• Biomolecules & Therapeutics
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• 제22권5호
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• pp.390-399
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• 2014

Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.

• 대한종양외과학회지
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• 제14권2호
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• pp.89-94
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• 2018

Purpose: To investigate the relationship between MUC expression and clinicopathologic factors in advanced gastric cancer. Methods: A total of 237 tumor specimens were assessed for MUC expression by immunohistochemistry. The clinicopathologic factors were investigated with MUC1, MUC2, MUC5AC, and MUC6. Results: MUC1, MUC2, MUC5AC, and MUC6 expression was identified in 148 of 237 (62.4%), 141 of 237 (59.5%), 186 of 237 (78.5%), and 146 of 237 (61.6%) specimens, respectively. MUC1 expression was correlated with age, human epidermal growth factor receptor 2 (HER2) status, lymphatic invasion, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC1expression and lymphatic invasion, diffuse type of Lauren classification. MUC5AC expression was correlated with HER2 status, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC5AC expression and HER2 status, diffuse and mixed type of Lauren classification. MUC2 and MUC6 expression were not correlated with clinicopathologic factors. The patients of MUC1 expression had poorer survival than those without MUC1 expression, but MUC2, MUC5AC or MUC6 were not related to survival. In an additional multivariate analysis that used the Cox proportional hazards model, MUC1 expression was not significantly correlated with patient survival independent of age, N-stage, and venous invasion. Conclusion: When each of these four MUCs expression is evaluated, in light of clinicopathologic factors, MUC1 expression may be considered as a prognostic factor in patients with advanced gastric cancer. Therefore, careful follow-up may be necessary because the prognosis is poor when MUC1 expression is present.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6955-6959
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• 2013

The incidence of hepatocellular carcinoma (HCC) is relatively high in Southeast Asia. Globally, HCC has a high fatality rate and short survival. The objectives of this retrospective cohort study were to review the epidemiology and survival of HCC patients at a tertiary centre in north-east of Peninsular Malaysia. Subjects were adult HCC patients diagnosed by histopathology or radio-imaging. Secondary liver carcinoma was excluded. Kaplan Meier and multiple Cox proportional hazard survival analyses were used. Only 210 HCC cases from years 1987-2008, were included in the final analysis. The number of cases was increasing annually. The mean age was 55.0 (SD 13.9) years with male:female ratio of 3.7:1. Approximately 57.6% had positive hepatitis B virus, 2.4% hepatitis C virus, 20% liver cirrhosis and 8.1% chronic liver disease. Only 2.9% had family history and 9.0% had frequently consumed alcohol. Most patients presented with abdominal pain or discomfort and had hepatomegaly, 47.9% had an elevated ${\alpha}$-fetoprotein level of 800 IU/ml or more, 51.9% had multiple tumors and 44.8% involved multiple liver lobes. Approximately 63.3% were in stage 3 and 23.4% in stage 4, and 82.9% did not receive any treatment. The overall median survival time was 1.9 months (95% confidence interval (CI): 1.5, 2.3). The 1-month, 6-month, 1-year and 2-year survival rates were 71.8%, 23.3%, 13.0% and 7.3% respectively. Significant prognostic factors were Malay ethnicity [Adjusted hazard ratio (AHR) 1.6; 95%CI: 1.0, 2.5; p=0.030], no chemotherapy [AHR 1.7; 95%CI: 1.1, 2.5; p=0.017] and Child-Pugh class C [AHR 2.6; 95%CI: 1.4, 4.9; p=0.002]. HCC in our study affected a wide age range, mostly male, in advanced stage of disease, with no treatment and very low survival rates. Primary prevention should be advocated in view of late presentation and difficulty of treatment. Vaccination of hepatitis virus and avoidance of liver toxins are to be encouraged.

• Journal of Preventive Medicine and Public Health
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• 제51권6호
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• pp.298-309
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• 2018

Objectives: The objective of this study was to assess the relationship between systolic and diastolic blood pressure (SBP, DBP) and the risk of death from specific causes other than cardiovascular diseases. Methods: We calculated the risk of specific death by SBP and DBP categories for 506 508 health examinees in 2002-2003 using hazard ratios (HRs) and 95% confidence intervals (CIs) in a Cox proportional hazards model. Results: Compared to normal levels (SBP <120 or DBP <90 mmHg), stage I systolic and diastolic hypertension (SBP 140-159, DBP 85-89 mmHg, respectively) were associated with an increased risk of death from diabetes mellitus, alcoholic liver disease, and renal failure (HR, 1.83; 95% CI, 1.51 to 2.22; HR, 1.24; 95% CI, 1.06 to 1.46; HR, 2.30; 95% CI, 1.64 to 3.21; HR, 1.67; 95% CI, 1.27 to 2.20; HR, 1.99; 95% CI, 1.41 to 2.81; HR, 1.31; 95% CI, 0.99 to 1.73, respectively), but a decreased risk of death from intestinal pneumonia (HR, 0.64; 95% CI, 0.42 to 0.98; HR, 0.59; 95% CI, 0.39 to 0.91). Only stage II systolic hypertension (SBP ${\geq}160mmHg$) was associated with an increased risk of death from pneumonia, liver cirrhosis, and intestinal ischemia (HR, 1.54; 95% CI, 1.19 to 1.98; HR, 1.46; 95% CI, 1.00 to 2.15; HR, 3.77; 95% CI, 1.24 to 11.40, respectively), and stage I and II diastolic hypertension (SBP 140-159 and ${\geq}160mmHg$) were associated with an increased risk of death from intestinal ischemia (HR, 3.07; 95% CI, 1.27 to 7.38; HR, 4.39; 95% CI, 1.62 to 11.88, respectively). Conclusions: An increase in blood pressure levels may alter the risk of death from certain causes other than cardiovascular diseases, a well-known outcome of hypertension, although the mechanism of these associations is not well documented.

• 한방재활의학과학회지
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• 제30권1호
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• pp.47-61
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• 2020

Objectives This study is carried out to investigate the effects of Lonicera japonica in wound-induced rats. Methods Rats were divided into 5 groups; normal (Nor), control (Veh), positive comparison (PC), Lonicera japonica 100 mg/kg (LL), Lonicera japonica 200 mg/kg (LH), each n=8. Total polyphenol and flavonoid were quantified. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3 ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging activation were measured. Reactive oxygen species (ROS) was measured in serum. Antioxidant factors and inflammatory factors were measured in skin tissue, and also hydroxyproline content. Skin tissue was analyzed by Hematoxylin & Eosin and Masson's trichrome staining method. Results Total polyphenol and flavonoid were 32.86±0.14 mg/g and 67.17±0.57 mg/g. The IC₅₀ values of DPPH and ABTS free radical scavenging activation were 26.69±1.50 ㎍/mL and 49.33±4.52 ㎍/mL. ROS was significantly lower in LL and LH groups. Nuclear factor-erythroid 2-related factor 2 (Nrf2) was significantly higher in LH group and higher in LL group but not significant. Superoxide dismutase 1 (SOD-1), catalase, and heme oxygenase 1 (HO-1) were significantly higher in LL and LH groups. Nuclear factor kappa-B p65 (NF-κBp65), phosphorylated iκBα (p-iκBα), cyclooxygenase 2 (COX-2), and tumor necrosis factor alpha (TNF-α) were significantly lower in LL and LH groups. Hydroxyproline was significantly higher in LL and LH groups. The histopathologic analysis showed that skin tissue had recovered further more in LL and LH groups than in Veh group. Conclusions These results suggest that Lonicera japonica has the anti-oxidant, anti-inflammatory and healing effects in wound-induced rats.

• Hip & pelvis
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• 제34권3호
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• pp.150-160
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• 2022

Purpose: The purpose of this study is to determine risk factors that affect mortality following osteoporotic hip fracture in patients 50 years or older using the National Health Insurance Service (NHIS) sample cohort 2.0 database. Materials and Methods: Data from 2,533 patients who satisfied the inclusion criteria for the NHIS sample cohort 2.0 database were used in this study. Data from patients who suffered osteoporotic hip fractures between 2002-2015 were used. An analysis of correlations between the incidence of osteoporotic hip fractures and various factors (sex, age, underlying diseases, etc.) was performed. Analysis of the associations between the mortality of osteoporotic hip fracture and the various factors with hazard ratio (HR) was performed using Cox regression models. Results: Patient observation continued for an average of 38.12±32.09 months. During the observation period, a higher incidence of hip fracture was observed in women; however, higher mortality following the fracture was observed in men (HR=0.728; 95% confidence interval [CI], 0.635-0.836). The incidence and mortality of fractures increased when there were increasing age, more than three underlying diseases (HR=1.945; 95% CI, 1.284-2.945), cerebrovascular diseases (HR=1.429; 95% CI, 1.232-1.657), and renal diseases (HR=1.248; 95% CI, 1.040-1.497). Also, higher mortality was observed in patients who were underweight (HR=1.342; 95% CI, 1.079-1.669), current smokers (HR=1.338; 95% CI, 1.104-1.621), and inactivity (HR=1.379; 95% CI, 1.189-1.601). Conclusion: Male gender, the presence of cerebrovascular or kidney disease, a more than three underlying diseases, underweight, a current smoker, and inactivity were risk factors that increased mortality.

• Journal of Gastric Cancer
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• 제23권4호
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• pp.584-597
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• 2023

Purpose: This study aimed to investigate the impact of different types of complications on long-term survival following total gastrectomy for gastric cancer. Materials and Methods: A total of 926 patients who underwent total gastrectomy between 2008 and 2016 were included. Patients were divided into the morbidity and no-morbidity groups, and long-term survival was compared between the 2 groups. The prognostic impact of postoperative morbidity was assessed using a multivariate Cox proportional hazard model, which accounted for other prognostic factors. In the multivariate model, the effects of each complication on survival were analyzed. Results: A total of 229 patients (24.7%) developed postoperative complications. Patients with postoperative morbidity showed significantly worse overall survival (OS) (5-year, 65.0% vs. 76.7%, P<0.001) and cancer-specific survival (CSS) (5-year, 74.2% vs. 83.1%, P=0.002) compared to those without morbidity. Multivariate analysis adjusting for other prognostic factors showed that postoperative morbidity remained an independent prognostic factor for OS (hazard ratio [HR], 1.442; 95% confidence interval [CI], 1.136-1.831) and CSS (HR, 1.463; 95% CI, 1.063-2.013). There was no significant difference in survival according to the severity of complications. The following complications showed a significant association with unfavorable long-term survival: ascites (HR, 1.868 for OS, HR, 2.052 for CSS), wound complications (HR, 2.653 for OS, HR, 2.847 for CSS), and pulmonary complications (HR, 2.031 for OS, HR, 1.915 for CSS). Conclusions: Postoperative morbidity adversely impacted survival following total gastrectomy for gastric cancer. Among the different types of complications, ascites, wound complications, and pulmonary complications exhibited significant associations with long-term survival.

• Journal of Gastric Cancer
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• 제20권2호
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• pp.202-211
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• 2020

Purpose: This study was to investigate the prognostic significance of the preoperative fibrinogen and systemic inflammation response index (F-SIRI) in a Chinese cohort of resectable gastric cancer. Materials and Methods: Baseline characteristics, preoperative fibrinogen levels and peripheral neutrophil, monocyte, and lymphocyte counts were retrospectively reviewed in 240 patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and SIRI were defined as 4.0 g/L and 1.2. Then patients with hyperfibrinogenemia (≥4.0 g/L) and high SIRI (≥1.2) were assigned with an F-SIRI of 2 (both of these hematological abnormalities), 1 (one of these abnormalities), and 0 (neither abnormality), respectively. The prognostic value was examined by univariate and multivariate survival analysis. Results: Preoperative F-SIRI was significantly correlated with tumor size, fibrinogen level, and adjuvant chemotherapy. Whereas there was no significant difference in age, gender, tumor location or other characteristics between groups. In addition, high preoperative F-SIRI was significantly associated with worse disease-free survival (DFS) (hazard ratio [HR], 2.299; 95% confidence interval [CI], 1.482-3.566; P<0.001) and overall survival (OS) (HR, 2.461; 95% CI, 1.584-3.824; P<0.001) by univariate survival analysis. Moreover, it remained an independent predictor for impaired DFS (HR, 2.023; 95% CI, 1.273-3.215; P=0.003) and OS (HR, 2.341; 95% CI, 1.480-3.705; P<0.001) in multivariate Cox regression analysis. Conclusions: Preoperative F-SIRI could serve as a significantly prognostic marker for long-term survival in Chinese patients who underwent radical gastrectomy.

• 동의신경정신과학회지
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• 제18권3호
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• pp.55-82
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• 2007

Ohjective: This research investigates the effect of the DJR on Alzheimer's disease. Method: 1.The effects of the DJR extract on IL.-$1{\beta}$, IL-6, TNF-${\alpha}$, cox-2, and NOS-II mRNA of BV2 microglia cell line treated with LPS; 2. the behavior: 3. the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}$A were investigated. Result: 1. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ mRNA in BV2 microglia cell line treated with LPS. 2. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ protein production in BV2 microglia cell line treated with LPS. 3. For the DJR extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by .${\beta}$A in the Moms water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The DJR extract suppressed the over-expression of IL-$1{\beta}$ protein, TNF-${\alpha}$ protein and CD68/CD11b, in the mice with Alzheimer's disease induced by ${\beta}$A 5. The DJR extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}$A. 6. The DJR extract reduced the tau protein, GFAP protein, and presenilin1/2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}$A. Conclusion: These results suggest that the DJR extract may he effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the DJR extract for Alzheimer's disease of suggested for future research.

• BMB Reports
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• 제53권2호
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• pp.106-111
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• 2020

Glutaredoxin 1 (GLRX1) has been recognized as an important regulator of redox signaling. Although GLRX1 plays an essential role in cell survival as an antioxidant protein, the function of GLRX1 protein in inflammatory response is still under investigation. Therefore, we wanted to know whether transduced PEP-1-GLRX1 protein inhibits lipopolysaccharide (LPS)- and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced inflammation. In LPS-exposed Raw 264.7 cells, PEP-1-GLRX1 inhibited cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), activation of mitogen activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-κB) expression levels. In a TPA-induced mouse-ear edema model, topically applied PEP-1-GLRX1 transduced into ear tissues and significantly ameliorated ear edema. Our data reveal that PEP-1-GLRX1 attenuates inflammation in vitro and in vivo, suggesting that PEP-1-GLRX1 may be a potential therapeutic protein for inflammatory diseases.