Search Results (808)

Chronic kidney disease, acute kidney injury and cardiorenal syndrome are major determinants of cardiovascular morbidity and mortality, yet conventional renal assessment based on serum creatinine, estimated glomerular filtration rate and urine output often fails to detect early structural injury or pathway-specific cardiorenal risk. This narrative review synthesized recent evidence on emerging renal and cardiorenal biomarkers with potential value for cardiovascular risk stratification beyond creatinine. Literature published between 2015 and April 2026 was reviewed, focusing on biomarkers of tubular injury, functional renal impairment, fibrosis/remodeling and mineral metabolism. NGAL and KIM-1 may detect tubular stress and proximal tubular injury before overt functional decline and have shown relevance in heart failure, acute coronary syndromes and post-cardiac surgery settings. Cystatin C and pro-enkephalin refine functional renal assessment and may improve prognostic classification when creatinine is confounded by frailty, muscle mass or acute hemodynamic changes. Soluble ST2 and galectin-3 reflect inflammation, fibrosis and cardiorenal remodeling, while FGF-23 links kidney dysfunction to cardiovascular risk through phosphate imbalance, vascular calcification and myocardial hypertrophy. Multi-biomarker panels may help identify dominant cardiorenal phenotypes and personalize monitoring intensity. However, routine implementation requires standardized assays, validated thresholds, cost-effectiveness data and prospective evidence that biomarker-guided management improves clinical outcomes. Full article

Background: This study evaluated the potential effects of different COVID-19 vaccine platforms (mRNA and inactivated) on acute coronary syndrome (ACS) through Galectin-3, a biomarker of chronic inflammation and fibrosis. It aimed to compare serum Galectin-3 levels among NSTEMI patients according to COVID-19 vaccination status and vaccine type. Methods: A total of 75 patients with NSTEMI were prospectively enrolled and categorized into three groups: inactivated vaccine recipients (n = 25), mRNA vaccine recipients (n = 25), and unvaccinated controls (n = 25). Serum Galectin-3 levels were measured to assess chronic inflammatory status. Additionally, markers of acute myocardial injury and inflammatory response were analyzed. Results: Galectin-3 levels were similar across the inactivated vaccine, mRNA vaccine, and unvaccinated NSTEMI group, with no statistically significant difference observed (p = 0.481). Although troponin I levels and acute inflammatory cell burden were higher in vaccinated patients compared with the unvaccinated NSTEMI group, Galectin-3 levels remained comparable among all groups. No significant differences in Galectin-3 levels were observed according to vaccination status or vaccine type. Conclusions: In this exploratory cohort of NSTEMI patients, serum Galectin-3 levels did not differ significantly according to COVID-19 vaccination status or vaccine type. These findings suggest no detectable association between vaccination history and Galectin-3 levels in the study population. Larger prospective studies with longitudinal follow-up are needed to confirm these observations. Full article

Neuroendocrine neoplasms (NENs) are a heterogeneous family of tumors that have traditionally been regarded as “immune cold” and largely refractory to PD-1/PD-L1 checkpoint blockade, with notable exceptions such as Merkel cell carcinoma (MCC). The advent of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics has enabled unprecedented dissection of the NEN tumor microenvironment (TME), but a cross-subtype synthesis is lacking. This review aims to integrate single-cell and spatial transcriptomic findings across major NEN subtypes to reframe NEN immunosuppression and delineate translational implications. To this end, we performed a structured narrative review of PubMed-indexed studies up to 30 April 2026, prioritizing original human scRNA-seq, single-nucleus RNA-seq, spatial transcriptomic, and spatial proteomic studies of NENs, supplemented by mechanistic, clinical, and biomarker-focused reports providing essential context. Across these studies, synthesis spanning pancreatic, pulmonary, gastrointestinal, cutaneous, pituitary, adrenal, and other NEN subtypes highlights conserved features beyond the PD-1/PD-L1 axis, including myeloid-dominated infiltration with alternative checkpoints (VISTA, TIM-3, Galectin-9), cancer-associated fibroblast-mediated immune exclusion, lineage-state-dependent immune visibility, and direct immunomodulation by neuroendocrine secretory products such as calcitonin gene-related peptide. We propose a four-layer framework integrating these mechanisms and linking them to emerging biomarkers and therapies, including DLL3-directed bispecifics, alternative checkpoint inhibitors, stromal-targeting agents, and peptide receptor radionuclide therapy combinations. Together, these findings indicate that single-cell and spatial transcriptomic studies reframe NEN immunosuppression as a multilayered, subtype-dependent process, providing a conceptual scaffold for biomarker-guided, subtype-adapted therapeutic strategies and prospective clinical trial design in neuroendocrine oncology. Full article

Cartilage oligomeric matrix protein (COMP) influences extracellular matrix remodeling. We investigated its clinical, prognostic, and immunomodulatory significance in colorectal cancer (CRC). COMP was quantified via ELISA in 107 paired CRC and normal tissues. Expression was correlated with clinicopathological features, mutational profiles, microsatellite instability (MSI), tumor-infiltrating lymphocytes (TILs), immune checkpoints, and multiplex cytokine networks. For transcriptomic validation, the FieldEffectCrc dataset was used for Gene Set Enrichment Analysis (GSEA), and The Cancer Genome Atlas (TCGA) CRC cohort for survival analysis. COMP was significantly upregulated in CRC tissues (p < 0.001) and correlated with advanced T, N, and overall pathological stages (all p < 0.05, tau = 0.18, 0.21, and 0.23, respectively). High COMP expression was linked to restricted immune infiltration (reduced stromal TILs, p < 0.05, tau = −0.23), elevated levels in microsatellite stable (MSS) compared to MSI tumors (p < 0.01), and correlated positively with immune exhaustion markers (T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), galectin-9 (GAL9), sialic acid-binding Ig-like lectin 9 (SIGLEC9)). Transcriptomic data linked high COMP to worse disease-specific and progression-free survival, and enrichment in pro-tumorigenic pathways (epithelial-to-mesenchymal transition, angiogenesis, IL-6 signaling). COMP upregulation defines an immunosuppressive microenvironment in CRC, particularly in MSS tumors. It represents an important prognostic biomarker and potential therapeutic target for overcoming immunotherapy resistance. Full article

Marine sponges represent a rich source of lectins with diverse biological activities and biotechnological potential. In this study, we report the purification and comprehensive biochemical and structural characterization of a lectin (CspL) from the marine sponge Cinachyrella sp. and evaluate its effects on bacterial agglutination, planktonic bacterial growth, and biofilm formation. CspL was isolated using classical chromatographic approaches and identified as a galectin-like protein based on sequence similarity, conserved carbohydrate-recognition motifs, and a predominance of β-sheet structures revealed by circular dichroism. Oligomeric analysis indicated a homotetrameric organization, consistent with the quaternary structure described for other sponge proto-type galectins. Carbohydrate-binding assays demonstrated that CspL preferentially recognizes galactoside-containing motifs, showing strong inhibition by mucin-type glycoproteins, while displaying lower affinity toward more complex glycan structures. This binding profile suggests a preference for accessible carbohydrate epitopes, likely associated with its canonical galectin architecture. Regarding antibacterial activity, CspL also exhibited selective, carbohydrate-dependent bacterial agglutination, particularly against Staphylococcus aureus strains. In addition, CspL exhibited antibiofilm activity against S. aureus and Escherichia coli, significantly reducing biofilm biomass and viable cell counts. Additionally, the lectin modulated antibiotic activity, showing synergistic effects with tetracycline and strain-dependent interactions with oxacillin. Together, these findings highlight CspL as a structurally conserved yet functionally relevant member of sponge galectins and reinforce the role of structural diversity in shaping glycan recognition and antimicrobial activity in marine lectins. Full article

Thermal ablation (TA) is an increasingly adopted minimally invasive treatment for benign thyroid nodules. However, TA induces marked histological alterations that may simulate thyroid malignancy, creating significant diagnostic pitfalls for pathologists. The present study expands our previous institutional series and further characterizes the morphologic, immunohistochemical, and molecular features of thermally ablated thyroid nodules in order to refine the differential diagnosis with thyroid carcinoma. Fourteen surgically excised thyroid nodules previously treated with laser thermal ablation were retrospectively analyzed. Histopathological evaluation focused on architectural changes, nuclear atypia, capsule alterations, degenerative phenomena, and evidence of invasion. Immunohistochemical analysis included galectin-3 (Gal-3), HBME-1, BRAF V600E, p53, and Ki-67. In addition, molecular profiling for the principal thyroid cancer-related alterations, including BRAF, RAS family genes, TERT promoter mutations, PIK3CA alterations, and RET rearrangements, was performed using targeted next-generation sequencing. All nodules showed treatment-related reactive and degenerative changes, including fibrosis/sclerosis, subcapsular hemorrhage, focal oncocytic metaplasia, and architectural distortion. No true capsular or vascular invasion was identified. Immunohistochemically, all cases were negative for Gal-3 and BRAF V600E, while HBME-1 expression was absent or only focally weak. Ki-67 proliferative activity remained consistently low (<3%) in all cases. Molecular analyses did not identify pathogenic alterations involving BRAF, RAS, TERT promoter, PIK3CA, or RET genes in any case. Thermal ablation induces reproducible reactive and degenerative histologic alterations that may closely mimic follicular or papillary thyroid neoplasms. The absence of malignancy-associated immunohistochemical and molecular alterations strongly supports the benign nature of these lesions and highlights the importance of an integrated morphologic, immunohistochemical, and molecular diagnostic approach in challenging post-ablation specimens. Thermally ablated thyroid nodules may display significant pseudo-neoplastic changes that can lead to overdiagnosis of carcinoma. Awareness of these treatment-related alterations, combined with immunohistochemical and molecular profiling, represents a reliable strategy to distinguish reactive post-ablation changes from true thyroid malignancy and to avoid inappropriate clinical management. Full article

Galectin-3 (Gal-3) is a β-galactoside-binding lectin implicated in metabolic inflammation, cardiovascular and renal dysfunction, neurodegenerative disorders, and obesity-related pathologies. Although Gal-3 is recognized as a clinically relevant biomarker, the mechanisms controlling its tissue expression and circulating abundance remain poorly defined. O-GlcNAcase (Oga; encoded by Mgea5), the enzyme that removes O-linked β-N-acetylglucosamine (O-GlcNAc) from proteins, regulates nutrient-sensitive signaling and transcriptional processes that overlap with Gal-3 associated disease pathways. To investigate the relationship between metabolic status and Gal-3 expression, male mice were fed a high-fat diet (HFD) for eight weeks to induce obesity. HFD-fed mice exhibited significant increases in body weight and fasting and fed blood glucose levels compared with lean controls, confirming metabolic dysregulation. ELISA revealed approximately threefold higher serum and plasma Gal-3 concentrations in obese mice, indicating enhanced Gal-3 production in diet-induced obesity. To determine whether Oga regulates Gal-3 expression, Oga wild-type (WT), heterozygous (HET), and knockout (KO) mice were analyzed. Circulating Gal-3 protein levels were significantly reduced in Oga KO mice, with intermediate levels in Oga HET animals. RT-qPCR revealed genotype-dependent modulation of Gal-3 (Lgals3) mRNA expression across multiple tissues, demonstrating tissue-specific regulation by Oga. These findings establish Oga as a critical regulator of Gal-3 expression and systemic abundance. The data reveal a mechanistic link between O-GlcNAc signaling enzyme Oga, and lectin-mediated metabolic inflammation, suggesting that Oga activity influences Gal-3 homeostasis and may affect its interpretation as a biomarker in metabolic disease. Full article

Human immunodeficiency virus and tuberculosis (HIV/TB) coinfection remains a major global health challenge. Immune dysregulation in HIV complicates TB diagnosis. The type of immune response mounted in tuberculosis is a key determinant in deciding the outcome of the infection. Hence, estimating immune markers is critical for developing diagnostic, monitoring and treatment approaches. A study was conducted to evaluate the diagnostic potential of host-based biomarkers in individuals with HIV/TB coinfection in comparison to HIV monoinfection receiving antiretroviral therapy. Host-based biomarkers were quantified using commercially available kits. Receiver operated curve (ROC) analysis was conducted to determine diagnostic performance. Routine investigations showed significantly raised ratios of neutrophils, monocytes, and platelets-to-lymphocytes and alkaline phosphatase levels in HIV/TB coinfection (AUC values > 0.76). Plasma galectin-9 and osteopontin levels had an AUC > 0.8. IFN-γ, TNF-α and IL-12 levels were also significantly raised (AUC values > 0.95) while levels of GM-CSF and IL-6 were significantly low in HIV TB coinfection. The ROC analysis revealed the highest diagnostic accuracy of IL-12, indicating its potential as an adjunct immunological biomarker in identifying TB among HIV-infected individuals. However, a large-scale prospective study is required to confirm the findings and to understand their role in predicting the development of tuberculosis disease in people living with HIV. Full article

Research in the last two decades has well established galectin-3 (Gal3), a member of the lectin family, as a clinical biomarker and mediator of cardiovascular as well as other diseases. Gal3 contributes to progression of diseases by promoting pathological components, including inflammation, fibrosis, cell death or proliferation, and metabolic remodeling, and hence forms an ideal therapeutic target. Notably, nearly all Gal3 inhibitors that are currently under intensive pre-clinical and clinical testing target carbohydrate recognition/binding domain (CRD) of Gal3 molecules. Whereas the role of Gal3 in cardiovascular disease (CVD) has been well established, research on Gal3 in cancer or immunology has been leading the frontiers in this discipline. Therefore, it is important to have an integrated understanding on the biology and pathophysiology of Gal3 in a spectrum of pathological conditions. This review describes current findings from studies on diverse disease conditions and examines the role of Gal3 in the pathogenesis of diseases focusing on its transcription, post-translational modifications, intracellular dynamics, extracellular exporting, and interactions with a variety of signaling molecules. By bridging findings from different disciplines on the role of Gal3 in diseased settings, we explore the diverse anti-Gal3 strategies in addition to inhibition of CRD binding and highlight the significance of interventions targeting the transcription and post-translational modifications of Gal3, as well as intracellular actions of Gal3. At the end of this review, we provide perspectives for future research and therapeutic implications in CVD. Full article

Background: Osteoporosis (OP) is a chronic disease characterized by decreased bone mass and altered microarchitecture, leading to bone fragility and fracture risk. To date, although carbohydrate-binding proteins Galectins 1 and 3 (Gal-1/Gal-3) have been implicated in bone metabolism, inflammation and aging, their levels and potential regulation by microRNAs (miRNAs) have not yet been investigated in OP. Methods: In this pilot study, 13 osteoporotic (OP) and 10 non-osteoporotic (NOP) patients, all undergoing hip or knee arthroplasty, were enrolled. Due to the unavailability of DXA measurements, OP classification was based on cortical bone ratio and distal femoral cortical index. Clinical parameters and blood samples were collected preoperatively, while bone biopsies were obtained intraoperatively. ELISA and qRT-PCR were used to quantify Gal-1, Gal-3, miR-22 and miR-21 in bones and sera. Correlations with clinical parameters were assessed. Results: Several OP biopsies exhibited a reduction in Gal-1 levels, whereas miR-22, Gal-3 and miR-21 were increased. Serum analysis revealed similar dysregulation patterns, with increased miR-21 and decreased Gal-1 and miR-22 levels in several OP patients. Conclusions: This pilot study suggests a putative association of Gal-1, Gal-3, and their previously reported related miRNAs with osteoporotic bone status, indicating their potential involvement in OP-related bone metabolism. Full article

The lysosomal enzyme α-galactosidase A (AGAL) degrades globotriaosylceramide (Gb₃). While this enzymatic function in lysosomal metabolism is well characterized, interaction partners and alternative functions are unknown. This study aims to identify new potential AGAL-interacting proteins. AGAL was fused to the mutated biotin ligase BirA from E. coli (TurboID). Expression of the fusion protein was confirmed by Western blot and immunofluorescence, while enzymatic activity was verified by functional assays. In three experimental settings (AGAL wild-type (WT), AGAL missense variant (p.N215S), and the control cell line), TurboID-biotinylated proximal proteins were enriched by streptavidin pull-down and analyzed by mass spectrometry. Gene Ontology (GO) terms were subsequently evaluated to characterize biological functions and localizations of the identified proteins. Selected candidates were co-immunoprecipitated with AGAL to confirm direct interactions. The AGAL-TurboID fusion protein was successfully expressed in AB8/13 podocytes. Immunofluorescence and enzyme activity assays confirmed the presence and functionality of the fusion protein. Subsequent functional analysis (GO term analysis) showed enrichment of driver terms, including extracellular matrix organization (ECM), multicellular organism development, and protein metabolic process, in the biological process category. The identified top-hit proteins were predominantly involved in the organization of ECM, cell proliferation and cytokinesis, unfolded protein response during endoplasmic reticulum stress, and protein ubiquitination. Co-immunoprecipitation confirmed the interaction between AGAL and the candidate Galectin-3-binding protein (Gal-3BP). Our results suggest that AGAL may play a role in other pathways and/or the ECM organization beyond its lysosomal function. The confirmed interaction with Gal-3BP can now be functionally investigated in further studies. Full article

Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) that occurs in most types of chronic liver diseases (CLDs) as a response to sustained liver injury. While the ECM comprises different proteins, collagen being the most abundant, the term matrisome refers to a plethora of ECM-related molecules, including collagen-associated proteins, growth factors, cytokines, enzymes and their endogenous inhibitors. The hepatic matrisome undergoes significant qualitative and quantitative changes during liver fibrosis. Despite intense research over recent years, our understanding of the matrisome in the liver—both in health and disease—and particularly of its function beyond its conventional structural role, remains poor. This review highlights how comprehending hepatic matrisome responses to liver injury can yield novel insights into disease progression and regression and could be exploited as a potential antifibrotic strategy. The antifibrotic potency of drugs that interfere with the matrisome at different levels has been demonstrated in preclinical studies, but translation to clinical trials remains still limited. So far, simtuzumab (LOXL2 inhibitor antibody), imatinib (small-molecule inhibitor against discoidin domain receptors—DDRs), bexotegrast (integrin inhibitor), GR-MD-02 (galectin 3 inhibitor), and BMS-986263 (siRNA-targeting HSP47) have been or are being evaluated in clinical trials related to CLD, and some of them have shown promising results. Full article

Galectins are β-galactosyl-binding lectins with key roles in immune regulation and as pattern recognition receptors. To address their potential role(s) in viral infection of mucosal epithelia we currently investigate adhesion and entry mechanisms of the infectious hematopoietic necrosis virus (IHNV) using the zebrafish (Danio rerio) model system. We previously reported the recognition of IHNV envelope glycoprotein by the zebrafish galectin Drgal1-L2 and its inhibitory activity for viral adhesion to epithelial cells. Subsequently, we determined the structure of Drgal1-L2 and proposed a mechanism for Drgal1-mediated inhibition of IHNV spike fusion to the host epithelial cell. We now show that Drgal1 can also hinder viral adhesion and infection by binding to glycans on the host cell surface and epidermal mucus. We identified fibronectin, the reported IHNV receptor, as the cell surface glycoprotein recognized by Drgal1-L2. Surprisingly, IHNV also adhered in vitro to purified β1integrin, and pre-exposure of either IHNV or the immobilized β1integrin to Drgal1-L2 hindered IHNV adhesion. Binding of either anti-fibronectin or anti-β1integrin antibodies to the cell surface partially inhibited IHNV adherence. Drgal1-L2 also hindered IHNV adhesion by binding to mucus glycans. Taken together, our results suggest complementary mechanisms by which Drgal1-L2 may protect mucosal epithelial cells against IHNV infection and tentatively identify β1integrin as a novel receptor for IHNV. Full article

Angiostrongyliasis, the primary cause of eosinophilic meningitis, represents an emerging disease caused by Angiostrongylus cantonensis larvae, inadvertently transmitted to humans. The diagnosis of human angiostrongyliasis relies on epidemiological features, clinical symptoms, medical history, and laboratory findings, notably hyper eosinophilia in blood and cerebrospinal fluid. Consequently, accurate diagnosis is challenging and prone to confusion with other parasitic diseases. The quest for an early, rapid, and specific diagnostic test for angiostrongyliasis persists, driven by the imperative for enhanced test specificity. This study focused on mapping IgM epitopes on galectin-1 (Gal-1) and galectin-2 (Gal-2) proteins derived from A. cantonensis. The specificity of the epitopes was assessed using database homology analysis. After selecting specific epitopes, researchers chemically synthesized 12 individual multi-antigen peptides (MAPs4) and one chimeric polypeptide that is 65 amino acids long. The effectiveness of these synthesized peptides was subsequently evaluated using enzyme-linked immunoassay (ELISA). A total of twelve unique IgM epitopes were discovered; five were linked to Gal-1, while seven were linked to Gal-2. An ELISA-peptide method confirmed the twelve epitopes, and then the chimeric polypeptide was employed as an antigen to coat ELISA plates. This setup was evaluated with patients’ sera to diagnose strongyloidiasis in vitro. This study provides a comprehensive representation of the IgM epitopes of Gal-1 and Gal-2 from A. cantonensis. ELISA data utilizing the chimeric polypeptide demonstrate that the selected sequences hold promise for the development of a specific immunological assay tailored for the acute diagnosis of angiostrongyliasis infections. Full article

Background/Objectives: Pediatric group 3 (G3) medulloblastomas (MB) are therapy resistant and have a significantly worse prognosis than the other MB subtypes. Aggressive radiation/chemotherapy improves survival, but potential long-term comorbidities include neurocognitive deficits. In previous work, we demonstrated that low-dose X-ray radiation (LDXR) acts as an immunological adjuvant. Recent studies have demonstrated that galectin-3 (Gal-3) expression in MB tumors accelerates M2 macrophage infiltration and restricts T cell receptor (TCR)-mediated signaling. Immunotherapy with an agonistic anti-4-1BB monoclonal antibody (mAb) activates CD8+ T cells, promoting their survival and acquisition of potent cytolytic properties. Building on these findings, we hypothesized that immune priming via sublethal LDXR, combined with a Gal-3 inhibitor and an anti-4-1BB mAb, would boost anti-tumor effects, resulting in survival benefits. Methods: We tested this hypothesis in vitro in co-cultures of human MB cells and in vivo, in an immunocompetent G3MB mouse model (MP1). Treatment effects were assessed using Western blot, flow cytometry, hematoxylin and eosin (H&E) staining, immunofluorescence imaging, and analysis of cytokine and chemokine expression. Results: Our data demonstrated higher Gal-3 expression in MB patient-derived tumor tissue than in non-tumor tissue. LDXR modulated major histocompatibility complex molecules, and, combined with a Gal-3 inhibitor and an anti-4-1BB mAb, altered T-cell/tumor-cell interactions, enhanced T-cell-mediated MB cell death, and shifted cytokine production to drive microglial polarization toward the M1 subtype. Furthermore, H&E-stained tumor sections showed a ~70% reduction in tumor size compared with untreated controls. Conclusions: These preclinical findings suggest that combining immune priming with sublethal LDXR, Gal-3 inhibition, and 4-1BB activation may be an effective treatment strategy for G3MB. Full article