625 nm Light Irradiation Prevented MC3T3-E1 Cells from Accumulation of Misfolded Proteins via ROS and ATP Production.

Osteoblasts must acquire a considerable capacity for folding unfolded and misfolded proteins (MPs) to produce large amounts of extracellular matrix proteins and maintain bone homeostasis. MP accumulation contributes to cellular apoptosis and bone disorders. Photobiomodulation therapy has been used to treat bone diseases, but the effects of decreasing MPs with photobiomodulation remain unclear. In this study, we explored the efficacy of 625 nm light-emitting diode irradiation (LEDI) to reduce MPs in tunicamycin (TM) induced-MC3T3-E1 cells. Binding immunoglobulin protein (BiP), an adenosine triphosphate (ATP)-dependent chaperone, is used to evaluate the capacity of folding MPs. The results revealed that pretreatment with 625 nm LEDI (Pre-IR) induced reactive oxygen species (ROS) production, leading to the increased chaperone BiP through the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1s (XBP-1s) pathway, and then restoration of collagen type I (COL-I) and osteopontin (OPN) expression relieving cell apoptosis. Furthermore, the translocation of BiP into the endoplasmic reticulum (ER) lumen might be followed by a high level of ATP production. Taken together, these results suggest that Pre-IR could be beneficial to prevent MP accumulation through ROS and ATP in TM-induced MC3T3-E1cells.

Effects of Red LED Irradiation in Enhancing the Mineralization of Human Dental Pulp Cells In Vitro.

Dentin regeneration is the preferred method used to preserve dental pulp vitality after pulp exposure due to caries. Red light-emitting diode irradiation (LEDI), which is based on photobiomodulation (PBM), has been used to promote hard-tissue regeneration. However, the underlying mechanism still needs elucidation. This study aimed to explore the mechanism involved in red LEDI affecting dentin regeneration. Alizarin red S (ARS) staining revealed that red LEDI induced mineralization of human dental pulp cells (HDPCs) in vitro. We further distinguished the cell proliferation (0-6 d), differentiation (6-12 d), and mineralization (12-18 d) of HDPCs in vitro and treated cells either with or without red LEDI in each stage. The results showed that red LEDI treatment in the mineralization stage, but not the proliferation or differentiation stages, increased mineralized nodule formation around HDPCs. Western blot also indicated that red LEDI treatment in the mineralization stage, but not the proliferation or differentiation stages, upregulated the expression of dentin matrix marker proteins (dentin sialophosphoprotein, DSPP; dentin matrix protein 1, DMP1; osteopontin, OPN) and an intracellular secretory vesicle marker protein (lysosomal-associated membrane protein 1, LAMP1). Therefore, the red LEDI might enhance the matrix vesicle secretion of HDPCs. On the molecular level, red LEDI enhanced mineralization by activating the mitogen-activated protein kinase (MAPK) signaling pathways (ERK and P38). ERK and P38 inhibition reduced mineralized nodule formation and the expression of relevant marker proteins. In summary, red LEDI enhanced the mineralization of HDPCs by functioning to produce a positive effect in the mineralization stage in vitro.

Gender differences in seizure recurrence and antiepileptic drug polytherapy predicting health-related quality of life of persons 1 year after diagnosis of epilepsy.

PURPOSE: The aim of this study was to determine whether gender influences the prediction of health-related quality of life (HRQoL) in persons with newly diagnosed epilepsy (NDE). METHODS: This was a 1-year longitudinal study. Persons with NDE were assessed with the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), the Hospital Anxiety Depression Scale (HADS), the Stigma Scale, and the Rosenberg Self-esteem Scale. An analysis of covariance (ANCOVA) with interaction terms was used. RESULTS: Among 134 adults with NDE, there were no gender differences in the scores of the QOLIE-31 and its subscales. A multivariate linear regression analysis showed that the HADS-anxiety scores at diagnosis (p = 0.005) and seizure recurrence after diagnosis (p = 0.050) negatively predicted QOLIE-31 scores in persons with NDE. There were significant effects of the gender interaction with seizure recurrence (F = 8.745, p = 0.004, partial eta2 = 0.066) and antiepileptic drug (AED) polytherapy (F = 6.320, p = 0.013, partial eta2 = 0.049) in the adjusted model. Specifically, seizure recurrence negatively predicted the QOLIE-31 scores only in men. By contrast, AED polytherapy negatively predicted the QOLIE-31 scores only in women. CONCLUSIONS: There are gender differences in certain epilepsy-related factors predicting HRQoL at 1 year in persons with NDE.

Raphanus sativus L. seed extracts induce apoptosis and reduce migration of oral squamous cell carcinoma KB and KBCD133+cells by downregulation of ß-catenin.

Although, oral cancer therapies have been developed for decades, patient survival rates have not changed. Side effects of chemotherapy and radiotherapy reduce quality of life of patients and it remains difficult to treat oral cancers due to the presence of cancer stem cells (CSCs) that cause recurrence and metastasis. Therefore, we search for natural products that affect oral cancer cells including oral cancer stem cells. In the present study, we investigated the anticancer effects of Raphanus sativus L. seed (RSLS) extracts on oral squamous cell carcinoma KB cells and CSC-like KBCD133+ cells. CD133 plays an important role in CSCs and physically binds to ß-catenin to activate the ß-catenin signaling targets. Therefore, a natural extract that can inhibit ß-catenin act in may be effective anticancer drug acquiring CSC. Of the natural product extract candidates, RSLS extracts induced apoptosis in KB and KBCD133+ cells and inhibited nuclear translocation of ß-catenin cell migration and invasion rates. Treatment of RSLS extracts resulted in increases of Axin and it leds to reductions of ß-catenin in KB and KBCD133+ cells. Hence, the result suggests that RSLS are potential candidate for anticancer drug against oral cancer cells and CSCs.AbbreviationsCSCcancer stem cellsOSCCsquamous cell carcinoma cellsRSLSRaphanus sativus L. seed.

The Protective Role of Feruloylserotonin in LPS-Induced HaCaT Cells.

Epidermal inflammation is caused by various bacterial infectious diseases that impair the skin health. Feruloylserotonin (FS) belongs to the hydroxycinnamic acid amides of serotonin, which mainly exists in safflower seeds and has been proven to have anti-inflammatory and antioxidant activities. Human epidermis mainly comprises keratinocytes whose inflammation causes skin problems. This study investigated the protective effects of FS on the keratinocyte with lipopolysaccharides (LPS)-induced human HaCaT cells and elucidated its underlying mechanisms of action. The mechanism was investigated by analyzing cell viability, PGE2 levels, cell apoptosis, nuclear factor erythroid 2-related factor 2 (Nrf2) translocation, and TLR4/NF-κB pathway. The anti-inflammatory effects of FS were assessed by inhibiting the inflammation via down-regulating the TLR4/NF-κB pathway. Additionally, FS promoted Nrf2 translocation to the nucleus, indicating that FS showed anti-oxidative activities. Furthermore, the antioxidative and anti-inflammatory effects of FS were found to benefit each other, but were independent. Thus, FS can be used as a component to manage epidermal inflammation due to its anti-inflammatory and anti-oxidative properties.

Sanguisorba officinalis L. extracts activate Wnt/ß-catenin pathway, and subsequently control adipo-osteogenic differentiation.

Wnt/ß-catenin pathway plays an important role in adipogenesis and osteogenesis. To search for novel activators of the Wnt/ß-catenin pathway, we screened plant extracts and found that Sangusorba officinalis L. extracts (SOE) could increase ß-catenin expression level and nuclear accumulation in 3T3-L1 and MC3T3-E1 cells. It was confirmed that SOE could effectively control adipo-osteogenic differentiation. SOE inhibited adipocyte differentiation of 3T3-L1 cells, markedly decreased intracellular lipid accumulation, and decreased expression levels of key adipogenic transcription factors including PPARγ, C/EBPα, and SREBP-1c. SOE enhanced ALP activity and terminal osteoblast differentiation which was confirmed by Alizarin Red S staining of MC3T3-E1 cells. In ex vivo culture, SOE significantly increased the thickness of calvarial bone in mice. Taken together, our results indicate that SOE could be used as a potential therapeutic agent for dual-treatment of anti-obesity and anti-osteoporosis via activation of Wnt/ß-catenin pathway.

Factors contributing to anxiety and depressive symptoms in adults with new-onset epilepsy.

PURPOSE: We investigated factors contributing to anxiety and depressive symptoms over a 1-year period in Korean adults with new-onset epilepsy. METHODS: This longitudinal multicenter study included adults diagnosed with epilepsy within 12 months of a first seizure. Using stepwise regression analyses, we determined whether Hospital Anxiety Depression Scale (HADS) scores could be predicted by demographic, clinical, and psychosocial variables at baseline and at 12 months. RESULTS: Of 141 patients included at baseline, 63 (44.7%) and 60 (42.6%) had Hospital Anxiety Depression Scale-Anxiety (HADS-A) and Hospital Anxiety Depression Scale-Depression (HADS-D) scores >7, respectively. Of 98 patients who completed the 12-month study, the corresponding figures decreased to 32.7% and 36.7%, respectively. Higher HADS-A scores both at baseline and 12 months were predicted by higher neuroticism, stigma, and lower self-esteem (p < 0.05). Higher HADS-D scores at baseline were predicted by higher neuroticism, lower self-esteem, marital status, and lower extroversion (p < 0.05) whereas those at 12 months were predicted by self-esteem, seizure recurrence, and age at epilepsy onset (p < 0.05). Neuroticism or self-esteem was the strongest predictor of psychological distress. CONCLUSIONS: Anxiety and depressive symptoms are common at the time of diagnosis in Korean adults with new-onset epilepsy. While these decrease over time, they remained high 12 months after epilepsy diagnosis. Psychological factors, particularly neuroticism and self-esteem, may be the most important risk factors. Epilepsy variables, such as seizure recurrence and age at onset, may also be important factors for depressed mood at 12 months.

Feruloylserotonin inhibits hydrogen peroxide-induced melanogenesis and apoptosis in B16F10 and SK-Mel-2 melanoma cells.

Feruloylserotonin (FS) is a major bioactive component of safflower seeds, with documented strong antibacterial, anti-inflammatory, and free radical scavenging activities. Reactive oxygen species (ROS) can strongly induce melanogenesis and cell apoptosis. The present study aimed to investigate the ability of FS in preventing hydrogen peroxide (H2O2)-induced melanogenesis and cell apoptosis. Melanogenesis and apoptotic cell death were induced by transient exposure to H2O2 in B16F10 and SK-Mel-2 melanoma cells. FS significantly inhibited melanogenesis and cell death in both cell lines. FS inhibited H2O2-induced melanin production by down-regulating CREB/MITF/TYR signaling via inhibited intracellular cAMP accumulation. Additionally, FS induced extracellular regulated kinase activation, which led to the degradation of MITF and consequently decreased TYR expression and melanin production in H2O2-stimulated cells. Furthermore, FS inhibited H2O2-induced apoptotic cell death by maintaining mitochondrial membrane potential. Therefore, FS might have potential use for cosmetic whitening and as a therapeutic agent for hyperpigmentation disorder.

Ectopic overexpression of CD133 in HNSCC makes it resistant to commonly used chemotherapeutics.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. Resistance to cytotoxic chemotherapy is a major cause of mortality in patients with HNSCC. A small subset of cancer cells called cancer stem cells (CSCs) may be key contributors to drug resistance and tumor recurrence in HNSCC. The aim of this study was to determine whether CD133, which maintains properties of CSCs, promotes chemoresistance by arresting cell cycle transition and reducing apoptosis in HNSCC cells. CD133 overexpression was examined in KB cells, and colony forming and aldehyde dehydrogenase activity assays were performed. To investigate the role of CD133 in chemoresistance, cell death was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Diff-Quick, flow cytometry, and western blot of apoptosis-related protein expression in fluorouracil (5-FU)- or cisplatin-treated cells. In addition, microarray and related protein expression assessments were performed to investigate the mechanism of chemoresistance against 5-FU and cisplatin in KB cells. Moreover, chemoresistance against 5-FU or cisplatin in a KB-inoculated mouse model was analyzed by hematoxylin and eosin staining, immunohistochemical study of CD133, and immunofluorescence of tumor tissue. In this study, we demonstrate that ectopic overexpression of CD133 significantly promotes properties of stemness in KB cell lines. Furthermore, CD133 promotes chemoresistance by arresting transition of the cell cycle and reducing apoptosis, which results in inhibition of tumor growth in 5-FU- or cisplatin-injected mouse tumor model. Taken together, our findings show that elevated levels of CD133 lead to HNSCC chemoresistance through increased stemness and cell cycle arrest.

Predictors of disclosure management behavior at the end of 1-year follow-up in Korean adults with newly diagnosed epilepsy.

PURPOSE: Epilepsy is a concealable stigmatizing condition. We investigated the factors predicting disclosure management behavior in Korean adults with newly diagnosed epilepsy. METHODS: This longitudinal multicenter study included Korean adults with newly diagnosed epilepsy. Using statistical analyses, we determined at the end of a 1-year follow-up whether Disclosure Management Scale (DMS) scores were predicted by demographic, clinical, and psychosocial variables, including felt stigma, stress coping style, personality traits, social support, and experienced discrimination from society. RESULTS: Of a total of 121 participants, 69% reported that they often or sometimes kept their diagnosis a secret from others and rarely or never talked to others about their epilepsy. The average DMS score was 5.8 (SD=2.9, range 0-11). In univariate analyses, DMS scores were significantly associated with an emotion-focused coping style (r=0.320, p<0.001), social support (r=-0.185, p<0.05), and experienced discrimination (p<0.05). Emotion-focused coping was the only independent predictor of a higher DMS score. Felt stigma, personality traits, and seizure freedom were not related to the DMS score. CONCLUSIONS: Two-thirds of Korean adults with newly diagnosed epilepsy often or sometimes keep their epilepsy a secret. Emotion-focused coping is the most important predictor of concealment of epilepsy diagnosis at the end of a 1-year follow-up, although social support and episodes of experienced discrimination are also associated with disclosure management strategies.

Factors contributing to the development of perceived stigma in people with newly diagnosed epilepsy: A one-year longitudinal study.

PURPOSE: We evaluated the course of perceived stigma and the factors associated with perceived stigma over the first year in newly diagnosed people with epilepsy (PWE). METHODS: We recruited newly diagnosed PWE from 12 tertiary hospitals in Korea. The perceived stigma of epilepsy was assessed using the Stigma Scale at baseline and one year later. At the time of diagnosis, demographic, clinical seizure-related, and psychological data were collected. The predictive factors for perceived stigma over one year were analyzed using logistic regression analyses. RESULTS: Two hundred eighteen newly diagnosed PWE were included at baseline, and 153 completed the study. The percentage of participants who felt stigmatized decreased from 30.7% at the time of diagnosis to 17.6% at the end of follow-up. Introverted personality and a high level of anxiety were independent factors contributing to stigma at the time of epilepsy diagnosis. At the one-year follow-up, introverted personality and lower economic status were predictive of the development of perceived stigma. CONCLUSION: Introverted personality was an important factor contributing to the development of perceived stigma at the time of diagnosis and at one year after diagnosis. In addition, a high level of anxiety and a low economic status were independently related to feelings of stigma at baseline and at one year after diagnosis, respectively. There may be a decrease in the perception of stigma over one year in newly diagnosed PWE.

Digital panoramic radiographs are useful for diagnosis of osteoporosis in Korean postmenopausal women.

OBJECTIVE: The purpose of this study was to determine whether digital panoramic radiographs could be used for the diagnosis of osteoporosis through evaluation of the radiographs based on the correlation with bone mineral density (BMD). METHODS: One hundred and ninety-four post-menopausal women were selected from participants who had participated in the Dong-gu study. Panoramic radiographic indices measured are mental index (MI), mandibular cortical index (MCI) and simple visual estimation (SVE). BMD at the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry (DXA). The Pearson's correlation test was performed to analyse the correlation between MI and age and BMD at the lumbar spine, femoral neck and total hip. Multiple linear regression analysis was performed to analyse the association of MI, MCI and SVE with BMD after adjusting for age, height and weight. To determine the optimal cut-off point of MI for the diagnosis of osteoporosis, the receiver operating characteristic analysis was performed. RESULTS: The MI was positively correlated with BMDs: lumbar spine: r = 0.36, femoral neck: r = 0.59 and total hip: r = 0.58 (p < 0.001). As age increased, MI decreased (r = -0.46). BMD at the lumbar spine and total hip were significantly lower in participants with reduction of mandibular width, thinning and resorption of mandibular cortex by the MI, SVE and MCI, respectively. The optimal cut-off value of MI for the diagnosis of spinal osteoporosis was 2.22 mm. CONCLUSION: Thickness and morphological changes of mandibular inferior cortical bone are associated with BMD, independent of age, height and weight. These results suggest that MI, MCI and SVE may be useful indices for the diagnosis of osteoporosis in a Korean population.

Anti-inflammatory effect of 635 nm irradiations on in vitro direct/indirect irradiation model.

Low-level laser therapy (LLLT) has been promoted for its beneficial effects on tissue healing and pain relief. As during laser treatment it is possible to irradiate only a small area of the surface body or wound and, correspondingly, of a very small volume of the circulating blood, it is necessary to explain how its photomodification can lead to a wide spectrum of therapeutic effects. To establish the experimental model for indirect irradiation, irradiation with 635 nm was performed on immortalized human gingival fibroblasts (IGFs) in the presence of Porphyromonas gingivalis lipopolysaccharides (LPS). The irradiated medium was transferred to non-irradiated IGFs which were compared with direct irradiated IGFs. The protein expressions were assessed by Western blot, and prostaglandin E2 (PGE2 ) was measured using an enzyme-linked immunoassay. Reactive oxygen species (ROS) were measured by DCF-DA; cytokine profiles were assessed using a human inflammation antibody array. Cyclooxygenase-2 (COX-2) protein expression and PGE2 production were significantly increased in the LPS-treated group and decreased in both direct and indirect irradiated IGFs. Unlike direct irradiated IGFs, ROS level in indirect irradiated IGFs was decreased by time-dependent manners. There were significant differences of released granulocyte colony-stimulating factor (G-CSF), regulated on activated normal T-cell expressed and secreted (RANTES), and I-TAC level observed compared with direct and indirect irradiated IGFs. In addition, in the indirect irradiation group, phosphorylations of C-Raf and Erk1/2 increased significantly compared with the direct irradiation group. Thus, we suggest that not only direct exposure with 635 nm light, but also indirect exposure with 635 nm light can inhibit activation of pro-inflammatory mediators and may be clinically useful as an anti-inflammatory tool.

The effect of recurrent seizures on cognitive, behavioral, and quality-of-life outcomes after 12 months of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy.

PURPOSE: The purpose of this study was to determine whether seizure recurrence has a negative impact on cognition, psychological function, and health-related quality of life (HRQoL) over a 12-month period of monotherapy in adults with newly diagnosed or previously untreated partial epilepsy. METHODS: Seizure freedom (SF) was defined as no seizure recurrence during the 40-week maintenance period of medication. Neuropsychological tests, the Symptom Checklist-90 (SCL-90), and the Quality of Life in Epilepsy-31 (QOLIE-31) were administered at baseline and after 48 weeks of carbamazepine or lamotrigine monotherapy. Seventy-three patients successfully continued treatment until the 48-week follow-up time point. Fifty patients (68.5%) had SF, and the remaining 23 were not seizure-free (NSF). A seizure outcome group-by-time interaction was analyzed using a linear mixed model. RESULTS: A group-by-time interaction was identified for the total QOLIE-31 score (p<0.05) and score on two QOLIE-31 subscales (social function: p<0.001 and seizure worry: p<0.001), with a significant improvement over time only present in the SF group (all p<0.001). There was no significant group-by-time interaction for most cognitive function tests, with the exception of the serial clustering score (p<0.01) and number of recognition hits on the California Verbal Learning Test (p<0.05). Serial clustering did not differ between the SF and NSF groups at baseline, but was significantly more used in the NSF group than in the SF group at 48 weeks (p<0.01). There was no significant group-by-time interaction for any dimension of the SCL-90. CONCLUSION: Recurrent seizures had a significant effect on HRQoL, a subtle effect on cognitive performance, and no effect on psychological symptoms over one year in newly diagnosed or previously untreated adults with partial epilepsy.

Effects of light-emitting diode irradiation on RANKL-induced osteoclastogenesis.

BACKGROUND AND OBJECTIVE: Bone homeostasis is maintained by a balance between osteoblastic bone formation and osteoclastic bone resorption, where intracellular reactive oxygen species (ROS) are crucial mediators of osteoclastogenesis. Recently, low-level light therapy (LLLT), a form of laser medicine used in various clinical fields, was shown to alleviate oxidative stress by scavenging intracellular ROS. The present study aimed to investigate the impact of 635 nm irradiation from a light-emitting diode (LED) on osteoclastogenesis from receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-stimulated mouse bone marrow-derived macrophages (BMMs). STUDY DESIGN/MATERIALS AND METHODS: The effects of LED irradiation on osteoclastogenesis were assessed in tartrate-resistant acid phosphatase (TRAP), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell viability, and resorption pit formation, respectively. Quantitative real-time polymerase chain reaction (qPCR) and Western blot analyses were also performed to assess mRNA expression of osteoclastogenesis-related genes and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2), p38, and c-Jun-N-terminal kinase (JNK). NF-κB activity was assayed by luciferase reporter assay and Intracellular ROS generation was investigated by the 2',7'-dichlorodihydrofluorescein diacetate (H2 DCF-DA) detection method. RESULTS: LED irradiation significantly inhibited RANKL-mediated osteoclast differentiation from BMMs and mRNA expression of TRAP, osteoclast-associated immunoglobulin-like receptor (OSCAR), and dendrocyte-expressed seven-transmembrane protein (DC-STAMP). Exposure to LED light likewise significantly decreased RANKL-facilitated NF-κB activity, p38 and ERK phosphorylation and intracellular ROS generation, and increased gene expression of nuclear factor E2-related factor 2 (Nrf2). CONCLUSIONS: Taken together, the results presented herein show that LED irradiation downregulates osteoclastogenesis by reducing ROS production. Therefore, LED irradiation/LLLT might be useful as an alternative, conservative approach to osteoporosis management.

Effects of the antimicrobial peptide cathelicidin (LL-37) on immortalized gingival fibroblasts infected with Porphyromonas gingivalis and irradiated with 625-nm LED light.

Porphyromonas gingivalis causes chronic inflammatory diseases (periodontal diseases) that destroy the periodontal ligament and alveolar bone. Antimicrobial peptides are crucial components of the host defense response required to maintain cellular homeostasis during microbial invasion. Because light-emitting diode (LED) irradiation influences the host defense response against bacterial infections, we investigated its effect on immortalized gingival fibroblasts (IGFs) infected with P. gingivalis. IGFs were incubated with P. gingivalis following LED irradiation at 425, 525, and 625 nm. The dark 1 group comprised noninfected, nonirradiated IGFs, and the dark 2 group comprised nonirradiated IGFs infected with P. gingivalis. These groups served as controls. Infected cells and controls were assayed for reactive oxygen species (ROS) and were subjected to RT-PCR and Western blotting analyses to determine the levels of expression of antimicrobial peptides. LED irradiation enhanced the bactericidal effects of the antimicrobial peptide LL-37 in cells infected with P. gingivalis. Irradiation at 625 nm decreased inflammatory responses involving the release of prostaglandin E2 induced by ROS in P. gingivalis-infected IGFs. LED irradiation at 625 nm induces an anti-inflammatory response that elicits the production of antimicrobial peptides, providing an efficacious method of treatment for periodontal diseases.

Periodontal disease associated with blood glucose levels in urban Koreans aged 50 years and older: the Dong-gu study.

OBJECTIVE: To investigate the association of periodontal disease and the number of teeth present with the risk of prediabetes and diabetes as well as with blood glucose and HbA1c levels in adult Koreans. BACKGROUND: The relationship between periodontal disease and diabetes has not been fully elucidated. MATERIALS AND METHODS: Cross-sectional data from 5535 participants aged ≥50 years were obtained from 2008 to 2010. Periodontal status was measured as pocket depth (PD), clinical attachment loss (CAL) and bleeding on probing (BOP) recorded. The percentage of sites with a PD ≥4 mm, CAL ≥4 mm (CAL4) and BOP (BOP%) were recorded. Participants were divided into three groups according to PD4, CAL4 and BOP% measurements. Number of teeth present was divided into four groups. Participants were classified as normoglycaemic, prediabetic or diabetic based on HbA1c and fasting glucose levels. RESULTS: After full adjustment, the highest tertile of CAL4 (OR: 1.47, 95% CI: 1.18-2.02, p < 0.001), PD4 (OR: 1.58, 95% CI: 1.26-1.97, p < 0.001) and BOP% (OR: 1.37, 95% CI: 1.07-1.75, p = 0.012) had significantly increased odds of diabetes. The number of teeth present was inversely related to diabetes (p < 0.001) and prediabetes (p = 0.032) risk. Periodontal disease severity was positively associated with HbA1c and glucose levels. The number of teeth present was positively associated with HbA1c, but not glucose, levels. CONCLUSION: Periodontal disease and the number of teeth present are associated with an increased risk of diabetes and increased blood glucose and HbA1c levels in Koreans aged ≥50 years.

Anti-inflammatory effects of zinc in PMA-treated human gingival fibroblast cells.

OBJECTIVES: Abnormal cellular immune response has been considered to be responsible for oral lesions in recurrent aphthous stomatitis. Zinc has been known to be an essential nutrient metal that is necessary for a broad range of biological activities including antioxidant, immune mediator, and anti-inflammatory drugs in oral mucosal disease. The objective of this study was to investigate the effects of zinc in a phorbol-12-myristate-13-acetate (PMA)-treated inflammatory model on human gingival fibroblast cells (hGFs). STUDY DESIGN: Cells were pre-treated with zinc chloride, followed by PMA in hGFs. The effects were assessed on cell viability, cyclooxygenease-1,2(COX-1,2) protein expression, PGE2 release, ROS production and cytokine release, Results: The effects were assessed on cell viability, COX1/2 protein expression, PGE2 release, ROS production, cytokine release. The results showed that, in the presence of PMA, zinc treatment leads to reduce the production of ROS, which results in decrease of COX-2 expression and PGE2 release. CONCLUSIONS: Thus, we suggest that zinc treatment leads to the mitigation of oral inflammation and may prove to be an alternative treatment for recurrent aphthous stomatitis.

Cilostazol decreases cerebral arterial pulsatility in patients with mild white matter hyperintensities: subgroup analysis from the Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study.

BACKGROUND: The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume. METHODS: The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available. RESULTS: Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm(3) (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH volume and the changes in PIs from the baseline to the 90-day point. For the subgroup analysis, the WMH volume was dichotomized based on its median value (4.90 cm(3)). Cilostazol decreased the TCD PIs significantly at the 90-day point in patients with WMH volumes ≤ 4.9 cm(3) (p = 0.002). Significant treatment effects were observed in the cilostazol group. CONCLUSIONS: This study showed that cilostazol decreased cerebral arterial pulsatility in patients with WMH. Our findings indicate the unique effect of cilostazol in small vessel disease (SVD), especially in patients with mild WMH changes. Further clinical trials focusing on WMH volume and clinical outcomes are required to assess the unique efficacy of cilostazol in SVD.

Photodynamic therapy (PDT) resistance by PARP1 regulation on PDT-induced apoptosis with autophagy in head and neck cancer cells.

BACKGROUND: Photodynamic therapy (PDT) is an anticancer treatment that generates excessive reactive oxygen species after photosensitizer treatments following specific wavelength irradiation. In another reports, PDT was regulated with autophagic cell death and apoptotic cell death. However, the mechanism of PDT resistance in PDT-stimulated cell death is unclear. In this study, we determined PDT resistance by autophagy and apoptosis in HP-PDT-treated oral cancer cells. MATERIALS & METHODS: Cells were treated hematoporphyrin and then irradiation with or without inhibitor. Cell lysates were checked protein expression with specific antibody. PDT resistance cells were generated with PDT repeated treatments. RESULTS: In HP-PDT, PDT induced autophagy through mTOR, ATG5, and LC3 in dose-dependent manners. Also, PDT at high dose induced apoptosis through caspase activation and PARP-1. Moreover, PARP-1 inhibitor protected cells against HP-PDT-induced cell death, but not by caspase inhibitor. At low dose of HP, autophagy inhibitor partially protected from HP-PDT-induced cell death. In autophagy phases, at low doses, HP-PDT regulated autophagic cell death through the inhibition of LC3II. Although autophagy inhibitor did not alter cell death directly, autophagy has associated with HP-PDT-induced apoptotic cell death by PARP-1 regulation. CONCLUSION: Taken together, HP-PDT induces apoptotic cell death with autophagy in oral cancer cells. PDT resistance is related to autophagy by PARP-1 regulation in oral cancer cells.