Search Results (1,379)

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a five-year survival rate of approximately 13%, partly because of limited treatment options and resistance to therapies. Although the recently discovered KRAS G12D inhibitor MRTX1133 has shown promising efficacy in preclinical models, its clinical efficacy as a single agent is expected to be limited, as is the case with KRAS G12C inhibitors. Therefore, in this study, we evaluated potential combination strategies to enhance the therapeutic effect of MRTX1133. We combined MRTX1133 with the BCL-xL proteolysis-targeting chimera (PROTAC) DT2216 and the mTOR inhibitor everolimus. Methods: The sensitization of MRTX1133 by the combination of DT2216 + everolimus was tested in KRAS G12D-mutant PDAC cell lines using colony formation and apoptosis assays. The effects of MRTX1133 and/or DT2216 + everolimus on KRAS signaling and BCL-2 family proteins were assessed by immunoblotting and/or RT-PCR. The functional roles of BIM/NOXA were elucidated via immunoprecipitation (IP) and siRNA knockdown. Triple combination efficacy was evaluated in AsPC1 parental and MRTX1133-resistant xenografts, with pharmacodynamic effects confirmed by immunoblotting and immunohistochemistry. Results: The triple combination leads to significantly greater colony growth inhibition and apoptosis induction as compared with single agents or two-drug combinations in multiple KRAS G12D-mutant PDAC cell lines. Mechanistically, MRTX1133 treatment increased BIM and decreased NOXA levels, and the combination of DT2216/everolimus simultaneously enhanced BIM release and stabilized NOXA. In vivo, DT2216/everolimus combination significantly potentiated the anti-tumor activity of MRTX1133 in the AsPC1 PDAC xenograft model. Furthermore, the triple combination effectively overcame acquired MRTX1133 resistance in vitro and in the AsPC1 xenograft model. Conclusions: Collectively, our findings suggest that the combination of DT2216/everolimus potentiates the anti-tumor efficacy of MRTX1133 associated with enhanced apoptosis induction and inhibition of compensatory survival signaling. Full article

DNA polymerase beta (Polβ) is a 39 kDa, single polypeptide enzyme that possesses both gap tailoring and nucleotidyl transferase activity and is the key polymerase involved in base excision repair (BER) and the final steps of active gene demethylation. We demonstrated that residues in the mouse Polβ protein, L301 and V303, are critical for Polβ’s interaction with the BER scaffolding protein X-ray repair cross-complementing 1 (XRCC1), and mutation of these residues impairs Polβ’s ability to bind to XRCC1, negatively impacting BER complex assembly. We developed Polβ^{L301R-V303R/L301R-V303R} knock-in mice to explore how defects with this essential protein complex impact genome stability in the mouse. We found these mice to be viable and fertile yet exhibited a modest reduction in body weight. Here, we examined the protein and mRNA levels in tissues from wild-type (WT), heterozygous (HET), and homozygous (HOM) Polβ^{L301R-V303R/L301R-V303R} mice and the derived fibroblast cell lines. We show that HOM mice have significantly diminished Polβ protein levels, as compared to WT mice, in several tissues, yet Polβ mRNA levels were not significantly different, suggesting the decreased levels of Polβ protein could not be attributed to lower gene expression. Upon examination of Polβ stability in mouse ear fibroblasts derived from WT and HOM mice, results are consistent with human cell studies that the Polβ^L301R-V303R protein is unstable and undergoes proteasome-mediated degradation. Finally, we evaluated WT, and HOM, liver and brain genomic DNA samples for 5-methylcytosine/5-hydroxymethylcytosine (5mC/5hmC) levels by nanopore sequencing to investigate the impact of suppressed Polβ protein levels on active gene demethylation. As expected, we found tissue-specific trends in methylation, when comparing the brain and liver. However, we were unable to discern substantial differences in methylation levels between WT and HOM mice, suggesting that in the absence of external stressors, low Polβ levels do not impact methylation patterns. Full article

Background: Latent tuberculosis infection (LTBI) is the principal reservoir for active tuberculosis, with >85% of cases attributable to reactivation. Bacillus Calmette-Guérin fails to block this transition, leaving a critical gap in prevention. Methods: An immunoinformatics/reverse-vaccinology pipeline was applied to seven dormancy-related antigens retrieved from Mycobrowser. T-cell epitopes were predicted with NetMHCI/IIpan-4.1 and B-cell epitopes with ABCpred; antigenicity, allergenicity, and toxicity were evaluated with VaxiJen, AllerTOP, and ToxinPred. Secondary/tertiary structures were modeled with PSIPRED and AlphaFold-3; docking to Toll-like receptors (TLR) 2/4 and 100 ns molecular dynamics simulations assessed complex stability. Immune responses were simulated with C-ImmSim, and the mRNA sequence was human-codon-optimized using ExpOptimizer. Results: The resulting construct, RP14914P, encodes 14 cytotoxic T lymphocyte, 9 helper T lymphocyte, and 14 B-cell epitopes within an 866-aa, 90.4 kDa polypeptide. Antigenicity score = 0.7797, immunogenicity score = 8.58629. and no toxicity or allergenicity was predicted. Physicochemical analysis: instability index = 28.65, and solubility = 0.513. Estimated population coverage is 82.35% and 99.67% for Human Leukocyte Antigen (HLA)-I and HLA-II globally. Docking energies: −1477.8 kcal/mol (TLR2) and −1480.1 kcal/mol (TLR4). Molecular dynamics trajectories confirm stable binding. Immune simulation predicts potent activation of Natural Killer cells, macrophages, and dendritic cells, Th1 polarization, high interferon-γ/interleukin-2 secretion, and durable memory. Conclusions: In silico analyses predict that RP14914P exhibits favorable immunogenicity, safety, and broad population coverage, suggesting its potential as a promising mRNA vaccine candidate to prevent LTBI reactivation. However, these computational predictions require thorough experimental validation to confirm the vaccine’s immunogenicity and protective efficacy. Full article

Aspergillus flavus infection and accumulation of carcinogenic aflatoxins are detrimental to maize (Zea mays) production and consumption. We investigated lncRNA–RBP interactions during maize–A. flavus crosstalk using transcriptomic profiling, structural analysis, molecular docking simulations, and machine learning approaches. Analysis of 18 RNA-seq datasets identified 2104 lncRNAs in maize, of which 461 were differentially expressed under A. flavus infection. Distinct lncRNAs were preferentially induced under infection (e.g., Zm00001eb303170) or normal germination (e.g., Zm00001eb144150, Zm00001eb406410). RNA secondary structure predictions indicated high structural heterogeneity and thermodynamic stability, consistent with dynamic regulatory potential. Docking simulations with six key RNA binding proteins (RBPs)—including branch point bridging protein (BPB), KH domain protein, and pentatricopeptide repeat (PPR) proteins—demonstrated strong lncRNA–protein binding, with the lncRNA1–BPB complex exhibiting the highest binding affinity. ML algorithms identified the crucial role of tryptophan in determining interactions, while lncRNA17-KH and lncRNA1-BP complexes were found to have the best interaction under normal germination and A. flavus infection, respectively. The lncRNA–miRNA–mRNA regulatory network highlighted lncRNAs functioning as decoys or precursors of stress-responsive miRNAs (e.g., zma-miR156, zma-miR164, zma-miR399). These interactions targeted transcriptional regulators, splicing factors, and metabolic enzymes implicated in stress tolerance, seed germination, and systemic acquired resistance. The maize lncRNAs are active regulatory molecules embedded in complex RBP and miRNA interaction networks that fine-tune gene expression during A. flavus infection. The study provides novel insights into lncRNA-mediated resistance mechanisms and offers potential molecular targets for breeding or gene editing to mitigate aflatoxin contamination. Full article

Background/Objectives: Early detection of prostate cancer (PCa) enables timely therapeutic intervention and improved clinical outcomes. Screening strategies are increasingly individualized and now incorporate multiparametric MRI findings, reported using the Prostate Imaging Reporting and Data System (PI-RADS), to refine biopsy decision-making. PROSTest is a novel machine learning (ML)-enhanced, 30-gene mRNA liquid biopsy assay developed to detect PCa from whole blood. In this prospective study (NCT06872619), we evaluated whether PROSTest could function as a pre-biopsy triage tool to inform biopsy decisions while preserving sensitivity for clinically significant prostate cancer (csPCa). Methods: Of 121 men evaluated, 111 (91.7%) completed the full diagnostic work-up—including PSA testing, PROSTest analysis, and PI-RADS assessment—and subsequently underwent image-guided biopsy. Peripheral blood samples for PROSTest were collected prior to biopsy. RNA-stabilized samples underwent RNA isolation followed by reverse transcription and quantitative PCR. Gene expression data were processed using a proprietary machine learning algorithm to generate a continuous range from 0 to 100. A clinically validated cut-off ≥ 50 was applied to produce a binary (positive/negative) result. The diagnostic accuracy of PROSTest was assessed against histology-confirmed prostate cancer. Results: The median age of participants was 69 years (47–83 years) and the median PSA was 7.5 ng/mL (IQR: 5.8–11.4 ng/mL); most patients (104 of 111; 93.7%) had a PI-RADS score of three to five. PCa was diagnosed in 97 men (87.4%) including eight in ISUP Grade Group (GG) 1, 46 in GG2, 33 in GG3, three in GG4 and seven in GG5. PROSTest was positive in 102/111 (91.9%). Among men with biopsy-confirmed PCa, diagnostic accuracy was 99% (93/94). Of the 17 men without histologic evidence of disease, eight (47%) were PROSTest-negative. The overall accuracy was 91% (84.1–95.6%) with an NPV of 89% (51.6–98.4%). Among the nine patients with positive PROSTest but negative biopsy, PI-RADS scores were 4 (n = 6), 3 (n = 1), and 2 (n = 2). Conclusions: PROSTest demonstrated an overall accuracy of 91% (95% CI: 84.1–95.6%) with an NPV of 89%. Among men without a detectable prostate cancer on biopsy, 47% (8/17) were PROSTest-negative. These results suggest that PROSTest may serve as a useful pre-biopsy triage assay. Full article

RNA N7-methylguanosine (m7G) is an important post-transcriptional epigenetic modification that participates in key biological processes, including RNA processing, stability maintenance, and translational regulation. Medical research has shown that m7G modification and its related regulatory factors are closely related to many neurological diseases and tumors. The accurate prediction of m7G sites is thus critical for understanding their biological functions in diseases. In this work, we propose BF-m7GPred, a dual-branch deep learning framework that integrates single-nucleotide-level embeddings and motif-level embeddings for m7G modification site prediction. Our proposed context-aware module tokenizes RNA sequences using byte-pair encoding and encodes sequences with the pretrained foundation biological model DNABERT2. In parallel, the proposed feature fusion module transforms sequences into multiple feature matrices using multiple traditional encoders. We introduce a feature selection strategy tailored to the encoding characteristics of the two branches. On a benchmark dataset collected from m7G-Hub v2.0, BF-m7GPred achieves superior performance on the independent test set against existing methods. Furthermore, its generalization capability is validated through comparative experiments on 10 diverse RNA modification datasets. Full article

Background: Thermostability remains a key bottleneck for equitable access to mRNA-LNPs vaccines, mainly due to cold-chain requirements. Objectives and methods: Here, we optimized freeze-drying formulations by screening excipients (sugars, sugar alcohols, and proteins) and buffers to preserve mRNA-LNPs as solid formulations under ambient and refrigerated conditions. Physicochemical properties (size, polydispersity index [PDI], and encapsulation efficiency [EE]) and functional integrity, assessed by fluorescence-based in vitro transfection assays, were evaluated during long-term storage of up to six months. Results: Preliminary screening identified 20% sucrose and trehalose with Tris or histidine buffers as optimal for preserving physicochemical properties during freeze-drying, including high encapsulation efficiency (>90%), particle size (~200 nm), and low polydispersity (PDI < 0.2). Mannitol, gelatin, and PBS-based buffers showed adverse effects. At 4 °C, formulations F1–F3 maintained physicochemical stability and functional transfection activity for up to four months. In contrast, 20 °C storage caused progressive destabilization, with increased size, PDI, and encapsulation loss (>60% by six months). Among all formulations, 20% sucrose with 5 mM Tris (F1) showed the most robust preservation of physicochemical integrity and in vitro transfection efficiency under refrigerated and ambient conditions. Conclusions: Sugars outperformed sugar alcohols and gelatin as cryoprotectants. All formulations were stable, including functionally active at 4 °C for up to four months, while a sucrose/Tris formulation retained acceptable stability at 20 °C. Overall, the results demonstrate the feasibility of storing mRNA drug products as solid formulations at non-freezing temperatures. Full article

Background: Therapeutic resistance to CDK4/6 inhibitors (CDK4/6i) remains a critical barrier in HR⁺ breast cancer. While network-based approaches offer a route to identify salvage therapies, existing methods often rely on inconsistent centrality metrics or retrospective public transcriptomes, lacking a unified framework to translate topology into pharmacological actionability. Methods: We developed the Topology-Integrated Hubness Score (TIHS), a quantitative framework that integrates five orthogonal network metrics into a unified hubness vector. To rigorously validate this framework and overcome the limitations of public bulk datasets, we combined cross-cohort statistical benchmarking with original RNA-sequencing data generated from a laboratory-derived palbociclib-resistant model (MCF7-PR). TIHS was applied to prioritize repurposing candidates by overlaying network hubness with drug–target affinity profiles. Results: Methodologically, TIHS demonstrated robust cross-dataset stability (cosine similarity ≥ 0.98) and statistically outperformed single-metric approaches in predicting drug sensitivity. In application, the framework identified sorafenib as a top-ranked candidate for reversing CDK4/6i resistance. Experimental validation confirmed these predictions: sorafenib significantly resensitized resistant cells (IC₅₀ reduction from 6.57 μM to 1.15 μM), and molecular dynamics simulations supported stable binding to the TIHS-prioritized hub, FGFR3. Furthermore, functional assays involving siRNA-mediated knockdown validated that FGFR3 is mechanistically required for the sorafenib resensitization phenotype. Conclusions: This study presents TIHS as a mechanism-agnostic, experimentally validated bridge between resistance-state transcriptomes and clinical decision-making. By coupling computational prioritization with in vitro functional verification, we demonstrate that targeting topology-defined hubs is a viable strategy for overcoming therapy resistance. Full article

Therapeutics based on RNA are commonly produced via biocatalytic approaches using RNA polymerases. The most frequently applied enzyme is the RNA polymerase of Enterobacteria phage T7. However, this enzyme has unfavorable properties, like the formation of double-stranded RNA (dsRNA). This undesired by-product can activate the innate immune system via pattern recognition receptors and cause inflammation. Removal of the contaminant is time-consuming and expensive. In this work, we applied a genome mining approach to identify unidentified single-subunit RNA polymerases with minimal dsRNA generation. A large meta database was screened, and 74 sequences were selected. Two RNA polymerases generating barely detectable amounts of dsRNA were identified from the initial sequence portfolio. Their promoters were detected via a fluorescent RNA aptamer screening, and slightly acidic transcription conditions were established. Further activity characterization showed a significant reduction of dsRNA to 0.001% and 0.02%. Due to these beneficial attributes, these RNA polymerases generate mRNA with enhanced stability, which most likely lowers the immune response towards the desired mRNA. This could be especially useful for producing long RNAs, such as self-amplifying RNA, as these typically require improved stability and low dsRNA content. Full article

R-loops, three-stranded nucleic acid structures formed by an RNA-DNA hybrid, have emerged as important regulators of transcription and genome stability. Although advances in high-throughput sequencing have revealed widespread R-loop landscapes, platform-specific biases hinder the identification of conserved R-loops in specific cell types. Mouse embryonic stem cells, which are transcriptionally active, provide an ideal system for investigating the potential roles of stable R-loops in RNA biology. Here, we integrated 13 independent R-loop profiling datasets from four experimental platforms to define 27,950 Common R-loop regions in mouse embryonic stem cells and characterized their chromatin environment and associated biological functions. Common R-loop regions were reproducibly detected across methods and were preferentially localized to promoter-proximal and genic regions enriched in CpG islands. Genes associated with Common R-loops were highly and stably expressed, showing strong functional enrichment in RNA metabolic processes such as mRNA processing, RNA splicing, and ribonucleoprotein complex biogenesis. Chromatin state analysis revealed that Common R-loops are enriched in transcriptionally active and regulatory contexts. Sequence feature analysis further identified GC skew as a prominent signature of Common R-loops, particularly within transcribed chromatin states. Transcription factor motif analyses have identified distinct regulatory environments in Common R-loop regions, including pluripotency-associated OCT4-SOX2-TCF-NANOG motifs in enhancers, CTCF motifs in open chromatin, and YY1 motifs in promoters. Together, this study provides the first integrated analysis of conserved R-loop regions in mouse embryonic stem cells, revealing their preferential localization at regulatory loci linked to RNA metabolism and highlighting R-loops as structural and functional nodes in RNA biology. Full article

Mesenchymal stem cells (MSCs) exert biological effects in part through their secretome which includes extracellular vesicles. In this study, we isolated and characterized the secretome from clinically relevant stem cell lines: human embryonic stem cell–derived mesenchymal stem cell line (ES-MSCs) and Infrapatellar fat pad derived MSC (IPFP-MSC) cultured in xeno-free medium. We assessed the biological activity of concentrated cell secretome or isolated fractions of extracellular vesicles (EVs) on cell proliferation, microvascular formation, and cartilage degradation in a human osteoarthritic (OA) ex vivo model. Serum-free conditioned medium from ES-MSC (N = 1) or IPFP-MSC (N = 2) monolayer cultures were concentrated by ultrafiltration to generate concentrated conditioned medium (CCM). Size exclusion chromatography was used to fractionate extracellular vesicles (EVs). Vesicle size, concentration, morphology, and surface markers were characterized by nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry. Biological activity was evaluated by treating human umbilical vein endothelial cells (HUVECs), IPFP-MSCs, and ES-MSCs with CCM and EVs at defined particle concentrations. Endothelial network formation was tested in fibrin gels with different cell and secretome combinations. For analysis of cartilage degradation, human cartilage explants (N = 4; 3.5 mm in diameter) were harvested from patients undergoing total knee arthroplasty and subjected to IL-1β stimulation to induce an OA phenotype. Explants were treated with varying doses from CCM or EVs. Release of glycosaminoglycan in the medium and RNA analysis of catabolic genes were used as readouts. Secretome preparations yielded on average approximately 50 billion vesicles per mL with a similar particle size distribution between 50–200 nm in ES-MSC and IPFP-MSC cultures. Transmission electron microscopy confirmed vesicle morphology and flow cytometry confirmed expression of exosomal surface markers (CD9, CD63, CD81). Functionally, CCM and EVs enhanced proliferation in a dose-dependent manner. Endothelial networks formed by HUVECs in fibrin were stabilized over 7 days by CCMs, most notably by hypoxic ES-MSC CCM relative to no CCM treatment (control). In the OA cartilage model, IL-1β stimulation increased glycosaminoglycan release, whereas ES-MSC CCM treatment and EV treatment reduced glycosaminoglycan release and ES-MSC CCM reduced gene expression of IL-1β, MMP-1, and MMP-3. We isolated and characterized the concentrated secretome and the isolated vesicle-enriched fractions from xeno-free ES-MSC and IPFP-MSC and demonstrated bioactivity in promoting cell proliferation, modulating endothelial network formation, and mitigating cartilage degradation in osteoarthritic tissue. These findings support the bioactivity and therapeutic potential of stem cell–derived secretomes for OA. Full article

Oncometabolites and hypoxia-regulated exosomes orchestrate hypoxia-inducible factor (HIF)–driven macrophage reprogramming across chronic cardiometabolic and oncologic conditions. In type 2 diabetes (T2D) and obesity, regional hypoxia in expanding white adipose tissue (WAT) reconfigures macrophage immunometabolism and chemokine signaling, recruits C-C chemokine receptor 2 (CCR2⁺) monocytes, and skews adipose-tissue macrophages toward M1-like programs that sustain low-grade inflammation and blunt the physiological M1-to-M2 transition during wound repair. In atherosclerotic plaques, lipid-core hypoxia stabilizes HIF-1α, amplifies nuclear factor kappa-light-chain-enhancer of activated B cells/reactive oxygen species (NF-κB/ROS) signaling, increases matrix metalloproteinase-2/-9 (MMP-2/-9) release, and reduces ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux, weakening the fibrous cap. In tumors, poorly perfused niches accumulate lactate and succinate, which act as paracrine cues. Lactate activates PKA/cAMP pathways and promotes immunosuppressive tumor-associated macrophages (TAMs), whereas succinate signals through succinate receptor 1 (SUCNR1) to reinforce HIF-1α–dependent transcription and M2-like programming. In parallel, hypoxia-regulated exosomes deliver microRNAs such as miR-301a-3p, which suppress phosphatase and tensin homolog (PTEN) and activate PI3Kγ, thereby augmenting immunosuppression and programmed death-ligand 1 (PD-L1) expression. Clinically, this hypoxia–oncometabolite–exosome triad links oxygen debt with macrophage state, plaque destabilization, impaired wound repair, and tumor immune escape. Translational entry points include selective HIF-2α inhibition, phosphoinositide 3-kinase gamma (PI3Kγ) blockade, SUCNR1 targeting, and exosome-based miRNA modulation, while a biomarker panel comprising HIF-1α, vascular endothelial growth factor A (VEGF-A), and MMP-9 offers a pragmatic readout of hypoxia burden, macrophage programming, and therapeutic response. We conducted a focused narrative review (PubMed, Scopus, Web of Science; English; 2003–2025), prioritizing mechanistic and translational studies on hypoxia–HIF, lactate/succinate, and hypoxia-regulated exosomes across T2D, atherosclerosis, and cancer. Full article

Circular RNA (circRNA) has emerged as an alternative RNA modality for vaccine development due to its covalently closed structure and enhanced molecular stability compared with linear messenger RNA (mRNA). Following the clinical success of mRNA vaccines, circRNA-based platforms have gained attention in both prophylactic and cancer immunization. Unlike linear mRNA, circRNA relies on cap-independent translation and is commonly produced through in vitro transcription coupled with ribozyme-mediated self-circularization. In prophylactic vaccination, circRNA vaccines have demonstrated sustained antigen availability, robust humoral and cellular immune responses, and flexibility in multivalent designs and targeted delivery strategies that support germinal center reactions and neutralizing antibody generation. In cancer vaccines, circRNA has been applied to tumor-associated antigens, neoantigens, and non-canonical peptides, with a primary focus on inducing potent antigen-specific CD8⁺ T cell immunity and enabling combination immunotherapy approaches. This review summarizes recent applications of circRNA-based vaccines in prophylactic and cancer settings, emphasizing in vitro transcription-compatible self-circularization strategies and discussing how methodological choices in RNA design, translation control, purification, and delivery shape immunological outcomes. Full article

T-cell intracellular antigen 1 (TIA1) is a multifunctional RNA-binding protein (RBP) belonging to the RNA recognition motif (RRM) family. Under steady-state conditions, it is predominantly localized in the nucleus and highly expressed in the nervous system, where it regulates neuronal and glial functions. TIA1 modulates mRNA splicing, stability, and translation and promotes stress granule (SG) assembly under cellular stress. Recent studies indicate that the spatiotemporal dynamics of TIA1 in neurodegenerative contexts influence disease progression by regulating inflammatory responses, apoptosis, and related pathways. This review discusses the molecular structure and functions of TIA1, focusing on its expression in neurons and glia, as well as its implications in neurodegenerative disorders and stroke. The findings highlight TIA1 as a promising target for novel neuroprotective therapeutic strategies. Full article

Background/Objectives: Telomeres and telomerase play crucial roles in cellular aging and genome stability. Emerging evidence indicates that alterations in telomerase activity and telomerase reverse transcriptase (hTERT) gene expression may be involved in cardiovascular pathophysiology. However, data on telomerase regulation in patients with stable coronary artery disease (CAD) are limited. This study aimed to compare serum telomerase concentration and hTERT gene expression levels between patients with stable CAD and healthy controls. Methods: A total of 52 patients diagnosed with stable CAD and 50 age-matched healthy controls were enrolled prospectively. Telomerase concentrations were measured in serum samples using the ELISA method, and hTERT mRNA expression was measured in blood samples using RT-PCR. Results: Serum telomerase levels were significantly higher in patients with stable CAD compared with controls (p < 0.05). Similarly, hTERT gene expression was upregulated in the patient group (p < 0.05). Multivariable analysis showed that increased log-transformed telomerase levels (AOR: 2.12, 95% CI: 1.14–5.13, p = 0.024) and hTERT expression (AOR: 1.79, 95% CI: 1.09–3.27, p = 0.037) were independently associated with coronary vessel involvement in stable CAD. These findings indicate an increase in both telomerase level and hTERT transcriptional activity in stable CAD. Conclusions: Increased telomerase level and hTERT expression may reflect a compensatory response to chronic vascular stress and are associated with disease severity in stable CAD. Full article