Shiqing Feng

PEGlated magnetic polymeric liposome anchored with TAT for delivery of drugs across the blood-spinal cord barrier

Due to the existence of the blood-spinal cord barrier (BSCB), many therapeutic macromolecular agents, such as drugs, protein and gene, cannot pass through this barrier to reach the site of injury, all of which restricts the treatment of spinal cord injuries (SCI). In this study, TAT-conjugated PEGlated Magnetic polymeric liposomes (TAT-PEG-MPLs) formed from PEGlated amphiphilic octadecyl quaternized carboxymethyl chitosan (PEG-OQCMC), cholesterol (Chol), superparamagnetic nanoparticles, and transactivating-transduction protein (TAT), were prepared successfully and evaluated the properties in vitro and in vivo. The result indicated that TAT-PEG-MPLs were spherical in solution, with significantly small mean diameter (83.2 nm) and excellent magnetism (magnetization saturation values of 43.5 emu/g). In vitro experiment, the uptake of PEG-MPLs with TAT by MCF-7 cells was greater than that of the PEG-MPLs without TAT. Most importantly, in vivo experiment, a low MRI signal was observed in the T(2)-weighted images; Histological analysis, Cryo-TEM and flame atomic absorption spectrophotometry revealed that TAT-PEG-MPLs nanoparticles significantly accumulated around the site of the SCI even inside the nerve cells. These nanoparticles may provide a promising carrier to locate to the lesion site, deliver therapeutic macromolecular agents across the BSCB and penetrate into the nerve cells for the treatment of SCI.

Transplantation of autologous activated Schwann cells in the treatment of spinal cord injury: six cases, more than five years of follow-up.

Schwann cells (SCs) are the main glial cells of the peripheral nervous system, which can promote neural regeneration. Grafting of autologous SCs is one of the well-established and commonly performed procedures for peripheral nerve repair. With the aim to improve the clinical condition of patients with spinal cord injury (SCI), a program of grafting autologous activated Schwann cells (AASCs), as well as a series of appropriate neurorehabilitation programs, was employed to achieve the best therapeutic effects. We selected six patients who had a history of SCI before transplantation. At first, AASCs were obtained by prior ligation of sural nerve and subsequently isolated, cultured, and purified in vitro. Then the patients accepted an operation of laminectomy and cell transplantation, and no severe adverse event was observed in any of these patients. Motor and sensitive improvements were evaluated by means of American Spinal Injury Association (ASIA) grading and Functional Independence Measure (FIM); bladder and urethral function were determined by clinical and urodynamic examination; somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were used to further confirm the functional recovery following transplantation. The patients were followed up for more than 5 years. All of the patients showed some signs of improvement in autonomic, motor, and sensory function. So we concluded that AASC transplantation might be feasible, safe, and effective to promote neurorestoration of SCI patients.

Epidemiological profile of 239 traumatic spinal cord injury cases over a period of 12 years in Tianjin, China

Abstract Study design Hospital-based retrospective review. Objective To describe the epidemiological characteristics and trends of traumatic spinal cord injury in Tianjin, China. Setting Tianjin Medical University General Hospital. Methods Medical records of 239 patients with traumatic spinal cord injury admitted to a general hospital from 1998 to 2009 were reviewed. Variables included gender, age, marital status, occupation, etiology, time of injury, level, and severity of injury. Epidemiological characteristics of different countries were compared. Results Over this period, the mean age of patients with traumatic spinal cord injury was 45.4 ± 14.1 years, and the male/female ratio was 4.6:1. In all, 86.2% were married. The leading cause was fall (52.3%), followed by motor vehicle collision (36.4%). The most common injury site was the cervical spinal cord, accounting for 82.0%. Incomplete tetraplegia made up for 59.4%, followed by complete tetraplegia (22.6%). Eight patients died after operation, six of whom died from respiratory complications. Conclusion The results of this study are in accordance with that of most other developing countries; falls and motor vehicle collisions were the two leading causes, but the mean age was older. Percentage of the aged with traumatic spinal cord injury was increasing. The low-falls group tended to expand over this period. All these data indicated that the preventive programs should focus on the traffic accidents and falls, and more attention should be paid to the aged for the vulnerability to low fall.

MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1.

MicroRNAs have been implicated in drug resistance of osteosarcoma (OS). MicroRNA-301a (miR-301a) is up-regulated and functions as an oncogene in various cancers. However, little is known about the role of miR-301a in drug resistance of OS cells. In this study, we found that doxorubicin induced time-dependent expression of miR-301a in OS cells. Meantime, doxorubicin promoted HMGCR expression and inhibited AMPKα1 expression, which was further facilitated by miR-301a overexpression. Luciferase reporter assay identified AMPKα1 as direct target gene of miR-301a. Notably, miR-301a reduced doxorubicin-induced cell apoptosis whereas anti-miR-301a enhanced apoptosis in OS cells, suggesting that up-regulation of miR-301a contributed to chemoresistance of OS cells. Consistently, our data showed that miR-301a and HMGCR were up-regulated in chemotherapy-resistant OS compared to those in control OS. Our findings suggested that miR-301a might be a potential biomarker for chemotherapy-resistant OS and a promising therapeutic target for overcoming drug resistance of OS.

All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats

Laminectomy is a widely accepted treatment for lumbar disorders, and epidural fibrosis (EF) is a common complication. EF is thought to cause post-operative pain recurrence after laminectomy or discectomy. All-trans retinoic acid (ATRA) has shown anti-fibrotic, anti-inflammatory, and anti-proliferative functions. The object of this study was to investigate the effects of ATRA on the prevention of EF in post-laminectomy rats. In vitro, the anti-fibrotic effect of ATRA was demonstrated with cultured fibroblasts count, which comprised of those that were cultured with/without ATRA. In vivo, rats underwent laminectomy at the L1-L2 levels. We first demonstrated the beneficial effects using 0.05% ATRA compared to vehicle (control group). We found that a higher concentration of ATRA (0.1%) achieved dose-dependent results. Hydroxyproline content, Rydell score, vimentin-positive cell density, fibroblast density, inflammatory cell density and inflammatory factor expression levels all suggested better outcomes in the 0.1% ATRA rats compared to the other three groups. Presumably, these effects involved ATRAs ability to suppress transforming growth factor (TGF-β1) and interleukin (IL)-6 which was confirmed with reverse-transcriptase polymerase chain reaction (RT-PCR). Finally we demonstrated that ATRA down-regulated nuclear factor (NF)-κB by immunohistochemistry and western blotting for p65 and inhibition of κB (IκBα), respectively. Our findings indicate that topical application of ATRA can inhibit fibroblast proliferation, decrease TGF-β1 and IL-6 expression level, and prevent epidural scar adhesion in rats. The highest concentration employed in this study (0.1%) was the most effective. ATRA suppressed EF through down-regulating NF-κB signaling, whose specific mechanism is suppression of IκB phosphorylation and proteolytic degradation.

Comparative efficacy and tolerability of three treatments in old people with osteoporotic vertebral compression fracture: a network meta-analysis and systematic review.

Purpose The question which kind of methods is most suitable for treating the old people for osteoporotic vertebral compression fracture is still discussed and pairwise meta-analyses cannot get hierarchies of these treatments. Our aim is to integrate the evidence to provide hierarchies of the comparative efficacy measured by the change of VAS (Visual Analogue Scale) and tolerability measured by incidence of new fractures and risk of all-cause discontinuation on three treatments (percutaneous vertebroplasty (PVP)、balloon kyphoplasty (BK) and conservative treatment(CT)). Methods We performed a Bayesian-framework network meta-analysis of randomized controlled trials (RCTs) to compare three treatments for the old people with osteoporotic vertebral compression fracture. The eligible RCTs were identified by searching Amed, British Nursing Index, Embase, Pubmed, the Cochrane Central Register of Controlled Trials (CENTRAL), Google scholar, SIGLE, the National Technical Information Service, the National Research Register (UK) and the Current Controlled Trials databases. Data from three outcomes (e.g. VAS, risk of all-cause discontinuation and incidence of new fractures) were independently extracted by two authors. Results A total of five RCTs were finally included into this article. PVP and BK significantly decreased VAS when compared with CT. BK had a significantly lower risk of all-cause discontinuation contrast to CT. Three treatments (BK, PVP and CT) had no significant differences in the incidence of new fractures. Conclusions PVP may be the best way to relieve pain, CT might lead to the lowest incidence of new fractures and BK might had the lowest risk of all-cause discontinuation in old people with osteoporotic vertebral compression fracture. More large-scale and longer duration of follow-up studies are needed.

Epidemiology of traumatic spinal cord injury in Asia: A systematic review

Abstract Study design A systematic review. Background The number of traumatic spinal cord injury (TSCI) reports grows annually, especially in China and Korea. The epidemiological characteristics of TSCI in Asia differ from those in other countries. Thus, we compiled epidemiological factors from Asia to compare with those from other countries. Method We searched articles published in any language between January 1980 to December 2011 using the terms “spinal cord injury”, “traumatic spinal cord injury”, “epidemiology”, and “Asia”. The articles were reviewed for information regarding TSCI incidence, total cases, case criteria, case source, causes of injury, male/female ratio, mean age, prospective or retrospective, neurological level of injury, extent of injury, and America Spinal Injury Association Impairment Scale (AIS)/grade. Results Epidemiological data were extracted from 39 reports in the published literature that met the inclusion criteria. Only two studies reported prevalence rates. Incidence rates ranged from 12.06 to 61.6 per million. The average age ranged from 26.8 to 56.6 years old. Men were at higher risk than women. Motor vehicle collisions (MVCs) and falls were the main causes of TSCI. However, several countries reported war wounds as the major cause. The neurological level and extent of injury were mixed, and most patients were categorized as AIS/Frankel grade A. Conclusion TSCI is an important public health problem and a major cause of paralysis. We must understand the epidemiology to implement appropriate preventative measures. Asian epidemiology is different from that in other regions, so intervention measures must be established according to population-specific characteristics.

Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes cell proliferation and migration by upregulating angiomotin gene expression in human osteosarcoma cells

The long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) has a role in cell proliferation and migration. Angiomotin, encoded by the AMOT gene, is a protein that regulates the migration and organization of endothelial cells. SNHG12 and AMOT have been shown to play a role in a variety of human cancers but have yet to be studied in detail in human osteosarcoma. Tissue samples from primary osteosarcoma (n = 20) and adjacent normal tissues (n = 20), the osteosarcoma cell lines, SAOS-2, MG-63, U-2 OS, and the human osteoblast cell line hFOB (OB3) were studied using Western blot for angiomotin, and quantitative real-time polymerase chain reaction for the expression of SNHG12 and AMOT. The expression of SNHG12 was knocked down using RNA interference. Cell migration assays were performed. Cell apoptosis was studied using flow cytometry. SNHG12 and AMOT messenger RNA (mRNA) expression was upregulated in osteosarcoma tissues and cell lines when compared with normal tissues and cells. Upregulation of AMOT mRNA was associated with upregulation of SNHG12. Knockdown of SNHG12 reduced the expression of angiomotin in osteosarcoma cells and suppressed cell proliferation and migration but did not affect cell apoptosis. This preliminary study has shown that the lncRNA SNHG12 promotes cell proliferation and migration by upregulating AMOT gene expression in osteosarcoma cells in vivo and in vitro. Further studies are recommended to investigate the role of SNHG12 and AMOT expression in tumor cell proliferation and migration and angiogenesis in osteosarcoma and a range of malignant mesenchymal tumors.

A Silk Fibroin/Collagen Nerve Scaffold Seeded with a Co-Culture of Schwann Cells and Adipose-Derived Stem Cells for Sciatic Nerve Regeneration

As a promising alternative to autologous nerve grafts, tissue-engineered nerve grafts have been extensively studied as a way to bridge peripheral nerve defects and guide nerve regeneration. The main difference between autogenous nerve grafts and tissue-engineered nerve grafts is the regenerative microenvironment formed by the grafts. If an appropriate regenerative microenvironment is provided, the repair of a peripheral nerve is feasible. In this study, to mimic the body’s natural regenerative microenvironment closely, we co-cultured Schwann cells (SCs) and adipose-derived stem cells (ADSCs) as seed cells and introduced them into a silk fibroin (SF)/collagen scaffold to construct a tissue-engineered nerve conduit (TENC). Twelve weeks after the three different grafts (plain SF/collagen scaffold, TENC, and autograft) were transplanted to bridge 1-cm long sciatic nerve defects in rats, a series of electrophysiological examinations and morphological analyses were performed to evaluate the effect of the tissue-engineered nerve grafts on peripheral nerve regeneration. The regenerative outcomes showed that the effect of treatment with TENCs was similar to that with autologous nerve grafts but superior to that with plain SF/collagen scaffolds. Meanwhile, no experimental animals had inflammation around the grafts. Based on this evidence, our findings suggest that the TENC we developed could improve the regenerative microenvironment and accelerate nerve regeneration compared to plain SF/collagen and may serve as a promising strategy for peripheral nerve repair.

An Experimental Novel Study: Angelica sinensis Prevents Epidural Fibrosis in Laminectomy Rats via Downregulation of Hydroxyproline, IL-6, and TGF-β1

With laminectomy being widely accepted as the treatment for lumbar disorders, epidural fibrosis (EF) is a common complication for both the patients and the surgeons alike. Currently, EF is thought to cause recurrent postoperative pain after laminectomy or after discectomy. Angelica sinensis is a traditional Chinese medicine which has shown anti-inflammatory, antifibrotic, and antiproliferative properties. The object of this study was to investigate the effects of Angelica sinensis on the prevention of post-laminectomy EF formation in a rat model. A controlled double-blinded study was conducted in sixty healthy adult Wistar rats that underwent laminectomy at the L1-L2 levels. They were divided randomly into 3 groups according to the treatment method, with 20 in each group: (1) Angelica sinensis treatment group, (2) saline treatment group, and (3) sham group (laminectomy without treatment). All rats were euthanized humanely 4 weeks after laminectomy. The hydroxyproline content, Rydell score, vimentin cells density, fibroblasts density, inflammatory cells density, and inflammatory factors expressions all suggested better results in Angelica sinensis group than the other two groups. Topical application of Angelica sinensis could inhibit fibroblasts proliferation and TGF-β1 and IL-6 expressions and prevent epidural scar adhesion in postlaminectomy rat model.