Ethanol extract from radix of Actinidia chinensis and Evodiamine regulated CCR7 expression in SW480 cells

Objective To identify anti-tumor effects of the ethanol extract from radix of Actinidia chinensis(EERAC) and Evodiamine(Evo) on colon carcinoma SW480 cells,and investigate their regulation of CCR7 expression and the underlying mechanism in colon carcinoma.Methods Radix of Actinidia chinensis was extracted by ethanol.MTT assay and growth curve method were used to detect the inhibition of SW480 cells after being treated with EERAC and Evo.RT-PCT and Western-blot were used to detect the CCR7 expression regulated by EERAC and Evo at the level of protein and mRNA respectively in SW480 cells.Results MTT results showed that EERAC and Evo significantly inhibited the growth of SW480 cells with obvious time-and dose-dependent effect.The 50% inhibitory concentration(IC50) of EERAC was 9.14 mg/mL,while the IC50 of Evo was 2.11 μg/mL.RT-PCR results showed that the expression of CCR7 mRNA in EERAC and Evo group was 29.99% and 18.03% respectively,which was obviously lower than that(56.27%) in control group.Western-blot proved that the expression of CCR7 protein in EERAC and Evo group was 29.03% and 15.28% respectively,which was also significantly reduced when compared to that of 42.48% in control group.Conclusion Ethanol extract from radix of Actinidiae chinensis and Evodiamine could effectively inhibit proliferation and growth of SW480 cells,significantly down-regulate the functional expression of CCR7,and thereby suppress the tumor metastasis.

Combination of Evodiamine with Berberine Reveals a Regulatory Effect on the Phenotypic Transition of Colon Epithelial Cells Induced by CCD-18Co

Objective Transdifferentiation exists between stromal cells or between stromal cells and cancer cells.Evodiamine and berberine are predominant pharmacological components of Zuojin pill,a prescription of Traditional Chinese Medicine,playing crucial functions in remolding of tumor microenvironment.This study aimed to explore the effect of combination of evodiamine with berberine(cBerEvo)on the phenotypic transition of colon epithelial cells induced by tumor-associated fibroblasts,as well as the involved mechanisms.Methods Human normal colon epithelial cell line HCoEpiC cells were treated with the prepared conditioned medium of CCD-18 Co,a human colon myofibroblast line,to induce epithelial-mesenchymal transition.Phase contrast microscope was used to observe the morphological changes.Epithelial-mesenchymal transition markers including E-cadherin,vimentin and alpha-smooth muscle actin(α-SMA)were observed with immunofluorescence microscopy.Migration was assessed by wound healing assay.Western blotting was used to detect the expressions of E-cadherin,vimentin,α-SMA,Snail,ZEB1 and Smads.Results In contrast to the control,the tumor-associated fibroblasts-like CCD-18 Co cells induced downregulation of E-cadherin and up-regulation of vimentin,α-SMA,Snail and ZEB1(P<0.05),and promoted migration of HCoEpiCs(P<0.05),with over expression of Smads including Smad2,p-Smad2,Smad3,p-Smad3 and Smad4(P<0.05),which were abolished by a transforming growth factor-β(TGF-β)receptor inhibitor LY364947 and by cBerEvo in a concentration dependent manner.In addition,cBerEvo-inhibited ratios of p-Smad2/Smad2 and p-Smad3/Smad3 were also dose dependent.Conclusion The above results suggest that cBerEvo can regulate the differentiation of colon epithelial cells induced by CCD-18 Co through suppressing activity of TGF-β/Smads signaling pathway.

Evodiamine derivatives improve cognitive abilities in APP^(swe)/PS1^(ΔE9) transgenic mouse models of Alzheimer's disease

Background: Alzheimer's disease(AD) is a complex neurodegenerative disease. Due to the complexity of its molecular pathogenesis and the interaction of the numerous factors involved, the etiology and pathogenesis of AD have not been fully elucidated. Therefore, effective treatment for AD remains to be developed. Evodiamine, a quinolone alkaloid, has been found to improve learning and memory ability to in the APP^(swe)/PS1^(ΔE9) mouse model of dementia. However, the cytotoxicity and physicochemical properties of evodiamine have limited its use in the treatment of AD.Methods: Evodiamine and its derivatives were effectively synthesized by EDCImediated condensation at room temperature. These target compounds contained 1 thio-and 21 oxo-evodiamine derivatives with different substituted groups. The cytotoxicity of evodiamine and its derivatives and the neuroprotective effects of the evodiamine derivatives against H_2O_2-induced cell loss in SH-SY5 Y cells were investigated using the WST-8 assay. The Morris water-maze test was used to detect the effect of evodiamine and its derivatives on improving learning and memory in APP^(swe)/PS1^(ΔE9) mice.Results: In this study, a series of oxo-and thio-evodiamine derivatives was synthesized. Several derivatives showed lower cytotoxicity and stronger neuroprotective effects than evodiamine and elicited enhanced cognitive improvement, especially in the test of spatial memory in APP^(swe)/PS1^(ΔE9) mice.Conclusion: Our study provides insights for developing novel evodiamine derivatives for chemical intervention and treatment of AD.

Evodiamine activates cellular apoptosis through suppressing PI3K/AKT and activating MAPK in glioma

OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de.veloping new agents to treat GBM is important.This study aimed to evaluate the anti-tumor effect of evodiamine(Evo) on GBM cells,and to determine the underlying mechanisms involved.METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo.diamine(0-10 μmol·L^(-1)) for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS) production was detected using dichlorofluorescein diacetate(DCFH-DA) staining.The changes in mitochondrial mem.brane potential(MMP) were assessed by JC-1 after cells were treated with evodiamine.The expres.sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c,Caspase-3,cleaved Caspase-3,PRAP,and cleaved PARP were measured by Western blot analy.ses.RESULTS According to MTT assay results,Evo significantly inhibited the cell proliferation in a time-and dose-dependent manner.Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species(ROS) production and mitochondrial membrane potential(MMP) disruption.Finally,Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos.phorylation(p38 and JNK,but not ERK) to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas.pase-3,and PARP).CONCLUSION In summary,Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.

Research progress on the mechanism of evodiamine against gastrointestinal tumor

Evodiamine is an indole quinazoline alkaloid with anti-tumor activity,which may be developed into a drug for the treatment of tumor.It was found that evodiamine could inhibit or even block the signal pathways of Wnt/β-catenin,mTOR,NF--κB,PI3K/AKT,Hippo-YAP and BMP in many kinds of cancer cells,thus interfering with cell division and differentiation,increasing the rate of apoptosis,and down-regulating the expression of various cancer cell markers.Such as B-cell lymphoma 2(Bcl-2),B-cell lymphoma super-large(Bcl-XL),cyclooxygenase 2(COX-2),Survivin,vascular endothelial growth factor(VEGF)and matrix metallopeptidase 9(MMP-9),which have a strong inhibitory effect on asymmetric division,malignant proliferation and angiogenesis of tumor cells.This paper summarizes evodiamine in digestive system tumors by regulating Wnt/β-catenin,mTOR,PI3K/AKT,BMP and other signal pathways,interfering with cell division,differentiation and apoptosis,inhibiting the expression of tumor-related marker genes,and preventing tumor cell migration and invasion,so as to provide a basis for the clinical application and further research of evodiamine in the future.

Antitumor Activity and Theoretical Calculation of Evodiamine and Rutaecarpine

The antitumor activities of two alkaloids, evodiamine（EVO） and rutaecarpine（RUT）, against MCF-7, SMMC-7721 and SW-1353 cells growth in vitro were investigated by MTT assay. The results showed that the anti-tumor effects of two alkaloids were remarkably different. In order to discover the relationship of antitumor activity and structures of the compounds, the dihedral angle, Natural Electron Configuration, frontier molecular orbital profiles（HOMO, LUMO）and bandgaps of these two compounds have been studied based on density functional theory（DFT）by means of DFT-B3LYP/6-31G（d） in Gaussian 03. The calculation results of dihedral angle showed that EVO, due to the existence of methyl group attached to the N（14） atom, have non-planar and twisted structures, which decrease the stability of EVO and increase the activity of EVO. Furthermore, the bandgaps of RUT are lower than that of EVO, indicating RUT has higher stability than EVO, so the activity of EVO is higher than that of RUT. In addition, the negative charge of N14 atom in EVO is lower than that of in RUT, so the positive charge of N（14） atom in EVO is higher than that of in RUT, which suggests that the nucleophile is easier to aggress the N（14） atom in EVO than that in RUT, so the reason of the different antitumor activities of EVO and RUT may be attacked by nucleophile.

A new strategy of enhancing absorptivity and safety for evodiamine: polyamidoamine derivatives modified by polyethylene glycol chain

Background:Traditional Chinese medicine involves complex ingredients and mixtures of ingredients that often exhibit low bioavailability,and excipients are often lacking to increase the absorption-enhancing effects.This study modified the generation 4 polyamidoamine dendrimer with polyethylene glycol of different molecular weights(5000,2000,1000)to form a series of polyamidoamine-co-polyethylene glycol(PAMAM-co-PEG)as a novel class of oral absorption enhancers.Evodiamine,the major alkaloid found in the traditional Chinese medicine Wu Zhu Yu(Fructus Evodiae),was used as a model drug to verify the absorption-enhancing effects and the safety of this alkaloid.Methods:This study utilized the solubility determination method documented in the Pharmacopoeia of the People’s Republic of China(2015 edition)and the D0 values recommended in the US FDA guidelines to comprehensively evaluate the solubility of evodiamine.The permeability of evodiamine was assessed using the apparent permeability coefficient in experiments based on in vitro cell models.Multiple aspects of the biological safety of PAMAM-co-PEG were explored using the MTT assay,LDH assay,and total protein release of the rat intestinal tract.Moreover,the absorption-enhancing effects of PAMAM-co-PEG at different molecular weights on evodiamine were verified via the use of in vitro cell models and in vivo intestinal loop circulation experiments with rats.Results:Evodiamine exhibited low solubility and permeability and was classified into class IV compounds using the biopharmaceutical classification system.PAMAM-co-PEG 2000 demonstrated improvement in the biosafety and absorption-enhancement effect of evodiamine at a specific concentration.This study showed that 0.05%(w/v)of PAMAM-co-PEG 2000 increased the cumulative penetration of evodiamine via cell transport by 1.32 times,and 0.10%(w/v)of PAMAM-co-PEG 2000 increased the area under curve value of evodiamine by 1.31 times.Conclusion:Evodiamine possesses low solubility and permeability and leads to poor oral bioavailability and a certain degree of cytotoxicity.PAMAM-co-PEG 2000 was found to be a potentially safe and efficient oral absorption enhancer.The results of this study might create a foundation for the development of novel excipients suitable for the complex active ingredients of traditional Chinese medicine.

Theoretical development and mechanism research of evodiamine's antitumor effect

Evodiamine(EVO),one of the bioactive components of traditional Chinese medicine,has been widely concerned for its anti-tumor properties in recent years.In this review,the anti-tumor mechanism of EVO was reviewed from the aspects of inducing tumor cell apoptosis(internal pathway,external pathway and other pathways),inducing autophagy,inhibiting tumor stem cells,inhibiting cell proliferation and migration,inhibiting peripheral vascular proliferation,and recent research progress of EVO anti-tumor drugs.

Regulatory effects of evodiamine on glucose metabolism-related factors in CT26 colorectal carcinoma-bearing mice

Objective:To investigate the therapeutic effect of evodiamine(EVO)on the expression of hexokinase(HK),lactate dehydrogenase A(LDHA),and pyruvate kinase M(PKM),key enzymes of glycolysis,in the tumor-bearing mice after modeling mouse colon cancer cells(CT26).Methods:A tumor-bearing mouse model was generated by administering axillary injection of CT26 and intraperitoneally injecting different doses of EVO.The therapeutic effects of EVO on CT26 tumor-bearing mice were evaluated by measuring the thymus and spleen indices,tumor volume,tumor suppression rate,and other related indicators in the tumor tissues of mice in each group after the administration of EVO,in addition,histopathological changes in the tumor tissues of the mice in the groups were studied by hematoxylin and eosin staining.The expression levels of HK,LDHA,and PKM in the tumor tissues of each group of mice were measured by performing Western blot to investigate the mechanism of EVO treatment in CT26 tumor-bearing mice.Results:EVO inhibited the growth of tumors in CT26-bearing mice and enhanced their splenic and thymic indices.Western blot results showed that EVO reduced the expression levels of HK,LDHA,and PKM proteins in the tumor tissues of CT26 tumor-bearing mice.Conclusion:EVO has a therapeutic effect on CT26 tumor-bearing mice,and its mechanism of action may be related to the low expression of key enzymes HK,LDHA and PKM of glycolysis in tumor tissues.

EVO切丝机刀辊轴承动力学建模与振动响应分析

为了探究EVO切丝机刀辊轴承的振动特性,以圆柱滚子轴承为研究对象,考虑时变位移和Hertz接触,建立了含外滚道缺陷的圆柱滚子轴承四自由度动力学模型。通过求解动力学微分方程组,获得了仿真振动响应信号,分析了仿真信号特征并验证了模型的可行性。最后研究了不同转速对轴承振动响应的影响,研究表明,轴承振动幅值会随转速的增大而增大,为EVO切丝机刀辊轴承的状态监测提供了理论指导。

基于DIALux evo的坝内廊道照明系统优化方法与应用

以隔河岩水电站为例,探索通过技术改造实现坝内廊道照明系统的优化。经研究发现,适当调高坝内廊道照度标准,运用DIAlux evo软件对坝内廊道开展精细化照明设计;根据数值模型的计算结果不断优化评估,选择出最优方案并予以实施;将设计值与实测值对比分析,证明了照明系统的优化设计准确度较高,大幅提升了照明质量和用电效率,实现了节能环保绿色照明目的,可供类似照明工程参考。

基于DIALux evo的中型车库入口照明设计

针对中型车库入口照明中出现的黑洞和白洞效应,以及24h常亮照明耗能高的问题,文章通过利用DIALux evo软件完成对中型车库入口的建模,通过分段设计并建立4种不同场景模式,完成对中型车库入口的照度设计。仿真结果表明,该项设计能满足分段多场景下的照度要求,与采用同类型LED灯在常亮模式下的单日耗能进行对比,节能效果明显。

ARRI发布高级稳定云台产品360 EVO横滚轴支持360°旋转

ARRI日前发布了全新一线产品——360 EVO稳定云台。继SRH-360遥控稳定云台成功上市后,360 EVO稳定云台设计更加稳健,同时具备横滚轴与摇摄轴360度旋转功能,以及遥控功能。为剧集、广告和MV摄制打开全新可能。将云台安装在悬臂上,或直播现场摄影机上,还能拍摄更加动感的横滚轴镜头。

Truview^(TM)EVO_2光学喉镜与Macintosh直接喉镜用于颈椎手术患者气管插管的比较

目的:在颈椎手术患者中比较Truview^(TM)EVO_2光学喉镜与Macintosh直接喉镜在经口气管插管时对喉部结构的显露效果。探讨该光学喉镜在此类患者中的应用价值。方法:100例颈椎手术患者,随机分为A、B两组.每组50例.麻醉诱导后A组先用Macintosh直接喉镜显露喉部结构并记录Cormack—Lehane分级(C/L分级),不插管。再改用Truview^(TM)EVO_2光学喉镜显露喉部结构并插入气管导管。B组先用光学喉镜显露声门,再使用直接喉镜显露喉部结构并插管。观察指标包括患者术前一般情况及气道评估指标(体质指数、甲颏间距、下颌支长度、张口度、颈部活动度,Mallampati分级).喉镜显露的C/L分级.插管时间.喉镜力量,显露难度和插管并发症。结果:A、B两组间比较,一般情况、术前气道评估指标、C/L分级和插管时间均无显著性差异,而喉镜力量A组显著低于B组(P<0.05),即Truview^(TM)EVO_2光学喉镜插管时力量小于直接喉镜;光学喉镜的C/L分级(Ⅰ级:Ⅱ级;Ⅲ级为69:26:5)显著优于直接喉镜(Ⅰ级:Ⅱ级:Ⅲ级为26:46:28,P<0.001);光学喉镜显露困难有5%,显著优于直接喉镜的28%(P<0.001);C/L分级、喉镜力量与术前气道评估指标的分级相关(P均<0.05)。结论:Truview^(TM)EVO_2光学喉镜对喉部结构的显露和插管力量均优于Macintosh直接喉镜,提示应用光学喉镜有助于颈椎手术患者的气管插管处理。

肥胖患者应用Truview^(TM) EVO_2光学喉镜行气管插管的应用

目的评价对肥胖并有插管困难的患者应用TruviewTM EVO2光学喉镜行气管插管的方法。方法经全身麻醉气管插管肥胖患者12例,入选标准为体质量指数大于或等于30,术前行气道评估,包括Mallampati评分,甲颏间距离和张口度。常规麻醉诱导经Macintosh直接喉镜无法完成气管插管的患者,气管插管困难明确后使用TruviewTM EVO2光学喉镜插管,记录诱导前、插管前、插管后的血流动力学变化,插管时间,喉部结构显露Cormack-Lehane分级,同时随访插管后咽痛等不良反应。结果插管后收缩压和心率均有增加。所有患者均一次插管成功,平均插管时间为62.3s(45~103s),12例患者中仅有1例两种喉镜Cormack-Lehane喉部结构显露分级相同,均为Ⅲ级,余11例TruviewTMEVO2光学喉镜Cormack-Lehane喉部显露分级优于Macintosh喉镜,2例患者气管导管进入声门较困难。除1例术后咽痛,其余无不良反应。结论TruviewTM EVO2光学喉镜对于肥胖并潜在插管困难患者是一种简便易行的插管装置。

EVO 150磁珠法提取基因组DNA用于STR分型

1材料与方法 564份日常案件现场提取的生物检材,包括各种载体如泥土、木屑、金属刀具、砖块、衣服上附着的血迹352份,经过雨水、踩踏等因素影响的烟蒂89份,咀嚼过的口香糖32份,精斑25份,以及从手套、

Truview EVO2喉镜用于模拟颈项强直患者气管插管的效果

目的评价Truview EVO2喉镜用于模拟颈项强直患者气管插管的效果。方法择期经口气管插管全麻手术患者100例,静脉麻醉诱导后使用硬质颈托固定其颈部,所有患者随机先后使用Truview EVO2喉镜和Macintosh喉镜显露喉部,并采用后一种喉镜辅助气管插管。记录Cormack-Lehane(C-L)分级,喉部结构显露时间,气管插管完成时间,一次插管成功率等。结果 Truview EVO2喉镜C-L分级显著优于Macintosh喉镜(P<0.05),喉部结构显露时间短于Macintosh喉镜(P<0.05),插管一次成功率显著高于Macintosh喉镜(P<0.05);但两种喉镜的气管插管完成时间差异无统计学意义。结论 Truview EVO2喉镜用于模拟颈项强直患者气管插管效果明显优于Macintosh喉镜,对于颈部活动受限患者具有很好的应用价值。

Truview^(TM) EVO_2光学喉镜和Macintosh直接喉镜经口气管插管时血流动力学反应的比较

目的:比较TruviewTM EVO2光学喉镜和Macintosh直接喉镜经口气管插管时的血流动力学反应。方法:80例ASA分级Ⅰ~Ⅱ级,年龄18~65岁,拟在经口气管插管全身麻醉下实施择期手术的患者,随机分为T组和M组2组,每组各40例患者。在静脉麻醉诱导后,T组和M组分别应用TruviewTM EVO2光学喉镜和Macintosh直接喉镜实施经口气管插管操作。记录麻醉诱导前(T0)、气管插管前(T1)、气管插管即刻(T2)、气管插管后1 min(T3)、3 min(T4)、5 min(T5)时的心率(HR)、收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)及脉搏血氧饱和度(SpO2),并记录喉部结构显露时间、插管完成时间。结果:两组患者除插管即刻(T2)的HR差异显著外(P<0.05),观察期内其他各对应时间点的血流动力学指标无显著性差异(P>0.05)。两组患者喉部结构显露时间差异无统计学意义(P>0.05);T组患者的气管插管完成时间较M组延长(P<0.05),但无超过60 s者。结论:TruviewTM EVO2光学喉镜和Macintosh直接喉镜经口气管插管可引起相似的血流动力学反应。

Truview EVO_2光学喉镜在预计困难气管插管患者中的应用

目的:观察Truview EVO2光学喉镜在预计困难气管插管患者中的应用效果。方法:100例预计有困难气管插管的患者,随机分为两组,每组50例。分别使用TruviewEVO2光学喉镜(T组)和McCoy喉镜(M组)在清醒镇静加表面麻醉下气管插管,记录气道声门暴露C/L(Cormack&Lehane)分级、气管插管操作时间(镜片插入到插管成功)、一次插管成功率、插管过程中出血率及气道损伤率及插管前后MAP、HR变化。结果:T组C/L分级Ⅰ、Ⅱ级例数多于M组、一次插管成功率高于M组,差异有统计学意义(P<0.05)。两组插管操作时间、出血及气道损伤例数及各时间点MAP、HR差异比较无统计学意义(P>0.05)。结论:TruviewEVO2光学喉镜具有声门显露好、插管成功率高的特点,可应用于困难气管插管的患者。

基于DIALux evo的车库照明设计方案优化研究

分析车库照明常用的照明光源及灯具特点:直管型荧光灯、直管型LED灯搭配控照型灯具及LED一体化支架灯;利用DIALux evo仿真软件搭建典型的车库建筑空间环境,验证传统常用车库照明设计方案的不足;以规范要求标准值为目标,利用仿真软件的仿真试验,得出典型车库照明的优化方案。