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Naringenin-Loaded Bovine Serum Albumin Nanoparticles Inhibit Reactive Oxygen Species (ROS) to Prevent Ulcer and Gastric Cancer 柚皮苷载体牛血清白蛋白纳米粒子抑制活性氧 (ROS),预防溃疡和胃癌
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-06-01 DOI: 10.1166/jbn.2024.3846
Furong Liu, Ting Wen, Fangshan Chen, Jin Huang, Dazhong Liao
Gastric cancer is a malignance of digestive system and effective treatment measures are key to treatment of gastric cancer. In this experiment, we assessed the effect of bovine serum albumin nanoparticle (BASNP)-coated naringenin (NGN) on reactive oxygen species (ROS) in gastric cancer. After preparation of NGN-BASNP and animal model of gastric cancer, rats were administered with NGN-BASNP, ROS agonists and ROS inhibitors, when the model group was set. After one week of intervention, gastric ulcers in rats were measured and Hematoxylin-eosin (HE) staining was performed. Transwell chamber was used to detect cell invasion ability, while 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was detected proliferation ability of gastric cancer cells. Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot determined TNF-α mRNA expression and ROS. With about 100 nm diameter of NGN-BASNP nanoparticles, the nanoparticles presented in good shape. Compared with lesions in the model group, NGN-BASNP treatment greatly improved the condition, relieving the ulcer and decreasing the ulcer area (P < 0.05). After adding ROS agonist, inhibitory effect of NGN-BASNP intervention was amplified (P < 0.01) when the ROS level in the NGN-BASNP+ROS agonist group was decreased and TNF-α expression decreased. Moreover, NGN-BASNP effectively suppressed gastric cancer cell proliferation and migration but induced apoptosis. NGN-BASNP inhibited the expression of TNF-α mRNA and ROS level in gastric cancer cells, thereby alleviating gastric ulcer and delaying gastric cancer cell growth.
胃癌是消化系统的恶性肿瘤,有效的治疗措施是治疗胃癌的关键。本实验评估了牛血清白蛋白纳米颗粒(BASNP)包被柚皮苷(NGN)对胃癌活性氧(ROS)的影响。制备好 NGN-BASNP 和胃癌动物模型后,在设定模型组时给大鼠注射 NGN-BASNP、ROS 激动剂和 ROS 抑制剂。干预一周后,测量大鼠的胃溃疡,并进行苏木精-伊红(HE)染色。Transwell室用于检测细胞侵袭能力,3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑(MTT)用于检测胃癌细胞的增殖能力。实时定量聚合酶链式反应(RT-qPCR)和 Western 印迹检测 TNF-α mRNA 表达和 ROS。NGN-BASNP纳米颗粒直径约为100 nm,形状良好。与模型组病变相比,NGN-BASNP 治疗大大改善了病情,缓解了溃疡,缩小了溃疡面积(P < 0.05)。加入 ROS 激动剂后,当 NGN-BASNP+ROS 激动剂组的 ROS 水平下降、TNF-α 表达减少时,NGN-BASNP 干预的抑制作用被放大(P < 0.01)。此外,NGN-BASNP 还能有效抑制胃癌细胞的增殖和迁移,并诱导细胞凋亡。NGN-BASNP抑制了胃癌细胞中TNF-α mRNA的表达和ROS水平,从而缓解了胃溃疡并延缓了胃癌细胞的生长。
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引用次数: 0
Polymerase Chain Reaction Cleaner with Antibacterial Effect and Faster Elimination of Nucleic Acid Aerosol Pollution 具有抗菌效果并能更快消除核酸气溶胶污染的聚合酶链式反应清洁剂
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-06-01 DOI: 10.1166/jbn.2024.3851
Gui-Gui Hu, Yuting Chen, Yueying Pan, Xinyu Zhang, Hui Chen, Yanqi Wu, Nongyue He
With advancement of nucleic acid detection technology, most universities, biological testing companies, and hospitals have Polymerase Chain Reaction (PCR) laboratories. PCR detection technology is the core technology for nucleic acid detection. When nucleic acid detection is performed in a PCR laboratory, nucleic acid aerosol samples are often dispersed to the environment in the form of aerosols. At this time, there will be some nucleic acid contamination in the PCR laboratory, resulting in false positive samples. The purpose of this paper is to propose a new type of nucleic acid pollution scavenger called PCR Cleaner. Firstly, the best ratio of PCR Cleaner was obtained by a control experiment, and then the antibacterial test for the PCR Cleaner was carried by comparing the nucleic acid pollution removal efficiency of different ratios of PCR Cleaner and common nucleic acid pollution scavenger on the surface and in the air. Experiment results showed that, the removal efficiency of PCR Cleaner on the surface of nucleic acid was much higher than that of alcohol and aqueous solution. Its effect was good enough when compared to the two commonly used nucleic acid pollution scavengers (DNA/RNA-ExitusPlus and PCR clean). The antibacterial and bacteriostatic PCR Cleaner can significantly inhibit the growth of high concentration of E. coli, and can also completely inhibit the low concentration of E. coli.
随着核酸检测技术的发展,大多数大学、生物检测公司和医院都拥有聚合酶链式反应(PCR)实验室。PCR 检测技术是核酸检测的核心技术。在 PCR 实验室进行核酸检测时,核酸气溶胶样本往往会以气溶胶的形式散布到环境中。此时,PCR 实验室中会出现一些核酸污染,从而导致样本出现假阳性。本文旨在提出一种新型核酸污染清除剂--PCR Cleaner。首先,通过对照实验获得了 PCR Cleaner 的最佳配比,然后通过比较 PCR Cleaner 和普通核酸污染清除剂不同配比对物体表面和空气中核酸污染的去除效率,对 PCR Cleaner 进行了抗菌测试。实验结果表明,PCR Cleaner 对核酸表面的去除率远远高于酒精和水溶液。与两种常用的核酸污染清除剂(DNA/RNA-ExitusPlus 和 PCR Clean)相比,其效果也足够好。抗菌抑菌型 PCR Cleaner 能显著抑制高浓度大肠杆菌的生长,也能完全抑制低浓度大肠杆菌的生长。
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引用次数: 0
Microfibril-Associated Protein-3-Like Regulates TGFβ-Induced EMT Process via TNFR2/p38 MAPK Pathway in Endothelial Cells 微纤维关联蛋白-3-Like 通过 TNFR2/p38 MAPK 通路调控内皮细胞中 TGFβ 诱导的 EMT 过程
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-06-01 DOI: 10.1166/jbn.2024.3842
Sien Guo, Yongdong Liu, Yuanbiao Meng, Qishen Yao, Yulan Zhang, Xiaomei Qin
Abdominal aortic inflammation (AAI) is a major arterial vasculitis characterized by chronic inflammation and fibrosis. Endothelial cells transform into mesenchymal cells (EMT) is one of the significant mechanisms of vasculitis fibrosis. Despite its importance, the molecular mechanism of EMT in AAI remains poorly understood. In this study, we induced AAI in mice through intraperitoneal injection of tumor necrosis factor-alpha (TNFα). To analyze protein expression, we performed Western blotting. Additionally, we extracted RNA using the nanomagnetic bead method to investigate the expression of functionally related genes. We conducted cell migration and invasion assays using scratch and Transwell techniques. Western blot analysis revealed the upregulation of microfibril-associated protein-3-like (MFAP3L) and tumor necrosis factor (TNF) receptor 2 (TNFR2), along with p38 signaling pathway activation. Notably, MFAP3L expression played a crucial role in the transforming growth factor-beta (TGFβ)-induced EMT process in endothelial cells. Furthermore, we identified that MFAP3L-mediated EMT relied on both TNFR2 expression and the activity of the TNFR2/p38 signaling pathway.
腹主动脉炎(AAI)是一种以慢性炎症和纤维化为特征的主要动脉血管炎。内皮细胞转化为间充质细胞(EMT)是脉管炎纤维化的重要机制之一。尽管EMT在AAI中非常重要,但其分子机制仍鲜为人知。在本研究中,我们通过腹腔注射肿瘤坏死因子-α(TNFα)诱导小鼠AAI。为了分析蛋白质的表达,我们进行了 Western 印迹。此外,我们还使用纳米磁珠法提取了 RNA,以研究功能相关基因的表达。我们使用划痕和 Transwell 技术进行了细胞迁移和侵袭试验。Western 印迹分析显示,微纤维相关蛋白-3-样(MFAP3L)和肿瘤坏死因子(TNF)受体 2(TNFR2)上调,p38 信号通路激活。值得注意的是,MFAP3L 的表达在转化生长因子-β(TGFβ)诱导的内皮细胞 EMT 过程中起着至关重要的作用。此外,我们还发现 MFAP3L 介导的 EMT 依赖于 TNFR2 的表达和 TNFR2/p38 信号通路的活性。
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引用次数: 0
Mechanism of miR-126 Loaded in Albumin Nanoparticles for Reversing the Multidrug Resistance in Breast Carcinoma Cells 载入白蛋白纳米颗粒的 miR-126 逆转乳腺癌细胞多药耐药性的机制
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-06-01 DOI: 10.1166/jbn.2024.3845
Yang Zhang, Yiming Yang, Ning Li, Fen Hu, Faming Tian, Hao Dai, Haifeng Cai, Jinyin Yan
This study discussed the mechanism of miR-126 loaded in albumin nanoparticles in reversing the multi drug resistance (MDR) in breast carcinoma cells through EGFR-MEK-ERK signal pathway. MCF-7/ADM cells were divided into blank set, empty vector set, miR-126 set and set of vector and miR-126 randomly. The change of drug susceptibility, protein expression of P-gp, BCRP, EGFR, p-EGFR, MEK, p-MEK, ERK and p-ERK, correlation between miR-126 and EGFR-MEK- ERK signal pathway were observed. miR-126 expression in set of vector was the highest. The second was in miR-126 set. IC50 of ADM in miR-126 set was 4.6 µg/mL. The reversion times were two times. The reversion times in set of vector and miR-126 set was 2.8 times. The presentation of BCRP and P-gp in miR-126 set and set of vector and miR-126 was reduced notably. The activity of EGFR-MEK-ERK signal pathway was restrained by miR-126. The content of p-EGFR, p-MEK and p-ERK in miR-126 set and set of vector and miR-126 was reduced notably compared with blank set. EGFR-MEK-ERK signal activity was targeting regulated by miR-126 loaded in albumin nanoparticles. The level of phosphoric acid activators was reduced abnormally. The expression of BCRP and P-gp was reduced notably. The MDR in breast carcinoma cells was reversed and the drug susceptibility was elevated notably.
本研究探讨了载入白蛋白纳米颗粒的miR-126通过表皮生长因子受体-MEK-ERK信号通路逆转乳腺癌细胞多重耐药性(MDR)的机制。将 MCF-7/ADM 细胞随机分为空白组、空载体组、miR-126 组和载体与 miR-126 组。观察药物敏感性的变化、P-gp、BCRP、EGFR、p-EGFR、MEK、p-MEK、ERK 和 p-ERK 蛋白表达、miR-126 与 EGFR-MEK- ERK 信号通路的相关性。其次是 miR-126 组。miR-126 组中 ADM 的 IC50 为 4.6 µg/mL。逆转时间为两次。载体组和 miR-126 组的逆转时间为 2.8 倍。在 miR-126 组和载体与 miR-126 组中,BCRP 和 P-gp 的呈现明显减少。miR-126 抑制了表皮生长因子受体-MEK-ERK 信号通路的活性。与空白对照组相比,p-EGFR、p-MEK 和 p-ERK 在 miR-126 组和载体与 miR-126 组中的含量明显降低。载入白蛋白纳米颗粒的 miR-126 对表皮生长因子受体-MEK-ERK 信号活性具有靶向调节作用。磷酸激活剂的水平异常降低。BCRP 和 P-gp 的表达明显减少。乳腺癌细胞的 MDR 被逆转,对药物的敏感性显著提高。
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引用次数: 0
Expression of Long Non-Coding RNA H19 in the Endometrium of Mice During Peri-Implantation and Its Regulation on Embryo Implantation 长非编码 RNA H19 在小鼠子宫内膜着床期的表达及其对胚胎着床的调控
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-06-01 DOI: 10.1166/jbn.2024.3850
Haixia Li, Ning Su, Ya‐ning Zhu, Wei Wang, Meihong Cai, Sushi Jiang, Xiaohuan Luo, Wei Xia
In this study, we utilized magnetic nanobeads for the extraction of nucleic acids from tissues to investigate the expression levels and correlation between lncRNA H19, miR-612, and their target gene HOXA10 in peri-implantation endometrium of mice. Furthermore, we conducted overexpression or gene knockout experiments on lncRNA H19 to observe its impact on the expression of miR-612 and HOXA10. The targeted binding relationship between lncRNA H19, miR-612, and HOXA10 was detected by dual luciferase reporter assay. The regulatory relationship between lncRNA H19, miR-612, and HOXA10 was verified through silencing or overexpression of these genes. Intrauterine transfection was used to modulate the expression of lncRNA H19 in endometria during pregnancy, followed by the detection of the expression levels of miR-612 and HOXA10 as well as ITGB3 and IGFBP-1 proteins. Compared with non-pregnant mice, we observed a significant upregulation of both lncRNA H19 and HOXA10 in the endometria of pregnant mice, while miR-612 was found to be downregulated (P < 0.05). Further analysis revealed that the expression levels of lncRNA H19 and HOXA10 increased progressively with gestational days, peaking on Day 4 (P < 0.05). Moreover, Through database analysis, we identified binding sites for lncRNA H19-miR-612 as well as HOXA10-miR-612 interactions. The dual-luciferase reporter assay further supported our conjecture that lncRNA H19 could specifically bind the miR-612, which in turn targets HOXA10 to regulate its expression (P < 0.05). In conclusion, regulations of lncRNA H19 and HOXA10 expression contribute to enhancing endometrial receptivity and facilitating decidualization of endometrial stromal cells, ultimately promoting successful embryo implantation.
本研究利用纳米磁珠从组织中提取核酸,研究lncRNA H19、miR-612及其靶基因HOXA10在小鼠着床周围子宫内膜中的表达水平及其相关性。此外,我们还对lncRNA H19进行了过表达或基因敲除实验,观察其对miR-612和HOXA10表达的影响。通过双荧光素酶报告实验检测了lncRNA H19、miR-612和HOXA10之间的靶向结合关系。通过沉默或过表达这些基因,验证了lncRNA H19、miR-612和HOXA10之间的调控关系。通过宫腔内转染来调节妊娠期子宫内膜中lncRNA H19的表达,然后检测miR-612和HOXA10以及ITGB3和IGFBP-1蛋白的表达水平。与非妊娠小鼠相比,我们观察到妊娠小鼠子宫内膜中的lncRNA H19和HOXA10均显著上调,而miR-612则下调(P < 0.05)。进一步分析发现,lncRNA H19和HOXA10的表达水平随着妊娠天数的增加而逐渐升高,在第4天达到峰值(P < 0.05)。此外,通过数据库分析,我们确定了lncRNA H19-miR-612以及HOXA10-miR-612相互作用的结合位点。双荧光素酶报告实验进一步支持了我们的猜想,即lncRNA H19可以特异性地与miR-612结合,进而靶向HOXA10以调控其表达(P < 0.05)。总之,lncRNA H19和HOXA10的表达调控有助于提高子宫内膜的容受性和促进子宫内膜基质细胞的蜕膜化,最终促进胚胎成功着床。
{"title":"Expression of Long Non-Coding RNA H19 in the Endometrium of Mice During Peri-Implantation and Its Regulation on Embryo Implantation","authors":"Haixia Li, Ning Su, Ya‐ning Zhu, Wei Wang, Meihong Cai, Sushi Jiang, Xiaohuan Luo, Wei Xia","doi":"10.1166/jbn.2024.3850","DOIUrl":"https://doi.org/10.1166/jbn.2024.3850","url":null,"abstract":"In this study, we utilized magnetic nanobeads for the extraction of nucleic acids from tissues to investigate the expression levels and correlation between lncRNA H19, miR-612, and their target gene HOXA10 in peri-implantation endometrium of mice. Furthermore, we conducted overexpression\u0000 or gene knockout experiments on lncRNA H19 to observe its impact on the expression of miR-612 and HOXA10. The targeted binding relationship between lncRNA H19, miR-612, and HOXA10 was detected by dual luciferase reporter assay. The regulatory relationship between lncRNA H19, miR-612, and HOXA10\u0000 was verified through silencing or overexpression of these genes. Intrauterine transfection was used to modulate the expression of lncRNA H19 in endometria during pregnancy, followed by the detection of the expression levels of miR-612 and HOXA10 as well as ITGB3 and IGFBP-1 proteins. Compared\u0000 with non-pregnant mice, we observed a significant upregulation of both lncRNA H19 and HOXA10 in the endometria of pregnant mice, while miR-612 was found to be downregulated (P < 0.05). Further analysis revealed that the expression levels of lncRNA H19 and HOXA10 increased progressively\u0000 with gestational days, peaking on Day 4 (P < 0.05). Moreover, Through database analysis, we identified binding sites for lncRNA H19-miR-612 as well as HOXA10-miR-612 interactions. The dual-luciferase reporter assay further supported our conjecture that lncRNA H19 could specifically\u0000 bind the miR-612, which in turn targets HOXA10 to regulate its expression (P < 0.05). In conclusion, regulations of lncRNA H19 and HOXA10 expression contribute to enhancing endometrial receptivity and facilitating decidualization of endometrial stromal cells, ultimately promoting\u0000 successful embryo implantation.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141231569","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
Effect of TiO2 Nanotubes on Biological Activity of Osteoblasts and Focal Adhesion Kinase/Osteopontin Level 二氧化钛纳米管对成骨细胞生物活性和局部粘附激酶/骨蛋白水平的影响
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-05-01 DOI: 10.1166/jbn.2024.3877
Chunqing Che, Jinfeng Wang, Weixiao Guo
Osteoblasts are important cells for bone formation and play a major part in bone diseases and bone defects. Clinically, we usually adopt bone implants for related diseases. Also, nanotechnology is important in bones and joints. This study assessed the effects of TiO2 nanotubes of different diameters on osteoblast activity, FAK and OPN levels, aiming to provide an experimental foundation for selection of clinical bone implant materials. The morphology of MG-63 human osteosarcoma cells changed with expansion of TiO2 nanotubes’ diameter. From the biological activity, the cell proliferation and adhesion were enhanced as the diameter of the TiO2 nanotube was increased and its proliferation and adhesion were highest in the 100 nm TiO2 nanotube, which is related to increased ALP activity, FAK and OPN protein and mRNA expression. ELISA detected ALP activity and found that MG-63 cells cultured with 70 nm nanotube had strongest activity. Immune blotting and PCR results showed that, FAK and OPN activities were highest in 70 nm TiO2 nanotube cells. In summary, TiO2 nanotubes increased cell proliferation and adhesion by up-regulating the activities of FAK and OPN in a concentration-dependent relationship.
成骨细胞是骨形成的重要细胞,在骨病和骨缺损中发挥着重要作用。临床上,我们通常采用骨植入物来治疗相关疾病。此外,纳米技术对骨骼和关节也很重要。本研究评估了不同直径的 TiO2 纳米管对成骨细胞活性、FAK 和 OPN 水平的影响,旨在为临床骨植入材料的选择提供实验基础。MG-63人骨肉瘤细胞的形态随着TiO2纳米管直径的扩大而发生变化。从生物活性来看,随着TiO2纳米管直径的增大,细胞的增殖和粘附能力增强,其中100 nm TiO2纳米管的细胞增殖和粘附能力最强,这与ALP活性、FAK和OPN蛋白及mRNA表达量的增加有关。ELISA 检测 ALP 活性,发现用 70 nm 纳米管培养的 MG-63 细胞的 ALP 活性最强。免疫印迹和 PCR 结果表明,FAK 和 OPN 活性在 70 纳米 TiO2 纳米管细胞中最高。总之,TiO2 纳米管通过上调 FAK 和 OPN 的活性增加了细胞的增殖和粘附能力,其活性与浓度呈依赖关系。
{"title":"Effect of TiO2 Nanotubes on Biological Activity of Osteoblasts and Focal Adhesion Kinase/Osteopontin Level","authors":"Chunqing Che, Jinfeng Wang, Weixiao Guo","doi":"10.1166/jbn.2024.3877","DOIUrl":"https://doi.org/10.1166/jbn.2024.3877","url":null,"abstract":"Osteoblasts are important cells for bone formation and play a major part in bone diseases and bone defects. Clinically, we usually adopt bone implants for related diseases. Also, nanotechnology is important in bones and joints. This study assessed the effects of TiO2 nanotubes\u0000 of different diameters on osteoblast activity, FAK and OPN levels, aiming to provide an experimental foundation for selection of clinical bone implant materials. The morphology of MG-63 human osteosarcoma cells changed with expansion of TiO2 nanotubes’ diameter. From the biological\u0000 activity, the cell proliferation and adhesion were enhanced as the diameter of the TiO2 nanotube was increased and its proliferation and adhesion were highest in the 100 nm TiO2 nanotube, which is related to increased ALP activity, FAK and OPN protein and mRNA expression.\u0000 ELISA detected ALP activity and found that MG-63 cells cultured with 70 nm nanotube had strongest activity. Immune blotting and PCR results showed that, FAK and OPN activities were highest in 70 nm TiO2 nanotube cells. In summary, TiO2 nanotubes increased cell proliferation\u0000 and adhesion by up-regulating the activities of FAK and OPN in a concentration-dependent relationship.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141032682","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
Heat-Shock Protein 4 (HSP-4) Promote Renal Cell Carcinoma Metastasis via Negatively Regulating KLF6 热休克蛋白 4 (HSP-4) 通过负调控 KLF6 促进肾细胞癌转移
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-05-01 DOI: 10.1166/jbn.2024.3825
Cheng Li, Zhengqiang Wan, Dongbing Zheng, Yinglei Wang
This project investigates the role and mechanisms of HSP4 and KLF6 in renal clear cell carcinoma (RCC) metastasis at molecular, cellular, and clinical levels. HSP4 expression was analyzed in RCC tissue specimens, cell lines, and its relationship with clinicopathological indicators. RCC cell lines with elevated HSP4 were transfected with HSP4 knockdown vectors, and the impact on cell invasion was assessed. The interaction between HSP4 and KLF6 was confirmed through luciferase assays and cell experiments. HSP4 expression was significantly higher in RCC tissues and cell lines compared to normal samples. Higher HSP4 levels were associated with increased metastasis incidence in RCC patients. HSP4 knockdown suppressed cell migration. Luciferase assays showed that HSP4 targets KLF6. KLF6 mRNA levels were inversely correlated with HSP4 in RCC tissues. Knockdown of HSP4 increased KLF6 levels, and vice versa, indicating a negative correlation. Inhibition of KLF6 counteracted the inhibitory effect of HSP4 knockdown on RCC cell functions. In conclusion, elevated HSP4 expression is linked to lymph node and distant metastasis in RCC patients. HSP4 likely promotes RCC progression by negatively regulating KLF6, offering insights into RCC-specific biomarkers and its pathogenesis.
该项目从分子、细胞和临床层面研究了HSP4和KLF6在肾透明细胞癌(RCC)转移中的作用和机制。分析了HSP4在RCC组织标本、细胞系中的表达及其与临床病理指标的关系。用HSP4敲除载体转染HSP4表达升高的RCC细胞系,并评估其对细胞侵袭的影响。通过荧光素酶测定和细胞实验证实了HSP4和KLF6之间的相互作用。与正常样本相比,HSP4在RCC组织和细胞系中的表达明显较高。较高的HSP4水平与RCC患者转移发生率的增加有关。HSP4基因敲除抑制了细胞迁移。荧光素酶测定显示,HSP4靶向KLF6。在RCC组织中,KLF6 mRNA水平与HSP4成反比。敲除HSP4会增加KLF6的水平,反之亦然,表明两者呈负相关。抑制 KLF6 可以抵消 HSP4 敲除对 RCC 细胞功能的抑制作用。总之,HSP4表达的升高与RCC患者的淋巴结和远处转移有关。HSP4可能通过负调控KLF6来促进RCC的进展,这为RCC特异性生物标志物及其发病机制提供了启示。
{"title":"Heat-Shock Protein 4 (HSP-4) Promote Renal Cell Carcinoma Metastasis via Negatively Regulating KLF6","authors":"Cheng Li, Zhengqiang Wan, Dongbing Zheng, Yinglei Wang","doi":"10.1166/jbn.2024.3825","DOIUrl":"https://doi.org/10.1166/jbn.2024.3825","url":null,"abstract":"This project investigates the role and mechanisms of HSP4 and KLF6 in renal clear cell carcinoma (RCC) metastasis at molecular, cellular, and clinical levels. HSP4 expression was analyzed in RCC tissue specimens, cell lines, and its relationship with clinicopathological indicators.\u0000 RCC cell lines with elevated HSP4 were transfected with HSP4 knockdown vectors, and the impact on cell invasion was assessed. The interaction between HSP4 and KLF6 was confirmed through luciferase assays and cell experiments. HSP4 expression was significantly higher in RCC tissues and cell\u0000 lines compared to normal samples. Higher HSP4 levels were associated with increased metastasis incidence in RCC patients. HSP4 knockdown suppressed cell migration. Luciferase assays showed that HSP4 targets KLF6. KLF6 mRNA levels were inversely correlated with HSP4 in RCC tissues. Knockdown\u0000 of HSP4 increased KLF6 levels, and vice versa, indicating a negative correlation. Inhibition of KLF6 counteracted the inhibitory effect of HSP4 knockdown on RCC cell functions. In conclusion, elevated HSP4 expression is linked to lymph node and distant metastasis in RCC patients. HSP4 likely\u0000 promotes RCC progression by negatively regulating KLF6, offering insights into RCC-specific biomarkers and its pathogenesis.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141035454","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
Effects of MicroRNA-24 on Myocardial Fibrosis in Rats After Myocardial Infarction by Targeting Wnt Family Member 4/Dvl-1/β-Catenin Signaling Pathway MicroRNA-24 通过靶向 Wnt 家族成员 4/Dvl-1/β-Catenin 信号通路对心肌梗死后大鼠心肌纤维化的影响
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-05-01 DOI: 10.1166/jbn.2024.3821
Zhenhui Qi, Ling Tong, Jinxi Huang, Qingfeng Su
In this study, we investigated the impact of miR-24 on myocardial fibrosis severity in rats following myocardial infarction (MI) and explored its underlying mechanisms. We established an MI-induced myocardial fibrosis rat model and assessed cardiac function via echocardiography. We employed Western blotting and RT-qPCR to examine the effects of agomiR-24 on key fibrotic markers, including COL1A1, COL3A1, and α-SMA. Microarray analysis, pathway enrichment, and proteinprotein interaction network analysis revealed the signaling pathways and genes influenced by agomiR-24. Primary rat cardiac fibroblasts (CFs) were isolated, and miR-24’s direct target was confirmed using luciferase reporter assays. We modulated miR-24 expression in CFs and assessed cell proliferation and invasion through CCK-8 and Transwell assays, respectively. Furthermore, we investigated the impact of miR-24 on the Wnt4/Dvl-1/β-catenin signaling pathway by Western blotting. Finally, we examined mRNA expression levels of key genes (Cyclin D1, p27, p21, MMP-3, and MMP-9) through RT-qPCR. Our findings demonstrated that agomiR-24 improved cardiac function and reduced fibrotic marker expression in rat myocardial tissues. MiR-24 inhibited CF proliferation and invasion, potentially by targeting Wnt4/Dvl-1/β- catenin signaling. It also regulated mRNA expression of genes associated with cell proliferation and matrix remodeling. Overall, our study suggests that miR-24 may attenuate myocardial fibrosis in post-MI rats by suppressing the Wnt4/Dvl- 1/β-catenin pathway.
在这项研究中,我们研究了 miR-24 对心肌梗死(MI)后大鼠心肌纤维化严重程度的影响,并探讨了其潜在机制。我们建立了 MI 诱导的心肌纤维化大鼠模型,并通过超声心动图评估心功能。我们采用 Western 印迹法和 RT-qPCR 法研究了 agomiR-24 对主要纤维化标志物(包括 COL1A1、COL3A1 和 α-SMA)的影响。微阵列分析、通路富集和蛋白相互作用网络分析揭示了受 agomiR-24 影响的信号通路和基因。我们分离了原代大鼠心脏成纤维细胞(CFs),并利用荧光素酶报告实验证实了 miR-24 的直接靶标。我们调节了 miR-24 在 CFs 中的表达,并通过 CCK-8 和 Transwell 试验分别评估了细胞的增殖和侵袭。此外,我们还通过 Western 印迹法研究了 miR-24 对 Wnt4/Dvl-1/β-catenin 信号通路的影响。最后,我们通过 RT-qPCR 检测了关键基因(Cyclin D1、p27、p21、MMP-3 和 MMP-9)的 mRNA 表达水平。我们的研究结果表明,agomiR-24 可改善大鼠心肌组织的心脏功能并减少纤维化标志物的表达。MiR-24 可通过靶向 Wnt4/Dvl-1/β- catenin 信号抑制 CF 的增殖和侵袭。它还能调节细胞增殖和基质重塑相关基因的 mRNA 表达。总之,我们的研究表明,miR-24 可通过抑制 Wnt4/Dvl- 1/β-catenin 通路来减轻心肌梗死后大鼠的心肌纤维化。
{"title":"Effects of MicroRNA-24 on Myocardial Fibrosis in Rats After Myocardial Infarction by Targeting Wnt Family Member 4/Dvl-1/β-Catenin Signaling Pathway","authors":"Zhenhui Qi, Ling Tong, Jinxi Huang, Qingfeng Su","doi":"10.1166/jbn.2024.3821","DOIUrl":"https://doi.org/10.1166/jbn.2024.3821","url":null,"abstract":"In this study, we investigated the impact of miR-24 on myocardial fibrosis severity in rats following myocardial infarction (MI) and explored its underlying mechanisms. We established an MI-induced myocardial fibrosis rat model and assessed cardiac function via echocardiography. We\u0000 employed Western blotting and RT-qPCR to examine the effects of agomiR-24 on key fibrotic markers, including COL1A1, COL3A1, and α-SMA. Microarray analysis, pathway enrichment, and proteinprotein interaction network analysis revealed the signaling pathways and genes influenced\u0000 by agomiR-24. Primary rat cardiac fibroblasts (CFs) were isolated, and miR-24’s direct target was confirmed using luciferase reporter assays. We modulated miR-24 expression in CFs and assessed cell proliferation and invasion through CCK-8 and Transwell assays, respectively. Furthermore,\u0000 we investigated the impact of miR-24 on the Wnt4/Dvl-1/β-catenin signaling pathway by Western blotting. Finally, we examined mRNA expression levels of key genes (Cyclin D1, p27, p21, MMP-3, and MMP-9) through RT-qPCR. Our findings demonstrated that agomiR-24 improved cardiac function\u0000 and reduced fibrotic marker expression in rat myocardial tissues. MiR-24 inhibited CF proliferation and invasion, potentially by targeting Wnt4/Dvl-1/β- catenin signaling. It also regulated mRNA expression of genes associated with cell proliferation and matrix remodeling. Overall,\u0000 our study suggests that miR-24 may attenuate myocardial fibrosis in post-MI rats by suppressing the Wnt4/Dvl- 1/β-catenin pathway.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141049657","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
Effects of Remimazolam on Cognitive Function and Nervous System in Mice 雷马唑仑对小鼠认知功能和神经系统的影响
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-05-01 DOI: 10.1166/jbn.2024.3837
Minghong Liu, Jun Shi, Ju Li, Huichun Chen, Qizhu Feng, Yuanhai Li
This study investigated the safety and efficacy of remimazolam besylate by preparing remimazolam nanoemulsion. Field experiments were carried out in mice of different genders and ages. The treatment group was given intraperitoneal injection of Remimazolam nano-emulsion at different doses (0, 10, 15, 15, 20 mg/kg). The propofol group received intraperitoneal injections of propofol, while the control group received intraperitoneal injections of normal saline. The open-field of mice was detected to evaluate the effect of remimazolam on exercise response and sedation recovery time of mice. With the anesthetic effect of propofol as control, the level of P-tau phosphorylation was analyzed by westernblot, and the expression and distribution of P-tau in hippocampus was detected by immunohistochemistry. Golgi staining was used to detect the density of dendritic spines in the hippocampus. The results revealed that remimazolam could reduce the movement distance, movement speed and increase the resting time of mice. The higher the concentration of remimazolam, the stronger the sedative effect. Additionally, the inhibitory effect of low-dose rimazolam on the response of mice was the strongest in 15 min, and gradually recovered after 15 min, and the sedative effect had nothing to do with sex and sex of mice. The results of protein detection showed that compared with propofol group, remimazolam could reduce the expression and distribution of hippocampus P-tau and increase the number and density of dendritic spines. Therefore, low-dose administration of remimazolam has a short-term effectiveness, lacks toxic side effects, and provides a certain level of protection to neurological and cognitive function.
本研究通过制备纳米雷马唑仑乳剂,对苯磺酸雷马唑仑的安全性和有效性进行了研究。实验对象为不同性别和年龄的小鼠。治疗组腹腔注射不同剂量(0、10、15、15、20 毫克/千克)的纳米雷马唑仑乳剂。异丙酚组腹腔注射异丙酚,对照组腹腔注射生理盐水。通过检测小鼠的开放场,评估瑞马唑仑对小鼠运动反应和镇静恢复时间的影响。以丙泊酚的麻醉作用为对照,通过Westernblot分析P-tau的磷酸化水平,并通过免疫组化检测P-tau在海马中的表达和分布。高尔基染色用于检测海马树突棘的密度。结果表明,雷马唑仑能减少小鼠的运动距离、运动速度并增加静息时间。雷马唑仑的浓度越高,镇静作用越强。此外,小剂量利马唑仑对小鼠反应的抑制作用在15分钟内最强,15分钟后逐渐恢复,且镇静作用与小鼠性别无关。蛋白质检测结果显示,与异丙酚组相比,雷马唑仑能减少海马P-tau的表达和分布,增加树突棘的数量和密度。因此,小剂量服用雷马唑仑具有短期疗效,无毒副作用,对神经和认知功能有一定的保护作用。
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引用次数: 0
Identification of Potential Therapeutic Drugs for Diabetic Cardiomyopathy 糖尿病心肌病潜在治疗药物的鉴定
IF 2.9 4区 医学 Q1 Medicine Pub Date : 2024-05-01 DOI: 10.1166/jbn.2024.3827
Z. You, Yunhong Wang, Lin Huang
This study focused on identifying potential therapeutic drugs and mechanisms of action for diabetic cardiomyopathy (DCM). Using gene expression profiles from the GSE197850 dataset, we applied Weighted Correlation Network Analysis, Limma, and Gene Set Variation Analysis (GSVA) to uncover DCM-related gene sets and pathways. Subsequently, we conducted protein interaction network analysis with String and identified 10 hub genes through Cytoscape: ACTN2, ITGA1, CASP3, PXN, PCNA, CAV1, GAPDH, FEN1, PTPN11, and ESR1. In vitro validation using Rat H9C2 cardiomyocytes showed upregulation of FEN1, PCNA, PTPN11, CAV1, GAPDH, CASP3, PXN, and ACTN2, and downregulation of ESR1 and ITGA11 in high-glucose conditions. We further performed immune infiltration analysis with CIBERSORT and explored potential therapeutic agents through molecular docking with Autodock Vina. Our findings identified estradiol, valproic acid, acetaminophen, and resveratrol as potential drugs for DCM. Among these, resveratrol showed promise by promoting autophagy. This study leveraged comprehensive bioinformatic and experimental methods to pinpoint DCM-related genes, elucidate key hub genes, and propose resveratrol as a latent drug for DCM.
本研究的重点是确定糖尿病心肌病(DCM)的潜在治疗药物和作用机制。利用 GSE197850 数据集中的基因表达谱,我们应用加权相关网络分析、Limma 和基因组变异分析 (GSVA) 发现了与 DCM 相关的基因组和通路。随后,我们利用 String 进行了蛋白质相互作用网络分析,并通过 Cytoscape 发现了 10 个枢纽基因:ACTN2、ITGA1、CASP3、PXN、PCNA、CAV1、GAPDH、FEN1、PTPN11 和 ESR1。使用大鼠 H9C2 心肌细胞进行的体外验证显示,在高葡萄糖条件下,FEN1、PCNA、PTPN11、CAV1、GAPDH、CASP3、PXN 和 ACTN2 上调,ESR1 和 ITGA11 下调。我们还利用 CIBERSORT 进行了免疫浸润分析,并利用 Autodock Vina 进行了分子对接,以探索潜在的治疗药物。我们的研究结果发现,雌二醇、丙戊酸、对乙酰氨基酚和白藜芦醇是治疗 DCM 的潜在药物。其中,白藜芦醇具有促进自噬的作用。本研究利用全面的生物信息学和实验方法精确定位了 DCM 相关基因,阐明了关键枢纽基因,并提出白藜芦醇是治疗 DCM 的潜在药物。
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Journal of biomedical nanotechnology
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