Medicarpin Protects Cerebral Microvascular Endothelial Cells Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury via the PI3K/Akt/FoxO Pathway: A Study of Network Pharmacology Analysis and Experimental Validation.

Medicarpin, a pterocarpan class of naturally occurring phytoestrogen possesses various biological functions. However, the effect of medicarpin on oxygen-glucose deprivation-reoxygenation (OGD/R)-induced injury in human cerebral microvascular endothelial cells (HCMECs) remains largely unknown. Target genes of medicarpin were predicted from PharmMapper. Target genes of ischemic stroke were predicted from public databases GeneCards and DisGeNET. Kyoto Encyclopedia of Genes and Genomes pathway enrichment of the intersecting targets was analyzed via DAVID 6.8. Cell viability was evaluated using CCK-8 assay. Malondialdehyde content, superoxide dismutase activity, and glutathione level were detected using corresponding commercially available kits. Cell death was assessed by TUNEL assays. Expression of protein kinase B (Akt), phosphorylated-Akt, forkhead box protein O1, phosphorylated-FoxO1, FoxO3a, and phosphorylated-FoxO3a (p-FoxO3a) was detected by western blot analysis. The intersecting targets of medicarpin and ischemic stroke were significantly enriched in phosphatidylinositol 3-kinase (PI3K)/Akt and FoxO pathways. Medicarpina attenuated OGD/R-evoked viability inhibition, oxidative stress, and cell death in HCMECs. Additionally, medicarpin activated the PI3K/Akt and FoxO pathways in OGD/R-induced HCMECs. Inhibition of PI3K/Akt pathway abrogated the neuroprotective effect of medicarpin on OGD/R-induced injury and activation of FoxO pathway in HCMECs. In conclusion, medicarpin suppressed OGD/R-induced injury in HCMECs by activating PI3K/Akt/FoxO pathway.

MRI-based Bosniak Classification of Cystic Renal Masses, Version 2019: Interobserver Agreement, Impact of Readers' Experience, and Diagnostic Performance.

Background The 2019 Bosniak classification (version 2019) of cystic renal masses (CRMs) provides a systematic update to the currently used 2005 Bosniak classification (version 2005). Further validation is required before widespread application. Purpose To evaluate the interobserver agreement of MRI criteria, the impact of readers' experience, and the diagnostic performance between version 2019 and version 2005. Materials and Methods From January 2009 to December 2018, consecutive patients with CRM who had undergone renal MRI and surgical-pathologic examination were included in this retrospective study. On the basis of version 2019 and version 2005, all CRMs were independently classified by eight radiologists with different levels of experience. By using multirater κ statistics, interobserver agreement was evaluated with comparisons between classifications and between senior and junior radiologists. Diagnostic performance between classifications by dichotomizing classes I-IV into lower (I-IIF) and higher (III-IV) classes was compared by using the McNemar test. P < .05 was considered to indicate a statistically significant difference. Results A total of 207 patients (mean age ± standard deviation, 49 years ± 12; 139 male and 68 female patients) with CRMs were included. Overall, interobserver agreement was higher with version 2019 than version 2005 (weighted κ = 0.64 vs 0.50, respectively; P < .001). Interobserver agreement between senior and junior radiologists did not differ between version 2019 (weighted κ = 0.65 vs 0.64, respectively; P = .71) and version 2005 (weighted κ = 0.54 vs 0.46; P < .001). Diagnostic specificity for malignancy was higher with version 2019 than with version 2005 (83% [92 of 111] vs 68% [75 of 111], respectively; P < .001), without any difference in sensitivity (89% [85 of 96] vs 84% [81 of 96]; P = .34). Conclusion In the updated Bosniak classification, interobserver agreement improved and was unaffected by observers' experience. The diagnostic performance with version 2019 was superior to that with version 2005, with higher specificity. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Choyke in this issue.