-mix) on chronic reflux esophagitis (CRE) in rats. Methods : The antioxidant activity of AT-mix was measured through DPPH and ABTS radical scavenging activities in vitro. CRE was induced in SD rats (5 weeks, male) by ligating the border forestomach and granular portion with 2-0 silk and the duodenum near the pyloric portion was covered with 2-mm wide piece of 18-Fr Nélaton catheter. And then rats were treated AT-mix 200 mg/kg one daily for 14 days. The anti-oxidant and inflammatory protein levels were evaluated using western blotting. Results : Gross lesion of esophageal mucosa after AT-mix treatment showed a superior enhancement compared with that of CRE control rats. AT-mix treatment strongly reduced both DPPH and ABTS radical scavenging activities (DPPH, IC50 8.15±0.14 ㎍/mL; ABTS, IC50 24.69±0.03 ㎍/mL, repspectively). Levels of the NADPH oxidase subunit including NOX4 and p22phox increased in CRE control rats. Otherwise, AT-mix treatment significantly reduced. The activation of Nuclear factor-erythroid 2-related factor 2 (Nrf2) led to significantly the up-regulation of HO-1. The inhibition of IκBα phosphorylation led to NF-κB inactivation. Subsequently, NF-κB inactivation significantly induced the decrease of COX-2, iNOS, TNF-α, and IL-6 protein expressions. Conclusion : Taken together, these results suggest that AT-mix treatment can attenuate the esophageal mucosal ulcer though inhibiting NF-κB pathway and enhancing Nrf2/HO-1 pathway. Thus, the additional mechanism study about AT-mix would need for the development as a safe herbal therapy for CRE.