AIM: To study the role of an insertion/deletion polymorphism in the pepsinogen C (PGC) gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastr...AIM: To study the role of an insertion/deletion polymorphism in the pepsinogen C (PGC) gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions. METHODS: The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified: Allele 1 (510 bp), Allele 2 (480 bp), Allele 3/4 (450/460 bp), Allele 5 (400 bp) and Allele 6 (310 bp). RESULTS: Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion (OR = 0.34; P 〈 0.001), non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia (OR = 0.28; P 〈 0.001) or invasive GC (OR = 0.39; P = 0.004). CONCLUSION: Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.展开更多
Objective: To express the recombinant human bone morphogenetic protein-7(rhBMP-7) in Chinese hamster ovary(CHO) cells, and to establish the in vitro biological activity assay of rhBMP-7.Methods: Human BMP-7 cDNA was s...Objective: To express the recombinant human bone morphogenetic protein-7(rhBMP-7) in Chinese hamster ovary(CHO) cells, and to establish the in vitro biological activity assay of rhBMP-7.Methods: Human BMP-7 cDNA was subcloned into p114 mammalian expression vector and transfected to CHO cells by using the Lipofectamine 2000 transfection method. CHO cell supernatants were harvested and analyzed to identify the molecule mass of secreted rhBMP-7 and examine its biological activity in vitro to stimulate the synthesis of alkaline phophatase(ALP), a characteristic of osteoblast phenotypes. Results: rhBMP-7 was produced stably in CHO cells, as a processed mature disulfide-linked homodimer, with an apparent molecular mass of 36 000. Examination of the rhBMP-7 biological activity showed that rhBMP-7 specifically stimulated the production of ALP(4-fold increase at 100 ng of rhBMP-7/ml). Conclusion: The rhBMP-7 from CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates rhBMP-7 has the potential bone regeneration activity.展开更多
Being one of the most abundant intracellular proteins, heat shock proteins (HSPs) have many housekeeping functions which are crucial for the survival of organisms. In addition, some HSPs are new immunoactive molecules...Being one of the most abundant intracellular proteins, heat shock proteins (HSPs) have many housekeeping functions which are crucial for the survival of organisms. In addition, some HSPs are new immunoactive molecules which play important roles in both adaptive and innate immunity. They could activate CD8 + and CD4 + lymphocytes, induce innate immune response including natural killer (NK) cell activation and cytokine secretion, and induce maturation of dendritic cells (DCs). These characteristics have been used for immunotherapy of various types of cancers and infectious diseases. This review focuses on the main HSP families——HSP70 and 90 families. The mechanism of HSPs′ function in eliciting immune response are elucidated and various forms of HSPs used in immunotherapy are discussed in details. At the end of this review, authors summarize clinical trials related to HSPs and evaluate their clinical efficacy.展开更多
Genes associated with similar diseases are often functionally related.This principle is largely supported by many biological data sources,such as disease phenotype similarities,protein complexes,protein-protein intera...Genes associated with similar diseases are often functionally related.This principle is largely supported by many biological data sources,such as disease phenotype similarities,protein complexes,protein-protein interactions,pathways and gene expression profiles.Integrating multiple types of biological data is an effective method to identify disease genes for many genetic diseases.To capture the gene-disease associations based on biological networks,a kernel-based Markov random field(MRF)method is proposed by combining graph kernels and the MRF method.In the proposed method,three kinds of kernels are employed to describe the overall relationships of vertices in five biological networks,respectively,and a novel weighted MRF method is developed to integrate those data.In addition,an improved Gibbs sampling procedure and a novel parameter estimation method are proposed to generate predictions from the kernel-based MRF method.Numerical experiments are carried out by integrating known gene-disease associations,protein complexes,protein-protein interactions,pathways and gene expression profiles.The proposed kernel-based MRF method is evaluated by the leave-one-out cross validation paradigm,achieving an AUC score of 0.771 when integrating all those biological data in our experiments,which indicates that our proposed method is very promising compared with many existing methods.展开更多
基金Supported by the Portuguese League Against Cancer (Liga Por-tuguesa Contra o Cancro-Nucleo Regional do Norte) and Astra Zeneca Foundation
文摘AIM: To study the role of an insertion/deletion polymorphism in the pepsinogen C (PGC) gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions. METHODS: The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified: Allele 1 (510 bp), Allele 2 (480 bp), Allele 3/4 (450/460 bp), Allele 5 (400 bp) and Allele 6 (310 bp). RESULTS: Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion (OR = 0.34; P 〈 0.001), non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia (OR = 0.28; P 〈 0.001) or invasive GC (OR = 0.39; P = 0.004). CONCLUSION: Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.
文摘Objective: To express the recombinant human bone morphogenetic protein-7(rhBMP-7) in Chinese hamster ovary(CHO) cells, and to establish the in vitro biological activity assay of rhBMP-7.Methods: Human BMP-7 cDNA was subcloned into p114 mammalian expression vector and transfected to CHO cells by using the Lipofectamine 2000 transfection method. CHO cell supernatants were harvested and analyzed to identify the molecule mass of secreted rhBMP-7 and examine its biological activity in vitro to stimulate the synthesis of alkaline phophatase(ALP), a characteristic of osteoblast phenotypes. Results: rhBMP-7 was produced stably in CHO cells, as a processed mature disulfide-linked homodimer, with an apparent molecular mass of 36 000. Examination of the rhBMP-7 biological activity showed that rhBMP-7 specifically stimulated the production of ALP(4-fold increase at 100 ng of rhBMP-7/ml). Conclusion: The rhBMP-7 from CHO expression system has significant biological activity in induction of osteoblast phenotype, which demonstrates rhBMP-7 has the potential bone regeneration activity.
文摘Being one of the most abundant intracellular proteins, heat shock proteins (HSPs) have many housekeeping functions which are crucial for the survival of organisms. In addition, some HSPs are new immunoactive molecules which play important roles in both adaptive and innate immunity. They could activate CD8 + and CD4 + lymphocytes, induce innate immune response including natural killer (NK) cell activation and cytokine secretion, and induce maturation of dendritic cells (DCs). These characteristics have been used for immunotherapy of various types of cancers and infectious diseases. This review focuses on the main HSP families——HSP70 and 90 families. The mechanism of HSPs′ function in eliciting immune response are elucidated and various forms of HSPs used in immunotherapy are discussed in details. At the end of this review, authors summarize clinical trials related to HSPs and evaluate their clinical efficacy.
基金supported by the Natural Sciences and Engineering Research Council of CanadaNational Natural Science Foundation of China(61428209,61232001)
文摘Genes associated with similar diseases are often functionally related.This principle is largely supported by many biological data sources,such as disease phenotype similarities,protein complexes,protein-protein interactions,pathways and gene expression profiles.Integrating multiple types of biological data is an effective method to identify disease genes for many genetic diseases.To capture the gene-disease associations based on biological networks,a kernel-based Markov random field(MRF)method is proposed by combining graph kernels and the MRF method.In the proposed method,three kinds of kernels are employed to describe the overall relationships of vertices in five biological networks,respectively,and a novel weighted MRF method is developed to integrate those data.In addition,an improved Gibbs sampling procedure and a novel parameter estimation method are proposed to generate predictions from the kernel-based MRF method.Numerical experiments are carried out by integrating known gene-disease associations,protein complexes,protein-protein interactions,pathways and gene expression profiles.The proposed kernel-based MRF method is evaluated by the leave-one-out cross validation paradigm,achieving an AUC score of 0.771 when integrating all those biological data in our experiments,which indicates that our proposed method is very promising compared with many existing methods.