Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion.
Project description:Analysis of umbilical cord tissue in newborns of type 1 diabetic mothers at gene expression level. The hypothesis tested in the present study was that intrauterine diabetic milieu may effect of fetal umbilical cord gene expression, and via umbilical cord, the alterations may be produced in other fetal tissues as well. Results provide an information of the differentially expressed genes and enriched pathways, such as the dowregulated genes on the pathway on blood vessel development in umbilical cords from diabetic pregnancies. Umbilical cord tissue was collected after elective ceasarean section and was immediately flash frozen in liquid nitrogen and stored at -80C until total RNA extraction from the whole tissue sample. Six cords exposed to maternal diabetes (DM) and six control cords (C) from healthy pregnancies were analyzed.
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
Project description:To investigate the umbilical cord lncRNA profiles in gestational diabetes-induced macrosomia, the umbilical cord vein blood from normal and gestational diabetes-induced macrosomia was hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR) was used to validate selected differentially expressed lncRNAs. The gene ontology (GO), pathway and network analysis were performed. The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 2.0) in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts.
Project description:To investigate the umbilical cord lncRNA profiles in gestational diabetes-induced macrosomia, the umbilical cord vein blood from normal and gestational diabetes-induced macrosomia was hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR) was used to validate selected differentially expressed lncRNAs. The gene ontology (GO), pathway and network analysis were performed. The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change M-bM-^IM-% 2.0) in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts. Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray.
Project description:In this retrospective study, a diverse set of biological specimens was assembled, consisting of maternal blood, umbilical cord blood, and placenta tissue, from a cohort of 22 mothers with gestational diabetes mellitus and a matched group of 19 healthy mothers. Integrated proteomic characterization of these samples were performed, and functional enrichments based on GO and KEGG database, as well as Gene Set Enrichment Analysis were used to elucidate the pathways involved in the pathophysiology of gestational diabetes mellitus. Moreover, a weighted protein co-expression network was constructed to analysis the correlation of expression modules with clinical traits.
Project description:Exosomes are membranous extracellular vesicles 50–100 nm in size and are involved in cellular communication via the delivery of proteins, lipids, and RNAs. Emerging evidence shows that exosomes play a critical role in cancer. A recent study has revealed that maternal and umbilical cord serum-derived exosomes may enhance endothelial cell proliferation and migration. However, the role of exosomes isolated from the human umbilical cord in cancer development has not been investigated. To explore the potential differences in the composition and function of proteins from umbilical cord blood exosomes and maternal serum exosomes, we conducted a proteomic analysis of exosomes by mass spectrometry and bioinformatics analysis. We used the CCK-8 assay and flow cytometry to study the biological effects of umbilical serum exosomes on hepatoma cells. Our study shows that umbilical cord blood is enriched with proteins involved in ECM-receptor interactions, which may be closely related to cell metastasis and proliferation. Our findings indicate that exosomes derived from human umbilical serum can suppress the viability of hepatoma cells and may induce apoptosis of hepatoma cells. This evidence suggests that umbilical cord serum-derived exosomes may be potential leads for the development of biotherapy for liver cancer.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:The prevalence of metabolic syndrome comprising obesity, type 2 diabetes mellitus and cardiovascular disease has been on the rise world-wide in recent years. As non-communicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of GDM mothers compared to control subjects. Methods We have assessed primary umbilical cord derived cells such as human vascular endothelial cells (HUVECs) and Wharton’s jelly derived mesenchymal stem cells (WJMSCs) from both, the offspring of GDM and healthy mothers. We have compared the primary isolates in cell based assays measuring proliferation, mitochondrial oxygen consumption, as well as the ability to support blood vessel growth. We conducted gene expression microarray studies with subsequent pathway analysis and candidate gene validation. Results We observed striking differences between the two groups such as lower metabolic rates and impairment of tube formation in cells with GDM background. HUVECs from subjects with maternal GDM have lower expression of the anti-apoptotic protein BCL-Xl suggesting compromised angiogenic capabilities. Comparative gene expression analysis revealed blood vessel formation as a major pathway enriched in the GDM derived HUVECs with the surface marker CD44 as a significant gene under-expressed in the GDM group. Functional validation of CD44 revealed that it regulates tube formation in HUVECs thereby providing new insights into a novel pathway imprinted in primary umbilical cord derived cells from GDM offspring. Conclusions/interpretation Our data demonstrate that primary cells isolated from the umbilical cord of offspring born to GDM mothers maintain metabolic and molecular imprints of maternal hyperglycemia, which occurred during prenatal development reflecting an enhanced risk for cardiovascular disease later in life.