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.

Interventional radiologists have a higher rate of chromosomal damage due to occupational radiation exposure: a dicentric chromosome assay.

OBJECTIVES: There are growing concerns regarding radiation exposure in medical workers who perform interventional fluoroscopy procedures. Owing to the nature of certain interventional procedures, workers may be subjected to partial-body radiation exposure that is high enough to cause local damage. We aimed to investigate the level of radiation exposure in interventional radiologists in South Korea by performing cytogenetic biodosimetry, particularly focusing on partial-body exposure. METHODS: Interventional radiologists (n = 52) completed a questionnaire, providing information about their work history and practices. Blood samples were collected and processed for a dicentric chromosome assay. We determined Papworth's U-value to assess the conformity of dicentrics with the Poisson distribution to estimate the partial-body exposures of the radiologists. RESULTS: Radiologists had a higher number of dicentrics than the normal population and industrial radiographers. Indeed, subjects with a U-value of > 1.96, an indicator of heterogeneous exposure, were observed more frequently; 4.67 ± 0.81% of their body was irradiated at an average dose of 4.64 ± 0.67 Gy. Logistic regression analysis revealed that the total duration of all interventional procedures per week was associated with partial-body exposure levels. CONCLUSIONS: Our findings suggest that interventional radiologists had greater chromosomal damages than those in other occupational groups, and their partial-body exposure levels might be high enough to cause local damage. Use of special dosimeters to monitor partial-body exposure, as well as restricting the time and frequency of interventional procedures, could help reduce occupational radiation exposure. KEY POINTS: • Interventional radiologists had a higher number of dicentrics than the normal population and industrial radiographers. • The level of partial-body exposure of interventional radiologists might be high enough to cause occupational local damage such as a skin cancer in fingers. • Restricting the duration and frequency of interventional procedures might be helpful in reducing occupational radiation exposure.

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.

Lifetime cancer risks from occupational radiation exposure among workers at interventional radiology departments.

PURPOSE: Interventional medical radiation workers represent an under-studied population worldwide, although they receive relatively high occupational radiation doses. This study aimed to estimate the lifetime cancer risk from occupational radiation exposure among workers at interventional radiology departments. METHODS: A field survey of interventional medical workers in nationwide branches of the Korean Society of Interventional Radiology was conducted in 2017. Organ-specific radiation doses were estimated using national dose registry data and conversion coefficients provided by the International Commission on Radiological Protection. Lifetime attributable risk (LAR) and lifetime fractional risk (LFR) were calculated based on realistic exposure scenarios using a radiation risk assessment tool. RESULTS: LARs from occupational radiation exposure until the age of retirement for all cancers combined were 338 (90.3-796.1), 121 (33.5-288.7), and 156 (41.1-390.6) per 100,000 individuals for male radiologists, male radiologic technologists, and female nurses, respectively. LFR for all cancers combined ranged from 0.22% (0.06-0.53) to 0.63% (0.17-1.47). Regarding the organ site, the highest LAR and LFR among all groups were observed for thyroid cancer. CONCLUSION: This study provides timely evidence of potential cancer burden from the current levels of occupational radiation exposure among workers at interventional radiology departments. The risks varied by occupational groups, and workers, particularly interventional radiologists, need to be carefully monitored for radiation.

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.

Peripheral Nerve-Derived Stem Cell Spheroids Induce Functional Recovery and Repair after Spinal Cord Injury in Rodents.

Stem cell therapy is one of the most promising candidate treatments for spinal cord injury. Research has shown optimistic results for this therapy, but clinical limitations remain, including poor viability, engraftment, and differentiation. Here, we isolated novel peripheral nerve-derived stem cells (PNSCs) from adult peripheral nerves with similar characteristics to neural-crest stem cells. These PNSCs expressed neural-crest specific markers and showed multilineage differentiation potential into Schwann cells, neuroglia, neurons, and mesodermal cells. In addition, PNSCs showed therapeutic potential by releasing the neurotrophic factors, including glial cell-line-derived neurotrophic factor, insulin-like growth factor, nerve growth factor, and neurotrophin-3. PNSC abilities were also enhanced by their development into spheroids which secreted neurotrophic factors several times more than non-spheroid PNSCs and expressed several types of extra cellular matrix. These features suggest that the potential for these PNSC spheroids can overcome their limitations. In an animal spinal cord injury (SCI) model, these PNSC spheroids induced functional recovery and neuronal regeneration. These PNSC spheroids also reduced the neuropathic pain which accompanies SCI after remyelination. These PNSC spheroids may represent a new therapeutic approach for patients suffering from SCI.

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.

Rosiglitazone-dependent dissociation of HuR from PPAR-γ regulates adiponectin expression at the posttranscriptional level.

Peroxisome proliferator-activated receptor (PPAR)-γ has been implicated as a key player in the regulation of adiponectin levels via both transcriptional and posttranscriptional mechanisms. Herein, we show that PPAR-γ interacts with human antigen R (HuR) and that the PPAR-γ-HuR complex dissociates following activation of PPAR-γ by rosiglitazone, a specific ligand of PPAR-γ. This rosiglitazone-dependent dissociation of HuR from PPAR-γ leads to nucleocytoplasmic shuttling of HuR and its binding to the 3'-UTR of adiponectin mRNA. PPAR-γ with H321A and H447A double mutation (PPAR-γH321/447A), a mutant lacking ligand-binding activity, impaired HuR dissociation from the PPAR-γ-HuR complex, resulting in reduced nucleocytoplasmic shuttling, even in the presence of rosiglitazone. Consequently, rosiglitazone up-regulated adiponectin levels by modulating the stability of adiponectin mRNA, whereas these effects were abolished by HuR ablation or blocked in cells expressing the PPAR-γH321/447A mutant, indicating that the interaction of PPAR-γ and HuR is a critical event during adiponectin expression. Taken together, the findings demonstrate a novel mechanism for regulating adiponectin expression at the posttranscriptional level and suggest that ligand-mediated activation of PPAR-γ to interfere with interaction of HuR could offer a therapeutic strategy for inflammation-associated diseases that involve decreased adiponectin mRNA stability.-Hwang, J. S., Lee, W. J., Hur, J., Lee, H. G., Kim, E., Lee, G. H., Choi, M.-J., Lim, D.-S., Paek, K. S., Seo, H. G. Rosiglitazone-dependent dissociation of HuR from PPAR-γ regulates adiponectin expression at the posttranscriptional level.

Occupational radiation exposure and morbidity of circulatory disease among diagnostic medical radiation workers in South Korea.

OBJECTIVES: We investigated the association between low-dose external occupational radiation exposure and circulatory disease morbidity among diagnostic medical radiation workers. METHODS: A cohort of 11 500 diagnostic medical radiation workers was linked with the National Dosimetry Registry data and the National Health Insurance Service data. Relative risks (RRs) were calculated to explore the association between occupational factors and circulatory disease morbidity, and excess relative risks per 100 milligray (ERR/100 mGy) were estimated to quantify the radiation dose-response relationship. RESULTS: Overall, there were 2270 cases of circulatory diseases during 93 696 person-years of observation (average follow-up=8.1 years). RRs for hypertension were significantly increased for individuals who started working before 2000 compared with those who started in 2005 and later. ERR/100 mGy for all circulatory diseases was 0.14 (95% CI -0.57 to 0.99). Radiation risks of cerebrovascular diseases and ischaemic heart disease were non-significantly increased with estimates of individual cumulative doses to the heart (ERR/100 mGy=3.10 (-0.75 to 11.59) and 1.22 (-0.71 to 4.73), respectively). However, ERR estimates were generally more strongly positive for female versus male workers and for younger workers versus more than 50-year-old workers. CONCLUSIONS: This study provides little evidence in support of a positive association between occupational radiation exposure and the overall risk of circulatory disease over a short follow-up period among medical radiation workers in South Korea. However, significantly increased RR with earlier year first worked, elevated ERR in female workers and young workers should be further followed up.

Suicide deaths among diagnostic medical radiation workers in South Korea, 1996-2017.

OBJECTIVES: Suicide is a leading cause of death in the working-age population. We investigated suicide mortality among diagnostic medical radiation workers in relation to their demographic and occupational factors in South Korea. METHODS: The study population consisted of all diagnostic medical radiation workers enrolled in the National Dosimetry Registry from 1996 to 2011. The registry data were linked with mortality data through the end of 2017. We calculated age-standardised suicide rates, standardised mortality ratios (SMRs) and rate ratios (RRs) by demographic and occupational factors. RESULTS: A total of 207 suicides were identified among 94 367 medical radiation workers, exhibiting a suicide rate of 14.0 per 100 000 person-years. Compared with the general population, suicide rates were lower for both male and female workers (SMR 0.49, 95% confidence interval (CI) 0.42 to 0.57; SMR 0.54, 95% CI 0.41 to 0.70, respectively). Similarly, decreased SMRs were observed across job titles and other work-related factors. However, a shorter duration of employment was positively associated with RRs for suicide; risks were 2.74 (95% CI 1.56 to 4.81) and 4.66 (95% CI 1.53 to 14.20) times higher in male and female workers with less than 1 year of employment, respectively, than in those with at least 10 years of employment. CONCLUSIONS: Diagnostic medical radiation workers in South Korea showed lower suicide rates than in the general population. However, a shorter duration of employment was associated with higher risk of suicide. Suicide prevention efforts could target workers engaged in short-term employment.

Ginsenoside Re Mitigates 6-Hydroxydopamine-Induced Oxidative Stress through Upregulation of GPX4.

Ginsenosides are active components found abundantly in ginseng which has been used as a medicinal herb to modify disease status for thousands of years. However, the pharmacological activity of ginsenoside Re in the neuronal system remains to be elucidated. Neuroprotective activity of ginsenoside Re was investigated in SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) to induce cellular injury. Ginsenoside Re significantly inhibited 6-OHDA-triggered cellular damage as judged by analysis of tetrazolium dye reduction and lactose dehydrogenase release. In addition, ginsenoside Re induced the expression of the antioxidant protein glutathione peroxidase 4 (GPX4) but not catalase, glutathione peroxidase 1, glutathione reductase, or superoxide dismutase-1. Furthermore, upregulation of GPX4 by ginsenoside Re was mediated by phosphoinositide 3-kinase and extracellular signal-regulated kinase but not by p38 mitogen-activated protein kinase or c-Jun N-terminal kinase. Ginsenoside Re also suppressed 6-OHDA-triggered cellular accumulation of reactive oxygen species and peroxidation of membrane lipids. The GPX4 inhibitor (1S,3R)-RSL3 reversed ginsenoside Re-mediated inhibition of cellular damage in SH-SY5Y cells exposed to 6-OHDA, indicating that the neuronal activity of ginsenoside Re is due to upregulation of GPX4. These findings suggest that ginsenoside Re-dependent upregulation of GPX4 reduces oxidative stress and thereby alleviates 6-OHDA-induced neuronal damage.

Taurine and Ginsenoside Rf Induce BDNF Expression in SH-SY5Y Cells: A Potential Role of BDNF in Corticosterone-Triggered Cellular Damage.

This study shows that taurine and ginsenoside Rf act synergistically to increase the expression of brain-derived neurotrophic factor (BDNF) in SH-SY5Y human neuroblastoma cells in a dose- and time-dependent manner. The increase of BDNF mRNA by taurine and ginsenoside Rf was markedly attenuated by inhibitors of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. In addition, taurine and ginsenoside Rf protected cells from corticosterone-induced BDNF suppression and reduced cell viability and lactate dehydrogenase release. The results from this study showed that combined treatment with both taurine and ginsenoside Rf enhanced BDNF expression and protected cells against corticosterone-induced damage.

Activation of peroxisome proliferator-activated receptor delta suppresses BACE1 expression by up-regulating SOCS1 in a JAK2/STAT1-dependent manner.

Neuronal expression of beta-secretase 1 (BACE1) has been implicated in the progression of Alzheimer's disease. However, the mechanisms that regulate BACE1 expression are unclear. Here, we show that peroxisome proliferator-activated receptor delta (PPARδ) decreases BACE1 expression by up-regulating suppressor of cytokine signaling 1 (SOCS1) in SH-SY5Y neuroblastoma cells. The activation of PPARδ by GW501516, a specific PPARδ agonist, inhibited expression of BACE1. This effect was abrogated by shRNA-mediated knockdown of PPARδ and by treatment with the PPARδ antagonist GSK0660, indicating that PPARδ is involved in GW501516-mediated suppression of BACE1 expression. On the other hand, GW501516-activated PPARδ induced expression of SOCS1, which is a negative regulator of cytokine signal transduction, at the transcriptional level by binding to a PPAR response element in its promoter. This GW501516-mediated induction of SOCS1 expression led to down-regulation of BACE1 expression via inactivation of signal transducer and activator of transcription 1. GW501516-activated PPARδ suppressed the generation of neurotoxic amyloid beta (Aß) in accordance with the decrease in BACE1 expression. Taken together, these results indicate that PPARδ attenuates BACE1 expression via SOCS1-mediated inhibition of signal transducer and activator of transcription 1 signaling, thereby suppressing BACE1-associated generation of neurotoxic Aß.

Increasing risk of uterine cervical cancer among young Japanese women: Comparison of incidence trends in Japan, South Korea and Japanese-Americans between 1985 and 2012.

In Japan, cervical cancer incidence has increased since the late 1990s especially among young women, despite a decreasing trend in most developed countries. Here, we examined age, period and birth cohort trends in cervical cancer incidence rates from 1985 to 2012. Incidence rates were ascertained using three population-based cancer registries and analyzed using Joinpoint regression and age-period-cohort models. We compared the findings in Japan to trends among Japanese-Americans in the Surveillance, Epidemiology, and End Results Registries and among women in South Korea using the Korea Central Registry. Age-standardized incidence rates in Japan decreased by 1.7% per year (95% confidence interval - 3.3%, 0.0%) until 1997 and thereafter increased by 2.6% per year (1.1%, 4.2%). Incidence rates increased among women under age 50, were stable among women aged 50-54, and decreased or remained stable among women aged 55 and over. The age-standardized incidence rate ratio by birth cohort showed a U-shaped pattern with the lowest rates in women born in the late 1930s and 1940s. In comparison, women born before 1920 and after 1970 had about double the incidence. Increasing risk in recent birth cohorts was not evident in Japanese-American or South Korean women. The trends in Japan may be attributable to increasing prevalence of human papillomavirus (HPV) infection among young women. Screening and vaccination have been shown to be highly effective and would help reverse these trends.

Thyroid cancer risks among medical radiation workers in South Korea, 1996-2015.

BACKGROUND: Thyroid cancer rates, especially among children, are known to be increased by radiation exposure. However, little is known about the impact of chronic low-dose radiation exposure on thyroid cancer risk in adulthood. This study examined radiation effects on thyroid cancer rates as well as an overall evaluation of thyroid cancer risk among medical radiation workers. METHODS: Data on all diagnostic medical radiation workers enrolled in the national dosimetry registry between 1996 and 2011 were linked with the cancer registry data through 2015. Standardized incidence ratios (SIRs) were used to compare the observed cancer incidence rates in this population to those for the general population while internal comparisons were used to estimate relative risks (RRs) for occupational history and excess relative risks (ERRs) were used to quantify the radiation dose-response relationship. RESULTS: Overall, 827 thyroid cancer cases were reported among 93,922 medical radiation workers. Thyroid cancer SIRs were significantly higher than expected for both men (SIR 1.72, 95% confidence interval [CI] 1.53 to 1.91) and women (SIR 1.18, 95% CI 1.08 to 1.28). However, RRs for thyroid cancer by job title and duration of employment showed no particular pattern among diagnostic medical radiation workers. There were no indications of a significant dose effect on thyroid cancer rates for either men (ERR/100 mGy 0.07, 95% CI -0.38 to 0.53) or women (ERR/100 mGy -0.13, 95% CI -0.49 to 0.23). The findings were similar for different job titles or when limited to workers employed for at least one year. CONCLUSIONS: While thyroid cancer incidence rates among Korean medical radiation workers were somewhat higher than those in the general population, there was no significant evidence that this increase was associated with occupational radiation dose. Additional follow-up together with consideration of other risk factors should provide useful information on thyroid cancer rates in this cohort.

A Smart Recommender Based on Hybrid Learning Methods for Personal Well-Being Services.

The main focus of the paper is to propose a smart recommender system based on the methods of hybrid learning for personal well-being services, called a smart recommender system of hybrid learning (SRHL). The essential health factor is considered to be personal lifestyle, with the help of a critical examination of various disciplines. Integrating the recommender system effectively contributes to the prevention of disease, and it also leads to a reduction in treatment cost, which contributes to an improvement in the quality of life. At the same time, there exist various challenges within the recommender system, mainly cold start and scalability. To effectively address the inefficiencies, we propose combined hybrid methods in regard to machine learning. The primary aim of this learning method is to integrate the most effective and efficient learning algorithms to examine how combined hybrid filtering can help to improve the cold star problem efficiently in the provision of personalized well-being in regard to health food service. These methods include: (1) switching among content-based and collaborative filtering; (2) identifying the user context with the integration of dynamic filtering; and (3) learning the profiles with the help of processing and screening of reflecting feedback loops. The experimental results were evaluated by using three absolute error measures, providing comparable results with other studies relative to machine learning domains. The effects of using the hybrid learning method are gathered with the help of the experimental results. Our experiments also show that the hybrid method improves accuracy by 14.61% of the average error predicted in the recommender systems in comparison to the collaborative methods, which mainly focus on the computation of similar entities.

Activation of PPARδ attenuates neurotoxicity by inhibiting lipopolysaccharide-triggered glutamate release in BV-2 microglial cells.

Neuroinflammation-associated release of glutamate from activated microglia has been implicated in the progression of neurodegenerative diseases. However, the regulatory mechanisms underlying this glutamate release are poorly understood. Here, we show that peroxisome proliferator-activated receptor delta (PPARδ) modulates neurotoxicity by inhibiting glutamate release in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Activation of PPARδ by GW501516, a specific PPARδ agonist, inhibited glutamate release in BV-2 cells. This effect of GW501516 was significantly blocked by shRNA-mediated knockdown of PPARδ and by treatment with GSK0660, a specific PPARδ antagonist, indicating that PPARδ is associated with blockade of glutamate release. Additionally, GW501516-activated PPARδ suppressed generation of reactive oxygen species and expression of gp91phox, a functional subunit of NADPH oxidase 2, in BV-2 cells stimulated with LPS. The inhibitory effect of GW501516 on gp91phox expression and glutamate release was further potentiated in the presence of AG490, a specific inhibitor of janus kinase 2 (JAK2), leading to the inhibition of signal transducer and activator of transcription 1 (STAT1). By contrast, GW501516 upregulated the expression of suppressor of cytokine signaling 1 (SOCS1), an endogenous inhibitor of JAK2. Furthermore, neurotoxicity induced by conditioned media from LPS-stimulated BV-2 cells was significantly reduced when conditioned media from BV-2 cells treated with both LPS and GW501516 were used. These results indicate that PPARδ attenuates LPS-triggered neuroinflammation by enhancing SOCS1-mediated inhibition of JAK2/STAT1 signaling, thereby inhibiting neurotoxicity associated with glutamate release.

Ligand-activated interaction of PPARδ with c-Myc governs the tumorigenicity of breast cancer.

Peroxisome proliferator-activated receptor (PPAR) δ is a promising therapeutic target in metabolic and inflammatory disorders. However, its role in oncogenesis is controversial, and its therapeutic potential remains to be determined. In our study, we show that ligand-activated PPARδ forms a complex with the proto-oncogene product c-Myc. The interaction of PPARδ with c-Myc affected the transcriptional activity of c-Myc and the expression of its target genes. The PPARδ-dependent regulation of c-Myc activity was associated with decreased tumorigenicity in breast cancer cells. Administration of the PPARδ ligand GW501516 inhibited tumor growth in xenograft model mice bearing MDA-MB-231 cells stably expressing wild-type PPARδ, but not those expressing dominant-negative PPARδ, by interfering with c-Myc function through protein-protein interaction. Our results indicating that PPARδ forms an antitumorigenic complex with c-Myc in the presence of ligand suggest a potential role of PPARδ in breast cancer development.

Ligand-Activated Peroxisome Proliferator-Activated Receptor δ Attenuates Vascular Oxidative Stress by Inhibiting Thrombospondin-1 Expression.

Thrombospondin-1 (TSP-1) is implicated in vascular diseases associated with oxidative stress, such as abdominal aortic aneurysms, ischemia-reperfusion injury, and atherosclerosis. However, the regulatory mechanisms underlying TSP-1 expression are not fully elucidated. In this study, we found that peroxisome proliferator-activated receptor δ (PPARδ) inhibited oxidative stress-induced TSP-1 expression and migration in vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly attenuated hydrogen peroxide (H2O2)-induced expression of TSP-1 in VSMCs. Small interfering RNA-mediated knockdown of PPARδ and treatment with GSK0660, a selective PPARδ antagonist, reversed the effect of GW501516 on H2O2-induced expression of TSP-1, suggesting that PPARδ is associated with GW501516 activity. Furthermore, JNK (c-Jun N-terminal kinase), but not p38 and ERK (extracellular signal-regulated kinase), mediated PPARδ-dependent inhibition of TSP-1 expression in VSMCs exposed to H2O2. GW501516- activated PPARδ also reduced the H2O2-induced generation of reactive oxygen species, concomitant with inhibition of VSMC migration. In particular, TSP-1 contributed to the action of PPARδ in the regulation of H2O2-induced interleukin-1ß expression. These results suggest that PPARδ-modulated downregulation of TSP-1 is associated with reduced cellular oxidative stress, thereby inhibiting H2O2-induced pheno-typic changes in vascular cells.

Projected lifetime cancer risks from occupational radiation exposure among diagnostic medical radiation workers in South Korea.

BACKGROUND: Timely assessment of cancer risk from current radiation exposure among medical radiation workers can contribute to the development of strategies to prevent excessive occupational radiation exposure. The purpose of the present study is to estimate the lifetime risk of cancers induced by occupational radiation exposure among medical radiation workers. METHODS: Using estimated organ doses and the RadRAT risk assessment tool, the lifetime cancer risk was estimated among medical radiation workers who were enrolled in the Korean National Dose Registry from 1996 to 2011. Median doses were used for estimating the risk because of the skewed distribution of radiation doses. Realistic representative exposure scenarios in the study population based on sex, job start year, and occupational group were created for calculating the lifetime attributable risk (LAR) and lifetime fractional risk (LFR). RESULTS: The mean estimated lifetime cancer risk from occupational radiation exposure varied significantly by sex and occupational group. The highest LAR was observed in male and female radiologic technologists who started work in 1991 (264.4/100,000 and 391.2/100,000, respectively). Female workers had a higher risk of radiation-related excess cancer, although they were exposed to lower radiation doses than male workers. The higher LAR among women was attributable primarily to excess breast and thyroid cancer risks. LARs among men were higher than women in most other cancer sites. With respect to organ sites, LAR of colon cancer (44.3/100,000) was the highest in male radiologic technologists, whereas LAR of thyroid cancer (222.0/100,000) was the highest in female radiologic technologists among workers who started radiologic practice in 1991. Thyroid and bladder cancers had the highest LFR among radiologic technologists. CONCLUSIONS: Our findings provide an assessment of the potential cancer risk from occupational radiation exposure among medical radiation workers, based on current knowledge about radiation risk. Although the radiation-related risk was small in most cases, it varied widely by sex and occupational group, and the risk would be underestimated due to the use of median, rather than mean, doses. Therefore, careful monitoring is necessary to optimize radiation doses and protect medical radiation workers from potential health risks, particularly female radiologic technologists.