306 research outputs found

    Gomisin A Suppresses Colorectal Lung Metastasis by Inducing AMPK/p38-Mediated Apoptosis and Decreasing Metastatic Abilities of Colorectal Cancer Cells

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    Gomisin A (G.A) is a dietary lignan compound from Schisandra chinensis. In this study, the effect of G.A on the proliferation and metastasis of colorectal cancer (CRC) cells was investigated using several CRC cell lines and a lung metastasis mouse model. Both oral and intraperitoneal administration of G.A (50 mg/kg) inhibited lung metastasis of CT26 cells. Various concentrations of G.A were incubated with CRC cell lines and their viability was determined using a cell counting kit-8 assay. G.A significantly decreased the viability of various CRC cell lines, whereas it did not change the proliferation of normal colon cells. G.A induced G0/G1 phase arrest and apoptosis of CT26 and HT29 cells by regulating cyclin D1/cyclin-dependent kinase 4 (CDK4) expression and apoptotic proteins such as caspases and B-cell lymphoma-2 (Bcl-2) family proteins, respectively. G.A-induced apoptosis was mediated by AMPK/p38 activation in CRC cells. A non-cytotoxic concentration of G.A inhibited epithelial–mesenchymal transition of CRC cells by modulating E-cadherin and N-cadherin expression levels. Moreover, the migration and invasion of CRC cells were reduced by G.A treatment. Especially, G.A decreased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities. G.A ameliorated lung metastasis of CRC cells by decreasing cell survival and metastatic abilities of CRC cells. Thus, G.A might be a potential novel therapeutic agent for metastatic CRC

    Src Is a Prime Target Inhibited by Celtis choseniana

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    Celtis choseniana is the traditional plant used at Korea as a herbal medicine to ameliorate inflammatory responses. Although Celtis choseniana has been traditionally used as a herbal medicine at Korea, no systemic research has been conducted on its anti-inflammatory activity. Therefore, the present study explored an anti-inflammatory effect and its underlying molecular mechanism using Celtis choseniana methanol extract (Cc-ME) in macrophage-mediated inflammatory responses. In vitro anti-inflammatory activity of Cc-ME was evaluated using RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS), pam3CSK4 (Pam3), or poly(I:C). In vivo anti-inflammatory activity of Cc-ME was investigated using acute inflammatory disease mouse models, such as LPS-induced peritonitis and HCl/EtOH-induced gastritis. The molecular mechanism of Cc-ME-mediated anti-inflammatory activity was examined by Western blot analysis and immunoprecipitation using whole cell and nuclear fraction prepared from the LPS-stimulated RAW264.7 cells and HEK293 cells. Cc-ME inhibited NO production and mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and tumor necrosis factor-alpha (TNF-α) in the RAW264.7 cells and peritoneal macrophages induced by LPS, pam3, or poly(I:C) without cytotoxicity. High-performance liquid chromatography (HPLC) analysis showed that Cc-ME contained anti-inflammatory flavonoids quercetin, luteolin, and kaempferol. Among those, the content of luteolin, which showed an inhibitory effect on NO production, was highest. Cc-ME suppressed the NF-κB signaling pathway by targeting Src and interrupting molecular interactions between Src and p85, its downstream kinase. Moreover, Cc-ME ameliorated the morphological finding of peritonitis and gastritis in the mouse disease models. Therefore, these results suggest that Cc-ME exerted in vitro and in vivo anti-inflammatory activity in LPS-stimulated macrophages and mouse models of acute inflammatory diseases. This anti-inflammatory activity of Cc-ME was dominantly mediated by targeting Src in NF-κB signaling pathway during macrophage-mediated inflammatory responses

    Study on Threat Modeling in Smart Greenhouses

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    In the era of agriculture 4.0, cutting-edge technologies including Information and communication technology (ICT) is being introduced into traditional agriculture. As farm intelligence emerges as a key area of smart agriculture, the scope of agriculture has expanded from the seed industry to distribution and logistics, however the area that is still most directly connected to the physical agricultural environment is smart farming. Cybersecurity incidents or cybercrimes in smart farming can directly damage crops and harm human safety. Research on individual technical elements that constitute smart farming has been ongoing for a long time relatively, however it has not been long since the work of systematically identifying and classifying threats to smart agriculture as a whole. In this study, STRIDE threat modeling is used to identify cyber threats to greenhouse and make system design more robust. Through this work, we have derived 126 threats and have created 4 types of attack trees. It will be the basis to allow systematic threat classification more clearly in smart greenhouse

    Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine

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    Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance

    Population health outcomes in South Korea 1990-2019, and projections up to 2040: a systematic analysis for the Global Burden of Disease Study 2019

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    BACKGROUND: South Korea has one of the longest operating universal health coverage (UHC) systems. A comprehensive analysis of long-term trajectories of morbidity and mortality in the South Korean population after the inception of UHC is needed to inform health-care policy and practice. METHODS: We used data from the Global Burden of Disease Study (GBD) 2019 to present estimates of cause-specific mortality, incidence, prevalence, years of life lost (YLLs), years of life lived with disability, and disability-adjusted life-years (DALYs) in South Korea from 1990 to 2019. We also examined forecasted estimates of YLLs up to 2040 to investigate likely future changes in disease burden. Finally, we evaluated GBD estimates from seven comparator countries to place disease burden in South Korea within a broader context. FINDINGS: Age-standardised DALYs related to non-communicable diseases (NCDs) decreased by 43·6% (95% uncertainty interval [UI] 39·4-47·9) and mortality by 58·8% (55·9-60·5) from 1990 to 2019. In 2019, the ratio of male to female age-standardised rates of YLLs in South Korea was higher than the global average for 75·9% (22 of 29 diseases) of leading causes, indicating a disproportional disease burden on males in South Korea. Among risk factors, tobacco use accounted for the highest number of 2019 deaths (44 470 [95% UI 37 432-53 989]) in males and high systolic blood pressure for the highest number (21 014 [15 553-26 723]) in females. Among the top ten leading causes of YLLs forecast in South Korea in 2040, nine were NCDs, for both males and females. INTERPRETATION: Our report shows a positive landscape of population health outcomes in South Korea following the establishment of UHC. However, due in part to the effects of population ageing driving up medical expenditures for NCDs, financial pressures and sustainability challenges associated with UHC are pressing concerns. Policy makers should work to tackle population ageing and allocate resources efficiently by prioritising interventions that address the leading causes of death and disability identified in this study. FUNDING: Bill & Melinda Gates Foundation

    Truly form-factor–free industrially scalable system integration for electronic textile architectures with multifunctional fiber devices

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    Funding Information: This work was supported by the European Commission (H2020, 1D-NEON, grant agreement ID: 685758). J.M.K. and L.G.O. acknowledge the support from the U.K. Research and Innovation (EPSRC, EP/P027628/1). We thank Y. Bernstein and J. Faulkner for helping with grammar check. Funding Information: Acknowledgments Funding:ThisworkwassupportedbytheEuropeanCommission(H2020,1D-NEON,grant agreementID:685758).J.M.K.andL.G.O.acknowledgethesupportfromtheU.K.Researchand Innovation(EPSRC,EP/P027628/1).W ethankY .BernsteinandJ.Faulknerforhelpingwith grammarcheck.Authorcontributions:S.L.andJ.M.K.conceivedtheproject.S.L.,L.G.O.,P .B., R.Martins,andJ.M.K.supervisedtheproject.S.L.andH.L.developedF-PD.S.L.,Y .-W .L., G.-H.A., D.-W .S., J.I.S.,andS.C.developedF-SC.C.L.F ., A.S.,R.I.,P .B., andR.Martinsdevelopedfiber transistor.S.L.,H.L.,andS.C.developedF-LED.ThefiberdeviceswereevaluatedbyS.L.,H.W .C., D.-W .S., H.L.,S.J.,S.D.H.,S.Y .B., S.Z.,W .H.-C., Y .-H.S., X.-B.F ., T .H.L., J.-W .J., andY .K. The developmentofweavingprocesswasconductedbyS.L.,H.W .C., F .M.M., P .J., andV .G.C. Thelaser interconnectionwasdevelopedbyS.L.,H.W .C., K.U.,M.E.,andM.S.Thetextiledemonstrations werecharacterizedbyS.L.,H.W .C., D.-W .S., J.Y ., S.S.,U.E.,S.N.,A.C.,A.M.,R.Momentè,J.G.,N.D., S.M.,C.-H.K.,M.L.,A.N.,D.J.,M.C.,andY .C. ThismanuscriptwaswrittenbyS.L.andJ.M.K.and reviewed by H.W .C., D.-W .S., M.C.,L.G.O., P .B., E.F ., and G.A.J.A. All authors discussed the results andcommentedonthemanuscript.Competinginterests:Theauthorsdeclarethattheyhave nocompetinginterests.Dataandmaterialsavailability:Alldataneededtoevaluatethe conclusionsinthepaperarepresentinthepaperand/ortheSupplementaryMaterials. Publisher Copyright: Copyright © 2023 The Authors, some rights reserved.An integrated textile electronic system is reported here, enabling a truly free form factor system via textile manufacturing integration of fiber-based electronic components. Intelligent and smart systems require freedom of form factor, unrestricted design, and unlimited scale. Initial attempts to develop conductive fibers and textile electronics failed to achieve reliable integration and performance required for industrial-scale manufacturing of technical textiles by standard weaving technologies. Here, we present a textile electronic system with functional one-dimensional devices, including fiber photodetectors (as an input device), fiber supercapacitors (as an energy storage device), fiber field-effect transistors (as an electronic driving device), and fiber quantum dot light-emitting diodes (as an output device). As a proof of concept applicable to smart homes, a textile electronic system composed of multiple functional fiber components is demonstrated, enabling luminance modulation and letter indication depending on sunlight intensity.publishersversionpublishe
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