Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide, particularly in developed countries. Recently, microRNAs (miRs) have become popular research area to develop new treatment options of AMD. However, interaction between hsa-miR-184 and AMD remain largely unexplored. In this study, sub-lethal levels of Deforoxamine Mesylate salt (DFX) and HO were applied to ARPE-19 cells to establish a severe in vitro AMD model, via durable hypoxia and oxidative stress. We found that up-regulation of miR-184 level in AMD can suppress hypoxia-related angiogenic signals through HIF-1α/VEGF/MMPs axis. Also, miR-184 suppressed the hypoxia sensor miR-155 and genes in the EGFR/PI3K/AKT pathway, which is an alternative pathway in angiogenesis. To investigate the mechanism behind this protective effect, we evaluated the impact of miR-184 on retinal apoptosis in a model of AMD. miR-184 inhibited retinal apoptosis by upregulating BCL-2 and downregulating pro-apoptototic BAX, TRAIL, Caspase 3 and 8 signals as well as p53. Taken together, miR-184 attenuates retinal cell damage induced by severe AMD pathologies through suppressing hypoxia, angiogenesis and apoptosis. The safety profile of miR-184 was observed to be similar to Bevacizumab, which is in wide use clinically, but miR-184 was found to provide a more effective therapeutic potential by regulating simultaneously multiple pathologies.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tiv.2022.105413 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cystine/cysteine is critical for antioxidant response and sulfur metabolism in cancer cells and is one of the most depleted amino acids in the PDAC microenvironment. The effects of cystine limitation stress (CLS) on PDAC progression are poorly understood. Here we report that adaptation to CLS (CLSA) promotes PDAC cell proliferation and tumor growth through translational upregulation of the oxidative pentose phosphate pathway (OxPPP).
View Article and Find Full Text PDFPathophysiological effects of hypoxia on testis function and spermatogenesis.
Nat Rev Urol
January 2025
Discipline of Biological Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, New South Wales, Australia.
Multiple conditions can cause hypoxia in the testis, including exposure to high altitude, sleep apnoea, testicular torsion and varicocele. Varicocele accounts for up to 44% of instances of primary infertility, but the cumulative contribution of hypoxic conditions to male infertility is undefined. Results of controlled hypobaric hypoxia studies have demonstrated a substantial detrimental effect of short-term and long-term exposures on sperm; however, downstream effects on embryo development and offspring health are less well understood.
View Article and Find Full Text PDF6-hydroxygenistein attenuates hypoxia-induced injury via activating Nrf2/HO-1 signaling pathway in PC12 cells.
Sci Rep
January 2025
Department of Pharmacy, the First Affiliated Hospital of Xi'an Jiaotong University, NO.277 Yanta West Road, Yanta District, Xi'an, 710061, Shaanxi, People's Republic of China.
4',5,6,7-tetrahydoxyisoflavone (6-hydroxygenistein, 6-OHG) is a hydroxylated derivative of genistein with excellent antioxidant activity, but whether 6-OHG can protect hypoxia-induced damage is unclear. The objective of current study was to evaluate the protective effect and underling mechanism of 6-OHG against hypoxia-induced injury via network pharmacology and cellular experiments. 6-OHG-related and hypoxia injury-related targets were screened by public databases.
View Article and Find Full Text PDFTumor microenvironment-responsive engineered hybrid nanomedicine for photodynamic-immunotherapy via multi-pronged amplification of reactive oxygen species.
Nat Commun
January 2025
Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontier Science Center of the Materials Biology and Dynamic Chemistry, Shanghai Engineering Research Center of Hierarchical Nanomaterials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, China.
Reactive oxygen species (ROS) is promising in cancer therapy by accelerating tumor cell death, whose therapeutic efficacy, however, is greatly limited by the hypoxia in the tumor microenvironment (TME) and the antioxidant defense. Amplification of oxidative stress has been successfully employed for tumor therapy, but the interactions between cancer cells and the other factors of TME usually lead to inadequate tumor treatments. To tackle this issue, we develop a pH/redox dual-responsive nanomedicine based on the remodeling of cancer-associated fibroblasts (CAFs) for multi-pronged amplification of ROS (ZnPP@FQOS).
View Article and Find Full Text PDFDual-responsive stem cell microspheres modified with BDNF for enhanced neural repair in diabetic erectile dysfunction.
J Control Release
January 2025
Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Institute of Urology, Beijing Municipal Health Commission, Beijing 100050, China. Electronic address:
We previously established an effective method to ameliorate erectile dysfunction (ED) using intracavernous injection (ICI) of mesenchymal stem cell (MSC) microspheres. However, the expression of a key neurotrophic factor, brain-derived neurotrophic factor (BDNF), was low in both MSCs and MSC microspheres, restricting the associated neural repair. Based on the hypoxia and oxidative stress microenvironments within cell spheroids and lesion areas, BDNF-expressing nanocomplexes that are dual-responsive to hypoxia and reactive oxygen species were designed to modify MSCs, achieving high BDNF expression in MSC spheroids.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!