ABSTRACT
BACKGROUND: Bisphenol A (BPA) and phthalates metabolites are linked to a variety of adverse health consequences but studies have not explored their association with growth trajectories. OBJECTIVE: Explore body mass index (BMI) trajectories for tertile exposures to BPA and phthalates metabolites in the third trimester of pregnancy. METHODS: We constructed BMI (kg/m2 ) trajectories from birth to 14 years in a birth cohort of 249 children from Mexico City using tertiles of third trimester maternal urinary concentrations of BPA and phthalates metabolites. Fractional age polynomials and mixed effects models were fit separately by sex. Predicted models were plotted for each metabolite tertile with the covariates mother's education and BMI centered at average values. RESULTS: Highest predicted BMI trajectories for female children were observed for third tertile exposure to the phthalate metabolite mono(2-ethyl-5-carboxypentyl) phthalate. In male children, first tertile exposure to mono-isobutyl phthalate and monobenzyl phthalate and second tertile exposure to mono(2-ethylhexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate predicted the highest BMI trajectory by adolescence. There was no relationshsip between BPA and child growth trajectory. CONCLUSIONS: These results suggest sex-specific differences in BMI trajectories by levels of metabolite exposure. Additional studies are needed to consider growth through adolescence in assessing the association of pregnancy exposures on child's BMI.
Subject(s)
Benzhydryl Compounds/urine , Body Mass Index , Environmental Exposure/statistics & numerical data , Phenols/urine , Phthalic Acids/urine , Pregnancy Trimester, Third/drug effects , Prenatal Exposure Delayed Effects/epidemiology , Adolescent , Benzhydryl Compounds/metabolism , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Mexico/epidemiology , Phenols/metabolism , Phthalic Acids/metabolism , Pregnancy , Prospective StudiesABSTRACT
The aim of this study was to evaluate the clinical and radiographic outcomes of upper thoracic (UT) versus lower thoracic (LT) upper instrumented vertebrae (UIV) for adult scoliosis by meta-analysis. We conducted a literature search in three databases to retrieve related studies up to March 15, 2017. The preliminary screened studies were assessed by two reviewers according to the selection criteria. All analyses were carried out using the statistical software package R version 2.31. Odds ratios (OR) with 95% confidence intervals (CI) were used to describe the results. The I2 statistic and Q statistic test were used for heterogeneity assessment. Egger's test was performed to detect publication bias. To assess the effect of each study on the overall pooled OR or standardized mean difference (SMD), sensitive analysis was conducted. Ten trials published between 2007 and 2015 were eligible and included in our study. Meta-analysis revealed that the UT group was associated with more blood loss (SMD=0.4779, 95%CI=0.3349-0.6209, Z=6.55, P<0.0001) and longer operating time (SMD=0.5780, 95%CI=0.1971-0.958, Z=2.97, P=0.0029) than the LT group. However, there was no significant difference in Oswestry Disability Index, Scoliosis Research Society (SRS) function subscores, radiographic outcomes including sagittal vertical axis, lumbar lordosis, and thoracic kyphosis, length of hospital stay, and revision rates between the two groups. No evidence of publication bias was found between the two groups. Fusion from the lower thoracic spine (below T10) has as advantages a shorter operation time and less blood loss than upper thoracic spine (above T10) in posterior long-segment fixation for degenerative lumbar scoliosis.
Subject(s)
Lumbar Vertebrae/diagnostic imaging , Scoliosis/diagnostic imaging , Scoliosis/surgery , Spinal Fusion/instrumentation , Thoracic Vertebrae/diagnostic imaging , Adult , Evidence-Based Medicine , Follow-Up Studies , Humans , Publication Bias , Retrospective StudiesABSTRACT
Multiple growth factors can be administered to mimic the natural process of bone healing in bone tissue engineering. We investigated the effects of sequential release of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) from polylactide-poly (ethylene glycol)-polylactide (PELA) microcapsule-based scaffolds on bone regeneration. To improve the double emulsion/solvent evaporation technique, VEGF was encapsulated in PELA microcapsules, to which BMP-2 was attached. The scaffold (BMP-2/PELA/VEGF) was then fused to these microcapsules using the dichloromethane vapor method. The bioactivity of the released BMP-2 and VEGF was then quantified in rat mesenchymal stem cells (rMSCs). Immunoblotting analysis showed that BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblasts via the MAPK and Wnt pathways. Osteoblast differentiation was assessed through alkaline phosphatase expression. When compared with simple BMP-2 plus VEGF group and pure PELA group, osteoblast differentiation in BMP-2/PELA/VEGF group significantly increased. An MTT assay indicated that BMP-2-loaded PELA scaffolds had no adverse effects on cell activity. BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblast via the ERK1/2 and Wnt pathways. Our findings indicate that the sequential release of BMP-2 and VEGF from PELA microcapsule-based scaffolds is a promising approach for the treatment of bone defects.
Subject(s)
Animals , Rabbits , Rats , Polyesters/pharmacology , Polyethylene Glycols/pharmacology , Mitogen-Activated Protein Kinases/metabolism , Vascular Endothelial Growth Factors/metabolism , Tissue Scaffolds , Bone Morphogenetic Protein 2/metabolism , Mesenchymal Stem Cells/cytology , Time Factors , Bone Regeneration , Signal Transduction/physiology , Cells, Cultured , Models, Animal , Cell Proliferation , beta Catenin/physiology , Nanoparticles , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Wnt Signaling Pathway/physiologyABSTRACT
The aim of this study was to evaluate the clinical and radiographic outcomes of upper thoracic (UT) versus lower thoracic (LT) upper instrumented vertebrae (UIV) for adult scoliosis by meta-analysis. We conducted a literature search in three databases to retrieve related studies up to March 15, 2017. The preliminary screened studies were assessed by two reviewers according to the selection criteria. All analyses were carried out using the statistical software package R version 2.31. Odds ratios (OR) with 95% confidence intervals (CI) were used to describe the results. The I2 statistic and Q statistic test were used for heterogeneity assessment. Egger's test was performed to detect publication bias. To assess the effect of each study on the overall pooled OR or standardized mean difference (SMD), sensitive analysis was conducted. Ten trials published between 2007 and 2015 were eligible and included in our study. Meta-analysis revealed that the UT group was associated with more blood loss (SMD=0.4779, 95%CI=0.3349-0.6209, Z=6.55, P<0.0001) and longer operating time (SMD=0.5780, 95%CI=0.1971-0.958, Z=2.97, P=0.0029) than the LT group. However, there was no significant difference in Oswestry Disability Index, Scoliosis Research Society (SRS) function subscores, radiographic outcomes including sagittal vertical axis, lumbar lordosis, and thoracic kyphosis, length of hospital stay, and revision rates between the two groups. No evidence of publication bias was found between the two groups. Fusion from the lower thoracic spine (below T10) has as advantages a shorter operation time and less blood loss than upper thoracic spine (above T10) in posterior long-segment fixation for degenerative lumbar scoliosis.
Subject(s)
Humans , Adult , Lumbar Vertebrae/diagnostic imaging , Scoliosis/diagnostic imaging , Scoliosis/surgery , Spinal Fusion/instrumentation , Thoracic Vertebrae/diagnostic imaging , Evidence-Based Medicine , Follow-Up Studies , Publication Bias , Retrospective StudiesABSTRACT
Multiple growth factors can be administered to mimic the natural process of bone healing in bone tissue engineering. We investigated the effects of sequential release of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) from polylactide-poly (ethylene glycol)-polylactide (PELA) microcapsule-based scaffolds on bone regeneration. To improve the double emulsion/solvent evaporation technique, VEGF was encapsulated in PELA microcapsules, to which BMP-2 was attached. The scaffold (BMP-2/PELA/VEGF) was then fused to these microcapsules using the dichloromethane vapor method. The bioactivity of the released BMP-2 and VEGF was then quantified in rat mesenchymal stem cells (rMSCs). Immunoblotting analysis showed that BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblasts via the MAPK and Wnt pathways. Osteoblast differentiation was assessed through alkaline phosphatase expression. When compared with simple BMP-2 plus VEGF group and pure PELA group, osteoblast differentiation in BMP-2/PELA/VEGF group significantly increased. An MTT assay indicated that BMP-2-loaded PELA scaffolds had no adverse effects on cell activity. BMP-2/PELA/VEG promoted the differentiation of rMSCs into osteoblast via the ERK1/2 and Wnt pathways. Our findings indicate that the sequential release of BMP-2 and VEGF from PELA microcapsule-based scaffolds is a promising approach for the treatment of bone defects.
Subject(s)
Bone Morphogenetic Protein 2/metabolism , Mesenchymal Stem Cells/cytology , Mitogen-Activated Protein Kinases/metabolism , Polyesters/pharmacology , Polyethylene Glycols/pharmacology , Tissue Scaffolds , Vascular Endothelial Growth Factors/metabolism , Animals , Bone Regeneration , Cell Proliferation , Cells, Cultured , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Models, Animal , Nanoparticles , Rabbits , Rats , Signal Transduction/physiology , Time Factors , Wnt Signaling Pathway/physiology , beta Catenin/physiologyABSTRACT
Myocardial ischemia is a major cause of death and remains a disease with extremely deficient clinical therapies and a major problem worldwide. Cold inducible RNA-binding protein (CIRBP) is reported to be involved in multiple pathological processes, including myocardial ischemia. However, the molecular mechanisms of myocardial ischemia remain elusive. Here, we first overexpressed CIRBP by transfection of pc-CIRBP (pcDNA3.1 containing coding sequenced for CIRBP) and silenced CIRBP by transfection of small interfering RNA targeting CIRBP (siCIRBP). pcDNA3.1 and the negative control of siCIRBP (siNC) were transfected into H9C2 cells to act as controls. We then constructed a cell model of myocardial ischemia through culturing cells in serum-free medium with hypoxia in H9C2 cells. Subsequently, AlamarBlue assay, flow cytometry and western blot analysis were used, respectively, to assess cell viability, reactive oxygen species (ROS) level and apoptosis, and expression levels of IκBα, p65 and Bcl-3. We demonstrated that CIRBP overexpression promoted cell proliferation (P<0.001), inhibited cell apoptosis (P<0.05), reduced ROS level (P<0.001), down-regulated phosphorylated levels of IκBα and p65 (P<0.01 or P<0.001), and up-regulated expression of Bcl-3 (P<0.001) in H9C2 cells with myocardial ischemia. The influence of CIRBP knockdown yielded opposite results. Our study revealed that CIRBP could protect H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway.
Subject(s)
Myocardial Ischemia/metabolism , Myocardial Ischemia/prevention & control , NF-kappa B/antagonists & inhibitors , Protective Agents/pharmacology , RNA-Binding Proteins/pharmacology , Animals , Apoptosis/drug effects , Blotting, Western , Cell Proliferation/drug effects , Cell Survival , Cells, Cultured , Flow Cytometry , Gene Expression Regulation , NF-kappa B/metabolism , RNA, Small Interfering , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Rats , Reactive Oxygen Species/analysis , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Transfection/methodsABSTRACT
Sex hormone receptors play critical roles in development and reproduction. However, it is not known whether they exist in Raillietina tapeworms, and if they do, whether they have a similar function to that in vertebrates. We examined the immunohistochemical distributions of androgen receptors (ARs), estrogen receptors (ERs), and progesterone receptors (PRs) in the tissues of two tapeworm species: Raillietina echinobothrida and Raillietina tetragona. Immunopositive ARs were found in the entire reproductive system of R. echinobothrida, including the testes, ovaries, and oocysts, and weakly immunopositive ERs and PRs were found in the testes, ovaries, and oocysts. Immunopositive ARs were also found throughout the entire reproductive system of R. tetragona, including the testes, ovaries, and oocysts, and weakly immunopositive ERs were in the testes and oocysts; the PRs were distributed in an immunonegative manner. The results show that androgens and their receptors play critical roles in reproductive system development in the two tapeworms. The immunoreactivity and tissue localizations of the sex hormone receptors suggest that, in both species, they have similar functions as in vertebrates, and modulate reproduction.
Subject(s)
Cestoda/metabolism , Androgens/metabolism , Animals , Gonadal Steroid Hormones/metabolism , Immunohistochemistry , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolismABSTRACT
Propofol is a frequently used intravenous anesthetic agent. Recent studies show that propofol exerts a number of non-anesthetic effects. The present study aimed to investigate the effects of propofol on lung cancer cell lines H1299 and H1792 and functional role of microRNA (miR)-486 in these effects. H1299 and/or H1792 cells were treated with or without propofol and transfected or not with miR-486 inhibitor, and then cell viability and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry. The expression of miR-486 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) with or without propofol treatment. Western blot was performed to analyze the protein expression of Forkhead box, class O (FOXO) 1 and 3, Bcl-2 interacting mediator of cell death (Bim), and pro- and activated caspases-3. Results showed that propofol significantly increased the miR-486 levels in both H1299 and H1792 cells compared to untreated cells in a dose-dependent manner (P<0.05 or P<0.01). Propofol statistically decreased cell viability but increased the percentages of apoptotic cells and protein expressions of FOXO1, FOXO3, Bim, and pro- and activated caspases-3; however, miR-486 inhibitor reversed the effects of propofol on cell viability, apoptosis, and protein expression (P<0.05 or P<0.01). In conclusion, propofol might be an ideal anesthetic for lung cancer surgery by effectively inhibiting lung cancer cell viability and inducing cell apoptosis. Modulation of miR-486 might contribute to the anti-tumor activity of propofol.
Subject(s)
Lung Neoplasms/metabolism , MicroRNAs/metabolism , Propofol/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Real-Time Polymerase Chain ReactionABSTRACT
Propofol is a frequently used intravenous anesthetic agent. Recent studies show that propofol exerts a number of non-anesthetic effects. The present study aimed to investigate the effects of propofol on lung cancer cell lines H1299 and H1792 and functional role of microRNA (miR)-486 in these effects. H1299 and/or H1792 cells were treated with or without propofol and transfected or not with miR-486 inhibitor, and then cell viability and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry. The expression of miR-486 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) with or without propofol treatment. Western blot was performed to analyze the protein expression of Forkhead box, class O (FOXO) 1 and 3, Bcl-2 interacting mediator of cell death (Bim), and pro- and activated caspases-3. Results showed that propofol significantly increased the miR-486 levels in both H1299 and H1792 cells compared to untreated cells in a dose-dependent manner (P<0.05 or P<0.01). Propofol statistically decreased cell viability but increased the percentages of apoptotic cells and protein expressions of FOXO1, FOXO3, Bim, and pro- and activated caspases-3; however, miR-486 inhibitor reversed the effects of propofol on cell viability, apoptosis, and protein expression (P<0.05 or P<0.01). In conclusion, propofol might be an ideal anesthetic for lung cancer surgery by effectively inhibiting lung cancer cell viability and inducing cell apoptosis. Modulation of miR-486 might contribute to the anti-tumor activity of propofol.
Subject(s)
Humans , Lung Neoplasms/metabolism , MicroRNAs/metabolism , Propofol/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Real-Time Polymerase Chain ReactionABSTRACT
Mineral elements in barley (Hordeum vulgare) play an important physiological role in global human health. In this study, quantitative trait loci (QTLs) for concentration of nine mineral elements in barley grain and grass powder were detected in a population of 193 recombinant inbred lines of the barley cross Ziguangmangluoerling x Schooner and the parents. We observed large genetic variation contributing to element concentrations in both grains and grass powder. The mean K, Ca, and Fe concentrations in grass powder were 6.67, 12.00, and 4.58 times that of regenerating barley grains. In grains, 17 QTLs that accounted for 6.36-64.08% of the phenotypic variation in Zn, Mg, Ca, K, Na, Mn, Fe, and P concentrations were identified. In grass powder, seven QTLs were identified; these accounted for 6.03-21.86% of the variation in Ca, Zn, Mg, K, Fe, and Cu concentrations. These QTLs affecting elements in grain and grass powder are so far unreported in barley. To our knowledge, QTLs with pleiotropic effects for three elements were also identified for the first time in barley. The qK1/qMg1/qCa1 region between markers Bmag0211 and GBMS0014 on chromosome 1H was shown to have large additive effects for Mg, Ca, and K concentrations in grains. These additive effects indicated that the high element (Mg, Ca, Zn, Mn, and K) alleles were contributed by Ziguangmangluoerling. These results will further our understanding of the genetic basis of mineral elements and help us develop markers linked with mineral elements for marker-assisted selection breeding in barley.
Subject(s)
Hordeum/genetics , Minerals/analysis , Quantitative Trait Loci , DNA, Plant/genetics , Edible Grain/genetics , Genetic Variation , Plant Breeding , Selection, GeneticABSTRACT
Cinnamon is the main component of Sanyangxuedai, which is one of the effective traditional Chinese medicines for treating malignancies. Leukemia is a prevalent malignant disease that Sanyangxuedai has been used to treat. Although successful in several studies, there is a lack of solid evidence as to why Sanyangxuedai has an effect on leukemia, and little is known about the underlying mechanisms. In this study, the active ingredients of cinnamon were isolated, purified, and identified. The transwell transport pool formed with the Caco-2 cell model was used to filter the active ingredients of cinnamon by simulating the gastrointestinal barrier in vitro. Moreover, the cell morphology, cell cycle status, apoptosis status, and antigenic variation of the cell surface antigens were observed and measured in K562 cells after treatment with the active ingredients of cinnamon. Our results showed that 50-75 µM was a safe concentration of cinnamon extract for treatment of K562 cells for 72 h. The cinnamon extract caused growth inhibition of K562 cells. Cinnamon extract seemed to arrest the cells at the G1 stage and increased the apoptosis rate significantly. Interestingly, cinnamon extract treatment upregulated the expression of erythroid and myeloid differentiation antigens and downregulated that of the megakaryocytic differentiation antigens in a dose-dependent manner. Our findings indicate that cinnamon extract from Sanyangxuedai may be effective for treating leukemia.
Subject(s)
Cinnamomum zeylanicum/chemistry , Leukemia/drug therapy , Plant Extracts/pharmacology , Stem Cells/drug effects , Apoptosis/drug effects , Caco-2 Cells , Cell Cycle/drug effects , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Humans , K562 Cells , Leukemia/pathology , Stem Cells/metabolism , Stem Cells/pathologyABSTRACT
An F3 population consisting of 117 F2:3 families derived from a cross between two varieties of rice, Gongmi No. 3 and Diantun 502, with a large difference in their resistant starch and total alkaloid content, was used for quantitative trait locus (QTL) mapping. Two QTLs of resistant starch for rice (qRS7-1, qRS7-2) were identified in a linkage group on chromosome 7, which could explain phenotypic variance from 7.6 to 17.3%, due to additive effects for resistant starch from Gongmi No. 3 or over-dominance effects for qRS7-2 of the marker interval (RM3404-RM478) on chromosome 7 from Gongmi No. 3, accounting for 13.8-17.3% of the phenotypic variance. Two QTLs of total alkaloids for brown rice (qALb7-1, qALb7-2) were identified in the same linkage group, which could explain phenotypic variance from 7.7 and 19.3%, respectively, due to dominance or over-dominance effects for total alkaloids on chromosome 7 from Diantun 502. To our knowledge, these are the first QTLs to be identified, which are related to resistant starch and total alkaloid content in rice. These results are beneficial for understanding the genetic basis of, as well as for developing markers linked with, resistant starch and total alkaloids of functional components for marker-assisted selection breeding in rice.
Subject(s)
Chromosomes, Plant/genetics , Oryza/genetics , Quantitative Trait Loci , Alkaloids/genetics , Alkaloids/metabolism , Chromosome Mapping , Crosses, Genetic , Genes, Plant , Genetic Association Studies , Genetic Linkage , Genetic Loci , Genetic Markers , Oryza/metabolism , Phenotype , Plant Breeding , Starch/genetics , Starch/metabolismABSTRACT
Many studies have shown that microRNA (miR)-133 functions as a tumor suppressor in a variety of metastatic cancers, including breast cancer, gastric cancer, and liver fibrosis. However, the influence of miR-133 on pituitary tumor malignancy has not yet been reported. The purpose of this study was to explore the role of miR-133 in pituitary tumor cell migration and invasive ability and the molecular mechanisms involved. Our findings suggest that in pituitary adenoma cell lines, through direct targeting and negative control of forkhead box C1 (FOXC1), miR-133 can inhibit pituitary adenoma cell migration and invasion. In addition, epithelial-to-mesenchymal transition can be induced by miR-133. Additionally, a negative correlation was found between FOXC1 and miR-133 expression when comparing their expression levels between cancerous tissue and adjacent normal tissue. This suggests that miR-133 can inhibit cell migration and invasion by directly targeting FOXC1, implying that miR-133 could be a potential therapeutic target for treatment of invasive pituitary adenoma.
Subject(s)
Forkhead Transcription Factors/metabolism , MicroRNAs/physiology , Pituitary Neoplasms/genetics , Pituitary Neoplasms/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Movement/physiology , Forkhead Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Real-Time Polymerase Chain ReactionABSTRACT
Several case-control studies have been conducted to investigate the association between the tumor necrosis factor-α (TNF-α)-308G/A polymorphism and vitiligo risk. However, the results of these studies are inconsistent; therefore, we attempted to comprehensively evaluate the association between TNF-α-308G/A polymorphism and vitiligo risk via a meta-analysis. Studies reporting the association between TNF-α-308G/A polymorphism and vitiligo risk were retrieved from PubMed and EmBase databases. Data were extracted from these studies and the pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. Six case-control studies including 1391 vitiligo cases and 2455 control subjects were included in this meta-analysis. The overall results showed the lack of a significant difference in TNF-α-308G/A genotype distribution between the patients and controls when the G allele and GG, GG + GA, GG, and GG genotypes were compared against the A allele and the GA + AA, AA, AA, and GA genotypes, respectively (ORs = 0.65, 0.53, 0.63, 0.41, 0.55; 95%CI = 0.35-1.23, 0.24-1.18, 0.10-4.09, 0.08-1.97, 0.25-1.21; P = 0.188, 0.121, 0.627, 0.264, 0.135, respectively). This meta-analysis suggests that the TNF-α-308G/A polymorphism may not be associated with vitiligo risk. As few studies are available in this field and current evidence remains limited, these results must be corroborated with well-designed and larger studies in the future.
Subject(s)
Alleles , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Tumor Necrosis Factor-alpha/genetics , Vitiligo/genetics , Case-Control Studies , Genetic Association Studies , Genotype , Humans , Odds Ratio , Publication Bias , Risk , Vitiligo/epidemiologyABSTRACT
Gene expression data acquired at different times after traumatic brain injury (TBI) were analyzed to identify differentially expressed genes (DEGs). Interaction network analysis and functional enrichment analysis were performed to extract valuable information, which may benefit diagnosis and treatment of TBI. Microarray data were downloaded from Gene Expression Omnibus and pre-treated with MATLAB. DEGs were screened out with the SAM method. Interaction networks of the DEGs were established, followed by module analysis and functional enrichment analysis to obtain insight into the molecular mechanisms. A total of 39 samples at six time points (30 min, 4, 8, 24 , 72 h, and 21 days) were analyzed and generated 377 DEGs. Eight modules were identified from the networks and network ontology analysis revealed that cell surface receptor-linked signaling pathway, response to wounding and signaling pathway were significantly overrepresented. Altered risk genes and modules in TBI were uncovered through comparing the gene expression data acquired at various time points. These genes or modules could be potential biomarkers for diagnosis and treatment of TBI.
Subject(s)
Brain Injuries/genetics , Gene Expression Profiling , Gene Regulatory Networks , Oligonucleotide Array Sequence Analysis , Animals , Down-Regulation/genetics , Mice , Up-Regulation/geneticsABSTRACT
Breast cancer remains the second largest cause of death in women from cancer. By analyzing gene expression profiles in samples from breast cancer patients, 844 differentially expressed genes (DEGs) were identified in breast cancer metastasis. The 10 most significant signaling pathways identified through enrichment analysis contained DEGs were involved in oxidative phosphorylation, DNA replication, extracellular matrix-receptor interactions and others. Furthermore, survival analysis demonstrated that 5 of these signaling pathways were closely related to the survival time of breast cancer patients including basal transcription factors, cell cycle, ECM-receptor interaction, spliceosome, and DNA replication. Our findings increase the understanding of the network of signaling pathways involved in breast cancer metastasis and may provide theoretical support for further therapeutic study.
Subject(s)
Breast Neoplasms/genetics , Neoplasm Recurrence, Local/genetics , Signal Transduction/genetics , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Survival Analysis , Time FactorsABSTRACT
This study aimed to investigate the effects of mitochondrial ATP-sensitive potassium (MitoKATP) channel opening on the translocation of protein kinase C epsilon (PKCε). In addition, we aimed to determine the relationship between PKCε translocation and the production of reactive oxygen species (ROS). PKCε protein expression in cultured adult rat ventricular myocytes was investigated by immunofluorescence and Western blotting. Diazoxide (DZ), a selective MitoKATP channel activator, caused a significant translocation to myofibrillar-like structures in cultured adult rat ventricular myocytes. N-2-Mercaptopropionylglycine, a free radical scavenger, could partially inhibit the translocation of PKCε induced by DZ. By contrast, chelerythrine, a selective PKC inhibitor, could completely block the translocation of PKCε induced by DZ. The opening of MitoKATP channels might activate and cause PKCε to translocate into myofibrillar-like structures. PKCε activation occurred downstream of the MitoKATP channel, possibly as a result of ROS production that occurred after the MitoKATP channels opened.
Subject(s)
Diazoxide/pharmacology , KATP Channels/metabolism , Myocytes, Cardiac/drug effects , Protein Kinase C-epsilon/metabolism , Animals , Benzophenanthridines/pharmacology , Cell Membrane/metabolism , Cells, Cultured , Mitochondria/metabolism , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Tiopronin/pharmacologyABSTRACT
The cytochrome P450c17α gene (CYP17) encodes a key biosynthesis enzyme of estrogen, which is critical in regulating adipogenesis and adipocyte development in humans. We therefore hypothesized that CYP17 is a candidate gene for predicting obesity. In order to test this hypothesis, we performed a family-based association test to investigate the relationship between the CYP17 gene and obesity phenotypes in a large sample comprising 1873 subjects from 405 Caucasian nuclear families of European origin recruited by the Osteoporosis Research Center of Creighton University, USA. Both single SNPs and haplotypes were tested for associations with obesity-related phenotypes, including body mass index (BMI) and fat mass. We identified three SNPs to be significantly associated with BMI, including rs3740397, rs6163, and rs619824. We further characterized the linkage disequilibrium structure for CYP17 and found that the whole CYP17 gene was located in a single-linkage disequilibrium block. This block was observed to be significantly associated with BMI. A major haplotype in this block was significantly associated with both BMI and fat mass. In conclusion, we suggest that the CYP17 gene has an effect on obesity in the Caucasian population. Further independent studies will be needed to confirm our findings.
Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Obesity/enzymology , Obesity/genetics , Steroid 17-alpha-Hydroxylase/genetics , White People/genetics , Adiposity/genetics , Adult , Base Sequence , Body Mass Index , Family , Female , Haplotypes/genetics , Humans , Linkage Disequilibrium/genetics , Male , Middle Aged , Molecular Sequence Data , Polymorphism, Single Nucleotide/geneticsABSTRACT
Osteoporosis is a heritable disease characterized mainly by low bone mineral density (BMD) and/or osteoporotic fractures (OF). Most genome-wide association studies on osteoporosis have focused on BMD, whereas little effort has been expended to identify genetic variants directly linked to OF. To determine whether BMD-loci are also associated with OF risk, we performed a validation study to examine 23 BMD-loci reported by recent genome-wide association studies for association with hip OF risk. Our sample consisted of 700 elderly Chinese Han subjects, 350 with hip OF and 350 healthy matched controls. We identified four BMD-loci that were significantly associated with hip OF in this Chinese population, including 7q21 (FLJ42280, P = 1.17 × 10(-4) for rs4729260; P = 0.008 for rs7781370), 6p21 (MHC, P = 0.004 for rs3130340), 13q14 (TNFSF11, P = 0.012 for rs9533090; P = 0.018 for rs9594759; P = 0.020 for rs9594738; P = 0.044 for rs9594751), and 18q21 (TNFRSF11A, P = 0.015 for rs884205). The SNP rs4729260 at 7q21 remained significantly associated, even after conservative Bonferroni's correction. Our results further highlight the importance of these loci in the pathogenesis of osteoporosis, and demonstrate that it is feasible and useful to use OF as the direct phenotype to conduct genetic studies, to enhance our understanding of the genetic architecture of osteoporosis.