Background/Aims: The present study aimed to investigate whether tocotrienol regulates interleukin 17 (IL-17)-induced osteoclastogenesis in rheumatoid arthritis (RA). Methods: We evaluated the effect of tocotrienol on IL-17-induced receptor activator of nuclear factor kappa B ligand (RANKL) production using RA fibroblast-like synoviocyte (FLS), together with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Osteoclast differentiation was confirmed after culturing IL-17-treated RA FLS and Th17 cells with tocotrienol and monocytes. We analyzed the suppressive effect of tocotrienol on Th17 cells percentage or Th17-cytokine levels among peripheral blood mononuclear cells using flow cytometry. Results: We found that IL-17 stimulated FLS to produce RANKL and tocotrienol decreased this IL-17-induced RANKL production. Tocotrienol decreased the IL-17-induced activation of mammalian target of rapamycin, extracellular signal-regulated kinase, and inhibitor of kappa B-alpha. When monocytes were incubated with IL-17, RANKL, IL-17-treated FLS or Th17 cells, osteoclasts were differentiated and tocotrienol decreased this osteoclast differentiation. Tocotrienol reduced Th17 cell differentiation and the production of IL-17 and sRANKL; however, tocotrienol did not affect Treg cell differentiation. Conclusions Tocotrienol inhibited IL-17- activated RANKL production in RA FLS and IL-17-activated osteoclast formation. In addition, tocotrienol reduced Th17 differentiation. Therefore, tocotrienol could be a new therapeutic choice to treat bone destructive processes in RA.

A pregnane steroid, 3α-hydroxy-pregn-7-ene-6,20-dione (1), was isolated from a Hydractinia-associated Cladosporium sphaerospermum SW67 by repetitive column chromatographic separation and highperformance liquid chromatography (HPLC) purification. The planar structure of 1 was elucidated from the analysis of the spectroscopic data (1D and 2D NMR spectra) and LC-MS data. The absolute configuration of 1 was determined by interpretation of ROESY spectrum of 1, together with the comparison of reported spectroscopic values in previous studies. To the best of our knowledge, this is the first report of the identification of the pregnane scaffold from C. sphaerospermum, a natural source. Compound 1 was evaluated for its effects on lipid metabolism and adipogenesis during adipocyte maturation and showed that compound 1 substantially inhibited lipid accumulation compared to the control. Consistently, the expression of the adipocyte marker gene (Adipsin) was reduced upon incubation with 1. Further, we evaluated the effects of 1 on lipid metabolism by measuring the transcription of lipolytic and lipogenic genes. The expression of the lipolytic gene ATGL was significantly elevated upon exposure to 1 during adipogenesis, whereas the expression of lipogenic genes FASN and SREBP1 was significantly reduced upon treatment with 1. Thus, our findings provide experimental evidence that the steroid derived from Hydractinia-associated C. sphaerospermum SW67 is a potential therapeutic agent for obesity.

The demineralized bone matrix (DBM) as the bone graft material to increase the fusion rate was widely used in spinal fusion. The current study aimed to compare the fusion rate of DBM to the fusion rate of autograft in lumbar spine fusion via meta-analysis of published literature. After systematic search, comparative studies were selected according to eligibility criteria. Checklist (risk of bias assessment tool for non-randomized study) was used to evaluate the risk of bias of the included nonrandomized controlled studies. The corresponding 95% confidence interval (95% CI) were calculated. We also used subgroup analysis to analyze the fusion rate of posterolateral lumbar fusion and lumbar interbody fusion. Eight studies were finally included in this meta-analysis. These eight studies included 581 patients. Among them, 337 patients underwent spinal fusion surgery using DBM (DBM group) and 204 patients underwent spinal fusion surgery with mainly autologous bone and without using DBM (control group). There was no significant differences of fusion rate between the two groups in posterolateral fusion analysis (risk ratio [RR], 1.03; 95% CI, 0.90–1.17; p=0.66) and interbody fusion analysis (RR, 1.13; 95% CI, 0.91–1.39; p=0.27). Based on the available evidence, the use of DBM with autograft in posterolateral lumbar spine fusion and lumbar interbody fusion showed a slightly higher fusion rate than that of autograft alone; however, there was no statistically different between two groups.

The guidelines for chronic obstructive pulmonary disease (COPD) treatment are important for the management of the disease. However, studies regarding the treatment adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been scarce in Korea. Therefore, to examine the adherence to the GOLD guidelines, we examined the patterns of prescribed medication in COPD patients from 2011 to 2018. Patients were classified as having been appropriately and inappropriately treated (overtreatment or undertreatment) for the GOLD group. Appropriate medical therapy was defined as using the first choice or alternative choice drug recommended in the GOLD guidelines. Inappropriate therapy was classified as overtreatment or undertreatment in accordance with the categorization in the GOLD guidelines. According to treatment of 2011 GOLD guidelines, there was inappropriate treatment in 52.3% in group A, 47.3% in group B, 56.3% in group C, and 17.8% in group D. According to treatment of 2017 GOLD guidelines, there was inappropriate treatment in 66.7% in group A, 45.3% in group B, 14.3% in group C, and 24.0% in group D. The common type of inappropriate COPD treatment is overtreatment, with inhaled corticosteroid (ICS) containing regimens. In conclusions, adherence to the GOLD guideline by the pulmonologist in clinical practice is still low in Korea. Therefore, we need better strategies to both optimize the use of the guidelines and adhere to the guidelines as well.
Humans ; Korea* ; Lung Diseases ; Medical Overuse ; Pulmonary Disease, Chronic Obstructive*

PURPOSE: The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS: At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION: A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.
Cohort Studies ; Disease-Free Survival ; Education ; Follow-Up Studies ; Humans ; Nasopharyngeal Neoplasms ; Radiotherapy ; Radiotherapy, Intensity-Modulated ; Retrospective Studies* ; Treatment Outcome

BACKGROUND: Cancer risk and epidemiology in pre-dialysis chronic kidney disease (CKD) warrant further investigation in a large-scale cohort. METHODS: We performed a nationwide population-based study using the national health insurance database of Korea. We screened records from 18,936,885 individuals who received a national health examination ≥ 2 times from 2009 to 2016. Pre-dialysis CKD was identified based on serum creatinine and dipstick albuminuria results. Individuals with preexisting cancer history, renal replacement therapy, or transient CKD were excluded. A control group without evidence of kidney function impairment and matched for age, sex, low-income status, and smoking history was included. Risk of cancers, as identified in the claims database, was investigated using a multivariable Cox regression model including matched variables and other unmatched clinical characteristics as covariates. RESULTS: A total of 471,758 people with pre-dialysis CKD and the same number of matched controls were included. Urinary (adjusted hazard ratio [HR], 1.97; 95% confidence interval [95% CI], 1.82–2.13) and hematopoietic (adjusted HR, 1.53; 95% CI, 1.38–1.68) malignancy risk was increased in pre-dialysis CKD and all CKD stages. However, the risk of digestive cancer was lower in the pre-dialysis CKD group (adjusted HR, 0.89; 95% CI, 0.87–0.92). The risk of digestive, respiratory, thyroid, and prostate malignancy demonstrated a non-linear association with CKD stage, with stage 1 or stage 4/5 CKD without dialysis demonstrating relatively lower risk. CONCLUSION: Cancer risk varied in pre-dialysis CKD compared to controls, and the association between cancer risk and CKD stage varied depending on the cancer type.
Albuminuria ; Cohort Studies ; Comorbidity ; Creatinine ; Dialysis ; Epidemiology ; Kidney ; Korea ; National Health Programs ; Prostate ; Renal Insufficiency, Chronic ; Renal Replacement Therapy ; Smoke ; Smoking ; Thyroid Gland

Female ; Forced Expiratory Volume ; Humans ; Linear Models ; Lung ; Male ; Radiography, Thoracic ; Spirometry ; Vital Capacity

PURPOSE: This prospective study aimed to investigate the therapeutic efficacy of lamivudine in children with chronic hepatitis B virus (HBV) infection. METHODS: During July 2003 through October 2015, children with chronic hepatitis B who visited our institution were included in this study. Fifty-five patients, who received first-line treatment of lamivudine (3 mg/kg, 100 mg maximum) for over three months, were enrolled. After initiating lamivudine, alanine aminotransferase (ALT), HBV-DNA, and HBV markers were followed up at 1 month, 3 months, and every 3 months, thereafter. The treatment endpoint was determined as 1) normalization of ALT, 2) HBeAg seroconversion, and 3) anti-HBe positivity for twelve consecutive months. RESULTS: Thirty-one male (56.4%) and 24 female (43.6%) patients were included. The mean age at treatment initiation was 8.1 years. The mean duration of treatment was 23.4 months. ALT normalization was found in 98.2% (54 of 55). Anti-HBe seroconversion was found in 70.6% (36/51). Loss of HBsAg was found in 10.9% (6/55). All biochemical responses occurred under age seven. The rate of virologic response (defined as HBV-DNA <2,000 IU/mL) at six months after treatment initiation was 78.7% (37/47). At twelve months after reaching treatment endpoint, 87.2% (34/39) maintained their virologic response. Resistance to lamivudine was found in 16.4% (9/55). CONCLUSIONS: Lamivudine treatment in Korean pediatric patients with chronic hepatitis B showed better outcomes compared with other studies that implemented similar protocols in foreign populations. Further studies are needed to investigate the efficacy of newly recommended antiviral drugs on the Korean pediatric population.
Adolescent ; Alanine Transaminase ; Antiviral Agents ; Child ; Female ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Lamivudine ; Male ; Prospective Studies ; Seroconversion

The purpose of this study was to investigate the immunomodulatory activity of ice plant (Mesembryanthemum crystallinum) extract (IPE) in vitro and in vivo. Raji (a human B cell line) and Jurkat (a human T cell line) cells were treated with various doses of IPE and cell proliferation was measured by WST assay. Results showed that IPE promoted the proliferation of both Raji and Jurkat cells in a dose-dependent manner. IPE also enhanced IL-6 and TNF-α production in macrophages in the presence of lipopolysaccharide (LPS), although IPE alone did not induce cytokine production. Moreover, IPE treatment upregulated iNOS gene expression in macrophages in a time- and dose-dependent manner and led to the production of nitric oxide in macrophages in the presence of IFNγ. In vivo studies revealed that oral administration of IPE for 2 weeks increased the differentiation of CD4+, CD8+, and CD19+ cells in splenocytes. These findings suggested that IPE has immunomodulatory effects and could be developed as an immunomodulatory supplement.
Administration, Oral ; Cell Proliferation ; Cytokines ; Ethanol* ; Gene Expression ; Humans ; Ice* ; In Vitro Techniques ; Interleukin-6 ; Jurkat Cells ; Lymphocytes ; Macrophages ; Mesembryanthemum* ; Nitric Oxide

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world and is the only major disease that is continuing to increase in both prevalence and mortality. The second Korean National Health and Nutrition Survey revealed that the prevalence of COPD in Korean subjects aged > or =45 years was 17.2% in 2001. Further surveys on the prevalence of COPD were not available until 2007. Here, we report the prevalence of spirometrically detected COPD in Korea, using data from the fourth Korean National Health and Nutrition Survey (KNHANES IV) which was conducted in 2007~2009. METHODS: Based on the Korean Statistical Office census that used nationwide stratified random sampling, 10,523 subjects aged > or =40 years underwent spirometry. Place of residence, levels of education, income, and smoking status, as well as other results from a COPD survey questionnaire were also assessed. RESULTS: The prevalence of COPD (defined as forced expiratory volume in 1 sec/forced vital capacity <0.7 in subjects aged > or =40 years) was 12.9% (men, 18.7%; women, 7.5%). In total, 96.5% of patients with COPD had mild-to-moderate disease; only 2.5% had been diagnosed by physicians, and only 1.7% had been treated. The independent risk factors for COPD were smoking, advanced age, and male gender. CONCLUSION: The prevalence of COPD was 12.9% in the KNHANES IV data. Most patients with COPD were undiagnosed and untreated. Based on these results, a strategy for early COPD intervention is warranted in high risk subjects.
Aged ; Censuses ; Female ; Forced Expiratory Volume ; Humans ; Hypogonadism ; Korea ; Male ; Mitochondrial Diseases ; Nutrition Surveys ; Ophthalmoplegia ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; Surveys and Questionnaires ; Risk Factors ; Smoke ; Smoking ; Spirometry ; Vital Capacity