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This study aimed to investigate the mediating effect of the screen media time of young children on the relationship between mothers’ reasons for allowing young children to use screen media and their children’s ability to regulate screen media. The participants consisted of 614 children aged 5-6 (312 boys and 302 girls), and all the survey questions were answered by their mothers. Descriptive statistics, Pearson’s correlation, structural equation modeling, and bootstrapping analysis were employed to analyze the data using SPSS 25.0 and Mplus 8.6. The results were as follows. First, mothers’ educational and ritualized reasons for allowing young children to use screen media and children’s screen media time directly affected young children’s ability to regulate screen media. Second, children’s screen media time mediated the relationship between mothers’ educational and ritualized reasons for allowing their children to use screen media and children’s ability to regulate screen media. When mothers permitted their children to use screen media for educational purposes, their children were likely to spend less time on screen media usage which, in turn, increased their ability to regulate screen media. Conversely, the more mothers allowed their children to use screen media for ceremonial purposes, the more time their children spent on screen media and the less ability they had to regulate screen media usage. These outcomes suggest that, to improve children’s screen media regulation ability, mothers must not routinely allow their children to use screen media and should manage their children’s screen media time.

Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma.Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of E-cadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens.Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0-2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0-2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01).This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Today, the number of technology users is rapidly increasing due to the development of science and technology and the popularization of smartphone use. Users build their social networks online by sharing and connecting their lives and interests with others through platforms provided by social media. In the beauty industry, various social mediamarketing activities are also increasing. Therefore, this study aims to analyze beauty management behavior according to the motivation for use among college students who have the most access to and use of social media. The method of study was conducted for college students attending a four-year university located in Jeonnam, and 382 copies of the questionnaire were independently answered by them to be analyzed and used in this study. The summarized results of the study areas follows. Looking at the correlation between social media usage motivation and beauty management behavior, skin management behavior of beauty management behavior was positively related in the order of functional, social, and self-expression motivation. It was found that the higher the functional motivation of social media, the higher the level of skin care behavior. Upon investigating the influence of college students’social media usage motivation on beauty management behavior, it was found that onlythe functional motivation of social media usage motivation has a significant effect on skin management behavior. Amultiple regression analysis to investigate the effect of social media usage motivation on body shape management behavior revealed that self-expression motivation and social motivation of social media usage motivation had significant effects on body shape management behavior. Therefore, this study is expected to provide basic data for the research of university students that can lead the beauty industry. It is expected that the beauty industry can provide information related to beauty product sales and beauty information contents using social media targeting the students.

We report the response process of the Laboratory Analysis Task Force (LATF) for Unknown Disease Outbreaks (UDOs) at the Korea Disease Control and Prevention Agency (KDCA) during January 2020 to coronavirus disease 2019 (COVID-19), which developed as a UDO in Korea. The advanced preparedness offered by the laboratory diagnostic algorithm for UDOs related to respiratory syndromes was critical for the rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enabled us to establish and expand the diagnostic capacity for COVID-19 on a national scale in a timely manner.

Particulate matter has interest of the entire nation is increasing as its severity and risk are rising every day. particulate matter further threaten human health and cause various diseases unless environmental problems are improved, raising the need for continuous research. Therefore, the purpose of this study is to strengthen the awareness of the harmfulness of particulate matter among general public, and to suggest a way to practice proper skin care by investigating the harmfulness of particulate matter perceived by modern people and analyzing skin health management behavior. As for the research method, online Google survey form was used targeting male and female in their 20s to 50s residing in Korea, and a total of 502 questionnaires were statistically processed and used for the final analysis. The results of this study are summarized as follows. examination on the relationship between the awareness of the harmfulness of particulate matter and skin health management behavior showed that there is a high positive correlation between them, and there is a positive correlation between skin health management behavior and the use of cosmetics, nutrition and exercise management, and professional skin care in the order. the examination showed that modern people’s awareness of the harmfulness of particulate matter has a significant effect on skin health management behavior. It implies that the higher the awareness of the harmfulness of particulate matter, the higher the skin health management behavior. Based on the above results, it is considered that accurate information on particulate matter and appropriate skin care methods are needed. Based on this, it is expected to greatly contribute to the promotion of public health and activation of the skin care industry in the future.

Prostate cancer patients primarily receive androgen receptor (AR)-targeted drugs as a primary treatment option because prostate cancer is associated with highly activated AR signaling. AR amplification made prostate cancer cells viable under treatment of AR-targeted therapy, leading to castration resistance. AR amplification was more common in enzalutamide-resistant patients. As a strategy to overcome castration resistance and to improve the efficacy of enzalutamide, second-generation nonsteroidal antiandrogen drugs for castration-resistant prostate cancer (CRPC) including topoisomerase II (topo II) poisons such as etoposide and mitoxantrone, have been administered in combination with enzalutamide. In the present study, it was confirmed that amplification of topo IIα, but not I and IIβ, was directly and proportionally associated with poor clinical outcome of Prostate cancer. Among a novel series of newly designed and synthesized 7-(3-aminopropyloxy)-substituted flavone analogues, compound 6, the most potent derivative, was further characterized and identified as a topo IIα catalytic inhibitor that intercalates into DNA and binds to the DNA minor groove with better efficacy and less genotoxicity than etoposide, a topo II poison. Compound 6 showed remarkable efficacy in inhibiting AR-negative CRPC cell growth and sensitizing activity to enzalutamide in AR-positive CRPC cells, thus confirming the potential of topo IIα catalytic inhibitor to overcome resistance to androgen deprivation therapy.

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers despite a relatively low incidence. Angiogenesis, one of the hallmarks of cancer, is essential for the pathogenesis of EOC, which is related to the induction of angiogenic factors. We found that ELF3 was highly expressed in EOCs under hypoxia and functioned as a transcription factor for IGF1. The ELF3-mediated increase in the secretion of IGF1 and VEGF promoted endothelial cell proliferation, migration, and EOC angiogenesis. Although this situation was much exaggerated under hypoxia, ELF3 silencing under hypoxia significantly attenuated angiogenic activity in endothelial cells by reducing the expression and secretion of IGF1 and VEGF. ELF3 silencing attenuated angiogenesis and tumorigenesis in ex vivo and xenograft mouse models. Consequently, ELF3 plays an important role in the induction of angiogenesis and tumorigenesis in EOC as a transcription factor of IGF1. A detailed understanding of the biological mechanism of ELF3 may both improve current antiangiogenic therapies and have anticancer effects for EOC.

The coronavirus disease 2019 (COVID-19) pandemic has affected the utilization of healthcare services, including participation in cancer screening programs. We compared cancer screening participation rates for colorectal, gastric, breast, and cervical cancers among participants in the National Cancer Screening Program (NCSP) in 2019 and 2020 to address the potential distraction effect of COVID-19 on cancer screening.Data from the NCSP for 4 cancer types (stomach, colorectal, breast, and cervical) in 2019 and 2020 were used to calculate cancer screening participation rates by calendar month, gender, age group, and geographical region. Monthly participation rates were analyzed per 1,000 eligible individuals.The screening participation rate decreased in 2020 compared to 2019 for all 4 cancers: colorectal (40.5 vs. 35.3%), gastric (61.9 vs. 54.6%), breast (63.8 vs. 55.8%), and cervical (57.8 vs. 52.2%) cancers. Following 2 major COVID-19 waves in March and December 2020, the participation rates in the 4 types of cancer screening dropped compared with those in 2019. The highest decline was observed in the elderly population aged 80 years and older (percentage change: -21% for colorectal cancer; -20% for gastric cancer; -26% for breast cancer; -20% for cervical cancer).After the 2 major COVID-19 waves, the screening participation rate for 4 types of cancer declined compared with 2019. Further studies are needed to identify the indirect effects of the COVID-19 pandemic on cancer patients, such as delayed diagnoses of cancer or excess cancer deaths.

HER2 overexpression induces cancer aggression and frequent recurrences in many solid tumors. Because HER2 overproduction is generally followed by gene amplification, inhibition of protein-protein interaction (PPI) between transcriptional factor ELF3 and its coactivator MED23 has been considered an effective but challenging strategy.This study aimed to determine the hotspot of ELF3-MED23 PPI and further specify the essential residues and their key interactions in the hotspot which are controllable by small molecules with significant anticancer activity.Intensive biological evaluation methods including SEAP, fluorescence polarization, LC-MS/MS-based quantitative, biosensor, GST-pull down assays, and in silico structural analysis were performed to determine hotspot of ELF3-MED23 PPI and to elicit YK1, a novel small molecule PPI inhibitor. The effects of YK1 on possible PPIs of MED23 and the efficacy of trastuzumab were assessed using cell culture and tumor xenograft mouse models.ELF3-MED23 PPI was found to be specifically dependent on H-bondings between D400, H449 of MED23 and W138, I140 of ELF3 for upregulating HER2 gene transcription. Employing YK1, we confirmed that interruption on these H-bondings significantly attenuated the HER2-mediated oncogenic signaling cascades and exhibited significant in vitro and in vivo anticancer activity against HER2-overexpressing breast and gastric cancers even in their trastuzumab refractory clones.Our approach to develop specific ELF3-MED23 PPI inhibitor without interfering other PPIs of MED23 can finally lead to successful development of a drug resistance-free compound to interrogate HER2 biology in diverse conditions of cancers overexpressing HER2.

This study investigated the infectivity of severe acute respiratory syndrome (SARS-CoV-2) in individuals who re-tested positive for SARS-CoV-2 RNA after recovering from their primary illness. We investigated 295 individuals with re-positive SARS-CoV-2 polymerase chain reaction (PCR) test results and 836 of their close contacts. We attempted virus isolation in individuals with re-positive SARS-CoV-2 PCR test results using cell culture and confirmed the presence of neutralizing antibodies using serological tests. Viral culture was negative in all 108 individuals with re-positive SARS-CoV-2 PCR test results in whom viral culture was performed. Three new cases of SARS-CoV-2 infection were identified among household contacts using PCR. Two of the three new cases had had contact with the index patient during their primary illness, and all three had antibody evidence of past infection. Thus, there was no laboratory evidence of viral shedding and no epidemiological evidence of transmission among individuals with re-positive SARS-CoV-2 PCR test results.

Background: As of February 21, 2021, 86,992 cases of coronavirus disease 2019 (COVID-19) were confirmed in the Republic of Korea, with 1,557 deaths and 85,435 cases discharged from isolation. This study investigated the infectivity of individuals with COVID-19 who were retested and found to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-positive after recovering from their primary illness. Methods: We investigated 295 individuals with recurrent SARS-CoV-2 positive results, and 836 of their close contacts. We attempted virus isolation in 108 individuals with recurrent SARS-CoV-2 positivity using cell culture and confirmed the presence of neutralizing antibodies by means of serological tests. Findings: The average age was 45·2 years (range, 1–95 years) and 64% were female. At the time of retesting, 55·6% were asymptomatic, and symptoms included cough (18·0%), expectoration (11·2%), sore throat (10·8%), and fever (9·2%). The reasons for retesting were screening (46%), persistent symptoms (37·6%), and new contact with a confirmed COVID-19 case (9·5%). Virus isolation was attempted in 108 individuals with recurrent SARS-CoV-2 positivity, and all tested negative. Three new cases were identified among household contacts based on SARS-CoV-2 polymerase chain reaction testing. Two of the three new cases had had contact with the index patient during their primary illness, and all three had antibody evidence of past infection. Interpretation: There was no laboratory evidence of viral shedding and no epidemiological evidence of transmission among individuals with recurrent positivity. Funding Statement: This study was funded by the Korea Disease Control and Prevention Agency (No. 4800-4837-301). Declaration of Interests: The authors declare no conflicts of interest related to the study. Ethics Approval Statement: The study was approved by the KDCA Institutional Review Board (2020-03-01-P-A). The board waived the requirement for written informed consent.

Background: The COVID-19 pandemic has disrupted healthcare delivery, which is widely discussed as the distraction effect. This study aimed to estimate the distraction effect of the COVID-19 pandemic in Korea by analyzing colorectal and gastric cancer screening rates in the years 2019 and 2020. Methods: Information of eligible population who had colorectal and gastric cancer screening provided by the National Cancer Screening Program in the years 2019 and 2020 was collected. Participation rates were analyzed by age group, sex, geographic region, and calendar month. Percentage change was calculated by dividing the percentage point difference by the screening rate of the reference period (2019). Results: Overall, the colorectal and gastric cancer screening rates had decreased in 2020, compared to the reference period. For colorectal cancer, the screening rate decreased from 68.3% in 2019 (5,886,319 participants/14,526,424 eligible population) to 54.6% in 2020 (5,135,218/9,410,525) For gastric cancer, the screening rates decreased from 61.9% in 2019 (7,194,489/11,625,627) to 54.6% in 2020 (6,244,491/11,439,246). In March, during the first wave, the screening rates declined sharply (percentage change: colorectal, 56.6%; gastric, 57.3%). Although the screening rates had rebounded aftermath, they declined again in December, during the third wave (percentage change: colorectal, 17.0%; gastric, 13.8%). According to specific-age group, we found a substantial decline in screening rates for older adults aged 80~84, and those over 85 (percentage change: colorectal, 19.0% & 23.0%; gastric, 17.4% & 25.1% respectively). Conclusion: During the COVID-19 pandemic, the screening rates for both colorectal and gastric cancer decreased. There was a substantial decline during the first and the third waves of the epidemic, in March and in December. The older adults group showed the highest reduction in screening rates. However, comparing the screening rate by region and sex, we did not find a significant difference. Delayed cancer diagnosis or excess death due to distraction effect of the COVID-19 pandemic has not yet been detected in Korea, therefore, further studies are needed. Citation Format: Seung Hee Seo, Hyeree Park, Jong Heon Park, Bhumsuk Keam, Shin Hye Yoo, Aesun Shin. Colorectal and gastric cancer screening rates in Korea during the COVID-19 pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 433.

Trastuzumab (TZMB) is widely used as first line therapy for breast cancer (BC) patients overexpressing human epidermal growth factor receptor 2 (HER2). Despite its clinical benefits, many patients suffer from primary or secondary resistance to this drug within one year. As diverse molecular mechanisms occur contemporaneously during the resistance development, we focused on elucidating the role of heat shock protein 27 (HSP27) in TZMB-resistance, as this protein simultaneously regulates the function of diverse client molecules that are involved in the resistance mechanism. By extensively utilizing TZMB-refractory breast cancer cell lines transduced with diverse phosphovariants of HSP27, our study newly revealed that specific phosphorylation of HSP27 at S15 promoted its S78 phosphorylation and served as key mediator to promote direct interactions that increase the stability of HER2 and protein kinase B (AKT). This phosphorylation promoted nuclear translocation of HER2, enhancing the distinct nuclear function of HER2 that promoted AKT activation and cyclin D1 expression. Co-administration of TZMB and a functional inhibitor of HSP27, J2, significantly reduced the S15/78 phosphorylation of HSP27, which downregulated HER2 and its downstream signals, sensitizing TZMB-refractory cell, and JIMT1-xenograft mouse models to TZMB. Collectively, p-HSP27S15 could serve as a valuable predictive marker and also a therapeutic target for TZMB-resistance.

Simple Summary Although biological information and the molecular classification of ependymoma have been studied, the treatment systems for ependymoma are still insufficient. In addition, because the disease occurs infrequently, it is difficult to obtain sufficient data to conduct large-scale or randomized clinical trials. Therefore, this study is intended to emphasize the importance of understanding its pathological characteristics and prognosis as well as developing treatments for ependymoma through multilateral studies. Abstract Glial cells comprise the non-sensory parts of the central nervous system as well as the peripheral nervous system. Glial cells, also known as neuroglia, constitute a significant portion of the mammalian nervous system and can be viewed simply as a matrix of neural cells. Despite being the “Nervenkitt” or “glue of the nerves”, they aptly serve multiple roles, including neuron repair, myelin sheath formation, and cerebrospinal fluid circulation. Ependymal cells are one of four kinds of glial cells that exert distinct functions. Tumorigenesis of a glial cell is termed a glioma, and in the case of an ependymal cell, it is called an ependymoma. Among the various gliomas, an ependymoma in children is one of the more challenging brain tumors to cure. Children are afflicted more severely by ependymal tumors than adults. It has appeared from several surveys that ependymoma comprises approximately six to ten percent of all tumors in children. Presently, the surgical removal of the tumor is considered a standard treatment for ependymomas. It has been conspicuously evident that a combination of irradiation therapy and surgery is much more efficacious in treating ependymomas. The main purpose of this review is to present the importance of both a deep understanding and ongoing research into histopathological features and prognoses of ependymomas to ensure that effective diagnostic methods and treatments can be developed.

The objective of this study was to discover potential topoisomerase (topo) targeting anticancer agents. Novel series of hydroxylated and halogenated(-F, -Cl, and -CF3) 2,4-diaryl benzofuro[3,2-b]pyridin-7-ols were systematically designed and synthesized by faster, economic, and environmentally friendly l-proline catalyzed and microwave-assisted one pot reaction method. The synthesized compounds were assessed for topo I and IIα inhibitory and anti-proliferative activities. The in vitroevaluation displayed that most of the compounds have selective topo IIα inhibitoryactivity as well as selectivity towards T47D human cancer cell line. Structure-activity relationship study suggested that the introduction of additional hydroxyl functionality at 7-positon of benzofuro[3,2-b]pyridine skeleton is crucial for selective topo IIα inhibitory activity. Placement of phenolic moiety on the 4-position of the tricyclic system imparts better topo IIα inhibitory and anti-proliferative activity.

PURPOSE This study investigated the incidence of urinary tract infection (UTI) in community-dwelling adults and identified the association between obesity and UTI. METHODS The participants were 4,926 adults aged over 40 years who had no UTIs at the baseline survey of the Korean Genome Epidemiology Study. Obesity was defined according to the cirtieria of Korean Society for the Study of Obesity using body mass index (BMI) data. UTI was defined as those who had self-reported UTI or had either nitrite, or both leukocytes and blood in the urine dipstick test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariate Cox proportional hazards regression analysis to identify the association between the obesity and UTI. RESULTS The incidence proportion of UTI was 5.1%, and the incidence density per 1,000 person-years was 25.5. After controlling general characteristics, people with BMI ≥30.0 kg/m² remained 1.66 times (HR = 1.66, 95% CI = 1.06~2.60; p < .05) more likely to have UTI than those with normal weight. This trend was also present in men or people aged ≥ 60 years. Among women aged ≥ 60 years, people with BMI ≥ 30.0 kg/m² were 1.98 times (HR = 1.98, 95% CI = 1.01~3.86; p < .05) more likely to have UTI than those with normal weight. CONCLUSION The BMI ≥ 30.0 kg/m² is a risk factor of UTIs in Korean adult men over 40 years and women aged ≥ 60 years. It is necessary to emphasize the importance of obesity management to men or women aged ≥ 60 years, specifically.

Summary Although the gut microbiome is generally symbiotic or commensal, some microbiome members become pathogenic under certain circumstances. However, the factors driving this pathogenic switch are largely unknown. Pathogenic bacteria can generate uracil that triggers host dual oxidase (DUOX) to produce antimicrobial reactive oxygen species (ROS). We show that pathogens generate uracil and ribose upon nucleoside catabolism of gut luminal uridine, which triggers not only host defenses but also inter-bacterial communication and pathogenesis in Drosophila. Uridine-derived uracil triggers DUOX-dependent ROS generation, whereas ribose induces bacterial quorum sensing (QS) and virulence gene expression. Genes implicated in nucleotide metabolism are found in pathogens but not commensal bacteria, and their genetic ablation blocks QS and the commensal-to-pathogen transition in vivo. Furthermore, commensal bacteria lack functional nucleoside catabolism, which is required to achieve gut-microbe symbiosis, but can become pathogenic by enabling nucleotide catabolism. These findings reveal molecular mechanisms governing the commensal-to-pathogen transition in different contexts of host-microbe interactions.

Human DNA topoisomerases (topos) have been recognized as a good target molecule for the development of anticancer drugs because they play an important role in solving DNA topological problems caused by DNA strand separation during replication and transcription. In this study, we designed and synthesized 11 novel chromone backbone compounds possessing epoxy and halohydrin substituents with chirality. In the topos inhibition test, compounds 2, 9, 10, and 11 showed comparable topo I inhibitory activity at concentration of 100 μM compared to camptothecin, and all of the synthesized compounds showed moderate topo IIα inhibitory activity. Among them, compounds 9, 10 and 11 were more potent than the others in both topo I and IIα inhibitory activity. Compound 11 showed the most potent cell antiproliferative activity against all tested cancer cell lines with particularly strong inhibition (an IC50 of 0.04 µM) of K562 myelogenous leukemia cancer cell proliferation. In the brief structure-activity relationship analysis, there was no clear correlation between stereochemistry and topos inhibitory and cytotoxic activity. 5(R),7(S)-bisepoxy-substituted compound 11 was the most potent DNA cross-linker and induced G2/M arrest in a cell cycle assay in a dose- and time-dependent manner. After the treatment time period induced apoptosis in K562 cells without increasing G2/M-phase cells. Overall, compound 11 showed good consistent inhibitory biological activity related to cancer cell proliferation.

As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines. Total eighteen compounds were synthesized and tested for their ability to inhibit the function of topo I and IIα, and proliferation of human breast (T47D), colorectal (HCT15), and cervix (HeLa) cancer cells. Except compound 11, all of the tested compounds displayed selective topo IIα inhibitory activity. Compounds 8–18, 22, 24, and 25 showed excellent topo IIα inhibitory activity than a positive control, etoposide. Most of the compounds appeared to be superior to reference compounds in their antiproliferative activity. Structure-activity relationship (SAR) study has shown that it is better to place the hydroxyphenyl group at the 4-position of the central pyridine for superior topo IIα inhibition and antiproliferative activity. Similarly, the 3′-, or 4′-hydroxyphenyl substitution at the 2- and 4-positon of pyridine ring is important for better activity than 2′-substitution.

In this study, we investigated a possible mechanism of β2-microglobulin (β2M) function in cancer metastases in vitro, using a human ovarian carcinoma cell line. β2M, a modulator acts as a cell growth-promoting and cellular signaling factors, was identified as a dickkopf-3 (DKK-3) interacting protein. We also observed that DKK-3 suppresses endothelial cell angiogenesis of β2M through vascular endothelial growth factor receptor-2 (VEGFR-2) in tumorigenesis. Luciferase activity was remarkably reduced by the transfection of DKK-3 in a dose-dependent manner. In addition, over-expression of β2M activates cell growth by suppressing DKK-3-induced apoptosis. The effect of β2M on cell cycle and apoptosis-regulatory components was also confirmed through the silencing of β2M expression. Furthermore, induction of β2M-mediated VEGFR-2/Akt/mTOR phosphorylation and tumor angiogenesis was significantly suppressed by over-expression of DKK-3. Taken together, our results suggest an underlying mechanism for an increase of β2M-related activity in ovarian tumor cells.

Guggulsterone (GS), a plant steroid and a compound found at high levels in Commiphora myrrha, exhibits anti-inflammatory, anti-cancer, and cholesterol-lowering effects. However, the potential of GS to ameliorate acute pancreatitis (AP) is unknown. The aim of this study was to evaluate the effects of GS on cerulein-induced AP. AP was induced by intraperitoneally injecting supramaximal concentrations of the stable cholecystokinin analog cerulein (50 μg/kg) hourly for 6 h. In the GS-treated group, GS was administered intraperitoneally (10, 25, or 50mg/kg) 1 h before the first cerulein injection. Mice were sacrificed 6 h after the final cerulein injection. Blood samples were collected to measure serum lipase levels and evaluate cytokine production. The pancreas and lung were rapidly removed for morphologic and histological examinations, flow cytometry analysis, myeloperoxidase (MPO) assay, and real-time reverse transcription-polymerase chain reaction analysis. Pre-treatment with GS attenuated cerulein-induced histological damage, reduced pancreas weight/body weight ratio, decreased serum lipase levels, inhibited infiltrations of macrophages and neutrophils, and suppressed cytokine production. Additionally, GS treatment suppressed the activation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) in the pancreas in cerulein-induced pancreatitis. In conclusion, our results suggest that GS attenuates AP via deactivation of ERK and JNK.

Objectives We aimed to evaluate the anti-inflammatory and inhibitory effects of Lithospermum erythrorhizon (LE) on cerulein-induced acute pancreatitis (AP) in a mouse model. Methods Acute pancreatitis was induced via intraperitoneal injection of cerulein (50 μg/kg) every hour for 6 times. In the LE, water extract (100, 250, or 500 mg/kg) was administered intraperitoneally 1 hour before the first injection of cerulein. Six hours after AP, blood, the pancreas, and the lung were harvested for further examination. In addition, pancreatic acinar cells were isolated using a collagenase method, and then, we investigated the acinar cell viability and cytokine productions. Results Treatment with LE reduced pancreatic damage and AP-associated lung injury and attenuated the severity of AP, as evidenced by the reduction in neutrophil infiltration, serum amylase and lipase levels, trypsin activity, and proinflammatory cytokine expression. In addition, treatment with LE inhibited high mobility group box 1 expression in the pancreas during AP. In accordance with in vivo data, LE inhibited the cerulein-induced acinar cell death, cytokine productions, and high-mobility group box 1 expression. Furthermore, LE also inhibited the activation of p38 mitogen-activated protein kinases. Conclusions These results suggest that LE plays a protective role during the development of AP by inhibiting the activation of p38.

Wnt inhibitory factor-1 (WIF1) is a conserved lipid-binding protein that interrupts Wnt ligands by interacting with their Frizzled receptors. Thus, they may suppress the activation of the Wnt/β-catenin triggered signaling cascade. Recently, we found that WIF1 can effectively co-regulate pro-apoptotic activity through the combination with Dickkopf-1 (DKK1). The tumor suppressor p53 protein expression was remarkably increased in the WIF1- and DKK1-transfected cells, along with p21. In contrast, expressions of the anti-apoptotic proteins, c-Myc and Bcl-2, were noticeably reduced. In addition, WIF1 and/or DKK1 significantly activated the transcription of p21 and p53, whereas c-Myc and Bcl-2 activities were remarkably reduced. The tumor suppressor WIF1 was also found to be capable of suppressing tumor growth through the inhibition of tumor angiogenesis in the cellular biological/physiological condition through the targeting of the PI3K/Akt/mTOR signaling pathway, while also being recognized as a Wnt antagonist factor in the Wnt cascade. Consistently, WIF1 conspicuously decreased the VEGF-induced phosphorylation of the PI3K/Akt signaling cascade components, including PDK1, mTOR, TSC-2, GSK-3β, and the p70S6K protein. Collectively, our results indicate for the first time that the tumor suppressor WIF1 is involved in angiogenesis and supplies a possible molecular target for the treatment of distinct malignant cancers, as well as several other associated diseases.

Acute pancreatitis (AP) is a complicated disease which is largely undiscovered. Fisetin, a natural flavonoid from fruits and vegetables, has been shown to have anti-inflammatory, antioxidant, and anti-cancer activities in various disease models. However, the effects of fisetin on AP have not been determined. Pre- and post- treatment of mice with fisetin reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (pancreatic weight to body weight ratio, amylase, lipase, and myeloperoxidase activity) and production of inflammatory cytokines. In pancreatic acinar cells, fisetin also inhibited cell death and production of inflammatory cytokines. In addition, fisetin inhibited activation of c-Jun NH2-terminal kinase (JNK) and nuclear factor (NF)-κB in vivo and in vitro. In conclusion, these results suggest that fisetin exhibits anti-inflammatory effect on AP and could be a beneficial agent in the treatment of AP and its pulmonary complications.

// Boh-Ram Kim 1,* , Kyungsil Yoon 1,* , Hyun-Jung Byun 1 , Seung Hee Seo 1 , Seung-Hoon Lee 2 and Seung Bae Rho 1 1 Research Institute, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do, Republic of Korea 2 Department of Life Science, Yong In University, 470, Samga-dong, Cheoin-gu, Yongin-si Gyeonggi-do, Republic of Korea * These Authors contributed equally to this work Correspondence: Seung Bae Rho, email: // Keywords : sMEK1 anti-activator; cell cycle arrest; caspase activity; traditional chemotherapeutic agent; ovarian cancer Received : May 13, 2014 Accepted : June 17, 2014 Published : June 19, 2014 Abstract Recently, we found that sMEK1 effectively regulates pro-apoptotic activity when combined with a traditional chemotherapeutic drug. Therefore, combinational therapeutic strategies targeting critical molecular and cellular mechanisms are urgently required. In this present work, we evaluated whether sMEK1 enhanced the pro-apoptotic activity of chemotherapeutic drugs in ovarian carcinoma cells. Combined with a chemotherapeutic drug, sMEK1 showed an additive effect on the suppression of ovarian cancer cell growth by inducing cell cycle arrest and apoptosis and regulating related gene expression levels or protein activities. In addition, the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was strongly inhibited by the combined treatment, showing de-repression of the tuberous sclerosis complex (TSC) and suppression of ras homolog enriched in the brain (Rheb) and mTOR and raptor in aggressive ovarian carcinoma cells and mouse xenograft models. Treatment with sMEK1 and paclitaxel reduced phosphorylation of ribosomal S6 kinase (S6K) and 4E-binding protein (4E-BP), two critical downstream targets of the mTOR-signaling pathway. Furthermore, both sMEK1 and paclitaxel significantly inhibited the expression of signaling components downstream of S6K/4E-BP, such as hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), both in vitro and in vivo . Therefore, our data suggest that the combination of sMEK1 and paclitaxel is a promising and effective targeted therapy for chemotherapy-resistant or recurrent ovarian cancers.

Thioridazine, a member of the phenothiazine family, is a powerful anti-anxiety and anti-psychotic drug. It can also suppress the growth of several types of tumor in vitro. In the current study, we evaluated the direct anti-tumor and anti-angiogenic effects of thioridazine in vivo. The injection of thioridazine into human ovarian tumor xenografts in nude mice significantly inhibited tumor growth by ~fivefold, and also decreased tumor vascularity. In addition, thioridazine inhibited the phosphorylation of the signaling molecules downstream of phosphatidylinositol-3'-kinase (PI3K), including Akt, phosphoinositide-dependent protein kinase 1 (PDK1), and mammalian target of rapamycin (mTOR), during ovarian tumor progression via vascular endothelial growth factor receptor 2 (VEGFR-2). These results provide convincing evidence that thioridazine regulates endothelial cell function and subsequent angiogenesis by inhibiting VEGFR-2/PI3K/mTOR signal transduction. Collectively, these results strongly suggest that thioridazine might be a novel anti-tumor and anti-angiogenic agent for use in ovarian cancer.

The aim of this study was to evaluate the effects of Opuntia humifusa (OH) on cerulein-induced acute pancreatitis (AP).Acute pancreatitis was induced via intraperitoneal injection of cholecystokinin analog cerulein (50 μg/kg). In the OH pretreatment group, OH was administered intraperitoneally (100, 250, or 500 mg/kg) 1 hour before first cerulein injection. In the posttreatment group, OH was administered intraperitoneally (500 mg/kg) 1 hour after the first cerulein injection. Furthermore, we isolated the pancreatic acinar cells using collagenase method, then investigated the acinar cell viability, cytokine productions, and the regulating mechanisms.The both pretreatment and posttreatment of OH treatment attenuated the severity of AP, as shown by the histology of the pancreas and lung, and inhibited neutrophil infiltration; serum amylase and lipase activities; proinflammatory cytokine expression such as interleukin 1, interleukin 6, and tumor necrosis factor α; and cell death including apoptosis and necrosis. Furthermore, OH inhibited the activation of c-Jun N-terminal kinases.These results suggest that OH reduces the severity of AP by inhibiting acinar cell death through c-Jun N-terminal kinases.

We have previously reported that bee venom (BV) has a protective role against acute pancreatitis (AP). However, the effects of apamin, the major compound of BV, on AP have not been determined. The aim of this study was to evaluate the effects of apamin on cerulein-induced AP.AP was induced via intraperitoneal injection of supramaximal concentrations of the stable cholecystokinin analogue cerulein (50 μg/kg) every hour for 6 times. In the apamin treatment group, apamin was administered subcutaneously (10, 50, or 100 μg/kg) at both 18 and 1 h before the first cerulein injection. The mice were sacrificed at 6 h after the final cerulein injection. Blood samples were obtained to determine serum amylase and lipase levels, as well as cytokine production. The pancreas and lung were rapidly removed for morphologic and histological examination, myeloperoxidase (MPO) assay, and real-time reverse transcription-polymerase chain reaction. Furthermore, we isolated the pancreatic acinar cells to specify the role of apamin in AP.Pre-treatment with apamin inhibited histological damage, pancreatic weight/body weight ratio, serum level of amylase and lipase, MPO activity, and cytokine production. In addition, apamin treatment significantly inhibited cerulein-induced pancreatic acinar cell death. Furthermore, apamin treatment inhibited the cerulein-induced activation of c-Jun NH2-terminal kinases (JNK).These results could suggest that apamin could protect against AP by inhibition of JNK activation.

Objectives : Lonicerae Japonicae Flos (LJF) has been shown anti-oxidant, anti-inflammatory, anti-viral, anti-rheumatoid properties. However, it is still largely unknown whether LJF inhibits skin injury against oxidative stress in human keratin ocyte, HaCaT cells. The purpose of this study was to evaluate the protective effects of LJF against hydrogen peroxide(H2O2)-induced oxidative stress in human keratinocytes, HaCaT cells. Methods : To evaluate out the protective effects of LJF on oxidative inju ry in HaCaT cells, an oxidative stress model of HaCaT cells was established under a suitable concentration (500 µM) hydrogen peroxide. HaCaT keratinocyte cells were pre-treated with LJF (0.1, 0.25 or 0.5 mg/ml), and then stimulated with H2O2. Then, the cells were harvested to measure the cell viability, DNA damage, and release of reactive oxygen species (ROS). Results : LJF (0.1, 0.25 or 0.5 mg/ml) itself did not show any significant toxicity in HaCaT cells. The treatment of H2O2 caused the oxidative stress, leading to the cell death, and DNA injury. However, pretreatment with LJF reduced cell death, and DNA injury. The stimulation of H2O2 on HaCaT cells resulted in excessive release of ROS, which is the main factor of oxidative stress. The excessive release of ROS was inhibited by LJF treatment significantly. Conclusions : These results could suggest that LJF exhibited the protective effects of HaCaT cells against H2O2 -induced oxidative stress by inhibiting ROS release. It could be explained that LJF inhibit skin damages against oxidative stress. Thus, LJF would be useful for the dev elopment of drug or cosmetics treating skin troubles.

The modern fashion was developed the basis on the western dress structure and its historical flow was continued until today. Particularly, the Britain has coexised the unique cultural identity in the aristocratic high culture and rebellious tendency of the subculture so it is necessary to the consideration about whole culture in order to grasp the British fashion identity. The purpose of this study was shown the methodological framework of the culture identity research of one country through the background of this formation of culture and process high culture and subculture study by analysis the culture identity in the today`s Britain. Also, the purpose of this study that it draws whether the feature of the British fashion shows up as any aspect in this culture identity. The range of this study subdivides and considers with the imperialism, industrial revolution, aristocratism, union nations, and geographical aspect as the island country into the economy, politics, society, and natural characteristic about the Englishness and the notion of British culture then it draws the dichotomy of the British fashion through the culture identity formed in this society cultural background with both sides in the high culture and subculture aspect.

Objective ： Lithospermum Erythrorhizon (LE) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that LE aqueous extract could show the anti-inflammatory effects in RAW 264.7cells. The purpose of this study was to investigate the anti-inflammatory effect of aqueous extract from LE on lipopolysaccharide (LPS) - induced inflammatory response. Methods ： To measure out the cytotoxicity of LE, we performed the MTT assay. To evaluate the anti-inflammatory effects of LE, we examined the inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin, (IL)-1β and (IL)-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB) activation by western blot. Results ： Aqueous Extract from LE itself did not have any cytotoxic effect in RAW 264.7 cells. Aqueous extract from LE inhibited LPS-induced productions of inflammatory mediators such as NO, PGE2, and pro-inflammatory cytokines including TNF-α, IL-1β and IL-6 in RAW 264.7cells. In addition, LE inhibited the phosphorylation of p38 kinases (p38), c-Jun NH2-terminal kinase (JNK), and NF-κB activation in RAW 264.7 cells. Conclusion ： LE down-regulated LPS-induced production of inflammatory mediators through the inhibition of p38, JNK and NF-κB activation. Taken together, these results could provide the evidence for the anti-inflammatory effects of LE. Therefore, LE may be a novel target in the management of inflammation and help to support a potential strategy for prevention and therapy of inflammatory diseases.

The design of a 112-element millimeter-wave waveguide slot array antenna to reduce the grating lobe level is presented. A hybrid-phase feeding technique combining a cophase feed and an alternating-phase feed is applied to facilitate the suppression of grating lobes. In addition, a stepped feed waveguide and offset coupling slots aligned in a line are employed to realize a tapered aperture distribution. As a result, grating lobe suppression of 8.1 dB was achieved on the diagonal planes compared to a conventional alternating-phase-fed waveguide slot array antenna. A prototype of the proposed antenna was fabricated and measured. The measured results show that the proposed antenna exhibits a −15 dB reflection bandwidth of 3.4%and an average realized gain of 26.72 dBi within the measured frequency range. Good agreement between the simulated and measured radiation patterns is also observed.

Background Malnutrition in gastrectomized patients receiving chemotherapy is associated with the susceptibility to chemotherapy-related adverse events. This study evaluated pre-operative nutritional status-related indices associated with adverse events in post-operation gastric cancer patients receiving chemotherapy. Methods Medical records of 234 gastrectomized patients under adjuvant tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were analyzed. Nutritional status assessment included Patient-Generated Subjective Global Assessment (PG-SGA), body weight, body mass index, serum albumin concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse events were determined using Common Terminology Criteria for Adverse Events. Results PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the patients revealed serious malnutrition with PG-SGA score of ≥9. Fifteen % of patients lost ≥10% of the initial body weight, 14.5% of the patients had hypoalbuminemia (

Oxidative skin damage and skin inflammation play key roles in the pathogenesis of skin-related diseases. Fisetin is a naturally occurring flavonoid abundantly found in several vegetables and fruits. Fisetin has been shown to exert various positive biological effects, such as anti-cancer, anti-proliferative, neuroprotective and anti-oxidative effects. In this study, we investigate the skin protective effects and anti-inflammatory properties of fisetin in hydrogen peroxide- and TNF-α-challenged human keratinocyte HaCaT cells. When HaCaT cells were treated with non-cytotoxic concentrations of fisetin (1-20μM), heme oxygenase (HO)-1 mRNA and protein expression increased in a dose-dependent manner. Furthermore, fisetin dose-dependently increased cell viability and reduced ROS production in hydrogen peroxide-treated HaCaT cells. Fisetin also inhibited the production of NO, PGE2 IL-1β, IL-6, expression of iNOS and COX-2, and activation of NF-κB in HaCaT cells treated with TNF-α. Fisetin induced Nrf2 translocation to the nuclei. HO-1 siRNA transient transfection reversed the effects of fisetin on cytoprotection, ROS reduction, NO, PGE2, IL-1β, IL-6, and TNF-α production, and NF-κB DNA-binding activity. Moreover, fisetin increased Akt phosphorylation and a PI3K pathway inhibitor (LY294002) abolished fisetin-induced cytoprotection and NO inhibition. Taken together, these results provide evidence for a beneficial role of fisetin in skin therapy.

Myristoylated alanine-rich C kinase substrate-like 1 (MARCKSL1) plays a pivotal role in the regulation of apoptosis and has been shown to maintain antitumor and metastasis-suppressive properties. In the present study, we examined the effects of MARCKSL1 as a novel anti-angiogenic agent on the inhibition of angiogenesis-mediated cell migration. MARCKSL1 also reduced vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) proliferation, as well as capillary-like tubular structure formation in vitro. MARCKSL1 disrupted phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) in ovarian tumorigenesis. In addition, MARCKSL1 showed potent anti-angiogenic activity and reduced the levels of VEGF and hypoxia-inducible factor 1α (HIF-1α) expression, an essential regulator of angiogenesis. Consistently, MARCKSL1 decreased VEGF‑induced phosphorylation of the PI3K/Akt signaling pathway components, including phosphoinositide-dependent protein kinase 1 (PDK-1), mammalian target of rapamycin (mTOR), tuberous sclerosis complex 2 (TSC-2), p70 ribosomal protein S6 kinase (p70S6K), and glycogen synthase kinase 3β (GSK-3β) protein. Collectively, our results provide evidence for the physiological/biological function of an endothelial cell system involved in angiogenesis through suppression of Akt/PDK-1/mTOR phosphorylation by interaction with VEGFR-2.

// Boh-Ram Kim 1,3,* , Seung Hee Seo 1,* , Mi Sun Park 1 , Seung-Hoon Lee 2 , Youngjoo Kwon 3 and Seung Bae Rho 1 1 Research Institute, National Cancer Center, Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do, Republic of Korea 2 Department of Life Science, Yong In University, Samga-dong, Cheoin-gu, Yongin-si Gyeonggi-do, Republic of Korea 3 College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul, Republic of Korea * This authors have contributed equally to this work Correspondence to: Seung Bae Rho, email: // Keywords : sMEK1 tumor suppressor; hypoxic condition; anti-angiogenic activity; ovarian tumor; xenograft model Received : June 28, 2015 Accepted : August 15, 2015 Published : September 10, 2015 Abstract The suppressor of MEK null (sMEK1) protein possesses pro-apoptotic activities. In the current study, we reveal that sMEK1 functions as a novel anti-angiogenic factor by suppressing vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, and capillary-like tubular structure in vitro . In addition, sMEK1 inhibited the phosphorylation of the signaling components up- and downstream of Akt, including phospholipase Cγ1 (PLC-γ1), 3-phosphoinositide-dependent protein kinase 1 (PDK1), endothelial nitric oxide synthetase (eNOS), and hypoxia-inducible factor 1 (HIF-1α) during ovarian tumor progression via binding with vascular endothelial growth factor receptor 2 (VEGFR-2). Furthermore, sMEK1 decreased tumor vascularity and inhibited tumor growth in a xenograft human ovarian tumor model. These results supply convincing evidence that sMEK1 controls endothelial cell function and subsequent angiogenesis by suppressing VEGFR-2-mediated PI3K/Akt/eNOS signaling pathway. Taken together, our results clearly suggest that sMEK1 might be a novel anti-angiogenic and anti-tumor agent for use in ovarian tumor.