Use of a combination strategy to improve neuroprotection and neuroregeneration in a rat model of acute spinal cord injury

Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides(INDP), inhibition of glial scar formation(dipyridyl: DPY), as well as the use of biocompatible matrix(fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells(MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord(hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy(DPY+ INDP + FG+ MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy(DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee(approval No. 178544; CSNBTBIBAJ 090812960)on August 15, 2016.

Repair, protection and regeneration of peripheral nerve injury

Reading guide 1778Repair of long-segment peripheral nerve defects1779Bionic reconstruction of hand function after adult brachial plexus root avulsion1780Optimized design of regeneration material for the treatment of peripheral nerve injury1781Synergism of electroactive polymeric materials and electrical stimulation promotes peripheral nerve repair1783Schwann cell effect on peripheral nerve repair and regeneration .

The Natural Forest Protection Program in China： A Contingent Valuation Study in Heilongjiang Province

In 1998, the Chinese Government implemented the NFPP （Natural Forest Protection Program）, which included logging restrictions, protected areas, replanting, and a range of other policies aimed at safeguarding the state of the country＇s forests and reducing the risk of erosion and flooding. A second phase of this program is currently being discussed. In this paper, contingent valuation is used to estimate the WTP （willingness to pay） for maintaining the program among the inhabitants in Heilongjiang Province in northern China. The results show that, even with fairly conservative assumptions, the aggregated WTP for maintaining the program for another five years is some 3.24 billion yuan per year. This can be compared with the current cost of the Program in the province, which is some 1.57 billion yuan per year.

Investor Protection,Ownership Structure and Corporate Valuation

The purpose of this paper is to investigate the relationship between investor protection, ownership structure and corporate valuation. La Porta showed that there existed a simple linear relationship between corporate valuation and the holding percentage of controlling shareholders. But recent empirical evidence does not support it. A nonlinear relationship is proved between ownership structure and corporate valuaton by relaxing the assumption of La Porta＇s model in this paper. There exists a positive relation between investor protection and corporate valuation. Our empirical research shows that this relation is significantly positive indeed.

Olfactory ensheathing cell transplantation alters the expression of chondroitin sulfate proteoglycans and promotes axonal regeneration after spinal cord injury

Cell transplantation is a potential treatment for spinal cord injury. Olfactory ensheathing cells(OECs) play an active role in the repair of spinal cord injury as a result of the dual characteristics of astrocytes and Schwann cells. However, the specific mechanisms of repair remain poorly understood. In the present study, a rat model of spinal cord injury was established by transection of T10. OECs were injected into the site, 1 mm from the spinal cord stump. To a certain extent, OEC transplantation restored locomotor function in the hindlimbs of rats with spinal cord injury, but had no effect on the formation or volume of glial scars. In addition, OEC transplantation reduced the immunopositivity of chondroitin sulfate proteoglycans(neural/glial antigen 2 and neurocan) and glial fibrillary acidic protein at the injury site, and increased the immunopositivity of growth-associated protein 43 and neurofilament. These findings suggest that OEC transplantation can regulate the expression of chondroitin sulfate proteoglycans in the spinal cord, inhibit scar formation caused by the excessive proliferation of glial cells, and increase the numbers of regenerated nerve fibers, thus promoting axonal regeneration after spinal cord injury. The study was approved by the Animal Ethics Committee of the Medical College of Xi'an Jiaotong University, China(approval No. 2018-2048) on September 9, 2018.

The key target of neuroprotection after the onset of ischemic stroke: secretory pathway Ca^(2+)-ATPase 1

The regulatory mechanisms of cytoplasmic Ca2＋ after myocardial infarction-induced Ca2＋ overload involve secretory pathway Ca2＋-ATPase 1 and the Golgi apparatus and are well understood. However, the effect of Golgi apparatus on Ca2＋ overload after cerebral ischemia and reperfusion remains unclear. Four-vessel occlusion rats were used as animal models of cerebral ischemia. The expression of secretory pathway Ca2＋-ATPase 1 in the cortex and hippocampus was detected by immunoblotting, and Ca2＋ concentrations in the cytoplasm and Golgi vesicles were determined. Results showed an overload of cytoplasmic Ca2＋ during ischemia and reperfusion that reached a peak after reperfusion. Levels of Golgi Ca2＋ showed an opposite effect. The expression of Golgi-specific secretory pathway Ca2＋-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion, and increased after reperfusion for 6 hours. This variation was similar to the alteration of calcium in separated Golgi vesicles. These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload, and that secretory pathway Ca2＋-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells. Thus, we concluded that secretory pathway Ca2＋-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress, responding to cerebral ischemia and reperfusion. The secretory pathway Ca2＋-ATPase 1 can be an important neuroprotective target of ischemic stroke.

Protection of 3'-methoxy-puerarin against focal brain ischemia and its association with c-fos expression

The present study established a rat model of focal brain ischemia by occlusion of the middle cerebral artery covered with FeCl3, and investigated the protective effect of 3＇-methoxy-puerarin. Hippocampal and cortical c-fos gene expression was determined using in situ hybridization. Results showed that 3＇-methoxy-puerarin reduced neurological deficit scores, cerebral infarcted zone and water content of brain tissues, dramatically increased the activity of catalase and glutathione peroxidase in the ischemia zone of the hippocampus, increased the activity of catalase in the cortex, decreased lipid peroxide and lactic acid contents in the hippocampus and cerebral cortex, and down-regulated c-fos gene expression in brain ischemic rats. Results demonstrated that 3＇-methoxy-puerarin exhibited cerebroprotective effects against focal brain ischemia, which involved c-fos gene expression.

Renovation of Urban Green Space Based on Regeneration of Historical Place——A Case Study of Jianqiao Historical Block in Hangzhou

The protected historical blocks always fail to undertake some necessary functions of modern cities because they inherit texture and skyline of historical spaces,and also traditional building density,so these blocks lack in popularity and fall into rigid display of folk customs.In view of the contradiction between protection and vitality,this study proposes the concept of"intergrowth between underground space and urban block"on the basis of theoretic researches and construction practices,aims at renovating urban public green spaces by following the principle of regeneration of place,so as to improve and make up modern urban functions of historical blocks,stimulate vitality of the community,provide an effective solution to the development of new cities and renovation of old cities.

Neuroprotective effect of ischemic preconditioning in focal cerebral infarction: relationship with upregulation of vascular endothelial growth factor

Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.

Protective effects of human umbilical cord mesenchymal stem cell vein transplantation against spinal cord ischemia/reperfusion injury in rats

BACKGROUND： The majority of studies addressing spinal cord ischemia/reperfusion injury （SCIRI） have focused on drugs, proteins, cytokines, and various surgical techniques. A recent study reports that human umbilical cord mesenchymal stem cell （hUCMSC） transplantation achieves good therapeutic effects, but the mechanisms underlying nerve protection remain poorly understood. OBJECTIVE： To observe survival of transplanted hUCMSCs in SCIRI rat models and the influence on motor function in the hind limbs, to determine interleukin-8 expression and cellular apoptosis in spinal cord tissues, and to verify the hypothesis that hUCMSC transplantation exhibits protective effects on SCIRI. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of the Department of Orthopedics in the First Affiliated Hospital of Soochow University, China between January 2007 and December 2008. MATERIALS： hUCMSCs were harvested from umbilical cord blood of healthy pregnant women after parturition in the Obstetrical Department of the First Affiliated Hospital of Soochow University, China. Rabbit anti-human BrdU monoclonal antibody was provided by DAKO, USA. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） Kit and enzyme-linked immunosorbent assay （ELISA） Kit were purchased by Wuhan Boster, China. METHODS： A total of 72 healthy, Wistar, adult rats were randomly assigned to three groups： sham-surgery, model, and transplantation, with 24 rats in each group. SCIRI was induced in the model and transplantation groups via the abdominal aorta block method. The infrarenal abdominal aorta was not blocked in the sham-surgery group. Prior to abdominal aorta occlusion, 0.2 03 mL bromodeoxyuridine （BrdU）-Iabeled hUCMSCs suspension （cell concentration 5 × 10 3/uL） was injected through the great saphenous vein of the hind limb, and an equal volume of physiological saline was administered to the model and sham-surgery groups. MAIN OUTCOME MEASURES： Pathological observation of rat spinal cord tissues was performed by hematoxylin-eosin staining at 6, 24, and 48 hours post-surgery. Immunohistochemistry was applied to determine hUCMSCs survival in the spinal cord. The amount of cellular apoptosis and interleukin-8 expression in spinal cord tissues was assayed utilizing the TUNEL and ELISA methods, respectively. Motor function in the hind limbs was evaluated according to Jacob＇s score. RESULTS： Numerous BrdU-positive cells were observed in spinal cord tissues from the transplantation group. The number of apoptotic cells and interleukin-8 levels significantly decreased in the transplantation group （P 〈 0.05）, pathological injury was significantly ameliorated, and motor function scores significantly increased （P 〈 0.05） compared with the model group. CONCLUSION： Via vein transplantation, hUCMSCs were shown to reach and survive in the injury area. Results suggested that the transplanted hUCMSCs contributed to significantly improved pathological changes in the injured spinal cord, as well as motor function, following SCIRI. The protective mechanism correlated with inhibition of cellular apoptosis and reduced production of inflammatory mediators.

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

Previous studies have shown that vagus nerve stimulation can improve the prognosis of trau- matic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain ex- plosive injury received continuous stimulation （10 V, 5 Hz, 5 ms, 20 minutes） of the right cervical vagus nerve. Tumor necrosis factor-a, interleukin-l~ and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-a and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-a, interleukin-1 β and interleukin-10 in the serum and brain tissue.

Brain-derived neurotrophic factor protects against acrylamide-induced neuronal and synaptic injury via the TrkB-MAPK-Erk1/2 pathway

Acrylamide has been shown to be neurotoxic.Brain-derived neurotrophic factor(BDNF)can alleviate acrylamide-induced synaptic injury;however,the underlying mechanism remains unclear.In this study,dibutyryl-cyclic adenosine monophosphate-induced mature human neuroblastoma(NB-1)cells were exposed with 0–100μg/mL acrylamide for 24–72 hours.Acrylamide decreased cell viability and destroyed synapses.Exposure of co-cultured NB-1 cells and Schwann cells to 0–100μg/mL acrylamide for 48 hours resulted in upregulated expression of synapsin I and BDNF,suggesting that Schwann cells can activate self-protection of neurons.Under co-culture conditions,activation of the downstream TrkB-MAPK-Erk1/2 pathway strengthened the protective effect.Exogenous BDNF can increase expression of TrkB,Erk1/2,and synapsin I,while exogenous BDNF or the TrkB inhibitor K252a could inhibit these changes.Taken together,Schwann cells may act through the BDNF-TrkB-MAPK-Erk1/2 signaling pathway,indicating that BDNF plays an important role in this process.Therefore,exogenous BDNF may be an effective treatment strategy for acrylamide-induced nerve injury.This study was approved by the Laboratory Animal Welfare and Ethics Committee of the National Institute of Occupational Health and Poison Control,a division of the Chinese Center for Disease Control and Prevention(approval No.EAWE-2017-008)on May 29,2017.

Triptolide protects astrocytes from hypoxia/reoxygenation injury

Astrocytes in an in vitro murine astrocyte model of oxygen and glucose deprivation/hypoxia and reoxygenation were treated with different concentrations of triptolide （250, 500, 1 000 ng/mL） in a broader attempt to elucidate the protection and mechanism underlying triptolide treatment on astrocytes exposed to hypoxia/reoxygenation injury. The results showed that the matrix metalloproteinase-9, interleukin-1β, tumor necrosis factor α and interleukin-6 expressions were significantly decreased after triptolide treatment in the astrocytes exposed to hypoxia/ reoxygenation injury, while interleukin-10 expression was upregulated. In addition, the vitality of the injured astrocytes was enhanced, the triptolide＇s effect was apparent at 500 ng/mL. These experimental findings indicate that triptolide treatment could protect astrocytes against hypoxia/ reoxygenation injury through the inhibition of inflammatory response and the reduction of matrix metalloproteinase-9 expression.

FOXO3-engineered human ESC-derived vascular cells promote vascular protection and regeneration

With the support by the National Natural Science Foundation of China and the Chinese Academy of Sciences,the research team led by Prof.Liu GuangHui(刘光慧)at the CAS National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,generated the world's first genetically enhanced human vascular cells by targeting a single longevity gene,FOXO3.This study was recently published in Cell Stem Cell(2019)as a cover story.

Neuroprotective effect of panax notoginseng saponins and its main components

Stroke is the third leading cause of death and the first cause of adult disability in industrial countries [1]. It is charicaterized by hemiplegia, hemianopsia, aphasia, mouth askew and sever sequelae. It is considered that an ischemic disease without any specific treatment method and few effective drugs such as tPA (human tissue-type plasminogen activator) and Edarovone with specific therapeutic window will cause a lot of disadvantages if being used inaccurate. Root of Panax notoginseng (PN) which is one of traditional Chinese medicines (TCMs), was first found in “Shennong’s Classic of Materia Medica” around 200 AD. Panax notogineng saponins(PNS) is a multi-components mixture containing ginseng and saponins as the most important bioactive components which are commonly used in clinical treatment. Also, ginseng and saponins form the main components of many herbal medicines in the market, e.g., Xueshuantong injection [2], Xuesaitong injection [3], Xuesaitong soft capsule [4] and so on. The main monomers of Panax notoginseng saponins (PNS) are Ginsenoside-Rb1, Gensenoside-Rg1, Gensenoside-Re, Gensenoside-Rd and Panax notoginseng saponins-R1 [5]. In this review, we found some important points as well as shortcomings that require special consideration. We therefore highlighted the advances in neuro-protection of PNS and its main monomers in the area of experimental research.

Fault Waveform Regenerator and Its Digital Closed-Loop Modification Technique

In order to provide a novel and more effective alternative to the commonly used relay protection testing device that outputs only the sinusoidal testing signals, the concept of fault waveform regenerator is proposed in this paper, together with its hardware structure and software flow chart. Fault waveform regenerator mainly depends on its power amplifiers (PAs) to regenerate the fault waveforms recorded by digital fault recorder (DFR). To counteract the PA’s inherent nonlinear distortions, a digital closed-loop modification technique that is different from the predistortion technique is conceived. And the experimental results verify the effectiveness of the fault waveform regenerator based on the digital closed-loop modification technique.

郑州国棉三厂纺织工业遗产保护与再生研析

中国近代纺织工业是洋务运动实现“自强求富”、民族资本“实业救国”的重要工业类型之一,是中国近代工业化的重要内容,在中国近代工业史上具有十分重要的意义。中华人民共和国成立初期的6大纺织工业基地中,郑州国棉三厂是其中规模较大、质量较高、延续时间较长的工业厂区。基于工业遗产病害分析、结构评估和博物馆展示利用需求,采取文物建筑修缮加固、文物建筑风貌恢复、展览空间活化利用、新旧建筑融合共生的策略,实现工业建筑遗产向工业遗址博物馆的活化利用,为近代纺织工业遗产的保护与再生提供借鉴。

城市更新背景下历史文化街区的保护与更新——基于国内外研究进展的对比分析

历史文化街区作为城市历史文化的核心载体,在其保护与更新的过程中面临着如何在历史文化遗产保护与适应存量时代发展之间取得平衡的挑战。运用文献计量方法与可视化分析软件CiteSpace对比分析了近30年来国内外历史文化街区的研究进展、研究内容和发展演变趋势,对未来城市更新背景下的历史文化街区研究发展提出如下建议:(1)未来以人本视角为研究主体,基于环境行为学理论探索“空间—感知需求—行为模式”的历史文化街区空间营造方法应极具潜力;(2)以多源数据为基础的支持历史文化街区保护与更新决策的方法和工具研究具有重要价值;(3)公众参与机制对于提高历史文化街区保护与更新的协同决策水平和平衡利益关系具有重要意义。

Hippo/Yap信号通路在调控听觉和前庭系统中的研究进展

Hippo/Yap信号通路广泛参与听觉系统发育过程、听力损伤修复和听觉系统障碍。胚胎发育过程中对Yap的调控可能导致听觉器官的形态和功能缺陷。Hippo/Yap信号通路通过与多种信号分子相互作用,参与听力系统损伤或听觉系统疾病的相关进程,这些信号分子受JNK信号通路、Wnt信号系统和机械信号转导的影响。本文综述了听觉系统中Hippo/Yap信号通路的研究进展,为多种形式的听力损失的分子生物学过程和治疗提供了新的思路。

针刺干预阿尔茨海默病作用机制的研究进展

阿尔茨海默病(AD)是多种原因导致的一种神经退行性疾病,该病以记忆障碍为特征。AD的有效治疗一直存在严重的阻碍。针刺作为中医学的组成部分,在AD的治疗中发挥着重要的作用。针刺可保护神经元免受退化并促进神经退行性疾病(如AD)的轴突再生。针刺对AD的作用机制包括以下几个方面:调节Aβ代谢、tau磷酸化、胆碱能神经递质、神经炎症、突触和神经元功能、自噬、脑葡萄糖代谢、肠道菌群,抑制神经细胞凋亡,进而改善认知。