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Triptolide-Loaded Solid Lipid Nanogel: Preparation and In-Vitro Evaluation 雷公藤内酯负载固体脂质纳米凝胶:制备与体外评估
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3781
Chun-Feng Lu, Ye Dai, Yun Tao, Qiu-Yi Yin, Yan Jiang, Ting-Wang Jiang
In order to topically deliver triptolide (TPL), we sought to develop and characterize solid lipid nano-particles based gel (SLNs-gel) before we investigated its inhibitory activity on HaCaT cells. Preparation of TPL-loaded SLNs (TPL-SLNs) was performed with a method involving melt-emulsion ultra-sonication and solidification at low temperature. The determined characteristics of TPL-SLNs were particle size (PS), encapsulation efficiency (EE), zeta potential (ZP), microscopic mor phology and release of TPL In-Vitro. After TPL-SLNs have been formulated into gel, we used the Franz diffusion cell method to evaluate the skin permeation and penetration characteristics of TPL-SLNs-gel on rat’s skin. Imaging results showed that particles of TPL-SLNs were homogeneous and well-dispersed. Meanwhile, the PS and ZP of TPL-SLNs were 89.21 ± 9.68 nm and −41.3 ± 6.23 mV, respectively, with EE being 89.3%. Also, we observed a significant improvement in pattern of In-Vitro TPL release from TPL-SLNs compared to free TPL. Furthermore, the cumulative penetration of TPL-SLNs-gel was higher (5.28 times) compared to free TPL. Besides, TPL-SLNs-gel demonstrated substantial higher cytostatic activity on HaCaT cells comparable to both free TPL and TPL-SLNs. Altogether, it is evident that a delivery system like SLNs-gel can potentially increase the transdermal bioavailability of TPL for effective inhibition of proliferous HaCaT cells
为了局部递送曲普内酯(TPL),在研究其对 HaCaT 细胞的抑制活性之前,我们试图开发并表征基于固体脂质纳米颗粒的凝胶(SLNs-凝胶)。TPL-SLNs(TPL-SLNs)的制备方法包括熔融-乳液超超声和低温凝固。确定的 TPL-SLNs 特性包括粒度(PS)、封装效率(EE)、Zeta 电位(ZP)、显微形态学和 TPL 体外释放。将 TPL-SLNs 配制成凝胶后,我们采用弗朗兹扩散细胞法评估了 TPL-SLNs 凝胶在大鼠皮肤上的渗透性和渗透特征。成像结果表明,TPL-SLNs 颗粒均匀且分散良好。同时,TPL-SLNs 的 PS 和 ZP 分别为 89.21 ± 9.68 nm 和 -41.3 ± 6.23 mV,EE 为 89.3%。我们还观察到,与游离 TPL 相比,TPL-SLNs 的体外 TPL 释放模式有了明显改善。此外,与游离 TPL 相比,TPL-SLNs-凝胶的累积渗透率更高(5.28 倍)。此外,TPL-SLNs-凝胶对 HaCaT 细胞的细胞抑制活性大大高于游离 TPL 和 TPL-SLNs。总之,SLNs-凝胶等递送系统有可能提高 TPL 的透皮生物利用度,从而有效抑制 HaCaT 细胞的增殖。
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引用次数: 0
Hyper-Methylation of CpG Island in 5′ UTR of the HLA-G Gene Reduces Its Expression in Individuals with Immune Thrombocytopenia HLA-G 基因 5′ UTR 中 CpG 岛的高甲基化会降低免疫性血小板减少症患者的 HLA-G 基因表达量
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3767
Ji Ma, Yunna Ning, Ke Lu, Hui Wang, Ping Li, Lili Feng, Jianing Zhang, Linna Xie, Qiang He
This study investigated the impact of DNA methylation in the 5′ untranslated region-CpG island (5′ UTR) of the HLA-G gene on soluble HLA-G (sHLA-G) levels in immune thrombocytopenia (ITP) patients, shedding light on sHLA-G’s regulatory mechanisms in ITP. Using a cohort of 53 participants, including ITP patients, DNA methylation profiles in the HLA-G gene’s 5′ UTR were analyzed with Sequenom MassARRAY Methylation Analysis. sHLA-G levels were measured by enzyme-linked immunosorbent assay, and platelet antibodies were assessed using modified MAIPA. Results showed increased DNA methylation at specific CpG sites (CpG3, CpG18, CpG19, and CpG20.21) in ITP patients. A negative correlation between DNA methylation and sHLA-G expression, particularly at CpG18, was found. Patients with Anti-GPIb/IX antibodies had higher CpG18 methylation. Age and gender didn’t correlate significantly with methylation. This underscores 5′ UTR hypermethylation’s role in influencing circulating HLA-G levels, revealing insights into ITP development and potential therapeutic targets. By linking DNA methylation to sHLA-G expression, this advances ITP understanding, suggesting new therapeutic strategies.
本研究调查了免疫性血小板减少症(ITP)患者体内 HLA-G 基因 5′ 非翻译区-CpG 岛(5′ UTR)DNA 甲基化对可溶性 HLA-G (sHLA-G)水平的影响,从而揭示了 sHLA-G 在 ITP 中的调控机制。利用包括ITP患者在内的53名参与者组成的队列,采用Sequenom MassARRAY甲基化分析仪分析了HLA-G基因5′UTR的DNA甲基化图谱。结果显示,ITP 患者特定 CpG 位点(CpG3、CpG18、CpG19 和 CpG20.21)的 DNA 甲基化增加。DNA 甲基化与 sHLA-G 表达呈负相关,尤其是在 CpG18 位点。抗 GPIb/IX 抗体患者的 CpG18 甲基化程度较高。年龄和性别与甲基化无明显相关性。这强调了5′UTR高甲基化在影响循环HLA-G水平中的作用,揭示了ITP的发展和潜在的治疗靶点。通过将DNA甲基化与sHLA-G表达联系起来,这加深了人们对ITP的了解,并提出了新的治疗策略。
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引用次数: 0
Determination of Cytotoxicity and Anti-Human Lung Cancer Properties of Silver Nanoparticles Green-Formulated by Foeniculum vulgare Extract 确定茴香提取物绿色银纳米粒子的细胞毒性和抗人类肺癌特性
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3775
Yang Xue, An Yan, Sara Amirpour Amraii, S. Goorani
Foeniculum vulgare is a plant with many therapeutic effects. In the current research, silver nanoparticles were synthesized by the Foeniculum vulgare extract. The properties of silver nanoparticles against lung cancer cell lines i.e., H69, COR-L47, DMS53, DMS79, NCI-H69/LX20, SHP-77, NCI-H69/CPR, and NCI-H69/LX4 were evaluated. The green-formulated silver nanoparticles were characterized by various tests such as FE-SEM, EDX, FT-IR, and XRD. The FE-SEM findings prove spherical morphology for the AgNPs with the size of 19.34 to 47.93 nm. The IC50 of the silver nanoparticles was 426, 547, 370, 377, 500, 384, 329, and 330 against H69, COR-L47, DMS53, DMS79, NCI-H69/LX20, SHP-77, NCI-H69/CPR, and NCI-H69/LX4, respectively. After doing the studies of clinical trial, the current nanoparticles may be used as an anti-lung cancer supplement in humans.
茴香是一种具有多种治疗功效的植物。本研究利用茴香提取物合成了银纳米粒子。评估了银纳米粒子对肺癌细胞株(即 H69、COR-L47、DMS53、DMS79、NCI-H69/LX20、SHP-77、NCI-H69/CPR 和 NCI-H69/LX4)的特性。通过 FE-SEM、EDX、傅立叶变换红外光谱和 XRD 等各种测试对绿色配方银纳米粒子进行了表征。FE-SEM 检测结果表明,银纳米粒子呈球形,大小为 19.34 至 47.93 nm。银纳米粒子对 H69、COR-L47、DMS53、DMS79、NCI-H69/LX20、SHP-77、NCI-H69/CPR 和 NCI-H69/LX4 的 IC50 分别为 426、547、370、377、500、384、329 和 330。在进行临床试验研究后,目前的纳米粒子可用作人类的抗肺癌辅助药物。
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引用次数: 0
Study on the Mechanism and Protection of Salt-Sensitive Hypertensive Rats’ Myocardial Fibrosis by Regulating Striatin with Sacubatrovalsartan 用沙考巴曲沙坦调节纹蛋白对盐敏感性高血压大鼠心肌纤维化的机制和保护作用研究
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3766
Qingxian Tu, Qianhang Xia, Meihong Chen, Haiyan Zhou, Qianfeng Jiang, Wei Li
This study aims to explore the relationship between STRN, TGF-β1, Caspase-3, PD-1 expression, and myocardial fibrosis in salt-sensitive hypertensive rats. It investigates the correlation between STRN expression and myocardial fibrosis, along with the protective effects of Sacubitril/Valsartan (ARNI). Fifteen 18-week-old rats were divided into three groups: Control, high salt (SSH), and ARNI+SSH. Blood pressure was monitored weekly for 8 weeks. Echocardiography evaluated cardiac parameters, while H&E and Masson staining visualized myocardial morphology and fibrosis. Immunohistochemistry measured protein expression of collagen-1, collagen-3, TGF-β1, PD-1, Caspase-3, and STRN. Western blot assessed STRN protein levels. High-salt diet increased fibrosis, collagen expression, TGF-β1, PD-1, Caspase-3, and reduced STRN expression compared to Control (P < 0.05). ARNI treatment decreased fibrosis, collagen expression, TGF-β1, PD-1, Caspase-3 (P <0.05), and increased STRN expression compared to SSH (P <0.05). STRN expression correlated positively with myocardial fibrosis. ARNI demonstrated potential in attenuating fibrosis by modulating STRN expression and suppressing apoptosis and inflammation in salt-sensitive hypertensive rats.
本研究旨在探讨盐敏感性高血压大鼠的 STRN、TGF-β1、Caspase-3、PD-1 表达与心肌纤维化之间的关系。该研究探讨了 STRN 表达与心肌纤维化之间的相关性,以及沙库比曲利/缬沙坦(ARNI)的保护作用。15 只 18 周大的大鼠被分为三组:对照组、高盐组(SSH)和 ARNI+SSH 组。8 周内每周监测一次血压。超声心动图评估心脏参数,H&E 和 Masson 染色观察心肌形态和纤维化。免疫组化检测了胶原-1、胶原-3、TGF-β1、PD-1、Caspase-3 和 STRN 的蛋白表达。Western 印迹评估了 STRN 蛋白水平。与对照组相比,高盐饮食增加了纤维化、胶原蛋白表达、TGF-β1、PD-1、Caspase-3,降低了STRN表达(P < 0.05)。与 SSH 相比,ARNI 治疗可减少纤维化、胶原表达、TGF-β1、PD-1、Caspase-3(P <0.05),增加 STRN 表达(P <0.05)。STRN 的表达与心肌纤维化呈正相关。ARNI 通过调节盐敏感性高血压大鼠的 STRN 表达、抑制细胞凋亡和炎症,证明了其在减轻纤维化方面的潜力。
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引用次数: 0
A Sustained-Release SP-Sr-CaS/NBD Microsphere for Promoting Bone Repair and Inhibiting Inflammation for the Treatment of Osteomyelitis 用于治疗骨髓炎的促进骨修复和抑制炎症的缓释 SP-Sr-CaS/NBD 微球
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3762
Xue Li, Xiao Xiao, Lei Wang, Weichun Liang, Jun Ruan, Jianyi Ou
In this study, we prepare sustained-release poly(lactide-co-glycolide) (PLGA)-based microspheres (SP), containing strontium (Sr), calcium sulfate (CaS), and NF-κB essential modifier-binding domain (NBD) peptide, namely SP-Sr-CaS/NBD, for the treatment of osteomyelitis. Our results demonstrate that the SP-Sr-CaS/NBD group exhibited enhanced bone repair speed and infection clearance rate compared to other groups. Moreover, histological staining revealed more comprehensive bone structure restoration in the SP-Sr-CaS/NBD group. Furthermore, we assessed the levels of bone growth factors and apoptosis factors in primary bone marrow mesenchymal stem cells and found that NBD effectively suppresses inflammation while Sr-CaS promotes bone healing by inhibiting cell apoptosis. Additionally, we conducted in vitro and in vivo toxicity evaluations of the microspheres, which confirmed their potential as a competitive filling material for osteomyelitis. In conclusion, SP-Sr-CaS/NBD microspheres hold great promise as therapeutic scaffolds for clinical cases involving bone infections by reducing pain and treatment duration. This study provides a new repair material for the treatment of osteomyelitis and promotes the development of repair material for osteomyelitis.
在这项研究中,我们制备了含有锶(Sr)、硫酸钙(CaS)和 NF-κB 重要修饰结合域(NBD)肽的缓释聚乳酸-聚乙二醇(PLGA)基微球(SP),即 SP-Sr-CaS/NBD,用于治疗骨髓炎。我们的研究结果表明,与其他组相比,SP-Sr-CaS/NBD 组的骨修复速度和感染清除率均有所提高。此外,组织学染色显示,SP-Sr-CaS/NBD 组的骨结构修复更为全面。此外,我们还评估了原发性骨髓间充质干细胞中骨生长因子和凋亡因子的水平,发现 NBD 能有效抑制炎症,而 Sr-CaS 能通过抑制细胞凋亡促进骨愈合。此外,我们还对微球进行了体外和体内毒性评估,证实了其作为骨髓炎竞争性填充材料的潜力。总之,SP-Sr-CaS/NBD 微球作为骨感染临床病例的治疗支架,具有减轻疼痛和缩短治疗时间的巨大潜力。这项研究为治疗骨髓炎提供了一种新的修复材料,促进了骨髓炎修复材料的发展。
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引用次数: 0
LncRNA AC003090.1 Mediates miR-203a-3p/FOXP1 Axis to Promote the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells LncRNA AC003090.1 介导 miR-203a-3p/FOXP1 轴促进人骨髓间充质干细胞的成骨分化
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3744
Huafeng Zhuang, Xuedong Yao, Aifei Wang, Junjie Li, Miao Zheng, Yu Dong, Youjia Xu, Yizhong Li, Yongjun Lin
We investigated the regulatory mechanism of lncRNA AC003090.1 in human bone marrow stem cells (hBMSCs). Tissues from patients with osteoporosis (OP) were collected for the detection and analysis of AC003090.1, miR-203a-3p, and FOXP1 expression by QPCR. The expression and activity of alkaline phosphatase (ALP), an osteogenic marker, were detected using a modified Gomori calcium-cobalt assay and PNP colorimetric assay. Calcium deposition on the extracellular surface was demonstrated using alizarin red staining. Using the Oil Red O staining assay to detecte the Intracellular lipid content. Dual luciferase reporting system verified the targeting relationship between AC003090.1 or FOXP1 and miR-203a-3p. qRT-PCR and Western blot were used to measure the expression level of β-catenin in hBMSCs after different intervention treatments. The expression levels of AC003090.1 and FOXP1 were downregulated in Osteoporosis (OP), whereas those of miR-203a-3p were upregulated. An increase in AC003090.1 expression could enhance hBMSC osteogenic differentiation (OD) and reduce the adipogenic ability of hBMSCs. Furthermore, miR-203a-3p mimics or FOXP1 knock-down reversed the effect of increased AC003090.1 expression on OD and adipogenic differentiation of hBMSCs. Dual luciferase reporter assays showed that AC003090.1 can sponge miR-203a-3p, which targets FOXP1 in hBMSCs. LncRNA AC003090.1 promotes OD of hBMSCs by regulating the miR-203a-3p/FOXP1 axis.
我们研究了lncRNA AC003090.1在人类骨髓干细胞(hBMSCs)中的调控机制。我们收集了骨质疏松症(OP)患者的组织,通过 QPCR 检测和分析了 AC003090.1、miR-203a-3p 和 FOXP1 的表达。使用改良的 Gomori 钙钴测定法和 PNP 比色法检测成骨标志物碱性磷酸酶(ALP)的表达和活性。茜素红染色法显示了细胞外表面的钙沉积。使用油红 O 染色法检测细胞内脂质含量。双荧光素酶报告系统验证了 AC003090.1 或 FOXP1 与 miR-203a-3p 之间的靶向关系。 qRT-PCR 和 Western 印迹用于测量不同干预处理后 hBMSCs 中 β-catenin 的表达水平。在骨质疏松症(OP)中,AC003090.1和FOXP1的表达水平下调,而miR-203a-3p的表达水平上调。AC003090.1表达的增加可增强hBMSC的成骨分化(OD),并降低hBMSC的成脂能力。此外,miR-203a-3p模拟物或FOXP1基因敲除可逆转AC003090.1表达增加对hBMSCs成骨分化和成脂分化的影响。双荧光素酶报告实验表明,AC003090.1可以海绵状表达miR-203a-3p,而miR-203a-3p靶向hBMSCs中的FOXP1。LncRNA AC003090.1通过调节miR-203a-3p/FOXP1轴促进hBMSCs的OD。
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引用次数: 0
Effect of Polystyrene Targeting Nanoparticles on Lung Injury in Severe Acute Pancreatitis and NOX2/ROS/NF-κB Pathway 聚苯乙烯靶向纳米粒子对重症急性胰腺炎肺损伤及 NOX2/ROS/NF-κB 通路的影响
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3783
Changbo Liu, Liya Luo, Shuzhen Suo, Yongkang Song
Relationship between polyethylene targeting nanoparticles and key components of the NOX2/ROS/NF-κB signaling pathway has not yet been fully clarified, and their regulatory role in lung injury in severe acute pancreatitis has not yet been confirmed. In this study, severe acute pancreatitis lung injury cells were exposed to polyethylene targeting nanoparticles and MTT method was used to detect cell proliferation. Cell cycle and apoptosis rate were detected using flow cytometry and the expression of NOX2/ROS/NF-κB pathway was detected. The compound polyethylene targeting nanoparticles inhibited proliferation of lung-damaged cells in severe acute pancreatitis dose-dependently (5, 10 and 20 μmol/L), induced G2/M phase arrest, and increased cell apoptosis. In addition, it reduced the expression of NOX2, ROS, and NF-κB, indicating that NOX2/ROS/NF-κB pathway may be inhibited. Polystyrene targeting nanoparticles reduced the expression of IL-6, TNF-α, JAK, STAT, and IL-10. As a targeted drug delivery system, nano-drug-carrying systems help to dissolve drugs that are difficult to dissolve in the drug solution and intervene in the corresponding tissues and cells in a targeted manner. The results of this study showed that polymer-targeted nano-drug systems could regulate the growth of lung-damaged cells in severe acute pancreatitis. Polyethylene targeting nanoparticles may be effective in inhibiting inflammation in lung-damaged cells in severe acute pancreatitis via regulation of NOX2/ROS/NF-κB pathway.
聚乙烯靶向纳米粒子与NOX2/ROS/NF-κB信号通路关键成分之间的关系尚未完全阐明,其在重症急性胰腺炎肺损伤中的调控作用也尚未得到证实。本研究将重症急性胰腺炎肺损伤细胞暴露于聚乙烯靶向纳米颗粒,采用 MTT 法检测细胞增殖。使用流式细胞仪检测细胞周期和凋亡率,并检测 NOX2/ROS/NF-κB 通路的表达。化合物聚乙烯靶向纳米粒子对重症急性胰腺炎肺损伤细胞的增殖有剂量依赖性抑制作用(5、10 和 20 μmol/L),诱导 G2/M 期停滞,并增加细胞凋亡。此外,它还能降低 NOX2、ROS 和 NF-κB 的表达,表明 NOX2/ROS/NF-κB 通路可能受到了抑制。聚苯乙烯靶向纳米颗粒降低了 IL-6、TNF-α、JAK、STAT 和 IL-10 的表达。作为一种靶向给药系统,纳米载药系统有助于溶解药液中难以溶解的药物,并以靶向方式介入相应的组织和细胞。这项研究结果表明,聚合物靶向纳米载药系统可以调节重症急性胰腺炎肺损伤细胞的生长。聚乙烯靶向纳米粒子可通过调节NOX2/ROS/NF-κB途径有效抑制重症急性胰腺炎肺损伤细胞的炎症反应。
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引用次数: 0
The Value of Near-Infrared Multifunctional Nanoprobe Combined with Artificial Intelligence Microsensor Technology in Molecular Diagnosis for Gastric Cancer 近红外多功能纳米探针与人工智能微传感器技术在胃癌分子诊断中的应用价值
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3769
Qiang Sun, Jun Yao, Shuxun Wei, Xinxing Li, Weijun Wang
Since the symptoms of early gastric cancer patients are not obvious, the majority of new gastric cancer cases are progressive gastric cancer every year. In this paper, we applied nanomedicine technology to design and prepare multifunctional nanoparticles for the diagnosis and treatment of gastric cancer. Through targeted imaging of gastric cancer, combined with phototherapy and the prepared nanoprobes are applied to the ectopic transplantation tumor model of gastric cancer. Meanwhile, a fluorescent microsensor based on graphene oxide and deoxyribonuclease is constructed in order to realize the rapid detection of gastric cancer exosomes. The near-infrared multifunctional nanoprobe is combined with artificial intelligence microsensor technology and applied to the molecular diagnosis of gastric cancer. The results shows that the P-P-I-M+ laser irradiation group has the highest fluorescence intensity and its average fluorescence intensity is 2.04 times higher than that of the P-P-I+ laser irradiation group. The relative cell viability of P-P-M+ laser irradiation group, P-P-I+ laser irradiation group and P-P-I-M+ laser irradiation group are 62.5%, 41.9% and 19.3%, respectively. Therefore, the method in this paper can reduce the non-specific toxicity to other organs as well as exert the effect of combining the diagnosis and treatment of gastric cancer.
由于早期胃癌患者症状不明显,每年新增的胃癌病例以进展期胃癌居多。本文应用纳米医学技术设计制备了多功能纳米探针,用于胃癌的诊断和治疗。通过胃癌靶向成像,结合光疗,将制备的纳米探针应用于胃癌异位移植肿瘤模型。同时,构建了基于氧化石墨烯和脱氧核糖核酸酶的荧光微传感器,以实现对胃癌外泌体的快速检测。将近红外多功能纳米探针与人工智能微传感器技术相结合,应用于胃癌的分子诊断。结果表明,P-P-I-M+激光照射组的荧光强度最高,其平均荧光强度是P-P-I+激光照射组的2.04倍。P-P-M+激光照射组、P-P-I+激光照射组和P-P-I-M+激光照射组的相对细胞活力分别为62.5%、41.9%和19.3%。因此,本文的方法既能减少对其他器官的非特异性毒性,又能发挥胃癌诊断与治疗相结合的效果。
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引用次数: 0
The Impact of LncRNA Nuclear-Enriched Abundant Transcript 1-Mediated Regulation of ASK1 Expression via miR-20a on High Glucose-Induced Retinal Vascular Endothelial Cell Injury LncRNA 核富集丰度转录本 1 通过 miR-20a 介导的 ASK1 表达调控对高血糖诱导的视网膜血管内皮细胞损伤的影响
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3768
Ling Zhao, Chunhua Cai, Congjian Yi, Chaobin Liu
This study investigates how long non-coding RNA (LncRNA) NEAT1 influences high glucose-induced damage in human retinal vascular endothelial cells (hRECs). Different experimental groups were established, including normal, high glucose, LncRNA NEAT1 knockdown, and miR-20a inhibition. Assessments were conducted for molecular and functional changes. In high glucose conditions, NEAT1 expression increased while miR-20a expression decreased in hRECs. Silencing NEAT1 reduced its levels and increased miR-20a expression. Consequently, reactive oxygen species (ROS), MDA, 4-HNE, IL-1β, TNF-α, ICAM-1, ASK1, VEGF, and p-p38 MAPK/p38 MAPK ratio decreased. This led to diminished cell proliferation, migration, and tube formation in hRECs. The impact of NEAT1 silencing was partially reversed by miR-20a inhibition, suggesting NEAT1′s regulatory role via miR-20a. NEAT1 suppressed miR-20a and ASK1 protein levels. Additionally, LncRNA NEAT1 sequestered miR-20a, contributing to ASK1 downregulation. This process also suppressed p38 MAPK activation, further inhibiting hREC functions. In summary, NEAT1 modulated high glucose-induced hREC injury by downregulating miR-20a and subsequently impacting ASK1 and p38 MAPK pathways, thereby impairing cell functions. This study provides insights into potential therapeutic targets for diabetic retinopathy.
本研究探讨了长非编码 RNA(LncRNA)NEAT1 如何影响高糖诱导的人视网膜血管内皮细胞(hRECs)损伤。实验中设立了不同的实验组,包括正常组、高糖组、LncRNA NEAT1敲除组和 miR-20a 抑制组。对分子和功能变化进行了评估。在高糖条件下,NEAT1的表达增加,而hRECs中miR-20a的表达减少。沉默 NEAT1 会降低其水平,增加 miR-20a 的表达。因此,活性氧(ROS)、MDA、4-HNE、IL-1β、TNF-α、ICAM-1、ASK1、血管内皮生长因子和 p-p38 MAPK/p38 MAPK 比率均下降。这导致 hRECs 的细胞增殖、迁移和管形成减少。抑制miR-20a可部分逆转NEAT1沉默的影响,这表明NEAT1可通过miR-20a发挥调控作用。NEAT1 抑制了 miR-20a 和 ASK1 蛋白水平。此外,LncRNA NEAT1封存了miR-20a,导致了ASK1的下调。这一过程还抑制了 p38 MAPK 的激活,进一步抑制了 hREC 的功能。总之,NEAT1 通过下调 miR-20a,进而影响 ASK1 和 p38 MAPK 通路,调节高糖诱导的 hREC 损伤,从而损害细胞功能。这项研究为糖尿病视网膜病变的潜在治疗靶点提供了启示。
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引用次数: 0
Antibacterial Effect of Nanostructured Cuprous Gold and Silver Oxide Composite Nanoshell on Keratitis 纳米结构亚铜金和氧化银复合纳米壳对角膜炎的抗菌效果
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-02-01 DOI: 10.1166/jbn.2024.3764
Chen Wang, Yang Liu, Mingchang Zhang
We developed novel inorganic nanomaterials to combat drug-resistant bacterial infections in keratitis. These infections cause rapid severe corneal ulcers. Traditional antibiotics face challenges due to bacterial resistance. We investigated new therapies by designing nanomaterials. In an animal model of diabetic keratitis, we studied the materials’ antibacterial properties and mechanisms. In vitro, nanomaterials displayed strong antibacterial effects, confirmed by quantitative analysis. In vivo, using thermal imaging, wound closure monitoring, clinical scores, and histopathology, we demonstrated nanomaterials’ efficacy against infections. Toxicity evaluations, including weight monitoring, hemolysis, biochemical, hematological analyses, and organ histology, revealed no adverse effects on the body or organs. Confocal microscopy showed effective bacterial eradication using nanomaterials combined with near-infrared laser treatment. Minimal impact on red blood cells was observed at therapeutic concentrations. Nanomaterials, particularly gold-silver-cuprous oxide composite nanoshells, demonstrated potent resistance against drug-resistant infections. Photothermal treatment using nanomaterials and near-infrared laser showed promise without harming normal tissues, blood, or organs. Our findings offer a potential clinical solution for keratitis treatment.
我们开发了新型无机纳米材料来对抗角膜炎中的耐药细菌感染。这些感染会迅速导致严重的角膜溃疡。由于细菌的耐药性,传统抗生素面临挑战。我们通过设计纳米材料研究了新的疗法。在糖尿病角膜炎动物模型中,我们研究了材料的抗菌特性和机制。在体外,纳米材料显示出很强的抗菌效果,并通过定量分析得到了证实。在体内,我们利用热成像、伤口闭合监测、临床评分和组织病理学证明了纳米材料的抗感染功效。包括体重监测、溶血、生化、血液学分析和器官组织学在内的毒性评估表明,纳米材料对人体或器官没有不良影响。共聚焦显微镜显示,纳米材料结合近红外激光治疗可有效消灭细菌。在治疗浓度下,对红细胞的影响极小。纳米材料,尤其是金-银-氧化亚铜复合纳米壳,对耐药性感染有很强的抵抗力。利用纳米材料和近红外激光进行的光热治疗显示出了良好的前景,不会对正常组织、血液或器官造成伤害。我们的研究结果为角膜炎治疗提供了一种潜在的临床解决方案。
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引用次数: 0
期刊
Journal of biomedical nanotechnology
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