• 【同种异体骨髓移植后人类细小病毒B19抗体的持久性:先前受体免疫的作用。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Ang HA,Apperley JF,Ward KN
    BACKGROUND & AIMS: Human parvovirus B19 (B19) IgG was studied retrospectively in 66 allogeneic bone marrow transplantation (BMT) patients using an enzyme-linked immunosorbent assay. Recipient and donor sera had been stored pre-BMT together with sequential sera thereafter. Approximately half of donors and recipients had anti-B19 IgG pre-BMT and thus the relative contributions of donor and recipient immunity to antibody production after transplantation could be assessed. For each patient, a serum taken 2 to 3 years after BMT was also tested and the results show that persistence of B19 antibody depends on prior recipient (P = .0003) but not on donor immunity (P = .8). The findings were similar in both sibling and (VUD) BMT volunteer unrelated donor patients. Analysis of sequential post-BMT sera from 41 of the patients, for whom appropriately timed samples were available, showed primary B19 infection in 3 seronegative individuals, whereas 5 others who were seropositive before BMT underwent recurrent infection. Sequential results from the remaining 33 patients without recent B19 infection showed no evidence for donor antibody transfer and confirmed that antibody persistence depends on prior recipient immunity. B19 IgG levels decreased variably with time and some patients eventually became seronegative. It is concluded that this long-term persistence of B19 antibody post-BMT is most probably due to the existence of long-lived recipient plasma cells.

    背景与目标: 使用酶联免疫吸附试验对66名同种异体骨髓移植(BMT)患者进行了人类细小病毒B19(B19)IgG回顾性研究。收件人和供体血清已在BMT之前与随后的顺序血清一起存储。大约一半的供体和受体在BMT前具有抗B19 IgG,因此可以评估移植后供体和受体免疫对抗体产生的相对贡献。对于每位患者,还对BMT后2至3年的血清进行了测试,结果表明B19抗体的持久性取决于先前的接受者(P = .0003),而不取决于供体的免疫力(P = .8)。在同级和(VUD)BMT自愿无关供者患者中,发现相似。对41位患者的BMT后连续血清进行分析,发现有适当定时的样本,在3例血清阴性患者中原发性B19感染,而在BMT之前5例血清阳性的其他患者则进行了复发性感染。其余33例近期未感染B19的患者的顺序结果显示,尚无转移供体抗体的证据,并证实抗体的持久性取决于先前的受体免疫力。 B19 IgG水平随时间而下降,有些患者最终呈血清阴性。结论是BMT后B19抗体的这种长期持久性很可能是由于存在长寿命的受体浆细胞。

  • 【非侵入性连续估计人pa骨的血流变化。】 复制标题 收藏 收藏
    DOI:10.1007/s11517-006-0070-0 复制DOI
    作者列表:Näslund J,Pettersson J,Lundeberg T,Linnarsson D,Lindberg LG
    BACKGROUND & AIMS: :A photoplethysmographic (PPG) technique to assess blood flow in bone tissue has been developed and tested. The signal detected by the PPG consists of a constant-level (DC) component-which is related to the relative vascularization of the tissue-and a pulsatile (AC) component-which is synchronous with the pumping action of the heart. The PPG probe was applied on the skin over the patella. The probe uses near-infrared (804 nm) and green (560 nm) light sources and the AC component of the PPG signals of the two wavelengths was used to monitor pulsatile blood flow in the patellar bone and the overlying skin, respectively. Twenty healthy subjects were studied and arterial occlusion resulted in elimination of PPG signals at both wavelengths, whereas occlusion of skin blood flow by local surface pressure eliminated only the PPG signal at 560 nm. In a parallel study on a physical model with a rigid tube we showed that the AC component of the PPG signal originates from pulsations of blood flow in a rigid structure and not necessarily from volume pulsations. We conclude that pulsatile blood flow in the patellar bone can be assessed with the present PPG technique.
    背景与目标: :已经开发并测试了用于评​​估骨组织中血流的光电容积描记(PPG)技术。 PPG检测到的信号由与组织的相对血管形成有关的恒定水平(DC)分量和与心脏的泵浦动作同步的脉动(AC)分量组成。将PPG探针施加到over骨上的皮肤上。该探头使用近红外(804 nm)和绿色(560 nm)光源,并且两个波长的PPG信号的AC分量分别用于监视the骨和周围皮肤中的脉动血流。对二十名健康受试者进行了研究,动脉闭塞导致两种波长的PPG信号均被消除,而局部表面压力对皮肤血流的闭塞仅消除了560 nm处的PPG信号。在具有刚性管的物理模型的并行研究中,我们显示了PPG信号的AC分量源自刚性结构中的血流脉动,而不一定源自体积脉动。我们得出的结论是,可以使用当前的PPG技术评估the骨中的搏动性血流。
  • 【继发性中耳和岩性胆脂瘤的计算机断层扫描】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Vasdev A,Boubagra K,Lavieille JP,Bessou P,Lefournier V
    BACKGROUND & AIMS: The authors present their experience of secondary cholesteatomas of the middle ear explored by computerized tomography (CT). Following a brief anatomicopathological description of secondary petrous bone cholesteatomas, and of the CT technique used for their exploration, they describe and illustrate the classical "bag-shaped" internal or external attical forms usually extended to the antrum and the mastoid process, and the less common locations often due to relapse or postoperative recurrences (anterior hypotympanic or posterior mastoidal). The holotympanic forms, usually due to "lamellar" cholesteatomas, create diagnostic problems with other opacities in the cavity, as also do certain forms that are evacuated spontaneously or by aspiration. One of the qualities of CT lies in the preoperative extension assessment. The lesion may extend towards the internal wall of the cavity (lateral semicircular canal, second portion of the facial nerve), towards the labyrinth to the petrosal apex and/or the geniculate ganglion, and above all towards the inferior labyrinth which might bring the cholesteatoma into contact with large vessels (e.g. jugular vein bulb for postero-inferior extensions, carotid canal for antero-inferior extensions). Extension into anfractuosities of the cavity walls (sinus tympani, subratubal fossette) must be systematically looked for in order to avoid postoperative recurrences.

    背景与目标: 作者介绍了他们通过计算机断层扫描(CT)探索的中耳继发性胆脂瘤的经验。在对继发性岩性胆脂瘤和用于探查的CT技术进行了简要的解剖病理学描述之后,他们描述并说明了通常延伸至窦腔和乳突的经典“袋状”内部或外部阁楼形式,其次常见部位通常是由于复发或术后复发(前鼓膜下或乳突后)。通常由于“片状”胆脂瘤而引起的全神贯腹形式,以及其他自发性或通过抽吸而排空的形式,也给腔内的其他混浊带来了诊断问题。 CT的特质之一是术前扩展评估。病变可向腔内壁(外侧半规管,面神经的第二部分),迷路延伸至椎尖和/或膝状神经节,最重要的是向下迷路延伸,可能导致胆脂瘤与大血管接触(例如,颈静脉球用于后下延伸,颈动脉用于前下延伸)。为了避免术后复发,必须系统地寻找腔壁(鼓膜窦,管下突窝)的畸形。

  • 【骨髓衰竭综合征的染色体不稳定。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Babu Rao V,Colah RB
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【骨髓嵌合体小鼠的肿瘤浸润基质细胞的制备和功能分析。】 复制标题 收藏 收藏
    DOI:10.1111/j.1348-0421.2006.tb03830.x 复制DOI
    作者列表:Ishigaki H,Yamamoto Y,Ishida H,Kajino K,Itoh Y,Fujiyama Y,Ogasawara K
    BACKGROUND & AIMS: :Tumor-infiltrating stroma cells (TISC) as well as tumors themselves are thought to be involved in tumor-related immunosuppression, which is one of the critical mechanisms of tumor escape from immune surveillance. However, preparation of TISC is difficult because of the small proportion of TISC in established tumors. Thus, the cells thought to be involved in tumor-related immunosuppression are generally prepared from spleens or draining lymph nodes in tumor-bearing mice. In this study, we developed a method for directly preparing TISC from established tumors in order to analyze their function. Using green fluorescent protein (GFP) transgenic (Tg) mice and C57BL/6 mice transplanted with bone marrow (BM) cells of GFPTg mice, we detected three subpopulations of TISC: one is compatible with immature myeloid cells (ImC) derived from BM and the two other subpopulations, CD11b(+) cells and CD11b(-) cells, do not originate from BM. The TISC including these subpopulations but not each subpopulation independently after culturing with tumors in the presence of GM-CSF could suppress T cell proliferation induced by anti-CD3. In our system, tumors did not inhibit T cell responses directly, but unknown factors from tumors affected immunosuppression by TISC.
    背景与目标: :肿瘤浸润基质细胞(TISC)以及肿瘤本身都被认为与肿瘤相关的免疫抑制有关,这是肿瘤逃避免疫监视的关键机制之一。然而,由于在已建立的肿瘤中TISC的比例很小,因此TISC的制备是困难的。因此,通常被认为与肿瘤相关的免疫抑制有关的细胞是从荷瘤小鼠的脾脏或引流淋巴结中制备的。在这项研究中,我们开发了一种从已建立的肿瘤中直接制备TISC的方法,以分析其功能。使用绿色荧光蛋白(GFP)转基因(Tg)小鼠和移植有GFPTg小鼠骨髓(BM)细胞的C57BL / 6小鼠,我们检测到TISC的三个亚群:一个与源自BM的未成熟髓样细胞(ImC)相容。其他两个亚群CD11b()细胞和CD11b(-)细胞并非源自BM。在存在GM-CSF的情况下与肿瘤培养后,TISC包括这些亚群,但并非每个亚群独立地抑制由抗CD3诱导的T细胞增殖。在我们的系统中,肿瘤并未直接抑制T细胞反应,但来自肿瘤的未知因素影响了TISC的免疫抑制。
  • 【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。

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