资源类型

期刊论文 7

年份

2022 1

2021 1

2018 1

2015 2

2014 1

2009 1

关键词

哺乳动物细胞文库 1

程序性细胞死亡配体-1 1

表位定向 1

诱饵程序性细胞死亡蛋白-1 1

检索范围：

排序： 展示方式：

Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal

《医学前沿（英文）》 2022年 第16卷 第5期   页码 784-798 doi: 10.1007/s11684-021-0911-0

摘要： More than 85% of patients with uveal melanoma (UM) carry a GNAQ or GNA11 mutation at a hotspot codon (Q209) that encodes G protein α subunit q/11 polypeptides (Gαq/11). GNAQ/11 relies on palmitoylation for membrane association and signal transduction. Despite the palmitoylation of GNAQ/11 was discovered long before, its implication in UM remains unclear. Here, results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells. Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11Q209L-induced malignant transformation in NIH3T3 cells. Importantly, the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells, which are much more dependent on Gαq/11 signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations. Furthermore, the palmitoylation inhibitor, 2-bromopalmitate, also specifically disrupted Gαq/11 downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor, ABT-199, in vitro. The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.

关键词： uveal melanoma     mutant GNAQ/11     palmitoylation     BCL2     combination target therapy    

HTML PDF 收藏

gene expression during melanoblasts migration in normal pigmented White Leghorn and hyperpigmented mutant

Yulin LI,Deping HAN,Junying LI,Dawn KOLTES,Xuemei DENG

《农业科学与工程前沿（英文）》 2014年 第1卷 第4期   页码 299-306 doi: 10.15302/J-FASE-2014040

摘要： Melanoblasts originating from neural crest cells can migrate through the mesenchyme of the developed embryo and give rise to melanocytes. Unlike the melanocytes that are confined to the integument in other vertebrates, melanocytes in Silky Fowl can reach the ventral regions of the embryos owing to differences in gene expression in the process of melanoblasts migration. In this study, we used microarray profiling to identify differences in gene expression between White Leghorn and Silky Fowl. Differential expression of 2517 microarray probes ( <0.01, Fold Change>2) was observed in Silky Fowl compared to White Leghorn. After filtration by cluster analysis, functional annotation and pathway analysis, eight differentially expressed genes were identified to be closely related to the development of melanocytes. Moreover, differences in expression of immune genes were also detected between Silky Fowl and White Leghorn. The differentially expressed genes associated with melanocyte development were verified by q-PCR, and results were highly consistent with the microarray data. The genes with significantly altered expression involved in melanoblast migration and development suggested that different microenvironments resulted in the abnormal melanoblast migration in Silky Fowl, although there were no big differences in melanoblast development between these two breeds. The candidate genes discovered in this study are beneficial to understand the molecular mechanism of hyperpigmentation in Silky Fowl.

关键词： Silky Fowl     White Leghorn     melanoblast migration     gene expression    

HTML PDF 收藏

and clinical application of anti-HBs monoclonal antibody that binds both wild-type and immune escape mutant

Fanghe LI BM , Chunyan ZHANG MS , Jinghua LIU MS , Xiaoyan ZHANG MS , Bing YAN , Bo ZHANG MS , Yongguo HUANG MS , Jingsong GONG BM , Yan CHEN BM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 277-283 doi: 10.1007/s11684-009-0047-0

摘要： Using a standard cellular fusion technique and indirect enzyme-linked immunosorbent assay (ELISA), a hybridoma cell line strain secreting anti-HBs monoclonal antibody (mAb) (defined G6 mAb) was obtained. The cells grew and secreted mAb stably. Antibody titers in the culture supernatant and ascites were 2.048×10 and 4.096×10, respectively. By applying the anti-HBs G6 mAb and horseradish peroxidase (HRP)-labeled goat anti-HBs antibody, we developed a sandwich ELISA (defined G6m ELISA) for detecting both wild-type and immune escape mutant HBsAgs (IEM HBsAg). The assay was performed to detect 17 species of genome recombinant expression HBsAg, including two wild-type species and 15 IEM HBsAg species, which varied in the “a” determinant, in a group of patients infected with hepatitis B virus (HBV). The patients previously had a lower ELISA detection signal [(absorbance of patients/absorbance of normal people (P/N): 1.0―4.5)]. The results demonstrated that the sensitivity of this assay to wild-type HBsAg was no less than 0.125g/L; 12 of 15 IEM HBsAg species (P/N≥2.5) were positive for G6 mAb. Of the positive IEM HBsAg species, two had a low absorbance value at 450nm (), one had an intermediate value and nine had a high value, which was 7.55%(mean), 59.4% and 92.1%―109.4% of the wild-type value, respectively. The two species with low value and the three negative species mutated at the bases 120―124 in the first loop of the HBV “a” determinant. Using the G6 ELISA and two commercial ELISA kits (A and B), 177 patients were tested. The G6 ELISA had a significantly higher detection rate than either commercial ELISAs (19.21% 14.89% and 6.21%, respectively; <0.01, <0.05, respectively).

关键词： hepatitis B virus     gene variation     hepatitis B surface antigen     immune escape     enzyme-linked immunosorbent assay    

HTML PDF 收藏

Mutant DNA methylation regulators endow hematopoietic stem cells with the preleukemic stem cell property

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 412-420 doi: 10.1007/s11684-015-0423-x

摘要：

Genetic mutations are considered to drive the development of acute myeloid leukemia (AML). With the rapid progress in sequencing technologies, many newly reported genes that are recurrently mutated in AML have been found to govern the initiation and relapse of AML. These findings suggest the need to distinguish the driver mutations, especially the most primitive single mutation, from the subsequent passenger mutations. Recent research on DNA methyltransferase 3A (DNMT3A) mutations provides the first proof-of-principle investigation on the identification of preleukemic stem cells (pre-LSCs) in AML patients. Although DNMT3A mutations alone may only transform hematopoietic stem cells into pre-LSCs without causing the full-blown leukemia, the function of this driver mutation appear to persist from AML initiation up to relapse. Therefore, identifying and targeting preleukemic mutations, such as DNMT3A mutations, in AML is a promising strategy for treatment and reduction of relapse risk.

关键词： preleukemic stem cell     acute myeloid leukemia     relapse     DNMT3A    

HTML PDF 收藏

High production of butyric acid by

Chao Ma,Jianfa Ou,Matthew Miller,Sarah McFann,Xiaoguang (Margaret) Liu

《化学科学与工程前沿（英文）》 2015年 第9卷 第3期   页码 369-375 doi: 10.1007/s11705-015-1525-3

摘要： The objective of this study was to improve the production of butyric acid by process optimization using the metabolically engineered mutant of (PAK-Em). First, the free-cell fermentation at pH 6.0 produced butyric acid with concentration of 38.44 g/L and yield of 0.42 g/g. Second, the immobilized-cell fermentations using fibrous-bed bioreactor (FBB) were run at pHs of 5.0, 5.5, 6.0, 6.5 and 7.0 to optimize fermentation process and improve the butyric acid production. It was found that the highest titer of butyric acid, 63.02 g/L, was achieved at pH 6.5. Finally, the metabolic flux balance analysis was performed to investigate the carbon rebalance in . The results show both gene manipulation and fermentation pH change redistribute carbon between biomass, acetic acid and butyric acid. This study demonstrated that high butyric acid production could be obtained by integrating metabolic engineering and fermentation process optimization.

关键词： Clostridium tyrobutyricum     butyric acid production     fermentation     mutant     pH     flux balance analysis    

HTML PDF 收藏

Comparative transcriptome analysis of purple-fleshed sweet potato provides insights into the molecular mechanism of anthocyanin biosynthesis

Hongyuan ZHAO, Shanshan ZHANG, Feibing WANG, Ning ZHAO, Shaozhen HE, Qingchang LIU, Hong ZHAI

《农业科学与工程前沿（英文）》 2018年 第5卷 第2期   页码 214-225 doi: 10.15302/J-FASE-2018219

摘要： Sweet potato, , is a globally important food crop. The purple-fleshed sweet potato, rich in anthocyanins, has great potential for both nutritional and pharmaceutical uses. In this study, we characterized the root transcriptomes of the purple-fleshed sweet potato cv. Jingshu 6 and its mutant JS6-5 with high anthocyanin content by high-throughput RNA sequencing. A total of 22873364 and 27955097 high quality reads were obtained from Jingshu 6 and JS6-5, respectively, and assembled into 35592 unigenes. In all, we obtained 1566 differentially expressed genes (DEGs). Among them, 994 were upregulated and 572 were downregulated in JS6-5 compared to the expression in Jingshu 6. A total of 1436 DEGs were annotated, in which 847 DEGs had gene ontology (GO) terms and 329 DEGs were assigned to 84 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most importantly, 23 differentially expressed genes and 24 transcription factors were identified as candidate genes involved in anthocyanin biosynthesis. In addition, 2349 SSRs were detected. This study not only provides the candidate genes but also provides insights into the molecular mechanism of anthocyanin biosynthesis in sweet potato.

关键词： anthocyanin     gene expression     mutant     purple-fleshed sweet potato     transcriptome    

HTML PDF 收藏

基于表位定向细胞库筛选高亲和力PD-1突变体诱骗分子 Article

刘昊, 乔春霞, 胡乃静, 王志宏, 王晶, 冯健男, 沈倍奋, 马远方, 罗龙龙

《工程（英文）》 2021年 第7卷 第11期   页码 1557-1565 doi: 10.1016/j.eng.2020.11.011

摘要：

抗程序性细胞死亡蛋白-1（programmed cell death protein-1, PD-1）/程序性细胞死亡配体-1（programmed cell death ligand-1, PD-L1）单克隆抗体的免疫疗法已成为治疗肺癌、肠癌和黑色素瘤等多种癌症的常规方法。PD-1/PD-L1信号通路在肿瘤微环境中可抑制T细胞活化，使其成为一个热门的抗癌靶点。野生型（wild type, WT）PD-1胞外结构域由于亲和力低而难以阻断PD-1/PD-L1复合物的形成。本文利用三维（3D）晶体复合结构分析了PD-1与PD-L1或PD-L2的相互作用。文中还报道了PD-1与其临床抗体Opdivo结合模式的理论研究。通过对PD-1及其配体（即PD-L1和PD-L2）或抗体Opdivo的理论结合分析，建立了PD-1的一个小库容量、表位定向的哺乳动物细胞文库。经过三轮细胞分选，筛选出对PD-L1有较高亲和力的PD-1突变体463（亲和力较野生型PD-1提高近3个数量级）。它对PD-1具有抑制作用，可阻止PD-1与PD-L1形成复合物，这与商品化的抗PD-L1抗体atezolizumab（ATE）的作用相似。突变体463的半数有效浓度（median effective concentration, EC50）为0.031 μg·mL−1，而ATE的EC50为0.063 μg·mL−1，两者均明显低于野生型PD-1的EC50 (2.571 μg·mL−1)。在MC38转基因小鼠模型中，463可有效逆转PD-1对T细胞活化的抑制作用，而且10 mg·kg−1的463突变体蛋白对肿瘤生长的抑制率约为75%，与同等剂量下ATE的抑制活性相似。更有趣的是，低剂量的463（2 mg·kg−1）显示出比10 mg·kg−1的野生型PD-1更好的抑瘤效果。这项工作提供了一种高亲和力诱饵骗分子463，其体内外活性较天然PD-1分子有明显提高，因此，它有可能成为靶向PD-1/PD-L1治疗相关肿瘤的良好选择。

关键词： 诱饵程序性细胞死亡蛋白-1     程序性细胞死亡配体-1     哺乳动物细胞文库     表位定向    

HTML PDF 收藏

标题 作者 时间 类型 操作

Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal

期刊论文

gene expression during melanoblasts migration in normal pigmented White Leghorn and hyperpigmented mutant

Yulin LI,Deping HAN,Junying LI,Dawn KOLTES,Xuemei DENG

期刊论文

and clinical application of anti-HBs monoclonal antibody that binds both wild-type and immune escape mutant

Fanghe LI BM , Chunyan ZHANG MS , Jinghua LIU MS , Xiaoyan ZHANG MS , Bing YAN , Bo ZHANG MS , Yongguo HUANG MS , Jingsong GONG BM , Yan CHEN BM ,

期刊论文

Mutant DNA methylation regulators endow hematopoietic stem cells with the preleukemic stem cell property

null

期刊论文

High production of butyric acid by

Chao Ma,Jianfa Ou,Matthew Miller,Sarah McFann,Xiaoguang (Margaret) Liu

期刊论文

Comparative transcriptome analysis of purple-fleshed sweet potato provides insights into the molecular mechanism of anthocyanin biosynthesis

Hongyuan ZHAO, Shanshan ZHANG, Feibing WANG, Ning ZHAO, Shaozhen HE, Qingchang LIU, Hong ZHAI

期刊论文

基于表位定向细胞库筛选高亲和力PD-1突变体诱骗分子

刘昊, 乔春霞, 胡乃静, 王志宏, 王晶, 冯健男, 沈倍奋, 马远方, 罗龙龙

期刊论文