Project description:To further investigate the pathogenesis of syphilis with diabetes, we used a gene chip expression profile from a rabbit model of syphilis with diabetes as a discovery platform to identify potential genes. Grouped into normal control group (n=2) and syphilis combined with diabetes group (n=3).
Project description:Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a gene signature distinguishing sarcoidosis from healthy controls, which also served as a molecular signature for complicated sarcoidosis.
Project description:Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a gene signature distinguishing sarcoidosis from healthy controls, which also served as a molecular signature for complicated sarcoidosis. Total RNA was isolated from PBMCs using standard molecular biology protocols without DNA contamination or RNA degradation. Sample processing (e.g., cDNA generation, fragmentation, end labeling, hybridization to Affymetrix GeneChip Human Exon 1.0 ST arrays) was performed per manufacturer’s instructions. A total of 29 African descent American (AA) and 10 European descent American (EA) patients with sarcoidosis were included in the overall sarcoidosis cohort with 18 AA and 4 EA patients diagnosed with complicated sarcoidosis.
Project description:<p>Pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are common chronic diseases that threaten human health. Patients with DM are susceptible to PTB, an important factor that aggravates the complications of diabetes. However, the molecular regulatory mechanism underlying the susceptibility of patients with DM to PTB infection remains unknown. Healthy subjects, patients with primary PTB and patients with primary PTB complicated by DM were recruited according to inclusion and exclusion criteria. Peripheral whole blood was collected, and alteration profiles and potential molecular mechanisms were further analyzed using integrated bioinformatics analysis of metabolomics and transcriptomics. In this study, transcriptional data revealed that lipocalin 2 (LCN2), defensin alpha 1 (DEFA1), peptidoglycan recognition protein 1 (PGLYRP1) and integrin subunit alpha 2b (ITGA2B) were significantly upregulated, while chloride intracellular channel 3 (CLIC3) significantly down-regulated in PTB-DM by contrast to HC group. Additionally, the IL-17, PI3K-AKT and PPAR signaling pathways are important for PTB infection and regulation of PTB-complicated diabetes. Metabolomic data showed that glycerophospholipid metabolism, carbon metabolism and fat digestion and absorption processes were enriched in the differential metabolic analysis. Finally, integrated analysis of both metabolomic and transcriptomic data indicated that the NOTCH1/JAK/STAT signaling pathway is important in PTB complicated by DM. In conclusion, PTB infection altered the transcriptional and metabolic profiles of patients with DM. Metabolomic and transcriptomic changes were highly correlated in PTB-infected patients with DM. Peripheral metabolite levels may be used as biomarkers for PTB management in patients with DM.</p><p><strong>IMPORTANCE:</strong> The comorbidity of diabetes mellitus (DM) significantly increases the risk of tuberculosis infection and adverse tuberculosis treatment outcomes. Most previous studies have focused on the relationship between the effect of blood glucose control and the outcome of anti-tuberculosis treatment in pulmonary tuberculosis (PTB)-DM; however, early prediction and the underlying molecular mechanism of susceptibility to PTB infection in patients with DM remain unclear. Here, transcriptome sequencing and untargeted metabolomics were performed to elucidatethe key molecules and signaling pathways involved in PTB infection and the susceptibility of patients with diabetes to PTB. Our findings contribute to the development of vital diagnostic biomarkers for PTB or PTB-DM and provide acomprehensive understanding of molecular regulation during disease progression.</p>
Project description:Epidemiologic studies have clearly identified modifications of fetal environment as a risk factor for the development of cardiovascular diseases and of metabolic syndrome in adulthood. In our experimental model, rats exposed to maternal diabetes develop a volume-dependent hypertension as early as 6 month of age. In order to determine if the development of hypertension results from an abnormal vascular fetal programming, gene expression profile of thoracic aorta were studied in adult rats exposed in utero to maternal hyperglycemia.
Project description:Identification of transcriptional profile of several genes involved in diabetes in islet-derived extracellular vesicles (Evs). Recently, EVs are identified as a new mechanism in cell-to-cell communication by transfer of protein and genic information (mRNA, microRNA). Their role is under investigation in immunology, stem cell and cancer, but not in islets and diabetes. The aim of this experiment is to identify mRNA transcripts (in particular, mRNA transcripts involved in diabetes pathophysiology) present in islet Evs.
Project description:The microRNA (miRNA) expression profile of plasma exosome in pregnant women complicated with gestational diabetes mellitus (GDM) has not been fully clarified. In this study, differentially expressed miRNAs in plasma exosomes were identified by high-throughput small RNA sequencing in 12 GDM and 12 normal glucose tolerance (NGT) pregnant women and validated in 102 GDM and 101 NGT pregnant women. A total of 22 exosomal miRNAs were found and five of them were verified by qRT-PCR. Exosomal miR-423-5p was upregulated, while miR-99a-5p, miR-192-5p, miR-148a-3p, and miR-122-5p were downregulated in pregnant women complicated with GDM.