In vivo

体内
  • 文章类型: Journal Article
    将生物活性离子掺入生物材料中作为在分子水平上增强骨组织再生的策略已经获得了极大的关注。然而,关于添加这些离子对免疫反应的影响,尤其是对最重要的细胞调节剂的影响,巨噬细胞。因此,本研究旨在研究涂覆有金属离子(Sr2/Mg2)和PLGA的双相骨替代物(BBS)的体外细胞相容性和体内骨重建和材料相关免疫反应的调节,以纯BBS为对照组。最初,根据根据DINENISO10993-5方案获得的体外结果鉴定了两种细胞相容性修饰的材料变体。使用SEM-EDX和ICP-OES表征了两种材料的表面结构和离子释放。然后使用颅骨缺损模型将材料植入Wistar大鼠10、30和90天。组织病理学和组织形态学分析用于评估材料降解,骨再生,骨传导性,和免疫反应。研究结果表明,在所有研究组中都发现了类似的新骨形成。然而,在植入早期,与其他两组相比,BBS_Sr2组的再生速度明显加快。此外,所有材料均可诱导类似的组织和免疫反应,包括大量促炎巨噬细胞和多核巨细胞(MNGC).总之,这项研究探讨了治疗性离子掺杂对骨再生模式和炎症反应的影响,为具有潜在临床适用性的新一代双相磷酸钙材料的发展提供见解。
    The incorporation of bioactive ions into biomaterials has gained significant attention as a strategy to enhance bone tissue regeneration on the molecular level. However, little knowledge exists about the effects of the addition of these ions on the immune response and especially on the most important cellular regulators, the macrophages. Thus, this study aimed to investigate the in vitro cytocompatibility and in vivo regulation of bone remodeling and material-related immune responses of a biphasic bone substitute (BBS) coated with metal ions (Sr2+/Mg2+) and PLGA, using the pure BBS as control group. Initially, two cytocompatible modified material variants were identified according to the in vitro results obtained following the DIN EN ISO 10993-5 protocol. The surface structure and ion release of both materials were characterized using SEM-EDX and ICP-OES. The materials were then implanted into Wistar rats for 10, 30, and 90 days using a cranial defect model. Histopathological and histomorphometrical analyses were applied to evaluate material degradation, bone regeneration, osteoconductivity, and immune response. The findings revealed that in all study groups comparable new bone formation were found. However, during the early implantation period, the BBS_Sr2+ group exhibited significantly faster regeneration compared to the other two groups. Additionally, all materials induced comparable tissue and immune responses involving high numbers of both pro-inflammatory macrophages and multinucleated giant cells (MNGCs). In conclusion, this study delved into the repercussions of therapeutic ion doping on bone regeneration patterns and inflammatory responses, offering insights for the advancement of a new generation of biphasic calcium phosphate materials with potential clinical applicability.
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  • 文章类型: Journal Article
    Boswellic酸(BA)是一组ursane和iianane类型的五环三萜类。它们已经显示出非常有趣的生物学特性,这导致了许多合成方案的发展。天然BA及其合成衍生物可用于治疗多种癌症。病毒感染和炎性疾病。
    本综述涵盖了与天然BA及其合成衍生物的治疗活性有关的专利。乳香酸的最新专利研究(通过使用关键词\'乳香酸,\'在SciFinder中,PubMed,以及2016年至2023年的Google专利和数据库。
    乳香酸已显示出有效的抗病毒作用,抗癌和抗炎潜力。通过在C24-CO2H官能团处的修饰已经制备了很少的BA类似物。特别是,与母体AKBA相比,C-24酰胺和氨基类似物显示出增强的抗癌作用。此外,BA具有与其他抗病毒药物形成缀合物的能力,抗炎和抗癌药物,协同增强其生物功效。此外,这种结合策略将增加BAs的溶解度和生物利用度,这是BAs发展中最重要的问题之一。
    UNASSIGNED: Boswellic acids (BAs) are a group of pentacyclic triterpenoids of the ursane and oleanane type. They have shown very interesting biological properties that have led to the development of a number of synthesis protocols. Both natural BAs and their synthetic derivatives may be useful in the treatment of a variety of cancers, viral infections and inflammatory diseases.
    UNASSIGNED: This review covers patents relating to the therapeutic activities of natural BAs and their synthetic derivatives. The latest patented studies of boswellic acids (are summarized by using the keywords \'boswellic acid,\' in SciFinder, PubMed, and Google Patents and databases in the year from 2016 to 2023.
    UNASSIGNED: Boswellic acids have shown potent antiviral, anticancer and anti-inflammatory potential. Few BAs analogues have been prepared by modification at the C24-CO2H functional groups. In particular, the C-24 amide and amino analogues have shown enhanced anticancer effects compared to the parent AKBA. In addition, BAs have the ability to form conjugates with other antiviral, anti-inflammatory and anticancer drugs that synergistically enhance their biological efficacy. In addition, this conjugation strategy will increase the solubility and bioavailability of BAs, which is one of the most important issues in the development of BAs.
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  • 文章类型: English Abstract
    This paper investigates the variation of lung tissue dielectric properties with tidal volume under in vivo conditions to provide reliable and valid a priori information for techniques such as microwave imaging. In this study, the dielectric properties of the lung tissue of 30 rabbits were measured in vivo using the open-end coaxial probe method in the frequency band of 100 MHz to 1 GHz, and 6 different sets of tidal volumes (30, 40, 50, 60, 70, 80 mL) were set up to study the trends of the dielectric properties, and the data at 2 specific frequency points (433 and 915 MHz) were analyzed statistically. It was found that the dielectric coefficient and conductivity of lung tissue tended to decrease with increasing tidal volume in the frequency range of 100 MHz to 1 GHz, and the differences in the dielectric properties of lung tissue for the 6 groups of tidal volumes at 2 specific frequency points were statistically significant. This paper showed that the dielectric properties of lung tissue tend to vary non-linearly with increasing tidal volume. Based on this, more accurate biological tissue parameters can be provided for bioelectromagnetic imaging techniques such as microwave imaging, which could provide a scientific basis and experimental data support for the improvement of diagnostic methods and equipment for lung diseases.
    本文针对在体条件下的肺组织介电特性随潮气量而发生变化展开研究,为微波成像等技术提供可靠有效的先验信息。本研究在100 MHz~1 GHz频段采用开端同轴探头法,对30只家兔肺组织的介电特性进行在体测量,设置6组不同的潮气量(30、40、50、60、70、80 mL)研究其介电特性变化趋势,并且对2个特定频率点(433、915 MHz)的数据进行统计学分析。结果发现,在100 MHz~1 GHz频率范围内,随着潮气量增大,肺组织的介电系数和电导率均呈现下降的趋势,在2个特定频率点和6组潮气量下,肺组织介电特性差异具有统计学意义。本文研究表明,肺组织的介电特性随潮气量增大呈非线性变化趋势。以此为依据,本文可为微波成像等生物电磁成像技术提供更精确的生物组织介电特性参数,为改进肺部疾病诊断方法和设备提供了科学依据和实验数据支持。.
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  • 文章类型: Journal Article
    目的:探讨超短回波时间(UTE)-MRI定量成像在体内检测早期软骨退变的可行性及潜在病理生化基础。
    方法:前瞻性招募了20名骨关节炎(OA)计划行全膝关节置换术(TKA)的志愿者。术前进行UTE-MRI序列和常规序列。在胫骨平台和股骨外侧髁图像上手动绘制感兴趣区域(ROI)以计算MRI值。在TKA期间,根据与MR图像对应的预设位置采集软骨样本。相应ROI的病理和生化成分,包括组织学分级,糖胺聚糖(GAG)含量,胶原蛋白完整性,并获得含水量。
    结果:评估了来自7名男性(年龄范围:68至78岁;74±3岁)和13名女性(年龄范围:57至79岁;67±6岁)志愿者的91个ROI。UTE-MTR(r=-0.619,p<0.001),UTE-AdabT1ρ(r=0.568,p<0.001),UTE-T2*值(r=-0.495,p<0.001)与Mankin评分的相关性高于T2(r=0.287,p=0.006)和T1ρ(r=0.435,p<0.001)。其中,UTE-MTR具有最高的诊断性能(AUC=0.824,p<0.001)。UTE-MTR,UTE-AdabT1ρ和UTE-T2*值主要与胶原结构完整性有关,PG含量和含水量,分别为(r=0.536,-0.652,-0.518,p<0.001)。
    结论:与常规T2和T1ρ值相比,UTE-MRI对早期软骨退变的体内诊断价值更高。其中,UTE-MTR具有最高的诊断效率。UTE-MTR,UTE-AdabT1ρ,和UTE-T2*值主要反映软骨退化的不同方面——胶原结构的完整性,PG含量,和含水量,分别。
    超短回波时间(UTE)-MRI有可能成为检测体内早期软骨退变的新型图像生物标志物,并与早期软骨退变的生化变化相关。
    结论:常规MR可能由于相对较长的回波时间而错过一些早期软骨改变。超短回波时间(UTE)-MRI显示了识别体内早期软骨退变的能力。UTE-MT,UTE-AdabT1ρ,UTE-T2*图谱主要反映软骨退变的不同方面。
    OBJECTIVE: To explore the feasibility of Ultra-short echo time (UTE) - MRI quantitative imaging in detecting early cartilage degeneration in vivo and underlying pathological and biochemical basis.
    METHODS: Twenty volunteers with osteoarthritis (OA) planning for total knee arthroplasty (TKA) were prospectively recruited. UTE-MRI sequences and conventional sequences were performed preoperatively. Regions of interests (ROIs) were manually drawn on the tibial plateau and lateral femoral condyle images to calculate MRI values. Cartilage samples were collected during TKA according to the preset positions corresponding to MR images. Pathological and biochemical components of the corresponding ROI, including histological grading, glycosaminoglycan (GAG) content, collagen integrity, and water content were obtained.
    RESULTS: 91 ROIs from volunteers of 7 males (age range: 68 to 78 years; 74 ± 3 years) and 13 females (age range: 57 to 79 years; 67 ± 6 years) were evaluated. UTE-MTR (r = -0.619, p < 0.001), UTE-AdiabT1ρ (r = 0.568, p < 0.001), and UTE-T2* values (r = -0.495, p < 0.001) showed higher correlation with Mankin scores than T2 (r = 0.287, p = 0.006) and T1ρ (r = 0.435, p < 0.001) values. Of them, UTE-MTR had the highest diagnostic performance (AUC = 0.824, p < 0.001). UTE-MTR, UTE-AdiabT1ρ and UTE-T2* value was mainly related to collagen structural integrity, PG content and water content, respectively (r = 0.536, -0.652, -0.518, p < 0.001, respectively).
    CONCLUSIONS: UTE-MRI have shown greater in vivo diagnostic value for early cartilage degeneration compared to conventional T2 and T1ρ values. Of them, UTE-MTR has the highest diagnostic efficiency. UTE-MTR, UTE-AdiabT1ρ, and UTE-T2* value mainly reflect different aspects of cartilage degeneration--integrity of collagen structure, PG content, and water content, respectively.
    UNASSIGNED: Ultra-short echo time (UTE)-MRI has the potential to be a novel image biomarkers for detecting early cartilage degeneration in vivo and was correlated with biochemical changes of early cartilage degeneration.
    CONCLUSIONS: Conventional MR may miss some early cartilage changes due to relatively long echo times. Ultra-short echo time (UTE)-MRI showed the ability in identifying early cartilage degeneration in vivo. UTE-MT, UTE-AdiabT1ρ, and UTE-T2* mapping mainly reflect different aspects of cartilage degeneration.
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  • 文章类型: Journal Article
    负重关节内植入物的体内动物模型对于研究由骨整合失败引起的植入物骨整合和无菌性松动至关重要。骨整合,定义为活骨组织和承载植入物表面之间的直接结构和功能附着,对于植入物的稳定性至关重要,并且被认为是全关节置换术中植入物长期临床成功的先决条件。与大型动物模型相比,小鼠模型为追踪细胞分化和增殖提供了广泛的遗传工具。18至22周龄的C57BL/6J背景小鼠接受了钛植入物的压配合或宽松植入,实现骨整合或纤维整合。为该程序的两个版本都开发了协议,包括相关解剖结构的描述。对样品进行显微计算机断层扫描,并进行生物力学测试以获得骨整合。最后,将样品固定并包埋以进行组织学评估。在松散的植入样品中没有矿化组织和减弱的最大拉出力表明,与术后4周的对照相比,这些植入物的机械稳定性较差。组织学分析表明,在4周时,松散植入样品的植入物周围区域存在广泛的纤维化组织,并且在压装样品中具有出色的植入物骨整合。在小鼠中实现了具有骨向内生长或稳健的假体周围纤维化的机械稳定和不稳定的半关节成形术模型。我们希望该模型可以帮助解决无菌性松动体内研究的当前局限性,并带来必要的转化益处。
    An in vivo animal model of a weight-bearing intra-articular implant is crucial to the study of implant osseointegration and aseptic loosening caused by osseointegration failure. Osseointegration, defined as a direct structural and functional attachment between living bone tissue and the surface of a load-carrying implant, is essential for implant stability and considered a prerequisite for the long-term clinical success of implants in total joint arthroplasty. Compared to large animal models, murine models offer extensive genetic tools for tracing cell differentiation and proliferation. The 18- to 22-week-old C57BL/6J background mice underwent either press-fitted or loose implantation of a titanium implant, achieving osseointegration or fibrous integration. A protocol was developed for both versions of the procedure, including a description of the relevant anatomy. Samples were subjected to microcomputed tomography and underwent biomechanical testing to access osseointegration. Lastly, samples were fixed and embedded for histological evaluation. The absence of mineralized tissue and weakened maximum pull-out force in loose implantation samples indicated that these implants were less mechanically stable compared to the control at 4 weeks postoperation. Histological analysis demonstrated extensive fibrotic tissue in the peri-implant area of loose implantation samples and excellent implant osseointegration in press-fitted samples at 4 weeks. Both mechanically stable and unstable hemiarthroplasty models with either osseous ingrowth or a robust periprosthetic fibrosis were achieved in mice. We hope that this model can help address current limitations for in vivo study of aseptic loosening and lead to necessary translational benefits.
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  • 文章类型: Journal Article
    在体内建立生物膜感染模型可以更好地了解细菌的潜在感染机制。在这里,我们描述了构建猪链球菌体内生物膜模型的方法。模拟的动物是一头小猪,这是S.Suis的天然水库,通过鼻内接种猪链球菌模拟临床感染模式。该模型符合临床实践,易于操作,具有良好的重复稳定性。
    Establishing a biofilm infection model in vivo allows a better understanding of the underlying infection mechanisms of bacteria. Here we describe a method for constructing an in vivo biofilm model of Streptococcus suis. The animal modeled is a piglet, which is the natural reservoir of S. suis, and the mode of clinical infection is simulated by intranasal inoculation of S. suis. This model is in line with clinical practice, easy to operate, and has good repeated stability.
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  • 文章类型: Journal Article
    精确切除肿瘤的开创性方法涉及荧光引导手术,虽然挑战依然存在,包括在肿瘤边界处观察到的低荧光对比度和对边缘处的正常组织的过度损伤的可能性。铅/硫化镉量子点(PbS@CdS量子点),拥有高量子产率(QYs)和生动的荧光,促进了第二个近红外窗口(NIR-II,900-1700nm)。然而,在荧光手术导航操作期间,这些无机纳米粒子(NPs)的亲水涂层保证了生物安全性;它也是以损失QY和NIR-II荧光的显著部分为代价的,对正常组织造成的高度损伤。在这里,我们提出了亲水的核-壳PbS@CdS@PEGNP,其直径异常小(〜8nm)和明亮的NIR-IIb(1500-1700nm)发射约1600nm。mPEG-SH(MW:2000)解决了PbS@CdSQD的疏水性并增强了其生物安全性。体内荧光引导的宫颈肿瘤切除术在注射PbS@CdS@PEGNP的水溶液后立即可实现。值得注意的是,这种方法导致对切除肿瘤边缘正常组织的损伤厚度显著减小(100-500μm).具有高QY(〜30.2%)和强大的抗光漂白能力,NIR-IIb成像在整个成像过程中持续。
    Pioneering approaches for precise tumor removal involve fluorescence-guided surgery, while challenges persist, including the low fluorescence contrast observed at tumor boundaries and the potential for excessive damage to normal tissue at the edges. Lead/cadmium sulfide quantum dots (PbS@CdS QDs), boasting high quantum yields (QYs) and vivid fluorescence, have facilitated advancements in the second near-infrared window (NIR-II, 900-1700 nm). However, during fluorescent surgical navigation operations, hydrophilic coatings of these inorganic nanoparticles (NPs) guarantee biosafety; it also comes at the expense of losing a significant portion of QY and NIR-II fluorescence, causing heightened damage to normal tissues caused by cutting edges. Herein, we present hydrophilic core-shell PbS@CdS@PEG NPs with an exceptionally small diameter (∼8 nm) and a brilliant NIR-IIb (1500-1700 nm) emission at approximately 1600 nm. The mPEG-SH (MW: 2000) addresses the hydrophobicity and enhances the biosafety of PbS@CdS QDs. In vivo fluorescence-guided cervical tumor resection becomes achievable immediately upon injection of an aqueous solution of PbS@CdS@PEG NPs. Notably, this approach results in a significantly reduced thickness (100-500 μm) of damage to normal tissues at the margins of the resected tumors. With a high QY (∼30.2%) and robust resistance to photobleaching, NIR-IIb imaging is sustained throughout the imaging process.
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  • 文章类型: Journal Article
    背景:舟骨骨折是最常见的腕关节损伤,占所有腕骨骨折的80-90%。5-15%的舟骨骨折骨不连报告,即使有适当的初级治疗,几十年后可能会发展为骨关节炎的变化。关于舟骨体外和体内生理特性的研究以及临床实践中的各种试验正在进行中,这对我们的临床实践有很大贡献。随着腕关节镜的推进,3D打印针对患者的钻孔导向器,术中透视引导,背侧入路(微创和经皮技术)正在流行,通过它,我们可以植入螺钉,与生物力学很好地吻合,并且舟骨的血液供应不那么令人不安。研究不同腕部位置的背侧近端舟骨的非接触区域可以有助于术前估计螺钉的插入点。
    方法:招募了8名志愿者,以6种极端的手腕体位接受CT扫描。将DICOM模式的图像输入模拟分析系统,分段的舟骨,lunate和radius以ASCIISTL模式导出,并在Geomagicstudio的软件中打开。我们基于半径和舟骨表面上的解剖标记创建了四个平面,以限制近端舟骨形成所谓的非接触区域。我们测量并比较了六个目标位置的区域。
    结果:在六个极端的手腕位置中,在极端的背部延伸(59.81±26.46mm2)的非接触区域的面积显著最小,极掌屈曲时最大(170.51±30.44mm2)。非接触区域按背侧延伸的顺序增加,仰卧起坐,尺位偏差,径向偏差,前旋和手掌屈曲。至于两组比较,除个别内旋外,非接触区域的手掌屈曲明显大于其他区域(p<0.05),径向偏差(p<0.05)高于背侧延伸。
    结论:尽管有腕部位置,但从背侧入路开始的螺钉仍有足够的空间。
    BACKGROUND: Fractures of the scaphoid are the most common carpal injuries, account for 80-90% of all carpal fractures. 5-15% nonunion of scaphoid fractures were reported even with adequate primary treatment, which probably progresses to osteoarthritic changes several decades later. Researches regarding to scaphoid physiological characteristic in vitro and in vivo and kinds of trials in clinical practice are being kept on going, which contribute much to our clinical practice. With the advancing wrist arthroscopy, 3D-print patient-specific drill guide, and intraoperative fluoroscopic guidance, dorsal approach (mini-invasive and percutaneous technique) is being popular, through which we can implant the screw in good coincidence with biomechanics and with less disturbing tenuous blood supply of the scaphoid. Investigating the noncontact area of the dorsal proximal scaphoid in different wrist positions can facilitate preoperatively estimating insert point of the screw.
    METHODS: Eight volunteers were recruited to accept CT scans in six extreme wrist positions. The images of DICOM mode were imput into the Mimics analytical system, the segmented scaphoid, lunate and radius were exported in mode of ASCII STL and were opened in the software of Geomagic studio. We created four planes based on anatomic markers on the surface of the radius and scaphoid to confine the proximal scaphoid to form the so-called non-contact regions. We measured and compared the areas in six targeted positions.
    RESULTS: Amidst six extreme wrist positions, area of the non-contact region in extreme dorsal extension (59.81 ± 26.46 mm2) was significantly the smallest, and it in extreme palmar flexion significantly was largest (170.51 ± 30.44 mm2). The non-contact regions increased in order of dorsal extension, supination, ulnar deviation, radial deviation, pronation and palmar flexion. As for two-group comparison, the non-contact region showed significantly larger (p < 0.05) in palmar flexion than the others except for in pronation individually, and in radial deviation (p < 0.05) than in dorsal extension.
    CONCLUSIONS: Sufficient space was available for the screw started from the dorsal approach despite the wrist positions.
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  • 文章类型: Journal Article
    在手术中,组织解剖和止血过程中产生的手术烟雾会降低图像质量,影响组织的可见性和干扰进一步的图像处理。开发可靠且可解释的计算成像方法来恢复受烟雾影响的手术图像至关重要,由于典型的图像恢复方法依赖于颜色纹理信息是不够的。这里演示了一种通过手术烟雾的计算偏振成像方法,包括基于离散电场方向的精细极化差估计,以及相应的基于先验的估计方法,更好的参数估计和图像复原性能。离体结果和分析,第一次体内动物实验,和人体口腔测试表明,该方法实现了更高质量的能见度恢复和颜色恢复,并在具有可解释性的不同成像场景中表现出良好的概括。该方法有望提高精密度,安全,先进的图像引导和机器人手术的效率。
    In surgery, the surgical smoke generated during tissue dissection and hemostasis can degrade the image quality, affecting tissue visibility and interfering with the further image processing. Developing reliable and interpretable computational imaging methods for restoring smoke-affected surgical images is crucial, as typical image restoration methods relying on color-texture information are insufficient. Here a computational polarization imaging method through surgical smoke is demonstrated, including a refined polarization difference estimation based on the discrete electric field direction, and a corresponding prior-based estimation method, for better parameter estimation and image restoration performance. Results and analyses for ex vivo, the first in vivo animal experiments, and human oral cavity tests show that the proposed method achieves visibility restoration and color recovery of higher quality, and exhibits good generalization across diverse imaging scenarios with interpretability. The method is expected to enhance the precision, safety, and efficiency of advanced image-guided and robotic surgery.
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  • 文章类型: Journal Article
    嵌合抗原受体T(CAR-T)细胞疗法在改善血液恶性肿瘤方面取得了显著的治疗成功。然而,在嵌合抗原受体T(CAR-T)细胞疗法之前,临床指南中关于最有效的化疗方案存在空白,以及化疗后CAR-T细胞输注的最佳时机。
    我们采用细胞来源的肿瘤异种移植(CDX)鼠模型来描绘最佳预处理化疗方案和CAR-T细胞治疗的时机。此外,实施转录组测序以鉴定治疗靶标并阐明控制治疗方案的潜在机制。
    我们的临床前体内评估确定环磷酰胺和氟达拉滨的组合,随后在化疗后五天输注CD19CAR-T细胞,在B细胞血液系统恶性肿瘤中发挥最有效的治疗作用。同时,RNA-seq数据表明,治疗功效主要扰乱肿瘤细胞代谢,主要通过抑制关键的线粒体靶标,例如C-Jun激酶酶(C-JUN)。
    总之,本研究为CD19CAR-T细胞疗法在B细胞恶性血液病治疗中的应用提供了重要的临床指导,并成为权威参考.
    UNASSIGNED: Chimeric antigen receptor T (CAR-T) cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies. However, there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T (CAR-T) cell therapy, as well as the optimal timing for CAR-T cell infusion post-chemotherapy.
    UNASSIGNED: We employed cell-derived tumor xenograft (CDX) murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment. Furthermore, transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.
    UNASSIGNED: Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine, followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy, exerts the most efficacious therapeutic effect in B-cell hematological malignancies. Concurrently, RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism, primarily through the inhibition of key mitochondrial targets, such as C-Jun Kinase enzyme (C-JUN).
    UNASSIGNED: In summary, the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.
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