Tumor extracellular acidity-activated nanoparticles as drug delivery systems for enhanced cancer therapy

pH-responsive nanoparticles (NPs) are currently under intense development as drug delivery systems for cancer therapy. Among various pH-responsiveness, NPs that are designed to target slightly acidic extracellular pH environment (pH_e) of solid tumors provide a new paradigm of tumor targeted drug delivery. Compared to conventional specific surface targeting approaches, the pH_e-targeting strategy is considered to be more general due to the common occurrence of acidic microenvironment in solid tumors. This review mainly focuses on the design and applications of pH_e-activated NPs, with special emphasis on pH_e-activated surface charge reversal NPs, for drug and siRNA delivery to tumors. The novel development of NPs described here offers great potential for achieving better therapeutic effects in cancer treatment.     

Salvianolic acid A reverses paclitaxel resistance in human breast cancer MCF-7 cells via targeting the expression of transgelin 2 and attenuating PI3 K/Akt pathway

Chemotherapy resistance represents a major problem for the treatment of patients with breast cancer and greatly restricts the use of first-line chemotherapeutics paclitaxel. The purpose of this study was to investigate the role of transgelin 2 in human breast cancer paclitaxel resistance cell line (MCF-7/PTX) and the reversal mechanism of salvianolic acid A (SAA), a phenolic active compound extracted from Salvia miltiorrhiza. Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) indicated that transgelin 2 may mediate paclitaxel resistance by activating the phosphatidylinositol 3-kinase (PI3 K)/Akt signaling pathway to suppress MCF-7/PTX cells apoptosis. The reversal ability of SAA was confirmed by MTT assay and flow cytometry, with a superior 9.1-fold reversal index and enhancement of the apoptotic cytotoxicity induced by paclitaxel. In addition, SAA effectively prevented transgelin 2 and adenosine-triphosphate binding cassette transporter (ABC transporter) including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), and breast cancer resistance protein (BCRP) up-regulation and exhibited inhibitory effect on PI3 K/Akt signaling pathway in MCF-7/PTX cells. Taken together, SAA can reverse paclitaxel resistance through suppressing transgelin 2 expression by mechanisms involving attenuation of PI3 K/Akt pathway activation and ABC transporter up-regulation. These results not only provide insight into the potential application of SAA in reversing paclitaxel resistance, thus facilitating the sensitivity of breast cancer chemotherapy, but also highlight a potential role of transgelin 2 in the development of paclitaxel resistance in breast cancer.     

Overexpression of CaDSR6 increases tolerance to drought and salt stresses in transgenic Arabidopsis plants

The partial CaDSR6 (Capsicum annuum Drought Stress Responsive 6) cDNA was previously identified as a drought-induced gene in hot pepper root tissues. However, the cellular role of CaDSR6 with regard to drought stress tolerance was unknown. In this report, full-length CaDSR6 cDNA was isolated. The deduced CaDSR6 protein was composed of 234 amino acids and contained an approximately 30 amino acid-long Asp-rich domain in its central region. This Asp-rich domain was highly conserved in all plant DSR6 homologs identified and shared a sequence identity with the N-terminal regions of yeast p23^fyp and human hTCTP, which contain Rab protein binding sites. Transgenic Arabidopsis plants overexpressing CaDSR6 (35S:CaDSR6-sGFP) were tolerant to high salinity, as identified by more vigorous root growth and higher levels of total chlorophyll than wild type plants. CaDSR6-overexpressors were also more tolerant to drought stress compared to wild type plants. The 35S:CaDSR6-sGFP leaves retained their water content and chlorophyll more efficiently than wild type leaves in response to dehydration stress. The expression of drought-induced marker genes, such as RD20, RD22, RD26, RD29A, RD29B, RAB18, KIN2, ABF3, and ABI5, was markedly increased in CaDSR6-overexpressing plants relative to wild type plants under both normal and drought conditions. These results suggest that overexpression of CaDSR6 is associated with increased levels of stress-induced genes, which, in turn, conferred a drought tolerant phenotype in transgenic Arabidopsis plants. Overall, our data suggest that CaDSR6 plays a positive role in the response to drought and salt stresses.     

桉树幼苗对难溶性磷的吸收及其根系对低磷胁迫的响应

以‘广林9号’桉树幼苗为试验材料,采用水培和土培试验方法研究了桉树幼苗对难溶性磷酸盐的吸收及其在低磷胁迫下的根构型和根系的生理反应,以揭示桉树高效吸收磷素的机制。结果显示:(1)桉树幼苗在含磷酸铝的缺磷培养液中吸收的磷达4.24mg/株,与供应水溶性磷和磷酸钙处理的相当。(2)土壤缺磷或仅在上土层(0~20cm)施磷肥处理均有利于桉树幼苗浅层根的分布,使根表面积及根数在上土层与下层(20~40cm)比值明显增高。(3)桉树幼苗根尖的H+-ATPase活性在缺磷处理15d后显著提高,其根尖周围的溴甲酚紫指示剂变黄,根基环境明显酸化;根尖分泌的酸性磷酸酶活性在低磷胁迫也显著提升,且随着处理时间(10、15、20d)的延长而进一步提高;铝和低磷胁迫能明显诱导桉树根系分泌草酸,其分泌量显著高于对照和缺磷处理。研究结果表明,桉树幼苗具有较强的难溶性磷吸收能力,而在缺磷及磷铝胁迫下根系的浅层化、根尖酸化及根分泌的酸性磷酸酶及草酸量增加可能是桉树幼苗适应酸性土壤铝毒和缺磷环境的重要机制。     

MBD结构域和SRA结构域识别甲基化DNA的结构机理

DNA胞嘧啶5-甲基化修饰是表观遗传重要的修饰之一,其对基因表达的调控依赖下游的识别蛋白识别和传递甲基化信号.本文围绕两种主要的甲基化DNA识别结构域——MBD结构域和SRA结构域,综述了它们识别不同修饰形式DNA的结构基础以及发挥功能的分子机理.     

中华金叶榆子代苗光合特性及叶片呈色机制探讨

中华金叶榆是普通白榆的天然黄叶突变体,黄叶性状在子代中可稳定遗传,自由授粉子一代出现黄绿性状分离。该研究以中华金叶榆子代黄叶苗和绿叶苗为试验材料,从生长速率、叶片色素含量、光合特性、叶绿素荧光及叶绿体超微结构等方面对黄叶苗的光合特性和叶片呈色机制进行了探讨。结果显示:(1)黄叶苗生长缓慢,净光合速率(12.5μmol·m-2·s-1)显著低于绿叶苗(17.5μmol·m-2·s-1),而蒸腾速率、气孔导度和叶片温度显著高于绿叶苗。(2)黄叶苗和绿叶苗叶片的光合色素种类基本相同,但黄叶苗的叶绿素a、叶绿素b、类胡萝卜素和花青素4种主要色素含量始终低于绿叶苗且相对稳定,各种色素含量在生育期内不同月份略有变化,类胡萝卜素含量始终低于叶绿素含量。(3)黄叶苗叶片光系统Ⅱ(PSⅡ)发育不完全,电子传递效率低。(4)黄叶苗叶绿体内膜系统发育紊乱,基粒垛叠失败。研究表明,中华金叶榆子代黄叶苗叶绿体内膜系统发育缺陷,基粒片层垛叠失败,进而多种色素含量大幅下降,光合系统发育不完全,致使其叶片呈现黄色、光合性能下降、植株生长缓慢。     

Design,synthesis and biological evaluation of hydroxy- or methoxy-substituted 5-benzylidene(thio) barbiturates as novel tyrosinase inhibitors

Here a new class of hydroxy- or methoxy-substituted 5-benzylidene(thio)barbiturates were designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed that several compounds had more potent tyrosinase inhibitory activities than the widely used tyrosinase inhibitor kojic acid (IC₅₀ = 18.25 μM). In particular, 3′,4′-dihydroxylated 1e was found to be the most potent inhibitor with IC₅₀ value of 1.52 μM. The inhibition mechanism analysis revealed that the potential compounds 1e and 2e exhibited such inhibitory effects on tyrosinase by acting as the irreversible inhibitors. Structure–activity relationships’ (SARs) analysis also suggested that further development of such compounds might be of interest.     

臭氧胁迫对植物主要生理功能的影响

近年来,由于光化学反应的臭氧前体增加,全球植物受对流层臭氧(O3)胁迫的程度越来越严重。臭氧污染被认为是造成东欧、西欧和整个美国的大片森林衰退和枯死的主要原因。臭氧胁迫严重影响植物叶片对光能的利用,通过气孔限制和非气孔限制,导致其光合速率的降低,影响光合产物的产量。臭氧对植物的影响与植物体内代谢物质的积聚量紧密联系。臭氧胁迫引发植物的各种防御保护机制,刺激抗氧化系统,影响膜系统,改变其体内碳和矿质养分的吸收并引起它们的重新分配,诱导其基因表达的深层变化。为了适应臭氧胁迫环境,植物通过生理生化机制的调节来保证其生命活动。如细胞通过调节渗透物质的含量来保持渗透势的平衡;细胞内各种抗氧化酶活性增加,以清除自由基,避免或者减轻细胞受到伤害;改变代谢途径以保持能量储备和降低代谢速率。可见,生态环境对生物进化具有重要影响。这个观点将在臭氧胁迫对植物生理的影响中得到证实,也是生物进化论的另一种证据。综述了臭氧对光合生理、呼吸代谢、抗氧化系统、膜系统、矿质养分的吸收和分配与分子生理等主要生理功能的影响,并提出臭氧胁迫对植物生理影响的今后研究方向与未来研究热点是:(1)加强在植物个体和群落水平上臭氧胁迫对植物生理影响的研究;(2)臭氧影响下植物的基因调控和相关信号传递网络系统的机理;(3)通过分子标记、基因图谱、基因组学和转基因技术等方法研究选育适应臭氧胁迫环境的植物;(4)尽可能在接近自然条件的环境中开展研究;(5)臭氧胁迫对亚热带和热带森林及其树种主要生理功能影响的研究;(6)建立模型评估臭氧对植物的影响。     

真菌对土壤N2O释放的贡献及其研究方法

N₂O是一种重要的温室气体,而土壤作为N₂O的重要来源之一,其N₂O主要产生于硝化和反硝化作用的生物过程.研究表明细菌和古菌是这些生物过程的主要参与者,然而在特定土壤生态系统中,真菌在N循环过程中起主要作用.但真菌对土壤N₂O释放贡献的研究报道甚少.本文阐述了土壤真菌N₂O产生机制的研究进展,介绍了自养硝化、异养硝化和反硝化过程的发生机理、关键微生物和功能基因.详细介绍了与真菌有关的N₂O产生过程,真菌的异养硝化作用和反硝化作用,并且比较了真菌和细菌反硝化系统的差异.此外,本文重点总结了研究土壤真菌N₂O产生的主要方法,包括选择抑制剂法、^15N标记、分离和纯培养以及免培养的分子生态学方法,对各种方法的优势和弊端进行了探讨,并对今后的研究工作提出了展望.