Red clover (Trifolium pratense L.) extract inhibits ferroptotic cell death by modulating cellular iron homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Red clover (Trifolium pratense L.) is a traditional Chinese medicine and use as herbal medicine which has the effects of regulating menopausal symptoms, heart problem, inflammatory disease, psoriasis and cognitive deficits. In previous reported, the studies of red clover were mainly focused on clinical practice. the pharmacological functions of red clover not fully elucidated. AIM OF THE STUDY: To identify the molecules that regulate ferroptosis, we examined whether red clover (Trifolium pratense L.) extracts (RCE) affected ferroptosis induced by chemical treatment or cystine/glutamate antiporter (xCT) deficiency. MATERIALS AND METHODS: Cellular models for ferroptosis were induced by erastin/Ras-selectiv lethal 3 (RSL3) treatment or xCT deficiency in mouse embryonic fibroblasts (MEFs). Intracellular iron and peroxidized lipid levels were determined using Calcein-AM and BODIPY-C11 fluorescence dyes, respectively. Protein and mRNA were quantified by Western blot and real-time polymerase chain reaction, respectively. RNA sequencing analysis was performed on xCT-/- MEFs. RESULTS: RCE significantly suppressed ferroptosis induced by both erastin/RSL3 treatment and xCT deficiency. The anti-ferroptotic effects of RCE correlated to ferroptotic phenotypic changes such as cellular iron accumulation and lipid peroxidation in cellular ferroptosis models. Importantly, RCE affected levels of iron metabolism-related proteins including iron regulatory protein 1, ferroportin 1 (FPN1), divalent metal transporter 1, and transferrin receptor. RNA sequencing analysis of xCT-/- MEFs identified that expression of cellular defense genes was upregulated, while expression of cell death-related genes was downregulated, by RCE. CONCLUSION: RCE potently suppressed ferroptosis triggered both by erastin/RSL3 treatment and xCT deficiency by modulating cellular iron homeostasis. This is the first report that RCE has therapeutic potential in diseases associated with ferroptotic cell death, particularly ferroptosis induced by dysregulation of cellular iron metabolism.

Occupational differences in personal care product use and urinary concentration of endocrine disrupting chemicals by gender.

BACKGROUND: In most societies, women and men systematically differ in consumption of cosmetics and household products, which are interlinked with gendered norms and occupational segregation. We investigated the differences in personal care product (PCP) use and exposure to endocrine disrupting chemicals (EDCs) based on occupation and gender. METHODS: We utilized data from the first to third Korean National Environmental Health Survey analyzing 9218 participants aged 20-59 years engaged in their current occupation for ≥3 months. Frequent PCP use (≥once/week) and exposure to EDCs were analyzed by gender and occupation. We used least-square geometric means (LSGMs) of urinary concentrations of the five EDCs adjusted for covariates. RESULTS: Manual occupation was most common in men and no paid occupation was most frequent in women. In general, clerical, service, and sales workers showed the highest prevalence of frequent use of hair and body products. Women used body and makeup products more frequently than men. For all five EDCs, similarly, women showed higher urinary levels in all occupation groups. When stratified by gender, the differences in urinary concentration of EDCs across occupation groups were not observed in men. Among women, clerical, service, and sales workers showed higher bisphenol A (BPA) and mono-n-butyl phthalate (MnBP) levels than manual workers. CONCLUSIONS: Differentials in exposure to EDCs by occupation groups were not evident for men. Given the higher urinary concentration of EDCs in women compared to men, interventions to reduce the exposure to EDCs would need to focus on women, especially in clerical, service, and sales occupations.

Effects of auricular acupressure on sleep and pain in elderly people who have osteoarthritis and live in nursing homes: A randomized, single-blind, placebo-controlled trial.

OBJECTIVE: This study aimed to examine the effects of auricular acupressure (AA) on sleep and pain among elderly people with osteoarthritis who live in nursing homes. METHOD: It was a randomized, single-blinded, and placebo-controlled comparative pretest-posttest study that applied AA for eight weeks. The study was conducted among 52 elderly people, comprising an experimental group (n=26), and a control group (n=26). Polysomnography, actigraphy, the levels of melatonin and pressure pain threshold (PPT) were measured. The standardized measurement on sleep quality and pain was also used. RESULTS: Experimental group scores on sleep quality significantly improved as compared to those of the placebo control group. The polysomnography (sleep efficiency, sleep latency, awakening, stage 2 sleep) and the actigraphy (sleep efficiency, sleep latency, number of awakenings) were shown to be significant. The levels of melatonin significantly increased after terminating the intervention. The result of the pain (visual analogue scale) significantly reduced and the PPT significantly increased among the elderly in the experimental groups. CONCLUSIONS: AA can be used as an effective intervention to improve their sleep of the elderly living in nursing homes, and it can also reduce the pain.

Circulatory disease mortality among male medical radiation workers in South Korea, 1996-2019.

OBJECTIVE: The aim of this study was to investigate the relationship between occupational radiation exposure and circulatory disease (CD) mortality among medical radiation workers. METHODS: The study included 53 860 male diagnostic medical radiation workers enrolled in the National Dosimetry Registry (NDR) between 1996 and 2011 in South Korea. NDR data were linked with mortality data obtained from the national registry at the end of 2019. Observed CD mortality rates in this population were compared to those in the general population using the standardized mortality ratio (SMR). The relative risk (RR) for occupational history was estimated by use of internal comparisons, and the excess relative risk (ERR) was used to quantify the radiation dose-response relationship. RESULTS: A total of 320 deaths due to CD were identified among 53 860 male medical radiation workers. The SMR of CD was significantly lower among male workers than the general population. A linear dose-response model provided an estimated ERR per 100 mGy for CD [0.85, 95% confidence interval (CI) -0.11-1.82], ischemic heart disease (1.18, 95% CI -0.69-3.05), and cerebrovascular disease (0.23, 95% CI -0.48-0.94) with a 10-years lag, showing no statistical evidence of a radiation dose-response relationship. Additional adjustments for non-radiation factors did not affect the findings on occupational radiation risk for CD mortality. Sensitivity analyses excluding workers employed <1 year or who had exposure to a cumulative badge dose of ≥1 mSv showed similar results. CONCLUSIONS: Occupational radiation doses were non-significantly positively associated with CD mortality among male diagnostic medical radiation workers. However, cautious interpretation is needed due to the limitations of short follow-up.

Ameliorative Effect of Ginsenoside Rg6 in Periodontal Tissue Inflammation and Recovering Damaged Alveolar Bone.

Periodontal disease is a chronic disease with a high prevalence, and in order to secure natural materials to prevent oral diseases, new materials that protect periodontal tissue from inflammation are being sought. Genes were identified using real-time quantitative polymerase chain reaction (RT-qPCR), and proteins were confirmed using Western blot. Dichlorodihydrofluorescein diacetate (DCF-DA) analysis was used, and the antibacterial effects were confirmed through Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) analysis. To confirm this effect in vivo, Sprague-Dawley rats, in which periodontitis was induced using ligation or Lipopolysaccharide of Porphyromonas gingivalis (PG-LPS), were used. In vitro experiments using human periodontal ligament (HPDL) cells stimulated with PG-LPS showed that Ginsenoside Rg6 (G-Rg6) had anti-inflammatory, antibacterial, antioxidant, and osteoblast differentiation properties. In vivo, G-Rg6 was effective in Sprague-Dawley rats in which periodontitis was induced using ligation or PG-LPS. Therefore, Ginsenoside Rg6 shows potential effectiveness in alleviating periodontitis.

Correction: Data integration of National Dose Registry and survey data using multivariate imputation by chained equations.

[This corrects the article DOI: 10.1371/journal.pone.0261534.].

Underestimation of Radiation Doses by Compliance of Wearing Dosimeters among Fluoroscopically-Guided Interventional Medical Workers in Korea.

This study aimed to estimate the level of underestimation of National Dose Registry (NDR) doses based on the workers' dosimeter wearing compliance. In 2021, a nationwide survey of Korean medical radiation workers was conducted. A total of 989 medical workers who performed fluoroscopically-guided interventional procedures participated, and their NDR was compared with the adjusted doses by multiplying the correction factors based on the individual level of dosimeter compliance from the questionnaire. Ordinal logistic regression analysis was performed to identify the factors for low dosimeter wearing. Based on the data from the NDR, the average annual effective radiation dose was 0.95 mSv, while the compliance-adjusted dose was 1.79 mSv, yielding an 89% increase. The risks for low compliance with wearing a badge were significantly higher among doctors, professionals other than radiologists or cardiologists, workers not frequently involved in performing fluoroscopically-guided interventional procedures, and workers who did not frequently wear protective devices. This study provided quantitative information demonstrating that the NDR data may have underestimated the actual occupational radiation exposure. The underestimation of NDR doses may lead to biased risk estimates in epidemiological studies for radiation workers, and considerable attention on dosimetry wearing compliance is required to interpret and utilize NDR data.

PPARδ Inhibits Hyperglycemia-Triggered Senescence of Retinal Pigment Epithelial Cells by Upregulating SIRT1.

Emerging evidence shows that peroxisome proliferator-activated receptor delta (PPARδ) plays a pivotal role in cellular aging. However, its function in retinal disease processes such as hyperglycemia-associated diabetic retinopathy is unclear. Here, we demonstrate that PPARδ inhibits premature senescence of retinal pigment epithelial (RPE) cells induced by high glucose (HG) through SIRT1 upregulation. A specific ligand GW501516-activation of PPARδ suppressed premature senescence and production of reactive oxygen species induced by HG in ARPE-19 cells, a spontaneously arising human RPE cell line. These effects were accompanied by the regulation of the premature senescence-associated genes p53, p21, and SMP-30. Furthermore, GW501516-activated PPARδ almost completely abolished the effects of HG treatment on the formation of phosphorylated H2A histone family member X (γ-H2A.X) foci, a molecular marker of aging. These inhibitory effects of GW501516 were significantly reversed in ARPE-19 cells stably expressing small hairpin RNA targeting PPARδ. Notably, GW501516 significantly increased the mRNA and protein levels of SIRT1, indicating that GW501516-activated PPARδ exerted its beneficial effects through SIRT1. In addition, GW501516 restored HG-suppressed SIRT1 expression, corroborating the role of SIRT1 in the anti-senescence function of PPARδ. The effects of PPARδ on HG-induced premature senescence and the expression of the senescence-associated genes p53, p21, and SMP-30 were mimicked by the SIRT1 activator resveratrol, but blocked by the SIRT1 inhibitor sirtinol. Collectively, these results indicate that GW501516-activated PPARδ inhibits HG-triggered premature senescence of RPE cells by modulating SIRT1 signaling.

Data integration of National Dose Registry and survey data using multivariate imputation by chained equations.

INTRODUCTION: Data integration is the process of merging information from multiple datasets generated from different sources, which can obtain more information in comparison to to one data source. All diagnostic medical radiation workers were enrolled in National Dose Registry (NDR) from 1996 to 2011, linked with mortality and cancer registry data. (https://kdca.go.kr/) Survey was conducted during 2012-2013 using self-reported questionnaire on occupational radiation practices among diagnostic medical radiation workers. METHODS: Data integration of NDR and Survey was performed using the multivariate imputation by chained equations (MICE) algorithm. RESULTS: The results were compared by sex and type of job because characteristics of target variables for imputation depend on these variables. There was a difference between the observed and pooled mean for the frequency of interventional therapy for nurses due to different type of medical facility distribution between observed and completed data. Concerning the marital status of males and females, and status of pregnancy for females, there was a difference between observed and pooled mean because the distribution of the year of birth was different between the observed and completed data. For lifetime status of smoking, the percentage of smoking experience was higher in the completed data than in the observed data, which could be due to reasons, such as underreporting among females and the distribution difference in the frequency of drinking between the observed and completed data for males. CONCLUSION: Data integration can allow us to obtain survey information of NDR units without additional surveys, saving us time and costs for the survey.

PPARδ Activation Mitigates 6-OHDA-Induced Neuronal Damage by Regulating Intracellular Iron Levels.

Intracellular iron accumulation in dopaminergic neurons contributes to neuronal cell death in progressive neurodegenerative disorders such as Parkinson's disease. However, the mechanisms of iron homeostasis in this context remain incompletely understood. In the present study, we assessed the role of the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) in cellular iron homeostasis. We identified that PPARδ inhibited 6-hydroxydopamine (6-OHDA)-triggered neurotoxicity in SH-SY5Y neuroblastoma cells. PPARδ activation with GW501516, a specific PPARδ agonist, mitigated 6-OHDA-induced neuronal damage. Further, PPARδ activation also suppressed iron accumulation, which contributes to 6-OHDA-induced neuronal damage. PPARδ activation attenuated 6-OHDA-induced neuronal damage in a similar manner to that of the iron chelator deferoxamine. We further elucidated that PPARδ modulated cellular iron homeostasis by regulating expression of divalent metal transporter 1, ferroportin 1, and ferritin, but not transferrin receptor 1, through iron regulatory protein 1 in 6-OHDA-treated cells. Interestingly, PPARδ activation suppressed 6-OHDA-triggered generation of reactive oxygen species and lipid peroxides. The effects of GW501516 were abrogated by shRNA knockdown of PPARδ, indicating that the effects of GW501516 were PPARδ-dependent. Taken together, these findings suggest that PPARδ attenuates 6-OHDA-induced neurotoxicity by preventing intracellular iron accumulation, thereby suppressing iron overload-associated generation of reactive oxygen species and lipid peroxides, key mediators of ferroptotic cell death.

Reliability and Validity of a Nationwide Survey (the Korean Radiation Workers Study).

BACKGROUND: This study aimed to evaluate the reliability and validity of the self-administered questionnaire for Korean radiation workers. METHODS: From May 24, 2016, to June 30, 2017, 20,608 participants completed the questionnaire, providing information on sociodemographics, lifestyle, work history and practices, medical radiation exposure, and medical history, which was linked to the National Dose Registry and the National Cancer Registry. The validity of the questionnaire was evaluated using the responses of 20,608 workers, and reliability was evaluated using the responses of 3043 workers who responded to the survey twice. RESULTS: Responses concerning demographic characteristics and lifestyle showed reliability with a moderate-to-high agreement (kappa: 0.43-0.99), whereas responses concerning occupation and medical radiation exposure had a wide range of agreement (kappa: 0.05-0.95), possibly owing to temporal variability during employment. Regarding validity, responses to the question about the first year of employment had an excellent agreement with the national registry (intraclass correlation coefficient = 0.9); however, responses on cancer history had a wide range of agreement (kappa: 0.22-0.85). CONCLUSION: Although the reliability and validity of the questionnaire were not distinguished by demographic characteristics, they tended to be low among participants whose occupational radiation exposure was minimal. Overall, the information collected can be reliable for epidemiological studies; however, caution must be exercised when using information such as medical exposure and work practices, which are prone to temporal variability.

Peroxisome proliferator-activated receptor δ rescues xCT-deficient cells from ferroptosis by targeting peroxisomes.

Ferroptosis is a recently recognized process of cell death characterized by accumulation of iron-dependent lipid peroxides. Herein, we demonstrate that peroxisome proliferator-activated receptor δ (PPARδ) inhibits ferroptosis of mouse embryonic fibroblasts (MEFs) derived from cysteine/glutamate transporter (xCT)-knockout mice. Activation of PPARδ by the specific ligand GW501516 led to a dose-dependent decrease in ferroptotic cell death triggered by xCT deficiency, along with decreased levels of intracellular iron accumulation and lipid peroxidation. These effects of GW501516 were abolished by PPARδ-targeting small interfering RNA (siRNA) and the PPARδ inhibitor GSK0660, indicating that PPARδ inhibits xCT deficiency-induced ferroptosis. In addition, GW501516-activated PPARδ time- and dose-dependently upregulated catalase expression at both the mRNA and protein levels. This PPARδ-mediated upregulation of catalase was markedly attenuated in cells treated with PPARδ-targeting siRNA and GSK0660, indicating that expression of catalase is dependent on PPARδ. Consistently, the effects of GW501516 on ferroptosis of xCT-deficient MEFs were counteracted in the presence of 3-amino-1,2,4-triazole, a specific inhibitor of catalase, suggesting that catalase is essential for the effect of PPARδ on ferroptosis triggered by xCT deficiency. GW501516-activated PPARδ stabilized peroxisomes through catalase upregulation by targeting peroxisomal hydrogen peroxide-mediated lysosomal rupture, which led to ferroptosis of xCT-deficient MEFs. Collectively, these results demonstrate that PPARδ modulates ferroptotic signals in xCT-deficient MEFs by regulating catalase expression.

A comparison of meta-analysis results with and without adjustment for the healthy worker effect: cancer mortality among workers in the semiconductor industry.

OBJECTIVES: This study compared the results of meta-analysis with and without adjustment for the healthy worker effect on the association between working in the semiconductor industry and cancer mortality. METHODS: Six studies that reported standardized mortality ratios (SMRs) for cancers were selected for meta-analysis. Using a random-effects model, the SMR results from each study were combined for all cancers and leukemias to estimate the summary SMRs (95% confidence interval, CI). To adjust for the healthy worker effect, the relative standardized mortality ratio (rSMR=SMRx/SMRnot x) were calculated using observed and expected counts for the specific cause of interest (i.e., all cancers and leukemias) and the observed and expected counts for all other causes of mortality. Then, the rSMR results were combined to estimate the summary rSMRs (95% CIs). RESULTS: The SMRs for all causes of mortality among semiconductor industry workers ranged from 0.25 to 0.80, which reflects a significant healthy worker effect. A remarkable difference was found between the summary SMRs and the summary rSMRs. The summary SMR for all cancers was 0.70 (95% CI, 0.63 to 0.79) whereas the summary rSMR was 1.38 (95% CI, 1.20 to 1.59). The summary SMR for leukemia was 0.88 (95% CI, 0.72 to 1.07), and the summary rSMR was 1.88 (95% CI, 1.20 to 2.95). CONCLUSIONS: Our results suggest that adjustment for the healthy worker effect (i.e., rSMR) may be useful in meta-analyses of cohort studies reporting SMRs.

Estimation of the historical radiation dose of Korean radiation workers, 1961-1983.

Accurate dosimetry plays a key role in evaluating the radiation-induced health risks of radiation workers. The National Dose Registry in Korea contains the dose records of radiation workers in nuclear-related occupations since 1984. Thus, radiation doses for workers before 1984 are often sparse or missing. This study aimed to estimate the historical radiation dose before 1984 for radiation workers in Korea based on dose reconstruction models. The dose reconstruction models were derived from the nationwide self-administered questionnaire survey and the personal badge doses for workers in the cohort of the Korean Radiation Worker Study. The mean estimated annual doses between 1984 and 2016 from the dose reconstruction model were 4.67-0.6 mSv, which closely matched the reported doses of 4.51-0.43 mSv. The mean estimated annual doses between 1961 and 1983 based on the exposure scenarios developed by factors associated with radiation doses ranged from 11.08 to 4.82 mSv. The mean estimated annual doses of individuals in the cohort from 1961 to 1983 ranged from 11.15 to 4.88 mSv. Although caution needs to be exercised in the interpretation of these estimations due to uncertainty owed to the nature of extrapolation beyond the range of observed data, this study offers a sense of the radiation doses for workers during Korea's early period of radiation-related activities, which can be a useful piece of information for radiation-induced health risk assessments.

Cancer Risk After Radioactive Iodine Treatment for Hyperthyroidism: A Systematic Review and Meta-analysis.

Importance: Whether radioactive iodine (RAI) therapy for hyperthyroidism can increase cancer risk remains a controversial issue in medicine and public health. Objectives: To examine site-specific cancer incidence and mortality and to evaluate the radiation dose-response association after RAI treatment for hyperthyroidism. Data Sources: The Medline and Cochrane Library electronic databases, using the Medical Subject Headings terms and text keywords, and Embase, using Emtree, were screened up to October 2020. Study Selection: Study inclusion criteria were as follows: (1) inclusion of patients treated for hyperthyroidism with RAI and followed up until cancer diagnosis or death, (2) inclusion of at least 1 comparison group composed of individuals unexposed to RAI treatment (eg, the general population or patients treated for hyperthyroidism with thyroidectomy or antithyroid drugs) or those exposed to different administered doses of RAI, and (3) inclusion of effect size measures (ie, standardized incidence ratio [SIR], standardized mortality ratio [SMR], hazard ratio [HR], or risk ratio [RR]). Data Extraction and Synthesis: Two independent investigators extracted data according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Overall quality assessment followed the recommendations of United Nations Scientific Committee on the Effects of Atomic Radiation. The SIR and SMRs and the RRs and HRs were pooled using random-effects meta-analysis. Main Outcomes and Measures: Cancer incidence and mortality for exposure vs nonexposure to RAI therapy and by level of RAI administered activity. Results: Based on data from 12 studies including 479 452 participants, the overall pooled cancer incidence ratio was 1.02 (95% CI, 0.95-1.09) and the pooled cancer mortality ratio was 0.98 (95% CI, 0.92-1.04) for exposure vs nonexposure to RAI therapy. No statistically significant elevations in risk were observed for specific cancers except thyroid cancer incidence (SIR, 1.86; 95% CI, 1.19-2.92) and mortality (SMR, 2.22; 95% CI, 1.37-3.59). However, inability to control for confounding by indication and other sources of bias were important limitations of studies comparing RAI exposure with nonexposure. In dose-response analysis, RAI was significantly associated with breast and solid cancer mortality (breast cancer mortality, per 370 MBq: 1.35; P = .03; solid cancer mortality, per 370 MBq: 1.14; P = .01), based on 2 studies. Conclusions and Relevance: In this meta-analysis, the overall pooled cancer risk after exposure to RAI therapy vs nonexposure was not significant, whereas a linear dose-response association between RAI therapy and solid cancer mortality was observed. These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose.

Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 Cardiomyocytes.

Hypertrophy of myocytes has been implicated in cardiac dysfunctions affecting wall stress and patterns of gene expression. However, molecular targets potentially preventing cardiac hypertrophy have not been fully elucidated. In the present study, we demonstrate that upregulation of catalase by peroxisome proliferator-activated receptor δ (PPARδ) is involved in the anti-hypertrophic activity of PPARδ in angiotensin II (Ang II)-treated H9c2 cardiomyocytes. Activation of PPARδ by a specific ligand GW501516 significantly inhibited Ang II-induced hypertrophy and the generation of reactive oxygen species (ROS) in H9c2 cardiomyocytes. These effects of GW501516 were almost completely abolished in cells stably expressing small hairpin (sh)RNA targeting PPARδ, indicating that PPARδ mediates these effects. Significant concentration and time-dependent increases in catalase at both mRNA and protein levels were observed in GW501516-treated H9c2 cardiomyocytes. In addition, GW501516-activated PPARδ significantly enhanced catalase promoter activity and protein expression, even in the presence of Ang II. GW501516-activated PPARδ also inhibited the expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which are both marker proteins for hypertrophy. The effects of GW501516 on the expression of ANP and BNP were reversed by 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor. Inhibition or downregulation of catalase by 3-AT or small interfering (si)RNA, respectively, abrogated the effects of PPARδ on Ang II-induced hypertrophy and ROS generation, indicating that these effects of PPARδ are mediated through catalase induction. Furthermore, GW501516-activated PPARδ exerted catalase-dependent inhibitory effects on Ang II-induced hypertrophy by blocking p38 mitogen-activated protein kinase. Taken together, these results indicate that the anti-hypertrophic activity of PPARδ may be achieved, at least in part, by sequestering ROS through fine-tuning the expression of catalase in cardiomyocytes.

Peroxisome proliferator-activated receptor-δ-mediated upregulation of catalase helps to reduce ultraviolet B-induced cellular injury in dermal fibroblasts.

BACKGROUND: Previous studies suggested that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-δ plays an essential role in cellular responses against oxidative stress. OBJECTIVE: To investigate how PPAR-δ elicits cellular responses against oxidative stress in primary human dermal fibroblasts (HDFs) exposed to ultraviolet B (UVB). METHODS: The present study was undertaken in HDFs by performing real-time polymerase chain reaction, gene silencing, cytotoxicity and reporter gene assay, analyses for catalase and reactive oxygen species, and immunoblot analyses. RESULTS: The PPAR-δ activator GW501516 upregulated expression of catalase and this upregulation was attenuated by PPAR-δ-targeting siRNA. GW501516-activated PPAR-δ induced catalase promoter activity through a direct repeat 1 response element. Mutation of this response element completely abrogated transcriptional activation, indicating that this site is a novel type of PPAR-δ response element. In addition, GW501516-activated PPAR-δ counteracted the reductions in activity and expression of catalase induced by UVB irradiation. These recovery effects were significantly attenuated in the presence of PPAR-δ-targeting siRNA or the specific PPAR-δ antagonist GSK0660. GW501516-activated PPAR-δ also protected HDFs from cellular damage triggered by UVB irradiation, and this PPAR-δ-mediated reduction of cellular damage was reversed by the catalase inhibitor or catalase-targeting siRNA. These effects of catalase blockade were positively correlated with accumulation of reactive oxygen species in HDFs exposed to UVB. Furthermore, GW501516-activated PPAR-δ targeted peroxisomal hydrogen peroxide through catalase in UVB-irradiated HDFs. CONCLUSION: The gene encoding catalase is a target of PPAR-δ, and this novel catalase-mediated pathway plays a critical role in the cellular response elicited by PPAR-δ against oxidative stress.

Decaying Post-Seismic Deformation Observed on the Korean Peninsula Following the 2011 Tohoku-Oki Earthquake.

We investigated decaying post-seismic deformation observed on the Korean Peninsula associated with the 2011 Mw 9.0 Tohoku-Oki earthquake using Global Navigation Satellite System (GNSS). The GNSS velocity vectors were estimated in five periods from 2005 to 2019. A co-seismic offset of the Korean Peninsula caused by the 2011 earthquake was inversely proportional to epicentral distances. According to the temporal variations of two components (magnitude and direction) of the GNSS velocity vector with the epicentral distance, the difference between the eastern and western regions for the two components becomes smaller over time. For approximately nine years after the 2011 event, the direction for the crustal movement in South Korea showed a recovery pattern returning to the pre-earthquake motion. In addition, the recovery patterns of the crustal movement were observed differently with the regional geologic structure (e.g., the crustal thickness) and each period. Our estimates of the decay in post-seismic deformation of the Korean Peninsula suggest that post-seismic relaxation will be complete within 5-20 years after the 2011 earthquake. The results suggest that the crustal movement on the Korean Peninsula is gradually recovering to its pre-earthquake motion.

Occupational radiation exposure and cancer incidence in a cohort of diagnostic medical radiation workers in South Korea.

OBJECTIVES: We investigated the association between protracted low-dose ionising radiation and the risk of cancer in medical radiation workers, the largest group of workers with occupational radiation exposures. METHODS: Data of all South Korean diagnostic medical radiation workers enrolled at the National Dose Registry during 1996-2011 were merged with the death and cancer incidence data until 31 December 2017. SIRs, relative risks and excess relative risks (ERRs) for cancer were calculated to quantify the radiation dose-response relationship using Poisson regression models. RESULTS: A total of 3392 first primary cancer cases were identified among 93 920 diagnostic medical radiation workers. The mean cumulative badge dose in the cohort was 7.20 mSv. The ERRs for solid cancer with a 5-year lag and haematopoietic cancers with a 2-year lag for all workers were 0.15 per 100 mGy (95% CI -0.20 to 0.51) and 0.09 per 100 mGy (95% CI -2.02 to 2.20), respectively. The ERRs for cancers did not significantly vary by job title, different lag years or after excluding thyroid and lung cancers. Sensitivity analyses restricted to workers employed for at least 1 year, or who were employed in or after 1996, or who had exposure to a cumulative badge dose of 1 mSv or more showed similar results. CONCLUSIONS: Occupational radiation doses were not significantly associated with cancer incidence among South Korean diagnostic medical radiation workers. However, cautious interpretation of ERRs is needed due to the limitations of short follow-up and low cumulative radiation doses.