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Folate Receptor-Targeted Nanodelivery of Apigenin in Breast Cancer: Formulation Development, Characterization and In Vitro Evaluation 叶酸受体靶向纳米递送芹菜素治疗乳腺癌:配方开发、表征和体外评估
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3803
Arjun Patra, Swaha Satpathy, Pradeep K. Naik, Mohsin Kazi, Muhammad Hussain Delwar
Cancer is a dreadful disease with a high mortality rate and breast cancer is the most common cancer among females in the world. Different strategies have been used for the treatment of breast cancer, including chemotherapy but it has a wide range of side effects. This problem can be overcome by delivering anticancer agents with nano-formulations. Apigenin (4′,5,7-trihydroxyflavone), present in many different medicinal plants, shows potential anticancer properties in various cancers. However, its use in clinical practice is limited due to its low water solubility and bioavailability. In this study, we examined folate receptor-targeted and PEGylated poly(lactide-co-glycolide) nanoparticles (PLGA-PEG-FA NPs) containing apigenin for targeted delivery to MCF-7 breast cancer cells. Apigenin-loaded PLGA-PEG and PLGA-PEG-FA NPs were small in size, had a negative zeta potential, showed sustained release of apigenin and showed significantly higher anticancer activity than the free drug in breast cancer cells. The half maximal inhibitory concentration (IC50) values of apigenin, apigenin-loaded PLGA, PLGA-PEG and PLGA-PEG-FA NPs were 50.2, 49.4, 18.1 and 13.3 μM, respectively. Apigenin-loaded PLGA-PEG and PLGA-PEG-FA NPs showed 2.79- and 3.77-fold higher cytotoxicity than the pristine drug. Folate-conjugated PLGA nanoparticles could be developed for potential target-specific delivery of apigenin in the treatment of breast cancer.
癌症是一种死亡率很高的可怕疾病,而乳腺癌是世界上女性最常见的癌症。治疗乳腺癌的方法多种多样,其中包括化疗,但化疗的副作用很大。利用纳米制剂递送抗癌药物可以克服这一问题。芹菜素(4′,5,7-三羟基黄酮)存在于多种药用植物中,对多种癌症具有潜在的抗癌作用。然而,由于其水溶性和生物利用度较低,在临床实践中的应用受到了限制。在本研究中,我们研究了含有芹菜素的叶酸受体靶向和 PEG 化聚乳酸-共聚乙二醇纳米颗粒(PLGA-PEG-FA NPs),用于靶向递送 MCF-7 乳腺癌细胞。负载芹菜素的 PLGA-PEG 和 PLGA-PEG-FA NPs 尺寸小,具有负 zeta 电位,能持续释放芹菜素,在乳腺癌细胞中的抗癌活性明显高于游离药物。芹菜素、芹菜素负载的 PLGA、PLGA-PEG 和 PLGA-PEG-FA NPs 的半数最大抑制浓度(IC50)值分别为 50.2、49.4、18.1 和 13.3 μM。芹菜素负载的 PLGA-PEG 和 PLGA-PEG-FA NPs 的细胞毒性分别是原药的 2.79 倍和 3.77 倍。叶酸共轭的 PLGA 纳米粒子可用于芹菜素治疗乳腺癌的潜在靶向给药。
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引用次数: 0
Effect of Piezo1 Channel-Mediated Mechanotransduction on Osteogenic Differentiation and Interleukin-6 Secretion in Bone Mesenchymal Stem Cells Under Tensile Strain Piezo1 通道介导的机械传导对拉伸应变下骨间质干细胞成骨分化和白细胞介素-6 分泌的影响
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3730
Xu Yan, Su Fu, Ying Xie, Xuejian Wu
Physical stimulation plays a crucial role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs). However, the mechanotransductive mechanisms remain uncleared. Recent studies have suggested that the Piezo1 channel is essential for transforming mechanical signals. Therefore, we investigate the Piezo1-mediated mechanisms in mechanical strain-regulated MSC osteogenic differentiation and release of proinflammatory cytokines. The tensile strain was applied to rat MSCs cultured in a monolayer to induce mechanical strain. The immuno-nanomagnetic bead enzyme-linked immunosorbent assay was employed to assess gene and protein expressions, as well as osteogenic biomarkers and interleukin-6 (IL-6) release, both in the presence or absence of a Piezo1 agonist/antagonist. Firstly, biophysical loading through mechanical strain was found to promote MSC osteogenic differentiation. Suppression of Piezo1 using GsMTx4 antagonist or transfection with Piezo1-siRNA effectively inhibited mechanical responses associated with osteogenic gene expressions and IL-6. Activation of Piezo1 by Yoda1 mimicked the effects induced by mechanical strain on osteogenic gene expressions and IL-6 release, which were associated with YAP activation, upregulation, and nuclear accumulation of β-catenin. In conclusion, these findings significantly enhance our understanding of MSC mechanotransduction and hold great promise for drug development to enhance skeletal mass.
物理刺激在骨髓间充质干细胞的成骨分化过程中起着至关重要的作用。然而,机械传导机制仍不清楚。最近的研究表明,Piezo1 通道是转化机械信号的关键。因此,我们研究了Piezo1介导的机械应变调节间充质干细胞成骨分化和释放促炎细胞因子的机制。对单层培养的大鼠间充质干细胞施加拉伸应变以诱导机械应变。采用免疫纳米磁珠酶联免疫吸附试验来评估基因和蛋白质的表达,以及成骨生物标志物和白细胞介素-6(IL-6)的释放。首先,通过机械应变进行生物物理加载可促进间充质干细胞成骨分化。使用 GsMTx4 拮抗剂抑制 Piezo1 或转染 Piezo1-siRNA 能有效抑制与成骨基因表达和 IL-6 相关的机械反应。Yoda1对Piezo1的激活模拟了机械应变对成骨基因表达和IL-6释放的影响,这些影响与YAP的激活、上调和β-catenin的核积累有关。总之,这些发现极大地促进了我们对间叶干细胞机械传导的了解,并为提高骨骼质量的药物开发带来了巨大希望。
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引用次数: 0
Preparation, Characterization, and Bioactivities of Cobalt, Strontium and Fluorine Co-Doped Oxide Films on Titanium Surface for Clinical Application 用于临床应用的钛表面钴、锶和氟共掺氧化物薄膜的制备、表征和生物活性
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3813
Xinglin Wu, Yang Jiao, Jieshi Wu, Sujiajun Zhang, Ruisheng Xu, Quanming Zhao, K. Lu, Pengpeng Zhang, Lu Zhang, Xiaohui Ni
Titanium and titanium alloys are receiving widespread attention due to their excellent comprehensive mechanical properties, corrosion resistances, and biocompatibilities. However, titanium metal itself is biologically inert in physiological environments, and after implantation, it is surrounded by a layer of encapsulating fibrous membrane, making it difficult to form solid bonds with the tissue. Plasma electrolytic oxidation is a new technology used to prepare bioactive porous ceramic membranes on the surfaces of titanium and titanium alloys. It has application prospects for biomimetic surface modifications of titanium alloys. In this study, a cobalt, strontium and fluorine codoped oxide film (TAM-CSF) was prepared on a titanium surface via plasma electrolytic oxidation. The surface characteristics of the film were evaluated with field emission scanning electron microscopy, energy spectrum analyses, atomic force microscopy, profilometry and X-ray photoelectron spectroscopy. Additionally, the corrosion performance of the material was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of the film were tested with in vitro cell experiments. The results showed that the TAM-CSF on the titanium surface had a porous morphology, and the CSF was uniformly doped on the film surface. TAM-CSF improved the surface roughness of the titanium. This film exhibited good biocompatibility and promoted the extension and proliferation of MC3T3-E1 cells. It was possible to prepare TAM-CSF on titanium surfaces via plasma electrolytic oxidation. The film exhibited a good morphology and good biological activity and has clinical application prospects.
钛和钛合金因其优异的综合机械性能、耐腐蚀性和生物相容性而受到广泛关注。然而,钛金属本身在生理环境中具有生物惰性,植入人体后被一层包裹性纤维膜包围,很难与组织形成牢固的结合。等离子电解氧化是一种在钛和钛合金表面制备生物活性多孔陶瓷膜的新技术。它在钛合金的仿生物表面改性方面具有应用前景。本研究通过等离子电解氧化法在钛表面制备了钴锶氟共掺氧化物薄膜(TAM-CSF)。利用场发射扫描电子显微镜、能谱分析、原子力显微镜、轮廓仪和 X 射线光电子能谱对薄膜的表面特性进行了评估。此外,还利用电化学工作站对材料的腐蚀性能进行了评估。体外细胞实验测试了薄膜的生物相容性和生物活性。结果表明,钛表面的 TAM-CSF 呈多孔状,CSF 均匀地掺杂在薄膜表面。TAM-CSF 改善了钛的表面粗糙度。这种薄膜具有良好的生物相容性,能促进 MC3T3-E1 细胞的扩展和增殖。通过等离子电解氧化法可以在钛表面制备 TAM-CSF。该薄膜具有良好的形态和生物活性,具有临床应用前景。
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引用次数: 0
Long-Noncoding RNA (lncRNA) EGOT Prevents the Malignant Process of Colorectal Carcinoma by Regulating BTG3 长非编码 RNA(lncRNA)EGOT 通过调控 BTG3 防止结直肠癌的恶性过程
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3823
Zhengdong Wang, Dezhi Gu, Aiming Zhou
This study investigates the role of the long non-coding RNA EGOT in colorectal cancer (CRC) by examining its expression in 40 pairs of CRC and adjacent normal tissues and assessing its impact on clinical outcomes. EGOT was found to be downregulated in CRC tissues, and low EGOT levels were associated with a higher likelihood of lymphatic and distant metastasis, as well as poorer overall and progression-free survival in CRC patients. Functional experiments revealed that overexpression of EGOT in SW480 cells reduced cell viability, migration, and wound closure, while knockdown of EGOT in LoVo cells had the opposite effect. In vivo experiments with nude mice confirmed that EGOT downregulation accelerated CRC growth, whereas its overexpression slowed tumor growth. The study identified BTG3 as the target gene of EGOT, and they exhibited a negative correlation in CRC tissues. Rescue experiments demonstrated that BTG3 could reverse the effects of EGOT on CRC cell phenotypes. In conclusion, EGOT is a downregulated molecule in CRC, closely associated with metastasis and patient prognosis. It exerts a suppressive influence on CRC cell proliferation, migration, and tumorigenesis by negatively regulating BTG3.
这项研究通过检测长非编码RNA EGOT在40对结肠直肠癌(CRC)和邻近正常组织中的表达,并评估其对临床结果的影响,从而研究长非编码RNA EGOT在结肠直肠癌(CRC)中的作用。研究发现,EGOT在CRC组织中被下调,EGOT水平低与CRC患者淋巴转移和远处转移的可能性较高以及总生存期和无进展生存期较差有关。功能实验显示,在 SW480 细胞中过表达 EGOT 会降低细胞活力、迁移和伤口闭合,而在 LoVo 细胞中敲除 EGOT 则会产生相反的效果。裸鼠体内实验证实,下调 EGOT 会加速 CRC 的生长,而过表达则会减缓肿瘤的生长。研究发现 BTG3 是 EGOT 的靶基因,两者在 CRC 组织中呈负相关。拯救实验表明,BTG3 可以逆转 EGOT 对 CRC 细胞表型的影响。总之,EGOT 是一种在 CRC 中下调的分子,与转移和患者预后密切相关。它通过负调控 BTG3 对 CRC 细胞的增殖、迁移和肿瘤发生产生抑制作用。
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引用次数: 0
Identification and Verification of Potential Ferroptosis-Related Biomarkers in Cervical Cancer 宫颈癌中潜在的铁蛋白沉积相关生物标记物的鉴定与验证
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3810
Zhaodi Liu, Yang Liu, Xinyue Wu, Xiangnan Feng, Wei Liang
This study screened important genes contributing to morbidity from differential ferroptosis-related genes (FRGs) in cervical cancer and to establish a risk assessment model with ferroptosis-related LncRNAs. Total RNA sequencing data were extracted from The cancer genome atlas (TCGA), Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx). By differential analysis, we identified ferroptosis-related hub genes close to prevalence of cervical cancer. According to receiver operator curves (ROC) curves, hub genes have good diagnostic performance. The diagnostic potential of hub genes for occurrence of the disease was further assessed and verified. Further, a risk-assessing model based on ferroptosis-related LncRNAs was established. Finally, the differential expressions of hub genes were verified through qRT-PCR. Five hub genes were identified, and we found through GO, KEGG and immune infiltration, that the hub genes are connection with cervical cancer. The Area Under Curve (AUC) values were all greater than 0.8 in ROC curve, and the hub genes presented differences between disease and control groups in validation set GSE29570. We created a risk assessment model with 16 ferroptosis-related LncRNAs. There was a difference in survival between high-risk and low-risk groups. The AUC result for risk assessment model reached 0.792, and there were significant expression differences of Hub genes in Huvec and Hela cells. The study screened 5 hub genes and constructed the risk-assessment model based on 16 LncRNAs associated with ferroptosis genes.
本研究从宫颈癌中不同的铁蛋白沉积相关基因(FRGs)中筛选出导致发病的重要基因,并利用铁蛋白沉积相关的LncRNAs建立风险评估模型。我们从癌症基因组图谱(TCGA)、基因表达总库(GEO)和基因型-组织表达(GTEx)中提取了总RNA测序数据。通过差异分析,我们发现了与宫颈癌发病率密切相关的铁突变相关枢纽基因。根据接收操作者曲线(ROC),中枢基因具有良好的诊断性能。我们进一步评估并验证了枢纽基因对疾病发生的诊断潜力。此外,还建立了一个基于铁突变相关 LncRNA 的风险评估模型。最后,通过 qRT-PCR 验证了枢纽基因的差异表达。通过GO、KEGG和免疫浸润,我们发现五个中枢基因与宫颈癌有关。在 ROC 曲线中,曲线下面积(AUC)值均大于 0.8,并且在验证集 GSE29570 中,中心基因在疾病组和对照组之间存在差异。我们用 16 个与铁沉着病相关的 LncRNA 建立了一个风险评估模型。高危组和低危组的生存率存在差异。风险评估模型的AUC结果达到0.792,Hub基因在Huvec细胞和Hela细胞中的表达存在显著差异。该研究筛选了5个Hub基因,并根据16个与铁突变基因相关的LncRNA构建了风险评估模型。
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引用次数: 0
Associations of Inflammation, Oxidative Stress and Prognosis with IL-37 Expression in Sepsis Rats with Lung Injury 脓毒症肺损伤大鼠的炎症、氧化应激和预后与 IL-37 表达的关系
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3822
Fei Hong, Jungang Zhao, Mei Yang, Qian Liu, Qin Chen, Feng Liu, Guoji Zhu
This study aimed to investigate the role of interleukin-37 (IL-37) expression in lung tissues of sepsis-induced acute lung injury (ALI) rats and its impact on ALI, along with the underlying mechanisms. Sprague-Dawley (SD) rats were categorized into three groups: Control, sepsis-induced ALI (via cecal ligation and puncture, CLP), and sepsis-induced ALI with antibiotics (CLP+An). ALI models were established, and lung tissue injuries were assessed through hematoxylineosin staining. mRNA levels of IL-1α, IL-1β, IL-37, and tumor necrosis factor-α (TNF-α) were measured via RT-PCR, while IL-37 protein levels in lung tissues were determined using Western blotting. Additionally, bronchoalveolar lavage fluid (BALF) and blood samples were collected to assess inflammatory factors through ELISA. In the CLP group, there was an increase in pro-inflammatory factors (IL-1α, IL-1β, and TNF-α) in lung tissues and serum. However, in the CLP+An group, these factors decreased, IL-37 expression increased, and oxidative stress levels decreased. IL-37 demonstrated an inhibitory effect on the release of pro-inflammatory factors (IL-1α, IL-1β, and TNF-α) in sepsis rats, leading to a reduction in lung tissue inflammation. Furthermore, IL-37 exhibited a protective role by reducing oxidative stress in sepsis-induced lung tissues. These findings highlight IL-37 as a potential therapeutic target for mitigating ALI in sepsis.
本研究旨在探讨白细胞介素-37(IL-37)在脓毒症诱导的急性肺损伤(ALI)大鼠肺组织中的表达作用及其对ALI的影响和潜在机制。斯普拉格-道利(SD)大鼠分为三组:对照组、脓毒症诱导的 ALI 组(通过盲肠结扎和穿刺,CLP)和脓毒症诱导的 ALI 加抗生素组(CLP+An)。通过 RT-PCR 测定 IL-1α、IL-1β、IL-37 和肿瘤坏死因子-α(TNF-α)的 mRNA 水平,通过 Western 印迹测定肺组织中 IL-37 蛋白水平。此外,还收集了支气管肺泡灌洗液(BALF)和血液样本,通过酶联免疫吸附法评估炎症因子。在CLP组中,肺组织和血清中的促炎因子(IL-1α、IL-1β和TNF-α)有所增加。但在 CLP+An 组,这些因子减少,IL-37 表达增加,氧化应激水平降低。IL-37 对败血症大鼠促炎因子(IL-1α、IL-1β 和 TNF-α)的释放具有抑制作用,从而减轻了肺组织炎症。此外,IL-37 还能降低败血症诱导的肺组织中的氧化应激,从而起到保护作用。这些发现突出表明,IL-37 是减轻脓毒症 ALI 的潜在治疗靶点。
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引用次数: 0
MiR-92a Promotes Apoptosis in Rats with Myocardial Ischemia-Reperfusion Injury via Regulating Wnt/β-Catenin Pathway MiR-92a 通过调节 Wnt/β-Catenin 通路促进心肌缺血再灌注损伤大鼠的细胞凋亡
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3818
Yong Ye, Guang Xia, Min Chen, Jifu Jin, Linxiang Lu, Xin Wang
In this study, the impact of micro ribonucleic acid (miR)-92a on rats with myocardial ischemia-reperfusion injury was investigated, with a focus on its regulation of the Wnt/β-catenin pathway. A total of 36 Sprague Dawley rats were divided into three groups: a sham operation group, a model group, and a miR-92a antagomir group. The sham group underwent thoracotomy without injury, while the model and miR-92a antagomir groups were subjected to myocardial ischemiareperfusion injury and treated with saline and miR-92a antagomir, respectively. Results showed that the myocardial infarction area was significantly reduced in the miR-92a antagomir group compared to the model group. Histological analysis revealed improved myocardial tissue structure in the miR-92a antagomir group. Western blotting demonstrated elevated levels of p-GSK-3β and β-catenin in both the model and miR-92a antagomir groups, with a notable decrease in the miR-92a antagomir group compared to the model group. Additionally, miR-92a expression was higher in both the model and miR-92a antagomir groups compared to the sham group. Lastly, apoptosis rates were increased in both the model and miR-92a antagomir groups, but significantly reduced in the miR-92a antagomir group compared to the model group. Overall, these findings suggest that miR-92a exacerbates apoptosis in rats with myocardial ischemia-reperfusion injury by up-regulating the Wnt/β-catenin signaling pathway.
本研究探讨了微核糖核酸(miR)-92a对心肌缺血再灌注损伤大鼠的影响,重点是其对Wnt/β-catenin通路的调控。研究人员将 36 只 Sprague Dawley 大鼠分为三组:假手术组、模型组和 miR-92a 抗凝剂组。假手术组大鼠在不受伤害的情况下接受开胸手术,模型组和 miR-92a 抗凝集物组大鼠在接受心肌缺血再灌注损伤后分别接受生理盐水和 miR-92a 抗凝集物治疗。结果表明,与模型组相比,miR-92a antagomir 组的心肌梗死面积明显缩小。组织学分析显示,miR-92a 抗凝剂组的心肌组织结构有所改善。Western 印迹显示,在模型组和 miR-92a 抗凝剂组中,p-GSK-3β 和 β-catenin 的水平均升高,与模型组相比,miR-92a 抗凝剂组的水平明显下降。此外,与假体组相比,模型组和 miR-92a 抗病毒组的 miR-92a 表达量都更高。最后,模型组和 miR-92a 抗病毒药物组的细胞凋亡率都有所增加,但与模型组相比,miR-92a 抗病毒药物组的细胞凋亡率明显降低。总之,这些研究结果表明,miR-92a 通过上调 Wnt/β-catenin 信号通路,加剧了心肌缺血再灌注损伤大鼠的细胞凋亡。
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引用次数: 0
Impact of Radiotherapy on Radiation-Induced Brain Injury in Patients with Nasopharyngeal Carcinoma Using Nano-Magnetic Resonance Imaging 利用纳米磁共振成像分析放疗对鼻咽癌患者放射性脑损伤的影响
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3809
Baomin Zheng, Hanyong Zhang, Weihu Wang
This study investigate the changes of white matter injury induced by radiation after radiotherapy in patients with nasopharyngeal carcinoma (NPC) and its association with cognitive dysfunction using multiple MRI methods. A total of 42 patients with NPC who underwent radiotherapy at xxx Hospital between December 2018 and June 2021 were included. The patients were randomly divided into 4 groups based on the timing of radiotherapy. Superparamagnetic iron oxide nanoparticles were used as MRI contrast agents. DTI and MRS scans were conducted to measure FA, ADC, NAA/Cho, Cho/Cr, and NAA/Cr ratios in the hippocampus of both temporal lobes. A cognitive assessment was performed using the MoCA and MMSE scales. After radiotherapy, patients experienced a decline in cognitive scores, which stabilized after 6 months. White matter changes were observed in the hippocampus, with decreased FA and increased ADC values that gradually returned to normal levels. Cho value increased and NAA value decreased initially but eventually returned to pre-treatment levels. No significant changes occurred in the Cr value. Metabolite ratios decreased within 3 months post-radiotherapy but gradually increased thereafter, remaining lower than pre-treatment levels at 6 months. Higher radiation doses did not significantly affect FA and ADC values but decreased white matter metabolite ratios. In conclusion, we reveal that the dosage and duration of radiotherapy can influence the degree of brain injury in patients with NPC and highlights the cognitive decline, white matter changes, and changes in metabolite ratios after radiotherapy for NPC, providing insights into the effects of radiation on brain structure and function.
本研究采用多种核磁共振成像方法研究鼻咽癌患者放疗后辐射诱导的白质损伤变化及其与认知功能障碍的关系。共纳入2018年12月至2021年6月期间在xxx医院接受放疗的42例鼻咽癌患者。根据放疗时间将患者随机分为4组。超顺磁性氧化铁纳米粒子被用作磁共振成像造影剂。进行DTI和MRS扫描,测量两个颞叶海马的FA、ADC、NAA/Cho、Cho/Cr和NAA/Cr比率。使用MoCA和MMSE量表进行了认知评估。放疗后,患者的认知评分有所下降,6个月后趋于稳定。海马白质发生了变化,FA值降低,ADC值升高,并逐渐恢复到正常水平。最初,Cho 值升高,NAA 值降低,但最终恢复到治疗前的水平。Cr值没有发生明显变化。代谢物比率在放疗后3个月内下降,但之后逐渐上升,6个月时仍低于治疗前水平。较高的放射剂量对FA值和ADC值没有明显影响,但会降低白质代谢物比率。总之,我们揭示了放疗的剂量和持续时间会影响鼻咽癌患者的脑损伤程度,并强调了鼻咽癌放疗后的认知能力下降、白质变化和代谢物比值变化,为了解放疗对脑部结构和功能的影响提供了见解。
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引用次数: 0
Improvement of Bone Homeostasis Imbalance in Osteoporotic Fractures by Mesoporous Silica Carrying miR-302b 携带 miR-302b 的介孔二氧化硅可改善骨质疏松性骨折的骨平衡失调状况
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1166/jbn.2024.3808
Jiaqi Chu, Yuan Si, Song Shao
miR-302b and DKK1 are two molecules related to the regulation of bone metabolism. Mesoporous silica is a potential drug carrier. This article aims to study the mechanism of mesoporous silica carrying miR-302b targeting DKK1 regulation to improve bone homeostasis imbalance in osteoporotic fractures. Mesoporous silica nanoparticles were synthesized and characterized. miR-302b was loaded into mesoporous silica to form composite nanoparticles. In vivo rat model experiments were performed to evaluate bone metabolism. X-ray examination and μCT scan were used to detect the bone content and trabecular bone status of rats. Alcian blue/hematoxylin/Orange G staining was used to observe changes in trabecular bone in the tibial metaphysis. Immunohistochemical staining showed the formation of trabecular bone in rats in each group and changes in the number of bone cells. Calcein double labeling experiment showed the bone mineralization speed of mice in each group. Pure and stable mesoporous silica nanoparticles were successfully synthesized and miR-302b was successfully loaded into the nanoparticles. The osteoporotic fracture rat model was successfully created. In vivo experimental results showed that after injecting composite nanoparticles into mice, bone density and bone strength were significantly increased and osteoporotic fractures were improved. Mesoporous silica carries miR-302b to target DKK1 regulation, which can improve bone homeostasis imbalance in osteoporotic fractures. Composite nanoparticles can inhibit the expression of DKK1, promote bone formation, and inhibit bone resorption, thereby improving bone density and bone strength.
miR-302b 和 DKK1 是两种与骨代谢调节有关的分子。介孔二氧化硅是一种潜在的药物载体。本文旨在研究介孔二氧化硅携带miR-302b靶向DKK1调控改善骨质疏松性骨折患者骨平衡失调的机制。研究人员合成了介孔二氧化硅纳米颗粒并对其进行了表征,将miR-302b载入介孔二氧化硅形成复合纳米颗粒。进行了大鼠体内模型实验,以评估骨代谢。X射线检查和μCT扫描用于检测大鼠的骨含量和骨小梁状况。阿尔新蓝/红霉素/橙 G 染色用于观察胫骨干骺端骨小梁的变化。免疫组化染色显示了各组大鼠骨小梁的形成和骨细胞数量的变化。钙素双标记实验显示了各组小鼠的骨矿化速度。成功合成了纯净稳定的介孔二氧化硅纳米颗粒,并将 miR-302b 成功载入纳米颗粒。成功建立了骨质疏松性骨折大鼠模型。体内实验结果表明,小鼠注射复合纳米粒子后,骨密度和骨强度明显增加,骨质疏松性骨折得到改善。介孔二氧化硅携带miR-302b靶向调控DKK1,可改善骨质疏松性骨折的骨平衡失调。复合纳米粒子可抑制DKK1的表达,促进骨形成,抑制骨吸收,从而改善骨密度和骨强度。
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引用次数: 0
Treatment Promotion of Osteoporotic Fractures by microRNA-320 Nanocapsules Through Stimulating Bone Marrow Mesenchymal Stem Cells microRNA-320 纳米胶囊通过刺激骨髓间充质干细胞促进骨质疏松性骨折的治疗
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-03-01 DOI: 10.1166/jbn.2024.3784
Ligang Qian, Qinggui Li, Qiao Ren
We aimed to explore the mechanism underlying microRNA-320 (miR-320)’s role in osteoporotic fractures. miR-320 nanoparticles were prepared and their characterization was detected by Zetasizer Nano and triethylamine (TEA). miR-320 nanoparticles were interacted with bone marrow mesenchymal stem cells (BMSCs). Then we conducted MTT to assess cytotoxicity in BMSCs and determined genes expression. A mouse fracture model was established and treated with miR-320 nanoparticles or pore nanoparticles. The release of miR-320 and the bone repair at the fracture site were detected. Treatment of Ceramic matrix composites (CMCS) (miR-320) sensitive to Matrix metalloproteinase (MMP) released miR-320 to bone defect, which promoted the transcription of osteogenic genes and stimulated the osteogenesis. Finally, treatment of miR-320 nanoparticles facilitated bone repair of mouse osteoporotic defect. MMP-sensitive nanocapsules loaded with miR-320 can promote osteogenic potential and stimulate fracture repair, providing insight into novel treatment against osteoporotic fracture.
我们旨在探索microRNA-320(miR-320)在骨质疏松性骨折中的作用机制。我们制备了miR-320纳米颗粒,并用Zetasizer Nano和三乙胺(TEA)检测了其特性。然后,我们用 MTT 评估骨髓间充质干细胞的细胞毒性,并测定基因表达。我们建立了小鼠骨折模型,并用 miR-320 纳米粒子或孔隙纳米粒子进行处理。检测了 miR-320 的释放和骨折部位的骨修复情况。对基质金属蛋白酶(MMP)敏感的陶瓷基质复合材料(CMCS)(miR-320)在骨缺损处释放了 miR-320,促进了成骨基因的转录,刺激了骨的生成。最后,miR-320纳米颗粒的处理促进了小鼠骨质疏松缺损的骨修复。装载了miR-320的MMP敏感纳米胶囊能促进成骨潜能并刺激骨折修复,为骨质疏松性骨折的新型治疗方法提供了启示。
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引用次数: 0
期刊
Journal of biomedical nanotechnology
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