A novel poly-ε-lysine based implant, Proliferate®, for promotion of CNS repair following spinal cord injury

Hosseinzadeh, Sara; Lindsay, Susan L.; Gallagher, Andrew; Wellings, Donald A.; Riehle, Mathis O.; Riddell, John S.; Barnett, Susan C.

doi:10.1039/d0bm00097c

Cited by 4 publications

(3 citation statements)

References 70 publications

(90 reference statements)

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“…SCI is a disorder of the central nervous system mainly characterized by functional disorder or deletion after direct or indirect violence (Gao et al, 2020). The inflammatory response caused by SCI has the dual effects of nerve damage and nerve protection (Hosseinzadeh et al, 2020;Hu et al, 2020;Li et al, 2020). Therefore, it is necessary to use its positive and negative roles in the repairing SCI, that is, selectively exerting its repair potential, while minimizing its destruction.…”

Section: Discussionmentioning

confidence: 99%

Clinic serum levels of Plin5 is therapeutic target of spinal cord injury and Plin5 reduced inflammation in spinal cord injury via silent information regulator 1 dependent inhibition of NLRP3 inflammasome

Liang

Zhao

et al. 2022

Food Sci. Technol

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The study investigated that clinic significance and molecular mechanism of Plin5 in spinal cord injury (SCI). Serum levels of Plin5 was down-regulated and there is a negative correlation between Plin5 and IL-1β levels in patients with SCI,. Human Plin5 protein could reduce inflammation, and prevented spinal cord injury in rat model of SCI. Over-expression of Plin5 reduced inflammation divisors via activation of SIRT1 and suppression of NLRP3 in vitro model of SCI; down-regulation of Plin5 promoted inflammation divisors via inactivation of SIRT1 and induction of NLRP3 in vitro model of SCI. SIRT1 is important targets of Plin5 in inflammation divisors of SCI. The inhibition of SIRT1 reduced the effects of Plin5 on inflammation divisors of SCI. The activation of NLRP3 also reduced the effects of Plin5 on inflammation divisors of SCI. We concluded that clinic Serum levels of Plin5 is therapeutic target of SCI and Plin5 reduced inflammation in SCI via SIRT1 dependent suppression of NLRP3 Inflammasome.

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Section: Discussionmentioning

confidence: 99%

Clinic serum levels of Plin5 is therapeutic target of spinal cord injury and Plin5 reduced inflammation in spinal cord injury via silent information regulator 1 dependent inhibition of NLRP3 inflammasome

Liang

Zhao

et al. 2022

Food Sci. Technol

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“…Blood samples were collected surplus to the study outcomes and were used in this study to maximise the output from animal experiments in the spirit of the 3R's of animal use (replacement, refinement and reduction) [11]. Blood samples were obtained at 1 day (n = 5) or 7 days (n = 5) after a contusion injury performed at the C6 level [12] or at 14 days (n = 8) or 112 days (n = 8) after a complete spinal cord transection performed at the T9 level [13]. Control blood samples were obtained from animals that underwent sham surgery performed at the same spinal level.…”

Section: Animals Used In the Studymentioning

confidence: 99%

Investigation of the blood proteome in response to spinal cord injury in rodent models

et al. 2021

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Study design Explanatory and mechanistic study. Objectives A better understanding of the ‘whole-body’ response following spinal cord injury (SCI) is needed to guide future research aimed at developing novel therapeutic interventions and identifying prognostic indicators for SCI. This study aimed to characterise the blood proteome following contusion or complete SCI compared to a sham injury in rat models. Setting United Kingdom. Methods Pooled blood samples from one and seven days after a contusion (serum; n = 5) or from 14 days and 112 days post-complete transection SCI (plasma; n = 8) and their sham-injured counterparts were subjected to independent iTRAQ nanoflow liquid chromatography tandem mass-spectrometry proteomic analyses. Pathway analyses of the proteins that were differentially abundant between SCI and their matched sham injured counterparts were completed to indicate biological pathways that may be changed in response to SCI. Results Eleven and 42 proteins were differentially abundant (≥±2.0 FC; p ≤ 0.05) between the contusion SCI and sham injured animals at 24 h and seven days post-injury, respectively. Seven and tweleve proteins were differentially abundant between complete and sham injured rats at 14 and 112 days post-injury, respectively. Acute-phase response signalling and Liver X Receptor/Retinoic X Receptor activation were identified as differentially regulated pathways in both models of SCI. Conclusions We have utilised longitudinal preclinical SCI models to provide an insight into the blood proteome changes that result following SCI and to highlight a number of biological pathways of interest for future studies.

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“…Poly(e-lysine)-MW4kD (e-PL) is one of the most preferred starting materials for the synthesis of polymers with novel architectures. poly(e-lysine) is a linear cationic homopolyamide of 25-35 L-lysine residues, having peptide linkage between a-carboxyl and e-amino groups (Shih et al, 2006;Hosseinzadeh et al, 2020). Recently, poly(e-lysine) is extensively explored in biomedical field, especially in drug and gene delivery (Tian et al, 2013;Liu et al, 2014;Lv et al, 2014;Yuan et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrin pendant polymer as an efficient drug carrier for scutellarin

Liao

Liu

et al. 2020

Drug Delivery

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A novel β-cyclodextrin pendant polymer (ε-PL-CD), composed of poly(ε-lysine) (ε-PL) main chain and glycine-β-cyclodextrin (Gly-CD) side chains, was prepared by a simple two-step procedure. The ε-PL-CD was investigated as a drug carrier of hydrophobic drug scutellarin (SCU). The characterization and complexation mode of the SCU:ε-PL-CD were researched in both solution and solid state by means of photoluminescence spectroscopy, 1 H and 2D NMR, X-Ray powder diffraction (XRPD), thermal gravimetric analysis, Particle size and Zeta potential. The solubility test indicated that the solubilizing ability of SCU:ε-PL-CD was significantly improved compared with SCU:β-CD and free SCU. Besides, in vitro cell experiment, it was found that SCU:ε-PL-CD has a strong inhibitory effect on the growth and invasion of tumor cells. The present study provides useful information for ε-PL-CD as a drug carrier material.

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A novel poly-ε-lysine based implant, Proliferate®, for promotion of CNS repair following spinal cord injury

Abstract: Prolierate® is a promisingcandidate for SCI implantation.

Cited by 4 publications

References 70 publications

Clinic serum levels of Plin5 is therapeutic target of spinal cord injury and Plin5 reduced inflammation in spinal cord injury via silent information regulator 1 dependent inhibition of NLRP3 inflammasome

Clinic serum levels of Plin5 is therapeutic target of spinal cord injury and Plin5 reduced inflammation in spinal cord injury via silent information regulator 1 dependent inhibition of NLRP3 inflammasome

Investigation of the blood proteome in response to spinal cord injury in rodent models

Cyclodextrin pendant polymer as an efficient drug carrier for scutellarin

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