It remains controversial whether targeting tumour vasculature can improve radiotherapeutic efficacy. We report that radiation-induced endothelial-to-mesenchymal transition (EndMT) leads to tumour ...vasculature with abnormal SMA
NG2
pericyte recruitment during tumour regrowth after radiotherapy. Trp53 (but not Tgfbr2) deletion in endothelial cells (ECs) inhibited radiation-induced EndMT, reducing tumour regrowth and metastases with a high CD44v6
cancer-stem-cell (CSC) content after radiotherapy. Osteopontin, an EndMT-related angiocrine factor suppressed by EC-Trp53 deletion, stimulated proliferation in dormant CD44v6
cells in severely hypoxic regions after radiation. Radiation-induced EndMT significantly regulated tumour-associated macrophage (TAM) polarization. CXCR4 upregulation in radioresistant tumour ECs was highly associated with SDF-1
TAM recruitment and M2 polarization of TAMs, which was suppressed by Trp53 deletion. These EndMT-related phenomena were also observed in irradiated human lung cancer tissues. Our findings suggest that targeting tumour EndMT might enhance radiotherapy efficacy by inhibiting the re-activation of dormant hypoxic CSCs and promoting anti-tumour immune responses.
The carbon encapsulation of nanosized Pt cathode catalysts for ultra-low Pt loading proton exchange membrane fuel cells is an effective approach to enhance their stability and catalytic activity for ...the oxygen reduction reaction (ORR). However, the synthesis procedures for such a catalyst are delicate and cumbersome. Therefore, it is difficult to use such procedures for mass production. Here, we have developed a facile strategy for synthesizing carbon-encapsulated Pt nanoparticles supported on carbon nanofibers (CNFs) using a Pt-aniline complex. This strategy begins with applying a wet Pt-aniline complex coating to CNFs. Heat-treating the coated CNFs produced 3-4 nm-sized Pt nanoparticles that were uniformly coated with a layer of carbon on the CNF surface (Pt@CS/CNF). Compared to other carbon-coated Pt catalysts, the stability and catalytic activity of Pt@CS/CNF for the ORR are high owing to the robustness of the carbon shells that secure the Pt nanoparticles. In a unit cell test, the performance of Pt@CS/CNF heat-treated at 900 °C was almost maintained for 30 000 accelerated stability test cycles, showing a negligible voltage loss at an operating current density of 0.8 A cm
−2
.
Ultra-stable Pt cathode catalysts in ultra-low Pt loading proton exchange membrane fuel cells were synthesized by facile carbon encapsulation.
Background: The incidence and prevalence of endometriosis remain unclear due to diagnostic difficulties. Especially, there has been little information regarding the population-based epidemiology of ...endometriosis. The purpose of this study is to estimate the prevalence and incidence of endometriosis in Korea based on the health insurance claims data.Methods: This study is a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort, which correspond to approximately 1 million Korean populations from 2002 to 2013. Patients aged 15–54 years were selected, and the prevalence and incidence of endometriosis were estimated by time and age groups.Results: The age-adjusted prevalence rate of endometriosis also increased from 2.12 per 1,000 persons (95% confidence interval CI, 2.01–2.24) in 2002 to 3.56 per 1,000 persons (95% CI, 3.40–3.71) in 2013. The average adjusted incidence showed no statistically significant increase. However, the age-specific incidence of the 15–19 and 20–24 years age groups increased significantly from 0.24 and 1.29 per 1,000 persons in 2003 to 2.73 and 2.71 per 1,000 persons in 2013 (R2 = 0.93 and 0.77, P < 0.001), while the incidence rate of the age group 40–44 and 45–49 years decreased from 2.36 and 1.72 per 1,000 persons in 2003 to 0.81 and 0.27 per 1,000 persons in 2013 (R2 = 0.83 and 0.89, P < 0.001).Conclusion: The prevalence and incidence of endometriosis in Korean women were lower than that of previous reports in high-risk population studies. Furthermore, we found a significant increase in the diagnosis of endometriosis in younger age groups.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Radiation therapy is the mainstay in the treatment of lung cancer, and lung fibrosis is a radiotherapy-related major side effect that can seriously reduce patient's quality of life. Nevertheless, ...effective strategies for protecting against radiation therapy-induced fibrosis have not been developed. Hence, we investigated the radioprotective effects and the underlying mechanism of the standardized herbal extract PM014 on radiation-induced lung fibrosis. Ablative radiation dose of 75 Gy was focally delivered to the left lung of mice. We evaluated the effects of PM014 on radiation-induced lung fibrosis in vivo and in an in vitro model. Lung volume and functional changes were evaluated using the micro-CT and flexiVent system. Fibrosis-related molecules were evaluated by immunohistochemistry, western blot, and real-time PCR. A orthotopic lung tumour mouse model was established using LLC1 cells. Irradiated mice treated with PM014 showed a significant improvement in collagen deposition, normal lung volume, and functional lung parameters, and these therapeutic effects were better than those of amifostine. PM104 attenuated radiation-induced increases in NF-κB activity and inhibited radiation-induced p65 translocation, ROS production, DNA damage, and epithelial-mesenchymal transition. PM104 effectively alleviated fibrosis in an irradiated orthotopic mouse lung tumour model while not attenuating the efficacy of the radiation therapy by reduction of the tumour. Standardized herbal extract PM014 may be a potential therapeutic agent that is able to increase the efficacy of radiotherapy by alleviating radiation-induced lung fibrosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Adenomyosis is associated with female infertility worldwide. With improvements in imaging methods, such as pelvic magnetic resonance imaging, the diagnosis and treatment of adenomyosis have changed. ...This study aimed to evaluate the overall prevalence, incidence, and treatment trends of adenomyosis in South Korea using data from the Korean National Health Insurance Service Database (NHIS).
Data were collected from the Korean NHIS, a population-based complete enumeration database. A total of 678 641 women aged 11-55 years diagnosed with adenomyosis (N80.0 ICD-10 code) from the database from 2002 to 2016 were enrolled. After applying a one-year look-back method, 629 592 patients were analyzed to estimate the prevalence, incidence, and treatment trends of adenomyosis.
The overall prevalence during the study period was 3.86 per 1000 people. The prevalence of adenomyosis has increased from 1.42 per 1000 individuals in 2002 to 7.50 per 1000 individuals in 2016. The crude annual incidence rate of adenomyosis was 1.62 per 1000 people in 2003, which increased to 4.12 per 1000 people in 2016. In addition, the proportion of uterus-preserving surgeries in adenomyosis treatments has increased from 7.51% to 21.29% over 15 years.
The prevalence and incidence of adenomyosis in South Korea increased between 2002 and 2016. Furthermore, the proportion of uterus-preserving surgeries and progestin prescriptions for adenomyosis treatment has increased. We expect that our findings will raise awareness of the necessity for fertility preservation through earlier diagnosis and proper management of patients with adenomyosis.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lung fibrosis is a major side effect experienced by patients after lung cancer radiotherapy. However, effective protection strategies and underlying treatment targets remain unclear. In an effort to ...improve clinical outcomes, pharmacologic treatment of fibrosis is becoming increasingly popular; however, no ideal therapeutic strategy is yet available.
We used a mouse model to irradiate high focal (90 or 75 Gy) to 3-mm volume of the left lung. Lung tissues of mice were subjected to microarray, mRNA expression, and immunohistochemical analysis. Correlations of radiation (IR)-induced epithelial-mesenchymal transition (EMT) were validated in lung cell lines using appropriate treatments to activate or inhibit selected pathways.
The expression of Hsp27 was increased during IR-induced lung fibrosis in a mouse model. Inhibition of functional Hsp27 using shRNA and a synthetic small molecule inhibitor (J2) in lung cells alleviated IR-mediated EMT. The activation of NFkB pathways via direct interaction between Hsp27 and IkBα resulted in increased expressions of Twist, IL-1β, and IL-6 and facilitated IR-mediated EMT, which was identified as an underlying mechanism of Hsp27-mediated fibrosis after IR. J2 also inhibited IR-induced lung fibrosis in an orthotopic lung cancer model, and IR-induced lung fibrotic tissues from patients showed higher expression of Hsp27 than unirradiated lungs.
Collectively, IkBα-NFkB signaling activation by Hsp27, which resulted in the facilitation of Twist, IL1β, and IL6 expression, is involved in the EMT process that is tightly connected to the development of IR-induced lung fibrosis. Our findings also suggest that inhibition of Hsp27 has the potential to become a valuable therapeutic strategy for IR-induced lung fibrosis.
In this study, we investigated whether total saponin extract (TSE), ginsenoside Rb1, and Rb1 metabolite compound K, which are isolated from red ginseng, have antinociceptive effects on peripheral and ...central neuropathic pain (PNP and CNP, respectively). PNP and CNP were induced by tail nerve injury (TNI) at S1 and by contusive spinal cord injury (SCI) at T9 in male Sprague–Dawley rats, respectively. Two weeks after TNI or 4 weeks after SCI, pain‐induced rats were orally administered vehicle, TSE (50 mg/kg), Rb1 (12.5 mg/kg), compound K (7 mg/kg), or gabapentin (GBP, 60 mg/kg), and the antinociceptive effects were examined by von Frey filament, cold/warm water, and hot plate analyses. Allodynia and hyperalgesia were significantly alleviated by TSE, Rb1, and GBP 1 hr after drug administration. The immunohistochemistry and real‐time RT‐PCR results showed that the activation of microglia/astrocytes and the expression of inflammatory mediators such as Il‐1β, Il‐6, iNOS, and Cox‐2 were also significantly inhibited in L4‐L5 spinal cord of CNP‐induced rats 1 hr after drug administration. Furthermore, the antinociceptive effects of TSE and Rb1 were reversed by treatment with the estrogen receptor (ER) antagonist ICI182780. In particular, compound K also significantly alleviated both PNP and CNP. Therefore, our results indicate that TSE, Rb1, and compound K have potential antinociceptive effects against neuropathic pain that might be mediated through the ER.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background/Aims: Radiation-induced skin fibrosis is a common side effect of clinical radiotherapy. Our previous next-generation sequencing (NGS) study demonstrated the reduced expression of the ...regulatory α subunit of phosphatidylinositol 3-kinase (PIK3r1) in irradiated murine skin. Metformin has been reported to target the PIK3-FOXO3 pathway. In this study, we investigated the effects of metformin on radiation-induced skin fibrosis. Methods: Metformin was orally administered to irradiated mice. Skin fibrosis was analyzed by staining with H&E and Masson’s trichrome stain. The levels of cytokines and chemokines associated with fibrosis were analyzed by immunohistochemistry and quantitative RT-PCR. The roles of PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl and transfecting FOXO3 siRNA in NIH3T3 cells and mouse-derived dermal fibroblasts (MDF). Results: The oral administration of metformin significantly reduced radiation-induced skin thickening and collagen accumulation and significantly reduced the radiation-induced expression of FOXO3 in murine skin. Additionally, the overexpression of PIK3r1 reduced the radiation-induced expression of FOXO3, while FOXO3 silencing decreased the radiation-induced expression of TGFβ in vitro. Conclusions: The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1. Collectively, the data obtained in this study suggested that metformin could be a potent therapeutic agent for alleviating radiation-induced skin fibrosis.
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