Modulation of Autophagy is a Potential Strategy for Enhancing the Anti-Tumor Effect of Mebendazole in Glioblastoma Cells

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC₅₀ of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC₅₀ of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.     

内源性HMGB1调节低氧乏养胰腺癌细胞脂肪酸代谢及其机制

目的 研究内源性高迁移率族蛋白B1(HMGB1)在低氧乏养胰腺癌细胞脂肪酸代谢重编程及线粒体融合/分裂中的作用及机制.方法 GEPIA数据库分析胰腺癌组织中HMGB1表达水平与胰腺癌患者生存率的相关性;CCK-8法、划痕实验和Transwell实验分别检测内源性HMGB1对低氧乏养Patu8988细胞增殖、侵袭及迁移的...     

老药新用:氯喹体内外抗病毒研究进展

氯喹是1934年德国学者合成的一种奎宁衍生物。除了具有抗疟疾、治疗系统性红斑狼疮和免疫调节作用外,氯喹还显示具有广谱的抗病毒作用,临床试验也证实其对艾滋病有较好的疗效。2019年出现了许多新型冠状病毒(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)感染的患者,初步的临床试验显示,氯喹对SARS-CoV-2感染患者有明显的疗效。作者通过总结氯喹对不同病毒的作用,阐述其作用机制,分析比较其在体内外作用的效果。氯喹抗病毒的体内与体外结果不一致,可能与动物模型、氯喹的剂量及体内分布、临床研究设计有关。     

1999-2018年天津市居民平均期望寿命变化分析

目的:分析近20年天津市居民期望寿命变化规律以及对期望寿命增量的影响因素。方法:应用简略寿命表、期望寿命差异的年龄和死因分解法对天津市户籍居民1999-2018年死因监测数据进行分析,计算不同年龄、不同疾病死亡率对期望寿命增量的贡献值和百分比。结果:20年间天津市户籍居民期望寿命增加了4.97岁,男性、女性期望寿命分别...     

基于右侧脑岛功能连接性的哮喘针刺fMRI研究

目的 观察哮喘患者与健康人群右侧脑岛各亚区与全脑的功能连接性(functional connectivity,FC)差异,以及电针干预前后,哮喘患者右侧脑岛FC值的变化.材料与方法 招募符合标准的健康对照组受试者与哮喘组患者各18名,采集两组受试者基线期静息态功能磁共振数据.哮喘组患者电针大椎、风门、肺俞30 min后...     

Electron transport properties of PtSe2 nanoribbons with distinct edge reconstructions

Edge reconstructions of two-dimensional (2D) materials play a central role in determining the electronic transport properties of nanodevices. However, it is not feasible to study the relationship between edge reconstruction and electronic properties using experimental methods because of the complexity of the experimental environment and the diversity of edge reconstruction. Herein, we have combined density functional theory (DFT) calculations and the nonequilibrium Green''s function (NEGF) method to investigate the inner physical mechanism of platinum diselenide (PtSe₂) nanoribbons, revealing distinctive negative differential resistance (NDR) behaviors in different nanoribbons with various edge reconstructions. The armchair PtSe₂ nanoribbons with different edge reconstructions are all metallic, while the zigzag PtSe₂ nanoribbons are semiconducting when the ratio of Pt to Se atoms at the edge is 1 : 2. These results reveal the internal source of the difference in the electron transport properties of PtSe₂ nanoribbons with different edge reconstructions, providing new ideas for the design of novel multifunctional PtSe₂ semiconducting and conducting electronic nanodevices with NDR properties.

Edge reconstructions of two-dimensional (2D) materials play a central role in determining the electronic transport properties of nanodevices.     

Molecular dynamics simulation study of adsorption of anionic–nonionic surfactants at oil/water interfaces

Four anionic–nonionic surfactants with the same headgroups and different units of oxygen ethyl (EO) and oxygen propyl (PO) were adopted to investigate the influence on oil/water interfacial tensions in this article. Molecular dynamics (MD) simulations were conducted to study the interfacial property of the four surfactants. Four parameters were proposed to reveal the effecting mechanism of molecular structure on interfacial tension, which included the interfacial thickness, order parameter of the hydrophobic chain, radial distribution function, and the solvent accessible surface area. In addition, the electrostatic potential of the four surfactants was calculated. The research results indicated that the interface facial mask formed by the surfactants, which contained three EO or three PO units was more stable, and it was easier for the surfactants of six EO or six PO units to form a microemulsion at higher concentrations. The adsorption mechanism of the anionic–nonionic surfactant systems at the oil/water interfaces was supplemented at a molecular level, which provided fundamental guidance for an in-depth understanding of the optimal selection of the surfactants in enhancing oil recovery.

Four anionic–nonionic surfactants with the same headgroups and different units of oxygen ethyl (EO) and oxygen propyl (PO) were adopted to investigate the influence on oil/water interfacial tensions in this article.     

Structural,optical, and magnetic properties of Ag+, Mn+ and Ar+ ions implanted ZnO thin films: effect of implantation dose and stopping energy

Herein, we systematically studied the effect of various excitation processes on the structural, optical, and magnetic properties of ZnO films implanted with 80 keV Ar⁺, 110 keV Mn⁺, and 190 keV Ag⁺ ions. Four different doses of 1 × 10¹³, 1 × 10¹⁴, 1 × 10¹⁵, and 2 × 10¹⁶ ions per cm² were used for implantation. It was observed that the structural, optical, and magnetic properties of the implanted samples were dominantly affected at the highest dose of 2 × 10¹⁶ ions per cm². For lower doses, insignificant changes in these properties were observed. A comparison of various processes involved in the implantation process shows that both the electronic excitation and nuclear excitation processes are responsible for the changes in the structural, optical, and magnetic properties of the implanted ZnO films.

Dominant changes in structural, optical, and magnetic properties were observed at the highest dose of implanted ions with larger ionic radii which is due to the large number of produced defects in the host.     

AMS对消化内镜围操作期预防性使用抗菌药物的干预效果

目的探讨抗菌药物科学化管理(AMS)策略对消化内镜诊疗操作患者围操作期抗菌药物预防使用的干预效果。方法以某附属医院2019年1—6月行消化内镜诊疗操作的1 006例患者为研究对象,采用AMS策略对患者围操作期预防使用抗菌药物进行管理和干预,措施包括成立组织、完善制度、优化信息系统、宣教与培训、持续干预和监督等。以2017年1—6月行消化内镜诊疗操作的822例患者为对照组,对比分析两组患者围操作期预防性抗菌药物使用率、抗菌药物使用强度(AUD)、抗菌药物品种、联合用药以及用药时长的变化;同时比较预防性抗菌药物不合理应用情况以及术后感染情况。结果干预前预防性抗菌药物使用率为24.82%(204/822),干预后为17.10%(172/1 006),干预前后比较,差异具有统计学意义(P0.001);AUD方面,干预后为2.18,低于干预前的14.95;联合用药比例、用药时长与干预前相比亦明显下降。AMS策略实施后,抗菌药物预防性应用的不合理率低于实施前(P0.001);而操作后感染发生率则无明显变化(P0.05)。结论 AMS策略能够优化消化内镜围操作期预防性抗菌药物的应用。