miR-208a-3p regulated by circUQCRC2 suppresses ischemia/reperfusion-induced acute kidney injury by inhibiting CELF2-mediated tubular epithelial cell apoptosis, inflammation and ferroptosis

Shock, Journal Year: 2024, Volume and Issue: 61(6), P. 942 - 950

Published: April 26, 2024

ABSTRACT Background : Acute kidney injury (AKI) is a prevalent clinical syndrome with persistent dysfunction. Renal ischemia/reperfusion (I/R) major cause of AKI. miR-208a-3p overexpression attenuated myocardial I/R injury. This study aims to investigate the role and mechanism in I/R-induced Methods AKI models were established using hypoxia/reoxygenation (H/R)-exposed tubule epithelial cell HK-2 mice. The function investigated by gain- or loss-of-function methods real-time PCR, CCK-8, flow cytometry, ELISA, western blot, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, detection Fe 2+ , reactive oxygen species, blood urea nitrogen creatinine, luciferase reporter assay. Results expression was suppressed, while CELF2 circular RNA ubiquinol-cytochrome c reductase core protein 2 (circUQCRC2) increased both models. upregulation circUQCRC2 silencing viability, decreased levels proinflammatory cytokines (TNF-α, IL-1β, IL-6), reduced apoptosis contents elevated GPX4 SLC7A11, ACSL4 H/R-stimulated cells. In addition, improved alleviating renal injury, apoptosis, inflammation, ferroptosis mouse model. target gene miR-208a-3p, which negatively modulated circUQCRC2. Overexpression blocked on H/R-treated Moreover, effects downregulation H/R-injured cells also reversed inhibitor. Conclusions regulated could attenuate inhibiting CELF2-mediated tubular inflammation ferroptosis. provides potential therapeutic targets for

Language: Английский

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Somatic repetitive element insertions Define New Biomarkers in Pan-cancer genome

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Abstract Repetitive elements insertions (REIs), including tandem repeat (TRIs) and transposable element (TEIs), constitute >90% of large-scale (>50bp) somatic are linked to diseases cancer biomarkers. However, the genomic landscape REIs in pan-cancer has not been well-characterized due short-read sequencing limitations. Here, we detected 325 genomes across 12 types using long-read whole-genome customized algorithms. The diverse sequence patterns TRIs insertion mechanisms TEIs were characterized different types. We identified 152 high-frequency TRIs, with 10 showing characteristics, SHROOM2, PALMD , enhancer PTPRZ1 . MHC class II gene cluster exhibited highest TEI abundance, affecting ∼40% tumors. Adenocarcinomas squamous cell carcinomas differing distributions within this region. Our study highlights as important but under-explored markers for personalized diagnosis immunotherapy.

Language: Английский

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Aregs-IGFBP3-mediated SMC-like cells apoptosis impairs beige adipocytes formation in aged mice

Molecular Metabolism, Journal Year: 2025, Volume and Issue: 95, P. 102125 - 102125

Published: March 19, 2025

Aging is associated with a decline in the browning capacity of white adipose tissue (WAT), contributing to metabolic dysfunction. Beige adipocytes, which dissipate excess energy as heat, are key feature this process. In study, we investigate role stem and progenitor cells (ASPCs), specifically Aregs (CD142+) subpopulation, regulating beige adipocyte formation aged mice under cold stimulation. Our findings reveal that significantly increase subcutaneous WAT (sWAT) following exposure. We further demonstrate secrete insulin-like growth factor binding protein 3 (IGFBP3), appears play pivotal cross-talk between adipogenesis-regulatory (Aregs) smooth muscle cell-like (SMC-like) cells, thereby leading inhibition adipocytes formation. Functional enrichment analysis highlighted activation TGFβ, MAPK p53 signaling pathways SMC-like all known induce cell apoptosis fibrosis. Moreover, IGFBP3 was found interact receptors molecules, including Egfr, Irf1 Cdkn1a, enhancing their apoptosis. Co-culture experiments confirmed suppressed corroborating its impairing browning. Overall, our study provides novel insights into molecular mechanisms by contribute age-related These suggest potential therapeutic targets for reversing impaired aging related disorders.

Language: Английский

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Instrumenting Carotid Sonography Biomarkers and Polygenic Risk Score As a Novel Screening Approach for Retinal Detachment

Translational Vision Science & Technology, Journal Year: 2025, Volume and Issue: 14(4), P. 16 - 16

Published: April 14, 2025

Retinal detachment (RD) is a vision-threatening condition that manifests silently before abrupt disease onset; thus, most of the RD at-risk individuals are left unchecked until first attack. To establish an risk-informing system for broader population, we utilized carotid ultrasonography (CUS) biometrics, polygenic risk score (PRSRD), and clinical covariates (COVs) to assess predisposition factors. First, backpropagation logistic regression model identified RD-associated CUS biomarkers further incorporated them as multivariable RD-risk nomogram. Next, PRSRD was established with selected single-nucleotide polymorphisms (SNPs) curated high functional expression candidates in retina single-cell RNA datasets. Finally, three-component prediction (CUS, PRSRD, COVs) assembled by cumulative analysis. Demographic analysis reported hypertension (HTN) status associated (odds ratio [OR] = 1.601). The revealed minimum flow right internal artery (ICA-Qmin; OR 1.04) time-averaged maximum velocity common (CCA-TAMAX; 1.03) were increased risk. Notably, genome-wide association studies (GWAS) three significant SNPs (IGFBPL1 rs117248428, 1.63; CELF2 rs56168975, 1.72; PAX6 rs11825821, 1.61; P < 5.00 × 10-6) highly expressed at border retinal pigment epithelium choroid. demonstrated state-of-the-art (AUCHTN+ 0.95, AUCHTN- 0.93). Based on instrumenting images genetic proposing screening method patients. Results from this study combination GWAS cost-effective, population-wide framework identifying individuals.

Language: Английский

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The HNRNPC/CELF2 signaling pathway drives glycolytic reprogramming and mitochondrial dysfunction in drug-resistant acute myeloid leukemia

Cell & Bioscience, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 16, 2025

Acute myeloid leukemia (AML) is an aggressive cancer with high treatment resistance, often leading to poor patient outcomes. Metabolic reprogramming plays a critical role in AML progression, influencing drug resistance (DR) and tumor survival. This study investigates the HNRNPC/CELF2 signaling pathway its impact on cell metabolism DR. The identified that HNRNPC regulates expression of CELF2 through m6 A modification. In drug-resistant cells, increased decreased were associated upregulated glycolysis, enhanced glucose consumption, lactate production, mitochondrial dysfunction. Knockdown reduced glycolysis invasion, while knockdown reversed these effects. Conversely, overexpression migration, which counteracted by overexpression. axis pivotal metabolic reprogramming, driving progression chemotherapy resistance. Targeting this may offer new therapeutic strategies overcome improve outcomes patients.

Language: Английский

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LINC00261 triggers DNA damage via the miR-23a-3p/CELF2 axis to mitigate the malignant characteristics of 131I-resistant papillary thyroid carcinoma cells

Biochemistry and Biophysics Reports, Journal Year: 2024, Volume and Issue: 40, P. 101858 - 101858

Published: Oct. 31, 2024

Language: Английский

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