Natural product-induced oxidative stress-synergistic anti-tumor effects of chemotherapeutic agents

Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.

PAX6基因突变的鉴定与中国家系无虹膜症合并妊娠期糖尿病的产前诊断

目的:探讨1个中国无虹膜症合并妊娠期糖尿病家系的基因缺陷及产前诊断。方法:收集1个患有无虹膜症合并妊娠期糖尿病的中国家系,从外周血中提取整个家系成员的基因组DNA,通过聚合酶链式反应结合直接测序法,分析人类配对盒基因(PAX6)的编码序列。妊娠18wk时对孕妇进行羊膜穿刺术,并根据突变筛查结果进行遗传学分析。结果:无虹膜患者在PAX6的第5外显子中存在杂合缺失突变(c.113_129del GGCCGTGCGACATTTCC,p.Arg38ProfsTer12),该患者同时合并妊娠期糖尿病,产前诊断结果提示胎儿具有相同的突变,易患先天性无虹膜症,经产后随访证实。结论:在中国先天性无虹膜患者中发现了PAX6基因缺失突变,为人类PAX6等位基因变异数据库提供了更多的文献资料,为产前诊断提供了分析依据。

单项血脂及其比值与翼状胬肉的相关性研究

目的:分析单项血脂和血脂比值与翼状胬肉的关系。方法:采用回顾性病例研究。纳入2016-01/2019-02在我院眼科和体检中心确诊的翼状胬肉患者500例(翼状胬肉组)和同期进行健康体检、年龄和性别匹配的健康体检者500例(正常对照组),检测两组研究对象外周静脉血中血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,计算TG/HDL、TC/HDL、LDL/HDL的比值。结果:翼状胬肉患者500例中,血脂异常者68.2%(341/500),翼状胬肉组血清TG、TC、LDL-C水平和TG/HDL、TC/HDL、LDL/HDL的比值均明显高于正常对照组(P<0.001),血清HDL水平低于正常对照组,但无差异(P>0.05)。Logistic回归分析提示,TG(OR=4.132)、TC(OR=2.194)、TG/HDL (OR=2.184)、TC/HDL (OR=2.007)均是翼状胬肉发病的影响因素(P<0.05)。结论:血脂代谢异常是翼状胬肉发病的影响因素,加强血脂管理对翼状胬肉患者的发病和治疗均具有重要的临床意义。

人翼状胬肉中miR-486-3p的表达及其潜在靶基因的生物信息学分析

目的:通过检测人翼状胬肉组织及正常结膜组织中miR-486-3p的表达情况,探寻其在翼状胬肉发生发展中可能的作用机制。方法:于2018-09/2019-12收集原发性翼状胬肉患者69例69眼,收集术中切除的翼状胬肉组织和术眼正常结膜组织,采用RT-PCR定量检测标本中miR-486-3p的相对表达量,并利用Targetscan数据库、miWalk3.0数据库、miRDB数据库对miR-486-3p进行靶基因预测后将得到的潜在靶基因取交集;采用DAVID数据库对miR-486-3p潜在靶基因进行功能和通路富集分析;采用String网站对miR-486-3p潜在靶基因进行互作分析。结果:miR-486-3p在翼状胬肉组织中的相对表达量[(6.183±1.366)×10-6]与正常结膜组织的相对表达量[(7.930±1.394)×10-5]有显著差异(P<0.0001)。通过对其靶基因预测及生物信息学分析发现miR-486-3p潜在靶基因436个,其生物学功能主要富集于对RNA聚合酶Ⅱ启动子转录的调控、囊泡介导的转运和转录调控、DNA依赖性RNA代谢过程的调控。KEGG通路主要富集于神经轴突导向(Axon guidance)通路及溶酶体通路上,其中Axon guidance通路可能对翼状胬肉的发生发展起着重要的调控作用。PPI网络分析进一步表明Axon guidance通路中的关键基因ABL1、PLXNA1对翼状胬肉具有重要作用。结论:miR-486-3p可能通过SLIT(神经导向因子Slit)/Robo(回旋引导受体)和SEMA3A(神经导向因子Semaphorin 3A)/PLXNA1(丛蛋白受体A1)等Axon guidance通路致翼状胬肉的新生血管异常,从而参与翼状胬肉的发生、发展。

Aberration changes of the corneal anterior surface following discontinued use of rigid gas permeable contact lenses

AIM: To record aberrations with a corneal topographic device on the anterior surface of the cornea at different time-points prior to wearing and following discontinued use of rigid gas permeable (RGP) contact lenses. The effect of wearing RGP on the anterior surface of the cornea was discussed to provide guidance for clinical refractive error correction.METHODS: The study objects were 24 eyes from 24 patients. All patients underwent identical examination procedures prior to lens use, as well as afterwards, including slit-lamp examination, non-contact tonometer measurement, computer optometry and corneal curvature measurement, subjective refraction test, and corneal topography analysis. The patients wore contact lenses everyday for 1 month and then discontinued. Corneal topographies were recorded at certain time points of 30 minutes, 1 day, 3, 7 and 14 days following use.RESULTS: Total corneal aberration at each time point following discontinued use of RGP contact lenses was less than the time point prior to use. Detailed results were as follows: root mean square (RMS) (pre)=(1.438± 0.328)μm, RMS (30 minutes) =(1.076 ±0.355)μm, RMS (1 day) =(1.362 ±0.402)μm, RMS (3 days) =(1.373 ±0.398)μm, RMS (7 days) =(1.387 ±0.415)μm, and RMS (14 days) = (1.430±0.423)μm. Results showed that at 30 minutes after discontinued use of RGP contact lenses, almost all 2 ndand 3 rd-order aberrations change. Quadrafoil Z10 and spherical Z12 of the 4 th-order were also changed. Alterations to Z5, Z6, and Z12 at 1 day after discontinued use were significant differences compared with the time period prior to RGP use: Z5 and Z6 decreased, and Z12 increased slightly. Z5 and Z6 remained decreased at 3 days after discontinued use, but Z9 and Z10 continued to increase and Z12 returned to levels prior to RGP use. At 14 days after discontinued use, all aberrations were notsignificantly different from the values prior to use.CONCLUSION: The use RGP contact lenses greatly reduced total aberration of the anterior surface of the cornea. Changes to 2 ndand 3 rd-order aberrations (including Z3, Z4, Z5, Z6, Z7, and Z8) were more significant. Following discontinued use of RGP contact lenses, the majority of lower order aberrations returned to original levels in a short period of time. During this process, a transient higher order aberration appeared, but all changes disappeared within 14 days after discontinued use of RGP contact lenses.

LC–MS/MS Method for Quantification of Liquiritigenin in Rat Plasma: Application to Pharmacokinetic Study of Liquiritin

Objective A simple, sensitive, and rapid LC-MS/MS method has been established and validated for the determination of liquiritigenin （LG） in rat plasma. Methods Naringenin was chosen as internal standard （IS）. LG and IS were separated on a Diamonsil C18 analytical column with a mobile phase of methanol-10% methanol in water containing 0.5 mmol/L ammonium formate and 0.2% formic acid （55：45） at the isocratic flow rate of 0.6 mL/min for 10 min. The multiple reaction monitoring （MRM） was performed on a mass spectrometer in the negative ion mode with electro-spray ionization （ESI） source and the transition from precursor ion to product ion was m/z255.0~119.0 for LG and m/z 271.04151.0 for IS, respectively. Results The linearity was acceptable in the range of 5-5000 ng/mL （r= 0.9973）. The inter-day and intra-day accuracies were in the ranges of -0.09%-3.25% and -5.02%-9.21%, respectively. The precision was in the ranges of 3.60%-12.4% and 0.909%-6.89%, respectively. LG was stable in the course of anarysis and storage. Conclusion The LC-MS/MS method was successfully applied to the pharmacokinetic study for the first time in rats after ig and iv administration of liquiritin （LQ）, a glycoside of LG, at pharmacologically effective levels.

Molecular Simulation Study on Bentysrepinine Metabolites Improving Binding Affinity of HBV DNA Polymerase

Objective To study the effect of bentysrepinine（Y101） metabolites on improving binding affinity of HBV DNA polymerase. Methods The binding mode of Y101 and its metabolites with DNA polymerase has been driven by hydrophobic interaction. Results Two compounds, T2 and T4, exhibited the improvement of the binding affinity to HBV DNA polymerase protein, which suggests that the inhibitory activity against HBV DNA polymerase protein can be enhanced. Conclusion The variant docking poses of T2 and T4 might imply the novel recognition of inhibitory effects of T2 and T4, in comparison with Y101.