Nuclear TAR DNA-binding protein 43 A new target for amyotrophic lateral sclerosis treatment

Abnormal TAR DNA-binding protein 43 （TDP-43） inclusion bodies can be detected in the degen- erative neurons of amyotrophic lateral sclerosis. In this study, we induced chronic oxidative stress injury by applying malonate to cultured mouse cortical motor neurons. In the later stages of the malonate insult, TDP-43 expression reduced in the nuclei and transferred to the cytoplasm. This was accompanied by neuronal death, mimicking the pathological changes in TDP-43 that are seen in patients with amyotrophic lateral sclerosis. Interestingly, in the early stages of the response to malonate treatment, nuclear TDP-43 expression increased, and neurons remained relatively intact, without inclusion bodies or fragmentation. Therefore, we hypothesized that the increase of nuclear TDP-43 expression might be a pro-survival factor against oxidative stress injury. This hypothesis was confirmed by an in vitro transgenic experiment, in which overexpression of wild type mouse TDP-43 in cultured cortical motor neurons significantly reduced malonate-induced neuronal death. Our findings suggest that the loss of function of TDP-43 is an important cause of neuronal degen- eration, and upregulation of nuclear TDP-43 expression might be neuroprotective in amyotrophic lateral sclerosis.     

Myelin-based inhibitors of oligodendrocyte myelination: clues from axonal growth and regeneration

The differentiation of and myelination by oligodendrocytes (OLs) are exquisitely regulated by a series of intrinsic and extrinsic mechanisms. As each OL can make differing numbers of myelin segments with variable lengths along similar axon tracts, myelination can be viewed as a graded process shaped by inhibitory/inductive cues during development. Myelination by OLs is a prime example of an adaptive process determined by the microenvironment and architecture of the central nervous system (CNS). in this review, we discuss how myelin formation by OLs may be controlled by the heterogeneous microenvironment of the CNS. Then we address recent findings demonstrating that neighboring OLs may compete for available axon space, and highlight our current understanding of myelin-based inhibitors of axonal regeneration that are potentially responsible for the reciprocal dialogue between OLs and determine the numbers and lengths of myelin internodes. Understanding the mechanisms that control the spatiotemporal regulation of myelinogenic potential during development may provide valuable insight into therapeutic strategies for promoting remyelination in an inhibitory microenvironment.     

Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy

A star-shaped biodegradable polymer, mannitol-core poly(d,l-lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (M-PLGA-TPGS), was synthesized in order to provide a novel nanoformulation for breast cancer chemotherapy. This novel copolymer was prepared by a core-first approach via three stages of chemical reaction, and was characterized by nuclear magnetic resonance, gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded M-PLGA-TPGS nanoparticles (NPs), prepared by a modified nanoprecipitation method, were observed to be near-spherical shape with narrow size distribution. Confocal laser scanning microscopy showed that the uptake level of M-PLGA-TPGS NPs was higher than that of PLGA NPs and PLGA-TPGS NPs in MCF-7 cells. A significantly higher level of cytotoxicity was achieved with docetaxel-loaded M-PLGA-TPGS NPs than with commercial Taxotere®, docetaxel-loaded PLGA-TPGS and PLGA NPs. Examination of the drug loading and encapsulation efficiency proved that star-shaped M-PLGA-TPGS could carry higher levels of drug than linear polymer. The in vivo experiment showed docetaxel-loaded M-PLGA-TPGS NPs to have the highest anti-tumor efficacy. In conclusion, the star-like M-PLGA-TPGS copolymer shows potential as a promising drug-loaded biomaterial that can be applied in developing novel nanoformulations for breast cancer therapy.     

Fabrication and characterization of biomimetic collagen–apatite scaffolds with tunable structures for bone tissue engineering

The objective of the current study is to prepare a biomimetic collagen–apatite scaffold for improved bone repair and regeneration. A novel bottom–up approach has been developed, which combines a biomimetic self-assembly method with a controllable freeze-casting technology. In this study, the mineralized collagen fibers were generated using a simple one-step co-precipitation method which involved collagen self-assembly and in situ apatite precipitation in a collagen-containing modified simulated body fluid (m-SBF). The precipitates were then subjected to controllable freeze casting, forming scaffolds with either an isotropic equiaxed structure or a unidirectional lamellar structure. These scaffolds were comprised of collagen fibers and poorly crystalline bone-like carbonated apatite nanoparticles. The mineral content in the scaffold could be tailored in the range 0–54 wt.% by simply adjusting the collagen content in the m-SBF. Further, the mechanisms of the formation of both the equiaxed and the lamellar scaffolds were investigated, and freezing regimes for equiaxed and lamellar solidification were established. Finally, the bone-forming capability of such prepared scaffolds was evaluated in vivo in a mouse calvarial defect model. It was confirmed that the scaffolds well support new bone formation.     

128层螺旋CT联合心电门控技术在支气管动脉成像中的应用

目的：探讨128层螺旋CT联合心电门控扫描技术在支气管动脉成像中的临床应用价值。方法：回顾性分析我院124例次胸部CT血管成像（CTA）数据,其中72例次行常规胸部CTA扫描数据列入对照组,52例次采用心电门控技术扫描数据列入观察组,对比分析观察两组支气管动脉的开口位置、走行、与相邻组织之间的解剖关系以及支气管动脉显示的清晰度。结果：对照组中33．33％（24／72）支气管动脉显示较清晰,58．33％（42／72）支气管动脉显示模糊,8．33％（6／72）没有发现支气管动脉;观察组52例次支气管动脉全部显示,其中86．54％（45／52）支气管动脉显示清晰,13．46％（7／52）支气管动脉显示模糊。结论：128层螺旋CT联合心电门控扫描技术与常规胸部血管成像相比,能更清晰地显示支气管动脉开口位置、形态、走行及其与相邻组织的关系,对支气管动脉源性疾病的治疗,特别是介入治疗术前评估有重要的临床应用价值。