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Finally, RAS-mediated ECM production was associated with lipid accumulation in HPMCs and depended on the dysregulation of the low-density lipoprotein receptor (LDLr) pathway. HG-stimulated HPMCs showed increased coexpression of LDLr and α-SMA, whereas blockade of RAS activity reversed the effect. Furthermore, inhibition of LDLr signaling decreased α-SMA and collagen type I expression in HPMCs when treated with HG and ANG II. In conclusion, increased intracellular RAS activity impaired lipid homeostasis and induced ECM accumulation in HPMCs by disrupting the LDLr pathway, which contributed to PF.Lysophosphatidic acid (LPA) increases platelet-derived growth factor-B (PDGFB) and connective tissue growth factor (CTGF) production and secretion by proximal tubule (PT) cells through LPA2 receptor-Gqα-αvβ6-integrin-mediated activation of transforming growth factor-β1 (TGFB1). LPA2, β6-integrin, PDGFB, and CTGF increase in kidneys after ischemia-reperfusion injury (IRI), coinciding with fibrosis. The TGFB1 receptor antagonist SD-208 prevents increases of β6-integrin, TGFB1-SMAD signaling, and PDGFB/CTGF expression after IRI and ameliorates fibrosis (Geng H, Lan R, Singha PK, Gilchrist A, Weinreb PH, Violette SM, Weinberg JM, Saikumar P, Venkatachalam MA. Am J Pathol 181 1236-1249, 2012; Geng H, Lan R, Wang G, Siddiqi AR, Naski MC, Brooks AI, Barnes JL, Saikumar P, Weinberg JM, Venkatachalam MA. Am J Pathol 174 1291-1308, 2009). We report now that LPA1 receptor signaling through epidermal growth factor receptor (EGFR)-ERK1/2-activator protein-1 cooperates with LPA2-dependent TGFB1 signaling to additively incrcts may also involve mitigation of injury caused by IRI-induced TGFB1 signaling in endothelial cells and monocytes. Our results have translational implications for using TGFB1 receptor antagonists, LPA1 and LPA2 inhibitors concurrently, and autotaxin inhibitors in acute kidney injury to prevent the development of chronic kidney disease.Renal ischemia-reperfusion (I/R) injury is associated with markedly reduced protein expression of aquaporins (AQPs). Membrane G protein-coupled bile acid receptor-1 (TGR5) has shown protective roles in some kidney diseases. The purpose of the current study was to investigate whether activation of TGR5 prevented the decreased protein expression of AQPs in rodents with renal I/R injury and potential mechanisms. TGR5 agonist lithocholic acid (LCA) treatment reduced polyuria after renal I/R injury in rats. LCA prevented the decreased abundance of AQP2 protein and upregulated hypoxia-inducible factor (HIF)-1α protein expression, which were associated with decreased protein abundance of NF-κB p65 and IL-1β. After renal I/R, mice with tgr5 gene deficiency exhibited further decreases in AQP2 and HIF-1α protein abundance and increases of IL-1β and NF-κB p65 protein expression compared with wild-type mice. In primary cultured inner medullary collecting duct cells with hypoxia/reoxygenation, LCA induced markedly increasGR5 activation exhibits a protective role in acute renal injury induced by I/R.This study aimed at finding the acceptable range, and the optimal value for the locking compression plate (LCP) thickness (THK), through simulating the osteogenic pathway of bone healing, and by checking bone-plate construct's strength and stability. To attain the goals of this research, a multi-objective approach was adopted, which should trade-off between some conflicting objectives. A finite element model of the long bone-plate construct was made first, and validated against an experimental study. The validated model was then employed to determine the initial strength and stability of the bone-plate construct, for the time right after surgery, for various thicknesses of the LCP. Afterward, coupling with a mechano-regulatory algorithm, the iterative process of bone healing was simulated, and follow up was made for each LCP thickness, over the first 16 post-operative weeks. Results of this study regarding the sequence of tissue evolution inside the fracture gap, showed a similar trend with the existing in-vivo data. For the material and structural properties assigned to the bone-plate construct, in this study, an optimal thickness for the LCP was found to be 4.7 mm, which provides an enduring fixation through secondary healing, whereas for an LCP with a smaller or greater thickness, either bone-implant failure, unstable fixation, impaired fracture consolidation, or primary healing may occur. This result is in agreement with a recent study, that has employed a comprehensive optimization approach to find the optimal thickness.Religion provides a powerful social identity. Building on previous work demonstrating that formerly religious individuals (i.e., religious dones) more closely resemble currently religious individuals than do never religious individuals (i.e., religious nones), we report three studies examining a potential religious residue effect for the endorsement of moral foundations. In Study 1 (N = 312), we found evidence of a stairstep pattern of endorsement of the five moral foundations, descending from currently religious to formerly religious to never religious individuals. Study 2 (N = 957) replicated these findings with a larger sample. In Study 3 (N = 2,071), we found evidence for the religious residue effect in a 4-wave longitudinal study of adolescents and young adults and suggest that the residual effects of religion on endorsement of moral foundations may erode over time. [https://www.selleckchem.com/products/BKM-120.html see more] These studies add to a recently burgeoning line of work on the nature and consequences of religious deidentification.<br />Moral courage as a part of nurses' moral competence has gained increasing interest as a means to strengthen nurses acting on their moral decisions and offering alleviation to their moral distress. To measure and assess nurses' moral courage, the development of culturally and internationally validated instruments is needed.<br />The objective of this study was to validate the Dutch-language version of the four-component Nurses' Moral Courage Scale originally developed and validated in Finnish data.<br />This methodological study used non-experimental, cross-sectional exploratory design.<br />A total of 559 nurses from two hospitals in Flanders, Belgium, completed the Dutch-language version of the Nurses' Moral Courage Scale.<br />Good scientific inquiry guidelines were followed throughout the study. Permission to translate the Nurses' Moral Courage Scale was obtained from the copyright holder, and the ethical approval and permissions to conduct the study were obtained from the participating university and hospitals, respectively.