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Circulating miRNAs as a predictive biomarkers of progression from prediabetes to diabetes: outcomes of 5-year prospective observational study

ABSTRACT: Circulating miRNAs as a predictive biomarkers of progression from prediabetes to diabetes: outcomes of 5-year prospective observational study

PROVIDER: PRJNA626629 | ENA |

REPOSITORIES: ENA

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Circulating miRNAs as a predictive biomarkers of progression from prediabetes to diabetes: outcomes of 5-year prospective observational study

Project description:The aim of this study was to conduct a baseline comparison of serum-circulating miRNA in prediabetic individuals with the distinction between those who later progressed to type 2 diabetes (T2DM) and those who did not. The expression level of 798 miRNAs using NanoString technology was examined. Spearman correlation, ROC curve analysis, and logistic regression modeling were performed. Gene ontology (GO), canonical pathways analysis were used to explore the biological functions of the miRNA target genes. The study revealed that 18 miRNAs were upregulated in serum samples of patients who later progressed to T2DM. Pathway analysis showed that miRNA target genes were mainly significantly enriched in neuroinflammation signaling, Myc mediated apoptosis signaling and tumoricidal function of hepatic natural killer (NK) cells. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (AUC=97.1%; 90.2%; 88.7%; respectively). Validation by qRT-PCR confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.

2020-07-21 | GSE148961 | GEO

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Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study.

Project description:Due to a global increase in the prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need for early identification of prediabetes, as these people have the highest risk of developing diabetes. Circulating miRNAs have shown potential as progression biomarkers in other diseases. This study aimed to conduct a baseline comparison of serum-circulating miRNAs in prediabetic individuals, with the distinction between those who later progressed to T2DM and those who did not. The expression levels of 798 miRNAs using NanoString technology were examined. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression modeling were performed. Gene ontology (GO) and canonical pathway analysis were used to explore the biological functions of the miRNA target genes. The study revealed that three miRNAs were upregulated in the serum samples of patients who later progressed to T2DM. Pathway analysis showed that the miRNA target genes were mainly significantly enriched in neuronal NO synthase (nNOS) signaling in neurons, amyloid processing, and hepatic cholestasis. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (area under the curve (AUC) = 94.0%, 88.0%, and 84.0%, respectively). Validation by real-time quantitative polymerase chain reaction (qRT-PCR) confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.

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CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: a prospective, single-center, observational study

Project description:Controversial data have been reported on the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) in chronic lymphocytic leukemia (CLL). This prospective, single-center, observational study aimed to evaluate the role of CXCR4 in the pathophysiology of CLL and its prognostic role. A total of 158 patients of CLL were enrolled, and CXCR4 expression on CLL cells was detected by flow cytometry (FCM) at initial diagnosis. The patients were divided into 2 groups according to the CXCR4 mean fluorescence intensity (MFI) median. Also, four patient specimens from the CXCR4low and CXCR4high groups were selected for whole transcriptome sequencing. The progression-free survival (PFS) of CLL patients in the CXCR4high group was significantly shorter than the CXCR4low group, with a median follow-up time of 27 months (log-rank P < 0.001). Moreover, CXCR4 overexpression (MFI > 3376) was an independent marker of poor PFS in CLL patients (P < 0.001). Analysis of whole transcriptome sequencing results revealed that CXCR4 plays an important role in the migration of CLL. Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time.

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Project description:This prospective observational study conducted at Osaka University Graduate School of Medicine aimed to compare host responses in sepsis and COVID-19 patients by analyzing mRNA and miRNA profiles. They included 22 sepsis patients, 35 COVID-19 patients, and 15 healthy subjects. Sepsis was diagnosed using Sepsis-3 criteria, while COVID-19 was confirmed through SARS-CoV-2 RT-PCR testing and chest CT scans for pneumonia assessment. For RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in sepsis patients. Numbers of genes showing upregulated:downregulated gene expression (false discovery rate <0.05, |log2 fold change| >1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in COVID-19 patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated:downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. Sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to COVID-19 patients, indicating a dynamic change in gene expression and pathway activation in sepsis.

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Comparative Analysis of Host Responses Between Sepsis and COVID-19: A Prospective Observational Study of Whole Blood Transcriptome (RNA-Seq)

2024-08-28 | GSE243217 | GEO

Cardiac miRNA expression changes induced by prediabetes

Project description:The aim of the experiment was the analysis of key molecular changes with an unbiased, transcriptomics-based approach in a prediabetes model. Small RNA sequencing analysis was applied to explore the expression changes resulted high-fat chow (supplemented with 40% lard) diet for 21 weeks and a single low dose of streptozotocin (20 mg/kg) treatment at week 4. Long-Evans rats were used in the present study. Left ventricular samples(n=6) of both prediabetic and control groups were analyzed.

2020-04-24 | E-MTAB-8204 | biostudies-arrayexpress

CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: a prospective, single-center, observational study

Project description:CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: a prospective, single-center, observational study

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Nicotinamide mononucleotide increases muscle insulin sensitivity in women with prediabetes

Project description:Studies in rodents have shown obesity and aging impair tissue nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. The availability of nicotinamide mononucleotide (NMN) is an important rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in 25 postmenopausal women with prediabetes who were overweight/obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic-clamp procedure, increased by 25±7% (P<0.01) in the NMN group, which was accompanied by an increase in insulin-stimulated phosphorylation of muscle AKT (P<0.01), whereas neither outcome changed after placebo treatment. Body composition (fat mass, fat-free mass, intra-abdominal fat, intrahepatic triglyceride content) and muscle mitochondrial respiratory capacity did not change after treatment with placebo or NMN. These results demonstrate NMN improves muscle insulin sensitivity in women with prediabetes who are overweight/obese, independent of changes in body composition or mitochondrial function.

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