Applying new regional background concentration criteria to assess heavy metal contamination in deep-sea sediments at an ocean dumping site, Republic of Korea.

It is crucial to establish appropriate background concentrations to discern heavy metal pollution in the marine environment. In this study, we analyzed heavy metals in deep-sea sediment cores to determine regional background concentrations at the East-Sea Byeong Ocean dumping site. The vertical profiles of heavy metals were categorized into three groups based on their contamination characteristics, and regional background levels for 12 metals were determined using pre-1900 averages. The enrichment factor, contamination factor, and pollution load index, calculated using regional background concentrations, indicated significant contamination by Cr, Co, Cu, Zn, Cd, Hg, and Pb during the ocean dumping period. These results differ from those obtained using global average concentrations. This underscores the importance of considering regional characteristics to minimize the risk of misinterpreting anthropogenic impacts. The approach based on local information is considered useful when sediment quality guidelines are absent or inapplicable.

Long-term effects of chromium from red mud (bauxite residue) ocean dumping on the benthic environment in South Korea.

Between 1999 and 2009, 344,000 m3 of red mud was released into the red mud dumping zone in the East Sea-Byeong ocean dumping site in South Korea. This study aimed to assess the impacts before and after the 2010 red mud dumping ban. We quantified total Cr concentrations by depth from core sediment samples at the red mud dumping station and evaluated benthic communities in 2004, 2009, 2012, 2017, and 2019. At the dumping station DB-085, the Cr content in the upper layer (0-10 cm) exceeded the effect range median criteria in all study years and decreased with time. Geochemical fraction studies using sequential extraction methods from core sediment samples in 2004, 2009, and 2017 showed high ratios of non-residual fractions (anthropogenic inputs), indicating persistent potential long-term risk after the 2010 ban. Additionally, we confirmed that Thyasira tokunagai, an opportunistic and contamination-stress-resistant species, dominated the study station.

Addition of cariogenic pathogens to complex oral microflora drives significant changes in biofilm compositions and functionalities.

BACKGROUND: Dental caries is a microbe and sugar-mediated biofilm-dependent oral disease. Of particular significance, a virulent type of dental caries, known as severe early childhood caries (S-ECC), is characterized by the synergistic polymicrobial interaction between the cariogenic bacterium, Streptococcus mutans, and an opportunistic fungal pathogen, Candida albicans. Although cross-sectional studies reveal their important roles in caries development, these exhibit limitations in determining the significance of these microbial interactions in the pathogenesis of the disease. Thus, it remains unclear the mechanism(s) through which the cross-kingdom interaction modulates the composition of the plaque microbiome. Here, we employed a novel ex vivo saliva-derived microcosm biofilm model to assess how exogenous pathogens could impact the structural and functional characteristics of the indigenous native oral microbiota. RESULTS: Through shotgun whole metagenome sequencing, we observed that saliva-derived biofilm has decreased richness and diversity but increased sugar-related metabolism relative to the planktonic phase. Addition of S. mutans and/or C. albicans to the native microbiome drove significant changes in its bacterial composition. In addition, the effect of the exogenous pathogens on microbiome diversity and taxonomic abundances varied depending on the sugar type. While the addition of S. mutans induced a broader effect on Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog abundances with glucose/fructose, S. mutans-C. albicans combination under sucrose conditions triggered unique and specific changes in microbiota composition/diversity as well as specific effects on KEGG pathways. Finally, we observed the presence of human epithelial cells within the biofilms via confocal microscopy imaging. CONCLUSIONS: Our data revealed that the presence of S. mutans and C. albicans, alone or in combination, as well as the addition of different sugars, induced unique alterations in both the composition and functional attributes of the biofilms. In particular, the combination of S. mutans and C. albicans seemed to drive the development (and perhaps the severity) of a dysbiotic/cariogenic oral microbiome. Our work provides a unique and pragmatic biofilm model for investigating the functional microbiome in health and disease as well as developing strategies to modulate the microbiome. Video Abstract.

Factor Analysis Related to the Change in Activities of Daily Living Performance of Stroke Patients.

This study is aimed at investigating the factors influencing the change (improvement) in the performance of activities of daily living (ADL) in stroke patients. This study utilized data collected from 123 stroke patients at admission and discharge from a local rehabilitation hospital in South Korea between 2019 and 2022. We analyzed the correlations between ADL (Korean version of the Modified Barthel Index) and spasticity (Modified Ashworth Scale), muscle strength (Manual Muscle Test), gait ability (Functional Ambulation Category), cognitive function (Korean version of Mini Mental Status Examination), upper extremity function (Manual Function Test), and balance function (Berg Balance Scale). In addition, to identify the factors influencing the change in ADL in line with the 3 months of rehabilitation, a multiple regression analysis was performed. The results of the correlation analysis showed that balance function (r = 0.925, p < 0.01) and gait ability (r = 0.921, p < 0.01) had strong positive correlations with ADL. Multiple regression analysis (F = 34.547, p ≤ 0.001, adj.R2 = 0.466) indicated that changes in the upper extremity (ß = 0.494, p ≤ 0.001), cognitive (ß = 0.197, p = 0.008), and balance (ß = 0.163, p = 0.029) functions influenced changes in ADL. Our results found that the recovery of upper extremity function along with the improvement of cognitive and balance functions had a significant effect on the improvement of independence in ADL in stroke patients.

D-galactose Intake Alleviates Atopic Dermatitis in Mice by Modulating Intestinal Microbiota.

Atopic dermatitis (AD) is one of the most prevalent, chronic and persistent inflammatory skin diseases closely associated with intestinal microbiota. To evaluate the effect of D-galactose intake on AD, we orally administered D-galactose to BALB/c mice whose ears and skin were treated with 2,4-dinitrochlorobenzene (DNCB). D-galactose alleviated DNCB-induced AD-like phenotypes such as redness, scaling/dryness and excoriation. Ear thickness was also decreased by D-galactose administration. Histopathological analysis revealed decreased epidermal thickening, infiltration of immune cells, especially mast cells, in the dermis. Total levels of serum IgE representing the immunological response of AD were decreased by D-galactose administration. Microbiota analysis showed that D-galactose administration restored gut microbiota profiles, which were altered in AD mice, characterized by increased abundance of Bacteroidetes and decreased abundance of Firmicutes. The increased abundance of Bacteroides and the decreased abundance of Prevotella and Ruminococcus were reversed by D-galactose treatment, following improvement of AD. Our results suggest the possible use of D-galactose as a prebiotic to alleviate AD by altering gut microbiota.

Distribution and assessment of heavy metal concentrations in the East Sea-Byeong ocean dumping site, Korea.

Sediment cores were collected from three sites, the Control, Dumping, and Resting sites in the East Sea-Byeong ocean dumping site, Korea, and the enrichment and degree of accumulation of heavy metals were investigated. Further, to assess the level of heavy metal pollution and understand the potential effects of the ocean dumping activities that began in 1993, the results obtained corresponding to the different sampling sites were compared, and various criteria were employed. Indices, including the enrichment factor and the modified contamination degree, demonstrated that the sediments were contaminated with various heavy metals at different contamination levels. The results also indicated a significant upward enrichment in heavy metals, with the uppermost 0-10 cm sediment layer showing relatively high concentrations. Overall, this study confirmed that anthropogenic heavy metal contamination at the study sites, and the implementation of continuous monitoring, alongside the application of proper management tools, is recommended.

Daily Life Changes and Life Satisfaction among Korean School-Aged Children in the COVID-19 Pandemic.

The recent COVID-19 pandemic has been disrupting the daily lives of people across the world, causing a major concern for psychological well-being in children. This study aimed to examine (1) how life satisfaction and its potential predictors have been affected by the pandemic among school-aged children in Korea, and (2) which factors would predict their life satisfaction during the pandemic. We surveyed 166 fourth-graders in the Seoul metropolitan area to assess their psychological well-being and potentially related variables during the pandemic. The data were compared with those available from two pre-COVID-19 surveys, the 2018 Korean Children and Youth Panel Survey (n = 1236) and the 2019 Korean Children and Youth Well-being Index Survey (n = 334). Higher levels of stress were observed in children during the COVID-19 pandemic; however, the level of their life satisfaction remained unchanged when compared with data from the pre-COVID-19 surveys. The pandemic also affected peer relationship quality and susceptibility to smartphone addiction, but not perceived parenting style nor academic engagement. Interestingly, peer relationship quality no longer predicted life satisfaction during the pandemic; perceived parenting styles and parent-child conversation time predicted life satisfaction. The results suggest a central role of parent-child relationship in supporting the psychological well-being of school-aged children during the pandemic.

Implication of Surface Properties, Bacterial Motility, and Hydrodynamic Conditions on Bacterial Surface Sensing and Their Initial Adhesion.

Biofilms are structured microbial communities attached to surfaces, which play a significant role in the persistence of biofoulings in both medical and industrial settings. Bacteria in biofilms are mostly embedded in a complex matrix comprised of extracellular polymeric substances that provide mechanical stability and protection against environmental adversities. Once the biofilm is matured, it becomes extremely difficult to kill bacteria or mechanically remove biofilms from solid surfaces. Therefore, interrupting the bacterial surface sensing mechanism and subsequent initial binding process of bacteria to surfaces is essential to effectively prevent biofilm-associated problems. Noting that the process of bacterial adhesion is influenced by many factors, including material surface properties, this review summarizes recent works dedicated to understanding the influences of surface charge, surface wettability, roughness, topography, stiffness, and combination of properties on bacterial adhesion. This review also highlights other factors that are often neglected in bacterial adhesion studies such as bacterial motility and the effect of hydrodynamic flow. Lastly, the present review features recent innovations in nanotechnology-based antifouling systems to engineer new concepts of antibiofilm surfaces.

Human Oral Motion-Powered Smart Dental Implant (SDI) for In Situ Ambulatory Photo-biomodulation Therapy.

Peri-implant disease is an inflammatory condition affecting the soft and hard tissues surrounding a dental implant. However, current preventative methods are insufficient due to the limited bioactivity on the dental implant and poor patient compliance. Recently, photo-biomodulation (PBM) therapy that can recover and regenerate peri-implant soft tissue has attracted considerable attention in dentistry. In this paper, a seamless human oral motion-powered dental implant system (called Smart Dental Implant or SDI) is presented as an ambulatory PBM therapy modality. SDI allows the in situ light delivery, which is enabled by the energy harvesting from dynamic human oral motions (chewing and brushing) via an engineered piezoelectric dental crown, an associated circuit, and micro light emitting diodes (LEDs). The SDI also offers adequate mechanical strength as the clinical standards. Using primary human gingival keratinocytes (HGKs) as a model host organism and Pseudomonas aeruginosa lipopolysaccharides (LPS) as a model inflammatory stimulus, effective SDI-mediated PBM therapy is demonstrated. A new class of dental implants could be an ambulatory PBM therapy platform for the prevention of peri-implant disease without patient dependency, warranting long-lasting dental implants.

A Comprehensive Analysis of Near-Contact Photobiomodulation Therapy in the Host-Bacteria Interaction Model Using 3D-Printed Modular LED Platform.

One well-studied bacterial factor recognized by the host immune system is lipopolysaccharides (LPS) that stimulate host cells, resulting in cell inflammation. Although photobiomodulation (PBM) therapy demonstrates its potency on anti-inflammatory activity, the complete mechanism of action in the host-bacteria interaction model is still elusive. In addition, many studies were performed regarding a distance between the light source and biological sample (non-contact therapy) that may result in disparate reports on the efficacy of PBM therapy. Thus, it is critical to clearly understand the effect of this approach to maximize efficacy and minimize side effects. Here, a custom-built light-emitting diode (LED) platform that mimics near-contact therapy is developed. The effect and mechanism of PBM therapy on epithelial cells in response to LPS is systematically investigated under various conditions (wavelength, irradiation-time, pulse-frequency). The data show that the irradiation of near-infrared (NIR-LED) significantly improves the viability of inflamed cells. It reveals that NIR-LED inhibits the production of reactive oxygen species by regulating the Nox4-NF-κB pathway. Interestingly, however, high-pulse frequency stimulus causes the collapse of the mitochondrial membrane potential (ΔΨm) of cells, resulting in cell death. These results suggest that the optimized "PBM condition" is critical to assist the healthy immune system of the host against bacterial invasion.

Synergism of Streptococcus mutans and Candida albicans Reinforces Biofilm Maturation and Acidogenicity in Saliva: An In Vitro Study.

Early childhood caries, a virulent-form of dental caries, is painful, difficult, and costly to treat that has been associated with high levels of Streptococcus mutans (Sm) and Candida albicans (Ca) in plaque-biofilms on teeth. These microorganisms appear to develop a symbiotic cross-kingdom interaction that amplifies the virulence of plaque-biofilms. Although biofilm studies reveal synergistic bacterial-fungal association, how these organisms modulate cross-kingdom biofilm formation and enhance its virulence in the presence of saliva remain largely unknown. Here, we compared the properties of Sm and Sm-Ca biofilms cultured in saliva by examining the biofilm structural organization and capability to sustain an acidic pH environment conducive to enamel demineralization. Intriguingly, Sm-Ca biofilm is rapidly matured and maintained acidic pH-values (~4.3), while Sm biofilm development was retarded and failed to create an acidic environment when cultured in saliva. In turn, the human enamel slab surface was severely demineralized by Sm-Ca biofilms, while there was minimal damage to the enamel surface by Sm biofilm. Interestingly, Sm-Ca biofilms exhibited an acidic environment regardless of their hyphal formation ability. Our data reveal the critical role of symbiotic interaction between S. mutans and C. albicans in human saliva in the context of pathogenesis of dental caries, which may explain how the cross-kingdom interaction contributes to enhanced virulence of plaque-biofilm in the oral cavity.

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.

Trends in Birth Weight and the Incidence of Low Birth Weight and Advanced Maternal Age in Korea between 1993 and 2016.

BACKGROUND: As the aging society progresses, the average age of mothers is also increasing. Advanced maternal age has been known to be associated with perinatal outcomes, as well as birth weight (BW). In this study, we aimed to investigate the perinatal factors associated with low birth weight infants (LBWIs) using birth statistics of the Korean population. METHODS: Birth statistics between 1993 and 2016 from the Korean Statistical Information Service were reviewed. We investigated 12,856,614 data points, which included the number of births, BWs, percentage of preterm births and LBWIs, multiple pregnancies, and maternal age. RESULTS: The proportion of LBWIs delivered by mothers of advanced maternal age has gradually increased since 1993. In addition, the proportion of older mothers (≥ 35 years old) giving birth to LBWIs has increased over the years. Average BW has a negative correlation with the ratio of preterm births, LBW, multiple births, and advanced maternal age. The mean BW also has a negative correlation with maternal age. CONCLUSION: This study shows that the average BW continues to decline, and the incidence of LBWIs is increasing in Korea since 1993. This study also revealed that several perinatal factors, including percentage of preterm births, LBWIs, multiple births, and maternal age influence the mean BW. Although this study did not investigate the effects of decreasing mean BW on perinatal health, future research is worth discussing.

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.

Red light-emitting diode irradiation regulates oxidative stress and inflammation through SPHK1/NF-κB activation in human keratinocytes.

Oxidative stress, in which the amount of oxidants exceeds the capacity of antioxidant defense system, is a well-accepted pathogenesis of several human diseases. Light-emitting diode irradiation (LEDI) is an efficient strategy to counteract this condition. The biological effect of phototherapy, using visible light, has attracted recent attention especially in dermatological practice. However, little is known about the molecular mechanism of the anti-oxidant and anti-inflammatory effects of red light irradiation. We evaluated these effects of LEDI in HaCaT human keratinocyte cells under phorbol-12-myristate-13-acetate (PMA) induced reactive oxygen species (ROS). Microarray analysis revealed changes in 309 genes after LEDI. LEDI at 625 nm produced ROS scavenging and anti-inflammatory effects. One of the most important genes identified by microarray analysis was sphingosine kinase-1 (SPHK1), which is a key molecule in sphingolipid metabolism. SPHK1 knock-down drastically reduced ROS scavenging efficiency as well as expression levels of inflammation-related proteins in PMA-treated HaCaT cells. These results not only indicate the potential for the clinical application of 625-nm LEDI in treating skin disorders via ROS and/or inflammation, but also suggest SPHK1 as a potential therapeutic target in phototherapy.

Development of Novel Photosensitizer Using the Buddleja officinalis Extract for Head and Neck Cancer.

Photodynamic therapy (PDT) is generally safer and less invasive than conventional strategies for head and neck cancer treatment. However, currently available photosensitizers have low selectivity for tumor cells, and the burden and side effects are so great that research is needed to develop safe photosensitizers. In this study, it was confirmed that the Buddleja officinalis (BO) extract, used in the treatment of inflammation and vascular diseases, shows fluorescence when activated by LED light, and, based on this, we aimed to develop a new photosensitive agent suitable for PDT. MTT, Diff-Quick® staining, and DCF-DA were performed to measure the effects of treating head and neck cancer cells with BO extract and 625 nm LED light (BO-PDT). Cell cycle, TUNEL, and western blot assays, as well as acridine orange staining, were performed to explore the mechanism of BO-PDT-induced cell death. We found that when the BO extract was irradiated with 625 nm LED light, it showed sufficient fluorescence and stronger intracellular toxicity and ROS effect than the currently commercially available hematoporphyrin. BO-PDT resulted in a decrease of mTOR activity that was correlated with an increase in the levels of ATG5, beclin-1, and LC3-II, which interfere with the formation of autophagosomes. In addition, BO-PDT induced the activation of PARP and led to an increase in the expression of proapoptotic protein Bax and a decrease in the expression of the antiapoptotic protein Bcl-2. Moreover, BO-PDT has been shown to induce the autophagy pathway 4 h after treatment, while apoptosis was induced 16 h after treatment. Finally, we confirmed that BO-PDT caused cell death of head and neck cancer cells via the intrinsic pathway. Therefore, we suggest that BO extract can be used as a new photosensitizer in PDT of head and neck cancer.

Chronic adverse effects of oil dispersed sediments on growth, hatching, and reproduction of benthic copepods: Indirect exposure for long-term tests.

Laboratory-scale sediment exposure was conducted as a preliminary study to assess the long-term effects of sediment contaminated with crude oil. For this purpose, indirect exposure using a glass filter crucible was tested and compared with direct exposure by observing several parameters (e.g., mortality, growth, reproduction, hatching, and uptake) in the benthic copepod Tigriopus japonicus. In direct exposure, short-term exposure caused significant damages to the eggs of ovigerous females, and there were difficulties in observing small oil droplets. However, indirect exposure did not induce any mortality during a 96-h exposure in adults. A 10-day exposure was also possible in an indirect exposure method and caused a decrease in reproduction and consequently a reduction in the hatching rate. In fact, the water phase collected from indirect exposure indicated significant polycyclic aromatic hydrocarbon (PAH) concentrations, although only a few components were present. The components of PAHs were similar to water-accommodated fractions (WAFs) of crude oil that are associated with the water-soluble part, but the relative portion of high-molecular-weight of PAHs was higher than WAF. In this approach, exposure tests caused reduction in the uptake rate in copepods even in the 24-h exposure. In conclusion, the biological effects of oil droplets from direct exposure were excluded by using a glass filter in indirect exposures, and several parameters could be derived in the long-term exposure. These results indicate that the indirect method could likely assess the chronic effects of oil-contaminated sediments on individual level parameters for deriving the ultimate effects on the population and community.

Cell proliferation and migration mechanism of caffeoylserotonin and serotonin via serotonin 2B receptor in human keratinocyte HaCaT cells.

Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary metabolite produced in pepper fruits with strong antioxidant activities. In this study, we investigated the effect of CaS on proliferation and migration of human keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte proliferation even under serum deficient condition. This effect of CaS was mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally involved in upregulated expression levels of cyclin D1 and cyclin E induced by CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration in HaCaT cells via 5-HT2BR. However, 5-HT regulated cell migration only through ERK/AP-1/MMP9 pathway while additional Akt/NF-κB/MMP9 pathway was involved in the cell migration effect of CaS. These results suggest that CaS can enhance keratinocyte proliferation and migration. It might have potential as a reagent beneficial for wound closing and cell regeneration. [BMB Reports 2018; 51(4): 188-193].

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.