Project description:The underlying causes of breast cancer are diverse, however, there is a striking association between type 2 diabetes (T2DM) and poor patient outcomes. Platelets become activated in both T2DM and breast cancer patients and have been implicated in tumorigenesis through a multitude of pathways. Here transcriptomic analysis of T2DM-patient derived PMVs revealed an altered micro-RNA (miRNA) signature compared with normoglycaemic control patients. Interestingly, interrogation of these data identifies a shift towards an oncogenic signature in T2DM-derived PMVs, with increased levels of several miRNA implicated in breast cancer progression and poor prognosis. Functional studies demonstrate that PMVs isolated from T2DM patient blood are internalised by triple-negative breast cancer (TNBC) cells in vitro, and that co-incubation with T2DM-patient derived PMVs led to significantly increased TNBC cell invasion compared with PMVs from healthy volunteers. Together, these data suggest that circulating PMVs in T2DM patients may contribute to the progression of TNBC.
Project description:Type 2 diabetes mellitus (T2DM) is an independent risk factor of Alzheimer's disease (AD), thus, identifying who among the increasing T2DM populations may develop into AD is important for early intervention. By using TMT-labeling coupled high-throughput mass spectrometry, we conducted a comprehensive plasma proteomic analysis in none-T2DM people (Ctrl, n=30), and the age-/sex-matched T2DM patients with mild cognitive impairment (T2DM-MCI, n=30) or T2DM without MCI (T2DM-nMCI, n=25). The candidate biomarkers identified by proteomics and bioinformatics analyses were verified by ELISA, and their diagnostic capabilities were evaluated with machine learning. A total of 53 differentially expressed proteins (DEPs) were identified in T2DM-MCI compared with T2DM-nMCI patients. These DEPs were significantly enriched in multiple biological processes, such as amyloid neuropathies, CNS disorders, and metabolic acidosis. Among the DEPs, alpha-1-antitrypsin (SERPINA1), major viral protein (PRNP), valosin-containing protein (VCP) showed strong collection with AD high-risk genes APP, MAPT, APOE, PSEN1, and PSEN2. And the levels of PP2A cancer inhibitor (CIP2A), PRNP, corticotropin releasing factor binding protein (CRHBP) were significantly increased, while the level of VCP was decreased in T2DM-MCI patients compared with the T2DM-nMCI, and these changes were correlated with the mini-mental state examination (MMSE) score. Further machine learning data showed that increases of CIP2A, ratio of β-amyloid (rAβ42/40), and rGSK-3β(T/S9) (ratio of total to serine-9-phosphorylated glycogen synthase kinase-3β) had the greatest power to identify mild cognitive decline in T2DM patients.
Project description:Impaired skeletal muscle function is a central feature in the pathophysiology of type 2 diabetes (T2DM). The disease phenotype could be due to immature muscle cell development, which in turn may occur as the result of disturbed microRNA-mediated regulation of muscle differentiation in T2DM. To address this hypothesis, we assessed global miRNA expression during in vitro differentiation of muscle stem cells derived from T2DM patients and healthy controls. We identified the mir-23b/27b cluster to be downregulated in the patients, and further demonstrated that a pro-myogenic effect of these miRNAs occurs through targeting of several genes in the p53 pathway, which was concordantly dysregulated in the muscle cells derived from humans with T2DM. In conclusion, we have identified a novel myogenesis-controlling pathway, the miR-23b/27b-p53 axis, potentially contributing to the sustained multiple muscular dysfunctions in T2DM in humans.
Project description:Increased morbidity and mortality associated with post-ischemic heart failure (HF) in diabetic patients underscore the need for a better understanding of the underlying molecular events. Indeed, effective HF therapy in diabetic patients requires a complex strategy encompassing the development of improved diagnostic and prognostic markers and innovative pharmacological approaches. Whole mRNAs expression was measured in the heart of patients with heart failure (HF) with or without concomitant Type 2 diabetes mellitus (T2DM) and compared it to control non-failing hearts. We identified distinct genes modulated in HF patients compared to controls, as well as to T2DM HF patients compared to not diabetic HF patients. Our study included left ventricle (LV) cardiac biopsies taken from the vital, non-infarcted zone (remote zone) derived from patients affected by dilated hypokinetic post-ischemic cardiomyopathy, undergoing surgical ventricular restoration procedure. Inclusion criteria for diabetic were: GLICEMIA: >=126 mg/dl, previous T2DM diagnosis or anti-diabetic therapy, while for non diabetic: GLICEMIA: <100 mg/dl and HbA1c: n.v. 4.8-6.0%. Moreover, HF patients were matched for End Systolic Volume (ESV), Ejection fraction (LVEF), Age, Sex, Ethnic distribution, Smoke habits, Hypertension, Glomerular filtration rate (GFR), Body Mass Index (BMI). Genes expression was assessed by Affymetrix GeneChips Human Gene 1.0 ST array, using total RNA extracted from 7 T2DM HF patients, 12 non-T2DM HF patients and 5 controls.
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.
Project description:Type 2 diabetes mellitus(T2DM)patients are a concern for dentists due to the lower success rate of healing period implant treatment. Here, we firstly calculated the success rate of in the healing period of diabetic and non-diabetic patients in the implant center of our hospital.Then we investigated the potential risk factors by proteomics analysis of 5 T2DM implant faliure patients in our implant center and compared the difference between high glucose induction study model and mesenchymal stem cell model from diabetic patients. The results suggested that the significantly higher implant failure rates in the T2DM group and the cell models derived from patients can be more comprehensive and accurate in reflecting the exact situation of BMSCs in patients with diabetes.
Project description:The goal of the project is to understand the mitochondrial proteome profiles related to T2DM. We performed comprehensive proteome profiling of mitochondria isolated from skeletal muscles in nine T2DM patients and nine control subjects with normal glucose tolerance (NGT).
Project description:The goal of the project is to understand the mitochondrial proteome profiles related to T2DM. We performed comprehensive proteome profiling of mitochondria isolated from skeletal muscles in nine T2DM patients and nine control subjects with normal glucose tolerance (NGT).
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%