Heart failure (HF) affects over 26 million people worldwide, yet the pathologies of this complex syndrome have not been completely understood. Here, we investigated the involvement of deacetylase Sirtuin 1 (Sirt1) in HF and its downstream signaling pathways. A HF model was induced by the ligation of the left coronary artery in rats, where factors associated with left ventricular echocardiography, heart hemodynamics and ventricular mass indexes were recorded. Collagen volume fraction in heart tissues was determined by Masson’s trichrome staining. Cell models of HF were also established (H 2 O 2 , 30 min) in cardiomyocytes harvested from suckling rats. HF rats presented with downregulated expressions of Sirt1, brain-derived neurotrophic factor (BDNF) and exhibited upregulated expressions of NF-κB p65 and miR-155. Repressed Sirt1 expression increased acetylation of NF-κB p65, resulting in the elevation of NF-κB p65 expression. NF-κB p65 silencing improved heart functions, decreased ventricular mass and reduced apoptosis in cardiomyocytes. MiR-155 inhibition upregulated its target gene BDNF, thereby reducing cardiomyocyte apoptosis. Sirt1 overexpression upregulated BDNF, improved heart function, and reduced apoptosis in cardiomyocytes. In conclusion, Sirt1 alleviates HF in rats through the NF-κB p65/miR-155/BDNF signaling cascade.
Ferroptosis is type of programmed cell death, which is known to be involved in certain cancers. Notch3 signaling is reported to be involved in the tumorigenesis of non‐small‐cell lung cancer (NSCLC) and regulates iron metabolism, lipid synthesis, and oxidative stress in some tissues. However, whether Notch3 signaling regulates ferroptosis is unclear. In this study, we found that ferroptosis inhibitors, ferrostatin‐1 and liproxstatin‐1, protected against cell death induced by Notch3 knockdown and that Notch3 knockdown initiated ferroptosis in NSCLC cells by increasing reactive oxygen species (ROS) levels, lipid peroxidation, and Fe2+ levels, accompanied by downregulation of glutathione peroxidase 4 (GPX4) and peroxiredoxin6 (PRDX6). Conversely, Notch3 intracellular domain overexpression suppressed erastin‐induced ferroptosis, which was synergistically enhanced by MJ33 in H1299 cells via a decrease in ROS levels and lipid peroxidation, accompanied by upregulation of GPX4 and PRDX6. Moreover, Notch3 knockdown decreased tumorigenesis in vivo with downregulation of GPX4 and PRDX6. In summary, here we have identified Notch3 as a potential negative regulator of ferroptosis in NSCLC.
Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system. Although deregulation of the Notch signaling pathway is common in RCC and is involved in the tumorigenic process, the exact role of Notch3 and its underlying molecular mechanism in RCC, particularly in hypoxia, remain unknown. In the present study, RO4929097, a Notch3 inhibitor, was used to alter NICD3 expression. A Cell Counting Kit-8 assay, EdU incorporation assay, colony formation assay, flow cytometry and western blot analysis were used to investigate the effects of altered NICD3 expression on cell proliferation, cell cycle progression and HIF-2α protein expression. The results of western blot analysis showed that RO4929097 dose-dependently decreased the expression of Notch3 intracellular domain (NICD3) in 786-O and ACHN cells, which originate from clear cell RCC (ccRCC). The results of the Cell Counting Kit-8, EdU incorporation and colony formation assays demonstrated that downregulation of NICD3 significantly suppressed cell proliferation in both normoxia and hypoxia. In addition, flow cytometry and western blot analysis demonstrated that hypoxia (2% O 2) promoted cell cycle progression in ccRCC cells with the increased expression of G 1-S transition-associated proteins, namely cyclin-dependent kinase (CDK)4 and cyclin D1, while downregulation of NICD3 exerted negative effects on cell cycle progression, and the expression levels of CDK4 and cyclin D1. Furthermore, western blot analysis revealed that 2% O 2-induced upregulated hypoxia-inducible factor-2α (HIF-2α) expression decreased following downregulation of NICD3 in 786-O and ACHN cells. Following transfection of the vector containing the NICD3 coding sequence, HIF-2α, CDK4, cyclin D1 and proliferating cell nuclear antigen expression,that were inhibited by RO4929097 in hypoxia, were rescued. Collectively, the results of the present study suggest that Notch3 is closely associated with the cell proliferation of ccRCC cells by regulating the cell cycle and HIF-2α.
A time-integration imaging polarimeter with continuous rotating retarder is presented, and its full-Stokes retrieving and configuration optimization are also demonstrated. The mathematical expression between the full-Stokes vector and the time-integration light intensities is derived. As a result, the state of polarization of incident light can be retrieved by only one matrix calculation. However, the modulation matrix deviates from the initial well-conditioned status due to time integration. Thus, we re-optimize the nominal angles for the special retardance of 132° and 90° with an exposure angle of 30°, which results in a reduction of 31.8% and 16.8% of condition numbers comparing to the original configuration, respectively. We also give global optimization results under different exposure angles and retardance of retarder; as a result, the 137.7° of retardance achieves a minimal condition number of 2.0, which indicates a well-conditioned polarimeter configuration. Besides, the frame-by-frame algorithm ensures the dynamic performance of the presented polarimeter. For a general brushless DC motor with a rotating speed of over 2000 rounds per minute, the speed of polarization imaging will achieve up to 270 frames per second. High precision and excellent dynamic performance, together with features of compactness, simplicity, and low cost, may give this traditional imaging polarimeter new life and attractive prospects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.