Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13381 - 13381

Published: Aug. 29, 2023

Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong terminal stage disease, i.e., type 2 diabetes (T2DM). The World Health Organization predicts that will be seventh leading cause death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists SGLT-2 inhibitors, single-target drugs are gradually failing to meet therapeutic requirements owing individual variability, diversity pathogenesis, organismal resistance. Therefore, there remains need investigate pathogenesis T2DM more depth, identify targets, provide improved glycemic control solutions. This review presents an overview mechanisms action development latest agents targeting years. It also discusses emerging target-based therapies new targets emerged within last three aim our theoretical basis for further advancement targeted T2DM.

Language: Английский

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Gender Differences and miRNAs Expression in Cancer: Implications on Prognosis and Susceptibility

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11544 - 11544

Published: July 17, 2023

MicroRNAs are small, noncoding molecules of about twenty-two nucleotides with crucial roles in both healthy and pathological cells. Their expression depends not only on genetic factors, but also epigenetic mechanisms like genomic imprinting inactivation X chromosome females that influence a sex-dependent manner onset, progression, response to therapy different diseases cancer. There is evidence correlation between miRNAs, sex, cancer solid tumors hematological malignancies; as an example, lymphomas, prevalence rate higher men than women, miR-142 “silenced” because its hypermethylation by DNA methyltransferase-1 it blocked normal activity regulating the migration cell. This condition corresponds clinical practice more aggressive tumor. In addition, treatment can have advantages from evaluation miRNAs expression; fact, estrogens hepatocellular carcinoma determines upregulation oncosuppressors miR-26a, miR-92, miR-122 and, consequently, apoptosis. The aim this review present exhaustive collection scientific data possible role sex differences through which cancerogenesis, autophagy, apoptosis cells diverse types tumors.

Language: Английский

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Microvesicle-associated and circulating microRNAs in diabetic dyslipidemia: miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 have biomarker potential

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Sept. 25, 2023

Abstract Background Circulating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiological and pathological functions post-transcriptional regulation of gene expression being considered markers for many diseases including diabetes dyslipidemia. We aimed to identify new common miRNAs both in MVs plasma that could be predictive biomarkers diabetic dyslipidemia evolution. Methods For this purpose, from 63 participants the study (17 type 2 patients, 17 patients with dyslipidemia, 14 alone 15 clinically healthy persons without or dyslipidemia) was used analysis circulating cytokines, MVs, MV-associated miRNAs. Results The results uncovered three miRNAs, miR-218, miR-132 miR-143, whose found significantly up-regulated These showed significant correlations important markers, representative pathology. Thus, MV/plasma miR-218 negatively correlated levels erythrocyte positively connected MV uric acid levels, miR-143 related creatinine diastolic blood pressure. Also, plasma, namely miR-21, miR-122, miR-155, were identified down-regulated up-regulated, respectively, In addition, miR-21 linked cholesterol TNFα miR-122 LDL-c pressure miR-126 miR-155 associated total HDL-c whereas Il-1β miR-223 levels. Conclusions conclusion, miR-132, show potential as but there is a need more in-depth studies. findings bring information regarding molecular specific implications treatment affected

Language: Английский

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Circulating microRNAs as potential biomarkers of physical activity in geriatric patients with HCV

BMC Molecular and Cell Biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: July 19, 2024

Abstract Background Circulating microRNAs have been implicated in a diverse array of biological and pathological phenomena. Their potential utility as noninvasive biomarkers for screening diagnosing various diseases has proposed. Objective This study aimed to explore the role miRNAs miR-122 miR-486 molecular pathogenesis hepatitis C virus (HCV) infection. Thus, were detected serum HCV patients healthy controls. Moreover, correlations with viral complications, such physical activity, pain, muscle fatigue, infection, identified. Methods A total 150 subjects aged 30 66 years included this study. The classified chronic (CHC) ( n = 110) or controls 40). Real-time polymerase chain reaction (PCR) analyses performed determine expression. Physical activity (PA), pain score, genotyping, overload, aspartate transaminase (AST), alanine (ALT), lactic acid dehydrogenase (LDH), creatine kinase (CK), antioxidant status also estimated by using prevalidated questionnaires, PCR, spectrophotometric analyses. Results Compared those normal controls, significant increases levels reported CHC. In physically active CHC patients, there was correlation between expression increased fibrosis scores, inflammation but no association RNA load. Additionally, decreases LDH, CK, GSSG, scores TAC, GSH, GSH/GSSG ratio reported. positively correlated changes body mass index (BMI) liver stage, well negatively sex, PA, ratio. Conclusion MiR-122 strongly perception, fatigue HCV-infected patients. These miRNA associated elevated AST, ALT, status, thus suggesting their disease severity oxidative stress. However, observed load HCV-RNA expression, implying that these may impact progression symptoms through host factors, rather than directly affecting replication. summary, results demonstrated studies miR-22 miR-468 associations adiposity, sex differences, routine biomarkers, could be useful prognostic nanoninvasive providing novel therapeutic targets

Language: Английский

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A compendium of noncoding RNAs as biomarkers in Type 2 Diabetes Mellitus

Journal of Pharmaceutical and Biomedical Analysis Open, Journal Year: 2025, Volume and Issue: unknown, P. 100057 - 100057

Published: Jan. 1, 2025

Language: Английский

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Exploratory Analysis of MicroRNA Alterations in a Neurodevelopmental Mouse Model for Autism Spectrum Disorder and Schizophrenia

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2786 - 2786

Published: Feb. 28, 2024

MicroRNAs (miRNAs) play a crucial role in the regulation of gene expression levels and have been implicated pathogenesis autism spectrum disorder (ASD) schizophrenia (SCZ). In this study, we examined adult profiles specific miRNAs prefrontal cortex (PFC) neurodevelopmental mouse model for ASD SCZ that mimics perinatal pathology, such as NMDA receptor hypofunction, exhibits behavioral neurophysiological phenotypes related to these disorders during adulthood. To early neuropathogenesis disorders, pups were administered subcutaneously with ketamine (30 mg/Kg) at postnatal days 7, 9, 11. We focused on set most frequently altered (miR-451a miR-486-3p) (miR-132-3p miR-137-3p) according human studies. Additionally, explored whose alterations identified both (miR-21-5p, miR-92a-2-5p, miR-144-3p, miR-146a-5p). placed particular emphasis studying sexual dimorphism dynamics miRNAs. Our findings revealed significant PFC ASD- SCZ-like model. Specifically, observed upregulated miR-451a downregulated miR-137-3p. Furthermore, miR-132-3p, miR-137-3p, miR-92a-2-5p. From translational perspective, our results emphasize potential involvement pathophysiology strengthen their biomarkers therapeutic targets disorders.

Language: Английский

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Silencing LncRNA SNHG16 suppresses the diabetic inflammatory response by targeting the miR-212-3p/NF-κB signaling pathway

Diabetology & Metabolic Syndrome, Journal Year: 2023, Volume and Issue: 15(1)

Published: June 7, 2023

Long noncoding RNAs (LncRNAs) have been identified to play an important role in diabetes. The aim of the present study was determine expression and function small nucleolar RNA host gene 16 (SNHG16) diabetic inflammation.For vitro experiments, quantitative real-time PCR (qRT-PCR), Western blotting immunofluorescence were used detect LncRNA SNHG16 high-glucose state. potential microRNA sponge target SNHG16, miR-212-3p, detected by dual-luciferase reporter analysis qRT-PCR. For vivo glucose changes mice after si-SNHG16 treatment, inflammatory factor kidney tissues qRT-PCR immunohistochemistry.LncRNA upregulated patients, HG-induced THP-1 cells, mice. Silencing inhibited response development nephropathy. miR-212-3p found be directly dependent on SNHG16. could inhibitor P65 phosphorylation cells. reversed action cells induced also higher peripheral blood patients than normal person. area under ROC curve is 0.813.These data suggested that silencing suppresses responses competitively binding regulate NF-κB. can as a novel biomarker for with type 2

Language: Английский

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Glycemia-Induced miRNA Changes: A Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7488 - 7488

Published: April 19, 2023

Diabetes is a rapidly increasing global health concern that significantly strains the system due to its downstream complications. Dysregulation in glycemia represents one of fundamental obstacles achieving glycemic control diabetic patients. Frequent hyperglycemia and/or hypoglycemia events contribute pathologies disrupt cellular and metabolic processes, which may development macrovascular microvascular complications, worsening disease burden mortality. miRNAs are small single-stranded non-coding RNAs regulate protein expression have been linked various diseases, including diabetes mellitus. proven useful diagnosis, treatment, prognosis There vast body literature examining role miRNA biomarkers diabetes, aiming for earlier diagnoses improved treatment This article reviews most recent discussing specific control, platelet activity, Our review examines different involved pathological processes leading type 2 mellitus, such as endothelial dysfunction, pancreatic beta-cell insulin resistance. Furthermore, we discuss potential applications next-generation with aim preventing, treating, reversing diabetes.

Language: Английский

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The relation between CircRNA0056618 and type 2 diabetes mellitus and insulin resistance through miRNA-206/PTPn-1 pathway

Egyptian Pharmaceutical Journal, Journal Year: 2024, Volume and Issue: 23(3), P. 482 - 490

Published: June 14, 2024

Background Diabetes mellitus (DM) is a well-known metabolic syndrome characterized by hyperglycemia produced defect in insulin synthesis, action, or combination of the two. Objective The aim this work was to find out how circular RNA 0056618 (circRNA 0056618) interacts with miRNA-206 control blood sugar levels type-2 diabetes (T2DM), as well test role PTPN-1 gene expression and protein phosphatase-2 (PP2A), receptor substrate (IRS) level diabetes. Also, whether circRNA 0056618, miRNA-206, PTPN-1, IRS, PP2A could be used biomarkers for T2DM diagnosis prognosis. Patients methods This cross-sectional analytic study carried on 110 patients. Participants were divided into two equal groups: patients’ group (T2DM) (normal participants). All participants subjected quantitative real-time PCR assessed RNAs PTPn-1 expression), enzyme-linked immunosorbent assay technique levels. Statistical analysis Package Social Sciences (SPSS), version 28 code enter data. data will presented means SDs. Correlations between variables done using Pearson correlation coefficient. Receiver operating characteristic (ROC) curve constructed area under (AUC) performed detect best cutoff value significant parameters detection cases. P considered less than 0.05. Results conclusion There increase ( <0.001), =0.002), <0.001) decrease IRS diabetic cases when compared normal controls. negative positive PTPN-1. at 0.840 showed 94.5% sensitivity 90.9% specificity AUC 0.905. 0.868, 96.4% 81.8%, 0.919. ROC 0.882, 89.1% 87.3%, 0.932, 0.785, 85.5% 85.5%, 0.869. 0.556, 67.3% 67.3%, 0.669. We concluded that PP2A, are diagnostic, predictive T2DM. Future RNA-based therapy approaches may benefit from an understanding such new pathways.

Language: Английский

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Preanalytical considerations in quantifying circulating miRNAs that predict end-stage kidney disease in diabetes

JCI Insight, Journal Year: 2024, Volume and Issue: 9(12)

Published: June 23, 2024

Our previous study identified 8 risk and 9 protective plasma miRNAs associated with progression to end-stage kidney disease (ESKD) in diabetes. This aimed elucidate preanalytical factors that influence the quantification of circulating miRNAs. Using EdgeSeq platform, which quantifies 2,002 plasma, including ESKD-associated miRNAs, we compared miRNA profiles whole versus RNA extracted from same specimens. Less than half were detected standard extraction plasma. Detection individual concentrations much lower when was quantified by sequencing (RNA-Seq) or quantitative reverse transcription PCR (qRT-PCR) platforms EdgeSeq. Plasma determined platform had excellent reproducibility assessment no variation age, sex, hemoglobin A1c, BMI, cryostorage time. The measured accurately only using platform. Protective all except qRT-PCR; however, correlations among obtained different weak nonexistent. In conclusion, have a profound effect on detection ESKD Quantification may be preferable method cell-free possibly other diseases.

Language: Английский

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