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.

Comparison of body water status and its distribution in patients with non-septic infection, patients with sepsis, and healthy controls

Objective@#Although fluid resuscitation is the cornerstone of treatment for sepsis, the role of body water status in sepsis is poorly understood. This study aimed to understand how body water and its distribution are modified in patients with sepsis and those with non-septic infection compared to healthy individuals. @*Methods@#Two groups of adults presumed to have non-septic infection (n=87) and sepsis (n=54) were enrolled in this prospective study in a single emergency department, and they were compared to sex-, age-, and height-matched (1:3 ratio) healthy controls (n=11,190) from retrospective data in a health promotion center. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW), determined using direct segmental multi-frequent bioelectrical impedance analysis (InBody S10) were expressed as indices for normalization by body weight (BW). The ratio of ECW to TBW (ECW/TBW) was evaluated to determine body water distribution. @*Results@#TBW/BW, ICW/BW, and ECW/BW were significantly higher in the non-septic infection group than in the healthy group (P<0.001), but ECW/TBW was not significantly different (P=0.690). There were no differences in TBW/BW and ICW/BW between the sepsis and healthy groups (P=0.083 and P=0.963). However, ECW/BW and ECW/TBW were significantly higher in the sepsis group than in the healthy group (P<0.001). @*Conclusion@#Compared to the healthy group, the ratio of body water to BW was significantly increased in the non-septic infection group, while ECW/BW and ECW/TBW were significantly increased in the sepsis group. These indices could be utilized as diagnostic variables of body water deficit in septic patients.

Comparison of body water status and its distribution in patients with non-septic infection, patients with sepsis, and healthy controls

Objective@#Although fluid resuscitation is the cornerstone of treatment for sepsis, the role of body water status in sepsis is poorly understood. This study aimed to understand how body water and its distribution are modified in patients with sepsis and those with non-septic infection compared to healthy individuals. @*Methods@#Two groups of adults presumed to have non-septic infection (n=87) and sepsis (n=54) were enrolled in this prospective study in a single emergency department, and they were compared to sex-, age-, and height-matched (1:3 ratio) healthy controls (n=11,190) from retrospective data in a health promotion center. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW), determined using direct segmental multi-frequent bioelectrical impedance analysis (InBody S10) were expressed as indices for normalization by body weight (BW). The ratio of ECW to TBW (ECW/TBW) was evaluated to determine body water distribution. @*Results@#TBW/BW, ICW/BW, and ECW/BW were significantly higher in the non-septic infection group than in the healthy group (P<0.001), but ECW/TBW was not significantly different (P=0.690). There were no differences in TBW/BW and ICW/BW between the sepsis and healthy groups (P=0.083 and P=0.963). However, ECW/BW and ECW/TBW were significantly higher in the sepsis group than in the healthy group (P<0.001). @*Conclusion@#Compared to the healthy group, the ratio of body water to BW was significantly increased in the non-septic infection group, while ECW/BW and ECW/TBW were significantly increased in the sepsis group. These indices could be utilized as diagnostic variables of body water deficit in septic patients.

The mediating effect of self-efficacy in the relationship between communication skills and practices of preventing infectious diseases among daycare center teachers in South Korea

Purpose@#This study investigated the practices of preventing infectious diseases by daycare center teachers. The focus was on the mediating effects of self-efficacy in the relationship between communication skills and practices of preventing infectious diseases. @*Methods@#This study used a descriptive correlational design. The participants were 164 daycare center teachers. Hierarchical regression was used to test the mediating effect of self-efficacy in the relationship between communication skills and practices of preventing infectious diseases. Data were analyzed using the independent t-test, one-way analysis of variance, Pearson correlation coefficients, and hierarchical regression. The mediation effect was analyzed using an SPSS Macro program, PROCESS. @*Results@#Significant relationships were found between communication skills and practices of preventing infectious diseases (β=.19, p<.001), self-efficacy and practices of preventing infectious diseases (β=.59, p<.001), and communication skills and self-efficacy (β=.27, p<.001). Self-efficacy had a significant mediating effect (β=.17, 95% confidence interval=0.07~0.29) on practices of preventing infectious diseases. @*Conclusion@#In order to improve practices of preventing infectious diseases among daycare teachers, it is necessary to develop and apply interventions and methods that can increase effective communication skills and self-efficacy.

Investigation of gene-gene interactions of clock genes for chronotype in a healthy Korean population

Chronotype is an important moderator of psychiatric illnesses, which seems to be controlled in some part by genetic factors. Clock genes are the most relevant genes for chronotype. In addition to the roles of individual genes, gene-gene interactions of clock genes substantially contribute to chronotype. We investigated genetic associations and gene-gene interactions of the clock genes BHLHB2, CLOCK, CSNK1E, NR1D1, PER1, PER2, PER3, and TIMELESS for chronotype in 1293 healthy Korean individuals. Regression analysis was conducted to find associations between single nucleotide polymorphism (SNP) and chronotype. For gene-gene interaction analyses, the quantitative multifactor dimensionality reduction (QMDR) method, a nonparametric model-free method for quantitative phenotypes, were performed. No individual SNP or haplotype showed a significant association with chronotype by both regression analysis and single-locus model of QMDR. QMDR analysis identified NR1D1 rs2314339 and TIMELESS rs4630333 as the best SNP pairs among two-locus interaction models associated with chronotype (cross-validation consistency [CVC] = 8/10, p = 0.041). For the three-locus interaction model, the SNP combination of NR1D1 rs2314339, TIMELESS rs4630333, and PER3 rs228669 showed the best results (CVC = 4/10, p < 0.001). However, because the mean differences between genotype combinations were minor, the clinical roles of clock gene interactions are unlikely to be critical.

Investigation of gene-gene interactions of clock genes for chronotype in a healthy Korean population

Chronotype is an important moderator of psychiatric illnesses, which seems to be controlled in some part by genetic factors. Clock genes are the most relevant genes for chronotype. In addition to the roles of individual genes, gene-gene interactions of clock genes substantially contribute to chronotype. We investigated genetic associations and gene-gene interactions of the clock genes BHLHB2, CLOCK, CSNK1E, NR1D1, PER1, PER2, PER3, and TIMELESS for chronotype in 1293 healthy Korean individuals. Regression analysis was conducted to find associations between single nucleotide polymorphism (SNP) and chronotype. For gene-gene interaction analyses, the quantitative multifactor dimensionality reduction (QMDR) method, a nonparametric model-free method for quantitative phenotypes, were performed. No individual SNP or haplotype showed a significant association with chronotype by both regression analysis and single-locus model of QMDR. QMDR analysis identified NR1D1 rs2314339 and TIMELESS rs4630333 as the best SNP pairs among two-locus interaction models associated with chronotype (cross-validation consistency [CVC] = 8/10, p = 0.041). For the three-locus interaction model, the SNP combination of NR1D1 rs2314339, TIMELESS rs4630333, and PER3 rs228669 showed the best results (CVC = 4/10, p < 0.001). However, because the mean differences between genotype combinations were minor, the clinical roles of clock gene interactions are unlikely to be critical.

A Study of Irritable Bowel Syndrome and Stress on Female College Students in Korea

OBJECTIVE: The purpose of this study was to provide a database for making better decisions of the treatment of the irritable bowel syndrome (IBS) patient, and for improving the recognition of IBS in the Korean society. METHODS: The survey was conducted on 174 female college students in Korea from January 2017 to January 2018. Out of the total students surveyed, 160 questionnaires were analyzed after excluding 14 uncompleted questionnaires. RESULTS: Based on the survey, the prevalence of IBS among female college students in Korea was found to be 13.8%. Statistically, the results proved that there were significant differences in the stress levels between the students with IBS and non-IBS diagnosed by ROME IV criteria. Students with IBS had higher stress levels than students without the ailment. CONCLUSIONS: Based on this study, stress management related treatment should be actively considered. Furthermore, it is necessary to develop more efficient and updated guidelines for the treatment of IBS and new patient care programs.

Relationships between Endogenous Estrogen and the Risk Factors for Vascular Disease / 대한뇌졸중학회지

BACKGROUND: This study evaluated the relationships between endogenous estrogen levels and vascular risk factors in healthy men and women. METHODS: Demographics and laboratory data were collected from normotensive subjects (123 men and 154 women) in their thirties, forties and fifties who had normal laboratory profiles and no cardiovascular risk factors. Initially, estradiol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol, systolic and diastolic blood pressure (SBP and DBP), NO2/NO3, homocysteine, and body mass index (BMI) were measured. Then, the relationships between estradiol and the evaluated items were analyzed with comparison of means and correlation, and stepwise multiple regression analysis based on genders and age-groups. RESULTS: Estradiol levels decreased with aging in women. Lower LDL and triglyceride, higher HDL levels, and lower SBP and DBP observed in women were correlated with decreasing age as well as increasing estradiol level. On the multivariate analysis, however, estradiol levels were negatively correlated with the changes in SBP, DBP, and triglyceride among the lipid variables. BMI was positively related with the increase of SBP and DBP and the estradiol levels. Although higher NO2/NO3 and lower homocysteine levels were observed in women than men, the NO2/NO3 and homocysteine levels had no significant correlation with estradiol changes. CONCLUSION: The study observed the beneficial relationships between endogenous estrogen, and blood pressures and lipids in healthy women. The estrogen-related benefits observed in this study were lower TG levels, SBP, and DBP in young women than those in older women or in men.

Receptor activator of NF-kappaB ligand enhances the activity of macrophages as antigen presenting cells

Receptor activator of NFkappaB ligand (RANKL) is known as a key regulator of osteoclastogenesis. However, the fact that fibroblasts and periodontal ligament cells express RANKL in response to bacterial substances, suggests that RANKL may have evolved as a part of the immunity to infection. As RANKL increases the survival and activity of dendritic cells, it may have similar effects on macrophages. To address this issue, we studied the effect of RANKL on various functions of macrophages using mouse bone marrow derived macrophages. RANKL enhanced the survival of macrophages and up-regulated the expression of CD86. RANKL-treated macrophages showed increased allogeneic T cell activation and phagocytic activity compared to control cells. In addition, RANKL increased the expression of TNFalpha, MCP-1, and IL-6 but not of IL-10, IL-12, IFN-gamma, and iNOS. Collectively, RANKL augmented the activity of macrophages especially as antigen presenting cells, suggesting its new role in immune regulation.