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Smart Harrell posted an update 6 months, 2 weeks ago
Such imaging methods could be valuable in the precise selection of patients that are likely to benefit from hypoxia-modifying nanotherapies.Claudin-4 (CLDN4) is a tight junction protein to maintain the cancer microenvironment. We recently reported the role of the CLDN4 not forming tight junction in the induction of epithelial-mesenchymal transition (EMT). Herein, we investigated the role of CLDN4 in renal cell carcinoma (RCC), focusing on CLDN4. Deutenzalutamide cell line CLDN4 expression in 202 RCCs was examined by immunostaining. CLDN4 phosphorylation and subcellular localization were examined using high metastatic human RCC SN12L1 and low metastatic SN12C cell lines. In 202 RCC cases, the CLDN4 expression decreased in the cell membrane and had no correlation with clinicopathological factors. However, CLDN4 was localized in the nucleus in 5 cases (2%), all of which were pT3. Contrastingly, only 6 of 198 nuclear CLDN4-negative cases were pT3. CLDN4 was found in the nuclear fraction of a highly metastatic human RCC cell line, SN12L1, but not in the low metastatic SN12C cells. In SN12L1 cells, phosphorylation of tyrosine and serine residues was observed in cytoplasmic CLDN4, but not in membranous CLDN4. In contrast, phosphorylation of serine residues was observed in nuclear CLDN4. In SN12L1 cells, CLDN4 tyrosine phosphorylation by EphA2/Ephrin A1 resulted in the release of CLDN4 from tight junction and cytoplasmic translocation. Furthermore, protein kinase C (PKC)-ε phosphorylated the CLDN4 serine residue, resulting in nuclear import. Contrarily, in SN12C cells that showed decreased expression of EphA2/Ephrin A1 and PKCε, the activation of EphA2/EphrinA1 and PKCε induced cytoplasmic and nuclear translocation of CLDN4, respectively. Furthermore, the nuclear translocation of CLDN4 promoted the nuclear translocation of Yes-associated protein (YAP) bound to CLDN4, which induced the EMT phenotype. These findings suggest that the release of CLDN4 by impaired tight junction might be a mechanism underlying the malignant properties of RCC. These findings suggest that the release of CLDN4 by impaired tight junction might be one of the mechanisms of malignant properties of RCC.Oral lichen planus (OLP) is a chronic inflammatory oromucosal disease. The N-acylethanolamines (NAEs), are a family of endogenous biologically active lipid mediators, with palmitoylethanolamide (PEA) being of particular interest here due to its anti-inflammatory and analgesic properties. In this study using oral mucosa biopsies from OLP patients and healthy controls, we investigated whether NAE synthesis was mobilized in response to the inflammation associated with OLP. PTGS2 levels, coding for cyclooxygenase-2 (COX-2), were increased approximately 4-fold in OLP compared to controls and a significant increase in the ratio of PTGS2 to NAPEPLD, the latter coding for a key enzyme in NAE synthesis, was seen. This was matched by an increased ratio of COX-2-derived prostaglandins to PEA in a second patient cohort. We conclude that there is an imbalance between prostaglandins and PEA in OLP, opening up the possibility that PEA might be a useful treatment for this disorder.Considering the importance of the food environments for health promotion, and the lack of simple, easy to use, low-cost measures of the quality of meals, the authors developed a qualitative menu index (KIMEHS-Kids’ Menu Healthy Score), tailored to children’s menu evaluation. Development of the tool was based on the Mediterranean food pattern. It includes 18 components, divided into seven main groups that reflect key aspects of menu quality, including protein source, side dishes, vegetables, dessert and beverages, and also allergens and nutritional information. The index was analysed for content and construct validity, as well as inter-rater reliability, and was applied to a sample of menus from restaurants in shopping centres in the Lisbon region. Possible index point ranges from -17 to 17, with a higher score indicating greater compliance with the recommendations. A value of 5.5 is obtained if all KIMEHS items are available, considering healthy and non-healthy options. The inter-rater reliability was assessed and values above 0.80 were obtained for Alpha Cronbach, as well as agreement % rate >75%. Agreement percentage is above 75% for all the components. Evaluated restaurants scored from -14 to 7, with an average KIMEHS of -6.15. Only four restaurants scored positive values, ranging from 0.25 to 7. KIMEHS was considered to be an adequate index to evaluate children’s menus, from the menu information displayed on restaurant websites and/or on restaurant displays or table menus. It is a simple, low-cost tool that may be used as a reference for health professionals as an objective measure to evaluate the food environment. Stakeholders could also be involved in their own assessment to help educate consumers about healthy food choices, strengthening the efforts to promote an adequate food pattern and health, contributing to the fight against obesity.Daily PM2.5 (particulate matter with aerodynamic diameter ≤2.5 μm) samples were simultaneously collected at two background sites (Wajima Air Monitoring Station (WAMS) and Fukue-Jima Atmosphere and Aerosol Monitoring Station (FAMS)) in Japan in the East Asian winter and summer monsoon periods of 2017 and 2019, to compare the characteristics of air pollutants among different regions and to determine the possible variation during the long-range transport process. Polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (NPAHs), and water-soluble inorganic ions (WSIIs) were analyzed. Despite the PM2.5 concentrations at FAMS (8.90-78.5 µg/m3) being higher than those at WAMS (2.33-21.2 µg/m3) in the winter monsoon period, the average concentrations of ∑PAHs, ∑NPAHs, and ∑WSIIs were similar between the two sites. Diagnostic ratios indicated PAHs mainly originated from traffic emissions and mostly aged, whereas NPAHs were mostly secondarily formed during long-range transport. WSIIs at WAMS were mainly formed via the combustion process and secondary reactions, whereas those at FAMS mainly originated from sea salt and dust. Backward trajectories revealed the air masses could not only come from Asian continental coastal regions but also distant landlocked areas in the winter monsoon period, whereas most came from the ocean in the summer monsoon period. These findings can provide basic data for the establishment of prediction models of transboundary air pollutants in East Asia.