Analysis of significance of collagen triple helix repeat containing 1 gene expression in colon adenocarcinoma based on bioinformatics / 肿瘤研究与临床

Objective:To investigate the significance of collagen triple helix repeat containing 1 (CTHRC1) gene expression in colon adenocarcinoma based on bioinformatics.Methods:The GEPIA2 analysis tool was used to analyze the expression of CTHRC1 gene in colon adenocarcinoma and the relationship between its expression and the survival prognosis of patients in The Cancer Genome Atlas (TCGA) database and GTEx database. ULACAN analysis tool was used to analyze the methylation level of CTHRC1 gene in colon adenocarcinoma tissues and normal colon tissues in TCGA database. The cBioportal network analysis tool was used to analyze the mutation of CTHRC1 gene. TIMER analysis tool was used to analyze the relationship between CTHRC1 expression and immune cells infiltration, tumor-associated fibroblasts infiltration and functional immune cells. STRING database was used to analyze the proteins interacted with CTHRC1, and the enrichment analyses were performed.Results:The expressions of CTHRC1 gene and protein in colon adenocarcinoma tumor tissues were higher than those in normal colon tissues, and the differences were statistically significant (both P < 0.05), and CTHRC1 gene showed high methylation level in normal colon tissues and low methylation level in tumor tissues ( P < 0.05). A total of 19 mutations were detected in 2 480 colorectal adenocarcinoma and colon adenocarcinoma samples. Among them, 3 cases of colon adenocarcinoma specimens had CTHRC1 mutations, the mutation sites were R235H, A124V and R193C, and the mutation types were all missense mutations. CTHRC1 gene expression was positively correlated with infiltrations of CD8 + T cells, CD4 + T cells, macrophages, neutrophils, dendritic cells and tumor-associated fibroblasts (all P < 0.01). The overall survival and disease-free survival of patients with high expression of CTHRC1 gene were worse than those of patients with low expression of CTHRC1 gene (all P < 0.05). Conclusions:The methylation of CTHRC1 gene and the infiltration of tumor-associated immune cells may have important significances in the pathogenesis of colon adenocarcinoma. CTHRC1 gene expression and immune cells infiltration can be used as predictors of the survival prognosis of colon adenocarcinoma patients.

CTHRC1 promotes proliferation of gastric cancer cells by overexpression of COL1A1 / 解放军医学杂志

Objective To investigate the proliferation and potential mechanism of CTHRC1 on gastric cancer cells. Methods The cancer tissues and adjacent tissues were collected of 8 gastric cancer patients diagnosed by pathology from Jun. 2017 to Jun. 2018 in Guangzhou Zengcheng People's Hospital. Human gastric mucosal GES-1 cells, and gastric cancer SGC-7901, BGC-823, BGC-803, MKN-45, and MKN-28 cells were purchased from Shanghai Cell Bank of Chinese Academy of Sciences. Western blotting was used to detect the expression of CTHRC1 protein in gastric cancer tissues, paracancerous tissues and gastric cancer cell lines SGC-7901, BGC-823, BGC-803, MKN-45, MKN-28 and human gastric mucosal GES-1 cells. After transfection of gastric cancer SGC-7901 cells with si-CTHRC1 and si-COL1A1, cell proliferation was detected by MTT assay, and the apoptosis rate was detected by flow cytometry. The target gene of CTHRC 1 was predicted by STRING database. Western blotting and immunofluorescence were performed to detect the expression of CTHRC1 and COL1A1 proteins in gastric cancer SGC-7901 cells transfected with si-CTHRC1. The expressions of CTHRC1 and COL1A1 proteins in gastric cancer tissues and the prognosis of gastric cancer patients were analyzed by Kaplan-Meier. Results The expression of CTHRC1 protein was significantly higher in gastric cancer tissues (0.87±0.13) than in adjacent tissues (0.31±0.20, P<0.05). The expression of CTHRC1 protein was higher in gastric cancer cell lines than in human gastric mucosa GES-1 cells with significant difference (P<0.05). The cell proliferation of gastric cancer SGC-7901 cells transfected by si-CTHRC1 decreased significantly. The cell vitality of gastric cancer SGC-7901 cells co-transfected by si-CTHRC1 and si-COL1A1 was lower (0.40±0.07) than those only transfected by si-CTHRC1 (0.87±0.05) or by si-COL1A1 groups (0.83±0.13, P<0.05). The apoptosis rate of gastric cancer SGC-7901 cells transfected by si-CTHRC1 (6.77%±1.55%) was higher than that in NC group (4.80%±1.93%) with statistical significance (P<0.05). The STRING database predicted that COL1A1 was a target gene for CTHRC1. For gastric cancer SGC-7901 cells transfected by si-CTHRC1, the relative expressions of CTHRC1 and COL1A1 proteins were 0.92±0.16 and 1.08±0.23, which were higher than those in NC group (0.55±0.15 and 0.65±0.12) with significant difference (P<0.05). Immunofluorescence showed that the expressions of CTHRC1 and COL1A1 proteins decreased significantly after transfection of si-CTHRC1 into gastric cancer SGC-7901 cells. Kaplan-Meier analysis showed that the 5-year survival rate of patients with high CTHRC1 expression in gastric cancer tissues was significantly lower (27.4%) than that of patients with low CTHRC1 expression (38.4%); The 5-year survival rate of patients with high COL1A1 expression in gastric cancer tissues (20.4%) was significantly lower than that in low expression patients (49.3%), the difference was statistically significant (P<0.001). Conclusion CTHRC1 promotes the proliferation of gastric cancer cells by overexpressing COL1A1 protein.

Expressions of Yes-associated protein 1 and collagen triple helix repeat containing 1 in triple-negative breast cancer and their correlations with expression of E-cadherin / 肿瘤研究与临床

Objective To investigate the clinical significances of the expressions of Yes-associated protein 1 (YAP1) and collagen triple helix repeat containing 1 (CTHRC1) in triple-negative breast cancer (TNBC) and their correlations with expression of E-cadherin. Methods Immunohistochemical analysis (SABC) was performed to detect expressions of YAP1 and CTHRC1 in 73 specimens of TNBC and adjacent cancer tissues collected from patients in Dandong First Hospital from January 2006 to December 2017. The correlations between the expressions of YAP1 and CTHRC1 and clinicopathologic features and E-cadherin expression were analyzed. Results The expression rates of YAP1 and CTHRC1 in TNBC were 71.23％(52/73) and 79.45％(58/73), and 13.70％(10/73) and 27.40％(20/73) in adjacent cancer tissues, respectively, and the differences were statistically significant (χ2 values were 49.452 and 39.748, both P< 0.01). The expressions of YAP1 and CTHRC1 were related to tumor grade, clinical stage and lymphatic metastasis (YAP1:χ2 values were 10.244, 8.754, and 6.914, all P<0.05;CTHRC1:χ2 values were 12.582, 13.172, and 6.400, all P< 0.05), but they were not related to patient's age, tumor diameter and menopausal status (all P>0.05). The expressions of YAP1 and CTHRC1 were negatively correlated with expression of E-cadherin in TNBC (r=-0.371, P=0.001;r=-0.323, P=0.005). Conclusion YAP1 and CTHRC1 is closely related to the occurrence and development of TNBC and may participate in the invasion of TNBC through epithelial mesenchymal transition.

Hélice Tríplice: inovação e empreendedorismo universidade-indústria-governo / Triple Helix: university-industry-government innovation and entrepreneurship

RESUMO A Hélice Tríplice tornou-se um modelo reconhecido internacionalmente, que está no âmago da disciplina emergente de estudos de inovação, e um guia de políticas e práticas nos âmbitos local, regional, nacional e multinacional. As interações universidade-indústria-governo, que formam uma "hélice tríplice" de inovação e empreendedorismo, são a chave para o crescimento econômico e o desenvolvimento social baseados no conhecimento. O artigo apresenta a origem do modelo, seu conceito, dinâmica, fontes e rotas alternativas.

ABSTRACT The Triple Helix has developed into an internationally recognized model that is at the heart of the emerging discipline of innovation studies, and a guide to policy and practice at the local, regional, national and multinational levels. University-industry-government interactions, forming a "triple helix" for innovation and entrepreneurship, are the key to knowledge-based economic growth and social development. The article discusses the model's origin, concept, dynamics, sources, and alternate routes.

Interação academia-indústria. Relato da experiência da Vale / Academy-industry interaction. Vale's experience report

RESUMO Abordamos aqui a nucleação de um modelo de inovação aberta na Vale (uma das maiores mineradoras do mundo) apresentando o contexto histórico em que se deu esse processo. Discutimos algumas das questões que possivelmente haviam até então dificultado a implantação de uma estrutura de pesquisa e desenvolvimento focando o longo prazo pela indústria no Brasil. Destacamos algumas das dificuldades encontradas ao longo do processo, bem como algumas das razões que levaram ao sucesso da iniciativa.

ABSTRACT We discuss how Vale (one of the world's largest diversified mining companies) implemented an organizational structure that enabled an open innovation model. We describe the historical perspective in which this process took place. In addition, we present some of the potential causes underlying the slow advance of Brazilian industry in undertaking long-term research and development agendas. Lastly, we list some of the obstacles encountered in this process, as well as some of the potential reasons that might have contributed to the success of the initiative.

Collaborative Innovation Measurement Method and Empirical Analysis of Clinical Medicine Frontier in the Government-in-dustry-academy Fields / 医学信息学杂志

Taking hepatitis C research field as an example,the paper introduces the existing study status on triple helix collaborative innovative model and expatiates on the collaborative innovation measurement method of clinical medicine frontier in the government-in-dustry-academy fields based on Web of Science and carries out empirical analysis to provide reference for scientific innovative management in the area.

Research progress of CTHRC1 in gastrointestinal cancers / 国际肿瘤学杂志

Collagen triple helix repeat containing 1 (CTHRC1) can repair the injured vessel by limiting the deposition of collagen and promoting cell migration.CTHRC1 is mainly regulated by Wnt-PCP signaling pathway,transforming growth factor (TGF)-bone morphogenetic protein (BMP) signaling pathway and extracellular signal-regulated kinase (ERK)-matrix metalloproteinase 9 (MMP9) signaling pathway.Recent studies have identified that CTHRC1 is aberrantly expressed in gastrointestinal cancers and associated with the occurring and development of cancers.

Expression and clinical significance of collagen three helix repeat protein 1 in human gastric carcinoma / 中国综合临床

Objective To investigate the expression level of collagen triple helix repeat containing 1 ( CTHRC1) in human gastric carcinoma and the relationship with the clinicopathological characteristics of gastric cancer?Methods The expression of CTHRC1 in human gastric carcinoma and normal gastric mucosa were detected by immunohistochemistry ( S?P method ) , and the correlation with various clinical characteristics, including gender,age,tumor diameter,degree of differentiation,depth of invasion,lymph node metastasis,TNM stage,was analyzed?Results ( 1 ) CTHRC1 expressed positive for 41 cases ( positive rate=53?95%) in 76 gastric carcinoma specimens, but only 1 case ( positive rate=3?33%) expressed positive in 30 normal gastric mucosa,the difference was statistically significant (χ2 =23?0332, P=0?000 )? ( 2 ) In early stage of gastric carcinoma,CTHRC1 was predominantly positive in the nucleus,but with the progression of the tumor,CTHRC1 expressed predominantly in cytoplasm?( 3) The expression of CTHRC1 was correlated with the depth of invasion (P=0?000),lymph node metastasis(P=0?009) and TNM?stage(P=0?007),but not with age,gender,size of the tumor and differentiated degree ( P>0?05 )?Conclusion CTHRC1 might play important roles in the occurrence,invasion and metastasis in human gastric carcinoma,and may be new therapy targets.

Study on the effect of influenza virus on the expression of collagen triple helix repeat containing 1 / 实用医学杂志

Objective To investigate the effect of influenza virus on the expression of collagen triple he-lix repeat containing 1 (CTHRC1). Methods A549 cells were infected with influenza virus. mRNA and protein levels of CTHRC1 were determined by RT-PCR and Western blot , CTHRC1 levels in the cell supernatants and sera of influenza virus infected patients were determined by enzyme-linked immunosorbent assay (ELISA). The difference of CTHRC1 levels between healthy controls and HCV patients was analyzed. Results Compared with controls, mRNA and protein levels of CTHRC1 were higher in A549 cells infected with H3N2. Serum CTHRC1 levels were higher in influenza virus infected patients than in healthy controls (P < 0.05). Conclusion Influenza virus can promote the synthesis and secretion of CTHRC1.

Cthrc1 Inhibits Proliferation of Hepatic Stellate Cells in Mice / 胃肠病学

Background:Collagen triple helix repeat containing protein-1(Cthrc1)has been reported playing an important role in liver diseases,especially in liver fibrosis,however,its effect on hepatic stellate cells proliferation is not fully clear. Aims:To investigate the effect of Cthrc1 on proliferation of hepatic stellate cells. Methods:Recombinant adenovirus vector of Cthrc1 was constructed. After injecting Ad-Cthrc1 through tail vein,mRNA and protein expressions of Cthrc1 were determined by real-time PCR and Western blotting,respectively. Liver fibrosis model was established by bile duct ligation and fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)in mice,respectively. The liver fibrosis mice were injected with Ad-Cthrc1 or Ad-GFP through tail vein. Immunofluorescence was used to determine number of hepatic stellate cells. Results:Recombinant Cthrc1-adenovirus vector was successfully constructed. Real-time PCR and Western blotting showed that mRNA and protein expressions of Cthrc1 were increased in Ad-Cthrc1 group than in control group. HE and Masson staining demonstrated that mice model of liver fibrosis was successfully established. Immunofluorescence showed that overexpression of Cthrc1 inhibited significantly the proliferation of hepatic stellate cells. Conclusions:Recombinant adenovirus vector of Ad-Cthrc1 constructed can express stably in vivo,and inhibit the proliferation of hepatic stellate cells. Therefore,Cthrc1 may become a potential target for treatment of liver fibrosis.

DNA triplex structures in neurodegenerative disorder, Friedreich’s ataxia.

It is now established that a small fraction of genomic DNA does adopt the non-canonical B-DNA structure or ‘unusual’ DNA structure. The unusual DNA structures like DNA-hairpin, cruciform, Z-DNA, triplex and tetraplex are represented as hotspots of chromosomal breaks, homologous recombination and gross chromosomal rearrangements since they are prone to the structural alterations. Friedreich’s ataxia (FRDA), the autosomal recessive degenerative disorder of nervous and muscles tissue, is caused by the massive expansion of (GAA) repeats that occur in the first intron of Frataxin gene X25 on chromosome 9q13-q21.1. The purine strand of the DNA in the expanded (GAA) repeat region folds back to form the (R∙R*Y) type of triplex, which further inhibits the frataxin gene expression, and this clearly suggests that the shape of DNA is the determining factor in the cellular function. FRDA is the only disease known so far to be associated with DNA triplex. Structural characterization of GAA-containing DNA triplexes using some simple biophysical methods like UV melting, UV absorption, circular dichroic spectroscopy and electrophoretic mobility shift assay are discussed. Further, the clinical aspects and genetic analysis of FRDA patients who carry (GAA) repeat expansions are presented. The potential of some small molecules that do not favour the DNA triplex formation as therapeutics for FRDA are also briefly discussed.

O Portal da Inovação do MCT e a sinergia entre universidade, empresa e governo no desenvolvimento da educação física / The MCT Innovation Portal and synergies between university, industry and government in the development of physical education

Este trabalho tem por objetivo apresentar o Portal da Inovação à comunidade acadêmica da educação física, focalizando alguns dados que estão disponibilizados à consulta pública, no sentido de explorar as possibilidades de sua utilização na promoção e desenvolvimento do país. Examinam-se três partes do Portal: especialistas, grupos de pesquisa e empresas, com a utilização da palavra-chave: "educação física". Procura-se observar a sinergia entre universidade, empresa e governo, no tocante à participação da educação física na promoção da inovação e do desenvolvimento no país.

This study has the purpose to presents and analyzes data from the Innovation Portal to the academic community of physical education, focusing on some data which are available to the public searching. The purpose is to present and explore the possibilities of using this tool to promote and develop the country. Three components areas of the Portal have been examined - specialists, research groups and industries - using the key word "physical education". It was observed the synergies between university, industry and government and the role of physical education to promote innovation and development to the country.

Analysis of Structural Characteristics of Polysaccharide from Ganoderma Lucidum / 分析化学

Polysaccharide was extracted by boiling water reflux method from the fruiting body of Ganoderma lucidum. Additionally, the purified polysaccharide was obtained by removing protein with Sevage way, ethanol precipitation, centrifugation, run water dialysis, membrane separation, concentration and frozen-drying. The structural characteristics, chain conformation and triple-helix conformation of ganoderma lucidum polysaccharide (GLP) were distinguished by Smith degradation, methylation analysis, and the wavelength change of the red shift of the mixture of polysaccharide and Congo red in alkaline solution, as well as IR, GC-MS, NMR, and visible spectrometry. The results indicated that GLP was a linear (1→3) β-D-Glcp main chain linkage. Its monosaccharide component was predominantly composed of D-Glc, and small amount of galactose, mannose, xylose and idose, residues of branches terminated with substituted at 1→6 by a small number of single-unit β-D-Glcp side-chains, it′s also observed that the (1→3)-linked β-D- glucan contained a triple-helical conformation, which was composed of a repeating unit with a structure as below:→3)-β-D-Glcp-(1→3)-[β-D-Glcp-(1→3)-]_n-β-D-Glcp-(1→.↑6/1β-D-Glcp