Diesel particulate matter permeation into normal human skin and intervention using a topical ceramide formulation.

INTRODUCTION: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAH). The skin, as well as airways, are directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. METHODS: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic polycyclic aromatic hydrocarbon (PAH), benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. RESULTS: 2-methylnaphthalene, triphenylene and benzo(a)pyrene were recovered from the epidermis. Although these PAH were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAH adsorbed to DPMs into the skin. CONCLUSION: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.

Trends in Distributions of Hearing Threshold Levels by Ages: A Comparison of the ISO 7029 and Newly Available Country-Specific Data.

Hearing thresholds provide essential information and references about the human auditory system. This study aimed to identify changing trends in distributions of hearing threshold levels across ages by comparing the International Organization for Standardization (ISO) 7029 and newly available data after publishing ISO 7029. To compare ISO 7029 and newly available hearing threshold data after publishing ISO 7029, four country-specific datasets that presented average hearing threshold levels under conditions similar to ISO 7029 were utilized. For frequencies between 125 Hz and 8,000 Hz, the deviations of hearing threshold values by ages from the hearing threshold of the youngest age group for each data point were utilized. For frequencies from 9,000 Hz to 12,500 Hz, the median threshold information was utilized. Hearing threshold data reported after publishing ISO 7029 from the four countries were mostly similar to the ISO 7029 data but tended to deviate in some age groups and sexes. As national hearing threshold trends change, the following ISO 7029 revision suggests the need to integrate hearing threshold data from different countries.

Barrier Abnormalities in Type 1 Diabetes Mellitus: The Roles of Inflammation and Ceramide Metabolism.

Xerosis is a common sign of both type 1 and type 2 diabetes mellitus (DM), and patients with DM and mouse models for DM show a compromised epidermal permeability barrier. Barrier defects then allow the entry of foreign substances into the skin, triggering inflammation, infection, and worsening skin symptoms. Characterizing how barrier abnormalities develop in DM could suggest treatments for xerosis and other skin disease traits. Because the proper ratio, as well as proper bulk amounts, of heterogeneous ceramide species are keys to forming a competent barrier, we investigated how ceramide metabolism is affected in type 1 DM using a mouse model (induced by streptozotocin). Chronic inflammation, evident in the skin of mice with DM, leads to (i) decreased de novo ceramide production through serine racemase activation-mediated attenuation of serine palmitoyl transferase activity by D-serine; (ii) changes in ceramide synthase activities and expression that modify the ratio of ceramide molecular species; and (iii) increased ceramide-1-phosphate, a proinflammatory lipid mediator, that stimulates inflammatory cytokine expression (TNFα and IFN-γ). Together, chronic inflammation affects ceramide metabolism, which attenuates epidermal permeability barrier formation, and ceramide-1-phosphate could amplify this inflammation. Alleviation of chronic inflammation is a credible approach for normalizing barrier function and ameliorating diverse skin abnormalities in DM.

The clinical availability of facial nerve enhancement in temporal bone MRI for the patients of idiopathic acute peripheral facial palsy.

PURPOSE: This study is to evaluate the duration of facial nerve enhancement in gadolinium-enhanced temporal bone MRI after the onset of acute facial palsy. METHODS: Gd-enhanced MRI imagines were examined in 13 patients with idiopathic acute facial palsy within 14 days after the onset. The degree of facial nerve function was measured according to the House-Brackmann (H-B) grading system at their first visit at outpatient clinic. The follow-up MRI was taken about 16.5 months (7-24 months) after onset of disease. The degree of facial nerve enhancement was measured with signal intensity (SI) which was quantitatively analyzed using the region-of-interest (ROI) measurements for each segment of the facial nerve. SI was statistically analyzed by comparing SI values of contralateral site and ipsilateral site using the paired t test with SPSS program. RESULTS: The gadolinium enhancement was statistically increased at labyrinthine segment and geniculate ganglion area of facial nerve at initial temporal bone MRI. The gadolinium enhancement was statistically decreased at all the segments of facial nerve except tympanic segment (p < 0.05) at follow-up MRI. CONCLUSIONS: The facial nerve enhancement in Gd-enhanced MRI images prolonged more than 21 months of the onset. The newly developed pathologic lesions of acute facial palsy especially occur at the site of labyrinthine and geniculate ganglion.

Analysis of temperature effects on the protein accumulation of the FT-FD module using newly generated Arabidopsis transgenic plants.

Arabidopsis flowering is dependent on interactions between a component of the florigens FLOWERING LOCUS T (FT) and the basic leucine zipper (bZIP) transcription factor FD. These proteins form a complex that activates the genes required for flowering competence and integrates environmental cues, such as photoperiod and temperature. However, it remains largely unknown how FT and FD are regulated at the protein level. To address this, we created FT transgenic plants that express the N-terminal FLAG-tagged FT fusion protein under the control of its own promoter in ft mutant backgrounds. FT transgenic plants complemented the delayed flowering of the ft mutant and exhibited similar FT expression patterns to wild-type Col-0 plants in response to changes in photoperiod and temperature. Similarly, we generated FD transgenic plants in fd mutant backgrounds that express the N-terminal MYC-tagged FD fusion protein under the FD promoter, rescuing the late flowering phenotypes in the fd mutant. Using these transgenic plants, we investigated how temperature regulates the expression of FT and FD proteins. Temperature-dependent changes in FT and FD protein levels are primarily regulated at the transcript level, but protein-level temperature effects have also been observed to some extent. In addition, our examination of the expression patterns of FT and FD in different tissues revealed that similar to the spatial expression pattern of FT, FD mRNA was expressed in both the leaf and shoot apex, but FD protein was only detected in the apex, suggesting a regulatory mechanism that restricts FD protein expression in the leaf during the vegetative growth phase. These transgenic plants provided a valuable platform for investigating the role of the FT-FD module in flowering time regulation.

Improving Accuracy and Reliability of Hearing Tests: An Exploration of International Standards.

This study explores the internal standards for hearing tests and benefits of implementing international standard protocols, including the International Organization for Standardization (ISO) and International Electrotechnical Commission (IEC), and discusses how ISO and IEC standards provide a framework for designing, calibrating, assessing hearing test instruments and methods, and exchanging and comparing data globally. ISO and IEC standards for hearing tests improve accuracy, reliability, and consistency of test results by applying standardized methods and environments. Moreover, they promote international harmonization and data interoperability, enabling information exchange and research collaboration. Those standards for hearing tests are beneficial but have challenges and limitations, such as variation in equipment and calibration, lag in updating standards, variation in implementation and compliance, and lack of coverage of clinical aspects, cultural diversity, and linguistic diversity. These affect the quality and interpretation of test results. Adapting ISO or IEC standards locally would improve their applicability and acceptability, while balancing customization and compatibility with global standards.

Ratio of Extracellular to Intracellular Water Is Associated with Permanent Catheter Patency Survival in Patients Receiving Maintenance Hemodialysis.

Patients undergoing dialysis through a permanent catheter often experience infection or malfunction. However, few studies have clarified the predictors of permanent catheter patency survival in patients undergoing hemodialysis. We assessed the relationship between the parameters of body composition monitoring (BCM), determined before the initiation of dialysis, and the patency survival of the permanent catheters inserted in 179 patients who commenced hemodialysis between 14 January 2020 and 31 August 2021. The relationships between permanent catheter patency at 6 weeks and BCM parameters, laboratory tests, age, sex, comorbidities, and medications at baseline were studied using Kaplan-Meier survival curves. Permanent catheter patency was observed to be superior at high extracellular-to-intracellular (ECW/ICW) ratio (p < 0.005). After adjustment for covariates, the ECW/ICW ratio remained an independent factor associated with permanent catheter patency survival. When patients with non-patent catheters were subdivided into infection and malfunction groups, and the associations of BCM parameters were evaluated in those groups, the ECW/ICW ratio was not significantly associated with permanent catheter patency survival in the infection group (p = 0.327); instead, a significant association was found for the lean tissue index (p < 0.001). In the malfunction group, the ECW/ICW ratio remained significantly associated with permanent catheter patency survival (p < 0.001).

Improving combination therapies: targeting A2B-adenosine receptor to modulate metabolic tumor microenvironment and immunosuppression.

BACKGROUND: We investigated the role of A2B-adenosine receptor in regulating immunosuppressive metabolic stress in the tumor microenvironment. Novel A2B-adenosine receptor antagonist PBF-1129 was tested for antitumor activity in mice and evaluated for safety and immunologic efficacy in a phase I clinical trial of patients with non-small cell lung cancer. METHODS: The antitumor efficacy of A2B-adenosine receptor antagonists and their impact on the metabolic and immune tumor microenvironment were evaluated in lung, melanoma, colon, breast, and epidermal growth factor receptor-inducible transgenic cancer models. Employing electron paramagnetic resonance, we assessed changes in tumor microenvironment metabolic parameters, including pO2, pH, and inorganic phosphate, during tumor growth and evaluated the immunologic effects of PBF-1129, including its pharmacokinetics, safety, and toxicity, in patients with non-small cell lung cancer. RESULTS: Levels of metabolic stress correlated with tumor growth, metastasis, and immunosuppression. Tumor interstitial inorganic phosphate emerged as a correlative and cumulative measure of tumor microenvironment stress and immunosuppression. A2B-adenosine receptor inhibition alleviated metabolic stress, downregulated expression of adenosine-generating ectonucleotidases, increased expression of adenosine deaminase, decreased tumor growth and metastasis, increased interferon γ production, and enhanced the efficacy of antitumor therapies following combination regimens in animal models (anti-programmed cell death 1 protein vs anti-programmed cell death 1 protein plus PBF-1129 treatment hazard ratio = 11.74 [95% confidence interval = 3.35 to 41.13], n = 10, P < .001, 2-sided F test). In patients with non-small cell lung cancer, PBF-1129 was well tolerated, with no dose-limiting toxicities; demonstrated pharmacologic efficacy; modulated the adenosine generation system; and improved antitumor immunity. CONCLUSIONS: Data identify A2B-adenosine receptor as a valuable therapeutic target to modify metabolic and immune tumor microenvironment to reduce immunosuppression, enhance the efficacy of immunotherapies, and support clinical application of PBF-1129 in combination therapies.

An Iridium/Aluminum Cooperative Strategy for the ß-C(sp3 )-H Borylation of Saturated Cyclic Amines.

Despite the widespread success in the functionalization of C(sp2 )-H bonds, the deliberate functionalization of C(sp3 )-H bonds in a highly site- and stereoselective manner remains a longstanding challenge. Herein, we report an iridium/aluminum cooperative catalytic system that enables the ß-selective C-H borylation of saturated cyclic amines and lactams. Furthermore, we have accomplished an enantioselective variant using binaphthol-derived chiral aluminum catalysts to forge C-B bonds with high levels of stereocontrol. Computational studies suggest that the formation of a Lewis pair with the substrates is crucial to lower the energy of the transition state for the rate-determining reductive elimination step.

The Epidermal Environment's Influence on the Dermal Environment in Response to External Stress.

INTRODUCTION: The outermost layer of the skin, the epidermis, is directly exposed to external stress (e.g., irradiation, allergens, and chemicals). Changes in epidermal conditions/environment in response to this stress could also influence conditions of the dermis, located directly beneath the epidermis. Yet, whether/how any epidermal environment changes in response to external stress affect dermal functions has not been completely clarified. METHODS: We employed ultraviolet irradiation B (UVB) (which hardly reaches the dermis) as a model of external stress. Human keratinocytes and human dermal fibroblasts were treated with UVB and conditioned medium of keratinocytes exposed to UVB (UVB-keratinocyte-M), respectively. We assessed (1) inflammatory cytokines and lipid mediators in keratinocytes; (2) matrix metalloprotease (MMP) levels and collagen degradation in fibroblasts; (3) ex vivo organ-cultured human skin was treated with UVB. MMP levels and collagen degradation were examined; (4) test whether the mixture of agent (agent cocktail) consisting of dihydroceramide, niacin amide, resveratrol, glucosyl hesperidin, and phytosterol ester that has been shown to improve skin barrier integrity can mitigate influence of UVB in skin; and (5) a pilot one-arm human clinical test to assess efficacy of formulation containing agent cocktail on stratum corneum hydration, skin elasticity, and wrinkle index. RESULTS: Inflammatory-cytokine and -lipid mediator production were increased in cultured keratinocytes treated with UVB, while matrix MMP-1, -3, and -9 production and collagen degradation were increased in fibroblasts incubated with UVB-keratinocyte-M. mRNA expression of COL1A1 (that codes type 1 collagen) levels was decreased in fibroblasts incubated with UVB-keratinocyte-M. The study using ex vivo organ-cultured human skin showed both MMP-1 and MMP-9 expression were increased in both epidermis and dermis and increased dermal collagen degradation following UVB irradiation. Increased MMP production and collagen degradation were attenuated by application of an agent cocktail. Finally, a pilot clinical study demonstrated that the formulation containing our agent cocktail likely has the ability to improve skin hydration, increase skin elasticity, and reduce the appearance of wrinkles. CONCLUSION: Epidermal changes in epidermal environment and conditions in response to external stress affect dermal conditions, and these negative effects of external stress on various skin layers can be pharmacologically mitigated.

Minimum required length of orthodontic microimplant: a numerical simulation and clinical validation.

INTRODUCTION: This study aimed to determine the minimum required length of microimplants (MIs) to prevent excessive micromotion during MI healing that can lead to MI failure. METHODS: Hypothesizing that the implantation depth of MI in cancellous bone (IDcancel) is the key to the control of micromotion during MI healing, we numerically investigated the minimum IDcancel required to maintain MI micromotion to below the threshold (30 µm) that would threaten MI survival. Twenty MI and bone models were built using MIs of 4 lengths and bone specimens with 5 different cortical bone thicknesses to create IDcancel in the 0.5-5.5 mm. Then, applying a horizontal force of 1.5 N on the MI head, we calculated the micromotion (peak and average MI micromotions) and determined the minimum IDcancel. A clinical test was performed to verify the numerical result by placing 160 MIs in the posterior maxilla and mandible. RESULTS: A strong correlation (r2= 0.694) was found to exist between IDcancel and MI micromotion. A minimum of 2.5 mm of IDcancel was needed to maintain the level of MI micromotion (peak micromotion) <30 µm threshold. The 6-month survival rate of MI was strongly correlated with IDcancel (r2= 0.744) and decreased sharply when IDcancel was ≤2 mm. CONCLUSIONS: The minimum lengths of MIs to provide the minimum IDcancel of 2.5 mm required to promote successful MI healing in the posterior maxilla and mandible are 5.2 and 6.5 mm, respectively.

Morus alba L. root decreases melanin synthesis via sphingosine-1-phosphate signaling in B16F10 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. has long been used for beauty in many Asian countries and regions, including anti-aging and hyperpigmentation. AIM OF THE STUDY: This study aimed at the inhibitory effect of Morus alba L. root on melanogenesis in B16F10 melanoma cells and the mechanism involved. MATERIALS AND METHODS: This study evaluated the anti-melanogenic effect of Morus alba L. root extract (MAR) on B16F10 melanoma cells by assessing cell viability, melanin accumulation, cellular tyrosinase activity, intra/inter-cellular S1P levels, cellular S1P-related metabolic enzyme activity, and western blot analysis. In addition, the potential S1P lyase (S1PL) inhibitory constituents in MAR were identified by LC-MS/MS. RESULTS: Without affecting the viability of B16F10 melanoma cells, MAR inhibited intracellular tyrosinase activity in a dose-dependent manner, thereby reducing the accumulation of melanin. MAR also downregulated the expression level of MITF via activating the ERK signaling pathway. Furthermore, MAR increased the intra/inter-cellular S1P by inhibiting S1PL. Several compounds with inhibitory S1PL activity have been identified in MAR, such as mulberroside A and oxyresveratrol. CONCLUSIONS: The anti-melanogenic effects of MAR mainly involve promoting MITF degradation mediated via S1P-S1PR3-ERK signaling through increasing cellular S1P levels by inhibiting S1PL activity.

The Gangwon Obesity and Metabolic Syndrome Study: Methods and Initial Baseline Data.

Background: The prevalence of obesity has been continuously increasing, especially in rural areas of South Korea. Therefore, it is important to examine various genetic, behavioral, and environmental factors associated with obesity in these rural areas. The Korean Society for the Study of Obesity commenced a community-based prospective cohort study of the Gangwon area called the Gangwon Obesity and Metabolic Syndrome (GOMS) study to investigate longitudinal changes in the status of obesity and its related factors. Methods: A total of 317 adults 40-69 years of age were recruited from Hongcheon and Inje districts, Gangwon province, as part of the first wave of this cohort study. Information on participants' demographic, behavioral, psychological, dietary, and environmental factors and past medical histories were collected by self-administered questionnaires and interviewer-administered questionnaires. Anthropometric measurements, blood tests, and a hand grip strength test were performed, and skin keratin and stool samples were collected. Among the 317 enrolled subjects, two participants who did not have anthropometric data were excluded from the data analyses, resulting in an inclusion of a total of 315 participants. Results: The mean age of the 315 participants in the GOMS initial baseline survey was 58.5 years old, 87 of them were men, and the mean body mass index was 24.7±3.7 kg/m2. Among all participants, 48.9% had hypertension, 21.4% had diabetes mellitus (DM), 55.6% had dyslipidemia, and 46.0% had metabolic syndrome (MS). Both the prevalence rates of DM and MS were significantly higher in men. Conclusion: The first baseline survey of the GOMS study was initiated, and a more detailed analysis of respondents' data is expected to be continued. Further follow-up and additional recruitment will allow the investigation of risk factors and the etiology of obesity and its comorbidities in rural areas of Gangwon province.

Facile one-pot iodine gas phase doping on 2D MoS2/CuS FET at room temperature.

Electronic devices composed of semiconducting two-dimensional (2D) materials and ultrathin 2D metallic electrode materials, accompanying synergistic interactions and extraordinary properties, are becoming highly promising for future flexible and transparent electronic and optoelectronic device applications. Unlike devices with bulk metal electrode and 2D channel materials, devices with ultrathin 2D electrode and 2D channel are susceptible to chemical reactions in both channel and electrode surface due to the high surface to volume ratio of the 2D structures. However, so far, the effect of doping was primary concerned on the channel component, and there is lack of understanding in terms of how to modulate electrical properties of devices by engineering electrical properties of both the metallic electrode and the semiconducting channel. Here, we propose the novel, one-pot doping of the field-effect transistor (FET) based on 2D molybdenum disulfide (MoS2) channel and ultrathin copper sulfide (CuS) electrodes under mild iodine gas environment at room temperature, which simultaneously modulates electrical properties of the 2D MoS2channel and 2D CuS electrode in a facile and cost-effective way. After one-pot iodine doping, effective p-type doping of the channel and electrode was observed, which was shown through decreased off current level, improvedIon/Ioffratio and subthreshold swing value. Our results open up possibility for effectively and conveniently modulating electrical properties of FETs made of various 2D semiconductors and ultrathin contact materials without causing any detrimental damage.

Clinical relevance of postoperative proteinuria for prediction of early renal outcomes after kidney transplantation.

BACKGROUND: Proteinuria is associated with poor allograft and patient survival in kidney transplant recipients. However, the clinical relevance of spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) as predictors of renal outcomes during the early postoperative period following kidney transplantation (KT) has not been determined. METHODS: This single-center retrospective cohort study included 353 kidney transplant recipients who underwent KT between 2014 and 2017 and were followed up for more than 3 years. Among them, 186 and 167 recipients underwent living donor KT and deceased donor KT, respectively. The PCR and ACR were measured during the immediate postoperative period (within 7 days postoperatively), before discharge (2-3 weeks postoperatively), and 3-6 months postoperatively. RESULTS: The median age of the patients was 51 years (interquartile range, 43-59 years), and 62.9% were male. An immediate postoperative PCR of ≥1 mg/mg was associated with old age, diabetes mellitus, high systolic blood pressure, delayed graft function, and donor factors (deceased donor KT, old age, and high serum creatinine concentrations). The PCR and ACR 3 to 6 months posttransplant were inversely associated with the estimated glomerular filtration rate at 1 year posttransplant. Deceased donor KT recipients with immediate postoperative PCR of ≥3 mg/mg showed a greater incidence of delayed graft function and lower estimated glomerular filtration rate before discharge than those with immediate postoperative PCR of <3 mg/mg. CONCLUSION: Early postoperative proteinuria is a useful biomarker to predict early renal outcomes after KT.

Expert recommendations on the assessment and management of complications due to hyaluronic acid soft tissue filler injections in Asians.

BACKGROUND: The use of hyaluronic acid (HA) fillers for medical aesthetic purposes is increasing worldwide. Nonetheless, adverse events do occur because of patient-specific issues, injection technique, or product factors. It would be mandatory to consider cultural and anatomical features of Asians in preventing and managing the complications of HA injections. METHODS: Literature search of studies looking at current evidence and guidelines on the management of complications following HA filler injections in Asian patients was conducted. This was followed by an expert group discussion that was convened to reach consensus recommendations on the best clinical practices. RESULTS: The expert panel provided specific recommendations focusing on the safe use of soft tissue fillers in Asian patients, including early identification of adverse events and how to prevent and comprehensively manage these outcomes. CONCLUSIONS: Here, we provide consensus statements of Asian experts in dermatology, plastic surgery, ophthalmology, and aesthetic medicine mainly focusing on AEs with higher risk for Asians and can be used to guide physicians in treating Asian population.

Exogenous Ceramide Serves as a Precursor to Endogenous Ceramide Synthesis and as a Modulator of Keratinocyte Differentiation.

Since ceramide is a key epidermal barrier constituent and its deficiency causes barrier-compromised skin, several molecular types of ceramides are formulated in commercial topical agents to improve barrier function. Topical ceramide localizes on the skin surface and in the stratum corneum, but certain amounts of ceramide penetrate the stratum granulosum, becoming precursors to endogenous ceramide synthesis following molecular modification. Moreover, exogenous ceramide as a lipid mediator could modulate keratinocyte proliferation/differentiation. We here investigated the biological roles of exogenous NP (non-hydroxy ceramide containing 4-hydroxy dihydrosphingosine) and NDS (non-hydroxy ceramide containing dihydrosphingosine), both widely used as topical ceramide agents, in differentiated-cultured human keratinocytes. NDS, but not NP, becomes a precursor for diverse ceramide species that are required for a vital permeability barrier. Loricrin (late differentiation marker) production is increased in keratinocytes treated with both NDS and NP vs. control, while bigger increases in involucrin (an early differentiation marker) synthesis were observed in keratinocytes treated with NDS vs. NP and control. NDS increases levels of a key antimicrobial peptide (an innate immune component), cathelicidin antimicrobial peptide (CAMP/LL-37), that is upregulated by a ceramide metabolite, sphingosine-1-phosphate. Our studies demonstrate that NDS could be a multi-potent ceramide species, forming heterogenous ceramide molecules and a lipid mediator to enhance differentiation and innate immunity.

Euphorbia supina Extracts Block NADPH Oxidase-Mediated, Ceramide-Induced Apoptosis Initiated by Diesel Particulate Matter.

Air pollutants contribute to the development of diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary cancer, cardiovascular problems, and some skin diseases. We recently found that a major air pollutant, diesel particulate matter (DPM), induces apoptosis in human keratinocytes by increasing a proapoptotic lipid mediator, ceramide. DPM activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), which stimulates sphingomyelinase, leading to an increased conversion of sphingomyelin to ceramide. Interestingly, we characterized that although NOX is a reactive oxygen species (ROS) generator, the activation of sphingomyelinases by NOX is an ROS-independent mechanism. A Korean weed, prostrate spurge Euphorbia supina Rafin (ESR), has been used for centuries as a folk medicine to treat bronchitis, hepatitis, hemorrhage, and skin inflammation. Flavonoids, terpenes and tannins are enriched in ESR, and although ESR has proven antioxidative activity, its biological activities are largely unknown. Here, we investigate whether and how ESR protects keratinocytes against DPM-mediated apoptosis. We found that ESR-extracts (ESR-Ex) protect keratinocytes from DPM-induced apoptosis by inhibiting NOX activation in keratinocytes in response to DPM. We also demonstrated that ESR-Ex suppresses NOX activation via a blockage of the aryl hydrocarbon receptor (AhR) activation-mediated transcription of neutrophil cytosolic factor 1 (NCF1)/p47phox, a subunit of NOX. Our study reveals previously uncharacterized biological activity of ESR-Ex; i.e., its inhibition of Ahr and NOX activation. Thus, because the inhibition of NOX has already been developed to treat NOX-mediated diseases, including various types of cardiovascular diseases and cancers, initiated by air pollutants and because AhR activation contributes to the development of chronic inflammatory diseases, our study provides further advantages for the medical use of ESR.