PURPOSE: Bone morphogenic protein (BMP)-7, a member of TGF-beta1 superfamily, is an endogenous antifibrotic protein highly expressed in normal kidney. It is not known, however, whether human peritoneal mesothelial cells (HPMC) express BMP-7 or if BMP-7 protects against peritoneal fibrosis and by what mechanism. We examined the effect of BMP-7 overexpression in TGF-beta1-induced epithelial-mesenchymal transition (EMT) of HPMC and in TGF-beta1 signaling in HPMC to elucidate the mechanisms of antifibrotic effect of BMP-7. METHODS: Growth arrested and synchronized HPMC were stimulated with 2 ng/mL of TGF-beta1 to induce EMT. HPMC were transiently transfected with adenovirus-mediated human BMP-7 (AdBMP-7) or with GFP (AdGFP). EMT was defined as downregulation of E-cadherin and upregulation of alpha-smooth muscle actin (SMA). RESULTS: HPMC constitutively expressed BMP-7 mRNA and protein. BMP-7 mRNA and protein expression were significantly inhibited by 50 mM D-glucose, 2x diluted commercial peritoneal dialysis solution, and 2 ng/ml of TGF-beta1. Transfection of AdBMP-7 resulted in 2.5-fold increase in BMP-7 mRNA expression in HPMC. TGF-beta1 significantly decreased E-cadherin and increased alpha-SMA expression in GFP transfected cells. BMP-7 overexpression effectively reversed TGF-beta1-induced E-cadherin and alpha-SMA expression and significantly suppressed TGF-beta1-induced phosphorylation of Smad2/3, ERK1/2, JNK, and p38 MAPK in HPMC as compared to GFP transfected cells. CONCLUSION: BMP-7 is an endogenous antifibrotic protein and downregulation of BMP-7 in HPMC by high glucose, PD solution, and TGF-beta1 may permit the development of peritoneal fibrosis during long-term PD. Our data demonstrate that BMP-7 overexpression reverses TGF-beta1-induced EMT of HPMC and consequent peritoneal fibrosis possibly through inhibition of Smad2/3 and MAPK phosphorylation.
Actins ; Bone Morphogenetic Protein 7* ; Cadherins ; Down-Regulation ; Epithelial-Mesenchymal Transition ; Glucose ; Humans ; Kidney ; p38 Mitogen-Activated Protein Kinases ; Peritoneal Dialysis ; Peritoneal Fibrosis ; Peritoneum* ; Phosphorylation ; RNA, Messenger ; Transfection ; Transforming Growth Factor beta1 ; Up-Regulation

OBJECTIVES: To estimate the prevalence of edentulism according to the socio-demographic variables of Korean adults between 2007 and 2018 and to analyze the trends. METHODS: This study was conducted using raw data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2007 to 2018. Edentulism was defined as the absence of upper and lower teeth or the retained root of the missing teeth. To obtain the prevalence of edentulism, complex sample frequency analysis and regression analysis were performed according to the socio-demographic variables to represent the national population. The Korean population structure in 2005 was exploited as a standard population to calculate age-standardized edentulism. RESULTS: The prevalence of edentulism in 2016-2018 was 9.7% in the Korean elderly, and the change of age-standardized edentulism steadily declined over time from 2007, 12.8%. In particular, it decreased by approximately 20% in the period between 2016 and 2018 compared to that in 2007 for those in their 80s. The trend of the prevalence according to gender decreased significantly in women. According to the level of education, the greatest decrease was seen in the group with the lowest education, although the prevalence itself was higher than that seen in those who were more educated. CONCLUSIONS The prevalence of edentulism among the older Korean population has decreased over time. However, the concern is on those with lower education and men as these groups are still at higher risk for edentulism.

OBJECTIVES: To estimate the prevalence of edentulism according to the socio-demographic variables of Korean adults between 2007 and 2018 and to analyze the trends. METHODS: This study was conducted using raw data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2007 to 2018. Edentulism was defined as the absence of upper and lower teeth or the retained root of the missing teeth. To obtain the prevalence of edentulism, complex sample frequency analysis and regression analysis were performed according to the socio-demographic variables to represent the national population. The Korean population structure in 2005 was exploited as a standard population to calculate age-standardized edentulism. RESULTS: The prevalence of edentulism in 2016-2018 was 9.7% in the Korean elderly, and the change of age-standardized edentulism steadily declined over time from 2007, 12.8%. In particular, it decreased by approximately 20% in the period between 2016 and 2018 compared to that in 2007 for those in their 80s. The trend of the prevalence according to gender decreased significantly in women. According to the level of education, the greatest decrease was seen in the group with the lowest education, although the prevalence itself was higher than that seen in those who were more educated. CONCLUSIONS The prevalence of edentulism among the older Korean population has decreased over time. However, the concern is on those with lower education and men as these groups are still at higher risk for edentulism.

Background: The International Classification of Primary Care-2 (ICPC-2) is a classification method designed for primary care. Although previous studies have found that ICPC-2 is a useful tool for demonstrating the relationship between patients’ expectations and health providers’ diagnoses, its utility of ICPC-2 has yet to be fully studied in Korea. This study aimed to evaluate the practicality of ICPC-2 in Korean primary care. Methods: The study was conducted at primary care clinics in Seoul and Gyeonggi areas from October to November 2015. Third-year family medicine residents examined and analyzed the medical records of patients who visited primary care physicians using ICPC-2, and the results were compared with those obtained using the International Classification of Diseases-10 (ICD-10) (Korean version: Korean Standard Classification of Diseases-7). Results: A total of 26 primary care physicians from 23 primary care clinics participated in the study. Furthermore, 2,458 ICD-10 codes and 6,091 ICPC-2 codes were recorded from the data of 1,099 patients. The common disease codes were vasomotor and allergic rhinitis (J30), according to ICD-10, and acute upper respiratory infection (R74) in ICPC-2. Comparing disease status by body systems, the proportion of gastrointestinal disease with ICD-10 codes was significantly higher than that with ICPC-2 codes (P<0.001). Furthermore, patients with >4 diagnoses accounted for 36% of the ICD-10 classifications, whereas those with >4 diagnoses accounted for 4% of the ICPC-2 classifications. Conclusion Introducing ICPC as a complementary means for diagnosing common diseases could be a practical approach in Korean primary care.

PURPOSE: This study compared the survival outcomes of different treatment methods for the ipsilateral breast of occult breast cancer (OBC) patients with axillary lymph node metastasis. METHODS: A retrospective study was conducted in which forty OBC patients with axillary lymph node metastasis were identified out of 15,029 patients who had been diagnosed with a primary breast cancer at between 1992 and 2010. The patients were categorized into three treatment groups based on ipsilateral breast management: breast-conserving surgery (BCS) (n=17), mastectomy (n=12), and nonsurgical intervention with or without radiation therapy (No surgery with or without radiation therapy [No Op+/-RT]) (n=11). All patients underwent axillary lymph node dissection. Cases were evaluated based on treatment and potential prognostic factors with respect to overall survival (OS) and disease-free survival (DFS). RESULTS: During the follow-up period (median follow-up of 71.5 months), the overall OS and DFS were 76.9% and 74.9%, respectively. The 5-year treatment-specific OS was 72.0% for the BCS group, 74.0% for the mastectomy group, and 87.5% for the No Op+/-RT group (log-rank p=0.49). The 5-year DFS was 70.6% for the BCS group, 66.7% for the mastectomy group, and 90.9% for the No Op+/-RT group (log-rank p=0.36). Recurrence rates for the BCS and No Op+/-RT groups were 5.9% and 18.2%, respectively. Histologic grade and lymph node status were inversely correlated with DFS (log-rank p=0.04 and p<0.01, respectively). CONCLUSION: There was no difference in survival outcomes between the three treatment methods for the ipsilateral breast (mastectomy, BCS, and No Op+/-RT) of OBC patients with axillary lymph node metastasis. A large-scale multicenter study is needed to validate the results from this small retrospective study.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes* ; Mastectomy ; Mastectomy, Segmental ; Methods* ; Neoplasm Metastasis* ; Recurrence ; Retrospective Studies

Cholangiocarcinoma (CC) is an intrahepatic bile duct carcinoma with a high mortality rate and a poor prognosis. Sarcomatous change/epithelial mesenchymal transition (EMT) of CC frequently leads to aggressive intrahepatic spread and metastasis. The aim of this study was to identify the genetic alterations and gene expression pattern that might be associated with the sarcomatous change in CC. Previously, we established 4 human CC cell lines (SCK, JCK1, Cho-CK, and Choi-CK). In the present study, we characterized a typical sarcomatoid phenotype of SCK, and classified the other cell lines according to tumor cell differentiation (a poorly differentiated JCK, a moderately differentiated Cho-CK, and a well differentiated Choi-CK cells), both morphologically and immunocytologically. We further analyzed the genetic alterations of two tumor suppressor genes (p53 and FHIT) and the expression of Fas/FasL gene, well known CC-related receptor and its ligand, in these four CC cell lines. The deletion mutation of p53 was found in the sarcomatoid SCK cells. These cells expressed much less Fas/FasL mRNAs than did the other ordinary CC cells. We further characterize the gene expression pattern that is involved in the sarcomatous progression of CC, using cDNA microarrays that contained 18,688 genes. Comparison of the expression patterns between the sarcomatoid SCK cells and the differentiated Choi-CK cells enabled us to identify 260 genes and 247 genes that were significantly over-expressed and under-expressed, respectively. Northern blotting of the 14 randomly selected genes verified the microarray data, including the differential expressions of the LGALS1, TGFBI, CES1, LDHB, UCHL1, ASPH, VDAC1, VIL2, CCND2, S100P, CALB1, MAL2, GPX1, and ANXA8 mRNAs. Immunohistochemistry also revealed in part the differential expressions of these gene proteins. These results suggest that those genetic and gene expression alterations may be relevant to the sarcomatous change/EMT in CC cells.
Acid Anhydride Hydrolases/genetics ; Animals ; Cell Line, Tumor ; Cholangiocarcinoma/*genetics ; Female ; *Gene Expression Profiling ; Humans ; Mice ; Mice, Inbred BALB C ; Mutation ; Neoplasm Proteins/genetics ; Oligonucleotide Array Sequence Analysis ; Sarcoma/*genetics ; Tumor Suppressor Protein p53/genetics

BACKGROUND: The basic treatment of malignant tumors is surgery, radiotherapy, chemotherapy. Even though, the object of these treatments is to kill cancer cells, they have limitations. So, in future studies of treatment of cancer, we should look into increasing human immune response using gene therapy in order to induce damage to tumor cells. OBJECTIVE: The cell growth inhibitory effect of cervical cancer cells was investigated by direct transfection using liposome(pRcCMVp53/lipofectin). and by indirect transfection using Adenovirus(AdCMVp53). METHODS: The cervical cancer cell lines we used in this study were HPV16 positive, having inhibitory gene, wild p53 gene, CaSki, SiHa, HPV18 positive HeLa, HeLaS3 and HPV negative C33A, HT3, LacZ gene was used as the marker gene for the transfection efficacy. Direct transfection was done by using lipofectin (pRcCMVp53/lipofectin) and indirect transfection was done by using virus, AdCMVp53. The effect of tumor cell growth inhibition was measured by cell counting assay. RESULT: Inhibition of growth of cervical cancer cells in cell counts of direct transfection was CaSki(88.5%), SiHa(59.1%), HeLa(86.0%), HeLaS3(78.0%), C33A(91.3%) and HT3(74.0%). Inhibition of growth of cervical cancer cells in cell counts of indirect transfection was CaSki(97.4%), SiHa(91.6%), HeLa(95.8%), HeLaS3(99.7%), C33A(97.3%) and HT3(87.4%). CONCLUSION: The inhibition of cell growth of cervical cancer cells by direct and indirect transfection was significantly reduced, and showed little differences depending on the type of cells. These results will have a great meaning in treating cervical cancer patients using gene therapy by direct or indirect transfection
Adenoviridae* ; Cell Count ; Cell Line ; Drug Therapy ; Genes, p53 ; Genetic Therapy* ; Humans ; Lac Operon ; Plasmids* ; Radiotherapy ; Transfection ; Uterine Cervical Neoplasms*

Endogenous endophthalmitis secondary to group B Streptococcus (GBS) is extremely rare, particularly in healthy adults. However, the visual prognosis is poor. We report the first South Korean case of GBS infective endocarditis presenting as endogenous endophthalmitis and skin and soft tissue infection. Cultures of blood, vitreous humor, and pus from skin aspirates yielded a penicillin-susceptible serotype V strain of Streptococcus agalactiae. After 6 weeks, the patient completely recovered from GBS infective endocarditis. However, despite early antibiotic treatment and early surgical intervention, the patient's right eye developed phthisis bulbi and was a candidate for evisceration.
Adult* ; Endocarditis* ; Endophthalmitis* ; Humans ; Patient Rights ; Prognosis ; Serogroup ; Skin ; Soft Tissue Infections ; Streptococcus agalactiae* ; Streptococcus* ; Suppuration ; Vitreous Body

We examined the anticancer effects of a novel sirtuin inhibitor, MHY2256, on HCT116 human colorectal cancer cells to investigate its underlying molecular mechanisms. MHY2256 significantly suppressed the activity of sirtuin 1 and expression levels of sirtuin 1/2 and stimulated acetylation of forkhead box O1, which is a target protein of sirtuin 1. Treatment with MHY2256 inhibited the growth of the HCT116 (TP53 wild-type), HT-29 (TP53 mutant), and DLD-1 (TP53 mutant) human colorectal cancer cell lines. In addition, MHY2256 induced G0/G1 phase arrest of the cell cycle progression, which was accompanied by the reduction of cyclin D1 and cyclin E and the decrease of cyclin-dependent kinase 2, cyclin-dependent kinase 4, cyclin-dependent kinase 6, phosphorylated retinoblastoma protein, and E2F transcription factor 1. Apoptosis induction was shown by DNA fragmentation and increase in late apoptosis, which were detected using flow cytometric analysis. MHY2256 downregulated expression levels of procaspase-8, -9, and -3 and led to subsequent poly(ADP-ribose) polymerase cleavage. MHY2256-induced apoptosis was involved in the activation of caspase-8, -9, and -3 and was prevented by pretreatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, the autophagic effects of MHY2256 were observed as cytoplasmic vacuolation, green fluorescent protein-light-chain 3 punctate dots, accumulation of acidic vesicular organelles, and upregulated expression level of light-chain 3-II. Taken together, these results suggest that MHY2256 could be a potential novel sirtuin inhibitor for the chemoprevention or treatment of colorectal cancer or both.

BACKGROUND: Smoking cessation is the most powerful intervention to modify progress of chronic obstructive pulmonary disease (COPD), and nicotine dependence is one of the most important determinants of success or failure in smoking cessation. We evaluated nicotine dependence status and investigated factors associated with moderate to high nicotine dependence in patients with COPD. METHODS: We included 53 current smokers with COPD in the Korean Obstructive Lung Disease II cohort enrolled between January 2014 and March 2016. Nicotine dependence was measured by using Fagerstrom test for nicotine dependence (FTND). Cognitive function was assessed by Korean version of Montreal Cognitive Assessment. RESULTS: The median FTND score was 3, and 32 patients (60%) had moderate to high nicotine dependence. The median smoking amount was 44 pack-years, which was not related to nicotine dependence. Multiple logistic regression analysis revealed that high education status (odds ratio, 1.286; 95% confidence interval, 1.036–1.596; p=0.023), age <70 (odds ratio, 6.407; 95% confidence interval, 1.376–29.830; p=0.018), and mild to moderate airflow obstruction (odds ratio, 6.969; 95% confidence interval, 1.388–34.998; p=0.018) were related to moderate to high nicotine dependence. CONCLUSION: Nicotine dependence does not correlate with smoking amount, but with education level, age, and severity of airflow obstruction. Physicians should provide different strategies of smoking cessation intervention for current smokers with COPD according to their education levels, age, and severity of airflow obstruction.
Cognition ; Cohort Studies ; Education ; Humans ; Logistic Models ; Lung Diseases, Obstructive ; Nicotine* ; Pulmonary Disease, Chronic Obstructive* ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Use Disorder*