Cisplatin selects for CD133+cells in lung cancer cells

Objective Platinum-based chemotherapy is the first-line treatment for non-small cell lung cancer,but the chemoresistance of tumor cells continues to be a considerable challenge in the management of NSCLCs,leading to recurrence of most patients.CD133(prominin-1)is a five-transmembrane glycoprotein,and recent evidence suggests that CD133+cells are the cause of drug resistance and tumor recurrence.In this study,the correlation between cisplatin and CD133+cells was investigated systematically.Methods Four lung cancer cell lines,including A549,H460,801D and H1299,were treated with different concentrations of cisplatin.Cell viability was determined by MTT assay.Sphere-forming assay was performed to detect the capability of sphere-forming.CD133+cells was detected by BD FACScaliber flow cytometer.Results The results showed that cisplatin could increase the number of CD133+cells in both time-and dose-dependent manner.The enrichment would weaken but the proportion of CD133+cells was still higher than the basic level as incubation time extended after cisplatin was withdrawn.Compared with adherent culture,the proportion of CD133+cells was higher when the cells were maintained suspension culture.The proportion of CD133+cells significantly increased when cisplatin was provided in suspension culture.Conclusion These results revealed that cisplatin induces the enrichment of CD133+cells and CD133 is a new therapeutic target.Our data partially explained drug resistance to second-line chemotherapy in cisplatin-treated patients with NSCLCs.

Expression and significance of cyclooxygenase-2 in human lung cancer

Objective: We aimed to examine the expression of cyclooxygenase-2 and the relationship with the pathological types, TNM stage, lymph node metastasis, the degree of differentiation, smoking and the survival. Methods: Immunohistochemical staining method was used to examine the expression of cyclooxygenase-2 of 121 cases of lung cancer and three control groups. The data were statistically analyzed. Results: Compared with the health group, cyclooxygenase-2 was over expressed in the inflammatory tissue(P = 0.036), lung adenocarcinoma(P = 0.005) and squamous carcinoma(P = 0.047). Compared with patients without lymph node metastasis, cyclooxygenase-2 was over expressed(P = 0.033) in patients with lymph node metastasis. Compared with high differentiation group, cyclooxygenase-2 was over expressed(P = 0.004) in low differentiation group. Compared with non-smokers, the expression of cyclooxygenase-2 increased in smokers(P = 0.000). The median survival time of patients that the expression of cyclooxygenase-2 were negative was 9 months(95% CI, 5.6–12.4 months). The median survival time of patients that the expression of cyclooxygenase-2 were positive was 5 months(95% CI, 3–7 months). They was statistical difference(P = 0.001). Conclusion: Overexpression of cyclooxygenase-2 is associated with pathological types, TNM stage, lymph node metastasis, degrees of differentiation, smoking and prognosis in lung cancer.

PIF4 interacts with ABI4 to serve as a transcriptional activator complex to promote seed dormancy by enhancing ABA biosynthesis and signaling

Transcriptional regulation plays a key role in the control of seed dormancy,and many transcription factors(TFs)have been documented.However,the mechanisms underlying the interactions between different TFs within a transcriptional complex regulating seed dormancy remain largely unknown.Here,we showed that TF PHYTOCHROME-INTERACTING FACTOR4(PIF4)physically interacted with the abscisic acid(ABA)signaling responsive TF ABSCISIC ACID INSENSITIVE4(ABI4)to act as a transcriptional complex to promote ABA biosynthesis and signaling,finally deepening primary seed dormancy.Both pif4 and abi4 single mutants exhibited a decreased primary seed dormancy phenotype,with a synergistic effect in the pif4/abi4 double mutant.PIF4 binds to ABI4 to form a heterodimer,and ABI4 stabilizes PIF4 at the protein level,whereas PIF4 does not affect the protein stabilization of ABI4.Subsequently,both TFs independently and synergistically promoted the expression of ABI4 and NCED6,a key gene for ABA anabolism.The genetic evidence is also consistent with the phenotypic,physiological and biochemical analysis results.Altogether,this study revealed a transcriptional regulatory cascade in which the PIF4–ABI4 transcriptional activator complex synergistically enhanced seed dormancy by facilitating ABA biosynthesis and signaling.

蛋白质磷酸化修饰与种子休眠及萌发调控

种子休眠与萌发是截然不同而又紧密联系的两个生理过程,也是植物生命周期中的关键阶段,对自然状态下的植物物种繁殖与地理分布以及农业生产均具有重要意义,且两个过程受不同内源激素和环境信号之间的精确互作调控。大量研究表明,蛋白质磷酸化修饰作为一种重要的翻译后修饰方式,参与调控种子休眠与萌发以及植物逆境胁迫响应等过程并发挥重要作用。该文简要介绍了蛋白质磷酸化、去磷酸化修饰过程及其功能,系统总结了蛋白质磷酸化修饰在种子休眠与萌发过程中的调控作用,并展望了未来的研究方向。

microRNA-182抑制人角膜上皮细胞增殖和迁移

目的:通过体内动物实验与体外细胞实验来阐明microRNA-182(miR-182)在角膜上皮损伤修复中的功能。方法:实验研究。体内实验选取5只C57BL/6J野生型小鼠,通过机械刮伤法构建小鼠角膜上皮损伤修复模型作为实验组,对侧眼作为对照组,通过实时定量RT-PCR法检测miR-182在损伤修复过程(损伤后48h)的表达。体外实验采用脂质体介导的方法将miR-182和随机序列寡核苷酸链转染入人角膜上皮细胞(HCECs),通过细胞增殖实验(MTS法)和细胞克隆形成实验检测细胞增殖和生长能力,流式细胞术检测细胞周期,细胞划痕实验检测细胞迁移能力。MiR-182表达量及细胞实验各参数2组间比较采用独立样本t检验。结果:体内实验中,与对照组相比,实验组中5个样本量的miR-182在角膜上皮损伤修复过程中表达水平显著下调(t=147.6、79.2、136.8、41.3、89.8,均P<0.001)。体外实验中,miR-182组相对细胞数目为(81±5)%,与阴性对照组(100%)相比显著减少(t=6.6,P=0.003),同时miR-182组细胞克隆数明显少于阴性对照组。细胞周期检测结果显示实验组处于G1期细胞数量比例为(49±7)%,明显高于阴性对照组的(35±4)%(t=-3.0,P=0.041)。此外,细胞迁移实验结果显示miR-182组HCECs细胞迁移的距离为(99±12)μm,而阴性对照组的迁移距离为(213±14)μm(t=10.8,P=0.001),迁移速度明显变慢。结论:miR-182通过抑制角膜上皮细胞的增殖与迁移,从而对角膜上皮损伤修复起到负调控的作用。

Triptolide-loaded microemulsion-based hydrogels: physical properties and percutaneous permeability

Triptolide is a diterpenoid compound that inhibits the inflammation of rheumatoid arthritis(RA).However,the use of triptolide is limited due to its strong gastrointestinal toxicity.The purpose of this work was to develop a transdermal delivery system for triptolide to reduce this toxicity.A microemulsion-based hydrogel(MBH)was prepared from the combination of Gemseal 40-oleic acid as oil phase,Tween 80-labrasol as surfactant,anhydrous ethanol as co-surfactant,water as aqueous phase and Poloxamer 407 as hydrogel matrix.Rheological measurements,environmental scanning electron microscopy(ESEM)and transdermal experiments in vitro were used to characterize triptolide-loaded and blank MBH preparations.The effects of Poloxamer 407 and triptolide on the rheological properties and microstructures of the MBH were determined.Transparent and homogeneous MBH could only be formed when the concentration of Poloxamer 407 in the selected O/W microemulsion was in the range of 14.0–16.0%(w/w).When the concentration of Poloxamer 407 increased,the rheological properties such as the yield stresses(sy),storage and loss moduli(G′,G″)of the formulations increased,and the network structures became more compact.The addition of triptolide did not change the interconnected network structures of the MBH preparations.MBH preparations afford a better sustained release profile when compared to microemulsions,a finding confirmed by an in vitro permeation test in mice.MBH appears to be a promising vehicle for transdermal delivery of triptolide.

All-solid anti-resonant single crystal fibers

In this paper,a novel all-solid anti-resonant single crystal fiber(AR-SCF)with high refractive index tubes cladding is proposed.By producing the cladding tubes with high refractive index material,the AR guiding mechanism can be realized for the SCF,which can reduce the mode number to achieve single-mode or few-mode transmission.The influences of dif-ferent materials and structures on the confinement loss and effective guided mode number for wavelengths of 2-3μm are investigated.Then,the optimal AR-SCF structures for different wavelengths are determined.Furthermore,the influences of different fabrication errors are analyzed.This work would provide insight to new opportunities in the novel design of SCFs by AR,which would greatly impact the fields of laser application,supercontinum generation,and SCF sensors.