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Chronic elevation of circulating ANG II is associated with cardiac remodeling in patients with hypertension and heart failure. The underlying mechanisms, however, are not completely defined. Herein, we studied ANG II-induced molecular and cellular events in the rat heart as well as their links to the redox state. We also addressed the potential contribution of aldosterone (ALDO) on ANG II-induced cardiac remodeling. In ANG II-treated rats, and compared with controls, we found: 1) the expression of proinflammatory/profibrogenic mediators was significantly increased in the perivascular space and at the sites of microscopic injury in both ventricles: 2) macrophages and myofibroblasts were primary repairing cells at these sites, together with increased fibrillar collagen volume; 3) apoptotic macrophages and myofibroblasts were evident at the same sites: 4) NADPH oxidase (gp[91.sup.phox]) was significantly enhanced at these regions and primarily expressed by macrophages, whereas superoxide dismutase and catalase levels remained unchanged; 5) plasma 8-isoprostane levels were significantly increased; and 6) blood pressure was significantly elevated. Losartan treatment completely prevented cardiac oxidative stress as well as molecular/cellular responses and normalized blood pressure. Spironolactone treatment partially suppressed the cardiac inflammatory/fibrogenic responses and redox state. Thus chronic elevation of circulating ANG II is accompanied by a proinflammatory/profibrogenic phenotype involving vascular and myocardial remodeling in both ventricles. Enhanced reactive oxygen species production at these sites and increased plasma 8-isoprostane indicate the involvement of oxidative stress in ANG II-induced cardiac injury. ALDO contributes, in part, to ANG II-induced cardiac molecular and cellular responses. cardiac remodeling; angiotensin II; aldosterone; oxidative stress: rats

TBC1Domain Family Member 25 (TBC1D25) is a protein that contains a TBC/RAB‐GTPase activating protein (GAP) domain, which was shown to participate in autophagy in previous studies. However, the role of TBC1D25 in cerebral ischemia‐reperfusion (I/R) injury remains unknown. In this study, we found that the mRNA and protein expression levels of TBC1D25 decreased in mouse brain after I/R injury and primary cortical neurons treated with oxygen and glucose deprivation/reoxygenation (OGD/R). Then TBC1D25 knockout (KO) mice were applied to demonstrate that TBC1D25 ablation aggravated cerebral I/R‐induced neuronal loss and infarct size. In addition, neuronal apoptosis and inflammation were significantly potentiated in the TBC1D25‐KO group. In in vitro OGD/R model, TBC1D25 knockdown can attenuate neuronal cell viability and aggravate the process of inflammation and apoptosis. Conversely, over‐expression of TBC1D25 in primary neurons ameliorated the aforementioned processes. Mechanistically, RNA‐sequencing (RNA‐seq) analysis revealed mitogen‐activated protein kinase (MAPK) signaling pathway was the most significant pathway that contributed to TBC1D25‐mediated brain I/R injury process. Through experimental verification, TBC1D25 deficiency increased the phosphorylation of the transforming growth factor‐β‐activated kinase 1 (TAK1)‐c‐Jun N‐terminal kinase (JNK)/p38 axis in neurons during the brain I/R injury. Furthermore, we found that TAK1 blockade abrogated the apoptosis and inflammatory response produced by TBC1D25 knockdown in vitro. In conclusion, this study is the first to demonstrate the functional significance of TBC1D25 in the pathophysiology of brain I/R injury, and the protective mechanism of TBC1D25 is dependent on the TAK1‐JNK/p38 pathway. [ABSTRACT FROM AUTHOR]

Background: To summarize the safety and effectiveness of high flow extracranial to intracranial saphenous vein bypass grafting in the treatment of complex intracranial aneurysms.Methods: The data of complex intracranial aneurysms patients for high flow extracranial to intracranial saphenous vein bypass grafting from January 2008 to January 2020 were retrospectively collected and analyzed. Eighty-two patients (31 men and 51 women) with 89 aneurysms underwent 82 saphenous vein bypass grafts followed by immediate parent vessel occlusion. The aneurysm was located at the internal carotid artery, middle cerebral artery, and basilar artery in 75, 11, and 3 cases, respectively.Results: The patency rate of bypass grafting was 100, 100, 96.3 and 92.4% on intraoperation, on the first postoperative day, at discharge and 6 months follow-up, respectively. At discharge and 6 months follow-up, 3 and 6 patients had graft occlusions. The main postoperative complications were transient hemiparesis and hemianopsia. 3 patients died due to bypass complications and poor physical condition.Conclusions: High flow extracranial to intracranial saphenous vein bypass grafting is safe and effective in the treatment of complex intracranial aneurysms and the saphenous vein can meet the requirements of brain blood supply. A high rate of graft patency and adequate cerebral blood flow can be achieved.Highlights: A single-centre long-term retrospective study was conducted to assess the safety and effectiveness of high flow EC-IC saphenous vein bypass grafting in the treatment of complex intracranial aneurysms. The data of 82 patients from January 2008 to January 2020 were retrospectively collected and analysed. We found the patency rate of bypass grafting was 100, 100, 96.3 and 92.4% on intraoperation, on the first postoperative day, at discharge and 6 months follow-up, respectively. At discharge and 6 months follow-up, 3 and 6 patients had graft occlusions. Finally, we conclude that high flow extracranial to intracranial saphenous vein bypass grafting is safe and effective in the treatment of complex intracranial aneurysms and the selected blood supply vessels can meet the requirements of blood supply. As far as we know, this study is one of the maximum number of cases in the treatment of complex intracranial aneurysms with saphenous vein bypass. [ABSTRACT FROM AUTHOR]

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P  < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20–v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P  = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability. [ABSTRACT FROM AUTHOR]