Intermittent Hypoxia Mediates Cancer Development and Progression Through HIF-1 and miRNA Regulation

Archivos de Bronconeumología, Год журнала: 2023, Номер 59(10), С. 629 - 637

Опубликована: Июль 9, 2023

There is still a debate for the link between obstructive sleep apnoea (OSA) and cancer. The mechanisms underlying this causality are poorly understood. Several miRNAs involved in cancer development progression with expression being influenced by hypoxia. aims of work were (i) to compare controls versus patients affected OSA without or (ONCO-OSA) (ii) colorectal cells exposed intermittent hypoxia (IH), evaluate impact on tumor vitro.We detected qRT-PCR patients' sera CaCo2 2-32h IH acriflavine (ACF), HIF-1 inhibitor. Viability transwell invasion test applied investigate proliferation migration treated miRNA inhibitors acriflavine. HIF-1α activity was evaluated after IH.The levels miR-21, miR-26a miR-210 increased ONCO-OSA compared controls. MiR-23b patients, miR-27b miR-145 but not patients. MiR-21, miR-26a, miR-23b IH. stimulated cell migration. This effect reduced either inhibition treatment. MiRNA reduces gene expression. Conversely, these miRNAs.We identified signature miRNAs, induced environment. They could be implicated through regulatory loop involving HIF-1.

Язык: Английский

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Relationship between REI and PSA in patients with obstructive sleep apnea: a prospective case-control study

Sleep And Breathing, Год журнала: 2025, Номер 29(1)

Опубликована: Янв. 3, 2025

Язык: Английский

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Clinically applicable semi-supervised learning framework for multiple organs at risk and tumor delineation in lung cancer brachytherapy

Physica Medica, Год журнала: 2025, Номер 133, С. 104968 - 104968

Опубликована: Апрель 3, 2025

Язык: Английский

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Identification of Overlapping Genetic Signatures Between Obstructive Sleep Apnea and Lung Cancer: Moving Beyond “One Drug, One Disease” Paradigm of Pharmaceutical Innovation

OMICS A Journal of Integrative Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Traditional paradigms of pharmaceutical innovation have long relied on the "one drug, one disease" premise. However, a network mindset in unpacking disease mechanisms can be fruitful to move toward polydisease" paradigm drug discovery and development. A case point is obstructive sleep apnea (OSA) lung cancer, which are two prevalent respiratory disorders that share common risk factors may potentially exhibit overlapping molecular mechanisms. The putative mechanistic linkages between OSA cancer remain underexplored; however, this study offers new evidence genetic signatures with an in-silico approach. Bioinformatics analysis publicly available datasets (GSE135917 GSE268175) identified 123 upregulated 13 downregulated genes 3175 2272 cancer. total four (C1GALT1, TMEM106B, ZNF117, ZNF486) were significantly both disorders, highlighting shared Pathway cell enrichment indicated mucin type O-glycan biosynthesis pathway endothelial cells strongly associated these genes, lending support for their potential roles diseases. Moreover, hsa-miR-34a-5p, hsa-let-7g-5p, hsa-miR-19a-3p found genes. Validation using GEPIA2 tool confirmed consistent expression patterns Machine learning highlighted TMEM106B as most significant biomarker candidate distinguishing from controls. In summary, supports overarching concept human diseases pathways specific example While findings call further research validation, they invite rethinking current beyond concept.

Язык: Английский

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Obstructive sleep apnea severity, circulating biomarkers, and cancer risk

Journal of Clinical Sleep Medicine, Год журнала: 2024, Номер 20(9), С. 1415 - 1422

Опубликована: Сен. 1, 2024

To determine whether obstructive sleep apnea (OSA) severity and/or biomarkers of inflammation/angiogenesis are associated with incident cancer in this clinical cohort.

Язык: Английский

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Differential Impact of Intermittent vs. Sustained Hypoxia on HIF-1, VEGF and Proliferation of HepG2 Cells

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 6875 - 6875

Опубликована: Апрель 7, 2023

Obstructive sleep apnea (OSA) is an emerging risk factor for cancer occurrence and progression, mainly mediated by intermittent hypoxia (IH). Systemic IH, a main landmark of OSA, local sustained (SH), classical feature at the core tumors, may act separately or synergistically on tumor cells. Our aim was to compare respective consequences HIF-1, endothelin-1 VEGF expression cell proliferation migration in HepG2 liver Wound healing, spheroid expansion, were evaluated cells following IH SH exposure. The HIF-1α, protein levels and/or mRNA assessed, as effects HIF-1 (acriflavine), (macitentan) (pazopanib) inhibition. Both stimulated wound expansion VEGF, but not endothelin-1, increased with exposure Acriflavine prevented both SH, pazopanib blocked those SH. Macitentan had no impact. Thus, stimulate hepatic via distinct signaling pathways that OSA patients cancer, leading enhanced progression.

Язык: Английский

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Inhibiting the CB1 receptor in CIH-induced animal model alleviates colon injury

Applied Microbiology and Biotechnology, Год журнала: 2024, Номер 108(1)

Опубликована: Июнь 18, 2024

Abstract Obstructive sleep apnea (OSA) can lead to intestinal injury, endotoxemia, and disturbance of flora. Additionally, as a crucial component the endocannabinoid system, some studies have demonstrated that cannabinoid 1 (CB1) receptors are closely linked multiple organ dysfunction triggered by OSA. However, role CB1 receptor in alleviating OSA-induced colon injury remains unclear. Here, through construction OSA classic model, we found tissue chronic intermittent hypoxia (CIH)–induced mice exhibited an overexpression receptor. The results hematoxylin-eosin staining transmission electron microscopy revealed inhibition could decrease gap between mucosa muscularis mucosae, alleviate mitochondrial swelling, reduce microvilli shedding, promote recovery tight junctions CIH-induced mice. Furthermore, reduced levels metabolic endotoxemia inflammatory responses, exhibiting significant protective effects on caused CIH. At molecular level, western blotting real-time polymerase chain reaction techniques, inhibiting significantly increase expression ZO-1 Occludin proteins, which related maintenance mucosal barrier function. Through 16S rRNA high-throughput sequencing short-chain fatty acid (SCFA) determination, increased diversity microbial flora controlled makeup Moreover, butyric concentration amount SCFA-producing bacteria, such Ruminococcaceae Lachnospiraceae , were both markedly elevated inhibition. spearman correlation study indicated showed positive association with but was negatively correlated receptor, IL-1β, TNF-α. According this study, improve regulating gut microbiota, reducing damage promoting junction recovery. Key points •CIH leads tissue. causes disorder, damage, disruption junctions. •Inhibition CIH Graphical abstract

Язык: Английский

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Multi-Omics Analysis of Circulating Exosomes in Adherent Long-Term Treated OSA Patients

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16074 - 16074

Опубликована: Ноя. 8, 2023

Obstructive sleep apnea (OSA) is a highly prevalent chronic disease affecting nearly billion people globally and increasing the risk of multi-organ morbidity overall mortality. However, mechanisms underlying such adverse outcomes remain incompletely delineated. Extracellular vesicles (exosomes) are secreted by most cells, involved in both proximal long-distance intercellular communication, contribute toward homeostasis under physiological conditions. A multi-omics integrative assessment plasma-derived exosomes from adult OSA patients prior to after 1-year adherent CPAP treatment lacking. We conducted multi-omic assessments following identify potential specific candidates. Fasting morning plasma isolated 12 with polysomnographically-diagnosed were analyzed before months therapy (mean ≥ 6 h/night) (OSAT). Exosomes characterized flow cytometry, transmission electron microscopy, nanoparticle tracking analysis. Endothelial cell barrier integrity, wound healing, tube formation also performed. Multi-omics analysis for exosome cargos was integrated. derived OSAT improved endothelial permeability dysfunction as well significant improvement compared OSA. Multi-omic approaches circulating included lipidomic, proteomic, small RNA (miRNAs) assessments. found 30 differentially expressed proteins (DEPs), 72 lipids (DELs), 13 miRNAs (DEMs). that cholesterol metabolism (has04979) pathway associated lipid classes patients. Among subjects OSAT, seven had complete comprehensive cargo information including lipids, proteins, miRNAs. signature biomarkers responsive treatment. These molecules may play mechanistic role OSA-induced morbidities their reversibility. Our data suggest approach might be useful understanding how function, origin, clinical relevance, all which merit future exploration context relevant phenotypic variance. Developing an integrated molecular classification should lead diagnostic classification, stratification, patient management assigning disease-specific therapies.

Язык: Английский

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PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 3, 2023

Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as novel immune checkpoint, which recognized hallmarks in several types and have revolutionized therapy.The expression PSGL-1 its ligands VISTA SIGLEC-5 was assessed leucocytes OSA patients control subjects exploring role intermittent hypoxia (IH) using vitro models. In addition, impact on T-cells function evaluated by ex vivo models.Data showed is upregulated T-lymphocytes from with severe OSA, indicating relevant hypoxemia mediated hypoxia. Besides, results suggest an inhibitory T-cell proliferation capacity. Finally, but increased monocytes suggesting regulatory hypoxia.In conclusion, might constitute additional checkpoint leading to dysfunction contributing disruption surveillance, provide biological plausibility aggressiveness tumors these patients.

Язык: Английский

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Prediction of the Sleep Apnea Severity Using 2D-Convolutional Neural Networks and Respiratory Effort Signals

Diagnostics, Год журнала: 2023, Номер 13(20), С. 3187 - 3187

Опубликована: Окт. 12, 2023

The high prevalence of sleep apnea and the limitations polysomnography have prompted investigation strategies aimed at automated diagnosis using a restricted number physiological measures. This study to demonstrate that thoracic (THO) abdominal (ABD) movement signals are useful for accurately estimating severity apnea, even if central respiratory events present. Thus, we developed 2D-convolutional neural networks (CNNs) jointly THO ABD automatically estimate evaluate event contribution. Our proposal achieved an intraclass correlation coefficient (ICC) = 0.75 root mean square error (RMSE) 10.33 events/h when apnea-hypopnea index, ICC 0.83 RMSE 0.95 index. CNN obtained accuracies 94.98%, 79.82%, 81.60% 5, 15, 30 evaluating complete hypopnea model improved nature was central: 98.72% 99.74% accuracy 5 15 events/h. Hence, information extracted from these CNNs could be powerful tool diagnose especially in subjects with density events.

Язык: Английский

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