Search Results (1,994)

Background: Head and neck squamous cell carcinoma remains a highly aggressive malignancy with limited predictive biomarkers for prognosis and radiotherapy response. Increasing evidence indicates that pseudogenes are functionally active regulators of cancer biology, yet their clinical relevance in HNSCC is poorly defined. Methods: Using transcriptomic and clinical data from The Cancer Genome Atlas, we analyzed the expression and clinical significance of two pseudogenes, ANXA2P2 and PA2G4P4, in HNSCC. Associations with clinicopathological features, HPV status, tumor subtypes, survival, genomic instability, radiotherapy response, and immune landscape were assessed using bioinformatic tools. Results: Both pseudogenes were significantly upregulated in HNSCC compared to normal tissues. Higher expression levels correlated with adverse clinicopathological features, increased tumor proliferation and wound-healing capacity, and unfavorable TCGA molecular subtypes. High ANXA2P2 and PA2G4P4 expression was associated with reduced overall survival, while their combined low-expression signature identified patients with significantly improved overall and disease-free survival. Notably, lower expression of both pseudogenes was observed in patients responding to radiotherapy, whereas higher expression was linked to genomic instability parameters and enrichment of oncogenic pathways, including MYC, PI3K/AKT/mTOR, cell cycle regulation, and DNA repair. ANXA2P2 expression differed significantly by HPV status, showing reduced levels in HPV-positive tumors. Furthermore, pseudogene expression stratified distinct immune profiles, including immune subtypes, stromal and immune scores, and specific immune cell populations. Conclusions:ANXA2P2 and PA2G4P4 are clinically relevant pseudogenes associated with tumor aggressiveness, immune modulation, and radiotherapy response in HNSCC. These findings support their potential utility as prognostic and predictive biomarkers and provide a rationale for further functional validation in experimental models. Full article

Pregnancies complicated by diabetes, including pregestational and gestational diabetes mellitus, are associated with increased maternal and fetal morbidity. Early identification of at-risk pregnancies is crucial for timely intervention and improved outcomes. Emerging evidence highlights the interplay of genetic predisposition, epigenetic modifications, and non-invasive biomarkers in the early detection of diabetic pregnancies. Genetic factors influencing insulin signaling, glucose metabolism, and pancreatic β-cell function may contribute to susceptibility to gestational hyperglycemia. Concurrently, epigenetic alterations, such as DNA methylation and histone modifications in maternal and placental tissues, have been linked to dysregulated metabolic pathways and adverse pregnancy outcomes. Non-invasive biomarkers, including circulating cell-free DNA and microRNAs in maternal blood, show promise for early diagnosis by offering a safer and more practical alternative to invasive testing. Integrating genetic, epigenetic, and molecular marker data could enhance risk stratification and enable personalized monitoring and management strategies. This review synthesizes current knowledge on the molecular underpinnings of diabetic pregnancies, evaluates the potential of emerging biomarkers for early diagnosis, and discusses the challenges and future perspectives for translating these findings into clinical practice. Understanding these mechanisms may pave the way for precision medicine approaches, ultimately improving maternal and neonatal outcomes in pregnancies affected by diabetes. Full article

The acute (single-session) and chronic (12-week) effects of whole-body vibration training (WBVT) on oxidative stress, muscle damage, and deoxyribonucleic acid (DNA) damage were evaluated in inactive women (20.48 ± 1.72 years). Participants were assigned to vibration training (EVG, n = 17), traditional exercise (EXG, n = 12), or control groups (CON, n = 17). Blood was collected pre- and post- the first and last sessions for EVG and EXG and at baseline and after 12 weeks for the CON. A significant main effect of time was observed for total antioxidant capacity (TAC, p < 0.001), indicating long-term enhancement of the antioxidant barrier across all groups. Analysis of change scores (Δ) revealed that the 12-week intervention significantly dampened the acute post-exercise response for white blood cells (WBCs, p < 0.001), neutrophils (NEUTs, p = 0.010), and myoglobin (Mb, p = 0.004), confirming systemic adaptation in both training groups. A significant reduction in total oxidant status (TOS, p = 0.042) was also noted between the first and last sessions. Significant main effects of group were found for WBCs, NEUTs, 8-hydroxy-2′-deoxyguanosine (8-OHdG), Mb, body mass, and fat-free mass, reflecting persistent baseline differences; however, no significant group-by-time interactions were identified. In conclusion, while WBVT did not show superior effects, it is a safe modality, comparable to traditional exercise, for improving oxidative stress tolerance and muscle recovery. Full article

Background/Objectives: Detecting copy number variations (CNVs) from next-generation sequencing (NGS) is challenging, particularly in targeted sequencing panels, especially for cell-free DNA (cfDNA), where the signal is weak and noise is high. Methods: We present BayesCNV, a Bayesian hierarchical model for gene-level copy ratio estimation from targeted amplicon read depths compared to a CNV-neutral reference sample. The model provides posterior uncertainty for each gene and supports interpretable calling based on effect size and posterior confidence. The model also provides a principled quality-control strategy based on the marginal log likelihood of each sample, with low values indicating low confidence in the calls. BayesCNV uses thermodynamic integration, a technique to reliably estimate this quantity. We benchmark our method against two publicly available CNV callers using Seracare^® reference samples with known CNVs on the OncoReveal^® Core Lbx panel. Results: Our method achieves a sensitivity of 0.87 and specificity of 0.996, dramatically outperforming two competitor methods, IonCopy and DeviCNV. In a separate FFPE dataset using the OncoReveal^® Essential Lbx panel, we show that the marginal log likelihood cleanly separates, degraded from high-quality samples, even when conventional sequencing QC metrics do not. Conclusions: BayesCNV provides accurate and interpretable gene-level CNV estimates and uncertainty quantification, along with an evidence-based quality control metric that improves robustness in targeted cfDNA workflows. Full article

Metastatic uveal melanoma (MUM) remains largely refractory to immune-checkpoint inhibition, so recent research has turned to bispecific T-cell engagers (BTCEs), adoptive-cell therapies (ACTs), and oncolytic viruses (OVs). To summarize the available clinical evidence, we performed a structured literature search across PubMed, Scopus, and Europe PMC for primary studies published between 1 January 2010 and 31 May 2025 that enrolled at least three adults with MUM, treated with one of these modalities, and that reported efficacy or grade-3+ safety outcomes; two reviewers independently performed screening, data extraction, and risk-of-bias assessment, and because of notable heterogeneity, we synthesized the findings narratively. Twenty-two studies met the criteria—thirteen phase I–III trials, eight observational cohorts, and one case series—covering fifteen BTCE cohorts, four ACT cohorts, and three OV cohorts. Tebentafusp, the dominant BTCE evaluated in roughly 1150 HLA-A*02:01-positive patients, extended median overall survival from 16.0 to 21.7 months (hazard ratio 0.51, with three-year follow-up HR 0.68) in its pivotal phase-III trial despite objective response rates of only 5–12%, with early skin rash and week-12 circulating-tumor-DNA clearance emerging as consistent markers of benefit. Tumor-infiltrating lymphocyte therapy, administered to about thirty patients, produced objective responses in 11–35% and occasional durable complete remissions, although median progression-free survival remained 2–6 months and severe cytopenias were universal. Three early-phase OV studies, totaling twenty-nine patients, yielded no radiographic responses but showed tumor-specific T-cell expansion and transient disease stabilization. Safety profiles reflected the mechanism of action: tebentafusp most often caused rash, pyrexia, and usually manageable cytokine-release syndrome with grade-3+ events in 40–70% yet discontinuation in roughly 2%; TIL therapy toxicity was driven by lymphodepleting chemotherapy and high-dose interleukin-2 with one treatment-related death; and OVs were generally well tolerated with no more than 20% grade-3 events. Full article

Liquid biopsy is moving beyond mutation-centric assays to multimodal frameworks that integrate cell-free DNA (cfDNA) signals with additional analytes such as circulating tumor cells (CTCs) and extracellular vesicles (EVs). In this review, we summarize emerging technologies across analytes for early cancer detection, emphasizing sequencing and error-suppression strategies and the growing evidence for multi-cancer early detection (MCED), tissue-of-origin (TOO) inference, diagnostic triage, and longitudinal surveillance. At low tumor fractions, fragmentomic and methylation features preserve tissue and chromatin context; when combined with radiomics using deep learning, they support blood-first, high-specificity risk stratification, increase positive predictive value (PPV), reduce unnecessary procedures, and enhance early prediction of treatment response and relapse. Building on these findings, we propose a pathway-aware workflow: initial blood-based risk scoring, followed by organ-directed imaging, and targeted secondary testing when indicated. We further recommend that model reports include not only discrimination metrics but also calibration, decision-curve analysis, PPV/negative predictive value (NPV) at fixed specificity, and TOO accuracy, alongside multi-site external validation and blinded dataset splits to improve generalizability. Overall, liquid biopsy is transitioning from signal discovery to deployable multimodal decision systems; standardized pre-analytical and analytical workflows, robust error suppression, and prospective real-world evaluations will be pivotal for clinical implementation. Full article

Exopolysaccharides (EPSs) produced by lactic acid bacteria (LAB) are bioactive polymers with significant potential for human health. This study aimed to isolate and systematically evaluate the in vitro probiotic properties of high exopolysaccharide-producing LAB strains from traditional Sayram yogurt. From fifteen strains, six strains with high exopolysaccharide production were identified using 16Sr DNA sequencing. We assessed their probiotic potential by testing acid resistance, bile salt tolerance, tolerance to artificial gastrointestinal fluid, self-aggregation, hydrophobicity, safety, antibacterial activity, and antioxidant capacity. Results showed these six strains exhibited a strong tolerance to acid, bile salts, and artificial gastrointestinal fluids, and had high self-aggregation abilities and surface hydrophobicity. The isolated strains exhibited varying degrees of sensitivity to the tested antibiotics, with no hemolysis, suggesting good safety. In addition, their cell-free supernatants significantly inhibited the growth of Staphylococcus aureus and showed stronger antioxidant activity than cell lysates. In conclusion, the six LAB strains screened in this study possess excellent in vitro probiotic properties and have potential value for further development, providing a preliminary strain reserve and theoretical reference for subsequent research and related product development. Full article

Background/Objectives: Ineffective erythropoiesis (IE) is a hallmark of β-thalassemia and contributes to major clinical complications, including severe anemia, extramedullary hematopoiesis, and progressive iron overload. Despite its central role in disease pathophysiology, there is no established biomarker for the reliable identification and monitoring of IE. This systematic review was conducted to evaluate potential serum markers that reflect IE in β-thalassemia. Methods: Across seven databases (PubMed, ScienceDirect, Web of Science, SpringerLink, Taylor & Francis, ProQuest, and SAGE), thirteen studies met the eligibility criteria and were analyzed to identify circulating biomarkers associated with IE in β-thalassemia. Results: The most consistently reported markers were growth differentiation factor-15 (GDF-15), soluble transferrin receptor (sTfR), erythropoietin (EPO), and erythroferrone (ERFE), all of which demonstrated strong correlations with the degree of IE and erythroid expansion. Additional markers, including circulating cell-free DNA (cfDNA), CA15.3, hepcidin, ferritin, and phosphatidylserine (PS)-exposed red blood cells, were also found to be elevated, reflecting increased erythroid turnover, apoptosis, and secondary iron dysregulation. These findings suggest that while individual markers capture different aspects of IE, their combined evaluation may provide a more comprehensive picture of disease burden. Conclusions: IE represents the central pathophysiological driver of β-thalassemia and is closely linked to disease complications. Early detection through circulating biomarkers offers the potential for timely identification of high-risk patients, monitoring of therapeutic responses, and prognostication. Although current evidence highlights GDF-15, sTfR, ERFE, and EPO as the most promising candidates, further validation in larger, longitudinal cohorts is required before clinical implementation. Full article

Neoantigen-based immunotherapies harness somatic mutations as tumor-specific targets and represent a major advance in personalized cancer treatment. Since neoantigens are presented exclusively on cancer cells, they enable highly selective T-cell recognition with minimal off-tumor toxicity. Neoantigen vaccines are rapidly emerging as a versatile class of personalized cancer immunotherapies designed to prime tumor-specific T cells by targeting somatic mutations unique to each patient’s tumor. Multiple types of neoantigen vaccines, using peptide, mRNA, and DNA, have shown feasibility, safety, and immunogenicity across diverse solid tumors. Emerging comparative data indicate that the vaccines using peptide-pulsed dendritic cells (DCs) elicit higher per-epitope CD8⁺ T cell responses than mRNA-based vaccines, likely due to more efficient class I presentation of synthetic peptides and ex vivo-loaded DCs. In contrast, mRNAs, despite their capacity of targeting multiple neoantigen peptides simultaneously, often induce CD4⁺-dominant responses due to immunodominance patterns during antigen processing. Recent clinical trials in melanoma, glioblastoma, pancreatic cancer, and other types of cancer have demonstrated not only robust immune activation but also encouraging relapse-free outcomes when administered in adjuvant settings. Treatment timing strongly influenced immune responsiveness; patients with early-stage disease or those vaccinated after surgical resection generally exhibit more preserved systemic immunity and greater vaccine-induced T cell expansion compared to those with advanced disease. Future progress will rely on improved neoantigen prediction, including incorporation of post-translationally modified antigenic targets and acceleration of manufacturing pipelines to ensure timely, personalized vaccine delivery. Collectively, neoantigen vaccines offer substantial promise for integration into next-generation cancer treatment strategies. Full article

Colorectal tumors consist of diverse cell populations, including cancer cells and immune cells. Sorafenib (Nexavar), an oral multikinase inhibitor, targets tumor growth and angiogenesis while inducing apoptosis. However, its clinical use is hindered by poor solubility, rapid metabolism, and low bioavailability. This study explores a nanotechnology-based approach to enhance Sorafenib’s efficacy against colon cancer. Nexavar was encapsulated into nanoparticles using an oil phase and Span 80 as a stabilizer to produce sub-100 nm droplets. The resulting Nano-Nexavar was evaluated for cytotoxicity on Caco-2 colorectal cancer cells and compared with free Nexavar on both Caco-2 and normal NCM-460 colon cells. Nano-Nexavar significantly reduced cancer cell viability at lower concentrations, with no observed toxicity to normal cells. Both formulations induced lactate dehydrogenase release and cell reduction at 2.5 µM, but Nano-Nexavar triggered nearly 60% apoptosis in Caco-2 cells. It inhibited Raf-1, NFκB, and ERK signaling, and reduced epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) levels over time. Notably, unlike Nexavar, the Nano-Nexavar suppressed aspartate β-hydroxylase (ASPH) and enhanced mitochondrial-mediated apoptosis by increasing Bax expression, mitochondrial accumulation, and mtDNA levels indicated by immunofluorescence, immunoblotting, flow cytometry, and qRT-PCR. These data demonstrate that Nano-Nexavar potentiates Sorafenib’s anticancer activity by targeting ASPH, thereby amplifying mitochondrial signaling–induced cell death. Full article

Background: Urothelial bladder carcinoma (UBC) is a disease that lacks robust non-invasive laboratory biomarkers. Recently, urine liquid biopsy has emerged as a promising tool for diagnosis and surveillance of patients with these tumors. The aim of this study was to evaluate the diagnostic potential of a urinary tumor DNA detection panel, which included eight common point mutations in TERT, GPR126, FGFR3, and PIK3CA genes, in UBC. Methods: The study included patients with histologically confirmed UBC (n = 88) and patients with cystitis, bladder leiomyomas, or other non-malignant conditions (control group; n = 72). DNA was extracted from whole urine specimens. ddPCR analysis was performed using the Bio-Rad QX200 AutoDG ddPCR system. Results: Urinary tumor DNA detection panel demonstrated a sensitivity of 78.4% and a specificity of 100% (AUC−ROC = 0.892). Detection rates for the analyzed mutations were the following: 54.5%, 37.5%, 28.4%, and 38.6% for TERT, GPR126, FGFR3, and PIK3CA, respectively. Pairwise comparisons of mutant allele fractions (MAFs) for samples simultaneously positive for ≥2 mutations revealed an absence of significant differences (p > 0.05), except for the pair of FGFR3 vs. PIK3CA (p = 0.03). MAFs were not associated with any clinical and demographic features (p > 0.05), with the only exception being the tumor size: patients with tumors larger than 2.16 cm³ had higher MAFs than the rest (23.4 [1.8; 46.3] vs. 1.6 [0; 24.6] %, respectively, p = 0.02). Conclusions: Upon further validation, the presented tumor DNA detection panel for ddPCR might become a useful tool for diagnostic purposes in UBC. Full article

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, with heart failure (HF) representing a major contributor to hospitalizations, healthcare costs, and death. Effective management of HF is hindered by the limitations of current biomarkers and diagnostic tools. Conventional biomarkers, such as natriuretic peptides, primarily reflect downstream hemodynamic stress and often lack specificity, particularly in HF with preserved ejection fraction or multiple comorbidities. While imaging provides valuable structural and functional information, it is resource-intensive, costly, and unsuitable for frequent longitudinal monitoring. As a result, these conventional approaches are inadequate to capture the dynamic and heterogeneous nature of HF pathophysiology. Circulating cell-free nucleic acids (cfNAs), including cell-free DNA (cfDNA) and RNA (cfRNA), have emerged as promising noninvasive liquid biopsy biomarkers capable of providing real-time insight into upstream pathological events, such as cardiomyocyte injury, immune activation, inflammation, and maladaptive remodeling. Importantly, cfNAs also act as active mediators of CVD pathology. When released under stress or injury, cfNAs interact with pattern recognition receptors (PRRs) that trigger sterile inflammation, cardiovascular cell dysfunction, and adverse cardiac remodeling. This review summarizes the origins, mechanistic roles, and clinical significance of cfNAs in HF and related CVD, highlighting their dual roles as diagnostic biomarkers and mechanistic effectors of disease. Finally, we discuss emerging cfNA-targeted therapeutic strategies, challenges, and future opportunities for precision medicine in HF and HF-associated CVD. Full article

Neutrophil extracellular traps (NETs)—webs of DNA and granular proteins expelled by neutrophils—have been implicated in hepatocellular carcinoma (HCC) progression. NETs promote tumor angiogenesis, facilitate invasion/metastasis, and enable immune evasion. Recent data suggest that perioperative factors, including anesthetic techniques, may modulate NET formation (NETosis), thus potentially influencing oncologic outcomes. We conducted a literature review of experimental and clinical studies on NETosis pathophysiology and involvement in HCC and how anesthetic techniques may modulate NET formation and, implicitly, cancer outcomes. NET biomarkers such as citrullinated histone H3 (CitH3), cell-free DNA (cfDNA), and myeloperoxidase–DNA complexes (MPO-DNA) are elevated in HCC patients and correlate with tumor spread, showing diagnostic and prognostic potential. Perioperative anesthetic choices may influence NET activity and immune function. Regional anesthesia and local anesthetics (e.g., lidocaine infusion) attenuate the surgical stress response and preserve anti-tumor immunity. Notably, lidocaine may modulate NET formation and, in a few studies published so far, was shown to reduce postoperative NET markers and other pro-metastatic factors (MMP-9, VEGF) in cancer surgery. In conclusion, NETosis is a process that is strongly implicated in HCC biology. Data published so far suggest that the clinical significance of NETosis may lie in its potential as a marker for disease evaluation and progression, including during the perioperative period. Preliminary results suggest that lidocaine may have a role in decreasing NETosis. Future large randomized trials are needed to exactly quantify these effects. Targeting NETs may be another way to influence HCC outcomes. Full article

Background: The senescence of testicular Leydig cells (LCs) is a key cause of age-related testosterone deficiency, in which oxidative stress (OS) and mitochondrial dysfunction are critical driving mechanisms. We explore whether the bioactive peptide C248 of PRDX4, an intracellular antioxidant, exerts mitochondrial protection to ameliorate LCs’ function. Methods: Based on the antioxidant domains of the PRDX4 protein, small molecular peptides were designed, and bioactive peptide C248 stood out from the crowd. An OS-induced senescence model of LCs was constructed by treating the MLTC-1 cell line with hydrogen peroxide (H₂O₂). C248 peptide or nicotinamide mononucleotide (NMN), as the positive control, was administered in the culture medium. The cellular function-related indicators, including DPPH free radical scavenging rate, cell viability, testosterone level, hydrogen peroxide (H₂O₂) content, senescence-associated β-galactosidase (SA-β-gal) activity, 8-hydroxy-2′-deoxyguanosine (8-OHDG) level, and 4-hydroxynonenal (4-HNE) level, were evaluated. The mitochondrial function and structural indicators, such as mitochondrial membrane potential, ATP production, mitochondrial morphology, and mitochondrial DNA (mtDNA) copy number, were subsequently tested. Results: In vitro experiments confirmed that C248 could scavenge DPPH free radicals in a dose-dependent manner, reduce the levels of reactive oxygen species, and increase antioxidant enzyme activity in LCs (p < 0.01). Both C248 and NMN increased testosterone secretion and improved cell viability (p < 0.01). Both C248 and NMN increased mitochondrial morphology and quantity, mitochondrial membrane potential (p < 0.01), ATP production (p < 0.01), and mitochondrial DNA (mtDNA) copy number (p < 0.01). Conclusion: This study reveals that the small molecular C248, a bioactive peptide of PRDX4, is a new candidate molecule for intervening in LC senescence and confirms that mitochondrial protection is a key strategy for improving age-related testicular dysfunction. Full article

Background/Objectives: Conventional next-generation sequencing (NGS) workflows often require more than two weeks to complete, delaying treatment decisions and limiting access to precision oncology in community settings. This report aimed to demonstrate the feasibility of performing rapid, comprehensive cell-free DNA (cfDNA)-based genomic profiling by introducing a fully automated NGS workflow in a community hospital environment. Case Presentation: A postoperative patient with pancreatic ductal adenocarcinoma and liver metastasis underwent cfDNA-based liquid biopsy using plasma collected in PAXgene^® Blood ccfDNA Tubes. Gene analysis was performed using the Oncomine Precision Assay GX5 on the Ion Torrent Genexus™ System (Thermo Fisher Scientific). Three pathogenic hotspot mutations—KRAS G12R, TP53 M246I/M246K, and GNA11—and one copy number gain in PIK3CA were identified, whereas no variants were detected in a healthy volunteer control. The total turnaround time from plasma separation to report generation was approximately 27 h, requiring only 40 min of total hands-on time. Discussion: This rapid, automated workflow enabled comprehensive cfDNA analysis within a clinically practical timeframe, overcoming key limitations of conventional multi-step NGS workflows that typically require external sample shipment and specialized personnel. The results confirm the technical feasibility of conducting high-quality molecular testing in a regional hospital setting. Conclusions: This report demonstrates that fully automated cfDNA-based NGS can achieve clinically meaningful genomic profiling within 27 h in a community hospital. This advancement addresses the time and cost barriers of traditional NGS analysis and represents a significant step toward promoting precision medicine in community healthcare. Full article