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Cardiomyocyte Exosomal Nanovesicles Mediating p53 to Regulate Autophagy and Protect Myocardial Infarction 心肌细胞外泌体纳米囊泡介导p53调节自噬保护心肌梗死
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3646
M. Fan, Fei Xie, Jianfeng Li, Junquan Li, Ting Liang
This study explores the protective mechanism of cardiomyocyte exosome nanovesicles on myocardial infarction. Enzyme activity was measured and apoptosis of rat cardiomyocytes was assessed by TdT-mediated dUTP Nick-End Labeling (TUNEL) along with analysis of myocardial function by color Doppler echocardiogram. In addition, triphenyl tetrazolium chloride (TTC) staining evaluated the myocardial ischemia. BMSCs were co-cultured with primary cardiomyocytes followed by measuring autophagy and exosome morphology of myocardial tissue by transmission electron microscope and protein expression by Western blot. Exosomes secreted by Bone marrow mesenchymal stem cells (BMSCs) were successfully isolated. LDH, CK, CK-MB activity, cardiomyocyte apoptosis rate, LVESD, LVEDD, LVEDP, myocardial infarction area, cell area occupied by autophagic vesicles and p53 expression in model group were higher than control group (P <0.05) and they were lower in exosome group than model group. In addition, LVEF, LVFS, and LVSP were lower in model group and higher in exosome group (P <0.05). Model group showed significantly promoted autophagy activation and autophagosome formation, which were inhibited by cardiomyocyte exosomes. Moreover, exosome-like vesicles were found with a diameter of 60–90 nm. Furthermore, PKH-26 staining showed that cardiomyocytes could uptake exosomes well. Myocardial injury significantly promotes autophagy activation. Moreover, the apoptosis rate of cardiomyocytes and the area of myocardial ischemia were reduced and the cardiac function of rats with myocardial infarction was improved.
本研究探讨心肌细胞外泌体纳米囊泡对心肌梗死的保护机制。通过TdT介导的dUTP缺口末端标记(TUNEL)测量酶活性并评估大鼠心肌细胞的凋亡,同时通过彩色多普勒超声心动图分析心肌功能。此外,氯化三苯基四氮唑(TTC)染色评估心肌缺血。BMSC与原代心肌细胞共培养,然后通过透射电子显微镜测量心肌组织的自噬和外泌体形态,并通过蛋白质印迹测量蛋白质表达。成功分离了骨髓间充质干细胞分泌的外泌体。模型组LDH、CK、CK-MB活性、心肌细胞凋亡率、LVESD、LVEDP、心肌梗死面积、自噬泡占细胞面积和p53表达均高于对照组(P<0.05),外泌体组低于模型组。此外,LVEF、LVFS和LVSP在模型组较低,在外泌体组较高(P<0.05)。此外,还发现了直径为60–90 nm的外泌体样囊泡。此外,PKH-26染色显示心肌细胞可以很好地摄取外泌体。心肌损伤显著促进自噬激活。此外,心肌梗死大鼠心肌细胞凋亡率和心肌缺血面积降低,心功能改善。
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引用次数: 0
Orthokeratology and Visual Motor Training for Juvenile Myopia 角膜塑形术与青少年近视的视觉运动训练
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3651
Yao Chen, Jingjing Zhang, Hui Huang, Bo Su
This study aimed to explore the effect of orthokeratology (Ortho-K) combined with visual motor training in juvenile myopia. We included 156 myopia patients, which were randomly divided into the combined (visual motor training+Ortho-K) and Ortho-K (only) groups. Corneal morphological changes (horizontal keratometry [HK], vertical keratometry [VK], central corneal thickness [CCT], and corneal endothelial cell density), regulatory function (positive and negative relative accommodation [PRA, NRA], regulatory amplitude, and regulatory sensitivity), ocular axis, visual acuity (naked visual acuity, Diopter), tear film stability (BUT test and SIT test), intraocular pressure, and safety before and after treatment were compared between groups. Moreover, we performed a Spearman correlation analysis on the effects of initial age and diopter on axial growth. After treatment, HK, VK of cornea, and CCT levels significantly decreased in both groups while no significant changes were found in endothelial cell density. In the combined group, there was a higher improvement in PRA, accommodation amplitude, and accommodation sensitivity, which could delay ocular axis growth and improve naked eye vision and diopters. Meanwhile, a significant negative correlation was found between patients’ initial age and axial growth. Moreover, BUT and SIT recovery in the combined group were relatively better after wearing Ortho-K. In conclusion, Ortho-K combined with visual motor training could better correct the vision of juvenile myopia patients and delay ocular axis growth. In addition, the earlier the intervention, the better the effect.
本研究旨在探讨角膜塑形术(orthokeratology, Ortho-K)联合视觉运动训练在青少年近视治疗中的作用。我们纳入156例近视患者,随机分为(视觉运动训练+Ortho-K)联合组和(仅)Ortho-K组。比较各组治疗前后角膜形态变化(水平角度数[HK]、垂直角度数[VK]、角膜中央厚度[CCT]、角膜内皮细胞密度)、调节功能(正、负相对调节[PRA、NRA]、调节幅度、调节灵敏度)、眼轴、视力(裸眼视力、屈光度)、泪膜稳定性(BUT试验和SIT试验)、眼压、安全性。此外,我们对初始年龄和屈光度对轴向生长的影响进行了Spearman相关分析。治疗后,两组患者角膜HK、VK、CCT水平均显著降低,内皮细胞密度无明显变化。联合用药组PRA、调节幅度、调节灵敏度均有较高的改善,可延缓眼轴生长,改善裸眼视力和屈光度。同时,患者的初始年龄与轴向生长呈显著负相关。此外,联合组在佩戴Ortho-K后的BUT和SIT恢复相对较好。综上所述,Ortho-K联合视觉运动训练能更好地矫正青少年近视患者的视力,延缓眼轴生长。此外,干预越早,效果越好。
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引用次数: 0
NOX4 Upregulation in Lung Cancer: A Potential Therapeutic Target Associated with Immune Infiltration NOX4在肺癌中的上调:与免疫浸润相关的潜在治疗靶点
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3644
Hong Li, Sifang Feng, Tian Yang, Jiejuan Ning, Yuegang Wu, Tian-jun Chen
Lung cancer is a common and highly lethal tumor worldwide. Research indicates that NOX4 plays a crucial role in apoptosis resistance and sustained proliferation of cancer cells in various types of tumors. In this study, NOX4 expression in lung cancer tissues was analyzed using the Wilcoxon rank sum test, while the Kruskal-Wallis Test was employed to explore the relationship between NOX4 expression and clinical characteristics in lung cancer patients. Prognostic evaluation was conducted using Kaplan-Meier plotter analysis, Cox regression, and receiver operating characteristic (ROC) curve construction. Gene set enrichment analysis (GSEA) was performed to investigate the correlation between NOX4 and immune infiltration. Results showed significantly higher NOX4 expression in lung cancer patients compared to normal tissues. High NOX4 expression was associated with shorter overall survival (OS) in lung cancer patients, as confirmed by Cox analysis. Furthermore, other clinicopathological factors predicted poor prognosis in lung adenocarcinoma (LUAD), and NOX4 demonstrated diagnostic value according to ROC analysis. Additionally, NOX4 overexpression correlated with macrophages and Th1 cells based on SsGSEA analysis. In summary, NOX4 serves as an independent prognostic biomarker and is associated with immune infiltration in lung cancer.
肺癌是世界范围内常见的高致死率肿瘤。研究表明,NOX4在多种类型肿瘤细胞的抗凋亡和持续增殖中起着至关重要的作用。本研究采用Wilcoxon秩和检验分析NOX4在肺癌组织中的表达,采用Kruskal-Wallis检验探讨NOX4表达与肺癌患者临床特征的关系。采用Kaplan-Meier绘图图分析、Cox回归和受试者工作特征(ROC)曲线构建进行预后评估。通过基因集富集分析(GSEA)研究NOX4与免疫浸润的相关性。结果显示,NOX4在肺癌患者中的表达明显高于正常组织。Cox分析证实,NOX4高表达与肺癌患者总生存期(OS)缩短相关。此外,其他临床病理因素预测肺腺癌(LUAD)预后不良,通过ROC分析,NOX4具有诊断价值。此外,基于SsGSEA分析,NOX4过表达与巨噬细胞和Th1细胞相关。综上所述,NOX4是一种独立的预后生物标志物,与肺癌的免疫浸润有关。
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引用次数: 0
Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Suppresses Ferroptosis in Non-Small Cell Lung Cancer via Stabilizing m6A Modification of Fanconi Anemia Group D2 Protein 胰岛素样生长因子2 mRNA结合蛋白3通过稳定范科尼贫血D2组蛋白的m6A修饰抑制非小细胞肺癌癌症中的铁蛋白脱失
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3643
Haotian Zhang, Junjie Tang, Xiaowei Gong, Chenjun Huang
This study investigated the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in non-small cell lung cancer (NSCLC) and its association with N6-methyladenosine (m6A) modification. The study analyzes the expression levels and stability of IGF2BP3, as well as its impact on NSCLC cell functions. The findings indicate that IGF2BP3 is upregulated in NSCLC patients and cell lines. Knocking down IGF2BP3 reduces cell proliferation and promotes ferroptosis in A549 and H1299 cells. Additionally, the study reveals that IGF2BP3 regulates the m6A modification of the fanconi anemia group D2 protein (FANCD2) and influences its mRNA stability. Overexpressing FANCD2 counteracts the effects of IGF2BP3 silencing and increases the aggressiveness of NSCLC. Furthermore, treatment with celastrol induces ferroptosis in NSCLC cells and inhibits tumor growth in vivo. In conclusion, these findings suggest that IGF2BP3 acts as an oncogene in NSCLC. Its interaction with FANCD2 through m6A modification suppresses ferroptosis in NSCLC cells. Thus, the IGF2BP3/FANCD2 signaling pathway may serve as a potential therapeutic target for NSCLC.
本研究探讨了胰岛素样生长因子2 mRNA结合蛋白3(IGF2BP3)在癌症(NSCLC)中的作用及其与N6-甲基腺苷(m6A)修饰的关系。本研究分析了IGF2BP3的表达水平和稳定性,以及其对NSCLC细胞功能的影响。研究结果表明,IGF2BP3在NSCLC患者和细胞系中上调。敲除IGF2BP3可减少A549和H1299细胞的细胞增殖并促进脱铁性贫血。此外,研究表明IGF2BP3调节fanconi贫血组D2蛋白(FANCD2)的m6A修饰并影响其mRNA稳定性。过表达FANCD2可抵消IGF2BP3沉默的作用,并增加NSCLC的侵袭性。此外,雷公藤红素治疗可诱导NSCLC细胞脱铁,并在体内抑制肿瘤生长。总之,这些发现表明IGF2BP3在NSCLC中起致癌基因的作用。其通过m6A修饰与FANCD2的相互作用抑制NSCLC细胞中的脱铁性贫血。因此,IGF2BP3/FANCD2信号通路可以作为NSCLC的潜在治疗靶点。
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引用次数: 0
A Novel Silica Hybrid Nanoparticle with Zwitterion-Functionalized Polymer Chains for Highly Efficient N-Glycan Enrichment 一种具有两性离子功能化聚合物链的新型二氧化硅杂化纳米颗粒用于n-聚糖的高效富集
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3553
Yiting Pan, H. Bai, Guocheng Zhang, Wei Liu, Yanqi Wu, Hui Chen, Ying Tian, Zhenqi Yang, Duan Feng, Jiaqi Liu, Dan Wu
N-Glycosylation is one of the most common and important protein posttranslational modifications. Structural aberrations of the N-glycans branching from glycoproteins are closely related to various disease occurrences and progressions. Therefore, global systematic identification of disease-related N-glycans not only largely facilitates the understanding of their cellular functions but also promotes the development of new diagnostic and therapeutic biomarkers. However, N-glycans are low in abundance and hydrophilic, thereby hindering high-throughput, and large-scale N-glycan analysis and N-glycoproteome research. Here, a zwitterion-functionalized polymer brush-grafted silica hybrid hydrophilic material (poly-SBMA-S) was fabricated by in situ growth of polymeric [2-(methacryloyloxy)ethyl]dimethyl(3-sulfopropyl)ammonium hydroxide (SBMA) chains on porous silica particles through a surface-initiated atom transfer radical polymerization technique, and it was used as a new stationary phase for highly selective N-glycan enrichment. Human plasma demonstrated 64 N-glycans due to the densely packed polyzwitterion chains and the significantly increased coverage of hydrophilic binding sites, demonstrating the high potential of the new hydrophilic matrix in the profiling and analysis of N-glycans and other hydrophilic targets.
N-糖基化是最常见和最重要的蛋白质翻译后修饰之一。从糖蛋白分支的N-聚糖的结构异常与各种疾病的发生和发展密切相关。因此,疾病相关N-聚糖的全球系统鉴定不仅在很大程度上促进了对其细胞功能的理解,而且促进了新的诊断和治疗生物标志物的开发。然而,N-聚糖的丰度低且具有亲水性,从而阻碍了高通量和大规模的N-聚糖分析和N-糖蛋白组研究。本文通过表面引发的原子转移自由基聚合技术,在多孔二氧化硅颗粒上原位生长聚合物[2-(甲基丙烯酰氧基)乙基]二甲基(3-磺丙基)氢氧化铵(SBMA)链,制备了两性离子功能化聚合物刷接枝二氧化硅杂化亲水材料(poly-SBMA-S),并将其用作高选择性N-聚糖富集的新固定相。由于密集的两性离子链和亲水性结合位点的覆盖率显著增加,人类血浆显示出64种N-聚糖,这表明新的亲水性基质在N-聚糖和其他亲水性靶标的分析和分析中具有很高的潜力。
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引用次数: 0
Crucial Biological Roles of Long Noncoding RNA-Mediated Pyroptosis in Urological Tumors 长链非编码rna介导的焦亡在泌尿系统肿瘤中的重要生物学作用
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3637
Jiaogui Xie, Ying Jiang, Yichao Wang, Dalin He
Urologic neoplasm is one of the most general neoplasms, including bladder neoplam, prostate neoplasm and renal neoplasm. Researches have shown that tumor formation is a very complicated process, and it is the result of cell proliferation that is seriously out of control. Long noncoding RNA (lncRNA) and pyroptosis act separately or together on the tumorigenesis, growth and metastasis of urinary tumors, and are related to their treatment and prognosis. In this review, we summarized existing studies and found that lncRNA-mediated pyroptosis can promote or inhibit the development of urinary tumors. Pyroptosis can be achieved by lncRNA-caspase-gasdermin axis. Abnormal lncRNA expression may cause uncontrolled pyroptosis, thus bringing tumor deterioration and adverse prognosis. Controlling pyroptosis of neoplasm cells by regulating pyroptosis-related lncRNAs may be a new entry for the treatment of urinary neoplasms.
泌尿系肿瘤是最常见的肿瘤之一,包括膀胱肿瘤、前列腺肿瘤和肾脏肿瘤。研究表明,肿瘤的形成是一个非常复杂的过程,是细胞增殖严重失控的结果。长链非编码RNA(lncRNA)和pyroptosis分别或共同作用于泌尿系肿瘤的发生、生长和转移,并与其治疗和预后有关。在这篇综述中,我们总结了现有的研究,发现lncRNA介导的焦下垂可以促进或抑制泌尿系统肿瘤的发展。Pyroptosis可以通过lncRNA半胱天冬酶gasdermin轴实现。lncRNA表达异常可能导致pyroptosis失控,从而导致肿瘤恶化和不良预后。通过调节焦下垂相关lncRNA来控制肿瘤细胞的焦下垂可能是治疗泌尿系肿瘤的一个新途径。
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引用次数: 0
A Convergent Fabrication of Silk Fibroin Coated Magnesium Oxide Conjugated Phosphate Functionalized Chitosan Hydrogel for Bone Regeneration 丝素包被氧化镁结合磷酸功能化壳聚糖骨再生水凝胶的聚合制备
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3652
Xi Li, Yong-tao Yi, P. Guo, Ru-dan Zhou, Hua Li
The potential of injectable hydrogels based on natural polysaccharides (NPH) for repairing significant bone defects seems promising. Yet their osteogenic, angiogenic, and mechanical characteristics fall short of expectations. To overcome these disadvantages of chitosan-based hydrogels, silk fibroin-coated magnesium oxide nanoparticles (SF-MgO-NPs) were integrated into fabricated aqueous-soluble phosphocreatine-functionalized chitosan (CMP) solution to create a CMP@SF-MgO-NPs injectable hydrogel via supramolecular assembly. This hydrogel’s phosphocreatine acts as a reservoir to regulate Mg2+ release and as a location for supramolecular interaction with MgO-NPs. Injectable CMP@SF-MgO hydrogels encouraged in vitro calcium phosphate (CaP) deposition, ALP activity, and proliferation to MC3T3-E1 cells. This hydrogel (CMP@SF-MgO-NPs(5)) was also highly effective in stimulating the growth of new bone in calvarial lesions of critical size in rats. Therefore, the injectable hydrogel made of CMP@SF-MgO-NPs shows promising potential for bone regeneration.
基于天然多糖(NPH)的可注射水凝胶修复重大骨缺损的潜力似乎是有希望的。然而,它们的成骨性、血管生成性和力学特性都没有达到预期的效果。为了克服壳聚糖基水凝胶的这些缺点,将丝素包被氧化镁纳米颗粒(SF-MgO-NPs)整合到制备的水溶性磷酸肌酸功能化壳聚糖(CMP)溶液中,通过超分子组装制备CMP@SF-MgO-NPs可注射水凝胶。这种水凝胶的磷酸肌酸作为一个储层来调节Mg2+的释放,并作为与mgo - np超分子相互作用的位置。可注射CMP@SF-MgO水凝胶可促进体外磷酸钙(CaP)沉积、ALP活性和MC3T3-E1细胞的增殖。这种水凝胶(CMP@SF-MgO-NPs(5))在刺激大鼠临界大小的颅骨病变中新骨的生长方面也非常有效。因此,CMP@SF-MgO-NPs制成的可注射水凝胶在骨再生方面显示出良好的潜力。
{"title":"A Convergent Fabrication of Silk Fibroin Coated Magnesium Oxide Conjugated Phosphate Functionalized Chitosan Hydrogel for Bone Regeneration","authors":"Xi Li, Yong-tao Yi, P. Guo, Ru-dan Zhou, Hua Li","doi":"10.1166/jbn.2023.3652","DOIUrl":"https://doi.org/10.1166/jbn.2023.3652","url":null,"abstract":"The potential of injectable hydrogels based on natural polysaccharides (NPH) for repairing significant bone defects seems promising. Yet their osteogenic, angiogenic, and mechanical characteristics fall short of expectations. To overcome these disadvantages of chitosan-based hydrogels,\u0000 silk fibroin-coated magnesium oxide nanoparticles (SF-MgO-NPs) were integrated into fabricated aqueous-soluble phosphocreatine-functionalized chitosan (CMP) solution to create a CMP@SF-MgO-NPs injectable hydrogel via supramolecular assembly. This hydrogel’s phosphocreatine acts as a\u0000 reservoir to regulate Mg2+ release and as a location for supramolecular interaction with MgO-NPs. Injectable CMP@SF-MgO hydrogels encouraged in vitro calcium phosphate (CaP) deposition, ALP activity, and proliferation to MC3T3-E1 cells. This hydrogel (CMP@SF-MgO-NPs(5)) was also highly\u0000 effective in stimulating the growth of new bone in calvarial lesions of critical size in rats. Therefore, the injectable hydrogel made of CMP@SF-MgO-NPs shows promising potential for bone regeneration.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45802880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Green Synthesis of Magnetic Nanoparticles from Oldenlandia diffusa: Characterization and Therapeutic Activities 绿色合成白花玉兰磁性纳米颗粒:表征及治疗活性
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3660
Yingying Kong, Periyannan Velu, A. Vijayalakshmi, Chao Yuan
This study investigated green synthesis of magnetic nanoparticles (MNP) using Oldenlandia diffusa, its cauterization, and therapeutic propertieson liver cancer cells via an in-vitro approach. Anti-cancer, anti-oxidant, and anti-diabetic properties of MNP were evaluated. Synthesis of MNP was confirmed via UV-visible spectroscopy. Oldenlandia diffusa MNP (20–40 nm) showed absorption peak at 327 nm in UV-visible, XRD, EDX and FTIR spectral analysis. MNP were monoclinic, and rhombohedral with two stretching peaks at 646 cm−1, and 1098 cm−1 confirming Fe–O–Fe mode and Fe = O due to the iron element. IC50 values for MNP (IC50 74 μg/ml & 58 μg/ml) using DPPH and ABTS methods were high as compared to aqueous leaf extract of Oldenlandia diffusa confirming anti-oxidant properties. MNP exhibited α-amylase inhibitory activity with maximum inhibition of 82.17±0.82 μg/ml for α-glucosidase inhibitory action of 84.82±0.89 μg/ml. MNP showed dose-dependant in-vitro tumor suppression activity against HepG2 cells (16.08% at 150 μg/ml and 28.31% at 150 μg/ml). MNP also demonstrated anti-leishmanial activity at 400 g/ml (74.26±0.82 g/ml for promastigotes and 69.40±0.69 μg/ml for amastigotes). Oldenlandia diffusa actively bonded with magnetic Fe-nanoparticles and suppressed the growth of HepG2 cells. It demonstrated anti-cancer, antioxidant, anti-leishmanaland anti-diabetic activities. Thus, Oldenlandia diffusa is a potential anti-cancer therapeutic drug for liver cancer.
本研究通过体外实验研究了白花玉兰草绿色合成磁性纳米颗粒(MNP)及其烧灼作用,以及对肝癌细胞的治疗作用。对MNP的抗癌、抗氧化和抗糖尿病特性进行了评价。通过紫外可见光谱证实了MNP的合成。白花石斛MNP (20 ~ 40 nm)的紫外可见光谱、XRD、EDX和FTIR光谱均在327 nm处出现吸收峰。MNP呈单斜斜和菱形,在646 cm−1和1098 cm−1处有两个拉伸峰,证实了Fe - O - Fe模式和铁元素导致的Fe = O。DPPH法和ABTS法对MNP的IC50值(74 μg/ml和58 μg/ml)均高于白花水仙叶提取物,证实了MNP的抗氧化性。MNP对α-淀粉酶具有抑制作用,对α-葡萄糖苷酶的最大抑制作用为84.82±0.89 μg/ml,最大抑制作用为82.17±0.82 μg/ml。MNP对HepG2细胞的体外肿瘤抑制活性呈剂量依赖性(150 μg/ml时为16.08%,150 μg/ml时为28.31%)。MNP在400 g/ml时也表现出抗利什曼原虫的活性(对promastigoi为74.26±0.82 g/ml,对amastigoi为69.40±0.69 g/ml)。白花兰与磁性铁纳米粒子结合,抑制HepG2细胞的生长。具有抗癌、抗氧化、抗利什曼原虫和抗糖尿病活性。因此,白花玉兰是一种潜在的肝癌抗癌治疗药物。
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引用次数: 0
Homeobox D9 Promotes Malignant Progression of Non-Small Cell Lung Cancer Through Negatively Regulating Kallikrein Related Peptidase 9 Homeobox D9通过负调控激肽释放酶相关肽酶9促进非小细胞肺癌的恶性进展
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3664
Juntao Hao, Zengqiang Shen, Junjun Ma
We investigated the association between HOXD9 expression and prognosis in non-small cell lung cancer (NSCLC) and explored its underlying mechanisms in tumor progression. HOXD9 expression was examined in 42 pairs of NSCLC tissue samples using qRT-PCR, and its effects were evaluated in NSCLC cell lines through lentiviral vector transfection, assessing cell growth and migration using CCK-8 and Transwell assays. Bioinformatics analysis identified KLK9 as a target gene of HOXD9, and their interaction was investigated in vitro and in vivo. HOXD9 mRNA expression was significantly higher in NSCLC tissues compared to adjacent tissues, positively correlating with metastasis incidence and poor prognosis. HOXD9 knockdown reduced NSCLC cell migration and proliferation, while overexpression had the opposite effect. Luciferase assays confirmed HOXD9′s binding to KLK9, leading to negative regulation of KLK9 expression. Knockdown of KLK9 reversed the inhibitory effect of HOXD9 on NSCLC cell migration and proliferation, while co-overexpression of KLK9 and HOXD9 had the opposite effect. Our findings demonstrate the close association of high HOXD9 expression in NSCLC tissues with metastasis incidence and poor prognosis. HOXD9 likely exerts its biological function in NSCLC by negatively regulating KLK9. These results provide valuable insights into the molecular mechanisms driving NSCLC progression, highlighting HOXD9 as a potential prognostic biomarker and therapeutic target.
我们研究了HOXD9在非小细胞肺癌(NSCLC)中的表达与预后的关系,并探讨了其在肿瘤进展中的潜在机制。采用qRT-PCR检测42对NSCLC组织样本中HOXD9的表达,并通过慢病毒载体转染评估其在NSCLC细胞系中的作用,采用CCK-8和Transwell检测评估细胞生长和迁移。生物信息学分析发现KLK9是HOXD9的靶基因,并在体内和体外研究了它们的相互作用。HOXD9 mRNA在NSCLC组织中的表达明显高于癌旁组织,与转移发生率和预后不良呈正相关。HOXD9敲低可降低NSCLC细胞的迁移和增殖,而过表达则相反。荧光素酶测定证实HOXD9与KLK9结合,导致KLK9表达负调控。KLK9的下调逆转了HOXD9对NSCLC细胞迁移和增殖的抑制作用,而KLK9和HOXD9的共过表达则起到相反的作用。我们的研究结果表明,HOXD9在NSCLC组织中的高表达与转移发生率和不良预后密切相关。HOXD9可能通过负调控KLK9在NSCLC中发挥其生物学功能。这些结果为推动NSCLC进展的分子机制提供了有价值的见解,突出了HOXD9作为潜在的预后生物标志物和治疗靶点。
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引用次数: 0
Ultrasound-Promoted Nanoreagent for Homologous Targeted Synergistic Chemodynamic/Sonodynamic Tumor Therapy 超声促进纳米试剂用于同源靶向协同化疗/声动力肿瘤治疗
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1166/jbn.2023.3655
Huiying Zuo, Hui Fang Xiao, Deqiang Wang, Ranran Wang
The establishment of a tumor theranostic platform with high efficacy is attracting considerable interest in cancer treatment. Nevertheless, considerable obstacles need to be overcome in developing such a platform. In this study, a versatile theranostic system (CM-FMNPs-Cur) was produced utilizing MnO2 nanoflowers, which provided targeted and synergistic therapy for cancer through the incorporation of sonodynamic and chemodynamic therapies. By integrating Fe3O4, MnO2, and curcumin, CM-FMNPs-Cur manifests a substantial amount of reactive oxygen species toward deep-seated cancers. As a sonosensitizer, curcumin was used for chemodynamic therapy (CDT)_and sonodynamic therapy (SDT). In the acidic environment of malignant cells, CM-FMNPs-Cur can decompose into Mn2+ and Fe2+, triggering a Fenton-like reaction and generating ·OH radicals and oxygen. Ameliorating tumor hypoxia also enhanced the effectiveness of SDT in neoplasms. The homologous targeting effect of CM-FMNPs-Cur on cancer cell membranes led to its accumulation in the tumor region. Here, the mutual promotion of CDT and SDT resulted in an amplified therapeutic outcome. All these results revealed the vast potential of CM-FMNPs-Cur for secure and highly effective collaborative tumor treatment, indicating future clinical applications.
建立高效的肿瘤治疗平台在癌症治疗中引起了相当大的兴趣。然而,在开发这样一个平台方面,需要克服相当大的障碍。在本研究中,利用MnO2纳米花生产了一种多功能治疗系统(CM-FMNPs-Cur),该系统通过结合声动力学和化学动力学疗法为癌症提供靶向和协同治疗。通过整合Fe3O4、MnO2和姜黄素,CM FMNPs Cur对深层癌症表现出大量的活性氧。姜黄素作为一种声敏剂被用于化学动力学治疗(CDT)和声动力学治疗(SDT)。在恶性细胞的酸性环境中,CM-FMNPs-Cur可以分解成Mn2+和Fe2+,引发类Fenton反应,产生·OH自由基和氧气。改善肿瘤缺氧也增强了SDT在肿瘤中的有效性。CM-FMNPs-Cur对癌症细胞膜的同源靶向作用导致其在肿瘤区域的积聚。在这里,CDT和SDT的相互促进导致了放大的治疗结果。所有这些结果都揭示了CM FMNPs Cur在安全高效的协同肿瘤治疗中的巨大潜力,预示着未来的临床应用。
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引用次数: 0
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Journal of biomedical nanotechnology
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