Effects of 625 nm light-emitting diode irradiation on preventing ER stress-induced apoptosis via GSK-3ß phosphorylation in MC3T3-E1.

Prolonged endoplasmic reticulum (ER) stress contributes to cell apoptosis and interferes with bone homeostasis. Although photobiomodulation (PBM) might be used for ER stress-induced diseases, the role of PBM in relieving cell apoptosis remains unknown. During ER stress, glycogen synthase kinase-3ß (GSK-3ß) is critical; however, its functions in PBM remain uncertain. Thus, this study aimed to investigate the role of GSK-3ß in 625 nm light-emitting diode irradiation (LEDI) relieving tunicamycin (TM)-induced apoptosis. Based on the results, pre-625 nm LEDI (Pre-IR) phosphorylated GSK-3ß via ROS production. Compared with the TM group, Pre-IR + TM group reduced the phosphorylation of the α-subunit of eukaryotic translation initiation factor 2 (eIF-2α) and B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax)/Bcl-2 ratio through regulating GSK-3ß. Furthermore, a similar tendency was observed between Pre-IR + TM and Pre-LiCl+TM groups in preventing TM-induced early and late apoptosis. In summary, this study suggests that the Pre-IR treatment in TM-induced ER stress is beneficial for preventing cell apoptosis via GSK-3ß phosphorylation.

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.

Effect of Coffee on Lipopolysaccharide-Induced Immortalized Human Oral Keratinocytes.

Periodontitis is a common inflammatory disease that is strongly influenced by dietary habits. Coffee is one of the most common dietary components; however, current research on the relationship between coffee consumption and periodontitis, as well as its underlying mechanisms, is limited. Based on a previous report, caffeine (CA) and chlorogenic acid (CGA) were formulated into artificial coffee (AC) for this experiment. Cell viability, prostaglandin E2 release, Western blotting, cellular reactive oxygen species (ROS) production, and NF-E2-related factor 2 (Nrf2) translocation analyses were performed to explore the effects of AC on lipopolysaccharide (LPS)-induced immortalized human oral keratinocytes (IHOKs) and elucidate their underlying mechanisms. AC pretreatment attenuated LPS-induced inflammatory mediator release, ROS production, and nuclear factor kappa B translocation in IHOKs. CA and CGA promoted AMP-activated protein kinase phosphorylation and down-regulated the nuclear factor-κB pathways to exert anti-inflammatory effects. Additionally, CGA promoted Nrf2 translocation and heme oxygenase-1 expression and showed anti-oxidative effects. Furthermore, AC, CA, and CGA components showed synergistic effects. Thus, we predict that coffee consumption may be beneficial for alleviating periodontitis. Moreover, the main coffee components CA and CGA seem to play a synergistic role in periodontitis.

A Novel Fluorescent Dye Extracted from Buddleja officinalis for Labeling Mitochondria after Fixation.

Mitochondria are versatile organelles and function by communicating with cellular ecosystems. The fluorescent colocalization analysis after fixation is a highly intuitive method to understand the role of mitochondria. However, there are few fluorescent dyes available for mitochondrial staining after fixation. In this study, a novel fluorescent dye (BO-dye), extracted from Buddleja officinalis, was applied for mitochondrial staining in fixed immortalized human oral keratinocytes. The BO-dye (excitation: 414 nm, emission: 677 nm) is a small fluorescent molecular dye, which can cross the cytomembrane without permeabilization. We assume that the BO-dye could aggregate and bind to the mitochondria stably. BO-dye exhibited a mega-Stokes shift (>250 nm), which is an important feature that could reduce self-quenching and enhance the signal-to-noise ratio. Analysis of photophysical properties revealed that the BO-dye is temperature and pH insensitive, and it exhibits superior photostability. These results indicate that BO-dye can be considered an alternative fluorescent dye for labeling mitochondria after fixation.

635 nm LED irradiation may prevent endoplasmic reticulum stress in MC3T3-E1 cells.

Although endoplasmic reticulum (ER) stress is thought to be involved in various diseases such as cancer, metabolic, and inflammatory disorders, the relationship between ER stress and bone diseases, are remains unclear. Tunicamycin-treated MC3T3-E1 osteoblasts were used as the ER stress model in this study. 635 nm light-emitting diode irradiation (635 nm-IR) was carried out for 1 h before and after inducing ER stress. To investigate the effects of 635 nm-IR on ER stress-induced MC3T3-E1 osteoblasts and the underlying mechanism, western blot, reverse transcription polymerase chain reaction, alkaline phosphatase and Alizarin red staining, 2',7'-dichlorodyhydrofluorescein diacetate assay, Fluo-3AM and immunocytochemistry were performed. Pretreatment with 635 nm-IR effectively prevented intracellular reactive oxygen species production and alleviated ER stress through the pancreatic ER kinase (PERK)-eukaryotic initiation factor 2 (eIF2)-activating transcription factor 4 (ATF4)-nuclear factor-like 2 (Nrf2) signaling pathway. Hence, 635 nm-IR may serve a protective role in the treatment of ER stress-related bone diseases.

Photochemical reaction to increase melanogenesis using Buddleja officinalis and blue light-emitting diode irradiation in B16F10.

Recently, the incidence of vitiligo has increased because of stresses induced by external environment. Ultraviolet (UV) light therapy is the most commonly used method of treating the disease; however, UV light therapy requires a long treatment period, and prolonged exposure to UV radiation has side effects. The purpose of the present study was to investigate the effects of natural products and LED irradiation (LED-IR) on the synthesis of melanin. It was not possible to effectively increase intracellular melanin production through individual applications of Buddleja officinalis (BO), which is a natural substance selected through screening, or blue light irradiation (Blue-IR). However, when used in combination, these two agents stimulated adenylyl cyclase (AC) and melanin production was induced in the stimulated cells via the CREB/MITF/TYR pathway. Furthermore, the combined treatment with BO and Blue-IR generated low levels of cellular reactive oxygen species (ROS) and induced p38 phosphorylation, which in turn activated MITF in ROS-stimulated synthetic melanocytes, resulting in the promotion of melanogenic pathways other than the CREB/MITF/TYR pathway. In addition, this treatment combination effected melanin transport. These results suggested that the combined therapies can be used to treat melanin-deficiency skin diseases such as vitiligo.

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.

Low serum 25-hydroxyvitamin D levels, tooth loss, and the prevalence of severe periodontitis in Koreans aged 50 years and older.

PURPOSE: Vitamin D deficiency may cause bone loss and increased inflammation, which are well-known symptoms of periodontal disease. This study investigated whether serum 25-hydroxyvitamin D (25(OH)D) levels are associated with periodontal disease status and tooth loss. METHODS: Cross-sectional data from 5,405 individuals aged ≥50 years (2,253 males and 3,152 females) were obtained from the 2008-2010 Dong-gu study, a prospective cohort study of risk factors for chronic diseases. Periodontal examinations were conducted to evaluate the number of remaining teeth, the periodontal probing depth (PPD), the clinical attachment level (CAL), and bleeding on probing. The percentages of sites with PPD ≥4 mm and CAL ≥4 mm were recorded for each participant. The severity of periodontitis was classified using the Centers for Disease Control and Prevention and the American Academy of Periodontology case definitions. Serum 25(OH)D levels were classified as reflecting severe deficiency, deficiency, insufficiency, or sufficiency. Multivariate linear regression analysis was performed to assess the associations of serum 25(OH)D levels with periodontal parameters and the number of remaining teeth after adjusting for confounders including age, smoking status, alcohol consumption status, month of blood collection, and physical activity. Multivariate logistic regression was used to evaluate the association between serum vitamin D levels and severe periodontitis. An overall statistical analysis and a stratified analysis by sex were performed. RESULTS: Overall, the rates of severe deficiency, deficiency, insufficiency, and sufficiency were 6.5%, 67.9%, 22.4%, and 3.2%, respectively. After adjustment for confounders, vitamin D levels were directly associated with the number of remaining teeth, an association that was significant in males, but not in females. Sufficient serum 25(OH)D was associated with a low frequency of severe periodontitis. CONCLUSIONS: This population-based cross-sectional study indicates that low serum 25(OH)D is significantly associated with tooth loss and severe periodontitis in Koreans aged 50 years and older.

Effect of a Er, Cr:YSGG laser and a Er:YAG laser treatment on oral biofilm-contaminated titanium.

OBJECTIVE: Implant surface decontamination is a challenging procedure for therapy of peri-implant disease. This study aimed to compare the effectiveness of decontamination on oral biofilm-contaminated titanium surfaces in Er:YAG laser, Er, Cr:YSGG laser, and plastic curette. METHODOLOGY: For oral biofilms formation, six participants wore an acrylic splint with eight titanium discs in the maxillary arch for 72 hours. A total of 48 contaminated discs were distributed among four groups: untreated control; decontamination with plastic curettes; Er, Cr:YSGG laser; and Er:YAG laser irradiation. Complete plaque removal was estimated using naked-eye and the time taken was recorded; the residual plaque area was measured and the morphological alteration of the specimen surface was observed by scanning electron microscopy. The total bacterial load and the viability of adherent bacteria were quantified by live or dead cell labeling with fluorescence microscopy. RESULTS: The mean treatment time significantly decreased based on the treatment used in the following order: Er:YAG, Er, Cr:YSGG laser, and plastic curettes (234.9±25.4 sec, 156.1±12.7 sec, and 126.4±18.6 sec, P=0.000). The mean RPA in the Er, Cr:YSGG laser group (7.0±2.5%) was lower than Er:YAG and plastic curettes groups (10.3±2.4%, 12.3±3.6%, p=0.023). The viable bacteria on the titanium surface after Er, Cr:YSGG laser irradiation was significantly lower compared to the decontamination with plastic curette (P=0.05) but it was not significantly different from the Er:YAG laser irradiation. CONCLUSION: We found that Er:YAG laser and Er, Cr:YSGG laser irradiation were effective methods for decontaminations without surface alterations.

Blood Neutrophil/Lymphocyte Ratio Is Associated With Cerebral Large-Artery Atherosclerosis but Not With Cerebral Small-Vessel Disease.

Background and Objective: The blood neutrophil/lymphocyte ratio (NLR) is a marker of peripheral inflammation, with a high NLR associated with an increased risk of cardiovascular events and poor prognosis in ischemic stroke. However, few data are available on the differential impact of the blood NLR on different silent cerebral vascular pathologies, including cerebral large-artery atherosclerosis (LAA) and cerebral small-vessel disease (CSVD), in neurologically healthy individuals. Methods: We evaluated cardiovascular risk factors, brain magnetic resonance imaging (MRI), and MR angiography of 950 individuals without any neurological diseases. The study participants were divided into three groups according to NLR tertile (low, middle, and high). The presences of extracranial (EC) and intracranial (IC) atherosclerosis were considered to indicate LAA on brain MR angiography. The presences of silent lacunar infarction (SLI) and cerebral white matter hyperintensities (WMHs) were analyzed as indices of CSVD on brain MRI. Results: In univariate analysis, the high NLR tertile group showed a high prevalence of old age, hyperlipidemia, and renal dysfunction and higher fasting glucose. Multivariable logistic regression analysis revealed that indices of LAA (EC atherosclerosis [odds ratio: 1.88; 95% confidence interval: 1.14-3.09; p = 0.01] and IC atherosclerosis [odds ratio: 1.87; 95% confidence interval: 1.15-3.06; p = 0.01]) were more prevalent in the highest NLR tertile group than in the lowest NLR tertile group after adjustment for cardiovascular risk factors. However, no significant differences were found in the prevalence of CSVD indices (SLI and WMHs) among the three NLR tertile groups. Conclusions: A high NLR is associated with the development of cerebral LAA but not CSVD.

Role of E2F1/SPHK1 and HSP27 During Irradiation in a PMA-Induced Inflammatory Model.

Background: Sphingosine kinase 1 (SPHK1) and heat shock protein 27 (HSP27) are important for antioxidant and anti-inflammatory effects after red light irradiation in an inflammatory model. Objective: The purpose of the present study was to evaluate whether SPHK1 and HSP27 work independently or are dependent on some other regulator after 625 nm light-emitting diode irradiation in the human keratinocyte (HaCaT) cell line. Methods: Differentially expressed genes (DEGs) were identified between groups with or without 625 nm photobiomodulation (PBM) in the inflammatory model. Potential transcription factors (TFs) of key DEGs were predicted using the iRegulon plugin. The mechanism was investigated by analyzing mRNA and protein expression levels, prostaglandin E2 levels, and intracellular reactive oxygen species (ROS) in phorbol 12-myristate 13-acetate (PMA)-induced HaCaT cells after 625 nm PBM. Results: A total of 6 TFs (e.g., E2F1) and 51 key DEGs (e.g., SPHK1) were identified after 625 nm PBM in PMA-stimulated HaCaT cells. E2F1 worked as a regulator of SPHK1; however, it did not affect HSP27. E2F1 knockdown drastically decreased the SPHK1 expression level and increased the intracellular ROS, as well as the expression levels of inflammation-related proteins in PMA-induced HaCaT cells. In addition, the inhibition of HSP27 decreased the anti-inflammatory effect of 625 nm PBM. Conclusions: E2F1 worked as a TF of SPHK1 and exhibited anti-inflammatory and antioxidative effects through SPHK1 in PMA-induced HaCaT cells after 625 nm PBM. HSP27 is essential for the 625 nm PBM-induced anti-inflammatory function. Therefore, E2F1/SPHK1 and HSP27 could be used as potential biomarkers for anti-inflammatory therapy with 625 nm PBM.

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.

Effect of a Er, Cr: YSGG laser and a Er: YAG laser treatment on oral biofilm-contaminated titanium

Abstract Implant surface decontamination is a challenging procedure for therapy of peri-implant disease. Objective: This study aimed to compare the effectiveness of decontamination on oral biofilm-contaminated titanium surfaces in Er:YAG laser, Er, Cr:YSGG laser, and plastic curette. Methodology: For oral biofilms formation, six participants wore an acrylic splint with eight titanium discs in the maxillary arch for 72 hours. A total of 48 contaminated discs were distributed among four groups: untreated control; decontamination with plastic curettes; Er, Cr:YSGG laser; and Er:YAG laser irradiation. Complete plaque removal was estimated using naked-eye and the time taken was recorded; the residual plaque area was measured and the morphological alteration of the specimen surface was observed by scanning electron microscopy. The total bacterial load and the viability of adherent bacteria were quantified by live or dead cell labeling with fluorescence microscopy. Results: The mean treatment time significantly decreased based on the treatment used in the following order: Er:YAG, Er, Cr:YSGG laser, and plastic curettes (234.9±25.4 sec, 156.1±12.7 sec, and 126.4±18.6 sec, P=0.000). The mean RPA in the Er, Cr:YSGG laser group (7.0±2.5%) was lower than Er:YAG and plastic curettes groups (10.3±2.4%, 12.3±3.6%, p=0.023). The viable bacteria on the titanium surface after Er, Cr:YSGG laser irradiation was significantly lower compared to the decontamination with plastic curette (P=0.05) but it was not significantly different from the Er:YAG laser irradiation. Conclusion: We found that Er:YAG laser and Er, Cr:YSGG laser irradiation were effective methods for decontaminations without surface alterations.

Differential Impact of Plasma Homocysteine Levels on the Periventricular and Subcortical White Matter Hyperintensities on the Brain.

Background: The clinical significance of cerebral white matter hyperintensities (WMH) on brain magnetic resonance imaging (MRI) has recently increased, and recognized now as a risk factor for future stroke and dementia. High levels of plasma homocysteine (Hcyt) are associated with cerebral WMH. Recent studies suggest a different anatomy and physiology in the arteriolar system may be supplied to the periventricular and deep subcortical white matter. We hypothesize that plasma Hcyt levels have differing impacts on periventricular WMH (PVWMH) than on deep subcortical WMH (DSWMH). Methods: We evaluated plasma Hcyt levels from 937 neurologically healthy participants. The severity of PVWMH and DSWMH was evaluated by the use of a manual grading scale. Moderate to severe PVWMH and DSWMH levels were defined when the Fazekas score was two or three, respectively. Predominant PVWMH (pred-PVWMH) and predominant DSWMH (pred-DSWMH) were defined as having a difference of Fazekas score between PVWMH and DSWMH of two or more. Other confounding variables including age, sex, vascular risk factors, and estimated glomerular filtration rate (eGFR) were also analyzed. Results: Logistic regression revealed that, after adjusting for the confounding variables, PVWMH was associated with old age, hypertension, diabetes mellitus, low eGFR, and high plasma Hcyt levels. DSWMH was associated with old age, hypertension, and hypercholesterolemia but not with plasma Hcyt levels. Plasma Hcyt levels were associated with pred-PVWMH but not with pred-DSWMH. Conclusions: High plasma Hcyt levels are strongly associated with the development of PVWMH but not DSWMH. Our results suggest the possibility that different pathogeneses exist for PVWMH and DSWMH and that dysregulated Hcyt metabolism associated with the development of PVWMH.

Primordial odontogenic tumor: a case report and literature review.

BACKGROUND: A primordial odontogenic tumor (POT) is a rare, benign, mixed epithelial and mesenchymal odontogenic tumor that has been included as a new entity in the latest World Health Organization (WHO) classification (2017). POT consists of dental papilla-like myxoid connective tissue covered with a delicate membrane of ameloblastic epithelium. Only 15 cases have been documented worldwide, and here, we report the sixteenth case and the first one of South Korea. CASE PRESENTATION: An asymptomatic lesion was discovered as an incidental radiographic finding in a 10-year-old boy. The patient had no complaints about the lesion. Cone-beam computerized tomograms revealed a round cavity with a defined cortical border measuring approximately 5 × 5 × 5 mm in size. The lesion was a POT. The patient was treated with enucleation. The tumor showed no recurrence for one year. CONCLUSION: This is the first report of POT in South Korea using the novel diagnosis of POT after it was recognized and defined in the latest WHO classification. This novel diagnosis will be useful for pathologists and clinicians in diagnosing and differentiating this new and rare disease from other odontogenic tumors.

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.

Acanthopanacis Cortex extract: A novel photosensitizer for head and neck squamous cell carcinoma therapy.

OBJECTIVES: The aim of this study was to develop a novel photosensitizer from traditional plant extracts and to investigate the photodynamic therapy (PDT) effect and mechanism of action of the novel photosensitizer on KB and Hep-2 cells. METHODS: Fluorescence emission, cell viability, and intracellular distribution of candidates were analyzed to screen potential photosensitizers from traditional plant extracts. Cellular reactive oxygen species (ROS) quantification, Annexin V-FITC/PI staining, and western blotting were performed to explore the mechanism of cell death in KB and Hep-2 cells. RESULT: Of 289 traditional plant extracts, 13 plant extracts with strong fluorescence were initially screened by fluorescence emission analysis. The cell viability assay and intracellular distribution of candidates showed that Acanthopanacis Cortex (AC) extract is a potential photosensitizer. Under optimal PDT conditions, high levels of ROS were produced in KB and Hep-2 cells, followed by cell death. However, there was no significant damage to HaCaT cells. Moreover, apoptosis induced by AC extract with 625 nm irradiation (IR) down-regulated the expression of Bcl-2 protein and up-regulated the expression of Bax protein, as well as that of cleaved PARP-1 protein in both KB and Hep-2 cells. CONCLUSION: The fluorescence intensity of AC extract at 420 nm is similar to that of the commercial Hematoporphyrin (HP). AC extract with 625 nm IR could enhance the PDT effect, induce ROS generation, and trigger apoptotic pathways in KB and Hep-2 cells. Therefore, we suggest that AC is a potential novel photosensitizer for PDT in head and neck squamous cell carcinoma.

Alteration of microRNA 340-5p and Arginase-1 Expression in Peripheral Blood Cells during Acute Ischemic Stroke.

Acute stroke alters the systemic immune response as can be observed in peripheral blood; however, the molecular mechanism by which microRNA (miRNA) regulates target gene expression in response to acute stroke is unknown. We performed a miRNA microarray on the peripheral blood of 10 patients with acute ischemic stroke and 11 control subjects. Selected miRNAs were quantified using a TaqMan assay. After searching for putative targets from the selected miRNAs using bioinformatic analysis, functional studies including binding capacity and protein expression of the targets of the selected miRNAs were performed. The results reveal a total of 30 miRNAs that were differentially expressed (16 miRNAs were upregulated and 14 miRNAs were downregulated) during the acute phase of stroke. Using prediction analysis, we found that miR-340-5p was predicted to bind to the 3'-untranslated region of the arginase-1 (ARG1) gene; a luciferase reporter assay confirmed the binding of miR-340-5p to ARG1. miR-340-5p was downregulated whereas ARG1 mRNA was upregulated in peripheral blood in patients experiencing acute stroke. Overexpression of miR-340-5p in human neutrophil and mouse macrophage cell lines induced downregulation of the ARG1 protein. Transfection with miR-340-5p increased nitric oxide production after LPS treatment in a mouse macrophage cell line. Our results suggest that several miRNAs are dynamically altered in the peripheral blood during the acute phase of ischemic stroke, including miR-340-5p. Acute stroke induces the downregulation of miR-340-5p, which subsequently upregulates ARG1 protein expression.

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.