1,725,523 research outputs found
Revista MultiAtual - ISSN 2675-4592 - v.1, n.3, 2020
No full textRevista MultiAtual - ISSN 2675-4592 - v.1, n.3, 202
Details of initial test result choices (N = 4592).
No full textDetails of initial test result choices (N = 4592).</p
Revista MultiAtual - ISSN 2675-4592 - v.1, n.5, 2020
No full textRevista MultiAtual - ISSN 2675-4592 - v.1, n.5, 202
Block Card 4592 Glenbrier Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Split-Level Style | 4592 Glenbrier Road (Toledo, Ohio) | Dwelling | Glendale Hills (Toledo, Ohio) | South Toledo Area (Toledo, Ohio
Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury
No full textRenal hypoxia occurs in acute kidney injury (AKI) of various etiologies. Activation of hypoxia-inducible transcription factor (HIF) has been identified as an important mechanism of cellular adaptation to low oxygen. Preconditional HIF activation protects against AKI, suggesting a new approach in AKI treatment. HIF is degraded under normoxic conditions mediated by oxygen-dependent hydroxylation of specific prolyl residues of the regulative α-subunits by HIF prolyl hydroxylases (PHD). FG-4592 is a novel, orally active, small-molecule HIF PHD inhibitor for the treatment of anemia in patients with chronic kidney disease (CKD). The current study aimed to evaluate the effect of FG-4592 (Roxadustat) on cis-diamminedichloroplatinum (cisplatin)-induced kidney injury. In mice, pretreatment with FG-4592 markedly ameliorated cisplatin-induced kidney injury as shown by the improved renal function (blood urea nitrogen (BUN), serum creatinine (Scr), and cystatin C) and kidney morphology (periodic acid-Schiff (PAS) staining) in line with a robust blockade of renal tubular injury markers of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Meanwhile, the renal apoptosis and inflammation induced by cisplatin were also strikingly attenuated in FG-4592-treated mice. Along with the protective effects shown above, FG-4592 pretreatment strongly enhanced HIF-1α in tubular cells, as well as the expressions of HIF target genes. FG-4592 alone did not affect the renal function and morphology in mice. In vitro, FG-4592 treatment significantly up-regulated HIF-1α and protected the tubular cells against cisplatin-induced apoptosis. In summary, FG-4592 treatment remarkably ameliorated the cisplatin-induced kidney injury possibly through the stabilization of HIF. Thus, besides the role in treating CKD anemia, the clinical use of FG-4592 also could be extended to AKI.</jats:p
Image1_Roxadustat (FG-4592) Facilitates Recovery From Renal Damage by Ameliorating Mitochondrial Dysfunction Induced by Folic Acid.jpg
No full textIncomplete recovery from acute kidney injury induced by folic acid is a major risk factor for progression to chronic kidney disease. Mitochondrial dysfunction has been considered a crucial contributor to maladaptive repair in acute kidney injury. Treatment with FG-4592, an inhibitor of hypoxia inducible factor prolyl-hydroxylase, is emerging as a new approach to attenuate renal damage; however, the underlying mechanism has not been fully elucidated. The current research demonstrated the protective effect of FG-4592 against renal dysfunction and histopathological damage on the 7th day after FA administration. FG-4592 accelerated tubular repair by promoting tubular cell regeneration, as indicated by increased proliferation of cell nuclear antigen-positive tubular cells, and facilitated structural integrity, as reflected by up-regulation of the epithelial inter-cellular tight junction molecule occludin-1 and the adherens junction molecule E-cadherin. Furthermore, FG-4592 ameliorated tubular functional recovery by restoring the function-related proteins aquaporin1, aquaporin2, and sodium chloride cotransporter. Specifically, FG-4592 pretreatment inhibited hypoxia inducible factor-1α activation on the 7th day after folic acid injection, which ameliorated ultrastructural abnormalities, promoted ATP production, and attenuated excessive reactive oxygen species production both in renal tissue and mitochondria. This was mainly mediated by balancing of mitochondrial dynamics, as indicated by down-regulation of mitochondrial fission 1 and dynamin-related protein 1 as well as up-regulation of mitofusin 1 and optic atrophy 1. Moreover, FG-4592 pretreatment attenuated renal tubular epithelial cell death, kidney inflammation, and subsequent interstitial fibrosis. In vitro, TNF-α-induced HK-2 cells injury could be ameliorated by FG-4592 pretreatment. In summary, our findings support the protective effect of FG-4592 against folic acid-induced mitochondrial dysfunction; therefore, FG-4592 treatment can be used as a useful strategy to facilitate tubular repair and mitigate acute kidney injury progression.</p
Linked collectors and determiners for: NMU Mammal Collection (Arctos).
No full textNatural history specimen data linked to collectors and determiners held within, "NMU Mammal Collection (Arctos)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/a909e61b-b5f6-4592-a699-428619b3dd55">https://bionomia.net/dataset/a909e61b-b5f6-4592-a699-428619b3dd55</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/a909e61b-b5f6-4592-a699-428619b3dd55">https://gbif.org/dataset/a909e61b-b5f6-4592-a699-428619b3dd55</a>. Formatted as a Frictionless Data package
Linked collectors and determiners for: Herbarium specimens of Jardins botaniques and Conservatoire Botanique of Nancy (NCY).
No full textNatural history specimen data linked to collectors and determiners held within, "Herbarium specimens of Jardins botaniques and Conservatoire Botanique of Nancy (NCY)". Claims or attributions were made on Bionomia by volunteer Scribes, <a href="http://bionomia.net/dataset/e553568e-2317-4592-8638-92e5ac93b40c">https://bionomia.net/dataset/e553568e-2317-4592-8638-92e5ac93b40c</a> using specimen data from the dataset aggregated by the Global Biodiversity Information Facility, <a href="https://gbif.org/dataset/e553568e-2317-4592-8638-92e5ac93b40c">https://gbif.org/dataset/e553568e-2317-4592-8638-92e5ac93b40c</a>. Formatted as a Frictionless Data package
Image3_FG-4592 relieves diabetic kidney disease severity by influencing metabolic profiles via gut microbiota reconstruction in both human and mouse models.TIF
No full textObjective: Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is highly associated with devastating outcomes. Hypoxia-inducible factor (HIF), the main transcription factor that regulates cellular responses to hypoxia, plays an important role in regulating erythropoietin (EPO) synthesis. FG-4592 is the HIF stabilizer that is widely used in patients with renal anemia. We investigated the effect of FG-4592 on DKD phenotypes and the pharmacologic mechanism from the perspective of gut microbiota and systemic metabolism.Design: We collected the clinical data of 73 participants, including 40 DKD patients with combined renal anemia treated with FG-4592, and 33 clinical index-matched DKD patients without FG-4592 treatment from The First Affiliated Hospital of Zhengzhou University at the beginning and after a 3–6-month follow-up period. We established DKD mouse models treated by FG-4592 and performed fecal microbiota transplantation from FG-4592-treated DKD mice to investigate the effects of FG-4592 on DKD and to understand this mechanism from a microbial perspective. Untargeted metabolome–microbiome combined analysis was implemented to globally delineate the mechanism of FG-4592 from both microbial and metabolomic aspects.Result: DKD phenotypes significantly improved after 3–6 months of FG-4592 treatment in DKD patients combined with renal anemia, including a decreased level of systolic blood pressure, serum creatinine, and increased estimated glomerular infiltration rate. Such effects were also achieved in the DKD mouse model treated with FG-4592 and can be also induced by FG-4592-influenced gut microbiota. Untargeted plasma metabolomics-gut microbiota analysis showed that FG-4592 dramatically altered both the microbial and metabolic profiles of DKD mice and relieved DKD phenotypes via upregulating beneficial gut microbiota-associated metabolites.Conclusion: FG-4592 can globally relieve the symptoms of DKD patients combined with renal anemia. In the animal experiment, FG-4592 can reconstruct the intestinal microbial profiles of DKD to further upregulate the production of gut-associated beneficial metabolites, subsequently improving DKD phenotypes.</p
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