Search Results (785)

Metabolic syndrome (MetS) drives cardiac remodeling and fibrosis, contributing to diastolic dysfunction and heart failure with preserved ejection fraction, but chamber-specific mechanisms remain poorly defined. New Zealand White rabbits were fed a high-fat/high-sucrose diet for 28 weeks to induce experimental MetS. Systemic phenotype, cardiac structure (echocardiography), myocardial fibrosis (Picrosirius red histology), myosin/collagen gene expression (qRT-PCR), and chamber-specific proteomics were assessed across left/right atria and ventricles. The model reproduced central obesity, glucose intolerance, dyslipidemia, and mild hypertension, with concentric left ventricular hypertrophy and selective ventricular fibrosis, as follows: increased collagen in left ventricle (LV) and right ventricle (RV), unchanged in atria. Ventricular α-myosin heavy-chain gene expression was upregulated, while collagen I and α-smooth muscle actin transcripts showed ventricular-specific downregulation. Proteomics revealed atrial metabolic and cytoskeletal adaptations with minimal extracellular matrix involvement; ventricles displayed early profibrotic cues (galectin-3 in LV), metabolic inefficiency (impaired glycolysis/ATP production in LV; lipid oxidation shift in RV), and diminished provisional matrix support. Conclusions: concentric LV hypertrophy and great vessel enlargement occurred without systolic/diastolic dysfunction; ventricular-selective fibrosis, α-myosin heavy-chain upregulation, type I collagen/α-smooth muscle actin downregulation, and chamber-specific proteomic changes showed atrial adaptation versus ventricular early profibrotic/metabolic inefficiency. Full article

Background: Myocardial fibrosis (MF) is a dynamic remodeling process characterized by excessive extracellular matrix (ECM) deposition, fibroblast activation, and dysregulated matrix turnover. Although initially reparative, persistent fibrotic remodeling promotes myocardial stiffening, electrical instability, and progressive cardiac dysfunction across diverse cardiovascular diseases. Circulating biomarkers reflecting collagen synthesis, degradation, proteolytic regulation, and inflammatory activation have emerged as potential tools for assessing fibrotic activity and risk stratification. Methods: This targeted narrative review was based on manually guided searches of PubMed and Scopus, supplemented by citation chaining and inclusion of landmark mechanistic and translational studies. Publications addressing myocardial extracellular matrix remodeling, circulating fibrosis-related biomarkers and imaging-derived fibrosis phenotypes were selected for qualitative synthesis. Results: Myocardial fibrosis reflects interconnected inflammatory, neurohormonal, oxidative, and extracellular matrix remodeling pathways. Among circulating biomarkers, C-terminal propeptide of procollagen type I (PICP) showed the most consistent association with myocardial collagen burden and adverse outcomes, whereas carboxy-terminal telopeptide of type I collagen (CITP), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), galectin-3, osteopontin, soluble suppression of tumorigenicity 2 (sST2), and natriuretic peptides provided more context-dependent signals. Standalone interpretation remains limited by restricted cardiac specificity, renal dysfunction, systemic inflammation, assay heterogeneity, and lack of standardized thresholds. Integration with cardiac magnetic resonance (CMR)-derived late gadolinium enhancement (LGE), T1 mapping, and extracellular volume (ECV) may improve biological and structural phenotyping. Conclusions: Circulating biomarkers capture complementary dimensions of myocardial remodeling but cannot replace structural imaging. We propose an updated, hypothesis-generating biomarker–imaging framework integrating inflammatory activation, collagen turnover, matrix quality, hemodynamic stress, and structural imaging to support phenotypic stratification and future validation of antifibrotic strategies. Full article

Background/Objectives: Coronary artery disease is a chronic inflammatory disorder characterized by progressive atherosclerosis and heterogeneous clinical presentations ranging from acute coronary events to stable ischemic conditions. Galectin-3 is a β-galactoside-binding lectin involved in inflammatory responses, fibrosis, and tissue remodeling, and has been investigated as a potential biomarker in cardiovascular diseases. However, its diagnostic significance across different clinical stages of coronary artery disease remains unclear. Methods: This prospective study included 180 participants who underwent coronary angiography and were classified into three groups: control (n = 60), acute coronary syndrome (n = 60), and chronic coronary syndrome (n = 60). Serum Galectin-3 concentrations were measured using an enzyme-linked immunosorbent assay. Group comparisons were performed using non-parametric statistical tests. Correlation analysis, receiver operating characteristic curve analysis, and multivariable logistic regression were conducted to evaluate diagnostic performance and independent associations. Results: Galectin-3 concentrations were significantly higher in both acute coronary syndrome and chronic coronary syndrome groups compared with the control group (p < 0.001), whereas no significant difference was observed between the two disease groups. Receiver operating characteristic analysis demonstrated limited diagnostic performance for identifying acute coronary syndrome (area under the curve 0.617, sensitivity 96.7%, specificity 43.3%, p = 0.027) and poor diagnostic performance for chronic coronary syndrome (area under the curve 0.541, sensitivity 91.7%, specificity 30.0%, p = 0.436). In multivariable analysis, Galectin-3 was not identified as an independent predictor of either clinical condition. Age and smoking were independently associated with acute coronary syndrome, while age and male sex were independently associated with chronic coronary syndrome. Conclusions: Galectin-3 levels are elevated in patients with coronary artery disease and appear to reflect the inflammatory burden associated with atherosclerosis. However, its diagnostic discrimination between different clinical stages of coronary artery disease remains limited. Larger prospective studies are required to clarify its clinical value. Full article

Background/Objectives: Primary Sjögren’s disease is a systemic autoimmune disease characterized by chronic inflammation of exocrine glands and heterogeneous clinical manifestations. There remains a need for objective, non-invasive biomarkers that reflect local glandular involvement and disease-related immune activity. Methods: This observational cross-sectional case–control study included 34 patients fulfilling the 2016 ACR/EULAR classification criteria for primary Sjögren’s disease and 34 healthy controls between December 2024 and February 2025. Unstimulated whole-saliva samples were collected in the morning using the passive drool method, and salivary galectin-9 concentrations were measured via the enzyme-linked immunosorbent assay. Disease activity and symptom burden were assessed using validated indices, and receiver operating characteristic analysis was performed to evaluate discriminatory performance. Results: Salivary galectin-9 levels were significantly higher in patients with primary Sjögren’s disease compared with healthy controls. However, no significant associations were observed between salivary galectin-9 levels and disease activity scores after correction for multiple comparisons, nor with patient-reported symptoms, autoantibody profiles, Schirmer test results, or minor salivary gland biopsy findings. Salivary galectin-9 demonstrated limited discriminative ability between patients and controls. Conclusions: Salivary galectin-9 levels were elevated in primary Sjögren’s disease and may be associated with local glandular immune processes. Further prospective studies are needed to determine their clinical relevance. Full article

Prostate cancer (PCa) management has evolved with biomarker-driven strategies, yet biological heterogeneity, adaptive resistance, and an immunosuppressive microenvironment limit their efficacy. Galectin-3 (Gal-3) has emerged as a central node in PCa pathobiology, influencing tumor survival, metastasis, and immune escape. This review comprehensively reviews Gal-3’s dual role as a biomarker and a therapeutic target. We first delineate the limitations of the current diagnostic, prognostic, and predictive biomarkers in PCa, establishing the unmet need. We then elucidate the multifunctional biology of Gal-3, detailing its compartment-specific roles in anti-apoptosis, angiogenesis, epithelial-to-mesenchymal transition, and, notably, its function as a master regulator of immunosuppression. The interaction between Gal-3 and prostate-specific antigen (PSA) is explored as a key regulatory interface. Furthermore, we catalog and analyze emerging Gal-3-targeted therapies, emphasizing their rationale for combination with immune checkpoint blockade to reverse therapeutic resistance. Finally, we outline a translational roadmap, advocating for standardized Gal-3 biomarker assays and biomarker-enriched clinical trials. Integrating Gal-3 into the PCa precision medicine toolkit offers a novel strategy to address heterogeneity and improve therapeutic durability. Full article

Ischemic heart disease (IHD) remains the leading cause of chronic heart failure (HF) worldwide, yet the biological processes underlying this transition are not fully elucidated. Growing evidence indicates that chronic, low-grade inflammation acts as a pivotal link between ischemic injury and progressive myocardial dysfunction. Our review is the most up-to-date and structured synthesis on the pathophysiological pathways, biomarkers, and therapeutic implications of subclinical inflammation in patients with IHD at risk of developing HF. Following acute or repetitive ischemic episodes, persistent immune activation—mediated through interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)—promotes endothelial dysfunction, microvascular instability, and extracellular matrix remodeling. These mechanisms culminate in ventricular stiffness, diastolic impairment, and adverse structural remodeling, even when left ventricular ejection fraction is preserved. Biomarkers such as Galectin-3, cancer antigen 125 (CA125), and high-sensitivity C-reactive protein (hsCRP) provide valuable insight into the interplay between fibrosis, congestion, and systemic inflammatory load, supporting early detection of subclinical myocardial injury. Advanced imaging modalities, including strain echocardiography and cardiac magnetic resonance imaging (MRI) mapping, enhance the phenotypic characterization of inflammatory cardiomyopathy. Understanding and targeting these inflammatory pathways may open new avenues for precision-based prevention and treatment, ultimately improving outcomes across the IHD–HF continuum. Full article

Background/Objectives: Acute intravascular hemolysis is associated with the release of labile heme, which contributes to systemic inflammation and organ dysfunction. Galectin-3 (Gal-3) is a known modulator of inflammatory responses. However, its specific role in heme-induced organ injury remains to be fully elucidated. Methods: We used a phenylhydrazine (PHZ)-induced model of acute hemolysis in wild-type (WT) and Gal-3 knockout (KO) mice to investigate the influence of Gal-3 on tissue alterations and the inflammatory response. Results: Despite equivalent levels of hemolysis and anemia in both genotypes, Gal-3 deficiency was associated with reduced injury in the liver, kidneys, and pancreas. In WT mice, Gal-3 was associated with a pro-inflammatory splenic microenvironment. Conversely, Gal-3 KO mice exhibited a shift toward an immunoregulatory phenotype, characterized by an increased frequency of CD4 + CD25 + FoxP3+ regulatory T cells and IL-10+ macrophages. This shift correlated with preserved organ architecture and a more controlled inflammatory profile. Conclusions: Our findings suggest that Gal-3 may act as a mediator of heme-induced systemic inflammation. By influencing the splenic immune microenvironment and promoting a regulatory phenotype, the absence of Gal-3 appears to alleviate multi-organ stress, suggesting its potential as a target for modulating complications during acute hemolytic crises. Full article

Oncogenic driver mutations in non-small cell lung cancer (NSCLC) activate defined signaling pathways that sustain tumor growth and influence the immune landscape. Yet, how coordinated interactions among diverse cell populations within the tumor immune microenvironment (TIME) contribute to this process remains largely unresolved. To address this, we profiled approximately 200,000 single cells from 45 treatment-naïve NSCLC patients representing seven major driver mutations. This analysis uncovered five multicellular modules (CM1–5) with distinct functional properties, each linked to specific malignant regulatory programs. Among them, CM2 and CM5 exhibited pronounced invasive features and were associated with unfavorable clinical outcomes. CM2 was predominantly observed in EGFR- and MET-driven brain metastases and was defined by strong crosstalk between astrocytes and myofibroblasts. Factors such as SPP1, PTN, and PSAP, together with metabolic alterations, contributed to a microenvironment supportive of metastatic colonization in the brain. By contrast, CM5 was enriched in ROS1-, KRAS-, and EGFR-mutant tumors and consisted of diverse myeloid and endothelial subsets characterized by immunosuppressive and pro-angiogenic signaling, including MIF, GALECTIN, and RETN, collectively facilitating immune escape and vascular remodeling. We further constructed and validated a driver mutation-specific prognostic signature (DMSP.sig) model integrating receptor–ligand interactions and core transcription factors, which effectively stratified patient survival. Leveraging this model, we also identified potential therapeutic candidates linked to these prognostic features, highlighting opportunities for clinical intervention. In summary, our study delineates how oncogenic drivers give rise to distinct TIME architectures, providing a framework for prognostic assessment and precision immunotherapy in high-risk NSCLC. Full article

Galectins are a functionally diverse family of β-galactosyl-binding lectins that are ubiquitously present in animal species, with key roles in development and immune regulation. Recently, galectins have been found to recognize microbial glycosylated moieties, but the detailed mechanisms of their innate immune functions in mucosal epithelia have remained elusive. The zebrafish (Danio rerio) represents an ideal genetically tractable model to address these questions, as the skin, gills, and gut display mucosal surfaces exposed to the environment. In this study, we investigated the range of endogenous and microbial glycans that are recognized by zebrafish galectin Drgal1 present in epidermal mucus, which would be consistent with defense functions against a bacterial challenge. Results revealed that zebrafish galectin isoform Drgal1-L2 can recognize selected bacterial glycans, as well as zebrafish mucus glycans and cell-surface receptors for bacterial adhesins such as fibronectin (K_D = 1.593 × 10⁻⁶ M) and CD147 (K_D = 1.115 × 10⁻⁶ M). Furthermore, preliminary experiments revealed that Drgal1-L2 may hinder bacterial adhesion to epidermal mucus in about 50% at 2.5 μg/mL. Our results suggest that Drgal1-L2 present in epidermal mucus can prevent access of pathogenic bacteria to the epithelial cell surface by alternate or synergic binding to bacterial glycans and to zebrafish mucus components and epithelial receptors for bacterial adhesins. Thus, the present study provides key information for the testing of the abovementioned hypothesis by implementing gene-silencing approaches targeting both zebrafish Drgal1-L2 and its ligands. Full article

Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η² = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation. Full article

Galectin-3 (Gal-3) is a multifunctional molecule that exerts pleiotropic effects in inflammatory responses and contributes to the pathogenesis of numerous immune-mediated diseases. Although Gal-3 has been known for more than five decades, it remains a lectin with intriguing and not yet fully elucidated properties. The existing body of evidence underscores the importance of Gal-3 in the regulation of homeostatic and inflammatory processes. Neurotrophins are traditionally recognized as key regulators of neuronal development, survival, and synaptic plasticity; nevertheless, accumulating evidence indicates that they also play important roles in immune regulation and neuroimmune communication. Importantly, neurotrophins are also produced by immune cells, including monocytes, macrophages, lymphocytes, and basophils, which express functional neurotrophin receptors including tropomyosin receptor kinase A (TrkA), tropomyosin receptor kinase A (TrkB), and p75 neurotrophin receptor (p75NTR). In this narrative review, we synthesize current evidence on neuroinflammation, neurotrophins, and Gal-3, with a particular focus on the molecular mechanisms involved in the crosstalk between neurotrophins and Gal-3 or immune cells. We further examine how this neuroimmune–neurotrophic crosstalk contributes to the pathogenesis of psychiatric and neurodegenerative disorders, as well as other neurological conditions. Finally, we discuss the emerging therapeutic potential of targeting neurotrophins and Gal-3 as modulators of neuroinflammation. Full article

Galectin-3 (Gal3) is one of the most pro-inflammatory proteins and a biomarker of inflammatory diseases and cancer. Previous studies showed that Gal3 binds to αv and β1 integrins, but it is unclear how Gal3 binds to integrins. Here, we show that Gal3 bound to soluble αvβ3 and αIIbβ3 integrins in 1 mM Mn²⁺ in cell-free conditions in a glycan-independent manner. Docking simulation predicts that Gal3 binds to the classical RGD-binding site (site 1) of αvβ3, but the predicted Gal3-binding site does not include galactose-binding site. RGDfV or eptifibatide inhibited Gal3 binding to αvβ3 and αIIbβ3, respectively, but lactose, a pan-galectin inhibitor, did not inhibit Gal3 binding to integrins. Point mutations of the predicted site 1 binding interface of Gal3 effectively inhibited Gal3 binding to site 1. Site 2 is involved in pro-inflammatory signaling (e.g., TNF and IL-6 secretion), and we previously showed that pro-inflammatory cytokines (e.g., CCL5 and TNF) bind to site 2 and allosteric integrin activation. Docking simulation predicted that Gal3 binds to site 2 of αvβ3 and α5β1. We found that Gal3 induced allosteric activation of soluble integrins αvβ3, αIIbβ3, and α5β1 in 1 mM Ca²⁺ in cell-free conditions. Point mutations in the predicted site 2 binding interface inhibited Gal3-induced integrin activation, suggesting that Gal3 binding to site 2 is required for Gal3-induced integrin activation. Known anti-inflammatory agents, Ivermectin, NRG1, and FGF1, inhibited integrin activation induced by Gal3 in αvβ3 and αIIbβ3. These findings suggest that Gal3 binding to site 2 may be a potential mechanism of pro-inflammatory and pro-thrombotic action of Gal3. Full article

Acute coronary syndrome patients undergoing percutaneous coronary intervention remain at high risk for major adverse cardiovascular events (MACE: cardiovascular mortality, non-fatal myocardial infarction, and stroke). Inflammatory–oxidative stress biomarkers are potential prognostic tools; however, the influence of sampling timing—pre-procedural versus post-procedural—remains unclear. This meta-analysis evaluated six biomarkers: sST2, GDF-15, OPG, sLOX-1, H-FABP, and Galectin-3. Pooled Hazard Ratios (HRs) for time-to-event outcomes and Standardized Mean Differences (SMDs) between event and non-event groups were synthesized using random-effects models involving 40 studies (18,933 patients). Elevated pre-procedural levels of sST2 (HR = 3.32, p < 0.0001), GDF-15 (HR = 3.00, p < 0.0001), sLOX-1 (HR = 2.61, p = 0.0023), and OPG (HR = 1.79, p = 0.0206) significantly predicted MACE. Notably, pre-PCI sST2 strongly predicted heart failure hospitalization (HR = 6.30, p < 0.0001). Additionally, pre-PCI H-FABP demonstrated a moderate significant effect on adverse outcomes (SMD = 0.67, p < 0.0001). While pre-PCI Galectin-3 was not significant, its post-procedural levels showed a large significant effect (SMD = 1.15, p < 0.0001). In conclusion, inflammatory and oxidative stress biomarkers, particularly sST2 and GDF-15, demonstrate consistent associations with adverse outcomes in ACS patients undergoing PCI, offering more reliable baseline risk stratification than post-procedural measurements. Full article

Myxomatous mitral valve disease (MMVD) is a common cardiac disorder in older small- to medium-sized dogs. Diagnosis and staging are primarily based on echocardiography; however, circulating cardiac biomarkers have gained increasing interest because they are rapid and easily measurable. In this context, the investigators’ aim was to study the clinical value of galectin-3 (Gal-3) and trimethylamine N-oxide (TMAO), in dogs affected by MMVD, in comparison to cardiac troponin I (cTnI), a well-established biomarker of myocardial injury, and echocardiography. Twenty-two dogs were classified as healthy controls or affected by MMVD and staged according to American College of Veterinary Internal Medicine (ACVIM) guidelines. Serum concentrations of Gal-3, TMAO, and cTnI were measured and compared among groups. No significant differences in serum Gal-3 concentration were detected among groups (p = 0.955). In contrast, TMAO levels were significantly higher in both asymptomatic and symptomatic dogs compared with healthy controls (both p < 0.001). Serum cTnI showed limited sensitivity, with increased values observed only in some symptomatic dogs. Despite study limitations, including small sample size and demographic differences among groups, these preliminary findings suggest that TMAO could be a potential biomarker associated with MMVD development and progression; however, further studies are needed to confirm this association. Full article

Melanoma remains a highly aggressive malignancy, particularly in advanced metastatic stages where therapeutic options are limited. Natural compounds provide a structural basis for discovering novel anticancer agents. In this study, we employed an integrated in silico approach to evaluate the pharmacokinetic properties, toxicity profiles, and molecular targets of key alkaloids from Chelidonium majus, including berberine, sanguinarine, chelerythrine, chelidonine, protopine, umbelliferone and coptisine. ADME/T predictions (SwissADME and DeepPK) revealed favorable drug-likeness and oral bioavailability for most compounds, with berberine exhibiting the most balanced safety and absorption profile. All compounds demonstrated high intestinal absorption (>99%) and implicated key melanoma targets, including APE1/Ref-1, CXCR4, CCR2, TLR8, galectin-3, and VEGFR2. These molecules represent valuable templates for the development of melanoma therapies. Among the tested compounds, chelidonine emerged as a potential APE1 inhibitor, exhibiting the highest binding affinity and forming specific interactions within the enzyme’s catalytic site, suggesting its potential as a DNA repair-targeted agent in melanoma. These findings support the further exploration of natural alkaloids, including structural optimization or advanced formulation strategies, to enhance safety, bioavailability, and therapeutic efficacy in melanoma. Full article