• Title/Summary/Keyword: systemic inflammation

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The Blood Neutrophil-to-lymphocyte Ratio Predicts Survival in Patients with Advanced Hepatocellular Carcinoma Receiving Sorafenib

  • Zheng, You-Bing;Zhao, Wei;Liu, Bing;Lu, Li-Gong;He, Xu;Huang, Jian-Wen;Li, Yong;Hu, Bao-Shan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5527-5531
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    • 2013
  • Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy. Methods: A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed. Results: Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (${\leq}4$) (P=0.01). Age ${\leq}65$, NLR>4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). Conclusions: High baseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.

The anti-allergy and anti-inflammatory effect of Anemarrhenae Rhizoma in vivo and in vitro

  • Kim, Su-Jin;Jeong, Hyun-Ja;Myung, Noh-Yil;Moon, Phil-Dong;Lee, Ju-Young;Yi, Byoung-Jae;Lee, Eun-Hyub;An, Nyeon-Hyung;Park, Seok-Jae;Kim, Min-Cheol;Jun, Suk-Min;Lee, Ji-Hyun;Kim, Hyung-Min;Hong, Seung-Heon;Um, Jae-Young
    • Advances in Traditional Medicine
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    • v.7 no.3
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    • pp.235-243
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    • 2007
  • Anemarrhenae Rhizoma (AR) is used in traditional oriental medicine for various medicinal purposes. However, the exact mechanism that accounts for the anti-allergy and anti-inflammatory effects of the AR is still not fully understood. The aim of The present study is to elucidate whether and how AR modulates the allergic reactions in vivo, and inflammatory reaction in vitro. In this study, we showed that AR significantly decreased compound 48/80-induced systemic anaphylaxis, paw oedema, and histamine release from preparation of rat peritoneal mast cells. Also, AR inhibited the expression of inflammatory cytokine in PMA plus A23187-stimulated human mast cells (HMC-1). In addition, we showed that anti-inflammatory mechanism of AR is through suppression of nuclear factor-${\kappa}B$ activation $I{\kappa}B-{\alpha}$degradation. These results provided new insight into the pharmacological actions of AR as a potential molecule for therapy of inflammatory allergic diseases.

Ghrelin Attenuates Dexamethasone-induced T-cell Apoptosis by Suppression of the Glucocorticoid Receptor (덱사메타손에 의해 유발된 흉선 T세포사멸에 대한 그렐린의 세포사멸억제효과)

  • Lee, Jun Ho
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1356-1363
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    • 2014
  • Ghrelin is a 28 amino acid orexigenic peptide hormone that is secreted predominantly by tX/A cells in the stomach, and it plays a major role in energy homeostasis. Activated ghrelin has an n-octanoyl group covalently linked to the hydroxyl group of the Ser3 residue, which is critical for its binding to the G-protein coupled growth hormone secretagogue receptor-1a (GHS-R1a). According to recent reports, both ghrelin and its receptor, GHS-R1a, are expressed by a variety of immune cells, including T- and B-lymphocytes, monocytes, and dendritic cells, and ghrelin stimulation of leukocytes provides a potent immunomodulatory signal controlling systemic and age-associated inflammation and thymic involution. Here, we report that ghrelin protected murine thymocytes from dexamethasone (DEX)-induced cell death both in vivo and in vitro. Subsequently, we explored the molecular mechanisms of the antiapoptotic effect of ghrelin. According to our experiments, ghrelin inhibited the expression of proapoptotic proteins via the regulation of glucocorticoid receptor (GR) phosphorylation. As a result, ghrelin inhibited the proapoptotic activation of proteins, such as Caspase-3, PARP, and Bim. These data suggest that ghrelin, through GHS-R, inhibits the pathway to apoptosis by regulation of the proapoptotic protein activation signal pathway. They provide evidence that blocking apoptosis is an essential function of ghrelin during the development of thymocytes.

Clinical Features of Kawasaki Disease with Pyuria (농뇨 동반 가와사키병의 임상적 특징)

  • Kim, Hyo-Jin;Lee, Joo-Young;Choi, Ui-Yoon;Lee, Soo-Young
    • Pediatric Infection and Vaccine
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    • v.24 no.3
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    • pp.141-145
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    • 2017
  • Purpose: Clinical and laboratory features of two Kawasaki disease (KD) groups were evaluated; the patient with pyuria and those without pyuria. Methods: From January 2015 to December 2016, the medical records of 140 (86 males and 54 females) inpatients with KD were retro-spectively analyzed. Results: Forty-eight KD patients (34.3%) presented with pyuria. KD patients with pyuria showed a higher level of C-reactive protein (CRP) and a higher proportion of elevated liver enzymes than those without pyuria. There were no differences in the proportions of unresponsiveness to intravenous immunoglobulin and coronary artery lesions between the two groups. Six KD patients (12.5%) with pyuria underwent a renal imaging study to rule out the possibility of a urinary tract infections. Thirty-two KD patients (66.7%) with pyuria received treatment with antibiotics in addition to the standard treatment for KD. Conclusions: KD patients with pyuria showed a higher level of CRP and elevated levels of liver enzymes than those without pyuria. These findings suggest that KD patients with pyuria have more severe systemic inflammation than those without pyuria.

The Activation of Stress-induced Heat Shock Protein 27 and the Relationship of Physical Therapy (스트레스-유도 열충격단백질 27(Heat Shock Protein 27)의 활성과 물리치료의 상관성)

  • Kim, Mi-Sun;Lee, Sung-Ho;Kim, Il-Hyun;Hwang, Byong-Yong;Kim, Jung-Hwan
    • The Journal of Korean Physical Therapy
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    • v.20 no.1
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    • pp.57-65
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    • 2008
  • Purpose: Heat shock proteins (HSPs) are a group of proteins that are activated when cells are exposed to a variety of environmental stresses, such as infection, inflammation, exposure to toxins, starvation, hypoxia, brain injury, or water deprivation. The activation of HSPs by environmental stress plays a key role in signal transduction, including cytoprotection, molecular chaperone, anti-apoptotic effect, and anti-aging effects. However, the precise mechanism for the action of small HSPs, such as HSP27 and mitogen-activated protein kinases (MAPKs: extracellular-regulated protein kinase 1/2 (ERK1/2), p38MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), is not completely understood, particularly in application of cell stimulators including platelet-derived growth factor (PDGF), angiotensin II (AngII), tumor necrosis factor $\alpha$ (TNF$\alpha$), and $H_2O_2$. This study examined the relationship between stimulators-induced enzymatic activity of HSP27 and MAPKs from rat smooth and skeletal muscles. Methods: 2-dimensional electrophoresis (2DE) and matrix assisted laser desorption ionizationtime-of-flight/time-of-flight (MALDI-TOF/TOF) analysis were used to identify HSP27 from the intact vascular smooth and skeletal muscles. Three isoforms of HSP27 were detected on silver-stained gels of the whole protein extracts from the rat aortic smooth and skeletal muscle strips. Results: The expression of PDGF, AngII, TNF$\alpha$, and $H_2O_2$-induced activation of HSP27, p38MAPK, ERK1/2, and SAPK/JNK was higher in the smooth muscle cells than the control. SB203580 (30${\mu}$M), a p38MAPK inhibitor, increased the level of HSP27 phosphorylation induced by stimulators in smooth muscle cells. Furthermore, the age-related and starvation-induced activation of HSP27 was higher in skeletal muscle cells (L6 myoblast cell lines) and muscle strips than the control. Conclusion: These results suggest, in part, that the activity of HSP27 and MAPKs affect stressors, such as PDGF, AngII, TNF$\alpha$, $H_2O_2$, and starvation in rat smooth and skeletal muscles. However, more systemic research will be needed into physical therapy, including thermotherapy, electrotherapy, radiotherapy and others.

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DA-7911, $^{188}Rhenium-tin$ Colloid, as a New Therapeutic Agent of Rheumatoid Arthritis

  • Shin, Chang-Yell;Son, Miwon;Ko, Jun-Il;Jung, Mi-Young;Lee, In-Ki;Kim, Soon-Hoe;Kim, Won-Bae;Jeong, Jae-Min;Song, Yeong-Wook
    • Archives of Pharmacal Research
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    • v.26 no.2
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    • pp.168-172
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    • 2003
  • Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.

Antiinflammatory and Antiallergic Activity of Fermented Turmeric by Lactobacillus johnsonii IDCC 9203 (Lactobacillus johnsonii IDCC 9203으로 발효한 울금의 소염 및 항알레르기 효과)

  • Kim, Seong-Beom;Kang, Byung-Hwa;Kwon, Hyuk-Sang;Kang, Jae-Hoon
    • Microbiology and Biotechnology Letters
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    • v.39 no.3
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    • pp.266-273
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    • 2011
  • Although turmeric has numerous pharmacological effects, the poor water-solubility of curcuminoids, active components of turmeric, restricts their systemic availability in orally administered formulations and limits their therapeutic potential. In this study we attempted turmeric fermentation using several probiotic bacteria to improve its solubility, and also investigated the effects of turmeric and fermented turmeric on anti-inflammatory activity. Fermented turmeric, by L. johnsonii IDCC 9203, more strongly inhibited LPS-induced expression of the pro-inflammatory cytokines than non-fermented turmeric and fermented turmeric by other probiotic strains. We used an NC/Nga mouse model for mite antigen-induced atopic dermatitis to examine the efficacy of the fermented turmeric. Fermented turmeric-fed mice exhibited a significantly reduced serum IgE level and mitigated acute inflammation. When the fermented turmeric was pre-treated by oral administration, it had more preventive activity against acute anaphylactic reaction than the non-fermented group. In addition, we observed that fermentation of turmeric leads to increased water-solubility of curcumin and a change in the active components ratios for bisdemethoxycurcumin, demethoxycrucumin and curcumin. Taken together, these results strongly suggest that fermented turmeric by L. johnsonii IDCC 9203 could be used as a functional food ingredient for improving treatments for atopic dermatitis.

Expression of Matrix metalloproteinase-1 between Simple Chronic Periodontitis and Type 2 Diabetes associated Chronic Periodontitis on Protein level (단순만성치주염환자와 2형 당뇨환자의 만성치주염에서 Matrix metalloproteinase-1의 발현양상)

  • Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • v.35 no.3
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    • pp.649-659
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    • 2005
  • The purpose of this study was to quantify and compare the level of MMP-1 in the healthy or inflamed gingival tissue of patients with or without type 2 diabetic mellitus. We investigated whether mean amount of MMP-1 was changed by chronic periodontitis and type 2 DM. Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was divided into the three group. Group 1(n=8) was clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2(n=8) was inflamed gingiva from patients with chronic periodontitis. Group 3(n=8) was inflamed gingiva from patients with chronic periodontitis and type 2 diabetes. Tissue samples were prepared and analyzed by Western blotting. The quantitative analysis of MMP-1 was performed using a densitometer and statistically analyzed by ANOVA. MMP-1 was expressed in all samples and an increased MMP-1 level was observed in group 2 compared to group 1 and decreased MMP-1 level was found group 3 compared to group 2, but the differences among 3 groups were not statistically significant. In conclusion, this study demonstrated that MMP-1 levels of inflamed gingiva of systemically healthy patient(group 2) were higher than normal gingiva of systemically health patients and although the severity of gingival inflammation in group 2 and 3 were similar, MMP-1 expression was decreased in diabetic patients than systemically healthy periodontal patients.

The Gingival Tissue Levels of Bone Resorptive Mediators in Human Chronic Periodontitis with Type 2 Diabetes Mellitus (2형 당뇨병환자의 만성 치주염 치은조직에서 골흡수 인자의 발현 양상 비교)

  • Kim, Mi-Jung;Ryu, Sang-Ho;Park, Jin-Woo;Suh, Jo-Young;Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • v.37 no.4
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    • pp.743-753
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    • 2007
  • Purpose: The purposes of this study were to compare and quantify the expression of MMP-3, $PGE_2$ and IL-6 in the gingival tissues of patients with $type_2$ diabetes mellitus and healthy adults with chronic periodontitis. Material and methods: Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was devided into three groups. Group 1(n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2(n=8) is inflamed gingiva from patients with chronic periodontitis. Group 3(n=8) is inflamed gingiva from patients with chronic periodontitis associated with type 2 DM. Tissue samples were prepared and analyzed by Westernblotting. The quantification of MMP-3, $PGE_2$ and IL-6 were performed using a densitometer and statistically analyzed by one-way ANOVA followed by Tukey test. Results: 1. The expression levels of MMP-3 were shown highest in group 3 compared to group 1 and 2, and It showed increasing tendency in group 2 and 3. 2. The expressions of $PGE_2$ and IL-6 were shown increasing tendency in group 2 and 3, and It was highest in group 3. 3. As expressions of MMP-3 were increased, $PGE_2$ and IL-6 expressions showed increasing tendency in group 3 than group1 and 2, although there were no proportional relationship. Conclusion: This study demonstrated that the expression levels of MMP-3, $PGE_2$ and IL-6 will be inflammatory markers of periodonta linflamed tissue and DM. It can be assumed that MMP-3 affect to expressions of $PGE_2$ and IL-6 in progression of periodontal inflammation with alveolar bone resorption to type 2 DM.

The Influence of Diabetes on of $PGE_2$, MMP-14 and TIMP Expressions in Human Chronic Periodontitis (만성 치주염 환자에서 2형 당뇨병이 $PGE_2$, MMP-14 및 TIMP의 발현양상에 미치는 영향)

  • Kim, Seon-Woo;Park, Jin-Woo;Suh, Jo-Young;Lee, Jae-Mok
    • Journal of Periodontal and Implant Science
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    • v.37 no.4
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    • pp.755-766
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    • 2007
  • Purpose: The purposes of this study were to compare and quantify the expression of $PGE_2$, MMP-14 and TIMP-1 in the gingival tissues of patients with type 2 diabetes mellitus and healthy adults of chronic periodontitis with alveolar bone resorption. Material and methods: Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was devided into three groups. Group 1 (n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2 (n=8) is inflammed gingiva from patients of chronic periodontitis with alveolar bone resorption. Group 3(n=8) is inflammed gingiva from patients of chronic periodontitis with alveolar bone resorption associated with type 2 diabetes. Tissue samples were prepared and analyzed by Western blotting. The quantification of $PGE_2$ MMP-14 and TIMP-1 were performed using a densitometer and statistically analyzed by one-way ANOVA followed by Tukey test. Results: The expressions of MMP-14 and TIMP-1 were showed increasing tendency in group 2 & 3 compared to group 1. The expressions of $PGE_2$, MMP-14 were showed increasing tendency in group 3 compared to group 1 and group 2. According to MMP-14 levels were increasing, $PGE_2$ showed increasing tendency in group 3, and although $PGE_2$, MMP-14 levels were increasing, TIMP-1 levels were similar expressed comparing to group 2. Conclusion: In conclusion, this study demonstrated that the expression levels of MMP-14 and TIMP-1 had increasing tendency in inflammed tissue. It can be assumed that $PGE_2$ and MMP-14 may be partly involved in alveolar bone resorptive process and the progression of periodontal inflammation associated to type 2 DM.