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Study design A systematic review and meta-analysis. Objective This study was performed to evaluate the effects of different rehabilitation interventions in spinal cord injury. Summary of background data Several activity-based interventions have been widely applied in spinal cord injury in the past, but the effects of these rehabilitation exercises are controversial. Methods Publications were searched from databases (PubMed, Embase, Cochrane, the database of the U.S. National Institutes of Health and World Health Organization International Clinical Trials Registry Platform) using the searching terms like spinal cord injury, transcranial magnetic stimulation, functional electrical stimulation, activity-based therapy, and robotic-assisted locomotor training. Randomized controlled trials and controlled trials were included. The primary outcomes included functional upper/lower extremity independence, walking capacity, spasticity, and life quality of individuals with spinal cord injury. Meta-analysis was performed using Revman 5.0 software. Results Thirty-one articles were included. Meta-analysis showed that transcranial magnetic stimulation improved walking speed (95% confidence interval [CI] 0.01, 0.16) and lower extremity function (95% CI 1.55, 7.27); functional electrical stimulation significantly increased upper extremity independence (95% CI 0.37, 5.48). Robotic-assisted treadmill training improved lower extremity function (95% CI 3.44, 6.56) compared with related controls. Conclusion Activity-based intervention like transcranial magnetic stimulation, functional electrical stimulation, and robotic-assisted treadmill training are effective in improving function in individuals with spinal cord injury.Level of Evidence: 1.

This study aimed to evaluate the clinical effects of percutaneous vertebroplasty (PVP) combined with postoperative radiotherapy (RT) in the treatment of spinal metastases. Nine patients (4 males and 5 females, mean age 59.56 years) with painful pathologic compression vertebral fractures caused by metastatic cancers of the spine (5 thoracic levels, 8 lumbar levels) were admitted to our hospital between July 17, 2016 and September 25, 2018. All patients were treated with PVP via bilateral pedicle approach combined with postoperative RT to treat metastatic lesions of the centrum. The clinical records of the patients were retrospectively analyzed. Patients’ demographic features and medical conditions including the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI) and Imageology data were observed. Patients’ mean VAS scores decreased from 8.67 ± 0.50 preoperatively to 1.78 ± 0.83 at 6 months after PVP. Moreover, the mean ODI score decreased from 74.07 ± 13.15 preoperatively to 31.87 ± 10.00 at 6 months after PVP. Significant improvement in the degree of pain and dysfunction among the enrolled patients were observed. Furthermore, the metastatic carcinoma lesion within the vertebral body was well controlled according to imaging. PVP in conjunction with postoperative RT is a good treatment strategy for vertebral compression fractures caused by metastases.

Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired cognitive functions. Fascaplysin is a β-carboline alkaloid isolated from marine sponge Fascaplysinopsis bergquist in 1988. Previous studies have shown that fascaplysin might act on acetylcholinesterase and β-amyloid (Aβ) to produce anti-AD properties. In this study, a series of fascaplysin derivatives were synthesized. The cholinesterase inhibition activities, the neuronal protective effects, and the toxicities of these compounds were evaluated in vitro. Compounds 2a and 2b, the two most powerful compounds in vitro, were further selected to evaluate their cognitive-enhancing effects in animals. Both 2a and 2b could ameliorate cognitive dysfunction induced by scopolamine or Aβ oligomers without affecting locomotor functions in mice. We also found that 2a and 2b could prevent cholinergic dysfunctions, decrease pro-inflammatory cytokine expression, and inhibit Aβ-induced tau hyperphosphorylation in vivo. Most importantly, pharmacodynamics studies suggested that 2b could penetrate the blood-brain barrier and be retained in the central nervous system. All these results suggested that fascaplysin derivatives are potent multitarget agents against AD and might be clinical useful for AD treatment.

Background How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances. Methods We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, Results In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI). Conclusions In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

As RNA interference (RNAi) received solicitous attention by many for its promising performance in gene therapy recently, and how to obtain a choice small interfering RNA (siRNA) vector has become a moot point at this moment. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency and easy penetration across the blood-brain/spinal cord barrier, renowned as excellent carriers of bioactive substances. Previous studies have confirmed the detrimental effect of connective tissue growth factor (CTGF) on axonal regeneration after spinal cord injury (SCI) via stimulating the unrestricted growth of glial scars. In this study, we applied mesenchymal stem cells (MSCs)-derived Exo as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosome-siRNA (Exo-siRNA) that could specifically silence Ctgf gene in the injury sites by electroporation.During the administration, we injected Exo-siRNAs into the tail vein of SCI rats, and their distribution and accumulation in the spinal cord were visualized by in vivo fluorescence imaging. Relevant in vivo and in vitro experiments in this study showed that Exo-siRNA not only effectively inhibited the expressions of Ctgf gene and glial scar formation related proteins, such as GFAP, vimentin fibronectin and laminin, in the injured spinal cord segments, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly up-regulated several neurotrophic factors and anti-inflammatory factors (e.g., TGF-β1), acting as a facilitator of axon regeneration of nerve-injured motor neurons. Thus, the motor function of SCI rats were remarkably promoted.In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired cognitive functions. Fascaplysin is a β-carboline alkaloid isolated from marine sponge

&beta, Amyloid (A&beta, ) is regarded as an important pathogenic target for Alzheimer&rsquo, s disease (AD), the most prevalent neurodegenerative disease. A&beta, can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, A&beta, aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits A&beta, fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of A&beta, fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with A&beta, directly reduced A&beta, oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of A&beta, 42 with polar binding energy. Hydrogen bonds and &pi, &ndash, &pi, interactions between the key amino acid residues of A&beta, 42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical A&beta, oligomer, A&beta, modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-A&beta, neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of A&beta, aggregation along with other target mechanisms.