• 【骨髓来源的内皮细胞前体的生物学。】 复制标题 收藏 收藏
    DOI:10.1152/ajpheart.00662.2006 复制DOI
    作者列表:Schatteman GC,Dunnwald M,Jiao C
    BACKGROUND & AIMS: :Over the past decade, the old idea that the bone marrow contains endothelial cell precursors has become an area of renewed interest. While some still believe that there are no endothelial precursors in the blood, even among those who do, there is no consensus as to what they are or what they do. In this review, we describe the problems in identifying endothelial cells and conclude that expression of endothelial nitric oxide synthase may be the most reliable antigenic indicator of the phenotype. The evidence for two different classes of endothelial precursors is also presented. We suggest that, though there is no single endothelial cell precursor, we may be able to use these phenotypic variations to our advantage in better understanding their biology. We also discuss how a variety of genetic, epigenetic, and methodological differences can account for the seemingly contradictory findings on the physiological relevance of bone marrow-derived precursors in normal vascular maintenance and in response to injury. Data on the impact of tumor type and location on the contribution of bone marrow-derived cells to the tumor vasculature are also presented. These data provide hope that we may ultimately be able to predict those tumors in which bone marrow-derived cells will have a significant contribution and design therapies accordingly. Finally, factors that regulate bone marrow cell recruitment to and function in the endothelium are beginning to be identified, and several of these, including stromal derived factor 1, monocyte chemoattractant factor-1, and vascular endothelial growth factor are discussed.
    背景与目标: :在过去的十年中,关于骨髓中含有内皮细胞前体的古老观念已经引起人们的广泛关注。尽管有些人仍然认为血液中没有内皮前体,即使在有血液的人中也没有,但是关于它们是什么或它们的行为尚无共识。在这篇综述中,我们描述了鉴定内皮细胞的问题,并得出结论,内皮一氧化氮合酶的表达可能是最可靠的表型抗原指示剂。还提供了两种不同类别的内皮前体的证据。我们建议,尽管没有单个内皮细胞前体,但我们也许能够利用这些表型变异来更好地了解它们的生物学特性。我们还将讨论各种遗传,表观遗传学和方法学上的差异如何解释在正常血管维持和对损伤的反应中骨髓来源的前体的生理相关性看似矛盾的发现。还提供了有关肿瘤类型和位置对骨髓来源的细胞对肿瘤脉管系统的影响的数据。这些数据提供了希望,使我们最终能够预测那些骨髓来源的细胞将发挥重要作用的肿瘤,并据此设计治疗方法。最后,已经开始确定调节骨髓细胞向内皮募集并在内皮中起作用的因子,并讨论了其中的几种,包括基质衍生因子1,单核细胞趋化因子-1和血管内皮生长因子。
  • 【腰椎骨矿物质密度分布的纵向变化可能会增加楔形骨折的风险。】 复制标题 收藏 收藏
    DOI:10.1016/j.clinbiomech.2012.10.005 复制DOI
    作者列表:Giambini H,Khosla S,Nassr A,Zhao C,An KN
    BACKGROUND & AIMS: BACKGROUND:Trabecular bone strength diminishes as a result of osteoporosis and altered biomechanical loading at the vertebral and spinal levels. The spine consists of the anterior, middle and posterior columns and the load supported by the anterior and middle columns will differ across different regions of the spine. Stress shielding of the anterior column can contribute to bone loss and increase the risk of wedge fracture. There is a lack of quantitative data related to regional spinal bone mineral density distribution over time. We hypothesize that there is an increase in the posterior-to-anterior vertebral body bone mineral density ratio and a decrease in whole-body bone mineral density over time. METHODS:Bone mineral density was measured in 33 subjects using quantitative computed tomography scans for L1-L3 vertebrae, region (anterior and posterior vertebral body), and time (baseline and 6 years after). FINDINGS:Lumbar bone mineral density decreased significantly (Δ: ~15%) from baseline to the 6th year visit. Individual vertebra differences over time (L1: ~14%, L2: ~14%, L3: ~17%) showed statistical significance. Anterior bone mineral density change was significantly greater than in the posterior vertebral body region (Δ anterior: ~18%; Δ posterior: ~13%). Posterior-to-anterior bone mineral density ratio was significantly greater in the 6th year compared to baseline values (mean (SD), 1.33 (0.2) vs. 1.23 (0.1)). INTERPRETATION:This study provides longitudinal quantitative measurement of bone mineral density in vertebrae as well as regional changes in the anterior and posterior regions. Understanding bone mineral density distribution over time may help to decrease the risk of wedge fractures if interventions can be developed to bring spine loading to its normal state.
    背景与目标: 背景:由于骨质疏松症以及椎体和脊柱水平的生物力学负荷改变,小梁的骨强度降低。脊柱由前,中和后柱组成,由前柱和中柱支撑的载荷在脊柱的不同区域会有所不同。前柱的应力屏蔽可能会导致骨质流失并增加楔形骨折的风险。缺乏与区域脊椎骨矿物质密度随时间分布有关的定量数据。我们假设随着时间的推移,椎体前后骨矿物质密度比增加,而全身骨矿物质密度降低。
    方法:采用定量计算机断层扫描技术对33名受试者的L1-L3椎骨,区域(椎体的前后)和时间(基线及术后6年)进行了骨矿物质密度测量。
    结果:从基线到第6年随访,腰椎骨矿物质密度显着降低(Δ:〜15%)。随时间变化的各个椎骨差异(L1:〜14%,L2:〜14%,L3:〜17%)显示出统计学意义。前骨矿物质密度变化显着大于后椎体区域(Δ前:〜18%;Δ后:〜13%)。与基线值相比,第6年的前后骨矿物质密度比显着更高(平均值(SD)为1.33(0.2)对1.23(0.1))。
    解释:这项研究提供了纵向定量测量椎骨中骨矿物质密度以及前后区域的变化的信息。如果可以采取干预措施使脊柱负荷恢复到正常状态,那么了解随着时间推移的骨矿物质密度分布可能有助于降低楔形骨折的风险。
  • 【水稻需要通过促进肌动蛋白周转来满足水稻肌动蛋白相互作用蛋白1的需求。】 复制标题 收藏 收藏
    DOI:10.1111/tpj.12065 复制DOI
    作者列表:Shi M,Xie Y,Zheng Y,Wang J,Su Y,Yang Q,Huang S
    BACKGROUND & AIMS: :Rapid actin turnover is essential for numerous actin-based processes. However, how it is precisely regulated remains poorly understood. Actin-interacting protein 1 (AIP1) has been shown to be an important factor by acting coordinately with actin-depolymerizing factor (ADF)/cofilin in promoting actin depolymerization, the rate-limiting factor in actin turnover. However, the molecular mechanism by which AIP1 promotes actin turnover remains largely unknown in plants. Here, we provide a demonstration that AIP1 promotes actin turnover, which is required for optimal growth of rice plants. Specific down-regulation of OsAIP1 increased the level of filamentous actin and reduced actin turnover, whereas over-expression of OsAIP1 induced fragmentation and depolymerization of actin filaments and enhanced actin turnover. In vitro biochemical characterization showed that, although OsAIP1 alone does not affect actin dynamics, it enhances ADF-mediated actin depolymerization. It also caps the filament barbed end in the presence of ADF, but the capping activity is not required for their coordinated action. Real-time visualization of single filament dynamics showed that OsAIP1 enhanced ADF-mediated severing and dissociation of pointed end subunits. Consistent with this, the filament severing frequency and subunit off-rate were enhanced in OsAIP1 over-expressors but decreased in RNAi protoplasts. Importantly, OsAIP1 acts coordinately with ADF and profilin to induce massive net actin depolymerization, indicating that AIP1 plays a major role in the turnover of actin, which is required to optimize F-actin levels in plants.
    背景与目标: :快速的肌动蛋白更新对于许多基于肌动蛋白的过程至关重要。但是,如何对其进行精确调节仍然知之甚少。肌动蛋白相互作用蛋白1(AIP1)通过与肌动蛋白解聚因子(ADF)/ cofilin协同作用来促进肌动蛋白解聚(肌动蛋白周转的限速因子),已被证明是一个重要因素。但是,在植物中,AIP1促进肌动蛋白更新的分子机制仍然是未知的。在这里,我们提供了一个证明AIP1促进肌动蛋白更新,这是水稻植物最佳生长所必需的。 OsAIP1的特定下调增加了丝状肌动蛋白的水平并减少了肌动蛋白的转换,而过表达的OsAIP1则诱导了肌动蛋白丝的断裂和解聚,并提高了肌动蛋白的转化率。体外生化特征表明,尽管仅OsAIP1不会影响肌动蛋白动力学,但它会增强ADF介导的肌动蛋白解聚作用。在存在ADF的情况下,它也可以盖住灯丝倒刺的末端,但是对于它们的协同作用,不需要盖盖活动。实时可视化的单丝动力学表明,OsAIP1增强了ADF介导的尖端亚基的切断和解离。与此相一致,OsAIP1过表达中的细丝切断频率和亚基解离速率增加,而RNAi原生质体中的减少。重要的是,OsAIP1与ADF和profilin协同作用,诱导大量的肌动蛋白净解聚,这表明AIP1在肌动蛋白周转中起主要作用,这是优化植物中F-肌动蛋白水平所必需的。
  • 【低水平激光治疗对链脲佐菌素诱发的糖尿病大鼠骨缺损愈合的影响:组织学和形态计量学评估。】 复制标题 收藏 收藏
    DOI:10.1080/14764172.2017.1341048 复制DOI
    作者列表:Yildirimturk S,Sirin Y,Soluk Tekkesin M,Gurler G,Firat D
    BACKGROUND & AIMS: BACKGROUND:The aim of the present study was to evaluate the effects of low-level laser therapy (LLLT) on the healing of bone defects in rats with streptozotocin (STZ)-induced DM. METHODS:28 male Sprague-Dawley rats were used in this study. 14 animals received a single dose of STZ intraperitoneally (65 mg/kg) to induce Type I DM, whereas others were injected only with sterile saline solution. Four weeks later, standard bone defects were created in the tibiae of rats. Surgical wounds in one group from each of the diabetic and non-diabetic animals were irradiated with diode laser for every other day for 4 weeks and they were described as DM + LLLT and CONT + LLLT groups, respectively. Remaining two groups received no laser treatment. New bone formation, osteoblast and blood vessel counts were calculated in histologic sections. RESULTS:DM group had significantly smaller bone area and lower blood vessel count when compared to DM + LLLT, CONT and CONT + LLLT groups (p < 0.05 for each). CONT and CONT + LLLT groups had significantly larger bone area than DM + LLLT group (p < 0.05 for both). CONCLUSIONS:LLLT application promoted vascularization and new bone formation in animals with DM to a limited extent, since it was unable to support the healing process up to the level of non-diabetic animals.
    背景与目标: 背景:本研究的目的是评估低剂量激光疗法(LLLT)对链脲佐菌素(STZ)诱导的DM大鼠骨缺损愈合的作用。
    方法:采用28只雄性Sprague-Dawley大鼠。 14只动物腹膜内接受单剂STZ(65 mg / kg)诱导I型DM,而其他动物仅注射无菌盐溶液。四周后,在大鼠胫骨中形成了标准的骨缺损。每隔一天用二极管激光照射来自糖尿病和非糖尿病动物中每组的一组手术伤口,持续4周,分别称为DM LLLT组和CONT LLLT组。其余两组未接受激光治疗。在组织学切片中计算新的骨形成,成骨细胞和血管计数。
    结果:与DM LLLT,CONT和CONT LLLT组相比,DM组的骨面积显着更小,血管计数更低(每组p <0.05)。 CONT和CONT LLLT组的骨面积明显大于DM LLLT组(两者均p <0.05)。
    结论:LLLT的应用在一定程度上促进了DM动物的血管形成和新骨形成,因为它无法支持非糖尿病动物的愈合过程。
  • 【骨的全基因组分布图揭示了骨质疏松症和骨关节炎中甲基化的差异区域。】 复制标题 收藏 收藏
    DOI:10.1002/art.37753 复制DOI
    作者列表:Delgado-Calle J,Fernández AF,Sainz J,Zarrabeitia MT,Sañudo C,García-Renedo R,Pérez-Núñez MI,García-Ibarbia C,Fraga MF,Riancho JA
    BACKGROUND & AIMS: OBJECTIVE:To determine genome-wide methylation profiles of bone from patients with hip osteoarthritis (OA) and those with osteoporotic (OP) hip fractures. METHODS:Trabecular bone pieces were obtained from the central part of the femoral head of 27 patients with hip fractures and 26 patients with hip OA. DNA was isolated, and methylation was explored with Illumina methylation arrays. RNA was extracted, pooled, and deep-sequenced to obtain the whole transcriptome. Differentially methylated regions were identified, and connections between genes with differentially methylated regions were explored by pathway and text-mining analyses. RESULTS:After quality control, methylation of 23,367 CpG sites (13,463 genes) was analyzed. There was a genome-wide inverse relationship between methylation and gene expression in both patient groups. Comparison of OP and OA bones revealed 241 CpG sites, located in 228 genes, with significant differences in methylation (false discovery rate<0.05). Of them, 217 were less methylated in OP than in OA. The absolute methylation differences were >5% in 128 CpG sites and >10% in 45 CpG sites. The differentially methylated genes were enriched for association with bone traits in the genome-wide association study catalog. Pathway analysis and text-mining analysis with Gene Relationships Across Implicated Loci software revealed enrichment in genes participating in glycoprotein metabolism or cell differentiation, and particularly in the homeobox superfamily of transcription factors. CONCLUSION:Genome-wide methylation profiling of bone samples revealed differentially methylated regions in OP and OA. These regions were enriched in genes associated with cell differentiation and skeletal embryogenesis, such as those in the homeobox superfamily, suggesting the existence of a developmental component in the predisposition to these disorders.
    背景与目标: 目的:确定髋骨关节炎(OA)和骨质疏松(OP)髋部骨折患者的骨骼全基因组甲基化分布。
    方法:从27例髋部骨折患者和26例髋部OA患者的股骨头中部获得小梁骨碎片。分离DNA,并用Illumina甲基化阵列探索甲基化。提取RNA,合并,并进行深度测序以获得完整的转录组。鉴定差异甲基化区域,并通过途径和文本挖掘分析探索具有差异甲基化区域的基因之间的联系。
    结果:质量控制后,分析了23,367个CpG位点(13,463个基因)的甲基化。在两个患者组中,甲基化和基因表达之间存在全基因组范围的逆向关系。 OP和OA骨骼的比较显示241个CpG位点,位于228个基因中,甲基化差异显着(假发现率<0.05)。其中,OP中的甲基化程度比OA中少217。在128个CpG位点中,绝对甲基化差异> 5%,在45个CpG位点中> 10%。在全基因组关联研究目录中,丰富了差异甲基化基因与骨骼特征的关联。涉及所有基因座软件的基因关系的途径分析和文本挖掘分析表明,参与糖蛋白代谢或细胞分化的基因,尤其是转录因子的同源异型超家族中的基因富集。
    结论:骨骼样品的全基因组甲基化分布图显示了OP和OA中甲基化区域的差异。这些区域富含与细胞分化和骨骼胚胎发生相关的基因,例如同源异型盒超家族中的那些基因,表明在这些疾病的易感性中存在发育成分。
  • 【电刺激通过肝素生物激活的导电支架调节成骨细胞的增殖和骨蛋白的产生。】 复制标题 收藏 收藏
    DOI:10.1002/bem.21766 复制DOI
    作者列表:Meng S,Rouabhia M,Zhang Z
    BACKGROUND & AIMS: :Electrical fields are known to interact with human cells. This principle has been explored to regulate cellular activities for bone tissue regeneration. In this work, Saos-2 cells were cultured on conductive scaffolds made of biodegradable poly(L-lactide) and the heparin-containing, electrically conducting polypyrrole (PPy/HE) to study their reaction to electrical stimulation (ES) mediated through such scaffolds. Both the duration and intensity of ES enhanced cell proliferation, generating a unique electrical intensity and temporal "window" within which osteoblast proliferation was upmodulated in contrast to the downmodulation or ineffectiveness in other ES regions. The favourable ES intensity (200 mV/mm) was further investigated in terms of the gene activation and protein production of two important osteoblast markers characterised by extracellular matrix maturation and mineralisation, that is alkaline phosphatase (ALP) and osteocalcin (OC). Both genes were found activated and the relevant protein production increased significantly following ES. In contrast, ES in the down-modulation region (400 mV/mm) suppressed the production of both ALP and OC. This work demonstrated that important osteoblast markers can be modulated with specific ES parameters mediated through conductive polymer substrates, providing a unique strategy for bone tissue engineering.
    背景与目标: :众所周知,电场会与人类细胞发生相互作用。已经探索了该原理以调节用于骨组织再生的细胞活性。在这项工作中,将Saos-2细胞培养在可生物降解的聚(L-丙交酯)和含肝素的导电聚吡咯(PPy / HE)制成的导电支架上,以研究它们对通过此类支架介导的电刺激(ES)的反应。 ES的持续时间和强度都增强了细胞增殖,产生了独特的电强度和暂时的“窗口”,其中成骨细胞的增殖被上调,而其他ES区域的下调或无效。根据两个重要的以细胞外基质成熟和矿化为特征的重要成骨细胞标志物,即碱性磷酸酶(ALP)和骨钙蛋白(OC),在基因激活和蛋白质产生方面进一步研究了有利的ES强度(200 mV / mm)。发现两个基因均被激活,ES后相关的蛋白质产量显着增加。相反,在下调制区域(400 mV / mm)的ES抑制了ALP和OC的产生。这项工作表明重要的成骨细胞标志物可以通过导电聚合物底物介导的特定ES参数进行调节,从而为骨组织工程学提供了独特的策略。
  • 【年龄,能量和蛋白质摄入量对肉鸡种鸡蛋白质更新和蛋白水解相关基因表达的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.cbpb.2012.10.002 复制DOI
    作者列表:Ekmay RD,Salas C,England J,Cerrate S,Coon CN
    BACKGROUND & AIMS: :A study was conducted to determine the changes that occur to proteolysis and related genes due to age, protein, and energy intake in high-yield broiler breeder hens (Gallus gallus). Cobb 700 broiler breeders were randomly assigned to one of six diets in a 2×3 factorial fashion. Two levels of energy (390 and 450 kcal/day) and three levels of protein (22, 24, and 26 g CP/day) were utilized. Protein turnover was determined in the left pectoralis at 22, 26, 31 and 44 weeks. Relative mRNA expression of calpain 2 (CAPN2), proteasome C2 subunit (PSMA1), and F box protein 32 (FBXO32) were determined via RT-PCR at 20, 25, and 44 weeks. Contrasts indicate fractional synthesis rate (FSR) and FBXO32 increase to a maximum at 25-26 weeks and a decrease thereafter. A significant drop in PSMA1 and FBXO32 was observed between 25 and 44 weeks and matched the decrease observed in FBR. No differences were detected in the levels of fractional synthesis and degradation, or the expression of CAPN2, PSMA1, and FBXO32, due to protein or energy intake. In summary, protein turnover was upregulated during the transition into sexual maturity and decreased thereafter. The observed changes in degradation appeared to be mediated by the ubiquitin-proteasome pathway.
    背景与目标: :进行了一项研究,以确定高产肉鸡种鸡(鸡)因年龄,蛋白质和能量摄入而引起的蛋白水解和相关基因的变化。将Cobb 700肉鸡育种家以2×3阶乘方式随机分配到六种日粮中的一种。利用了两个水平的能量(390和450 kcal /天)和三个水平的蛋白质(22、24和26 g CP /天)。在22、26、31和44周时测定左胸大肌的蛋白质更新。通过RT-PCR在20、25和44周确定钙蛋白酶2(CAPN2),蛋白酶体C2亚基(PSMA1)和F盒蛋白32(FBXO32)的相对mRNA表达。对比表明分数合成速率(FSR)和FBXO32在25-26周时增加到最大值,然后降低。在25至44周之间,观察到PSMA1和FBXO32显着下降,并且与FBR中的下降相符。由于蛋白质或能量的摄入,未检测到部分合成和降解水平或CAPN2,PSMA1和FBXO32的表达水平差异。总之,在向性成熟过渡的过程中蛋白质周转率上调,此后下降。观察到的降解变化似乎是由泛素-蛋白酶体途径介导的。
  • 【使用第三谐波生成显微镜对骨骼多尺度孔隙度和界面进行无标记成像。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-03548-5 复制DOI
    作者列表:Genthial R,Beaurepaire E,Schanne-Klein MC,Peyrin F,Farlay D,Olivier C,Bala Y,Boivin G,Vial JC,Débarre D,Gourrier A
    BACKGROUND & AIMS: :Interfaces provide the structural basis of essential bone functions. In the hierarchical structure of bone tissue, heterogeneities such as porosity or boundaries are found at scales ranging from nanometers to millimeters, all of which contributing to macroscopic properties. To date, however, the complexity or limitations of currently used imaging methods restrict our understanding of this functional integration. Here we address this issue using label-free third-harmonic generation (THG) microscopy. We find that the porous lacuno-canalicular network (LCN), revealing the geometry of osteocytes in the bone matrix, can be directly visualized in 3D with submicron precision over millimetric fields of view compatible with histology. THG also reveals interfaces delineating volumes formed at successive remodeling stages. Finally, we show that the structure of the LCN can be analyzed in relation with that of the extracellular matrix and larger-scale structures by simultaneously recording THG and second-harmonic generation (SHG) signals relating to the collagen organization.
    背景与目标: :接口提供基本的骨骼功能的结构基础。在骨组织的分层结构中,发现异质性(例如孔隙度或边界)的范围从纳米到毫米,所有这些都有助于宏观特性。然而,迄今为止,当前使用的成像方法的复杂性或局限性限制了我们对这种功能集成的理解。在这里,我们使用无标记的三次谐波(THG)显微镜来解决此问题。我们发现,多孔的腔管网络(LCN)揭示了骨基质中骨细胞的几何形状,可以在与组织学兼容的毫米视野中以亚微米精度直接在3D中可视化。 THG还揭示了描述在连续重塑阶段形成的体积的界面。最后,我们表明,通过同时记录与胶原组织有关的THG和第二谐波产生(SHG)信号,可以分析LCN的结构与细胞外基质的结构和更大尺度的结构。
  • 【提出了一种利用有限元方法模拟非骨水泥THA骨长入过程的方法。】 复制标题 收藏 收藏
    DOI:10.1016/j.medengphy.2012.10.010 复制DOI
    作者列表:Tarala M,Janssen D,Verdonschot N
    BACKGROUND & AIMS: :In cementless total hip arthroplasty, long-term implant stability is achieved by bone ingrowth. The strength of the new bond gradually increases in time, due to bone maturation and progression of ingrowth. In finite element simulations, osseointegration generally is implemented as an instant change in the mechanical behavior of the implant-bone interface, although this is a simplified interpretation of the bone ingrowth process. The aim of the present study was to build on previous bone ingrowth simulations and propose a new methodology to simulate bone ingrowth as a time-dependent process. We developed an algorithm to calculate the strength of the local implant-bone bond based of the magnitude of interface micromotions and gaps in time. Our algorithm was subsequently tested in multiple hip reconstructions in which the bone quality and implant-bone contact area were varied. The results of the simulations showed that in the ideal situation (good bone quality and no interface gaps), 91% of implant area could achieve ingrowth, while in the worst case only 17% of implant area showed ingrowth. The initial contact area had a significant effect on ingrowth, overruling the effect of variations in bone quality. The progression of ingrowth had a stabilizing effect on adjacent regions, especially in the high contact area cases. Further development and validation of the presented algorithm requires more information on the nature of the relation between the ingrowth rate and the magnitude of micromotions and gap.
    背景与目标: :在非骨水泥全髋关节置换术中,骨向内生长可实现长期的植入物稳定性。由于骨骼成熟和向内生长,新结合的强度会随着时间逐渐增加。在有限元模拟中,骨整合通常是植入物-骨界面机械行为的即时变化,尽管这是对骨长入过程的简化解释。本研究的目的是在以前的骨骼长入模拟的基础上,提出一种新的方法来模拟骨骼长入作为一个与时间有关的过程。我们开发了一种算法,可以根据界面微运动的大小和时间间隔来计算局部植入物-骨结合的强度。我们的算法随后在多种髋关节重建术中进行了测试,在这些重建术中,骨骼质量和植入物与骨的接触面积均发生了变化。仿真结果表明,在理想情况下(良好的骨骼质量和无界面间隙),91%的植入物区域可以实现向内生长,而在最坏的情况下,只有17%的植入物区域可以向内生长。最初的接触面积对内生长有显着影响,但不影响骨质变化的影响。向内生长对邻近区域具有稳定作用,尤其是在高接触面​​积的情况下。所提出算法的进一步开发和验证需要关于长入率与微动和间隙大小之间关系的性质的更多信息。
  • 【线粒体转化和脂肪酸去饱和之间的泛素依赖性平衡调节线粒体融合。】 复制标题 收藏 收藏
    DOI:10.1038/ncomms15832 复制DOI
    作者列表:Cavellini L,Meurisse J,Findinier J,Erpapazoglou Z,Belgareh-Touzé N,Weissman AM,Cohen MM
    BACKGROUND & AIMS: :Mitochondrial integrity relies on homotypic fusion between adjacent outer membranes, which is mediated by large GTPases called mitofusins. The regulation of this process remains nonetheless elusive. Here, we report a crosstalk between the ubiquitin protease Ubp2 and the ubiquitin ligases Mdm30 and Rsp5 that modulates mitochondrial fusion. Ubp2 is an antagonist of Rsp5, which promotes synthesis of the fatty acids desaturase Ole1. We show that Ubp2 also counteracts Mdm30-mediated turnover of the yeast mitofusin Fzo1 and that Mdm30 targets Ubp2 for degradation thereby inducing Rsp5-mediated desaturation of fatty acids. Exogenous desaturated fatty acids inhibit Ubp2 degradation resulting in higher levels of Fzo1 and maintenance of efficient mitochondrial fusion. Our results demonstrate that the Mdm30-Ubp2-Rsp5 crosstalk regulates mitochondrial fusion by coordinating an intricate balance between Fzo1 turnover and the status of fatty acids saturation. This pathway may link outer membrane fusion to lipids homeostasis.
    背景与目标: 线粒体的完整性依赖于相邻外膜之间的同型融合,这种融合是由称为线粒体融合蛋白的大型GTP酶介导的。尽管如此,对这一过程的规制仍然难以捉摸。在这里,我们报道了泛素蛋白酶Ubp2与泛素连接酶Mdm30和Rsp5之间的串扰,该串扰调节线粒体融合。 Ubp2是Rsp5的拮抗剂,可促进脂肪酸去饱和酶Ole1的合成。我们表明,Ubp2还抵消了酵母Mofmin Fzo1的Mdm30介导的营业额,并且Mdm30靶向Ubp2降解,从而诱导了Rsp5介导的脂肪酸去饱和。外源性不饱和脂肪酸抑制Ubp2降解,导致Fzo1含量更高,并维持有效的线粒体融合。我们的结果表明,Mdm30-Ubp2-Rsp5串扰通过协调Fzo1周转率与脂肪酸饱和状态之间的复杂平衡来调节线粒体融合。该途径可能将外膜融合与脂质稳态联系起来。
  • 【贫T细胞骨髓移植后慢性粒细胞性白血病患者嵌合和白血病复发的细胞遗传学分析。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Offit K,Burns JP,Cunningham I,Jhanwar SC,Black P,Kernan NA,O'Reilly RJ,Chaganti RS
    BACKGROUND & AIMS: :Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.
    背景与目标: :对64例T细胞贫乏的异基因骨髓移植(BMT)后的慢性粒细胞白血病(CML)患者进行了细胞遗传学研究。 40名慢性期(CP)慢性粒细胞白血病(CML)患者接受了细胞减少治疗,随后接受了BMT和HLA匹配的T细胞缺失同种异体骨髓。其余24例患者被移植到第二个慢性,加速或发育阶段,或接受了T细胞贫乏的移植物,并补充了一定剂量的T细胞。 Y染色体和常染色体异质性用于区分供体和宿主细胞。在第一次CP中90%的患者中发现了混合的造血嵌合体(存在供体和宿主细胞)。在40位首例CP CML患者中,有16位再次出现了费城(Ph)染色体。如预期的那样,在移植后的任何时间都有可检测的Ph染色体阳性细胞的患者极有可能随后发生临床复发。很少观察到Ph阳性克隆的瞬时消失,然后出现Ph染色体的重新出现或临床复发。与其他患者相比,在BMT后3个月内,移植患者中具有大于25%宿主细胞的亚组患者的存活时间明显缩短,且没有细胞遗传学或临床复发。在接受了捐献者T细胞补充至贫乏T细胞移植物中的患者中,完全嵌合体比例更高。观察到Ph阳性和阴性细胞的克隆进程,这可能是辐射诱导的断裂的结果。 BMT后患者的系列细胞遗传学研究可以提供有关CML的生物学和临床行为的有用信息。
  • 【微螺钉周围牙槽骨密度的变化:一项前瞻性临床研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.ajodo.2012.07.013 复制DOI
    作者列表:Al Maaitah EF,Safi AA,Abdelhafez RS
    BACKGROUND & AIMS: INTRODUCTION:Our objective was to assess the effects of miniscrews on interproximal alveolar bone density and adjacent gingival tissue health. METHODS:Forty-four titanium miniscrews were inserted between maxillary second premolars and first molars on both sides of the dentition in 22 consecutive patients (15 female, 7 male; ages, 14-24 years). A control area (between the maxillary first and second premolars) was also assessed. Both miniscrew (study) and control areas were monitored clinically and radiographically at different time points: before insertion of the miniscrews and at 1 month, 3 months, and 6 months after insertion. Software associated with a digital intraoral radiography machine was used to assess changes in alveolar bone density. Clinical gingival parameters of the study and control areas were also recorded. A repeated-measures analysis of variance and the Bonferroni post-hoc pairwise comparison tests were used to assess the changes at the different time points. RESULTS:Thirty-nine miniscrews were successful for the study duration. Male subjects had significantly (P <0.001) higher alveolar bone density than did the females at baseline. Alveolar bone density around the miniscrews increased significantly (P <0.001) between 3 and 6 months after insertion upon loading. Alveolar bone density of the control area did not change significantly during the experiment (P >0.05). The width of keratinized gingiva increased significantly (P <0.001) in the study and control areas after insertion of miniscrews and remained with no significant change throughout the study. CONCLUSIONS:Miniscrews increased the alveolar bone density significantly after 3 months of insertion and were not associated with detrimental effects on the adjacent gingival tissues.
    背景与目标: 简介:我们的目的是评估微螺钉对近牙槽骨密度和邻近牙龈组织健康的影响。
    方法:在连续的22例患者(女性15例,男性7例;年龄14-24岁)的上颌第二前磨牙和第一磨牙之间插入四十四个钛微螺钉。还评估了一个对照区域(在上颌第一和第二前磨牙之间)。在不同时间点分别对微型螺钉(研究)区域和对照区域进行了临床和影像学检查:微型螺钉插入之前以及插入后1个月,3个月和6个月。与数字口腔放射成像机相关的软件用于评估牙槽骨密度的变化。还记录了研究和对照区域的临床牙龈参数。方差的重复测量分析和Bonferroni事后成对比较测试用于评估不同时间点的变化。
    结果:在研究期间,三十九个小螺钉是成功的。在基线时,男性受试者的牙槽骨密度显着高于女性(P <0.001)。加载后3至6个月之间,微螺钉周围的牙槽骨密度显着增加(P <0.001)。在实验过程中,对照组的牙槽骨密度没有明显变化(P> 0.05)。插入小螺钉后,研究区域和对照区域的角化牙龈宽度显着增加(P <0.001),并且在整个研究过程中没有明显变化。
    结论:微螺钉在插入3个月后显着增加了牙槽骨密度,并且与相邻牙龈组织的有害影响无关。
  • 【壳聚糖磷酸甘油/血液植入物可增加钻孔软骨缺损中的细胞募集,短暂血管生成和软骨下骨重塑。】 复制标题 收藏 收藏
    DOI:10.1016/j.joca.2006.08.007 复制DOI
    作者列表:Chevrier A,Hoemann CD,Sun J,Buschmann MD
    BACKGROUND & AIMS: OBJECTIVE:Marrow-stimulation techniques are used by surgeons to repair cartilage lesions although consistent regeneration of hyaline cartilage is rare. We have shown previously that autologous blood can be mixed with a polymer solution containing chitosan in a glycerol phosphate (GP) buffer (chitosan-GP), and that implantation of this polymer/blood composite onto marrow-stimulated chondral defects in rabbit and sheep leads to the synthesis of more chondral repair tissue with greater hyaline character compared to marrow-stimulation alone. In the current study, we examined the modulation of cell recruitment and repair tissue characteristics at early post-surgical time points (from day 1 to 56) in a rabbit model to elucidate potential mechanisms behind this improved repair outcome. DESIGN:Thirty-three skeletally mature New Zealand White rabbits underwent bilateral arthrotomies, with each trochlea receiving a cartilage defect (3.5 mm x 4.5mm) bearing four microdrill holes (0.9 mm diameter, approximately 4 mm deep) into the subchondral bone. One defect per rabbit was treated with a chitosan-GP/blood implant, while the other defect was left as a microdrilled control. Repair tissues were stained by histochemistry, for collagen types I, II, and X by immunohistochemistry and analyzed using quantitative stereological tools. RESULTS:Histological analyses demonstrated that control defects followed a typical healing sequence observed previously in marrow-stimulation animal models while chitosan-GP/blood implants led to three significant modifications in the healing sequence at early stages: (1) increased inflammatory and marrow-derived stromal cell recruitment to the microdrill holes, (2) increased vascularization of the provisional repair tissue in the microdrill holes, and (3) increased intramembranous bone formation and subchondral bone remodeling (BR). CONCLUSIONS:These results suggest that the greater levels of provisional tissue vascularization and BR activity are main factors supporting improved cartilage repair when chitosan-GP/blood implants are applied to marrow-stimulated cartilage lesions.
    背景与目标: 目的:尽管透明软骨的持续再生很少见,但外科医生仍采用骨髓刺激技术修复软骨损伤。以前我们已经证明,自体血液可以与在磷酸甘油(GP)缓冲液中含有壳聚糖的聚合物溶液(chitosan-GP)混合,并将这种聚合物/血液复合物植入到兔和绵羊的骨髓刺激的软骨缺损中与单独的骨髓刺激相比,可以合成更多的具有更透明的玻璃质特征的软骨修复组织。在当前的研究中,我们在兔模型的手术后早期(从第1天到第56天)检查了细胞募集和修复组织特征的调节,以阐明这种改善的修复结果背后的潜在机制。
    设计:对33只骨骼成熟的新西兰白兔进行了双侧关节置换术,每只滑车都接受了软骨缺损(3.5 mm x 4.5mm),并在软骨下骨中带有四个微孔(直径0.9 mm,深约4 mm)。每只兔子的一个缺损用壳聚糖-GP /血液植入物治疗,而另一只缺损留作微钻孔对照。通过组织化学对修复组织进行染色,通过免疫组织化学对I,II和X型胶原进行染色,并使用定量立体工具进行分析。
    结果:组织学分析表明,对照缺陷遵循了先前在骨髓刺激动物模型中观察到的典型愈合顺序,而壳聚糖-GP /血液植入物在早期阶段对愈合顺序产生了三个重大改变:(1)炎症和骨髓来源的增加基质细胞募集到微孔中,(2)增加了微孔中临时修复组织的血管形成,(3)膜内骨形成和软骨下骨重塑(BR)增加。
    结论:这些结果表明,当将壳聚糖-GP /血液植入物应用于骨髓刺激的软骨病变时,更高水平的临时组织血管生成和BR活性是支持改善软骨修复的主要因素。
  • 【对于慢性髓样白血病,骨髓移植后的供体嵌合症是无病生存的重要指标。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Gardiner N,Lawler M,O'Riordan J,De'Arce M,McCann SR
    BACKGROUND & AIMS: Although Chronic Myeloid Leukaemia (CML) can be treated successfully with allogeneic bone marrow transplantation (BMT), leukaemia relapse remains a significant clinical problem. Molecular monitoring of the post transplant marrow can be useful in predicting relapse particularly in CML patients where the Philadelphia chromosome or its molecular counterpart, the BCR-ABL fusion messenger RNA can be used as a leukaemia specific marker of minimal residual disease (MRD). We have investigated chimaerism (using polymerase chain reaction of short tandem repeat sequences (STR-PCR)) and MRD status (using reverse transcriptase PCR of the BCR-ABL fusion mRNA) in a serial fashion in 18 patients who were in clinical and haematological remission post allogeneic BMT for chronic phase CML. Eleven patients exhibited complete donor chimaerism with no evidence of minimal residual disease. Five patients had transient or low level stable MC. Late MC and MRD was observed in two patients who relapsed > 6 years after T cell depleted BMT for CML. Thus STR-PCR is an appropriate screening test in the post transplant setting for CML patients, but those patients exhibiting mixed haemopoietic chimaerism should also be monitored using a leukaemia specific sensitive molecular assay.

    背景与目标: 尽管同种异体骨髓移植(BMT)可以成功治疗慢性粒细胞白血病(CML),但白血病复发仍然是一个重要的临床问题。移植后骨髓的分子监测可用于预测复发,特别是在CML患者中,在费城染色体或其分子对应物BCR-ABL融合信使RNA可以用作白血病特异性标记物(最小残留病(MRD))的CML患者。我们已对18例临床和血液学缓解的患者进行了系列研究(使用短串联重复序列的聚合酶链反应(STR-PCR))和MRD状态(使用BCR-ABL融合mRNA的逆转录酶PCR)进行了调查。后异基因BMT治疗慢性期CML。 11名患者表现出完全的供体嵌合症,没有最小残留病的证据。 5例患者有短暂或低水平的稳定MC。在T细胞耗尽BMT的CML后复发> 6年的两名患者中观察到晚期MC和MRD。因此,STR-PCR是适合于CML患者移植后环境的筛查测试,但对于那些表现出混合造血干细胞病的患者,也应使用白血病特异性敏感分子测定法进行监测。

  • 【同种异体骨髓移植后,闭塞性细支气管炎可引起肺炎,用于急性淋巴细胞白血病。】 复制标题 收藏 收藏
    DOI:10.1038/sj.bmt.1700816 复制DOI
    作者列表:Kanda Y,Takahashi T,Imai Y,Miyagawa K,Ohishi N,Oka T,Chiba S,Hirai H,Yazaki Y
    BACKGROUND & AIMS: :We report a patient who developed bronchiolitis obliterans organizing pneumonia (BOOP) after syngeneic BMT for ALL. The patient complained of persistent low-grade fever and non-productive cough after engraftment. Chest CT scan showed patchy infiltration bilaterally in the lower lung fields. Antibiotics were ineffective. Cultures, serological studies and polymerase chain reaction detected no infectious pathogens. We finally made a diagnosis of BOOP by thoracoscopical lung biopsy. The lung lesion disappeared in a month with corticosteroid therapy. While BOOP following allogeneic BMT has been reported, this is the first report after syngeneic transplantation.
    背景与目标: :我们报告了在所有患者的同种BMT后发生闭塞性细支气管炎的患者,并组织了肺炎(BOOP)。该患者抱怨移植后持续低烧和非生产性咳嗽。胸部CT扫描显示下肺野两侧有片状浸润。抗生素无效。文化,血清学研究和聚合酶链反应未发现传染性病原体。我们终于通过胸腔镜肺活检诊断出BOOP。皮质类固醇激素治疗一个月后,肺部病变消失了。虽然已经报道了异基因BMT后的BOOP,但这是同基因移植后的首次报道。

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