Cardiovascular disease (CVD) is the leading cause of death and a major contributor to disability worldwide. Currently, Korea is among countries with the lowest CVD mortality rates, and the ...age-adjusted CVD mortality rate is still decreasing. However, depending on the CVD type, the mortality and incidence trends vary. Without age-standardization, cerebrovascular disease mortality peaked in 1994 (82.1 per 100K) and continued to decline until 2018 (44.7 per 100K), while heart disease mortality recorded the lowest level in 2001 (44.9 per 100K) then increased again until 2018 (74.5 per 100K). Age-standardized mortality rates showed different trends: both cerebrovascular disease and heart disease mortality rates have declined over the past few decades, although the rate of decline varies. Based on the National Health Insurance claim database, the numbers of hospitalization for cerebrovascular disease and ischemic heart disease are increasing, but the age-standardized hospitalization rates are decreasing. Unlike other types of CVDs, heart failure is rapidly increasing in both mortality and hospitalization rates regardless of age-standardization. Seventy percent of Korean adults have at least one risk factor, 41% have ≥ 2 risk factors, and 19% have ≥ 3 risk factors including hypertension, diabetes, hypercholesterolemia, obesity, and smoking. Exposure to multiple risk factors increases with age, with 65% of senior citizens over 70 having ≥ 2 risk factors and 34% having ≥ 3 risk factors. As the elderly population, especially those with multiple risk factors and chronic disorders, is increasing, the management of this high-risk group will be an important challenge to prevent CVD in Korea.
The prerequisite function of vimentin for the epithelial-mesenchymal transition (EMT) is not clearly elucidated yet. Here, we show that vimentin phosphorylated by PLK1, triggers TGF-β-signaling, ...which consequently leads to metastasis and PD-L1 expression for immune suppression in lung adenocarcinoma. The clinical correlation between expression of both vimentin and PLK1, and overall survival rates of patients was significant in lung adenocarcinoma but not in squamous cell carcinoma. The phosphorylation of vimentin was accompanied by the activation of PLK1 during TGF-β-induced EMT in lung adenocarcinoma. Among the several phosphorylation sites determined by phospho-proteomic analysis and the site-specific mutagenesis, the phosphorylation at S339 displayed the most effective metastasis and tumourigenesis with the highest expression of PD-L1, compared with that of wild-type and other versions in both 3D cell culture and tail-vein injection metastasis models. Phosphomimetic vimentin at S339 interacted with p-Smad2 for its nuclear localization, leading to the expression of PD-L1. Clinical relevance revealed the inverse correlation between the survival rates of patients and the expressions of VIM, PLK1, and CD274 in primary and metastatic lung adenocarcinoma. Thus, PLK1-mediated phosphorylation of vimentin activates TGF-β signaling pathway, leading to the metastasis and immune escape through the expression of PD-L1, functioning as a shuttling protein in lung adenocarcinoma.
Diet is a major lifestyle-related risk factor of various chronic diseases. Dietary intake can be assessed by subjective report and objective observation. Subjective assessment is possible using ...open-ended surveys such as dietary recalls or records, or using closed-ended surveys including food frequency questionnaires. Each method has inherent strengths and limitations. Continued efforts to improve the accuracy of dietary intake assessment and enhance its feasibility in epidemiological studies have been made. This article reviews common dietary assessment methods and their feasibility in epidemiological studies.
Epithelial-to-mesenchymal transition (EMT) is the first step in the development of the invasive and migratory properties of cancer metastasis. Since the transcriptional reprogramming of a number of ...genes occurs in EMT, the regulation of EMT transcription factors has been intensively investigated. EMT transcriptional factors are commonly classified by the direct or indirect repression of E-cadherin because one of hallmarks of EMT is the loss of E-cadherin. This facilitates the expression of genes for EMT, tumor invasion, and metastasis. The posttranslational modification of EMT transcriptional factors, such as Snail and Slug, directly regulates their functions, including their stability, nuclear localization, protein-protein interaction, and ubiquitination for the promotion or termination of EMT at the specific points. Here, we discuss how posttranslational modifications regulate gene expression in a dynamic and reversible manner by modifying upstream signaling pathways, focusing in particular on the posttranslational modifications of Snail, Slug, ZEB1, ZEB2, and TWIST1. This review demonstrates that EMT transcription factors regulate metastasis through their posttranslational modifications and that the flexibility and reversibility of EMT can be modified by phosphorylation.
Accumulating evidence indicates that mitotic protein kinases are involved in metastatic migration as well as tumorigenesis. Protein kinases and cytoskeletal proteins play a role in the efficient ...release of metastatic cells from a tumor mass in the tumor microenvironment, in addition to playing roles in mitosis. Mitotic protein kinases, including Polo-like kinase 1 (PLK1) and Aurora kinases, have been shown to be involved in metastasis in addition to cell proliferation and tumorigenesis, depending on the phosphorylation status and cellular context. Although the genetic programs underlying mitosis and metastasis are different, the same protein kinases and cytoskeletal proteins can participate in both mitosis and cell migration/invasion, resulting in migratory tumors. Cytoskeletal remodeling supports several cellular events, including cell division, movement, and migration. Thus, understanding the contributions of cytoskeletal proteins to the processes of cell division and metastatic motility is crucial for developing efficient therapeutic tools to treat cancer metastases. Here, we identify mitotic kinases that function in cancer metastasis as well as tumorigenesis. Several mitotic kinases, namely, PLK1, Aurora kinases, Rho-associated protein kinase 1, and integrin-linked kinase, are considered in this review, as an understanding of the shared machineries between mitosis and metastasis could be helpful for developing new strategies to treat cancer.
This paper proposes an optimal design method in an asymmetric wireless power transfer (WPT) system for a 150 watt LED TV. The WPT system has three self-resonators: a Tx resonator, an Rx resonator, ...and an intermediate resonator. The Tx and Rx resonators are perpendicular and offset, respectively, to the intermediate resonator in the geometry. For optimal design, the WPT system is analyzed using an equivalent circuit. In particular, a calculation method for mutual inductance in the system is expressed. The calculation results of mutual inductance are used to determine the optimal position of each self-resonator for maximizing the power transfer efficiency. For verification, a WPT system for a 150 watt, 47 inch LED TV is fabricated at 250 kHz. The WPT system exhibits wireless power transfer efficiency of 80%.
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In this study, the concentrations of 10 organophosphorus flame retardants (PFRs) were determined in 89 human breast milk samples collected from Japan, the Philippines and Vietnam. ...Among the targeted PFRs, tris(2-chloroexyl) phosphate (TCEP) and triphenyl phosphate (TPHP) were the predominant compounds and were detected in more than 60% of samples in all three countries. The concentrations of PFRs in human breast milk were significantly higher (p<0.05) in the Philippines (median 70ngg−1lipidwt.) than those in Japan (median 22ngg−1lipidwt.) and Vietnam (median 10ngg−1lipidwt.). The present results suggest that the usage of products containing PFRs in the Philippines is higher than those of Japan and Vietnam. Comparing with a previous literature survey in Sweden, the levels of PFRs in human breast milk from the Philippines were 1.5–2 times higher, whereas levels in Japan and Vietnam were 4–20 times lower, suggesting that these differences might be due to their variation in the usage of flame-retarded products utilized in each country. When daily intake of PFRs to infants via human breast milk was estimated, some individuals accumulated tris(2-butoxyethyl) phosphate (TBOEP) and TCEP were close to reference dose (RfD). This is the first report to identify PFRs in human breast milk samples from Asian countries.
ObjectiveWe explored clinical implications of the new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) by assessing its prevalence and associated cardiovascular disease ...(CVD) risk.DesignFrom nationwide health screening data, we identified 9 775 066 adults aged 20–79 who underwent health examination in 2009. Participants were categorised into four mutually exclusive groups: (1) MASLD; (2) MASLD with increased alcohol intake (MetALD); (3) MASLD with other combined aetiology (the three collectively referred to as MASLD/related steatotic liver disease (SLD)); and (4) no MASLD/related SLD. SLD was determined by fatty liver index ≥30. The primary outcome was CVD event, defined as a composite of myocardial infarction, ischaemic stroke, heart failure or cardiovascular death.ResultsThe prevalence of MASLD, MetALD and MASLD with other combined aetiology was 27.5%, 4.4% and 1.5%, respectively. A total of 8 808 494 participants without prior CVD were followed up for a median of 12.3 years, during which 272 863 CVD events occurred. The cumulative incidence and multivariable-adjusted risk of CVD were higher in participants with MASLD/related SLD than in those without (HR 1.38 (95% CI 1.37 to 1.39)). Multivariable-adjusted HR (95% CI) of CVD events was 1.39 (1.38 to 1.40) for MASLD, 1.28 (1.26 to 1.30) for MetALD and 1.30 (1.26 to 1.34) for MASLD with other combined aetiology compared to the absence of any of these conditions. CVD risk was also higher in participants with metabolic dysfunction-associated fatty liver disease or non-alcoholic fatty liver disease than in those without the respective condition.ConclusionOver one-third of Korean adults have MASLD/related SLD and bear a high CVD risk.
To understand the mechanisms underlying tooth morphogenesis, we examined the developmental roles of important posttranslational modification, O‐GlcNAcylation, which regulates protein stability and ...activity by the addition and removal of a single sugar (O‐GlcNAc) to the serine or threonine residue of the intracellular proteins. Tissue and developmental stage‐specific immunostaining results against O‐GlcNAc and O‐GlcNAc transferase (OGT) in developing tooth germs would suggest that O‐GlcNAcylation is involved in tooth morphogenesis, particularly in the cap and secretory stage. To evaluate the developmental function of OGT‐mediated O‐GlcNAcylation, we employed an in vitro tooth germ culture method at E14.5, cap stage before secretory stage, for 1 and 2 days, with or without OSMI‐1, a small molecule OGT inhibitor. To examine the mineralization levels and morphological changes, we performed renal capsule transplantation for one and three weeks after 2 days of in vitro culture at E14.5 with OSMI‐1 treatment. After OGT inhibition, morphological and molecular alterations were examined using histology, immunohistochemistry, real‐time quantitative polymerase chain reaction, in situ hybridization, scanning electron microscopy, and ground sectioning. Overall, inhibition of OGT resulted in altered cellular physiology, including proliferation, apoptosis, and epithelial rearrangements, with significant changes in the expression patterns of β‐catenin, fibroblast growth factor 4 (fgf4), and sonic hedgehog (Shh). Moreover, renal capsule transplantation and immunolocalizations of Amelogenin and Nestin results revealed that OGT‐inhibited tooth germs at cap stage exhibited with structural changes in cuspal morphogenesis, amelogenesis, and dentinogenesis of the mineralized tooth. Overall, we suggest that OGT‐mediated O‐GlcNAcylation regulates cell signaling and physiology in primary enamel knot during tooth development, thus playing an important role in mouse molar morphogenesis.
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