T2DM patients with obesity and healthy volunteer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA560728 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Fecal samples from T2DM patients
| PRJNA1238196 | ENA
Project description:Rationale: The acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease’s complex pathophysiology, yet these cells have been little studied. Objectives: To examine the functional and transcriptional profiles of patient blood and alveolar neutrophils compared to healthy volunteer cells, and define their sensitivity to phosphoinositide 3-kinase inhibition. Methods: Twenty three ventilated patients underwent bronchoalveolar lavage. Alveolar and blood neutrophil apoptosis, phagocytosis and adhesion molecules were quantified by flow cytometry, and oxidase responses by chemiluminescence. Cytokine and transcriptional profiling utilized multiplex and GeneChip arrays. Measurements and Main Results: Patient blood and alveolar neutrophils were distinct from healthy circulating cells, with increased CD11b and reduced CD62L expression, delayed apoptosis and constitutively primed oxidase responses. Incubating control cells with disease bronchoalveolar lavage recapitulated the aberrant functional phenotype and this could be reversed by phosphoinositide 3-kinase inhibitors. In contrast, the pro-survival phenotype of patient cells was recalcitrant to phosphoinositide 3-kinase inhibition. RNA transcriptomic analysis revealed modified immune, cytoskeletal and cell death pathways in patient cells, aligning closely to sepsis and burns data sets but not with phosphoinositide 3-kinase signatures. Conclusions: Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed, pro-survival profile and transcriptional signature. The enhanced respiratory burst was phosphoinositide 3-kinase-dependent, but delayed apoptosis and the altered transcriptional profile were not. These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of evaluating novel therapeutic strategies in patient-derived cells.
2016-04-11 | GSE76293 | GEO
Project description:stool samples of T2DM Patients Raw sequence reads
| PRJNA1234893 | ENA
Project description:We identified that PBMC of individuals simultaneously affected by a combination of T2DM, dyslipidemia and periodontitis, showed altered molecular profile mainly associated to inflammatory response, immune cell trafficking, and infectious disease pathways Patients were divided into: T2DMpoorly-DL-P (n=5, Grupo 1), T2DMwell-DL-P (n=7, Grupo 2), DL-P (n=6, Grupo 3), P (n=6, Grupo 4) and Healthy (n=6, Control). T2DM poorly controlled = HbA1c ≥8.5%; T2DM well-controlled patients = HbA1c <7.0%
2020-08-28 | GSE156993 | GEO
Project description:Insulin resistance and Type 2 Diabetes Mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. To identify the underlying molecular processes in preadipocytes of T2DM patients that are a characteristic of the development of T2DM, preadipocyte cell cultures were prepared from subcutaneous fat biopsies of T2DM patients and compared with age- and BMI matched control subjects. Gene expression profiling showed changed expression of transcription factors involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were down-regulated, and inflammation/apoptosis was up-regulated in T2DM preadipocytes. The down-regulation of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage. 7 T2DM preadipocyte samples and 9 age- and BMI-matched control samples were hybridized using 70-mer oligonucleotide microarrays. Samples were labeled with either Cy3 or Cy5. A total of 20 arrays were used including dye swop. Per array, a T2DM sample was hybridized with a control sample of the same gender and matched based on age and BMI. To ensure hybridization of two samples with the same gender, three T2DM (5064, 5128, 5395) and one control sample (5616) were used twice and listed as technical replicates.
2010-05-16 | E-GEOD-15790 | biostudies-arrayexpress
Project description:Insulin resistance and Type 2 Diabetes Mellitus (T2DM) are associated with increased adipocyte size, altered secretory pattern and decreased differentiation of preadipocytes. To identify the underlying molecular processes in preadipocytes of T2DM patients that are a characteristic of the development of T2DM, preadipocyte cell cultures were prepared from subcutaneous fat biopsies of T2DM patients and compared with age- and BMI matched control subjects. Gene expression profiling showed changed expression of transcription factors involved in adipogenesis and in extracellular matrix remodeling, actin cytoskeleton and integrin signaling genes, which indicated decreased capacity to differentiate. Additionally, genes involved in insulin signaling and lipid metabolism were down-regulated, and inflammation/apoptosis was up-regulated in T2DM preadipocytes. The down-regulation of genes involved in differentiation can provide a molecular basis for the reduced adipogenesis of preadipocytes of T2DM subjects, leading to reduced formation of adipocytes in subcutaneous fat depots, and ultimately leading to ectopic fat storage.
2009-12-31 | GSE15790 | GEO
Project description:The diabetic complications are closely related with macro- and microcirculatory disorders, which are largely correlated with the highly procoagulant platelets inT2DM patients. Thus, 4-D label free proteomics of platelets from 5 Healthy volunteers and 5 T2DM patients was applied..
2024-07-22 | PXD054086 |
Project description:Dwivedi2014 - Healthy Volunteer IL6
Model
This model is comprised of four models:
[BIOMD0000000534]
Healthy Volunteer model
[BIOMD0000000535]
Crohn's Disease - IL-6 Antibody
[BIOMD0000000536]
Crohn's Disease - sgp130FC
[BIOMD0000000537]
Crohn's Disease - IL-6Ra Antibody
Possible avenues for Interleukin-6 (IL-6) inhibition in
treating Crohn's disease are compared here. Each model refers to
separate ligands. The system simulates differential activity of the
ligands on the signalling of IL-6.
This affects Signal Transducer and Activator of
Transcription 3 (STAT3) activity on the production of
biomarker C-Reactive Protein (CRP) expression.
Figures referring to this Healthy Volunteer model are 2c and
2d.
This model is described in the article:
A multiscale model of
interleukin-6-mediated immune regulation in Crohn's disease and
its application in drug discovery and development.
Dwivedi G, Fitz L, Hegen M, Martin
SW, Harrold J, Heatherington A, Li C.
CPT Pharmacometrics Syst Pharmacol
2014; 3: e89
Abstract:
In this study, we have developed a multiscale systems model
of interleukin (IL)-6-mediated immune regulation in Crohn's
disease, by integrating intracellular signaling with
organ-level dynamics of pharmacological markers underlying the
disease. This model was linked to a general pharmacokinetic
model for therapeutic monoclonal antibodies and used to
comparatively study various biotherapeutic strategies targeting
IL-6-mediated signaling in Crohn's disease. Our work
illustrates techniques to develop mechanistic models of disease
biology to study drug-system interaction. Despite a sparse
training data set, predictions of the model were qualitatively
validated by clinical biomarker data from a pilot trial with
tocilizumab. Model-based analysis suggests that strategies
targeting IL-6, IL-6R?, or the IL-6/sIL-6R? complex are less
effective at suppressing pharmacological markers of Crohn's
than dual targeting the IL-6/sIL-6R? complex in addition to
IL-6 or IL-6R?. The potential value of multiscale system
pharmacology modeling in drug discovery and development is also
discussed.CPT: Pharmacometrics & Systems Pharmacology
(2014) 3, e89; doi:10.1038/psp.2013.64; advance online
publication 8 January 2014.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000534.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000534 | BioModels
Project description:Type 2 diabetes mellitus (T2DM) is characterized by beta-cell dysfunction and insulin resistance, but the early molecular drivers remain elusive. The aim of this study was to identify blood long non-coding RNAs (lncRNAs) as a potential systemic biomarkers in patients with new-onset, unmedicated T2DM. We performed transcriptome sequencing of peripheral blood from eight T2DM patients and eight healthy individuals. The intersection of three differential expression analysis methods (Limma, DESeq2 and EdgeR) identified 1,709 lncRNAs with dysregulated expression in peripheral blood, of which , 853 lncRNAs were up-regulated and 856 lncRNAs were down-regulated. Weighted gene co-expression network analysis (WGCNA) identified two modules comprising a total of 1,617 lncRNAs that were significantly negatively associated with T2DM. By integrating differential expression analysis and WGCNA, we screened a total of 257 lncRNAs that were highly correlated with T2DM and exhibited significant changes in expression levels.Our findings provide valuable transcriptomic data for further studies of T2DM, and the screened blood lncRNAs may reflect systemic dysregulation as early biomarkers.
2025-06-04 | GSE298690 | GEO