Novel Histone Deacetylase 6 Inhibitor Confers Anti-inflammatory Effects and Enhances Gut Barrier Function

Background/Aims@#The purpose of the current study was to examine the anti-inflammatory effects of CKD-506, a novel histone deacetylase 6 inhibitor, on human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells and to explore the relationship between CKD-506 and gut epithelial barrier function. @*Methods@#Lipopolysaccharide-stimulated human PBMCs from inflammatory bowel disease (IBD) patients were treated with CKD-506, and tumor necrosis factor (TNF)-α expression was measured using an enzyme-linked immunosorbent assay. The proliferation of CD4+ T cells from IBD patients was evaluated using flow cytometric analysis. The effects of CKD-506 on gut barrier function in a cell line and colon organoids, based on examinations of mRNA production, goblet cell differentiation, and E-cadherin recovery, were investigated using quantitative reverse transcription polymerase chain reaction, immunofluorescence, and a fluorescein isothiocyanatedextran permeability assay. @*Results@#Secretion of TNF-α, a pivotal pro-inflammatory mediator in IBD, by lipopolysaccharidetriggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. E-cadherin mRNA expression and goblet cell differentiation increased significantly and dose-dependently in HT-29 cells in response to CKD-506, and inhibition of E-cadherin loss after TNF-α stimulation was significantly reduced both in HT-29 cells and gut organoids. Caco-2 cells treated with CKD-506 showed a significant reduction in barrier permeability in a dose-dependent manner. @*Conclusions@#The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4 T cells and improves gut barrier function, suggesting its potential as a smallmolecule therapeutic option for IBD.

Methylation Signature for Prediction of Progression Free Survival in Surgically Treated Clear Cell Renal Cell Carcinoma

BACKGROUND: Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC). METHODS: Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts. RESULTS: Using genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4–79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis. CONCLUSION: The promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens.

Positive Effect of Baby-Friendly Hospital Initiatives on Improving Mothers' Intention for Successful Breastfeeding in Korea

BACKGROUND: In Korea, the breastfeeding (BF) rate of infants aged 6 months or more is drastically decreasing, and this phenomenon is particularly worrisome for the future health of the population. The present study aimed to identify an antenatal strategy for initiation and continuation of human BF, and to identify how Baby-Friendly Hospitals (BFHs) may positively influence the intention to breastfeed. METHODS: A total of 414 pregnant Korean antenatal women were surveyed using questionnaires to determine current knowledge of the benefits of human breast milk, whether they planned to breastfeed after delivery, to continue BF after reinstatement in the workforce, are willing to abide by rooming-in care for infants, and plan to give birth at BFHs. RESULTS: We found that planning room-in care, greater awareness of BF benefits for infant and mother, participation in antenatal education programs, and provision of BF facilities in the workplace were positively associated with plans for exclusive breastfeeding (EBF) and longer BF duration. The mothers who planned to give birth at BFHs also desired to breastfeed immediately after birth, implement in-room care, continue BF at their workplace, participate in antenatal BF educational programs, and were more aware of the benefits of BF. CONCLUSION: If the beneficial effects of BFHs were well known to individuals, these would enhance the success rate of BF in Korea. Antenatal education and consequent acquisition of better knowledge of the benefits of BF are important for increasing the rate of BF practices.

A Single Center Analysis of the Positivity of Hepatitis B Antibody after Neonatal Vaccination Program in Korea

The antibody to hepatitis B surface antigen (anti-HBs) seropositivity rate after 3 doses of hepatitis B virus (HBV) vaccination during infancy period is known to be higher than 90%. However, a considerable number of vaccines do not form protective anti-HBs or chronologic decrease of anti-HBs. We retrospectively collected data of HBV serologic test results in 20,738 individuals from 2000 to 2015. After exclusion criteria were applied, 19,072 individuals were included. We analyzed the anti-HBs seropositivity rate, anti-HBs disappearance rate, anti-HBs positive seroconversion rate after receiving a booster vaccine, and the difference in anti-HBs positivity between the 2 groups; group A (born before 2005, while both recombinant vaccines and plasma-derived vaccines were used) and group B (born after 2005, when only recombinant vaccines were used by national regulation). The anti-HBs seropositivity rate was 55.8%, but there was a significant difference in the rate of seropositivity for anti-HBs between the group A and B (53.0% vs. 78.1%, P < 0.001). There was no significant age-adjusted difference in the mean seropositivity rate between the 2 groups (P = 0.058). In addition, the anti-HBs positivity rate was significantly lower in the group A as compared with the group B during infancy (83.1% vs. 92.1%, P < 0.001). A total of 1,106 anti-HBs-positive subjects underwent serologic tests more than twice. Of these, 217 subjects (19.6%) showed anti-HBs disappearance. After booster vaccinations, 87.4% (83/95) achieved seroconversion from seronegative to seropositive. Our results highlight the importance of lifelong protection against HBV and the possible necessity of booster vaccination after adolescent period.

Implementation of Hospital Examination Reservation System Using Data Mining Technique / 대한의료정보학회지

OBJECTIVES: New methods for obtaining appropriate information for users have been attempted with the development of information technology and the Internet. Among such methods, the demand for systems and services that can improve patient satisfaction has increased in hospital care environments. METHODS: In this paper, we proposed the Hospital Exam Reservation System (HERS), which uses the data mining method. First, we focused on carrying clinical exam data and finding the optimal schedule for generating rules using the multi-examination pattern-mining algorithm. Then, HERS was applied by a rule master and recommending system with an exam log. Finally, HERS was designed as a user-friendly interface. RESULTS: HERS has been applied at the National Cancer Center in Korea since June 2014. As the number of scheduled exams increased, the time required to schedule more than a single condition decreased (from 398.67% to 168.67% and from 448.49% to 188.49%; p < 0.0001). As the number of tests increased, the difference between HERS and non-HERS increased (from 0.18 days to 0.81 days). CONCLUSIONS: It was possible to expand the efficiency of HERS studies using mining technology in not only exam reservations, but also the medical environment. The proposed system based on doctor prescription removes exams that were not executed in order to improve recommendation accuracy. In addition, we expect HERS to become an effective system in various medical environments.

Decreased DBC1 Expression Is Associated With Poor Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer

PURPOSE: The deleted in bladder cancer 1 (DBC1) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of DBC1 as a prognostic marker in BC. MATERIALS AND METHODS: The expression of DBC1 was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model. RESULTS: DBC1 expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low DBC1 expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of DBC1 expression in NMIBC (log-rank test, each, p<0.05). CONCLUSIONS: The expression of DBC1 was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that DBC1 expression can be a useful prognostic marker for patients with NMIBC.

Ginkgo biloba extract (GbE) enhances the anti-atherogenic effect of cilostazol by inhibiting ROS generation

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis.