Dataset Information

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress.

ABSTRACT: Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy.

SUBMITTER: Giannaccini M

PROVIDER: S-EPMC5843686 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress.

Giannaccini Martina M Usai Alice A Chiellini Federica F Guadagni Viviana V Andreazzoli Massimiliano M Ori Michela M Pasqualetti Massimo M Dente Luciana L Raffa Vittoria V

Cellular and molecular life sciences : CMLS 20171102 7

Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), ...[more]

PMID: 29098325

Similar Datasets

Project description:Researchers recently focused on studying the nutritional and functional qualities of sprouts generated from seeds. The current study investigated the total phenolic content (TPC), total flavonoids (TF), total flavonols (TFL), antioxidant activity (AOA), specific phenolic acids, and volatile chemicals in fennel seeds (FS) and fennel seed sprouts (FSS). The oxidative DNA damage prevention activity of selected FS and FSS extracts against DNA was examined. Consequently, the antioxidative stress potential of FS and FSS extracts at 300 and 600 mg kg-1 on CCl4-induced hepatotoxicity and oxidative stress in rats weas investigated. The liver's functions and oxidative stress biomarkers in rat blood were examined. FSS exhibited rich phytochemical content such as TPC, TF, TFL, and AOA with altered phenolics and volatiles. HPLC identified nineteen compounds of phenolic acids and their derivatives in FS. Thirteen phenolics and six flavonoids were predominantly identified as Vanillic acid and Kaempferol, respectively. GC-MS analysis identified fifty and fifty-one components in FS and FSS, respectively. The predominant component was Benzene, [1-(2-propenyloxy)-3-butenyl] (trans-Anethole) (38.41%), followed by trans-Anethole (Benzene, 1-methoxy-4-(2-propenyl)) (23.65%), Fenchone (11.18%), and 1,7-Octadiene, 2-methyl-6-methylene- Cyclohexene (7.17%). Interestingly, α-Pinene, Fenchone, trans-Anethole (Benzene, 1-methoxy-4-(2-propenyl)), 4-Methoxybenzaldehyde (4-Anisaldehyde), Benzeneacetic acid, α-hydroxy-4-methoxy, and Nonacosane contents were increased. While Dillapiole, 7-Octadecenoic acid, and methyl ester were newly identified and quantified in FSS. The oxidative DNA damage prevention capability of FSS and FS extracts indicated remarkable DNA protection. Administrating FS and FSS extracts at 300 and 600 mg kg-1 ameliorated AST, ALT, and ALP, as well as GSH, CAT, MDA, and SOD, in a dose-dependent manner. The most efficient treatment of FS or FSS was using a dose of 600 mg Kg-1, which recorded an improvement rate of 20.77 and 24.17, 20.36 and 24.92, and 37.49 and 37.90% for ALT, AST, and ALP, respectively. While an improvement rate of 40.08 and 37.87%, 37.17 and 46.52%, 114.56 and 154.13%, and 66.05 and 69.69% for GSH, DMA, CAT, and SOD compared to the CCl4-group, respectively. The observed protection is associated with increased phenolics and volatiles in F. vulgare. Therefore, FS and FSS are recommended as functional foods with bioactive functionality, health-promoting properties, and desired prevention capabilities that may help prevent oxidative stress-related diseases.

Project description:ObjectiveRedox adaptation plays a critical role in cancer cells' drug tolerance and sensitivity. The antioxidative response is induced by nuclear factor erythroid 2-related factor 2 (Nrf2), which triggers the transcriptional activation of genes related to chemosensitivity, glutathione synthesis, and cell protection. Although Nestin1 is known to regulate cellular redox homeostasis by regulating Nrf2 in lung cancer cells, its regulatory effect on the antioxidative state of bladder cancer (BC) cells remains unclear.MethodsThe oxidative stress levels in two cisplatin-treated BC cell lines (T24 and J82) were examined using 2',7'-dichlorofluorescin diacetate staining and real-time quantitative reverse transcription-PCR (RT-qPCR) assays. The cell viability, growth, and apoptosis were determined using CCK-8, colony formation, and flow cytometric assays, respectively. The mRNA and protein levels of Nestin1, Nrf2, and several antioxidant enzymes were quantified using RT-qPCR and western blot assays. A mouse xenograft model was used to determine the effect of Nestin1 on the T24 tumor growth in vivo.ResultsCisplatin treatment induced reactive oxygen species (ROS) generation and antioxidative damage in the T24 and J82 cells, reducing their viability and growth and triggering their apoptosis. Moreover, the Nestin1 and Nrf2 protein levels were enhanced in both treated cell lines. Loss- and gain-of-function assays indicated that Nestin1 expression was positively correlated with the Nrf2 protein expression in the BC cells. Nestin1 overexpression reduced the ROS generation, alleviated the redox disorder, promoted cell viability, and reduced apoptosis, but its silencing had the opposite effects. Importantly, Nestin1 overexpression enhanced the chemoresistance of BC cells to cisplatin in vivo, but its knockdown improved the chemosensitivity of the cells and increased their apoptosis.ConclusionThese results provide a theoretical basis for further targeting the transcription factors, including Nestin1 and Nrf2, in the treatment of BC with cisplatin.

Dataset Information

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress.

Publications

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets