Atopic dermatitis (AD) is characterized by disturbances in epidermal barrier functions and the hyperactive immune response. Staphylococcus aureus (S. aureus) can be cultured from 90% of AD skin lesions and can exacerbate or contribute to the persistent skin inflammation in AD by secreting toxins with superantigenic properties. Superantigens can induce mast cell (MC) degranulation after penetrating the epidermal barrier. The role of MCs in AD is suggested by the increase in the MC number and MC activation. MCs are activated for degranulation and mediator release by allergens that cross-link IgE molecules or by microbial products. Therefore, MCs may be critically involved in the pathogenesis of AD. However, the understanding mechanisms of MC degranulation by S. aureus in relation to AD have still not been fully elucidated. In this study, we found that live S. aureus or methicillin-resistant S. aureus (MRSA) but not heat-killed bacteria induced MC degranulation. The heat-treatment partially inhibited MC degranulation by conditioned media (CM) of S. aureus or MRSA. The calcium chelator ethylene glycol tetraacetic acid (EGTA) did not block MC degranulation induced by live S. aureus or MRSA, but EGTA-treatment partially inhibited MC degranulation by CM from S. aureus or MRSA. These results suggest that live S. aureus and MRSA can degranulate MCs via direct interaction which may be important role in AD.
Allergens ; Bacteria ; Calcium ; Culture Media, Conditioned ; Dermatitis, Atopic ; Egtazic Acid ; Humans* ; Immunoglobulin E ; Inflammation ; Mast Cells ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Skin ; Staphylococcus aureus ; Superantigens

Atopic dermatitis (AD) is characterized by disturbances in epidermal barrier functions and the hyperactive immune response. Staphylococcus aureus (S. aureus) can be cultured from 90% of AD skin lesions and can exacerbate or contribute to the persistent skin inflammation in AD by secreting toxins with superantigenic properties. Superantigens can induce mast cell (MC) degranulation after penetrating the epidermal barrier. The role of MCs in AD is suggested by the increase in the MC number and MC activation. MCs are activated for degranulation and mediator release by allergens that cross-link IgE molecules or by microbial products. Therefore, MCs may be critically involved in the pathogenesis of AD. However, the understanding mechanisms of MC degranulation by S. aureus in relation to AD have still not been fully elucidated. In this study, we found that live S. aureus or methicillin-resistant S. aureus (MRSA) but not heat-killed bacteria induced MC degranulation. The heat-treatment partially inhibited MC degranulation by conditioned media (CM) of S. aureus or MRSA. The calcium chelator ethylene glycol tetraacetic acid (EGTA) did not block MC degranulation induced by live S. aureus or MRSA, but EGTA-treatment partially inhibited MC degranulation by CM from S. aureus or MRSA. These results suggest that live S. aureus and MRSA can degranulate MCs via direct interaction which may be important role in AD.
Allergens ; Bacteria ; Calcium ; Culture Media, Conditioned ; Dermatitis, Atopic ; Egtazic Acid ; Humans* ; Immunoglobulin E ; Inflammation ; Mast Cells ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Skin ; Staphylococcus aureus ; Superantigens

The striking increase in colorectal cancer (CRC) has shown the great fatality in Korea for more than 15 years. The leading edge of this rising incidence rate is mainly due to the people's dietary changes in Korea. Some studies have reported that the dietary fiber does not have significant cytotoxic effects on CRC cells, which contrasts to the effects of probiotics. It gives a positive evaluation that the nonpathogenic spore-forming Bacillus species among the probiotics including fermented bacteria might have optimistic effects on CRC incidence rate. Recently, we isolated Bacillus lentus (BL) from Korean soybean fermented food. BL showed the cytotoxic effect on human colon carcinoma cell lines HCT116 and SW480. Interestingly, BL did not have effect on human dermal fibroblast cells and human hepatoma cell line HepG2. It suggested that BL has the target cell-specific cytotoxicity toward human colon carcinoma cells. To clarify the death signaling pathway underlying the BL-induced apoptosis in cancer cells, we analyzed the expression of caspases, Bax and Bcl-2 by western blotting. The apoptotic effects by cytotoxic elements were executed by direct BL contact or membrane-derived vesicles isolated from BL. Treatment of HCT116 with BL activated caspase-9, -3 and increased cleavage form of poly (ADP-ribose) polymerase (PARP). However, caspase-8 activity was not increased by BL. BL-activated intrinsic pathway increased the pro-apoptotic Bax, decreased the anti-apoptotic Bcl-2 proteins on mitochondria, disrupted the mitochondrial membrane potential, and then released the cytochrome c from mitochondria. The membrane-derived vesicles (MVs) from BL induced apoptosis of the HCT116. Here, we propose that BL as a strong candidate for the development of apoptosis-specific anti-tumor agent will give great contribution to the understandings of the tumor-microbe interdisciplinary areas.
Apoptosis* ; Bacillus* ; Bacteria ; Blotting, Western ; Carcinoma, Hepatocellular ; Caspase 8 ; Caspase 9 ; Caspases ; Cell Line* ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; Cytochromes c ; Dietary Fiber ; Fibroblasts ; Humans* ; Incidence ; Korea ; Membrane Potential, Mitochondrial ; Membranes* ; Mitochondria ; Probiotics ; Soybeans ; Strikes, Employee

The purpose of this study was to evaluate the relationship between Body Mass Index (BMI) and dental caries by considering related factors in Korean children and adolescents. A total of 2,874 children, aged from 2 to 18, who participated in the Korea National Health and Nutrition Examination Survey 2013 – 2015 were included. BMI (kg/m²) was calculated, and participants were categorized into 4 groups using age and gender specific criteria. Decayed and filled teeth index were obtained. There were statistically significant differences in DMFT index between overweight group and other groups (p < 0.01). Underweight group showed the highest mean DMFT index compared to other groups. These findings suggest that children in obesity and underweight group tend to have more caries than normal group in this study.
Adolescent ; Body Mass Index ; Child ; Dental Caries ; Humans ; Korea ; Nutrition Surveys ; Obesity ; Overweight ; Thinness ; Tooth

This study aimed to evaluate the relationship between parenting styles and childhood dental caries using a sample of 3 to 6 years old children in Korea.
The subjects were 158 children aged 3 to 6 years old and their parents in Korea. The parenting styles were divided into three groups (authoritative, authoritarian, and permissive) using a translated version of the Parenting Styles and Dimensions Questionnaire (PSDQ).
Among the 353 parents/child dyads, 158 questionnaires were returned. Authoritative parenting style was the majority (95.6%), followed by authoritarian (3.8%), and permissive (0.6%). There were no statistically significant differences between dental caries and parenting styles. The mean of dft index in authoritative group was lower than others. In the authoritative domain, the higher the authoritative tendency, the lower the dft index.
Overall, authoritative parenting styles resulted in low rates of dental caries for the children. The stronger the authoritative tendency of the parents, the lower the experience of dental caries in the children. Therefore, parenting styles were likely to affect the oral health of a child, but it seemed necessary to supplement the evaluation tool to evaluate the parenting styles.

Tuberculosis (TB), a global and deadly infectious disease caused by Mycobacterium tuberculosis (Mtb), is manifested with host immune reaction. The balanced regulation between protective immune and pathologic inflammatory responses is critical to control progression to TB. Chemokines are a large family of cytokines that play an essential role for chemotaxis of immune and inflammatory cells to the sites of infection. Numerous chemokines including CXCL10 were reported as potential biomarkers of various stages of TB infection. In addition, several chemokines and their receptors play as key players to coordinate host immune defense as innate effectors and mediators of adaptive immune responses.Accumulating evidence suggests that some chemokines, if uncontrolled, are associated with host pathological inflammation during infection. In this review, we will discuss recent advances in understanding which chemokines have potentials as diagnostic markers. In addition, we focus the roles and mechanisms by which chemokines and their receptors are involved in both host immune protection and pathology during TB infection. The controlled activation of chemokine system will determine the coordinated biological outcomes of innate immune responses during pathogenic infection.

Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-kappaB together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-kappaB activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.
Adult ; Animals ; Bacterial Load ; Child ; Cytokines ; Humans ; Immunity, Innate ; Lung ; Lymphadenitis ; Macrophages* ; Mice ; Mycobacterium scrofulaceum* ; NF-kappa B ; Nontuberculous Mycobacteria ; Phosphotransferases ; Reactive Oxygen Species ; Virulence

Purpose: This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. Materials and Methods: We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. Results: Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). Conclusion Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.
Apoptosis ; Autophagy ; Blotting, Western ; Cell Cycle ; Cell Death ; Cell Line ; Cell Proliferation ; Cell Survival ; DNA Damage ; Fluorescent Antibody Technique ; Humans ; Phosphotransferases ; Protein Isoforms ; Stomach Neoplasms