• Journal of Life Science
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• v.34 no.7
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• pp.443-452
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• 2024

This study aimed to examine the influence of 3,6-anhydroxygalactose (L-AHG) on the pro-inflammatory M1 polarization and pro-inflammatory responses observed in the RAW264.7 mouse macrophage cell line following stimulation with lipopolysaccharides (LPS). L-AHG exhibited a significant and dose-dependent inhibition of inducible nitric oxide synthase (iNOS) expression, a hallmark of M1 polarization, and subsequent NO production in LPS-stimulated RAW264.7 cells. Furthermore, the LPS-induced upregulation of cyclooxygenase-2 (COX-2), which drives the production of prostaglandin E2, an inflammatory mediator, was also inhibited by L-AHG. L-AHG did not affect the LPS-triggered Toll-like receptor 4 (TLR4)-mediated pro-inflammatory signaling pathway, which culminated in the activation of transforming growth factor-β-activated kinase 1 (TAK1). However, it was observed to inhibit the generation of reactive oxugen species (ROS) in a dose-dependent manner, as well as the TAK1-driven activation of JNK and p38 MAPK. Given that the active p38 MAPK is known to contribute to the assembly of active nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which catalyzes the intracellular generation of pro-inflammatory ROS in LPS-stimulated macrophages, the dose-dependent reduction in the LPS-induced ROS generation by L-AHG may be mainly due to the prevention of TAK1-driven activation of p38 MAPK. Together, these results demonstrate that the L-AHG-mediated inhibition of the TAK1-JNK/p38 MAPK activation phase of the pro-inflammatory signaling pathway in LPS-stimulated RAW264.7 cells by L-AHG represents a promising mechanism for suppressing M1 polarization and pro-inflammatory responses in macrophages.

• Journal of Preventive Medicine and Public Health
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• v.51 no.2
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• pp.71-82
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• 2018

Objectives: Areca nut is widely consumed in many parts of the world, especially in South and Southeast Asia, where cardiovascular disease (CVD) is also a huge burden. Among the forms of CVD, acute coronary syndrome (ACS) is a major cause of mortality and morbidity. Research has shown areca nut chewing to be associated with diabetes, hypertension, oropharyngeal and esophageal cancers, and CVD, but little is known about mortality and re-hospitalization secondary to ACS among areca nut users and non-users. Methods: A prospective cohort was studied to quantify the effect of areca nut chewing on patients with newly diagnosed ACS by categorizing the study population into exposed and non-exposed groups according to baseline chewing status. Cox proportional hazards models were used to examine the associations of areca nut chewing with the risk of re-hospitalization and 30-day mortality secondary to ACS. Results: Of the 384 ACS patients, 49.5% (n=190) were areca users. During 1-month of follow-up, 20.3% (n=78) deaths and 25.1% (n=96) re-hospitalizations occurred. A higher risk of re-hospitalization was found (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.29 to 3.27; p=0.002) in areca users than in non-users. Moreover, patients with severe disease were at a significantly higher risk of 30-day mortality (aHR, 2.77; 95% CI, 1.67 to 4.59; p<0.001) and re-hospitalization (aHR, 2.72; 95% CI, 1.73 to 4.26; p<0.001). Conclusions: The 30-day re-hospitalization rate among ACS patients was found to be significantly higher in areca users and individuals with severe disease. These findings suggest that screening for a history of areca nut chewing may help to identify patients at a high risk for re-hospitalization due to secondary events.

• Journal of Microbiology and Biotechnology
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• v.33 no.1
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• pp.96-105
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• 2023

Probiotic supplements have promising therapeutic effects on chronic diseases. In this study, we demonstrated the anti-obesity effects of two potential probiotics, Bifidobacterium bifidum DS0908 (DS0908) and Bifidobacterium longum DS0950 (DS0950). Treatment with DS0908 and DS0950 postbiotics significantly induced the expression of the brown adipocyte-specific markers UCP1, PPARγ, PGC1α, PRDM16 and beige adipocyte-specific markers CD137, FGF21, P2RX5, and COX2 in C3H10T1/2 mesenchymal stem cells (MSCs). In mice with high-fat diet (HFD)-induced obesity, both potential probiotics and postbiotics noticeably reduced body weight and epididymal fat accumulation without affecting food intake. DS0908 and DS0950 also improved insulin sensitivity and glucose use in mice with HFD-induced obesity. In addition, DS0908 and DS0950 improved the plasma lipid profile, proved by reduced triglyceride, low-density lipoprotein, and cholesterol levels. Furthermore, DS0908 and DS0950 improved mitochondrial respiratory function, confirmed by the high expression of oxidative phosphorylation proteins, during thermogenesis induction in the visceral and epididymal fat in mice with HFD-induced obesity. Notably, the physiological and metabolic changes were more significant after treatment with potential probiotic culture-supernatants than those with the bacterial pellet. Finally, gene knockdown and co-treatment with inhibitor-mediated mechanistic analyses showed that both DS0908 and DS0950 exerted anti-obesity-related effects via the PKA/p38 MAPK signaling activation in C3H10T1/2 MSCs. Our observations suggest that DS0908 and DS0950 could potentially alleviate obesity as dietary supplements.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.2
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• pp.26-42
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• 2009

Purpose: This study was performed to evaluate the anti-inflammatory effect of Manbunbang extract (MBB). Methods: In order to understand the mechanism of anti-inflammatory effect of MBB, expression of cytokines and its levels in RAW 264.7 cell lines, as well as changes of cytokine gene expressions in serum, spleen, and liver tissues in acute inflammation induced mouse model were investigated. Results: 1. MBB significantly suppressed the expression levels of IL-1${\beta}$, TNF-${\alpha}$ and COX-2 mRNAs at 100 and 50 ${\mu}$g/m${\ell}$ concentrations, and IL-6 and NOS-II genes at 100, 50 and 10 ${\mu}$g/m${\ell}$ concentrations in RAW 264.7 cell lines, compared to those of the control. 2. MBB significantly reduced the production level of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ at 100 and 50 ${\mu}$g/m${\ell}$ concentrations in RAW 264.7 cell lines compared the those of the control. 3. MBB significantly reduced the production of IL-1${\beta}$, IL-6 and TNF-${\alpha}$ levels in sera of acute inflammation induced mice. 4. MBB significanlty suppressed the expression level of IL-1${\beta}$, TNF-${\alpha}$ mRNA in spleen tissues as well as IL-6 mRNA in liver tissues in acute inflammation induced mice. Conclusion: From the results above, anti-inflammatory effect of MBB through its immune regulation could be experimentally explained. Wide treatment of inflammatory diseases such as pelvic inflammation using MBB are recommended.

• Clinical Nutrition Research
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• v.11 no.1
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• pp.32-41
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• 2022

We evaluated the association between obesity status by body mass index (BMI) or waist circumference (WC) and osteoporotic fracture risk. We collected data of 143,673 women with a mean age of 58.5 years without history of osteoporotic fracture from the Korean National Health Insurance Service Cohort. Participants were divided into four groups according to obesity by BMI and WC, normal BMI/WC (BMI 18.5-24.9 kg/m² and WC < 85 cm, reference), obese BMI/normal WC (BMI ≥ 25 kg/m² and WC < 85 cm), normal BMI/obese WC (BMI < 25 kg/m² and WC ≥ 85 cm), and obese BMI/WC (BMI ≥ 25 kg/m² and WC < 85cm). Cox proportional hazards regression analyses were performed to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for the subsequent median 6.0 years, which were adjusted for age, socioeconomic status, lifestyle, morbidity index, and osteoporosis medication. Compared with the normal group, normal BMI/obese WC was associated with a higher osteoporotic fracture risk after multivariable adjustment (HRs [95% CI], 1.13 [1.05-1.21]), and obese BMI/normal WC was associated with a lower osteoporotic fracture risk (0.89 [0.84-0.94]). Obese BMI/normal WC was associated with a lower risk for hip fractures (0.75 [0.57-0.99]). Obese BMI/normal WC was associated with decreased risk of osteoporotic fracture, whereas normal BMI/obese WC was associated with increased risk of osteoporotic fracture compared with the normal group among East Asian women in their late 40s or more.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.1
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• pp.14-23
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• 2020

This study was conducted to evaluate the efficacy of Cheongawongagam on osteoporosis rat. A total of 35 rats were divided into seven groups; Normal control(SD-Nr), experimental control group(OVX-CTL), positive control group(OVX-17β-E2) and herb extracts group[Eucommia ulmoides(OVX-EU-E), Juglandis semen(OVX-JR-SE), Acanthopanax senticosus(OVX-AS-E) extract and Cheongawongagam extracts(OVX-JAEG-E)]. All control group, and herb extracts group were ovariectomized. After the 3 weeks recovery period, herb extract group were orally administered 200 mg / kg of the EU-E, JR-SE, AS-E and JAEG-E for 12 weeks. In the OVX-CTL, 17β-estradiol(E2) was administered subcutaneously on the back of the rats at a dose of 0.03 ug/sc. Their body weight, serum total cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Leukotriene B4 (LTB4), calcium (Ca), estradiol, osteocalcin, and deoxypyridinoline (DPD) concentration were measured. Also, we investigated mRNA expression of inflammatory cytokine, MMP-2, MMP-9, and bone tissue. As a result, total cholesterol was significantly decreased in the OVX-AS-E and OVX-JAEG-E. ALP was significantly increased and osteocalcin, DPD was significantly decreased in OVX-JAEG-E. The expression of inflammatory mediators (TNF-α, IL-1β, LTB4, COX-2, NOS-2), inflammatory cytokines IL-1β and MMP-9 mRNA were significantly decreased in OVX-JAEG-E. Histologic examination of the femur showed that bone mineral density, and bone mass were increased and bone marrow were decreased in the OVX-JAEG-E group. The above experiment shows that cheongawongagam extract were effective in the prevention and treatment of osteoporosis.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.179-186
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• 2014

Purpose: To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. Materials and Methods: The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. Results: The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). Conclusion: In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.2 s.33
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• pp.10-35
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• 2007

Objectives : To investigate the effects of Ohbaesangami (OBSGM) on mucosa and skin diseases, anti-microbial and anti-inflammatory tests were performed using several in vitro test models. Results : In anti-microbial test, OBSGM showed the slight inhibitory effect against Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus). In anti-oxidant test, OBSGM showed the potent radical scavenging activity. In anti-inflammatory test, OBSGM weakly inhibited the lipopolysaccharide (LPS)-induced nitric oxide(NO) release from the RAW 264.7 macrophage cells. OBSGM also inhibited the LPS-induced $interleukin-1{\beta}(IL-1{\beta})$ and cyclooxygenase-2 (COX-2) expressions. The inhibitory effects of OBSGM on macrophage activation was via the inhibition of $NF-{\kappa}B$, evidenced by transient transfection assay. Furthermore, OBSGM markedly inhibited the activation of Jun-N-terminal kinase (JNK) and p38 MAP kinase in RAW 264.7 cells. In skin wrinkle formation assay, OBSGM strongly inhibited collagnease and elastase, whose activities are tightly related with the wrinkle formation. In addition, OBSGM inhibited the activities of MMP-1, MMP-2 on the mRNA levels in RAW 264.7 cells. However, OBSGM did not show an inhibitory potential on tyrosinase activity and melanin synthesis, indicating that it could not be applicable for skin whitening. Conclusion : These results suggest that the anti-inflammatory effect of OBSGM may be due to its inhibitory potentials on the macrophage activation. And, the anti-wrinkle effects of OBSGM may be due to its inhibitory potential on the collagnease and elastase activities. Therefore, OBSGM could be applicable for the treatment of mucosa and skin diseases.

• Natural Product Sciences
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• v.23 no.3
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• pp.183-191
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• 2017

Luteolin 5-O-glucoside is the major flavonoid from Korean thistle, Cirsium maackii. We previously reported the anti-inflammatory activities of luteolin 5-O-glucoside in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In this study, we determined the anti-inflammatory mechanisms of luteolin 5-O-glucoside through the inhibition of nitric oxide (NO) production in vitro and in vivo. Results revealed that luteolin 5-O-glucoside dose-dependently inhibited NO production and expression of iNOS and COX-2 in LPS-induced RAW 264.7 cells. Luteolin 5-O-glucoside also significantly inhibited the translocation of $NF-{\kappa}B$, the activation of MAPKs, and ROS generation in LPS-induced RAW 264.7 cells. In addition, protein expressions of Nrf-2 and HO-1 were also upregulated by luteolin 5-O-glucoside treatment. Moreover, luteolin 5-O-glucoside inhibited ${\lambda}-carrageenan-induced$ mouse paw edema by 65.34% and 48.31% at doses of 50 and 100 mg/kg body weight, respectively. These findings indicate potential anti-inflammatory effect of luteolin 5-O-glucoside particularly by downregulating $NF-{\kappa}B$ and upregulating HO-1/Nrf-2 pathway.

• Korean Journal of Clinical Oncology
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• v.14 no.2
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• pp.128-134
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• 2018

Purpose: Previous studies have addressed the role of the hypercoagulable state in the pathogenesis of cancer progression and metastasis. In this study, we investigated the association between coagulation factors, including tissue factor (TF) expression, platelet count, and fibrinogen level, and disease recurrence in patients with non-metastatic colorectal cancer. Methods: Patients who underwent curative resection for stage II or III colorectal cancer between 2000 and 2007 were included in this study. Data from a prospectively maintained database were retrospectively reviewed. TF expression was determined by immunohistochemistry using an anti-TF monoclonal antibody. The Kaplan-Meier method was used to estimate 5-year disease-free survival. Results: TF was highly expressed in 257 of 297 patients (86.5%). TF expression was not significantly associated with the platelet counts (P=0.180) or fibrinogen level (P=0.281). The 5-year disease-free survival rate was lower in patients with high TF expression than in patients with low TF expression (72.3% vs. 83.9%, P=0.074). In Cox hazard analysis, high TF expression was an independent risk factor for tumor recurrence (hazard ratio [HR] 2.446; 95% confidence interval [CI], 1.054-5.674; P=0.037). Undifferentiated histologic type (HR, 2.911; 95% CI, 1.308-6.481; P=0.009), venous invasion (HR, 2.784; 95% CI, 1.431-5.417; P=0.003), and lymph node metastasis (HR, 2.497; 95% CI, 1.499-4.158; P<0.001), were also significantly associated with disease recurrence. Conclusion: TF expression is associated with a recurrence in patients with non-metastatic colorectal cancer. However, further studies are required to clarify the underlying mechanisms relating TF expression with oncologic outcomes and its potential role as a therapeutic target.