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31.
To increase the beta-carotene (provitamin A) content and thus the nutritional value of Golden Rice, the optimization of the enzymes employed, phytoene synthase (PSY) and the Erwinia uredovora carotene desaturase (CrtI), must be considered. CrtI was chosen for this study because this bacterial enzyme, unlike phytoene synthase, was expressed at barely detectable levels in the endosperm of the Golden Rice events investigated. The low protein amounts observed may be caused by either weak cauliflower mosaic virus 35S promoter activity in the endosperm or by inappropriate codon usage. The protein level of CrtI was increased to explore its potential for enhancing the flux of metabolites through the pathway. For this purpose, a synthetic CrtI gene with a codon usage matching that of rice storage proteins was generated. Rice plants were transformed to express the synthetic gene under the control of the endosperm-specific glutelin B1 promoter. In addition, transgenic plants expressing the original bacterial gene were generated, but the endosperm-specific glutelin B1 promoter was employed instead of the cauliflower mosaic virus 35S promoter. Independent of codon optimization, the use of the endosperm-specific promoter resulted in a large increase in bacterial desaturase production in the T(1) rice grains. However, this did not lead to a significant increase in the carotenoid content, suggesting that the bacterial enzyme is sufficiently active in rice endosperm even at very low levels and is not rate-limiting. The endosperm-specific expression of CrtI did not affect the carotenoid pattern in the leaves, which was observed upon its constitutive expression. Therefore, tissue-specific expression of CrtI represents the better option. 相似文献
32.
Hai Hu Hong Li Feng Jiao Ting Han Meng Zhuo Jiujie Cui Yixue Li Liwei Wang 《Journal of hematology & oncology》2017,10(1):158
Background
Multiple primary cancers (MPC) have been identified as two or more cancers without any subordinate relationship that occur either simultaneously or metachronously in the same or different organs of an individual. Lynch syndrome is an autosomal dominant genetic disorder that increases the risk of many types of cancers. Lynch syndrome patients who suffer more than two cancers can also be considered as MPC; patients of this kind provide unique resources to learn how genetic mutation causes MPC in different tissues.Methods
We performed a whole genome sequencing on blood cells and two tumor samples of a Lynch syndrome patient who was diagnosed with five primary cancers. The mutational landscape of the tumors, including somatic point mutations and copy number alternations, was characterized. We also compared Lynch syndrome with sporadic cancers and proposed a model to illustrate the mutational process by which Lynch syndrome progresses to MPC.Results
We revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent. Integrative analysis showed that truncating mutations of DNA mismatch repair (MMR) genes were significantly enriched in the patient. A mutation progress model that included germline mutations of MMR genes, double hits of MMR system, mutations in tissue-specific driver genes, and rapid accumulation of additional passenger mutations was proposed to illustrate how MPC occurs in Lynch syndrome patients.Conclusion
Our findings demonstrate that both germline and somatic alterations are driving forces of carcinogenesis, which may resolve the carcinogenic theory of Lynch syndrome.33.
34.
Hai‐Yan Liu Huhe Chao Zhen‐Kun Liu Hong‐Fei Xia Zhihui Song Ying Yang Jing‐Pian Peng 《Journal of cellular and molecular medicine》2014,18(3):455-467
Cytochrome P450 26A1 (cyp26a1) is expressed in the mouse uterus during peri‐implantation. The repression of this protein is closely associated with a reduction in implantation sites, suggesting a specific role for cyp26a1 in pregnancy and prompting questions concerning how a metabolic enzyme can generate this distinct outcome. To explore the effective downstream targets of cyp26a1 and confirm if its role in peri‐implantation depends on its metabolic substrate RA (retinoic acid), we characterized the changes in the peripheral blood, spleen and uterine implantation sites using the cyp26a1 gene vaccine constructed before. Flow cytometry results showed a significant increase in CD4+RORγt+ Th17 cells in both the peripheral blood and spleen in the experimental group. The expression of RORγt and IL‐17 presented the Th17 cells reduction in uterus followed by the suppression of cyp26a1 expression. For greater certainty, cyp26a1 antibody blocking model and RNA interference model were constructed to determine the precise target immune cell group. High performance liquid chromatography results showed a significant increase in uterine at‐RA followed by the immunization of cyp26a1 gene vaccine. Both the ascertain by measuring RARα protein levels in peri‐implantation uterus after gene vaccine immunization and researches using the specific agonist and antagonist against RARα suggested that RARα may be the main RA receptor for signal transduction. These results provided more evidence for the signal messenger role of RA in cyp26a1 regulation from the other side. Here, we showed that the cyp26a1‐regulated Th17 cells are dependent on at‐RA signalling, which is delivered through RARα in mouse peri‐implantation. 相似文献
35.
Bo-Hwa Choi Souvik Chattopadhaya Le Nguyen Thanh Lin Feng Quoc Toan Nguyen Chuan Bian Lim Amaravadhi Harikishore Ravi Prakash Reddy Nanga Nagakumar Bharatham Yan Zhao Xuewei Liu Ho Sup Yoon 《PloS one》2014,9(10)
Microtubules are a highly validated target in cancer therapy. However, the clinical development of tubulin binding agents (TBA) has been hampered by toxicity and chemoresistance issues and has necessitated the search for new TBAs. Here, we report the identification of a novel cell permeable, tubulin-destabilizing molecule - 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [1p-tolyl-meth-(E)-ylidene]-hydrazide (termed as Suprafenacine, SRF). SRF, identified by in silico screening of annotated chemical libraries, was shown to bind microtubules at the colchicine-binding site and inhibit polymerization. This led to G2/M cell cycle arrest and cell death via a mitochondria-mediated apoptotic pathway. Cell death was preceded by loss of mitochondrial membrane potential, JNK - mediated phosphorylation of Bcl-2 and Bad, and activation of caspase-3. Intriguingly, SRF was found to selectively inhibit cancer cell proliferation and was effective against drug-resistant cancer cells by virtue of its ability to bypass the multidrug resistance transporter P-glycoprotein. Taken together, our results suggest that SRF has potential as a chemotherapeutic agent for cancer treatment and provides an alternate scaffold for the development of improved anti-cancer agents. 相似文献
36.
近年来在许多肿瘤细胞系中发现Notch基因的表达失常,失控的Notch信号对维持肿瘤细胞表型性起着重要作用。在宫颈癌细胞中,异常上调的Notch信号通路由人乳头瘤病毒(HPV)相关蛋白“E6/7”介导,并能与之发生协同作用维持肿瘤的生长及异型性,另一方面,激活的Notch1又能通过抑制Fos蛋白家族进而抑制“E6/7”的表达,并能通过抑制E47蛋白引起细胞增殖抑制。结合对不同时期宫颈癌细胞的研究结果,目前认为低水平的Notch1表达对维持发生癌变的角质细胞的生存相当重要,过多或过少的Notch1信号都会对细胞增殖造成负面影响。 相似文献
37.
Leslie W. Tari Michael Trzoss Daniel C. Bensen Xiaoming Li Zhiyong Chen Thanh Lam Junhu Zhang Christopher J. Creighton Mark L. Cunningham Bryan Kwan Mark Stidham Karen J. Shaw Felice C. Lightstone Sergio E. Wong Toan B. Nguyen Jay Nix John Finn 《Bioorganic & medicinal chemistry letters》2013,23(5):1529-1536
The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity. 相似文献
38.
Nguyen Thuy Trang Nguyen Thi Thuy Dung Tran Nguyen-Minh-An Van Vo Giau 《Neurochemical research》2022,47(3):552-573
Neurochemical Research - Neurodegenerative disorders are distinguished by the gradual deterioration of the nervous system’s structure and function due to oxidative stress, mitochondrial... 相似文献
39.
Wu H Kao SC Barrientos T Baldwin SH Olson EN Crabtree GR Zhou B Chang CP 《The Journal of biological chemistry》2007,282(42):30673-30679
40.
Plum is a highly perishable fruit and postharvest fruit softening limits its shelf life. The aim of this work was to study
the specific effects of 1-methylcyclopropene (1-MCP) treatment on physiological changes in ‘Zaohong’ plums. Plums were treated
with 500 nL L−1 1-MCP at 20°C for 18 h followed by 20°C storage. The results showed that 1-MCP treatment significantly reduced endogenous
ethylene production and the activities of ethylene biosynthetic enzymes’ (1-aminocyclopropane-1-carboxylic acid synthase,
ACS and 1-aminocyclopropane-1-carboxylic acid oxidase, ACO) in plum fruit during storage when compared with untreated fruit.
Although 1-MCP treatment inhibited ethylene production and 1-aminocyclopropane-1-carboxylic acid (ACC) accumulation, it did
not inhibit the accumulation of N-malonyl-ACC (MACC). Higher firmness was also found in 1-MCP-treated plums than in controls. During storage, superoxide anion
(O2−·) and hydrogen peroxide (H2O2) levels decreased in 1-MCP-treated fruit. 1-MCP treatment also regulated superoxide dismutase (SOD) and catalase (CAT) activities
during storage. Xylanase activity was upregulated while activities of polygalacturonase (PG), pectin methyl esterase (PME)
and cellulase enzymes in the fruit were downregulated by 1-MCP treatment. In conclusion, 1-MCP might be a potent compound
for extending both storage period and shelf life of ‘Zaohong’ plums by suppressing ethylene biosynthesis, regulating cell
wall degradation enzymes and reducing fruit softening. 相似文献