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Journal of Orthopaedic Surgery and... Jun 2024Long non-coding RNAs (LncRNAs) are recognized as a pivotal element in the processes of fracture healing and the osteogenic differentiation of stem cells. This study...
BACKGROUND
Long non-coding RNAs (LncRNAs) are recognized as a pivotal element in the processes of fracture healing and the osteogenic differentiation of stem cells. This study investigated the molecular mechanism and regulatory significance of lncRNA MAGI2-AS3 (MAGI2-AS3) in fracture healing.
METHODS
Serum levels of MAGI2-AS3 in patients with normal and delayed fracture healing were verified by RT-qPCR assays. The predictive efficacy of MAGI2-AS3 for delayed fracture healing was analyzed by ROC curve. Osteogenic markers were quantified by RT-qPCR assays. MC3T3-E1 cell viability was detected using CCK-8 assay, and flow cytometry was utilized to measure cell apoptosis. The dual-luciferase reporter gene assay was used to determine the targeted binding between MAGI2-AS3 and miR-223-3p.
RESULTS
Serum MAGI2-AS3 expression was decreased in patients with delayed fracture healing compared with patients with normal healing. Elevated MAGI2-AS3 resulted in an upregulation of the proliferative capacity of MC3T3-E1 cells and a decrease in mortality, along with increased levels of both osteogenic markers. However, after transfection silencing MAGI2-AS3, the trend was reversed. Additionally, miR-223-3p was the downstream target of MAGI2-AS3 and was controlled by MAGI2-AS3. miR-223-3p mimic reversed the promoting effects of MAGI2-AS3 overexpression on osteogenic marker levels and cell growth, and induced cell apoptosis.
CONCLUSION
The upregulation of MAGI2-AS3 may expedite the healing of fracture patients by targeting miR-223-3p, offering a novel biomarker for diagnosing patients with delayed healing.
Topics: MicroRNAs; RNA, Long Noncoding; Fracture Healing; Humans; Down-Regulation; Mice; Animals; Osteogenesis; Male; Female; Apoptosis; Adaptor Proteins, Signal Transducing; Adult; Cell Proliferation; Cell Differentiation
PubMed: 38907263
DOI: 10.1186/s13018-024-04850-5 -
Communications Biology Jun 2024Mammalian reproduction relies on precise maternal-fetal communication, wherein immune modifications foster tolerance toward the semi-allogeneic embryo. Extracellular... (Review)
Review
Mammalian reproduction relies on precise maternal-fetal communication, wherein immune modifications foster tolerance toward the semi-allogeneic embryo. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as crucial mediators, transporting molecules like microRNAs securely. EVs influence various reproductive stages, from gamete maturation to implantation, and impact pathologies like pregnancy loss. In the embryo-maternal dialogue, EVs notably affect oviductal interactions, gene expression, and the embryo-endometrial interface, crucial for successful implantation. Key queries persist about EV uptake, cargo delivery, and the specific biomolecules driving communication. Their potential in diagnostics, therapeutics, and understanding environmental impacts on fertility signals an exciting future, reliant on collaborative efforts for transformative strides in reproductive health.
Topics: Extracellular Vesicles; Humans; Female; Pregnancy; Animals; Maternal-Fetal Exchange; Embryo, Mammalian; Cell Communication; Embryo Implantation; MicroRNAs
PubMed: 38906986
DOI: 10.1038/s42003-024-06442-9 -
Scientific Reports Jun 2024Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction....
Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression.
Topics: Animals; MicroRNAs; Astrocytes; Mice; Septins; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Male; Neuralgia; Disease Models, Animal
PubMed: 38906977
DOI: 10.1038/s41598-024-65096-z -
Cardiovascular Pathology : the Official... Jun 2024The potential of the pericardial space as a therapeutic delivery tool for cardiac fibrosis and heart failure (HF) treatment has yet to be elucidated. Recently, miRNAs... (Review)
Review
The potential of the pericardial space as a therapeutic delivery tool for cardiac fibrosis and heart failure (HF) treatment has yet to be elucidated. Recently, miRNAs and exosomes have been discovered to be present in human pericardial fluid (PF). Novel studies have shown characteristic human PF miRNA compositions associated with cardiac diseases and higher miRNA expressions in PF compared to peripheral blood. Five key studies found differentially expressed miRNAs in HF, angina pectoris, aortic stenosis, ventricular tachycardia, and congenital heart diseases with either atrial fibrillation or sinus rhythm. As miRNA-based therapeutics for cardiac fibrosis and HF showed promising results in several in vivo studies for multiple miRNAs, we hypothesize a potential role of miRNA-based therapeutics delivered through the pericardial cavity. This is underlined by the favorable results of the first phase 1b clinical trial in this emerging field. Presenting the first human miRNA antisense drug trial, inhibition of miR-132 by intravenous administration of a novel antisense oligonucleotide, CDR132L, established efficacy in reducing miR-132 in plasma samples in a dose-dependent manner. We screened the literature, provided an overview of the miRNAs and exosomes present in PF, and drew a connection to those miRNAs previously elucidated in cardiac fibrosis and HF. Further, we speculate about clinical implications and potential delivery methods.
PubMed: 38906439
DOI: 10.1016/j.carpath.2024.107671 -
Biomedicine & Pharmacotherapy =... Jun 2024Malignant tumors and central nervous system (CNS) disorders are intricately linked to a process known as "aberrant cell cycle re-entry," which plays a critical role in... (Review)
Review
Malignant tumors and central nervous system (CNS) disorders are intricately linked to a process known as "aberrant cell cycle re-entry," which plays a critical role in the progression of these diseases. Addressing the dysregulation in cell cycles offers a promising therapeutic approach for cancers and CNS disorders. MicroRNAs (miRNAs) play a crucial role as regulators of gene expression in cell cycle transitions, presenting a promising therapeutic avenue for treating these disorders and their comorbidities. This review consolidates the progress made in the last three years regarding miRNA-based treatments for diseases associated with aberrant cell cycle re-entry. It encompasses exploring fundamental mechanisms and signaling pathways influenced by miRNAs in cancers and CNS disorders, particularly focusing on the therapeutic effects of exosome-derived miRNAs. The review also identifies specific miRNAs implicated in comorbidity of cancers and CNS disorders, discusses the future potential of miRNA reagents in managing cell cycle-related diseases.
PubMed: 38906026
DOI: 10.1016/j.biopha.2024.116979 -
Poultry Science May 2024Within the poultry industry, hens' reproductive performance is of great economic significance. The development and growth of follicles is a key aspect of hen egg...
Within the poultry industry, hens' reproductive performance is of great economic significance. The development and growth of follicles is a key aspect of hen egg production, and ovarian follicle growth and development are closely associated with granulosa cells (GCs) proliferation and the synthesis of steroid hormones. It has been confirmed by numerous studies that microRNAs (miRNAs) play important roles in the steroid hormone synthesis and proliferation of GCs. In this study, we examined the main miRNAs influencing hens' ability to reproduce, identified the miR-223 that is mainly expressed in atretic follicles based on sequencing, and investigated its role in GCs. Then, we used miR-223 mimic and inhibitor to knockdown or overexpress miR-223 expression. The result showed that miR-223 significantly inhibits both the steroid hormone synthesis and the proliferation of GCs. Subsequently, the results of the dual luciferase reporter experiment and bioinformatics prediction demonstrated that cysteine rich transmembrane BMP regulator 1 (CRIM1) was a downstream target gene of miR-223, and overexpression of miR-223 prevented CRIM1 expression. The function of CRIM1 was further investigated, and we observed a significant reduction in the synthesis of steroid hormones and the proliferation of GCs after transfection with CRIM1 siRNA. The opposite function of miR-223 was observed for CRIM1 in our study. Additionally, we demonstrated the involvement of the miR-223/CRIM1 axis in GCs through modulation of the AKT signaling pathway. Our data demonstrate the pivotal role of the miR-223 in the proliferation and steroid hormone synthesis of chicken GCs, which helps to explain how non-coding RNA (ncRNA) affects chicken reproductive function.
PubMed: 38905756
DOI: 10.1016/j.psj.2024.103910 -
Journal of Obstetrics and Gynaecology :... Dec 2024MiR-381 can regulate the expression of cyclin A2 (CCNA2) to inhibit the proliferation and migration of bladder cancer cells, but whether miR-381 has the same function in...
BACKGROUND
MiR-381 can regulate the expression of cyclin A2 (CCNA2) to inhibit the proliferation and migration of bladder cancer cells, but whether miR-381 has the same function in breast cancer is not well know.
METHODS
The over express or silence miR-381 expressing cell lines were constructed by lentivirus infection to reveal the biological functions of miR-381 . The expression of miR-381 and CCNA2 in 162 breast cancer patients were detected to further reveal their impact and predictive value on progression-free survival (PFS) and overall survival (OS).
RESULTS
After transfection of MDA-MB-231 and MCF-7 cells with miR-381 mimics, the expression of miR-381 was effectively up-regulated and CCNA2 was effectively down-regulated, while the opposite results were observed in tumour cell which transfected with miR-381 inhibitors. After transfection of cell lines with miR-381 mimics, tumour cell activity was significantly reduced, while the opposite results were observed in tumour cell which transfected with miR-381 inhibitors. The area under curves (AUCs) of miRNA-381 and CCNA2 for predicting PFS and OS were 0.711, 0.695, 0.694 and 0.675 respectively. Cox regression analysis showed that miRNA-381 ≥ 1.65 2 and CCNA ≥ 2.95 2 were the influence factors of PFS and OS, the hazard ratio (HR) values were 0.553, 2.075, 0.462 and 2.089, respectively.
CONCLUSION
miR-381 inhibitors breast cancer cells proliferation and migration by down-regulating the expression of CCNA2, both of them can predict the prognosis of breast cancer.
Topics: Humans; MicroRNAs; Female; Breast Neoplasms; Cell Proliferation; Cyclin A2; Prognosis; Middle Aged; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; MCF-7 Cells; Adult
PubMed: 38904638
DOI: 10.1080/01443615.2024.2360547 -
Iranian Journal of Kidney Diseases May 2024Diabetic nephropathy (DN) belongs to the major cause of end-stage kidney disease. We probed the functions of a microRNA miR-33a in inducing podocytes injury during...
INTRODUCTION
Diabetic nephropathy (DN) belongs to the major cause of end-stage kidney disease. We probed the functions of a microRNA miR-33a in inducing podocytes injury during childhood DN (CDN).
METHODS
Kidney samples were collected from 20 children with DN. Matrix deposition and glomerular basement membranes thickness were examined by periodic acid-Schiff staining. Immunofluorescence staining was performed to assess kidney function-related proteins. MicroRNA (MiR)-33a mimic together with miR-33a inhibitor was transfected into podocytes for determining the roles of miR-33a. Glomerular podocyte apoptosis was determined by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining along with flow cytometry.
RESULTS
Down-regulation of Nephrin and Podocin and increased podocyte apoptosis rate were observed in the glomerulus of CDN as well as podocytes treated with high glucose. MiR-33a was up regulated in the glomeruli and glucose-treated podocytes. Injury in podocytes was aggravated with miR-33a elevation but alleviated with miR-33a inhibition. Moreover, the expression of Sirtuin 6 (Sirt6) was decreased while the levels of notch receptor 1 (Notch1) and notch receptor 4 (Notch4) were elevated in the glomerulus and glucose-treated podocytes. Decreased level of Sirt6 upon glucose treatment was abrogated by miR-33a inhibition, and the podocytes injury induced by glucose exposure was relieved by Sirt6 via Notch signaling.
CONCLUSION
These findings indicated that miR-33a promoted podocyte injury via targeting Sirt6-dependent Notch signaling in CDN, which might provide a novel sight for CDN treatment. DOI: 10.52547/ijkd.7904.
Topics: MicroRNAs; Diabetic Nephropathies; Podocytes; Humans; Signal Transduction; Sirtuins; Apoptosis; Male; Child; Membrane Proteins; Female; Receptors, Notch; Intracellular Signaling Peptides and Proteins; Glucose; Up-Regulation; Receptor, Notch1; Down-Regulation
PubMed: 38904337
DOI: 10.52547/g7kbp983 -
BMJ Open Jun 2024WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to... (Observational Study)
Observational Study
Performance of and methylation as triage markers for early detection of cervical cancer in self-collected and clinician-collected samples: an exploratory observational study in Papua New Guinea.
OBJECTIVE
WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples.
DESIGN
Exploratory observational study.
SETTING
Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea.
PARTICIPANTS
44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal).
PRIMARY AND SECONDARY OUTCOME MEASURES
Methylation levels of and analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain.
RESULTS
In clinician-collected samples, and methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). was the best predictor of HSIL (area under the curve, AUC 0.819) while of SCC (AUC 0.856). In self-collected samples, best predicted HSIL (AUC 0.595) while SCC (AUC 0.812). Combined methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%).
CONCLUSION
methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country.
Topics: Humans; Female; MicroRNAs; Uterine Cervical Neoplasms; Papua New Guinea; Early Detection of Cancer; Cell Adhesion Molecule-1; Adult; Triage; DNA Methylation; Middle Aged; Myelin and Lymphocyte-Associated Proteolipid Proteins; Papillomavirus Infections; Biomarkers, Tumor; Carcinoma, Squamous Cell; Specimen Handling; Young Adult; Sensitivity and Specificity; Vaginal Smears
PubMed: 38904134
DOI: 10.1136/bmjopen-2023-081282 -
BMJ Open Jun 2024The 'Biomarkers of heterogeneity in type 1 diabetes' study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed...
Cohort profile: the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands.
PURPOSE
The 'Biomarkers of heterogeneity in type 1 diabetes' study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D).
PARTICIPANTS
Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected.
FINDINGS TO DATE
Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia.
FUTURE PLANS
Research groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function.
TRIAL REGISTRATION NUMBER
NCT04977635.
Topics: Humans; Female; Diabetes Mellitus, Type 1; Male; Netherlands; Adult; Prospective Studies; Middle Aged; Glycated Hemoglobin; Biomarkers; Cross-Sectional Studies; Phenotype; Blood Glucose; Young Adult; Disease Progression; C-Peptide; Aged; Adolescent
PubMed: 38904129
DOI: 10.1136/bmjopen-2023-082453