Association Between Individual Air Pollution (PM10, PM2.5) Exposure and Adverse Pregnancy Outcomes in Korea: A Multicenter Prospective Cohort, Air Pollution on Pregnancy Outcome (APPO) Study.

BACKGROUND: Prenatal exposure to ambient air pollution is linked to a higher risk of unfavorable pregnancy outcomes. However, the association between pregnancy complications and exposure to indoor air pollution remains unclear. The Air Pollution on Pregnancy Outcomes research is a hospital-based prospective cohort research created to look into the effects of aerodynamically exposed particulate matter (PM)10 and PM2.5 on pregnancy outcomes. METHODS: This prospective multicenter observational cohort study was conducted from January 2021 to June 2023. A total of 662 women with singleton pregnancies enrolled in this study. An AirguardK® air sensor was installed inside the homes of the participants to measure the individual PM10 and PM2.5 levels in the living environment. The time-activity patterns and PM10 and PM2.5, determined as concentrations from the time-weighted average model, were applied to determine the anticipated exposure levels to air pollution of each pregnant woman. The relationship between air pollution exposure and pregnancy outcomes was assessed using logistic and linear regression analyses. RESULTS: Exposure to elevated levels of PM10 throughout the first, second, and third trimesters as well as throughout pregnancy was strongly correlated with the risk of pregnancy problems according to multiple logistic regression models adjusted for variables. Except for in the third trimester of pregnancy, women exposed to high levels of PM2.5 had a high risk of pregnancy complications. During the second trimester and entire pregnancy, the risk of preterm birth (PTB) increased by 24% and 27%, respectively, for each 10 µg/m3 increase in PM10. Exposure to high PM10 levels during the second trimester increased the risk of gestational diabetes mellitus (GDM) by 30%. The risk of GDM increased by 15% for each 5 µg/m3 increase in PM2.5 during the second trimester and overall pregnancy, respectively. Exposure to high PM10 and PM2.5 during the first trimester of pregnancy increased the risk of delivering small for gestational age (SGA) infants by 96% and 26%, respectively. CONCLUSION: Exposure to high concentrations of PM10 and PM2.5 is strongly correlated with the risk of adverse pregnancy outcomes. Exposure to high levels of PM10 and PM2.5 during the second trimester and entire pregnancy, respectively, significantly increased the risk of PTB and GDM. Exposure to high levels of PM10 and PM2.5 during the first trimester of pregnancy considerably increased the risk of having SGA infants. Our findings highlight the need to measure individual particulate levels during pregnancy and the importance of managing air quality in residential environment.

Smoothed quantile residual life regression analysis with application to the Korea HIV/AIDS cohort study.

BACKGROUND: The residual life of a patient with human immunodeficiency virus (HIV) is of major interest to patients and their physicians. While existing analyses of HIV patient survival focus mostly on data collected at baseline, residual life analysis allows for dynamic analysis based on additional data collected over a period of time. As survival times typically exhibit a right-skewed distribution, the median provides a more useful summary of the underlying distribution than the mean. In this paper, we propose an efficient inference procedure that fits a semiparametric quantile regression model assessing the effect of longitudinal biomarkers on the residual life of HIV patients until the development of dyslipidemia, a disease becoming more prevalent among those with HIV. METHODS: For estimation of model parameters, we propose an induced smoothing method that smooths nonsmooth estimating functions based on check functions. For variance estimation, we propose an efficient resampling-based estimator. The proposed estimators are theoretically justified. Simulation studies are used to evaluate their finite sample performances, including their prediction accuracy. We analyze the Korea HIV/AIDS cohort study data to examine the effects of CD4 (cluster of differentiation 4) cell count on the residual life of HIV patients to the onset of dyslipidemia. RESULTS: The proposed estimator is shown to be consistent and normally distributed asymptotically. Under various simulation settings, our estimates are approximately unbiased. Their variances estimates are close to the empirical variances and their computational efficiency is superior to that of the nonsmooth counterparts. Two measures of prediction performance indicate that our method adequately reflects the dynamic character of longitudinal biomarkers and residual life. The analysis of the Korea HIV/AIDS cohort study data shows that CD4 cell count is positively associated with residual life to the onset of dyslipidemia but the effect is not statistically significant. CONCLUSIONS: Our method enables direct prediction of residual lifetimes with a dynamic feature that accommodates data accumulated at different times. Our estimator significantly improves computational efficiency in variance estimation compared to the existing nonsmooth estimator. Analysis of the HIV/AIDS cohort study data reveals dynamic effects of CD4 cell count on the residual life to the onset of dyslipidemia.

Five-year recurrence pattern of mature cystic teratoma according to operation type in young women.

OBJECTIVE: To find cumulative recurrence rate and risk factors for recurrence in young women with mature cystic teratoma (MCT). METHODS: Patients aged 10-29 years with MCT confirmed by their first ovarian surgery between 2000 and 2018 were included in the study. To rule out residual lesions, only patients with no MCT-suspected lesions on imaging within 1 year after surgery were included in the study. Patients who had not undergone imaging tests from 1 year after surgery or had other findings on biopsy were excluded. RESULTS: The present study included 372 (84.2%) patients with cystectomy and 70 (15.8%) patients with oophorectomy. The 5-year cumulative recurrence rates for each patient group were 11.2% and 20.3%, respectively. The hazard rate of recurrence was higher in the oophorectomy group than the cystectomy group within 5 years after surgery. Large tumor size (hazard ratio [HR] 2.59; 95% confidence interval [CI] 1.11-6.08) and bilaterality (HR 2.65; 95% CI 1.27-5.52) were significant predictors of recurrence in the cystectomy group. CONCLUSION: The 5-year cumulative recurrence rate after surgery in young women with ovarian MCT was 11.2% in the cystectomy group and 20.3% in the oophorectomy group. Risk factors for recurrence after cystectomy were large tumor size and bilaterality.

Sequential Growth of Vertical Transition-Metal Dichalcogenide Heterostructures on Rollable Aluminum Foil.

Vertical van der Waals heterostructures (vdWhs), which are made by layer-by-layer stacking of two-dimensional (2D) materials, offer great opportunities for the development of extraordinary physics and devices such as topological superconductivity, robust quantum Hall phenomenon, electron-hole pair condensation, Coulomb drag, and tunneling devices. However, the size of vdWhs is still limited to the order of a few micrometers, which restricts the large-scale roll-to-roll processes for industrial applications. Herein, we report the sequential growth of a 14 in. vertical vdWhs on a rollable Al foil via chemical vapor deposition. By supplying chalcogen precursors to liquid transition-metal precursor-coated Al foils, we grew a wide range of individual 2D transition-metal dichalcogenide (TMD) films, including MoS2, VS2, ReS2, WS2, SnS2, WSe2, and vanadium-doped MoS2. Additionally, by repeating the growth process, we successfully achieved the layer-by-layer growth of ReS2/MoS2 and SnS2/ReS2/MoS2 vdWhs. The chemically inert Al native oxide layer inhibits the diffusion of chalcogen and metal atoms into Al foils, allowing for the growth of diverse TMDs and their vdWhs. The conductive Al substrate enables the effective use of vdWhs/Al as a hydrogen evolution reaction electrocatalyst with a transfer-free process. This work provides a robust route for the commercialization of 2D TMDs and their vdWhs at a low cost.

Prenatal Exposure to Alcohol, Tobacco, and Coffee: Associated Congenital Complications and Adverse Birth Outcomes.

A few studies to date have examined the association between prenatal exposure to alcohol, tobacco, and coffee, and congenital complications/adverse birth outcomes among South Korean populations. Thus, this study analyzed the data of 1675 Korean women with birth experience within the last 3 years for pregnancy-related health and nutritional behaviors and relative outcomes. During their pregnancies, 11.58% of the study population consumed alcohol at least once, 1.43% drank throughout all three trimesters, 1.13% smoked, 25.43% were exposed to secondhand smoking, and 28.18% consumed 3 coffees or more every day. Prenatal alcohol exposure was associated with 11.24 times increased risk of birth defects/disabilities [Odds Ratio (OR): 11.24, 95% Confidence Interval (CI) 1.07-117.86] and 10.66 times increased risk of inherited metabolic diseases (OR: 10.66, 95% CI: 1.08-104.82). Prenatal secondhand smoke exposure (OR: 1.62, 95% CI: 1.01-2.62) and coffee consumption (OR: 1.92, 95% CI: 1.22-3.03) was associated with increased risk of low birth weight. Such results were in alignment with that of previous studies and confirmed that prenatal alcohol, tobacco, and coffee exposure can have detrimental neonatal and maternal consequences.

Serum estradiol level according to dose and formulation of oral estrogens in postmenopausal women.

This study was performed to evaluate serum estradiol level in postmenopausal women using oral menopausal hormone therapy (MHT) with different doses and formulations of estrogens. A total of 344 postmenopausal women who received oral MHT was included in this cross-sectional study. Serum estradiol level was compared according to formulation (estradiol hemihydrate [EH] or valerate [EV], conjugated estrogen [CE]) and dose (estradiol 1 or 2 mg, CE 0.45 or 0.625 mg) of the estrogens. Mean age and years since menopause were 56.9 and 7.9 years, respectively. Mean duration of MHT was 27.4 months. Since serum estradiol levels were not significantly different at either dose, EH and EV at the same dose were combined for comparisons: estradiol 1 mg and 2 mg. The serum estradiol level with estradiol 2 mg (107.6 pg/mL) was significantly higher by 60% than with estradiol 1 mg (65.8 pg/mL) or CE 0.45 mg (60.1 pg/mL), and it was also significantly higher than with CE 0.625 mg (76.8 pg/mL). Our findings suggest that serum estradiol level is not directly proportional to estrogen dose. In terms of serum concentration, CE 0.45 mg is equivalent to estradiol 1 mg.

Acrylonitrile induced cell cycle arrest and apoptosis by promoting the formation of reactive oxygen species in human choriocarcinoma cells.

Acrylonitrile (AN), which is widely utilized in the manufacture of plastics, acrylamide, acrylic fibers, and resins, is also one of main components of cigarette smoke (CS). In this study, we examined the effects of AN on the cell viability and apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cell lines. A cell viability assay confirmed that AN decreased the cell proliferation of JEG-3 and BeWo cells in a dose-dependent manner. Additionally, Western blot assay revealed that protein expression of cyclin D and cyclin E decreased, while protein expression of p21 and p27 increased in response to AN treatment for 48 hr. The changes in reactive oxygen species (ROS) levels in JEG-3 and BeWo cells exposed to AN were also measured by a dichlorofluorescein diacetate (DCFH-DA) assay, which revealed that ROS levels increased in response to AN treatment for 48 hr. Moreover, western blot assay confirmed that AN treatment of JEG-3 and BeWo cells for 4 hr promoted the expression of phosphorylated eukaryotic initiation factor 2 alpha protein (p-eIF2α), C/EBP homologous protein (CHOP) and caspase 12, which are known to be involved in ROS-mediated endoplasmic reticulum stress (ER-stress)-related apoptosis. Overall, the protein expression of p53 and Bax (a pro-apoptosis marker) increased, while the expression of Bcl-xl (an anti-apoptotic marker) decreased and the number of apoptotic cells increased in response to AN treatment for 48 hr. Taken together, these results suggest that AN has the potential to induce apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cells by activating ROS.

Tissue-remodelling M2 Macrophages Recruits Matrix Metallo-proteinase-9 for Cryotherapy-induced Fibrotic Resolution during Keloid Treatment.

Cryotherapy is used to treat keloid scars; however, the molecular and pathological mechanisms are not clearly understood. This study retrospectively evaluated the efficacy of combined treatment with cryotherapy and intralesional triamcinolone injection (Cryo+TA) or intralesional TA monotherapy (TA) in 40 Asian patients with keloid scars. Scar improvement was assessed using the Vancouver Scar Scale and Global Improvement Scale. Clinical improvement in scars, especially reduced vascularity and redness, was significantly greater in the Cryo+TA group than in the TA group. Cryotherapy-treated and untreated keloid tissue was collected from six patients for analysis. Histo-logically, collagen bundles from cryotherapy-treated keloid tissue were more fibrillar and abnormal thickness was reduced. Immunohistochemical staining showed a reduced number of dermal vessels after cryotherapy. Moreover, CD163+ M2 macrophages and matrix metalloproteinase-9 (MMP-9) were significantly increased in cryotherapy-treated tissue. Double immunofluorescence staining revealed co-expression of CD163 and MMP-9. These data indicate that cryotherapy recruits tissue-remodelling M2 macrophages with accompanying MMP-9, suggesting that cryotherapy-recruited M2 macrophages function in fibrotic resolution during keloid treatment.

Inhibitory effect of therapeutic genes, cytosine deaminase and interferon­ß, delivered by genetically engineered stem cells against renal cell carcinoma.

Although the effects of stem cells expressing anticancer genes on tumor growth have been demonstrated by many researchers in various types of cancer, relatively few studies have investigated their inhibitory effects on cancer metastasis. In the present study, we examined the inhibitory effects of cytosine deaminase (CD)/5­fluorocytosine (5­FC) and interferon­ß (IFN­ß) using genetically engineered neural stem cells (hNSCs) in a cellular and metastasis model of renal cell carcinoma (RCC). The CD/5­FC method has the advantage of minimizing damage to normal tissues since it selectively targets cancer cells by the CD gene, which converts prodrug 5­FC to the drug 5­fluorouracil. Moreover, we used hNSCs as a tool to effectively deliver the anticancer genes to the tumor site. These stem cells are known to possess tumor­tropism because of chemoattractant factors expressed in cancer cells. Therefore, we ascertained the expression of these factors in A498 cells, a cell line of RCC, and identified the A498­specific migration ability of hNSCs. We also confirmed that the proliferation of A498 cells was significantly reduced by therapeutic hNSCs in the presence of 5­FC. Furthermore, we established an A498 metastasis model. In the animal experiment, the weight of the lungs increased in response to cancer metastasis, but was normalized by hNSCs expressing CD and/or IFN­ß genes, while the incidence of liver metastasis was suppressed by the hNSCs. Overall, the results of this study demonstrate that stem cells expressing anticancer genes have the potential for use as an alternative to conventional therapy for metastatic cancer.

Studies on Chemical IR Images of Poly(hydroxybutyrate⁻co⁻hydroxyhexanoate)/Poly(ethylene glycol) Blends and Two-Dimensional Correlation Spectroscopy.

Biodegradable poly-[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoates] (PHBHx) have been widely studied for their applications in potentially replacing petroleum-based thermoplastics. In this study, the effect of the high molecular weight (Mn = 3400) poly(ethylene glycol) (PEG) blended in the films of PHBHx with different ratios of PEG was investigated using chemical FTIR imaging. Chemical IR images and FTIR spectra measured with increasing temperature revealed that PEG plays an important role in changing the kinetics of PHBHx crystallization. In addition, two-dimensional correlation spectra clearly showed that thermal properties of PHBHx/PEG blend film changed when the blending ratio of PHBHx/PEG were 60/40 and 50/50. Consequently, PEG leads to changes in the thermal behavior of PHBHx copolymers.

Exposure to cigarette smoke via respiratory system may induce abnormal alterations of reproductive organs in female diabetic rats.

Cigarette smoke (CS) has harmful effects on human fertility, reproduction, and development as well as on patients suffering from metabolic diseases such as diabetes than on healthy individuals. This study was conducted to investigate the relationship between CS exposure and histological alterations of reproductive organs in female diabetic rats. We evaluated the histology of uteruses and ovaries obtained from female rats exposed to smoke from standard cigarettes for 4 weeks (28 hours a week). After CS exposure, tissue slides were made from uterine and ovarian samples and examined after hematoxylin and eosin staining. Immunohistochemistry was used for detection of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), and estrogen receptor (ER)α in the uterus and ovary. MMP9 is an inflammatory biomarker that increases during progression to endometriosis. As a chemokine receptor, CXCR4 is involved in development of the inner wall of the uterus and cell adhesion. In the uterus, the occurrence of MMP9, CXCR4, and ERα and the number of endometrial glands were increased by CS exposure, while in the ovary, occurrence of MMP9, CXCR4, ERα, proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Collectively, this study indicates that CS induced abnormal development of the uterus and ovary under induced diabetes, leading to adverse effects on normal function of reproductive organs in female rats. HIGHLIGHTS: Cigarette smoke (CS) exposure adversely affected reproductive organs of diabetic female rats. In the uterus, expression of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), estrogen receptor (ER)α, and the number of endometrial glands were increased by CS exposure, In the ovary, the expression of MMP9, CXCR4, ERα, and proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Exposure to CS via the respiratory system exerted a harmful impact on the uterus and ovary in female rats with diabetes.

The cigarette smoke components induced the cell proliferation and epithelial to mesenchymal transition via production of reactive oxygen species in endometrial adenocarcinoma cells.

Cigarette smoke (CS) causes about 480,000 deaths each year worldwide and is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. In the present study, the effects of acrylonitrile (AN), benzo(a)pyrene (B(a)P), formaldehyde (FOR), isoprene (ISO), nicotine-derived nitrosamine ketone (NNK), which are the main components of CS, on the proliferation, invasion, and the epithelial-mesenchymal transition (EMT) process of human Ishikawa endometrial adenocarcinoma cells were investigated. Treating Ishikawa cells with CS components resulted in increased cell growth and altered expression of cell cycle-related genes: the protein expression of cyclin D & E increased, while the levels of p21 & p27 were reduced following treatment of these five CS components. In addition, CS components increased the invasion capacity of Ishikawa cells. The expression of the epithelial markers, E-cadherin and occludin, were significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by CS components. In dichloro-dihydro-fluorescein diacetate (H2DCF-DA) assay, ROS production increased by treatment of CS components. The CS components activated the ROS-p38 MAPK-EMT pathway by increasing the level of phosphorylated p38 MAPK and p44/42 (ERK1/2), and by up-regulating Snail and Slug, the transcription factors for EMT. Taken together, these results indicate that CS components can promote progression of endometrial adenocarcinoma via increasing cell proliferation and the ROS-mediated EMT process.

Potential roles of reactive oxygen species derived from chemical substances involved in cancer development in the female reproductive system.

Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately by reprogramming cancer cell metabolism. This review provides up to date findings regarding the roles of ROS generation induced by diverse biological molecules and chemicals in representative women's cancer. Specifically, we describe the cellular signaling pathways that regulate direct or indirect interactions between ROS homeostasis and metabolism within female genital cancer cells. [BMB Reports 2018; 51(11): 557-562].

Resveratrol induced reactive oxygen species and endoplasmic reticulum stress­mediated apoptosis, and cell cycle arrest in the A375SM malignant melanoma cell line.

Resveratrol, a dietary product present in grapes, vegetables and berries, regulates several signaling pathways that control cell division, cell growth, apoptosis and metastasis. Malignant melanoma proliferates more readily in comparison with any other types of skin cancer. In the present study, the anti­cancer effect of resveratrol on melanoma cell proliferation was evaluated. Treating A375SM cells with resveratrol resulted in a decrease in cell growth. The alteration in the levels of cell cycle­associated proteins was also examined by western blot analysis. Treatment with resveratrol was observed to increase the gene expression levels of p21 and p27, as well as decrease the gene expression of cyclin B. In addition, the generation of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress were confirmed at the cellular and protein levels using a 2',7'­dichlorofluorescein diacetate assay, TUNEL assay and western blot analysis. Resveratrol induced the ROS­p38­p53 pathway by increasing the gene expression of phosphorylated p38 mitogen­activated protein kinase, while it induced the p53 and ER stress pathway by increasing the gene expression levels of phosphorylated eukaryotic initiation factor 2α and C/EBP homologous protein. The enhanced ROS­p38­p53 and ER stress pathways promoted apoptosis by downregulating B­cell lymphoma­2 (Bcl­2) expression and upregulating Bcl­2­associated X protein expression. In conclusion, resveratrol appears to be an inducer of ROS generation and ER stress, and may be responsible for growth inhibition and cell cycle arrest of A375SM melanoma cells.

Double-tiered subchondral support fixation with optimal distal dorsal cortical distance using a variable-angle volar locking-plate system for distal radius fracture in the elderly.

BACKGROUND: Double-tiered subchondral support (DSS) procedures with optimal distal dorsal cortical distance (DDD) have been reported to be effective in treating distal radius fractures, but there have been no studies of osteoporotic distal radius fractures in elderly patients. In this study, we demonstrated the efficacy of the DSS procedure with optimal DDD using a variable-angle volar locking-plate system for the treatment of osteoporotic distal radius fractures in elderly patients. METHODS: One hundred and twenty-two patients (mean age, 73.3 years; age range, 65-88 years) with distal radius fracture were treated using a variable-angle volar locking-plate system with DSS. Patients were divided into DSS and non-DSS groups based on postoperative and 12-month follow-up radiographs, and radiological and clinical assessment was performed. Finally, we divided all 122 patients into two groups based on volar tilt of 6° on 12-month follow-up radiographs, and postoperative DDD values were compared. RESULTS: Volar tilt decreased (p=0.02), and ulnar variance increased (p=0.01) more in the non-DSS group. The non-DSS group showed a significant correlation between postoperative DDD value and change in DDD value (p=0.00). The mean postoperative DDDs in the group with final volar tilt<6° and in the group with final volar tilt≥6° were 6.4mm (SD±1.7mm) and 4.6mm (SD±1.4mm) respectively (p=0.02). At 4-month follow-up, pronation (p=0.05) and supination (p=0.04) were improved, and at 12-month follow-up, supination (p=0.05) was improved in the DSS group. CONCLUSION: The use of the DSS procedure and reduction of DDD to 4.6mm or less using a variable-angle volar locking-plate system was effective in maintaining anatomical reduction for the treatment of osteoporotic distal radius fractures in elderly patients. LEVEL OF EVIDENCE: III Therapeutic study.

3,3'-Diindolylmethane Suppressed Cyprodinil-Induced Epithelial-Mesenchymal Transition and Metastatic-Related Behaviors of Human Endometrial Ishikawa Cells via an Estrogen Receptor-Dependent Pathway.

Cyprodinil (CYP) is a pyrimidine amine fungicide that has been extensively used in agricultural areas. 3,3'-Diindolylmethane (DIM) is a derivative of the dietary phytoestrogen, indole-3-carbinol (I3C), which is derived from cruciferous vegetables and considered to be a cancer-preventive phytonutrient agent. In this study, the effects of CYP and DIM were examined on the cell viability, invasion, and metastasis of human endometrial cancer cells, Ishikawa, via epithelial mesenchymal transition (EMT). CYP increased the level of cell viability of Ishikawa cells compared to DMSO as a control, as did E2. Ishikawa cells lost cell-to-cell contact and obtained a spindle-shaped or fibroblast-like morphology in response to the application of E2 or CYP by the cell morphology assay. In the cell migration and invasion assay, CYP enhanced the ability of migration and invasion of Ishikawa cells, as did E2. E2 and CYP increased the expressions of N-cadherin and Snail proteins, while decreasing the expression of E-cadherin protein as EMT-related markers. In addition, E2 and CYP increased the protein expressions of cathepsin D and MMP-9, metastasis-related markers. Conversely, CYP-induced EMT, cell migration, and invasion were reversed by fulvestrant (ICI 182,780) as an estrogen receptor (ER) antagonist, indicating that CYP exerts estrogenic activity by mediating these processes via an ER-dependent pathway. Similar to ICI 182,780, DIM significantly suppressed E2 and CYP-induced proliferation, EMT, migration, and invasion of Ishikawa cancer cells. Overall, the present study revealed that DIM has an antiestrogenic chemopreventive effect to withdraw the cancer-enhancing effect of E2 and CYP, while CYP has the capacity to enhance the metastatic potential of estrogen-responsive endometrial cancer.

Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene Induced Growth and Epithelial Mesenchymal Transition via Induction of an Antioxidant Effect.

Cigarette smoke (CS) causes about 480,000 deaths each year worldwide, and it is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. In this study, the effects of formaldehyde (FA) and benzene (Bz), the main components of CS, on cell proliferation and epithelial mesenchymal transition (EMT) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS components and placenta carcinoma. Upon MTT assay, FA (10-8 M to 10-5 M) and Bz (10-11 M to 10-8 M) increased JEG-3 cell proliferation. Western blot assay revealed that the protein expression of cyclin D1 and E1 increased, while the levels of p21 and p27 were reduced following treatment. In Scratch assay, FA (10-8 M and 10-5 M) and Bz (10-11 M and 10-8 M) increased migration of JEG-3 cells at 24 h and 48 h compared with that at 0 h. In addition, the expression of the epithelial marker, E-cadherin, was significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by FA (10-8 M and 10-5 M) and Bz (10-11 M and 10-8 M). snail and slug transcriptional factors were associated with EMT, which were also up-regulated by FA and Bz, indicating that FA and Bz lead to an increase in the EMT process in JEG-3 choriocarcinoma cells. We further evaluated reactive oxygen species (ROS) and activation of antioxidant effect using dichlorofluorescin diacetate (DCFH-DA) and Western blot assay. FA and Bz increased the ROS production and an antioxidant related marker, Nrf2, in JEG-3 cells. However, eIF2α levels were reduced by FA and Bz via activation of the antioxidant reaction. Taken together, these results indicated that FA and Bz induce the growth and migration of human choriocarcinoma cells via regulation of the cell cycle and EMT and activation of ROS and antioxidant related markers.

Benzo(a)pyrene induced cell cycle arrest and apoptosis in human choriocarcinoma cancer cells through reactive oxygen species-induced endoplasmic reticulum-stress pathway.

Cigarette smoke (CS) contains over 60 well established carcinogens. In this study, we examined the effects of benzo(a)pyrene (B(a)P), a main CS component, on the viability and apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cell lines. An MTT assay confirmed that B(a)P decreased the cell viability of JEG-3 and BeWo cells in a dose-dependent manner. Additionally, Western blot (WB) assay revealed that protein expression of cyclin D and cyclin E decreased, while protein expression of p21 and p27 was increased in response to B(a)P treatment for 48 h. The changes in reactive oxygen species (ROS) levels in JEG-3 and BeWo cells exposed to B(a)P were also measured by a dichlorofluorescein diacetate (DCF-DA) assay, which revealed that ROS levels increased in response to B(a)P treatment for 48 h. WB assay also confirmed that each B(a)P treatment of JEG-3 and BeWo cells for 4 h promoted the expression of phosphorylated eukaryotic initiation factor 2 alpha protein (p-eIF2α) and C/EBP homologous protein (CHOP), which are known to be involved in ROS-mediated endoplasmic reticulum stress (ER-stress) related apoptosis. Overall, the protein expression of Bax (a pro-apoptosis marker) increased, while the expression of Bcl-xl (an anti-apoptotic marker) decreased and the number of apoptotic cells increased in response to B(a)P treatment for 48 h. Taken together, these results suggest that B(a)P has the potential to induce apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cells by increasing the ROS level and simultaneously activating ER-stress.

Decreased PD-1 positive blood follicular helper T cells in patients with psoriasis.

Follicular helper T (Tfh) cells are recently characterized subset of helper T cells, which are initially found in the germinal centers of B cell follicles. The major role of Tfh cells is helping B cell activation and antibody production during humoral immunity. Recently, blood Tfh cells were shown to be associated with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid and psoriasis. There is only one study which investigated Tfh cells in psoriasis patients. Therefore, in this study, we evaluated and analyzed blood Tfh cells in Korean patients with psoriasis. A total of 28 psoriasis patients and 16 healthy controls were enrolled. The frequency and absolute number of CXCR5(+)PD-1(+) Tfh cells were decreased in patients with psoriasis compared to healthy controls. CD4(+)CXCR5(+) T cells and CXCR5(+)ICOS(+) Tfh cells did not show differences. The frequency and absolute number of CXCR5(+)PD-1(+) Tfh cells in psoriasis patients negatively correlated with erythrocyte sedimentation rate and positively correlated with disease duration. The absolute number of CXCR5(+)ICOS(+) Tfh cells also showed positive correlation with disease duration. However, the subpopulations of Tfh cells did not correlate with Psoriasis Area and Severity Index. Serum interleukin-21 level was significantly increased in psoriasis patients compared to healthy controls, however, its level did not correlate with clinical and experimental parameters of psoriasis patients. These findings suggest the decreased function of Tfh cells in psoriasis, which could result in attenuated B cell immune responses in the pathogenesis of psoriasis. However, further investigations are necessary to confirm the function of Tfh cells in psoriasis vulgaris.

Tailored CVD graphene coating as a transparent and flexible gas barrier.

The chemical vapor deposition (CVD) method to obtain tailored graphene as a transparent and flexible gas barrier has been developed. By separating nucleation step from growth, we could reduce early graphene nucleation density and thus induce better stitching between domain boundaries in the second growth step. Furthermore, two step growth in conjunction with electrochemical polishing of Cu foils achieved large graphene domains and improved graphene quality with minimized defects. The performance of resulting graphene as a gas barrier was superior to the graphene obtained by one-step growth on polished or unpolished Cu foils. The CVD graphene reported here could open up the possibility for exploring graphene-based gas barrier due to the minimized density of defect area.