Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive...Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive thyroid-related cell lines cultured under simulated microgravity.Methods:Five thyroid-related cell lines—normal thyrocytes(Nthy-ori 3-1),papillary thyroid cancer(PTC)cells(SNU-790,TPC-1),poorly differentiated thyroid cancer cell(BCPAP),and anaplastic thyroid cancer cell(SNU-80)—were cultured under simulated microgravity(10-3 g)using a clinostat.Differentially expressed genes(DEGs)were analyzed using cDNA microarray,followed by functional annotation and assessment of aggressiveness via Transwell migration and invasion assays.Results:DEG analysis under simulated microgravity revealed distinct gene expression profiles by gravity condition,with 2980 DEGs in SNU-790,1033 in BCPAP,562 in TPC-1,477 in Nthy-ori 3-1,and 246 in SNU-80,as confirmed by hierarchical clustering.In PTC cell lines(SNU-790,TPC-1),G2–M phase–related genes were upregulated.In non-PTC cell lines(BCPAP,SNU-80),genes associated with innate immune response,Toll-like receptor signaling,were upregulated,whereas Hypoxia-Inducible Factor 1-alpha(HIF-1α)signaling-related genes were downregulated.Additionally,under simulated microgravity,significant migration was observed in SNU-790(3×104 cells)and BCPAP(2×104 and 3×104),while significant invasion occurred in SNU-790,Nthy-ori 3-1,and BCPAP at a seeding density of 2×104.Other conditions showed no significant differences.Conclusion:This study comprehensively evaluates the effects of simulated microgravity using a diverse panel of thyroid-related cell lines.Thesefindings provide valuable insight into how microgravity could influence cancer biology,emphasizing the importance of further research on cancer behavior in space environments and its implications for human health during long-term space missions.展开更多
OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by using cDNA microarray and detect target genes for further study. METHODS: Three mixed samples from 2 cases of normal pancreatic tissue and ...OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by using cDNA microarray and detect target genes for further study. METHODS: Three mixed samples from 2 cases of normal pancreatic tissue and 4 cases of moderate-differentiated pancreatic carcinoma were studied by means of cDNA microarray consisting of 18 000 genes. RESULTS: 1484 and 1353 different expressed genes were observed in two cancer samples respectively. We identified 455 genes altered with the same tendency in both samples, including 102 up-regulated and 353 down-regulated genes. There were 274 known genes and 181 unknown genes; 27.8% and 52.0% genes respectively had an expression level in cancer that was 2-fold higher or lower than that in normal samples. Tumor suppressor genes, growth factors and receptor genes, signal conduction genes, transcription factor genes were identified. CONCLUSIONS: cDNA microarray is an efficient and high-throughout method to investigate gene expression profiles in pancreatic carcinoma. MBD1, EDG1 and gene hypermethylation mechanism would play an important role in the pathogenesis of pancreatic carcinoma.展开更多
Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emo...Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially- expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdhl, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.展开更多
Menopause is one of the key physiological events in the female life and can increase the risk for a number of complex autoimmune, neurodegenerative, metabolic, and cardiovascular disorders. Circulating monocytes can d...Menopause is one of the key physiological events in the female life and can increase the risk for a number of complex autoimmune, neurodegenerative, metabolic, and cardiovascular disorders. Circulating monocytes can differentiate into various cell types and play an important role in tissue morphogenesis and immune response. We studied gene expression profiles of peripheral blood monocytes in healthy pre- and postmenopausal women using Affymetrix Human U133A GeneChip array that contains probes for -14,500 genes. Comparative analyses between the samples showed that 20 genes were up- and 20 were down-regulated. Of these genes, 28 were classified into six major GO categories relevant to such biological processes as the cell proliferation, immune response, cellular metabolism, and the others. The remaining 12 genes have yet unidentified biological functions. Our results support the hypothesis that functional state of circulating monocytes is indeed affected by menopause, and resulting changes may be determined through the genomewide gene expression profiling. Several differentially expressed genes identified in this study may be candidates for further studies of menopause-associated systemic autoimmune, neurodegenerative, and cardiovascular disorders. Our study is only the first attempt in this direction, but it lays a basis for further research.展开更多
AIM: To find out key genes responsible for hepatocarc inogenesis and to further understand the underlying molecular mechanism through investigating the differential gene expression between human normal liver tissue an...AIM: To find out key genes responsible for hepatocarc inogenesis and to further understand the underlying molecular mechanism through investigating the differential gene expression between human normal liver tissue and hepatocellular carcinoma (HCC).METHODS: DNA microarray was prepared by spotting PCR products of 1 000 human genes including 445 novel genes, 540 known genes as well as 12 positive (housekeeping) and 3 negative controls (plant gene) onto treated glass slides. cDNA probes were prepared by labeling normal liver tissue mRNA and cancer liver tissue mRNA with Cy3-dUTP and Cy5-dUTP separately through reverse transcription. The arrays were hybridized against the cDNA probe and the fluorescent signals were scanned. The dataobtained from repeated experiments were analyzed. RESULTS: Among the 20 couple samples investigated (from cancerous liver tissue and normal liver tissue), 38 genes including 21 novel genes and 17 known genes exhibited different expressions. CONCLUSION: cDNA microarray technique is powerful to identify candidate target genes that may play important roles in human carcinogenesis. Further analysis of the obtained genes is helpful to understand the molecular changes in HCC progression and ultimately may lead to the identification of new targets for HCC diagnosis and intervention.展开更多
Objective: A single mechanistic pathway cannot explain the genesis of drug resistance in cancer. Drug resistance in cancer is a major obstacle to successful chemotherapy. KB cells provide a useful starting point for s...Objective: A single mechanistic pathway cannot explain the genesis of drug resistance in cancer. Drug resistance in cancer is a major obstacle to successful chemotherapy. KB cells provide a useful starting point for selection of the multidrug resistant (MDR) cell lines. Methods: We used cDNA microarrays containing 12,720 sequences of known genes, expressed sequence tags and unknown clones to monitor gene expression profiles in MDR KB cells. Results: Preliminary data analysis showed that 18 genes were up-regulated and 18 genes were down-regulated by comparison of expression patterns between KB 3-1 and MDR KB-V1 cells. Furthermore, the highly over-expressed CGA, CLU genes in MDR KB-V1 cell were verified with conventional Northern blot analysis. These genes contain information predictive of drug resistance of cancer cells. Conclusion: Our study demonstrates that genome-wide gene expression profiling by using cDNA microarray technique is a valuable approach in obtaining molecular mechanism of drug resistance in cancer cells.展开更多
Pathogenesis of the endometriosis is complex and the etiology is still unclear. The objective of this study was to examine that endometrial gene expression in late secretory phase endometrium differs between patients ...Pathogenesis of the endometriosis is complex and the etiology is still unclear. The objective of this study was to examine that endometrial gene expression in late secretory phase endometrium differs between patients with and without endometriosis. Five patients with proven advanced-stage endometriosis and 5 controls underwent endometrial biopsy in the late secretory phase. Analysis of eutopic endometrial gene expression was performed using Affymetrix gene arrays and differentially expressed genes were assigned to gene ontology groups based on overrepresented analysis using Database for Annotation, Visualization, and Integrated Discovery software. Four hundred sixty two genes were identified as up-regulated such as matrix metalloproteinase 10, cytochrome P450 family 24 subfamily A polypeptide 1, matrix metalloproteinase 3, chemokine (C-C motif) ligand 20, Rho family GTPase 1, interleukin 1-beta, and insulin-like growth factor binding protein 1. Six hundred forty three genes were down-regulated in all endometriotic samples. A lot of genes related with metabolic process, cellular ketone metabolic process and ncRNA metabolic processing were included. Expression patterns of selected five genes were validated by quantitative real time PCR. The results of this analysis support that the eutopic endometrium from patients with advanced-stage endometriosis has distinct gene expression profile from eutopic endometrium of control without endometriosis.展开更多
This study was carried out to identify gene expression patterns in different wool densities of rex rabbit. The mid-dorsal skin samples from 8 rex rabbits were studied. They were divided into two groups according to di...This study was carried out to identify gene expression patterns in different wool densities of rex rabbit. The mid-dorsal skin samples from 8 rex rabbits were studied. They were divided into two groups according to different wool densities. Total RNA was isolated and labeled by reverse transcription reaction with Cy5-dCTP and Cy3-dCTP for cDNA probe. The cDNA probe was hybridized with cDNA microarrays containing 14 601 rabbit’s genes. The differently expressed genes were analysed with the Gene Ontology （GO） classification and the pathway analysis. Hierarchical clustering was performed to clarify genes in association with different wool densities. The 2 657 differentially expressed genes were identified. Among them, 1 103 genes were functionally known genes, 687 genes were up-regulated and 419 were down-regulated. GO analysis indicated that these altered genes were associated with metabolism, signal transduction, cell cycle, cell adhesion, cell proliferation, cell division, apoptosis, and other processes. KEGG analysis showed that 95 signal pathways associated with up-regulated genes and 87 signal pathways associated with down-regulated genes had changed significantly （P0.05）. Some important differentially expressed genes in different wool densities of rex rabbit were identified, such as MMP2, TGF-β1, TGF-β2, IGF-1, ITGB1, RPS6KB1, BMP2, ActRIIB, CDK2, and CCNA2. Hierarchical clustering analysis separated the differentially expressed genes into 5 main characteristic groups. Data from cDNA microarray experiments clearly distinguished between group A and group B. Some important genes were identified, which might be useful in further study on wool density markers of rex rabbit.展开更多
Gene expression profile of the lung adenosquamous carcinoma was characterized by using cDNA microarray chip containing 4096 human genes.Among target genes,508 differentially expressed genes were identified in adenosqu...Gene expression profile of the lung adenosquamous carcinoma was characterized by using cDNA microarray chip containing 4096 human genes.Among target genes,508 differentially expressed genes were identified in adenosquamous carcinoma of the lung,232 genes were overexpressed and 276 genes were underexpressed.Among them,92 genes are cell signals transduction genes,34 genes are proto-oncogenes and tumor suppressor genes or cell cycle related genes or cell apoptosis related genes,29 genes are cell skeleton genes,28 genes are DNA synthesis,repair and recombination genes,12 genes are DNA binding and transcription genes.These genes may be associated with the occurence and development of adenosquamous carinome of the lung.展开更多
In bioinformatics applications,examination of microarray data has received significant interest to diagnose diseases.Microarray gene expression data can be defined by a massive searching space that poses a primary cha...In bioinformatics applications,examination of microarray data has received significant interest to diagnose diseases.Microarray gene expression data can be defined by a massive searching space that poses a primary challenge in the appropriate selection of genes.Microarray data classification incorporates multiple disciplines such as bioinformatics,machine learning(ML),data science,and pattern classification.This paper designs an optimal deep neural network based microarray gene expression classification(ODNN-MGEC)model for bioinformatics applications.The proposed ODNN-MGEC technique performs data normalization process to normalize the data into a uniform scale.Besides,improved fruit fly optimization(IFFO)based feature selection technique is used to reduce the high dimensionality in the biomedical data.Moreover,deep neural network(DNN)model is applied for the classification of microarray gene expression data and the hyperparameter tuning of the DNN model is carried out using the Symbiotic Organisms Search(SOS)algorithm.The utilization of IFFO and SOS algorithms pave the way for accomplishing maximum gene expression classification outcomes.For examining the improved outcomes of the ODNN-MGEC technique,a wide ranging experimental analysis is made against benchmark datasets.The extensive comparison study with recent approaches demonstrates the enhanced outcomes of the ODNN-MGEC technique in terms of different measures.展开更多
Background PANoptosis has the features of pyroptosis,apoptosis,and necroptosis.Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure(ALF),but limited attention has bee...Background PANoptosis has the features of pyroptosis,apoptosis,and necroptosis.Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure(ALF),but limited attention has been given to the crosstalk among them.In this study,we aimed to explore the role of PANoptosis in ALF and uncover new targets for its prevention or treatment.Methods Three ALF-related datasets(GSE14668,GSE62029,and GSE74000)were downloaded from the Gene Expression Omnibus(GEO)database to identify differentially expressed genes(DEGs).Hub genes were identified through intersecting DEGs,genes obtained from weighted gene co-expression network analysis(WGCNA),and genes related to PANoptosis.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein–protein interaction(PPI)analyses and gene set enrichment analysis(GSEA)were performed to determine functional roles.Verification was performed using an ALF mouse model.Results Our results showed that expression of seven hub genes(B-cell lymphoma-2-modifying factor(BMF),B-cell lymphoma-2-interacting protein 3-like(BNIP3L),Caspase-1(CASP1),receptor-interacting protein kinase 3(RIPK3),uveal autoantigen with coiled-coil domains and ankyrin repeats protein(UACA),uncoordinated-5 homolog B receptor(UNC5B),and Z-DNA-binding protein 1(ZBP1))was up-regulated in liver samples of patients.However,in the ALF mouse model,the expression of BNIP3L,RIPK3,phosphorylated RIPK3(P-RIPK3),UACA,and cleaved caspase-1 was up-regulated,while the expression of CASP1 and UNC5B was down-regulated.The expression of ZBP1 and BMF increased only during the development of ALF,and there was no significant change in the end stage.Immunofluorescence of mouse liver tissue showed that macrophages expressed all seven markers.Western blot results showed that pyroptosis,apoptosis,and necroptosis were always involved in lipopolysaccharide(LPS)/D-galactosamine(D-gal)-induced ALF mice.The ALF cell model showed that bone marrow-derived macrophages(BMDMs)form PANoptosomes after LPS stimulation.Conclusions Our results suggest that PANoptosis of macrophages promotes the development of ALF.The seven new ALF biomarkers identified and validated in this study may contribute to further investigation of diagnostic markers or novel therapeutic targets of ALF.展开更多
Background:Microarray analysis is a popular tool to investigate the function of genes that are responsi-ble for the phenotype of the disease.Keloid is a intricate lesion which is probably modulated by interplay of man...Background:Microarray analysis is a popular tool to investigate the function of genes that are responsi-ble for the phenotype of the disease.Keloid is a intricate lesion which is probably modulated by interplay of manygenes.We ventured to study the differences of gene expressions between keloids and normal skins with the aid ofcDNA microarray in order to explore the molecular mechanism underlying keloid formation.Methods:The PCRproducts of 8400 human genes were spotted on a chip in array.The DNAs were t...展开更多
To better understand the toxicity of an antifouling booster biocide Irgarol-1051 degradation product M2 3-4-tert-butylamino-6-methylthiol-s-triazin-2-ylamino pro-pionaldehyde this study utilized a DNA microarray techn...To better understand the toxicity of an antifouling booster biocide Irgarol-1051 degradation product M2 3-4-tert-butylamino-6-methylthiol-s-triazin-2-ylamino pro-pionaldehyde this study utilized a DNA microarray technique to explore the genotoxicity of M2. The Affymetrix Inc. rat genome 230 2.0 GeneChip was employed to examine alterations in gene regulation in rat hepatoma cells exposed to 30 μmol/L of M2 for 96 h.The results showed that 38 genes were significantly p＆lt;0.002 5 altered by M2 at two-fold changes in all the four possible control/exposure comparisons. Accn5 was the only well described gene consistently being suppressed which likely altered the epithelial sodium channel ENaC .10 and 82 annotated genes were up-and down-regulated in at least one of the control/exposure comparisons respectively. The induced genes were mainly involved in the nucleus belonging to the cellular component. The largest categories of suppression concerned G-protein coupled receptor protein signaling pathways belonging to the biological process and integral to membranes belonging to the cellular component.展开更多
Background： The objective of this study was to characterize the mRNA expression profile related to rumen epithelial inflammation through the in vivo and in vitro experiments. In the in vivo experiment, rumen papillae...Background： The objective of this study was to characterize the mRNA expression profile related to rumen epithelial inflammation through the in vivo and in vitro experiments. In the in vivo experiment, rumen papillae were collected from four dairy cows adapted to either a 40 % （LC） or 70 % （HC） concentrate feeds for microarray analysis. Results： Results showed that 245 differentially expressed genes （DEGs） were detected in the cows fed the HC relative to the LC diet. The DEGs were first annotated, and results revealed that the expression of inflammation- related genes, including IL-1t8, 1L-2, IL-22, CCL19, CCLS, CX3CR1, CXCL6, INHBE, LEPR, PRL, and TNFRSF9 found in the cytokine-cytokine receptor pathway were up-regulated in the HC-fed cows, indicating local inflammation in the rumen epithelium was triggered. The expression of IL-1~, 1l_-2, and IL-6 was further validated by qRT-PCR. To demonstrate whether there were relationships between cytokine mRNA expression and ruminal factors （pH and LPS）, the isolated ruminal epithelial cells were cultured in vitro. Results showed that the mRNA expression of IL-1, IL-2, IL-6, and IL-8 increased after the LPS treatment, while Iow-pH treatment elevated the mRNA expression of TNF-a, suggesting that Iow-pH coupled with higher levels of LPS in rumen of cows fed the HC may be mainly responsible for the triggered local ruminal inflammation. Conclusions： Our results indicate that ruminal local inflammation response might be triggered during HC feeding and these findings also enhance the knowledge of rumen epithelial adaptation to HC at the molecular level.展开更多
Catalpol,a major bioactive component from Rehmannia glutinosa,which has been used to treat diabetes.The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mi...Catalpol,a major bioactive component from Rehmannia glutinosa,which has been used to treat diabetes.The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice.The db/db mice were randomly divided into six groups(10/group) according to their blood glucose levels:db/db control,metformin(positive control),and four dose levels of catalpol treatment(25,50,100,and 200 mg·kg^(-1)),and 10 db/m mice were used as the normal control.All the groups were administered orally for 8 weeks.The levels of fasting blood glucose(FBG),random blood glucose(RBG),glucose tolerance,insulin tolerance,and glycated serum protein(GSP) and the globe gene expression in liver tissues were analyzed.Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner.Catalpol treatment also remarkably reduce fasting blood glucose(FBG) and random blood glucose(RBG) in a dose-dependent manner.The RBG-lowering effect of catalpol was better than that of metformin.Furthermore,catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity.Catalpol treatment significantly decreased GSP level.The comparisons of gene expression in liver tissues among normal control mice,db/db mice and catalpol treated mice(200 and 100 mg·kg^(-1)) indicated that there were significant increases in the expressions of 287 genes,whichwere mainly involved in lipid metabolism,response to stress,energy metabolism,and cellular processes,and significant decreases in the expressions of 520 genes,which were mainly involved in cell growth,death,immune system,and response to stress.Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways,including Irs1(insulin receptor substrate 1),Idh2(isocitrate dehydrogenase 2(NADP+),mitochondrial),G6pd2(glucose-6-phosphate dehydrogenase 2),and SOCS3(suppressor of cytokine signaling 3).In conclusion,catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.展开更多
文摘Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive thyroid-related cell lines cultured under simulated microgravity.Methods:Five thyroid-related cell lines—normal thyrocytes(Nthy-ori 3-1),papillary thyroid cancer(PTC)cells(SNU-790,TPC-1),poorly differentiated thyroid cancer cell(BCPAP),and anaplastic thyroid cancer cell(SNU-80)—were cultured under simulated microgravity(10-3 g)using a clinostat.Differentially expressed genes(DEGs)were analyzed using cDNA microarray,followed by functional annotation and assessment of aggressiveness via Transwell migration and invasion assays.Results:DEG analysis under simulated microgravity revealed distinct gene expression profiles by gravity condition,with 2980 DEGs in SNU-790,1033 in BCPAP,562 in TPC-1,477 in Nthy-ori 3-1,and 246 in SNU-80,as confirmed by hierarchical clustering.In PTC cell lines(SNU-790,TPC-1),G2–M phase–related genes were upregulated.In non-PTC cell lines(BCPAP,SNU-80),genes associated with innate immune response,Toll-like receptor signaling,were upregulated,whereas Hypoxia-Inducible Factor 1-alpha(HIF-1α)signaling-related genes were downregulated.Additionally,under simulated microgravity,significant migration was observed in SNU-790(3×104 cells)and BCPAP(2×104 and 3×104),while significant invasion occurred in SNU-790,Nthy-ori 3-1,and BCPAP at a seeding density of 2×104.Other conditions showed no significant differences.Conclusion:This study comprehensively evaluates the effects of simulated microgravity using a diverse panel of thyroid-related cell lines.Thesefindings provide valuable insight into how microgravity could influence cancer biology,emphasizing the importance of further research on cancer behavior in space environments and its implications for human health during long-term space missions.
文摘OBJECTIVES: To survey the gene expression profiles in pancreatic carcinoma by using cDNA microarray and detect target genes for further study. METHODS: Three mixed samples from 2 cases of normal pancreatic tissue and 4 cases of moderate-differentiated pancreatic carcinoma were studied by means of cDNA microarray consisting of 18 000 genes. RESULTS: 1484 and 1353 different expressed genes were observed in two cancer samples respectively. We identified 455 genes altered with the same tendency in both samples, including 102 up-regulated and 353 down-regulated genes. There were 274 known genes and 181 unknown genes; 27.8% and 52.0% genes respectively had an expression level in cancer that was 2-fold higher or lower than that in normal samples. Tumor suppressor genes, growth factors and receptor genes, signal conduction genes, transcription factor genes were identified. CONCLUSIONS: cDNA microarray is an efficient and high-throughout method to investigate gene expression profiles in pancreatic carcinoma. MBD1, EDG1 and gene hypermethylation mechanism would play an important role in the pathogenesis of pancreatic carcinoma.
基金supported by the National Natural Science Foundation of China(81371213,81070987,and30971531)the grants from the Ministry of Science and Technology of China(2010CB945600 and 2010CB945601)
文摘Neuroplastin 65 （Np65） is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout （KO） mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially- expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdhl, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.
文摘Menopause is one of the key physiological events in the female life and can increase the risk for a number of complex autoimmune, neurodegenerative, metabolic, and cardiovascular disorders. Circulating monocytes can differentiate into various cell types and play an important role in tissue morphogenesis and immune response. We studied gene expression profiles of peripheral blood monocytes in healthy pre- and postmenopausal women using Affymetrix Human U133A GeneChip array that contains probes for -14,500 genes. Comparative analyses between the samples showed that 20 genes were up- and 20 were down-regulated. Of these genes, 28 were classified into six major GO categories relevant to such biological processes as the cell proliferation, immune response, cellular metabolism, and the others. The remaining 12 genes have yet unidentified biological functions. Our results support the hypothesis that functional state of circulating monocytes is indeed affected by menopause, and resulting changes may be determined through the genomewide gene expression profiling. Several differentially expressed genes identified in this study may be candidates for further studies of menopause-associated systemic autoimmune, neurodegenerative, and cardiovascular disorders. Our study is only the first attempt in this direction, but it lays a basis for further research.
基金Supported by the Special Fund of Chinese Academy of Sciences, No. KSCX1-06
文摘AIM: To find out key genes responsible for hepatocarc inogenesis and to further understand the underlying molecular mechanism through investigating the differential gene expression between human normal liver tissue and hepatocellular carcinoma (HCC).METHODS: DNA microarray was prepared by spotting PCR products of 1 000 human genes including 445 novel genes, 540 known genes as well as 12 positive (housekeeping) and 3 negative controls (plant gene) onto treated glass slides. cDNA probes were prepared by labeling normal liver tissue mRNA and cancer liver tissue mRNA with Cy3-dUTP and Cy5-dUTP separately through reverse transcription. The arrays were hybridized against the cDNA probe and the fluorescent signals were scanned. The dataobtained from repeated experiments were analyzed. RESULTS: Among the 20 couple samples investigated (from cancerous liver tissue and normal liver tissue), 38 genes including 21 novel genes and 17 known genes exhibited different expressions. CONCLUSION: cDNA microarray technique is powerful to identify candidate target genes that may play important roles in human carcinogenesis. Further analysis of the obtained genes is helpful to understand the molecular changes in HCC progression and ultimately may lead to the identification of new targets for HCC diagnosis and intervention.
基金This work is supported by the City University of Hong Kong through a Strategic Research Grant (CityU Project No. 7001113).
文摘Objective: A single mechanistic pathway cannot explain the genesis of drug resistance in cancer. Drug resistance in cancer is a major obstacle to successful chemotherapy. KB cells provide a useful starting point for selection of the multidrug resistant (MDR) cell lines. Methods: We used cDNA microarrays containing 12,720 sequences of known genes, expressed sequence tags and unknown clones to monitor gene expression profiles in MDR KB cells. Results: Preliminary data analysis showed that 18 genes were up-regulated and 18 genes were down-regulated by comparison of expression patterns between KB 3-1 and MDR KB-V1 cells. Furthermore, the highly over-expressed CGA, CLU genes in MDR KB-V1 cell were verified with conventional Northern blot analysis. These genes contain information predictive of drug resistance of cancer cells. Conclusion: Our study demonstrates that genome-wide gene expression profiling by using cDNA microarray technique is a valuable approach in obtaining molecular mechanism of drug resistance in cancer cells.
文摘Pathogenesis of the endometriosis is complex and the etiology is still unclear. The objective of this study was to examine that endometrial gene expression in late secretory phase endometrium differs between patients with and without endometriosis. Five patients with proven advanced-stage endometriosis and 5 controls underwent endometrial biopsy in the late secretory phase. Analysis of eutopic endometrial gene expression was performed using Affymetrix gene arrays and differentially expressed genes were assigned to gene ontology groups based on overrepresented analysis using Database for Annotation, Visualization, and Integrated Discovery software. Four hundred sixty two genes were identified as up-regulated such as matrix metalloproteinase 10, cytochrome P450 family 24 subfamily A polypeptide 1, matrix metalloproteinase 3, chemokine (C-C motif) ligand 20, Rho family GTPase 1, interleukin 1-beta, and insulin-like growth factor binding protein 1. Six hundred forty three genes were down-regulated in all endometriotic samples. A lot of genes related with metabolic process, cellular ketone metabolic process and ncRNA metabolic processing were included. Expression patterns of selected five genes were validated by quantitative real time PCR. The results of this analysis support that the eutopic endometrium from patients with advanced-stage endometriosis has distinct gene expression profile from eutopic endometrium of control without endometriosis.
基金supported by the Science and Technol- ogy Support Project of Hebei, China (06220402D-4)the Modern Agriculture (Rabbit) Industrial Science and Technology System, China (nycyti-44)
文摘This study was carried out to identify gene expression patterns in different wool densities of rex rabbit. The mid-dorsal skin samples from 8 rex rabbits were studied. They were divided into two groups according to different wool densities. Total RNA was isolated and labeled by reverse transcription reaction with Cy5-dCTP and Cy3-dCTP for cDNA probe. The cDNA probe was hybridized with cDNA microarrays containing 14 601 rabbit’s genes. The differently expressed genes were analysed with the Gene Ontology （GO） classification and the pathway analysis. Hierarchical clustering was performed to clarify genes in association with different wool densities. The 2 657 differentially expressed genes were identified. Among them, 1 103 genes were functionally known genes, 687 genes were up-regulated and 419 were down-regulated. GO analysis indicated that these altered genes were associated with metabolism, signal transduction, cell cycle, cell adhesion, cell proliferation, cell division, apoptosis, and other processes. KEGG analysis showed that 95 signal pathways associated with up-regulated genes and 87 signal pathways associated with down-regulated genes had changed significantly （P0.05）. Some important differentially expressed genes in different wool densities of rex rabbit were identified, such as MMP2, TGF-β1, TGF-β2, IGF-1, ITGB1, RPS6KB1, BMP2, ActRIIB, CDK2, and CCNA2. Hierarchical clustering analysis separated the differentially expressed genes into 5 main characteristic groups. Data from cDNA microarray experiments clearly distinguished between group A and group B. Some important genes were identified, which might be useful in further study on wool density markers of rex rabbit.
基金Supported by the National Natural Science Foun-dation of China(39870305)
文摘Gene expression profile of the lung adenosquamous carcinoma was characterized by using cDNA microarray chip containing 4096 human genes.Among target genes,508 differentially expressed genes were identified in adenosquamous carcinoma of the lung,232 genes were overexpressed and 276 genes were underexpressed.Among them,92 genes are cell signals transduction genes,34 genes are proto-oncogenes and tumor suppressor genes or cell cycle related genes or cell apoptosis related genes,29 genes are cell skeleton genes,28 genes are DNA synthesis,repair and recombination genes,12 genes are DNA binding and transcription genes.These genes may be associated with the occurence and development of adenosquamous carinome of the lung.
基金The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work under grant number(RGP 2/42/43)This work was supported by Taif University Researchers Supporting Program(project number:TURSP-2020/200),Taif University,Saudi Arabia.
文摘In bioinformatics applications,examination of microarray data has received significant interest to diagnose diseases.Microarray gene expression data can be defined by a massive searching space that poses a primary challenge in the appropriate selection of genes.Microarray data classification incorporates multiple disciplines such as bioinformatics,machine learning(ML),data science,and pattern classification.This paper designs an optimal deep neural network based microarray gene expression classification(ODNN-MGEC)model for bioinformatics applications.The proposed ODNN-MGEC technique performs data normalization process to normalize the data into a uniform scale.Besides,improved fruit fly optimization(IFFO)based feature selection technique is used to reduce the high dimensionality in the biomedical data.Moreover,deep neural network(DNN)model is applied for the classification of microarray gene expression data and the hyperparameter tuning of the DNN model is carried out using the Symbiotic Organisms Search(SOS)algorithm.The utilization of IFFO and SOS algorithms pave the way for accomplishing maximum gene expression classification outcomes.For examining the improved outcomes of the ODNN-MGEC technique,a wide ranging experimental analysis is made against benchmark datasets.The extensive comparison study with recent approaches demonstrates the enhanced outcomes of the ODNN-MGEC technique in terms of different measures.
基金supported by the National Science and Technology Major Project of China(No.2018ZX10302206).
文摘Background PANoptosis has the features of pyroptosis,apoptosis,and necroptosis.Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure(ALF),but limited attention has been given to the crosstalk among them.In this study,we aimed to explore the role of PANoptosis in ALF and uncover new targets for its prevention or treatment.Methods Three ALF-related datasets(GSE14668,GSE62029,and GSE74000)were downloaded from the Gene Expression Omnibus(GEO)database to identify differentially expressed genes(DEGs).Hub genes were identified through intersecting DEGs,genes obtained from weighted gene co-expression network analysis(WGCNA),and genes related to PANoptosis.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein–protein interaction(PPI)analyses and gene set enrichment analysis(GSEA)were performed to determine functional roles.Verification was performed using an ALF mouse model.Results Our results showed that expression of seven hub genes(B-cell lymphoma-2-modifying factor(BMF),B-cell lymphoma-2-interacting protein 3-like(BNIP3L),Caspase-1(CASP1),receptor-interacting protein kinase 3(RIPK3),uveal autoantigen with coiled-coil domains and ankyrin repeats protein(UACA),uncoordinated-5 homolog B receptor(UNC5B),and Z-DNA-binding protein 1(ZBP1))was up-regulated in liver samples of patients.However,in the ALF mouse model,the expression of BNIP3L,RIPK3,phosphorylated RIPK3(P-RIPK3),UACA,and cleaved caspase-1 was up-regulated,while the expression of CASP1 and UNC5B was down-regulated.The expression of ZBP1 and BMF increased only during the development of ALF,and there was no significant change in the end stage.Immunofluorescence of mouse liver tissue showed that macrophages expressed all seven markers.Western blot results showed that pyroptosis,apoptosis,and necroptosis were always involved in lipopolysaccharide(LPS)/D-galactosamine(D-gal)-induced ALF mice.The ALF cell model showed that bone marrow-derived macrophages(BMDMs)form PANoptosomes after LPS stimulation.Conclusions Our results suggest that PANoptosis of macrophages promotes the development of ALF.The seven new ALF biomarkers identified and validated in this study may contribute to further investigation of diagnostic markers or novel therapeutic targets of ALF.
文摘Background:Microarray analysis is a popular tool to investigate the function of genes that are responsi-ble for the phenotype of the disease.Keloid is a intricate lesion which is probably modulated by interplay of manygenes.We ventured to study the differences of gene expressions between keloids and normal skins with the aid ofcDNA microarray in order to explore the molecular mechanism underlying keloid formation.Methods:The PCRproducts of 8400 human genes were spotted on a chip in array.The DNAs were t...
基金The Research Grants Council of Hong Kong SAR,China(No.City U,1445/05M)the National Natural Science Foundation of China(No.41301546)
文摘To better understand the toxicity of an antifouling booster biocide Irgarol-1051 degradation product M2 3-4-tert-butylamino-6-methylthiol-s-triazin-2-ylamino pro-pionaldehyde this study utilized a DNA microarray technique to explore the genotoxicity of M2. The Affymetrix Inc. rat genome 230 2.0 GeneChip was employed to examine alterations in gene regulation in rat hepatoma cells exposed to 30 μmol/L of M2 for 96 h.The results showed that 38 genes were significantly p＆lt;0.002 5 altered by M2 at two-fold changes in all the four possible control/exposure comparisons. Accn5 was the only well described gene consistently being suppressed which likely altered the epithelial sodium channel ENaC .10 and 82 annotated genes were up-and down-regulated in at least one of the control/exposure comparisons respectively. The induced genes were mainly involved in the nucleus belonging to the cellular component. The largest categories of suppression concerned G-protein coupled receptor protein signaling pathways belonging to the biological process and integral to membranes belonging to the cellular component.
基金support of the National Basic Research Program of China(2011CB100801)
文摘Background： The objective of this study was to characterize the mRNA expression profile related to rumen epithelial inflammation through the in vivo and in vitro experiments. In the in vivo experiment, rumen papillae were collected from four dairy cows adapted to either a 40 % （LC） or 70 % （HC） concentrate feeds for microarray analysis. Results： Results showed that 245 differentially expressed genes （DEGs） were detected in the cows fed the HC relative to the LC diet. The DEGs were first annotated, and results revealed that the expression of inflammation- related genes, including IL-1t8, 1L-2, IL-22, CCL19, CCLS, CX3CR1, CXCL6, INHBE, LEPR, PRL, and TNFRSF9 found in the cytokine-cytokine receptor pathway were up-regulated in the HC-fed cows, indicating local inflammation in the rumen epithelium was triggered. The expression of IL-1~, 1l_-2, and IL-6 was further validated by qRT-PCR. To demonstrate whether there were relationships between cytokine mRNA expression and ruminal factors （pH and LPS）, the isolated ruminal epithelial cells were cultured in vitro. Results showed that the mRNA expression of IL-1, IL-2, IL-6, and IL-8 increased after the LPS treatment, while Iow-pH treatment elevated the mRNA expression of TNF-a, suggesting that Iow-pH coupled with higher levels of LPS in rumen of cows fed the HC may be mainly responsible for the triggered local ruminal inflammation. Conclusions： Our results indicate that ruminal local inflammation response might be triggered during HC feeding and these findings also enhance the knowledge of rumen epithelial adaptation to HC at the molecular level.
文摘Catalpol,a major bioactive component from Rehmannia glutinosa,which has been used to treat diabetes.The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice.The db/db mice were randomly divided into six groups(10/group) according to their blood glucose levels:db/db control,metformin(positive control),and four dose levels of catalpol treatment(25,50,100,and 200 mg·kg^(-1)),and 10 db/m mice were used as the normal control.All the groups were administered orally for 8 weeks.The levels of fasting blood glucose(FBG),random blood glucose(RBG),glucose tolerance,insulin tolerance,and glycated serum protein(GSP) and the globe gene expression in liver tissues were analyzed.Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner.Catalpol treatment also remarkably reduce fasting blood glucose(FBG) and random blood glucose(RBG) in a dose-dependent manner.The RBG-lowering effect of catalpol was better than that of metformin.Furthermore,catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity.Catalpol treatment significantly decreased GSP level.The comparisons of gene expression in liver tissues among normal control mice,db/db mice and catalpol treated mice(200 and 100 mg·kg^(-1)) indicated that there were significant increases in the expressions of 287 genes,whichwere mainly involved in lipid metabolism,response to stress,energy metabolism,and cellular processes,and significant decreases in the expressions of 520 genes,which were mainly involved in cell growth,death,immune system,and response to stress.Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways,including Irs1(insulin receptor substrate 1),Idh2(isocitrate dehydrogenase 2(NADP+),mitochondrial),G6pd2(glucose-6-phosphate dehydrogenase 2),and SOCS3(suppressor of cytokine signaling 3).In conclusion,catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
