Nanoparticles with antioxidant enzymes protect injured spinal cord from neuronal cell apoptosis by attenuating mitochondrial dysfunction

Andrabi, Syed Suhail; Yang, Jun; Gao, Yue; Kuang, Youzhi; Labhasetwar, Vinod

doi:10.1016/j.jconrel.2019.12.001

Cited by 79 publications

(62 citation statements)

References 39 publications

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“…Similar to previous studies, we observed that Brd4 expression is elevated in neurons using a ROS donor, and JQ1 treatment promotes the increased expression of HO-1 and SOD1, both of which have been identified as effective antioxidant enzymes. In addition, oxidative stress is important in promoting apoptosis, and the occurrence of neural apoptosis results in irreversible neural tissue loss both in primary and adjacent injury sites after SCI ( Andrabi et al, 2020 ). In the present study, the results suggested that the inhibition of Brd4 by JQ1 maintains the neural homeostasis and survival of injured spinal cord tissue.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Brd4 by JQ1 Promotes Functional Recovery From Spinal Cord Injury by Activating Autophagy

Xiang

Lin

et al. 2020

Front. Cell. Neurosci.

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Spinal cord injury (SCI) is a destructive neurological disorder that is characterized by impaired sensory and motor function. Inhibition of bromodomain protein 4 (Brd4) has been shown to promote the maintenance of cell homeostasis by activating autophagy. However, the role of Brd4 inhibition in SCI and the underlying mechanisms are poorly understood. Thus, the goal of the present study was to evaluate the effects of sustained Brd4 inhibition using the bromodomain and extraterminal domain (BET) inhibitor JQ1 on the regulation of apoptosis, oxidative stress and autophagy in a mouse model of SCI. First, we observed that Brd4 expression at the lesion sites of mouse spinal cords increased after SCI. Treatment with JQ1 significantly decreased the expression of Brd4 and improved functional recovery for up to 28 day after SCI. In addition, JQ1-mediated inhibition of Brd4 reduced oxidative stress and inhibited the expression of apoptotic proteins to promote neural survival. Our results also revealed that JQ1 treatment activated autophagy and restored autophagic flux, while the positive effects of JQ1 were abrogated by autophagy inhibitor 3-MA intervention, indicating that autophagy plays a crucial role in therapeutic effects Brd4 induced by inhibition of the functional recovery SCI. In the mechanistic analysis, we observed that modulation of the AMPK-mTOR-ULK1 pathway is involved in the activation of autophagy mediated by Brd4 inhibition. Taken together, the results of our investigation provides compelling evidence that Brd4 inhibition by JQ1 promotes functional recovery after SCI and that Brd4 may serve as a potential target for SCI treatment.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Brd4 by JQ1 Promotes Functional Recovery From Spinal Cord Injury by Activating Autophagy

Xiang

Lin

et al. 2020

Front. Cell. Neurosci.

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“…PVAX has shown effectiveness in different types of I/R injuries, including hind limb I/R, liver I/R as well as cardiac I/R [97,98]. Andrabi et al used biodegradable nanoparticles (nano-SOD/CAT) to encapsulate the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) to effectively deliver those enzymes at the lesion site to protect mitochondria from oxidative stress, therefore protecting the spinal cord from secondary injury [99]. Tapeinos et al have developed biodegradable PLGA microspheres coated with collagen type I and MnO 2 nanoparticles to scavenge ROS and protect cells from apoptosis induced by oxidative stress [100].…”

Section: Antioxidant Deliverymentioning

confidence: 99%

Systemic Review of Biodegradable Nanomaterials in Nanomedicine

2020

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Background: Nanomedicine is a field of science that uses nanoscale materials for the diagnosis and treatment of human disease. It has emerged as an important aspect of the therapeutics, but at the same time, also raises concerns regarding the safety of the nanomaterials involved. Recent applications of functionalized biodegradable nanomaterials have significantly improved the safety profile of nanomedicine. Objective: Our goal is to evaluate different types of biodegradable nanomaterials that have been functionalized for their biomedical applications. Method: In this review, we used PubMed as our literature source and selected recently published studies on biodegradable nanomaterials and their applications in nanomedicine. Results: We found that biodegradable polymers are commonly functionalized for various purposes. Their property of being naturally degraded under biological conditions allows these biodegradable nanomaterials to be used for many biomedical purposes, including bio-imaging, targeted drug delivery, implantation and tissue engineering. The degradability of these nanoparticles can be utilized to control cargo release, by allowing efficient degradation of the nanomaterials at the target site while maintaining nanoparticle integrity at off-target sites. Conclusion: While each biodegradable nanomaterial has its advantages and disadvantages, with careful design and functionalization, biodegradable nanoparticles hold great future in nanomedicine.

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“…[18][19][20][21][22] Moreover, the easy distribution of ROS into the neighboring area of the injured site often causes the expansion of the injured site, leading to aggravated secondary injury with more serious locomotion defects. 16,23 Therefore, the scavenging of ROS has been established to be an effective route to attenuate secondary injury in acute TSCI treatment. 20,21,[23][24][25] In the present study, a type of selenium-doped carbon quantum dots (Se-CQDs) was prepared and used for effectively ameliorating secondary TSCI ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…16,23 Therefore, the scavenging of ROS has been established to be an effective route to attenuate secondary injury in acute TSCI treatment. 20,21,[23][24][25] In the present study, a type of selenium-doped carbon quantum dots (Se-CQDs) was prepared and used for effectively ameliorating secondary TSCI ( Figure 1). The Se-CQDs were prepared via a simple approach, ie, hydrothermal treatment of L-selenocystine.…”

Section: Introductionmentioning

confidence: 99%

“… 18–22 Moreover, the easy distribution of ROS into the neighboring area of the injured site often causes the expansion of the injured site, leading to aggravated secondary injury with more serious locomotion defects. 16 , 23 Therefore, the scavenging of ROS has been established to be an effective route to attenuate secondary injury in acute TSCI treatment. 20 , 21 , 23–25 …”

Section: Introductionmentioning

confidence: 99%

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<p>Selenium-Doped Carbon Quantum Dots Efficiently Ameliorate Secondary Spinal Cord Injury via Scavenging Reactive Oxygen Species</p>

Luo¹,

Wang²,

Liu³

et al. 2020

IJN

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Background The excess production of reactive oxygen species (ROS) after traumatic spinal cord injury (TSCI) has been identified as a leading cause of secondary injury, which can significantly exacerbate acute damage in the injured spinal cord. Thus, scavenging of ROS has emerged as an effective route to ameliorate secondary spinal cord injury. Purpose Selenium-doped carbon quantum dots (Se-CQDs) with the ability to scavenge reactive oxygen species were prepared and used for efficiently ameliorating secondary injury in TSCI. Methods Water-soluble Se-CQDs were easily synthesized via hydrothermal treatment of l -selenocystine. The chemical structure, size, and morphology of the Se-CQDs were characterized in detail. The biocompatibility and protective effects of the Se-CQDs against H 2 O 2 -induced oxidative damage were investigated in vitro. Moreover, the behavioral test, bladder function, histological observation, Western blot were used to investigate the neuroprotective effect of Se-CQDs in a rat model of contusion TSCI. Results The obtained Se-CQDs exhibited good biocompatibility and remarkable protective effect against H 2 O 2 -induced oxidative damage in astrocytes and PC12 cells. Moreover, Se-CQDs displayed marked anti-inﬂammatory and anti-apoptotic activities, which thereby reduced the formation of glial scars and increased the survival of neurons with unscathed myelin sheaths in vivo. As a result, Se-CQDs were capable of largely improving locomotor function of rats with TSCI. Conclusion This study suggests that Se-CQDs can be used as a promising therapeutic platform for ameliorating secondary injury in TSCI.

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Nanoparticles with antioxidant enzymes protect injured spinal cord from neuronal cell apoptosis by attenuating mitochondrial dysfunction

Cited by 79 publications

References 39 publications

Inhibition of Brd4 by JQ1 Promotes Functional Recovery From Spinal Cord Injury by Activating Autophagy

Inhibition of Brd4 by JQ1 Promotes Functional Recovery From Spinal Cord Injury by Activating Autophagy

Systemic Review of Biodegradable Nanomaterials in Nanomedicine

<p>Selenium-Doped Carbon Quantum Dots Efficiently Ameliorate Secondary Spinal Cord Injury via Scavenging Reactive Oxygen Species</p>

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