Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro

Aim:

To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro.

Methods:

The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The expression of proteins and phosphorylated kinases was detected using Western blotting.

Results:

Treatment of U251 and U87 cells with anisomycin (0.01–8 μmol/L) inhibited the cell growth in time- and concentration-dependent manners (the IC₅₀ values at 48 h were 0.233±0.021 and 0.192±0.018 μmol/L, respectively). Anisomycin (4 μmol/L) caused 21.5%±2.2% and 25.3%±3.1% of apoptosis proportion, respectively, in U251 and U87 cells. In the two cell lines, anisomycin (4 μmol/L) activated p38 MAPK and JNK, and inactivated ERK1/2. However, neither the p38 MAPK inhibitor SB203580 (10 μmol/L) nor the JNK inhibitor SP600125 (10 μmol/L) prevented anisomycin-induced cell death. On the other hand, anisomycin (4 μmol/L) reduced the level of PP2A/C subunit (catalytic subunit) in a time-dependent manner in the two cell lines. Treatment of the two cell lines with the PP2A inhibitor okadaic acid (100 nmol/L) caused marked cell death.

Conclusion:

Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit. The regulation of PP2A/C exression by anisomycin provides a clue to further study on its role in glioma therapy.     

中性粒细胞相关载脂蛋白表达与胃癌进展、转移及预后的关系

目的:探讨中性粒细胞相关载脂蛋白(NGAL)在胃癌组织中的表达及与胃癌进展、转移及预后的关系.方法:应用免疫组化法检测NGAL在102例胃癌、32例正常胃组织中的表达,分析其与胃癌临床病理特征及预后的关系.结果:NGAL在胃癌组织中的阳性表达率为56.9%,明显高于在正常胃组织中的21.9%(χ2>=11.938,P<0.01),不同胃癌组织学分型患者NGAL阳性表达差异有统计学意义(χ=10.180,P<0.05),胃癌患者NGAL表达与浆膜侵犯、TNM分期、淋巴结转移以及T分期呈正相关(r,分别为0.307、0.211、0.220、0.201,P<0.05或P<0.01). NGAL表达阳性组和阴性组5年累积生存率分别为24.3%和43.7%,差异有统计学意义(P=0.018).结论:NGAL在胃癌中表达上调,与胃癌进展和淋巴结转移显著相关,提示预后不良,可作为评价胃癌预后新的生物学指标.     

阿莫西林颗粒治疗小儿感染性疾病1983例

目的:评价阿莫西林颗粒(再林)对小儿感染性疾病的疗效及安全性.方法:采用随机对照开放试验,试验组1 983例,口服阿莫西林颗粒40～80mg·kg-1,tid;对照组693例,口服头孢拉定干混悬剂6.25～12.5mg·kg-1,tid,疗程7～14d.结果:试验组痊愈率和总有效率分别为69.49%和91.88%,优于对照组的35.93%和60.46%(P＜0.05);细菌清除率试验组96.67%,对照组83.33%,2组比较差异有极显著性(P＜0.01);不良反应发生率试验组1.46%,对照组4.91%,差异有极显著性(P＜0.01).结论:阿莫西林颗粒治疗儿科感染性疾病疗效较好,在服药前需详细询问青霉素及其他药物过敏史,首剂应在医护人员密切观察下服药.     

SFE-CGC法测定七宝美髯胶囊中补骨脂素和异补骨脂素的含量

目的 建立中成药七宝美髯胶囊中有效成分补骨脂素和异补骨脂素的含量测定方法。方法 采用超临界流体萃取(SFE)技术和毛细管气相色谱(CGC)非在线联用技术测定补骨脂素和异补骨脂素的含量,HP-5毛细管柱,FID检测器,蒽为内标。结果 SFE-CGC法测定七宝美髯胶囊中补骨脂素和异补骨脂素简便快速,结果准确可靠,加样回收率分别为97,76％(RSD2.31％),101.21％(RSD2.12％)。结论 SFE-CGC法可以作为七宝美髯颗粒质量控制的方法之一。     

路由监控分析系统的设计和实现

BGP和OSPF是目前网络中普遍使用的域间和域内路由协议,路由协议的运行状态直接影响网络性能.本文设计和实现了一个通用的路由监控分析系统,能实时收集路由信息,自动生成域间域内拓扑,提供历史拓扑信息的浏览和重放、拓扑图的比较、路由信息的解析和统计等功能,并能够分析路由收敛和稳定性,从而辅助网管人员掌握网络路由系统实时运行状况,做出相应的管理决策.     

Increasing nodal vulnerability and nodal efficiency implied recovery time prolonging in patients with supplementary motor area syndrome

Supplementary motor area (SMA) syndrome is a surgery‐related complication that commonly occurs after removing SMA glioma, and needs weeks to recover. However, susceptible factors of patients suffering from SMA syndrome remain unknown. Graphic theory was applied to reveal topological properties of sensorimotor network (SMN) by processing resting‐state functional magnetic resonance images in 66 patients with SMA gliomas. Patients were classified into SMA and non‐SMA groups based on whether they suffered from SMA syndrome. We collected recovery time and used causal mediation analysis to find association between topological properties and recovery time. Compared with the non‐SMA group, higher vulnerability (left: p = .0018; right: p = .0033) and lower fault tolerance (left: p = .0022; right: p = .0248) of the whole SMN were found in the SMA group. Moreover, higher nodal properties of lesional‐hemispheric cingulate cortex (nodal efficiency: left, p = .0389; right, p = .0169; nodal vulnerability: left, p = .0185; right, p = .0085) and upper limb region of primary motor cortex (PMC; nodal efficiency: left, p = .0132; right, p = .0001; nodal vulnerability: left, p = .0091; right, p = .0209) were found in the SMA group. Nodal efficiency and nodal vulnerability of cingulate cortex and upper limb region of PMC were important predictors for SMA syndrome occurring and recovery time prolonging. Neurosurgeons should carefully deal with upper limb region of PMC and cingulate cortex, and protect them if these two region were unnecessary to damage during SMA glioma resection.     

Numerical Analysis of Microcrack Propagation Characteristics and Influencing Factors of Serrated Structural Plane

The serrated structural plane is the basic unit of structural plane morphology. However, the understanding of its internal stress distribution, failure mode and crack evolution law was not clear enough in previous studies. In this paper, the shear mechanical properties of the serrated structural planes were studied by numerical simulation, and the crack evolution law of the serrated structural planes and the effects of four microscopic parameters on the shear properties were analyzed. The results show that: (1) the number of microcracks increases with the increase in normal stress; the crack expansion rate is slow before the shear stress reaches the peak. After the shear stress reaches the peak, the crack expansion rate continues to increase, and the microcracks keep sprouting and expanding, and the number of microcracks tends to stabilize when the shear stress reaches the residual shear strength. (2) The particle contact stiffness ratio kn∗/ks∗ and parallel bond stiffness ratio kn/ks were negatively correlated with the shear strength; and the particle contact modulus E and parallel bond modulus E∗ were positively correlated with the shear strength. As the particle contact modulus E and parallel bond modulus E∗ increase, the peak shear displacement gradually decreases. The parallel bond stiffness ratio kn/ks has a negative correlation with the peak shear displacement. This study is expected to provide theoretical guidance for the microscopic parameter calibration and shear mechanical analysis of serrated structural planes. (3) Several XGBoost, WOA-XGBoost, and PSO-XGBoost algorithms are introduced to construct the quantitative prediction model, and the comparative analysis found that WOA-XGBoost has the best fitting effect and can be used for the prediction of shear strength. When using this model to calculate the weight shares of micro-parameters, it was found that kn∗/ks∗ has the greatest influence on shear strength, followed by E∗; E and kn/ks had the least influence.     

IL-4/STAT6在变应性鼻炎豚鼠鼻黏膜的表达及鼻用糖皮质激素对其表达的影响

目的:研究IL-4/STAT-6在变应性鼻炎豚鼠鼻黏膜的表达和丙酸氟替卡松鼻喷雾剂对其表达的影响,进一步探讨变应性鼻炎的发病机制。方法:45只豚鼠随机分为对照组(NC组)、变应性鼻炎无干预组(AR组)和变应性鼻炎糖皮质激素干预组(Glu组),每组15只。其中AR、Glu组采用卵清白蛋白致敏法制备变应性鼻炎豚鼠模型;NC组用生理盐水替代卵清白蛋白进行同步处理。动物建模后用丙酸氟替卡松鼻喷雾剂(每次50μl/侧)治疗,每天2次,连续5d。观察各组大鼠行为学改变及鼻黏膜病理学改变,免疫组织化学法检测各组豚鼠鼻黏膜中IL-4、STAT6蛋白的表达并观察其变化情况及相关性。结果:与NC组比较,AR组豚鼠喷嚏及搔鼻次数明显增加,IL-4、STAT6表达增强;与AR组比较,Glu组激素干预后豚鼠喷嚏及搔鼻次数明显减少,IL-4、STAT6表达减弱,NC组与Glu组相比结果无明显差异。结论:IL-4/STAT6在Th2分化中起关键作用,丙酸氟替卡松鼻喷雾剂干预后可以通过影响IL-4/STAT6的表达发挥治疗作用。     

CDK4和p16在喉鳞状细胞癌中的表达

目的:探讨CDK4、p16在喉鳞状细胞癌中的表达。方法:采用免疫组织化学SP法检测30例喉鳞状细胞癌组织和20例癌旁组织中CDK4和p16的表达情况,并分析二者分别与喉鳞状细胞癌临床分期和病理分级的关系。结果:在喉鳞状细胞癌中CDK4、p16的表达率分别为63.3%、46.7%,在癌旁组织中CDK4、p16的表达率分别为25%、90%。CDK4在喉鳞状细胞癌中的表达高于癌旁组织(P<0.05),与病理分级、临床分期均无显著相关性(P>0.05);p16在喉鳞状细胞癌中的表达低于癌旁组织(P<0.05),与病理分级有相关性(P<0.05),与临床分期无显著相关性(P>0.05);CDK4与p16的表达呈负相关(rs=-0.786,P<0.05)。结论:p16的低表达和CDK4的高表达可能在喉鳞状细胞癌的发生发展中起重要作用,且p16的低表达可能作为判断肿瘤恶性程度的指标。     

Exosomes with FOXP3 from gene-modified dendritic cells ameliorate the development of EAE by regulating the balance of Th/Treg

Objective: To investigate the efficiency and potential mechanisms of exosomes from dendritic cells (DCs) transfected with Forkhead box protein P3 (FOXP3) in the development of experimental autoimmune encephalomyelitis (EAE).Method: Mouse bone marrow-derived immature DCs were loaded with adenovirus carrying FOXP3 gene, and exosomes were generated. Then the exosomes with FOXP3 (FOXP3-EXOs) were co-cultured with CD4+T cell in vitro to evaluate their potential on CD4+T cell proliferation and differentiation, and injected into EAE mice to assess their effects on the development of EAE.Result: FOXP3-EXOs were effective to inhibit the CD4⁺T cell proliferation and the production of Interferon gamma (IFN-γ), interleukin (IL)-6, and IL-17, while they promoted the production of IL-10 in vitro. Moreover, FOXP3-EXOs treatment significantly decreased the neurological scores, reduced the infiltration of inflammatory cells into the spinal cord, and decreased demyelination in comparison to saline and Con-EXOs treated EAE mice. Moreover, the FOXP3-EXOs treatment resulted in obvious increases in the levels of regulatory T (Treg) cells and IL-10, whereas levels of T helper 1 (Th1) cells, Th17 cells, IFN-γ, IL-6, and IL-17 decreased significantly in the splenocyte culture of EAE mice.Conclusion: The present study preliminarily investigated the effects and potential mechanisms of FOXP3-EXOs in EAE and revealed that the FOXP3-EXOs could inhibit the production of Th1 and Th17 cells and promote the production of Treg cells as well as ameliorate the development of EAE. The neuroprotective effects of FOXP3-EXOs on EAE are likely due to the regulation of Th/Treg balance.