Search Results (3,736)

Diabetic cardiomyopathy (DCM) features progressive fibrotic remodeling, but the shared molecular circuitry connecting diabetes mellitus (DM) to cardiomyopathy (CM) remains unclear. We integrated three DM- and three CM-related Gene Expression Omnibus (GEO) datasets and corrected batch effects with sva, verified by violin plots, principal component analysis (PCA), and silhouette coefficients computed on all common genes (DM: 0.9489 to −0.1016; CM: 0.9693 to −0.045; PC1/PC2 inter-batch differences abolished after normalization). Differential expression analysis identified 2562 DM Differentially expressed genes (DEGs) and 1414 CM DEGs, and their intersection yielded 91 common DEGs (51 upregulated, 40 downregulated). Protein–protein interaction (PPI) analysis prioritized 25 hub genes, whose enrichment profiles implicated insulin resistance/insulin signaling and adrenergic signaling in cardiomyocytes. TRRUST-based inference further defined a regulatory network centered on seven key genes (HIF-1α, ACTN4, ABCB1, LTBP1, CLU, TIMP2, and MYH11). To nominate a candidate target of oxymatrine (OMT), we performed docking and molecular dynamics (MD) simulations for representative complexes; OMT showed the most stable interaction with LTBP1, maintaining a consistently short pocket distance (~0.2 nm), the highest contact frequency, and the lowest MM/PBSA binding free energy (−15.32 kcal/mol), with favorable contributions dominated by van der Waals and nonpolar solvation terms. In primary cardiac fibroblasts (CFs), high glucose (HG, 30 mM glucose) induced proliferative and profibrotic activation, whereas OMT (0.4–0.8 mM) reduced HG-driven proliferation without detectable toxicity below 1.2 mM, suppressed FN, collagen I/III, and α-SMA expression, and inhibited migration. OMT also normalized HG-induced cell-cycle skewing by restoring G0/G1-phase occupancy and reducing S-phase entry, with effects comparable to metformin. Finally, HG increased LTBP1 expression and upregulated SMAD3/SMAD4, while OMT attenuated LTBP1 induction and suppressed downstream TGF-β/SMAD activation. Together, these data integrate cross-dataset transcriptomics with mechanistic validation to position LTBP1 as a putative antifibrotic node targeted by OMT, supporting inhibition of the LTBP1/TGF-β/SMAD axis as a candidate strategy to counter DCM-associated fibrosis. Full article

Prostate cancer (PC) progression is increasingly recognized as a dynamic, inflammation-driven process in which chronic immune dysregulation contributes to disease aggressiveness and therapeutic resistance. Among inflammatory signaling pathways, nuclear factor kappa B (NF-κB) has been consistently implicated in prostate tumorigenesis, castration resistance, and apoptosis resistance. However, despite the extensive literature on NF-κB biology, the mechanisms by which its dysregulation is sustained and functionally shaped during PC progression remain incompletely understood. This review synthesizes current evidence on prostate cancer-specific NF-κB signaling, with an emphasis on stage-dependent activation, molecular regulation within the tumor microenvironment, and downstream transcriptional programs linked to survival and treatment resistance. Particular attention is given to the regulatory role of B-cell lymphoma-3 (BCL-3), an atypical nuclear IκB protein, and its potential interplay with B-cell lymphoma-2 (BCL-2), a well-established NF-κB-regulated anti-apoptotic factor in PC. Available clinical, molecular, and transcriptomic data support constitutive NF-κB activation across multiple stages of PC, particularly in advanced and castration-resistant disease. Although BCL-2 overexpression is well documented as a mediator of apoptosis resistance in PC, evidence directly linking BCL-3 to BCL-2 regulation in this disease remains limited. Data from other malignancies suggest that BCL-3 can modulate NF-κB transcriptional output and enhance BCL-2 expression; however, prostate-specific mechanistic validation is lacking. We propose a testable, hypothesis-driven model in which BCL-3 may function as a context-dependent regulator of NF-κB-mediated survival signaling in PC, potentially influencing BCL-2 expression and therapeutic resistance. However, this relationship remains speculative and is not yet supported by direct mechanistic evidence in PC. By distinguishing between established evidence and inferred mechanisms, this review highlights critical knowledge gaps and outlines experimental strategies to clarify the functional relevance of the BCL-3/BCL-2 axis. Improved understanding of NF-κB regulatory dynamics may inform the development of more precise, stage-adapted therapeutic strategies for advanced PC. Full article

The cell membrane serves as the first line of defense against adverse environmental factors and is first to adapt to changing conditions. Cell membranes in both coral and its symbionts, which use different membrane adaptation strategies, have to acclimatize to various abiotic stressors. As our molecular-genetics analysis showed, colonies of Junceella fragilis were associated with dinoflagellates Cladocopium thermophilum, Gerakladium endoclionum and Breviolum minutum. We analyzed the phospholipid (PL) molecular species of the wild and cultivated Junceella fragilis and their dinoflagellates (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), ceramideaminoethylphosphonate (CAEP)), as well as thylakoid membrane lipids of dinoflagellates (glycolipids and betaine lipids). When comparing wild and cultivated J. fragilis colonies, there were no significant differences in thylakoid lipids, but there were differences in host membrane phospholipids, namely in PC, PE and PS. Thus, the profile of PL molecular species of the membrane is very sensitive to environmental factors, which probably explains the observed differences in the profiles of molecular PL species in this study. Full article

Aeromonas hydrophila is a major seafood-borne pathogen capable of persisting under preservative-associated stress by entering a viable but non-culturable (VBNC) state, thereby evading culture-based detection. Here, untargeted metabolomics was applied as the primary analytical approach to elucidate metabolic reprogramming during VBNC formation under seafood-relevant preservation conditions. Cells were incubated at 4 °C for 30 days in sodium benzoate-supplemented saline, comparing 0.85% NaCl (culturable condition) and 4% NaCl (VBNC-inducing condition), with sampling every 6 days. Under 4% NaCl with sodium benzoate, culturability declined from 6.18 log CFU/mL at day 0 to undetectable levels by day 30, while cell viability was retained, confirming VBNC induction. UHPLC–ESI–QTOF–MS profiling detected over 893 intracellular metabolic features, of which 518 metabolites were significantly altered between VBNC and culturable states at day 30. Principal component analysis revealed clear, time-dependent metabolic divergence, with the VBNC trajectory explaining 34.4% (PC1) and 11.5% (PC2) of total variance. Pathway enrichment analysis demonstrated significant remodeling of alanine, aspartate and glutamate metabolism (8/28 hits, FDR = 5.7 × 10⁻⁴); arginine biosynthesis (5/14 hits, FDR = 5.44 × 10⁻³); purine metabolism (10/70 hits, FDR = 8.34 × 10⁻³); and pyrimidine metabolism (7/39 hits, FDR = 1.35 × 10⁻²), indicating nitrogen conservation and metabolic downshifting. A robust biomarker panel, including depleted cyclic AMP, aminoadipic acid, hypotaurine, O6-CM-dG, and betaine, and enriched urocanic acid, pipecolic acid, proline, azelaic acid, and orcinol perfectly discriminated VBNC from culturable cells. These findings demonstrate that sodium benzoate-based preservation can induce a metabolically reprogrammed VBNC state in A. hydrophila, highlighting a hidden food safety risk beyond culture-based assessment. Full article

Propolis produced by honeybees, Apis mellifera, has been valued since ancient times as a remedy for different ailments for its broad medicinal properties. This wide range of biological activities may arise from the production of distinct propolis types within the hive, each serving specific functions and containing unique molecular compositions. In this study, we investigated the effects of four propolis types—masonry, sealing, brood-protection, and intruder-neutralizing—on hydrogen peroxide (H₂O₂)-induced oxidative injury in human skeletal muscle cells. Among these, only brood-protection propolis significantly prevented the H₂O₂-induced loss of cell viability. Bio-guided fractionation of this active propolis identified five major compounds: benzyl caffeate (BC), caffeic acid phenethyl ester (CAPE), cinnamyl caffeate (CC), prenyl caffeate (PC), and (E)-3-methyl-3-butenyl caffeate (MBC), all displaying stronger cytoprotective effects than their ferulate equivalents. We finally demonstrated that propolis extract and its active compounds reduced lipid peroxidation in post-mortem minced mouse skeletal muscle and compared their efficacy to other natural compounds. Chemical analysis of resins from neighboring flora suggested that black poplar (Populus nigra) buds are the primary botanical source of these caffeate derivatives. Collectively, these results highlight the functional diversity of hive propolis and its potential applications in food preservation as well as in complementary and preventive medicine. Full article

Circulating tumor cells (CTCs) are valuable liquid-biopsy biomarkers, yet their extreme rarity makes high-purity, high-throughput enrichment challenging. In spiral inertial microfluidics, high cell loading induces long-range hydrodynamic interactions that broaden the focused blood-cell stream; consequently, a subpopulation completes the ~0.5 and ~1.0 Dean-cycle migrations with a phase delay, compressing the CTC–blood cell gap and degrading purity. Here we propose a Dean-cycle phase-regulated double-spiral design informed by this phenomenon. This design aims to mitigate the stream-broadening effect by boosting the Dean number during the first half-cycle to promote synchronized blood-cell migration and shifting the CTC equilibrium position near one full cycle to further widen the CTC–blood cell separation. We implement this strategy in a second-generation double-spiral microfluidic chip (SDMC) and scale it to a four-channel parallel array (ASDMC). Under optimized conditions, ASDMC processes diluted whole blood (hematocrit = 4%) without the need for red blood cell (RBC) lysis or antibody labeling, achieving a sample throughput of 1200 μL·min⁻¹. Specifically, it exhibits a mean recovery rate of 98.8% across three spiked tumor cell lines (MCF-7, PC-9, and Mahlavu) and a mean white blood cell (WBC) depletion efficiency of 93.3%. In a pilot clinical testing of 20 patients (NSCLC and HCC), enriched fractions enabled immunofluorescence identification of CK⁺CD45⁻DAPI⁺ CTCs, with an exploratory trend of increasing CTC counts with advanced disease stage (4–34 cells·mL⁻¹). These results describe a scalable, label-free platform, and the observed purification performance aligns with our proposed mechanism: Dean-cycle phase regulation to mitigate blood-cell migration lag. Our findings support further technical validation and clinical assessment in larger cohorts. Full article

Marine-derived bioactive peptides have attracted increasing attention as value-added functional ingredients. In this study, peptides (<3 kDa) were prepared from yellowfin tuna processing by-products and further fractionated by Sephadex G-25 gel filtration. The major fraction (TBP-MF) exhibited markedly improved compositional homogeneity compared with the unfractionated hydrolysate (TBP), providing a well-defined peptide system for subsequent characterization and biological evaluation. Physicochemical analyses demonstrated that TBP-MF possessed enhanced thermal stability and a more ordered secondary structure, characterized by pronounced β-sheet enrichment, as revealed by TGA/DSC, FTIR, and circular dichroism analyses. Morphological and colloidal characterization further showed that TBP-MF formed relatively uniform lamellar and fibrous assemblies with a narrower particle size distribution and reduced electrostatic stabilization, indicating a higher tendency toward ordered self-association. Peptidomic profiling combined with in silico analysis revealed that TBP-MF was enriched in short peptides with relatively higher PeptideRanker scores and a functional motif distribution containing relatively more neuro-related annotations, although angiotensin-converting enzyme (ACE)- and dipeptidyl peptidase IV (DPP-IV)-related motifs remained predominant in both groups. In differentiated PC12 cells, TBP-MF exhibited excellent cytocompatibility and induced a stable, concentration-dependent increase in the Cell Counting Kit-8 (CCK-8) readout (OD₄₅₀), indicating enhanced cellular metabolic activity and/or increased cell number. In addition, TBP-MF significantly increased intracellular levels of key neurochemical factors associated with sleep-related regulation, including tetrahydrobiopterin (BH4), serotonin (5-HT), and γ-aminobutyric acid (GABA). Overall, this study highlights yellowfin tuna by-products as a promising marine resource for bioactive peptides and suggests that fractionation-driven structural refinement is associated with neuro-related biological activity in differentiated PC12 cells. These findings support the potential application of marine by-product-derived peptides as functional ingredients in health-related fields. Full article

Excessive alcohol consumption causes millions of deaths annually, yet current pharmacological treatments for alcohol use disorders show limited efficacy and poor adherence, creating an urgent need for new therapeutic alternatives. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde, a key mediator of the rewarding effects of alcohol in the brain, making ALDH2 activation a promising therapeutic target. This study investigated whether flurbiprofen, an FDA-approved nonsteroidal anti-inflammatory drug that activates ALDH2, reduces alcohol intake compared to the experimental ALDH2 activator Alda-1 and the structurally similar NSAID ibuprofen. Male alcohol-preferring UChB rats received oral flurbiprofen (2.5–10 mg/kg), Alda-1 (5 mg/kg), or ibuprofen (5 mg/kg) during acquisition and chronic phases of voluntary alcohol consumption under a two-bottle free-choice paradigm. Both flurbiprofen and Alda-1 reduced alcohol intake by approximately 60% and similarly increased ALDH2 activity 3–4-fold in brain and liver tissues. Ibuprofen showed modest effects (25% alcohol intake reduction). In vitro assays confirmed that flurbiprofen and Alda-1, but not ibuprofen, activated ALDH2 in PC-12 cells. Enzymatic assays and molecular docking revealed that Alda-1 lacks cyclooxygenase-inhibitory activity, unlike flurbiprofen, suggesting that ALDH2 activation is the primary mechanism underlying reduced alcohol consumption. These findings identify flurbiprofen as a clinically available ALDH2 activator with significant translational potential for treating alcohol use disorders. Full article

Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). Methods: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [⁶⁸Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [⁶⁸Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. Results: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [⁶⁸Ga]Ga, a dual-modality radionuclide-fluorescence probe ([⁶⁸Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/10⁶ cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [⁶⁸Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. Conclusions: This preclinical study demonstrates that [⁶⁸Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery. Full article

Background/Objectives: The G protein-coupled oestrogen receptor (GPER) has anti-tumorigenic effects in several human cancers. However, its role in prostate cancer (PCa) remains incompletely defined. The present study investigated GPER’s role in targeting the hallmarks of PCa. Methods: Tissue microarrays were used to analyse GPER immunoexpression in PCa samples. Non-neoplastic (PNT1A) and neoplastic (LNCaP, DU145 and PC3) prostate cells were treated with the GPER-specific agonist, G1. Cell viability, proliferation, cell cycle, apoptosis, migration and invasion were evaluated. Glucose consumption, lactate production, lactate dehydrogenase activity and oxidative status were determined spectrophotometrically. Results: GPER immunoreactivity was higher in PCa than in benign prostatic hyperplasia and inversely correlated with PSA serum levels. G1 modulated GPER subcellular location in prostate cells, being detected at the cell membrane, endoplasmic reticulum, and residually in the nucleus. GPER activation decreased cell viability and proliferation, induced cell cycle arrest at G2/M phase, and increased PCa cells apoptosis. Additionally, GPER activation inhibited the migration and invasion of DU145 cells, and long-term exposure to G1 reduced epithelial–mesenchymal transition, an effect not observed in PC3 cells, indicating the importance of cell-specific contexts. Our results also showed that G1 treatment modulated the metabolic profile of PCa cells, changing glucose, amino acids and lipid metabolism. Finally, G1 increased oxidative stress in PCa cells. Conclusions: Overall, this study demonstrated that GPER activation affects a broad range of PCa hallmarks. These findings support an anti-cancer role for GPER in PCa and encourage further exploration of its action in regulating metabolism and as a therapeutic target. Full article

Braided nerve guidance conduits (NGCs) composed of decellularized porcine small intestinal submucosa (SIS) were developed to achieve an appropriate balance between mechanical performance and biological compatibility for peripheral nerve repair. This study aimed to compare four SIS-braided conduits with silicone tubes in terms of bending compliance, tensile strength, swelling behavior, and cytocompatibility. SIS-braided conduit exhibited a favorable combination of flexibility, tensile strength, and dimensional stability. In vitro evaluations using PC12 and SW10 cells demonstrated that SIS-braided conduit supported neurite outgrowth and Schwann cell adhesion, confirming its favorable cytocompatibility. Based on these findings, SIS-braided conduits and silicone tubes were subsequently evaluated in a rat sciatic nerve defect model. Functional recovery assessed using the Sciatic Functional Index suggested preliminary functional recovery in the SIS-braided conduit, and histological analyses revealed evidence of axonal regeneration and myelin formation within the conduit. Overall, the results indicate that the integration of mechanical robustness with biological activity is essential for the design of nerve graft substitutes. The conduit braided from decellularized small intestinal submucosa represents a promising biodegradable alternative, a considerable biodegradable alternative to conventional non-degradable silicone conduits for peripheral nerve repair. Full article

Background/Objectives: The F3 peptide, a tumor-homing peptide known to bind cell-surface nucleolin, is frequently employed as a targeting vector in cancer research. However, the impact of the modification site on its cellular binding properties has not been investigated yet. In this work, we aimed to design an improved F3-based radioconjugate by identifying the optimal conjugation site and establishing a protocol for its biological evaluation in vitro. To achieve this, we compared F3 peptide derivatives modified at their N- or C-termini with DOTA for complexation of indium-111 (¹¹¹In) for SPECT or Auger electron therapy or a fluorophore (FITC) for optical imaging. Methods: N-and C-terminal DOTA-modified F3 peptides were radiolabeled with indium-111 and compared for their in vitro stability in different physiologically relevant media. Suitable nucleolin-positive cell lines for further in vitro studies were identified by confocal microscopy of a FITC-labeled F3 peptide derivative. The radioconjugates were then investigated on MDA-MB-231 (breast cancer) and PC-3 (prostate cancer) cells for nucleolin-specific cell binding and uptake, and several parameters of the in vitro assays were varied to establish a suitable protocol. Results: In general, in vitro assays with F3 peptide conjugates are challenging, as the outcome depends on a number of experimental parameters, leading, in some cases, to varying results. In particular, the presence of Ca²⁺ and Mg²⁺ had a decisive impact on the results, likely because the metal ions compete with the binding of F3 conjugates to nucleolin. The C-terminal modified, ¹¹¹In-labeled F3 radioconjugate performed better than the N-terminal modified analog. While several parameters of the in vitro experiments were optimized, the overall cell uptake in vitro of radioactivity was still low (<2% of applied radioactivity). Conclusions: A standardized in vitro protocol for evaluating F3 peptide conjugates on cancer cells was established, revealing that the C-terminus is the preferred site for modification. Because the cellular uptake of the radiotracer was shown to likely not be sufficient for radiotracer development, further studies on the optimization of the F3 peptide conjugates, including structural modifications, are required. Full article

Background: Neuronal apoptosis is the core pathological mechanism of cerebral ischemic–reperfusion injury (CIRI); although Astragaloside IV (AS-IV) has demonstrated neuroprotective activity against CIRI, its specific molecular mechanisms underlying the regulation of this apoptosis-related pathway remain to be systematically elucidated. Methods: We establish an in vivo model of middle cerebral artery occlusion/reperfusion (MCAO/R) in rats and an in vitro model of oxygen–glucose deprivation/reperfusion (OGD/R) in PC12 cells. Six core apoptotic proteins, including CytC, Apaf-1, BAX, Bcl-2, Caspase3, and Caspase9, were detected using neurological function scoring, TTC/HE/Nissl staining, TUNEL staining, Western blot, and immunofluorescence techniques. Molecular docking and molecular dynamics simulation were utilized to analyze the binding affinity between AS-IV and the aforementioned apoptotic proteins. Results: Molecular docking and dynamics simulation demonstrated AS-IV stably binds six core apoptotic proteins, and comparative analysis with target-specific reference ligands identified Apaf-1 as its primary target with the most favorable binding properties. In rat MCAO/R models, AS-IV alleviated neurological deficits, reduced cerebral infarct volume and improved brain pathological damage; in PC12 cell OGD/R models, it decreased neuronal apoptosis. Western blot and immunofluorescence confirmed AS-IV downregulated pro-apoptotic proteins (cytoplasmic CytC, Apaf-1, BAX, cleaved-Caspase9/3) and upregulated anti-apoptotic Bcl-2. Conclusions: This study clarifies the anti-apoptotic molecular mechanism of AS-IV, it alleviates CIRI by targeting the CytC/Apaf-1 mitochondrial apoptotic pathway. Full article

Erlotinib (ER) and gefitinib (GB) are frequently prescribed for patients with advanced lung adenocarcinoma (ADC). Although both ER and GB significantly extend median survival, several patients experience early disease relapse due to treatment resistance. This study aimed to identify common genes associated with acquired resistance to ER or GB. This integrative analysis of transcriptomic data identified differentially expressed genes by comparing sensitive PC-9 cells with ER-resistant (PC-9/ER) or GB-resistant (PC-9/GB) cell lines. A Venn diagram was used to identify common genes. Candidate genes were confirmed in our generated drug-resistant cell lines. After six months, the PC-9/ER and PC-9/GB cell lines exhibited 40.7-fold and 109.2-fold increases in resistance to ER and GB, respectively. Flow cytometric analysis demonstrated that both resistant cell lines were resistant to cell cycle arrest and apoptosis induced by ER or GB. Through integrated analysis, we found that two genes, KRT13 and CEACAM5, were up-regulated in both the PC-9/ER and PC-9/GB cell lines. The expression patterns of these two genes did not align with the transcriptome, with only CEACAM5 exhibiting consistent gene and protein expressions. Our findings indicate that CEACAM5 serves as a biomarker for predicting the response of patients to ER and GB treatments. Full article

The mitochondrial anti-viral signaling protein, MAVS, is a central regulator of innate anti-viral immunity. Recently, we demonstrated that MAVS is overexpressed in cancer, where its downregulation resulted in reduced cell proliferation and the expression and nuclear translocation of proteins associated with transcriptional regulation and inflammation. In this study, we demonstrate that CRISPR/Cas9-mediated MAVS depletion in PC-3 prostate cancer cells suppresses proliferation, disrupts immune evasion, and alters the tumor microenvironment. Proteomic profiling of the MAVS-KO cells by LC-MS/MS revealed changes in the expression of proteins associated with immunity, cell signaling, mitochondrial function, metabolism, protein synthesis and degradation, and epigenetic regulation. In contrast to MAVS-expressing cells, MAVS-KO cells implanted subcutaneously in mice formed very small tumors. This inhibited tumor growth was linked to reduced proliferation, and enhanced apoptosis, as indicated by strong TUNEL staining and elevated activated caspase-3. Importantly, the small “tumors” derived from MAVS-KO cells displayed a distinct morphology: diminished cancer stem-cell populations, an altered tumor microenvironment and inflammatory response, increased immune cell infiltration, and reduced PD-L1 expression. Together, these findings establish MAVS as a key mediator of cancer-cell survival, inflammation, and immune regulation, and, thus, its upregulation in tumors makes it a potential anti-cancer target. Full article