The inhibitory effect of transthyretin gene on growth of human hepatoma cells

Transthyretin(TTR) gene was highly expressed in normal liver and it has been found to be deleted in part of DNA samples from human hepatic cancer.Its mRNA expression was suppressed in most hepatoma samples.In order to study the biological effect of TTR gene on the growth of hepatoma cells,a recombinant vector containing TTR cDNA was constructed by pCMV,then it was transfected into hepatoma cell lines SMMC-7721 and Q3.It has been demonstrated that the inhibition of growth rate of TTR cDNA transfected hepatoma cells was about 50% in strength compared with that of the control.This inhibition was further enhanced when the transfected hepatoma cells were treated with all-trans retinoic acid.Hepatoma cells of cell lines PLC/PRF/5,SMMC-7721 and Q3 as well as hepatoma cells SMMC-7721 transfected with pCMV or pCMV-TTR were analyzed for TTR expression by Northern hybridization.The low level of TTR expression was found in both hepatoma cell lines and in SMMC-7721 cells transfected with pCMV alone.However,a remarkable TTR mRNA expression was observed in hepatoma SMMV-7721 cells transfected with pCMV-TTR.It seems possible that TTR gene might be a candidate of cancer suppressor gene for human hepatic cancer.     

人──板系统最佳蹬伸动作的控制模型及数值分析

本文基于Hanavan模型和人体测量学参数,以人体各环节间的相对运动作为控制量,建立了人-板系统中起跳蹬伸动作的数学模型,给出了模型的数值计算方法,在此基础上给出了实现最佳蹬伸用力过程的计算实验途径与运动技术诊断方法。     

Dieckol,a natural polyphenolic drug,inhibits the proliferation and migration of colon cancer cells by inhibiting PI3K,AKT, and mTOR phosphorylation

This study investigated that dieckol (DKL), a natural drug, inhibits colon cancer cell proliferation and migration by inhibiting phosphoinositide-3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) phosphorylation in HCT-116 cells. The cells were treated with DKL in various concentrations (32 and 50 μM) for 24 h and then analyzed for various experiments. MTT (tetrazolium bromide) and crystal violet assay investigated DKL-mediated cytotoxicity. Dichlorodihydrofluorescein diacetate staining was used to assess the reactive oxygen species (ROS) measurement, and apoptotic changes were studied by dual acridine orange and ethidium bromide staining. Protein expression of cell survival, cell cycle, proliferation, and apoptosis protein was evaluated by western blot analysis. Results indicated that DKL produces significant cytotoxicity in HCT-116, and the half-maximal inhibitory concentration was found to be 32 μM for 24-h incubation. Moreover, effective production of ROS and enhanced apoptotic signs were observed upon DKL treatment in HCT-116. DKL induces the expression of phosphorylated PI3K, AKT, and mToR-associated enhanced expression of cyclin-D1, proliferating cell nuclear antigen, cyclin-dependent kinase (CDK)-4, CDK-6, and Bcl-2 in HCT-116. In addition, proapoptotic proteins such as Bax, caspase-9, and caspase-3 were significantly enhanced by DKL treatment in HCT-116. Hence, DKL has been considered a chemotherapeutic drug by impeding the expression of PI3K-, AKT-, and mTOR-mediated inhibition of proliferation and cell cycle-regulating proteins.     

嗜黏蛋白阿克曼氏菌治疗疾病的潜力与作用机制研究进展

嗜黏蛋白阿克曼氏菌(Akkermansia muciniphila, AKK)可促进肠道黏液分泌,维持肠道黏液动态平衡,调节肠黏膜屏障功能,在机体代谢调节、免疫应答中发挥重要作用。AKK对肠道炎症、神经炎症、机体代谢紊乱和癌症等疾病具有显著改善作用,被视为极具潜力的下一代益生菌。本文分别从消化系统、神经系统、代谢性紊乱和癌症等角度入手,系统概述AKK在疾病治疗中的潜力及作用分子机制。     

黔西水城晚二叠世长兴期钙藻和有孔虫及其古环境意义

在黔西水城地区的K576井长兴组共鉴定钙藻3属3种,包括Gymnocodium bellerophontis、Permocalculus sp.和Tauridiumkurdistanensis;有孔虫8属10种,其中(虫筳)类2属2种,有孔虫动物群主要由Reichelinasp.indet.、Nankinella sp.、Pachyphloia schwageri、Pachyphloia sp.、Geinitzina sp.、Nestellorella sp. indet.、Howchinella sp.、Hemigordius aff. saranensis、Hemigordius sp.和Midiella sp. indet.组成。将本井按照生物特征分为有孔虫-钙藻-介形虫组合、有孔虫-腕足类-介形虫组合、介形虫-双壳类-腹足类组合、有孔虫-钙藻-双壳类组合、有孔虫-腕足类-介形虫组合、有孔虫-钙藻-双壳类组合和介形虫组合等7个组合。按照层序地层划分、垂向沉积序列特征和测井资料的分析,有孔虫-钙藻-介形虫组合(SQ3-3)和有孔虫-腕足类-介形虫组合(SQ3-4)时期地层为三角洲前...     

The potato StMKK5-StSIPK module enhances resistance to Phytophthora pathogens through activating the salicylic acid and ethylene signalling pathways

Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in plant responses to both biotic and abiotic stress. A screen of a Nicotiana benthamiana cDNA virus-induced gene silencing (VIGS) library for altered plant responses to inoculation with Phytophthora infestans previously identified an NbMKK gene, encoding a clade D MAPKK that we renamed as NbMKK5, which is involved in immunity to P. infestans. To study the role of the potato orthologous gene, referred to as StMKK5, in the response to P. infestans, we transiently overexpressed StMKK5 in N. benthamiana and observed that cell death occurred at 2 days postinfiltration. Silencing of the highly conserved eukaryotic protein SGT1 delayed the StMKK5-induced cell death, whereas silencing of the MAPK-encoding gene NbSIPK completely abolished the cell death response. Further investigations showed that StMKK5 interacts with, and directly phosphorylates, StSIPK. Furthermore, both StMKK5 and StSIPK trigger salicylic acid (SA)- and ethylene (Eth)-related gene expression, and co-expression of the salicylate hydroxylase NahG with the negative regulator of Eth signalling CTR1 hampers StSIPK-triggered cell death. This observation indicates that the cell death triggered by StMKK5-StSIPK is dependent on the combination of SA- and Eth-signalling. By introducing point mutations, we showed that the kinase activity of both StMKK5 and StSIPK is required for triggering cell death. Genetic analysis showed that StMKK5 depends on StSIPK to trigger plant resistance. Thus, our results define a potato StMKK5-SIPK module that positively regulates immunity to P. infestans via activation of both the SA and Eth signalling pathways.     

来源于嗜热氢化杆菌的新型对苯二甲酸双(羟乙)酯水解酶的表达纯化与酶学性质

石化来源的聚对苯二甲酸乙二酯(polyethylene terephthalate,PET)被广泛用于矿泉水瓶、食品包装和纺织品等领域,因其在自然界中不易分解,大量使用后的PET废弃物造成了严重的环境污染与资源浪费。使用生物酶法对PET废弃物进行解聚,并对解聚产物进行升级循环利用是进行塑料污染治理的重要方向之一,其中关键的是PET水解酶的解聚效率。对苯二甲酸双(羟乙基)酯(bis(hydroxyethyl)terephthalate,BHET)是PET生物酶解的中间产物,其累积是限制PET水解酶催化效率的一个重要因素,BHET水解酶和PET水解酶的联用能提升PET的整体水解效率。来源于嗜热氢化杆菌(Hydrogenobacter thermophilus)的双烯内酯酶(HtBHETase)对BHET有显著水解效果,将该酶在大肠杆菌(Escherichia coli)中进行重组表达并纯化后,对其酶学性质进行了研究。结果显示,HtBHETase对短碳链的酯类如对硝基苯酚乙酸酯催化活性较高,HtBHETase以BHET为底物时的最适反应pH值和最适反应温度分别为5.0和55℃;该酶有较好的热稳定性,经80℃的条件处理1 h仍能保持80%以上活性,显示出了良好的热稳定性,HtBHETase有在PET塑料生物解聚中使用的潜力,本研究为推动生物酶法降解PET提供了新的参考。     

-cyano-substituted analogoues of decarboxylated S-adenosylmethionine as enzyme activated, irreversible inhibitors of S-adenosylmethionine decarboxylase

A pair of -cyano analogues of decarboxylated S-adenosylmethionine (2a and 2b) were synthesized as potential enzyme activated, irreversible inhibitors of the[pyruvoyl enzyme S-adenosylmethionine decarboxylase (AdoMet-DC). Each of these analogues acts as an irreversible inactivator for ADoMet-DC from Escherichia coli (IC₅₀ values of 9 and 50 μM, respectively). These analogues also inactivate human AdoMet-DC, with K_I values of 246.6 and 7.2 μM, and k_inact values of 0.29 and 0.03 min⁻¹, respectively.     

Preparation of the pure diastereomeric forms of S- (5′-deoxy-5′-adenosyl)-1-ammonio-4-methylsulfonio-2- cyclopentene and their evaluation as irreversible inhibitors of S-adenosylmethionine decarboxylase from Escherichia coli

The conformationally restricted S-adenosylmethionine analogue AdoMac (S-(5′-deoxy-5′-adenosyl)-1-ammonio-4-methylsulfonio-2-cyclopentene has been shown to act as an enzyme activated, irreversible inhibitor of theEscherichia coli form of the enzyme S-adenosylmethionine decarboxylase. Inactivation of the enzyme is presumably initiated by formation of an imine linkage between the inhibitor and the terminal pyruvate of the enzyme, followed by base-catalyzed elimination of methylthioadenosine and generation of a latent electrophile. Removal of the driving force for the elimination of methylthioadenosine resulted in a reversibly binding inhibitor. Thus, the thioether analogue corresponding to AdoMac, and the corresponding dihydro derivative (H₂-AdoMac), reversibly inhibit the enzyme. AdoMac was resolved into its four pure diastereomeric forms, and each diastereomer was evaluated as an irreversible inhibitor of the enzyme. The K_I values for the individual diastereomers range between 3.83 and 39.6 μM, with the cis-1S,4R diastereomer being the most potent inhibitor. However, the k_inact values for the four diastereomers are not significantly different, suggesting that the binding of each diastereomer to the enzyme is configuration-dependent, while the subsequent inactivation likely proceeds through a single intermediate which is formed from each of the four diastereomers. Since each pure diastereomer represents a distinct conformational mimic exhibiting restricted sidechain rotation, the data suggests that these and related analogues may be useful as conformational probes for the catalytic site of AdoMet-DC.