Search Results (732)

Galectins, a family of glycan-binding proteins, play crucial roles in various cellular functions, acting at both intracellular and extracellular levels. Among them, Galectin-3 (Gal-3) stands out as a unique member, possessing an intrinsically unstructured N-terminal oligomerization domain and a canonical carbohydrate-recognition domain (CRD). Gal-3 binding to glycosylated plasma membrane cargo leads to its oligomerization and membrane bending, ultimately resulting in the formation of endocytic invaginations. An interactomic assay using proteomic analysis of endogenous Gal-3 immunoprecipitates identified the orphan G protein-coupled receptor GPRC5A as a novel binding partner of Gal-3. GPRC5A, also known as Retinoic Acid-Induced protein 3 (RAI3), is transcriptionally induced by retinoic acid. Our results further demonstrate that extracellular recombinant Gal-3 stimulates GPRC5A internalization. In SW480 colorectal cancer cells, glycosylated GPRC5A interacts with Gal-3. Interestingly, while GPRC5A expression was upregulated by the addition of all-trans retinoic acid (ATRA), its endogenous internalization in SW480 cells was specifically triggered by extracellular Gal-3, but not by ATRA. This study provides new insights into the endocytic mechanisms of GPRC5A, for which no specific ligand has been identified to date. Further research may uncover additional Gal-3-mediated functions in GPRC5A cellular signaling and contribute to the development of innovative therapeutic strategies. Full article

Background/Objectives: Galectin-3 (Gal-3), encoded by LGALS3, is a β-galactoside-binding lectin involved in diverse tumor-associated processes, including immune modulation, cell cycle regulation, and stress adaptation. Despite its known roles in cancer biology, the full extent of its molecular functions and prognostic relevance across tumor types remains incompletely understood. This study aimed to systematically investigate the transcriptomic impact of LGALS3 deletion and assess its clinical significance in cancer. Methods: We analyzed CRISPR-Cas9 knockout transcriptomic data from the SigCom LINCS database to characterize the consensus gene signature associated with LGALS3 loss using functional enrichment analyses. Pan-cancer survival analyses were conducted using TIMER2.0. Differential Gal-3 protein levels in ductal adenocarcinoma and normal pancreatic tissues were evaluated using the Human Protein Atlas. Finally, functional analyses were performed in pancreatic ductal adenocarcinoma (PDAC). Results: LGALS3 deletion across multiple cancer cell lines led to transcriptomic changes involving mitotic progression, stress responses, and axonal guidance pathways. High LGALS3 expression was significantly associated with worse overall survival in lower-grade glioma, PDAC, uveal melanoma, and kidney renal papillary cell carcinoma. LGALS3 knockout in YAPC cells recapitulated the pan-cancer findings, linking LGALS3 to cell morphogenesis and proliferation. Conclusions: These findings identify Galectin-3 as a key regulator of oncogenic programs and a potential prognostic biomarker in PDAC and other malignancies, with implications for therapeutic targeting. Full article

Background: Circulating galectin-3 (Gal-3) levels have been indicated as a promising diagnostic, prognostic, and therapeutic target in breast cancer patients. Specifically, serum galectin-3 levels are traditionally measured using manual Enzyme-Linked Immunosorbent Assay (ELISA), but recent automated methods, such as Simple Plex assay by ProteinSimple™ run on an Ella instrument, have shown promising evidence of being more efficient and less error-prone than manual methods. This paper aims to assess whether there are differences in serum galectin-3 measurements between manual and automated ELISA methods. Methods: Serum galectin-3 levels were initially analyzed from one hundred and fifteen breast cancer samples using both manual ELISA and the Ella instrument. Following coefficient of variation (CV) and outlier analysis, ninety-five samples were analyzed further with JMP statistical software to perform Shapiro-Wilk, Spearman’s correlation, Wilcoxon signed-rank, and regression analyses. Results: The Ella instrument resulted in significantly lower CV values, confirming that it is more precise and reliable than manual ELISA methods. There was a moderate correlation between ELISA and Ella measurements (r = 0.49, p < 0.0001), but a Wilcoxon signed-rank test revealed that serum gaelectin-3 measurements obtained with the Ella instrument were significantly lower compared to those obtained with manual ELISA, with a mean difference of −5.19 ng/mL (p < 0.0001). Regression analysis showed a significant increase in the difference between manual ELISA and Ella measurements as serum galectin-3 levels increase (p < 0.0001). This difference in measurements between manual and automated ELISA techniques remained consistent when analyses were performed within each breast cancer stage, immunophenotype, and histology. Conclusions: While the Ella instrument is a fast and reliable tool, the discrepancies between manual ELISA and the Ella instrument in quantifying serum galectin-3 levels are important to consider prior to widespread use. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disease with heterogeneous clinical manifestations and uncertain systemic immune involvement. This study aimed to characterize peripheral immune profiles and circulating tumor markers in women with ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE), and to explore their associations with disease severity, symptom burden, and physical health perception. Peripheral blood leukocyte subsets, plasma cytokines, and tumor markers (CA125, CA19-9, CEA, HE4) were analyzed in 146 patients and 50 healthy controls. OE was associated with increased monocyte counts and reduced neutrophil proportions, while DIE showed elevated levels of IL-8 and Galectin-1. IL-33 levels correlated negatively with the revised American Society for Reproductive Medicine (rASRM) scores and positively with neutrophil proportion, suggesting a role in systemic immune regulation. Tumor marker levels varied by subtype: CA19-9 was higher in OE, and CEA in DIE. CA125 correlated with disease severity, and CEA with monocyte levels. Exploratory heatmaps revealed consistent immune-tumor associations linked to anatomical severity and symptom profiles. Although exploratory, these findings highlight the presence of distinct systemic immune patterns in endometriosis and support the potential of integrative blood-based biomarkers for future diagnostic and stratification strategies. Full article

Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and contextual interpretation often hinder optimal management. This narrative review synthesizes the current evidence on established and emerging biomarkers in CRS, with emphasis on their clinical relevance, integration into real-world practice, and potential to inform precision therapy. Markers of glomerular filtration rate beyond creatinine—such as cystatin C—offer more accurate assessment in frail or sarcopenic patients, while tubular injury markers such as NGAL, KIM-1, and urinary L-FABP (uL-FABP) provide early signals of structural renal damage. The FDA-approved NephroCheck^® test—based on TIMP-2 and IGFBP7— enables risk stratification for imminent AKI up to 24 h before functional decline. Congestion-related markers such as CA125 and bio-adrenomedullin outperform natriuretic peptides in certain CRS phenotypes, particularly in right-sided heart failure or renally impaired patients. Fibrosis and inflammation markers (galectin-3, sST2, GDF-15) add prognostic insights, especially when combined with NT-proBNP or troponin. Rather than presenting biomarkers in isolation, this review proposes a framework that links them to specific clinical contexts—such as suspected decongestion-related renal worsening or persistent congestion despite therapy—to support actionable interpretation. A tailored, scenario-based, multi-marker strategy may enhance diagnostic precision and treatment safety in CRS. Future research should prioritize prospective biomarker-guided trials and standardized pathways for clinical integration. Full article

Galectins represent a family of widely expressed lectins that have the ability to bind β-galactoside in modulating “cell-to-cell” and “cell-to-matrix” interactions in all organisms. These proteins are expressed in many inflammatory cells, such as macrophages, and depending on the inflammatory environment, they promote pro-inflammatory or anti-inflammatory responses. Galectin-3 (Gal-3) is predominantly located in the cytoplasm, but, as noted, it has also been detected in the nucleus, on the cell surface and in the extracellular environment, which indicates the multifunctionality of this molecule. It has been shown in many studies that Gal-3 is involved in immune regulation, fibrosis, and tissue remodeling, making it an important player in disorders such as inflammatory bowel disease (IBD), non-alcoholic steatohepatitis (NASH), and liver fibrosis. In IBD, this protein is associated with activation of the NLRP3 inflammasome, contributing to chronic intestinal inflammation. Also, in primary biliary cholangitis and autoimmune hepatitis, Gal-3 potentiate development of fibrosis through fibroblast-to-myofibroblast transition and extracellular matrix deposition, while in liver fibrosis, it is upregulated in hepatic stellate cells and macrophages, promoting fibrosis and inflammation. Studies show that Gal-3 inhibition reduces fibrosis and inflammation, making it a promising therapeutic target. Full article

Obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVDs) represent major global health burdens with overlapping pathophysiological mechanisms, including chronic low-grade inflammation, oxidative stress, and gut microbiota dysbiosis. Galectins, a family of β-galactoside-binding lectins, have been implicated in immune regulation, inflammation, and tissue remodeling. Among them, Galectin-4 (Gal-4), primarily expressed in the gastrointestinal tract, has emerged as a potential biomarker due to its roles in epithelial integrity, inflammatory signaling, and metabolic regulation. Despite its established involvement in cancer and inflammatory disease, the relevance of Gal-4 in cardiometabolic disorders remains poorly defined. A comprehensive literature search was conducted via the PubMed and ScienceDirect databases. The association between Gal-4 and obesity has been reported, indicating that elevated Gal-4 levels correlate with obesity, but primarily in individuals with diabetes. Circulating Gal-4 concentrations are consistently elevated in diabetic populations. In CVD, elevated Gal-4 levels are associated with ischemic heart disease, heart failure, aortic stenosis, carotid atherosclerosis, and adverse outcomes following myocardial infarction and stroke. Furthermore, prospective studies link Gal-4 to increased risk of cardiovascular events and mortality, underscoring its potential prognostic relevance. Available evidence regarding the mechanistic role of Gal-4 in the pathogenesis of obesity, diabetes, and cardiovascular disease remains limited; therefore, future studies should address whether Gal-4 actively contributes to cardiometabolic dysfunction or only reflects secondary inflammatory or fibrotic processes. Elucidating the biological functions of Gal-4 may provide insight into its utility in diagnostics and support the development of novel therapeutic strategies for cardiometabolic disorders. Full article

Background: Anthracycline-based chemotherapy, while highly effective for breast cancer, poses a significant risk for chemotherapy-related cardiac dysfunction (CTRCD), mainly determined by left ventricular ejection fraction (LVEF) reduction. Objectives: We aimed to evaluate the diagnostic utility of speckle tracking analysis (STA) and Diastolic Stress Test Echocardiography (DSTE) for the early detection of cardiac dysfunction either CTRCD or heart failure with preserved ejection fraction (HFpEF) in women undergoing chemotherapy for breast cancer and developed exertional dyspnea and/or fatigue during follow-up. Methods: In this prospective case–control study, 133 women receiving anthracycline-based chemotherapy (with or without anti-HER2 therapy) (chemotherapy group-CTG) and 65 age-matched healthy women as the control group (CG) underwent resting echocardiographic assessment, including LVEF, global longitudinal strain (GLS), myocardial work indices, biomarkers assay (NT-proBNP, troponin, galectin-3) and DSTE at baseline. That assessment was repeated after 12 months in CTG. Results: In this prospective case—control study, 133 women receiving anthracycline-based chemotherapy (with or without anti-HER2 therapy) were included. Based on the presence of CTRCD, they were further subdivided into a CTRCD subgroup (n = 37) and a CTRCD-free subgroup (n = 88). At the end of this study, CTG showed worse values of LVEF, GLS, myocardial work indices than baseline and CG (p < 0.05). Subgroup comparison (CTRCD vs. CTRCD-free) showed significant impairment in LVEF (53.60% vs. 62.60%, p < 0.001), GLS (–16.68% vs. −20.31%, p < 0.001), DSTE-derived tricuspid regurgitation maximum velocity (TRVmax) (3.05 vs. 2.31 m/s, p < 0.001) and elevated biomarkers (NT-proBNP: 200.06 vs. 61.49 pg/mL; troponin: 12.42 vs. 3.95 ng/L, p < 0.001) in the former subgroup. Regression analysis identified GLS, NT-proBNP, troponin, and TRVmax as independent predictors of CTRCD. Notably, a subgroup of CTRCD-free patients (n = 16) showed a high probability for HFpEF based on the HFA-PEFF score, with elevated GLS, NT-proBNP and DSTE-derived TRVmax compared to the rest of CTRCD-free patients and the CG (p < 0.001). Conclusions: STA and DSTE significantly outperform conventional LVEF in detecting subclinical cardiac dysfunction among women with breast cancer receiving chemotherapy. The combination of novel echocardiographic techniques and biomarkers may enable the detection of early CTRCD, including the under-estimated presence of HFpEF among breast cancer women with HF symptoms. Full article

Background/Objectives: Diabetic cardiomyopathy (DBCM) is characterized by cardiac dysfunction in the absence of ischemic heart disease, hypertension, or valvular disease, often manifesting as heart failure with preserved ejection fraction (HFpEF). Early recognition of DBCM is clinically important, as it enables timely initiation of tailored therapies and may slow down the progression to overt heart failure with reduced ejection fraction (HFrEF). This study aimed to evaluate the diagnostic utility of advanced echocardiographic techniques—myocardial work (MW), diastolic stress echocardiography (DSTE), Cardio-Ankle Vascular Index (CAVI)—and selected serum biomarkers in identifying DBCM. Methods: In this prospective observational study with 12-month follow-up, 125 diabetic patients with preserved ejection fraction and symptoms of HF or recent HF hospitalization were enrolled. Using the Heart Failure Association Pre-test Probability of HFpEF criteria, 37 were classified as DBCM-HFpEF and 88 as diabetic controls. An additional 47 age- and sex-matched non-diabetic individuals served as controls. All participants underwent resting echocardiography (MW, GLS), DSTE, CAVI assessment, and biomarker measurement (BNP, troponin, galectin-3). Results: Compared to non-diabetics, diabetic patients had significantly higher TRVmax (2.21 vs. 2.05 m/s), LAVI (39.70 vs. 33.50 mL/m²), E/e′ (8.64 vs. 7.59), CAVI (8.51 vs. 7.82 m/s), BNP (91.50 vs. 35.10 pg/mL), and troponin (3.94 vs. 2.43 ng/mL) (all p < 0.01), while galectin-3 levels showed no significant difference between groups. Differences were more pronounced between DBCM and No-DBCM diabetic groups. Multivariate analysis identified BNP (OR 5.45), TRVmax (OR 8.56), and CAVI (OR 1.91) as independent predictors of DBCM. Conclusions: DSTE and CAVI, alongside BNP and echocardiographic parameters, may provide valuable noninvasive tools for the early detection of DBCM in diabetic patients presenting with otherwise unexplained dyspnea, potentially enabling earlier intervention and improved outcomes. This is clinically important guiding an efficient management of an increasing number of diabetic patients presented with unexplained dyspnea. Full article

In malignant-type gastric cancer, peritoneal dissemination is the most frequent metastatic process and is an inoperable condition for which effective treatment is lacking. Our research has revealed that galectin-4 plays an important role in the peritoneal metastasis of gastric cancer cells. Based on this, we hypothesized that inhibiting galectin-4 could suppress peritoneal metastasis. The inhibitory activity towards galectin-4 binding was evaluated using an enzyme-linked immunosorbent assay, while the suppressive effect on gastric cancer cell proliferation was assessed using an adenosine triphosphate-based cell viability assay. Direct binding to galectin-4 was examined by surface plasmon resonance analysis. Chemically synthesized fucoidan analogs exhibited significant suppressive activity against the proliferation of gastric cancer cells, partly via a galectin-4-mediated pathway. Among the 13 fucoidan analogs tested, analog 10, whose sugar chains composed of repeating 2,3-O-sulfated α(1,4)-linked L-fucose, showed significant inhibitory activity against galectin-4 binding and cell proliferation. 14, the cholestanol-conjugated analog 10, exhibited a pronounced increase in inhibitory activity, consistent with potential multimerization. Molecular docking and site-directed mutagenesis studies revealed that Arginine-45 in galectin-4 is important for binding to fucoidan analogs. In conclusion, fucoidan analogs with a strong affinity for galectin-4 are promising candidates for inhibiting the peritoneal metastasis of galectin-4-positive gastric cancer cells. Full article

Background/Objectives: Familial Mediterranean fever (FMF) is the most common hereditary autoinflammatory syndrome, characterized by recurrent fever attacks and serositis. Galectin-3, a β-galactoside-binding lectin involved in inflammation and fibrosis, and presepsin, an established biomarker for bacterial infection and sepsis, have emerged as potential biomarkers for improving diagnostic and prognostic accuracy in autoinflammatory diseases. However, their use in FMF patients is not sufficiently evaluated. This study aims to compare serum galectin-3 and presepsin levels in children with FMF and healthy controls and assess their correlations with conventional acute-phase reactants. Methods: This prospective cross-sectional study included 74 children with confirmed FMF during attack-free periods and 67 age- and gender-matched healthy controls. Clinical and genetic characteristics, complete blood count, C-reactive protein (CRP), serum amyloid-A (SAA), and erythrocyte sedimentation rate (ESR) were recorded. Serum galectin-3 and presepsin levels were measured. Group comparisons and correlation analyses were performed using appropriate statistical tests. Results: Median serum galectin-3 and presepsin was significantly higher in FMF patients than controls (p < 0.001). ESR was significantly higher in FMF patients (p < 0.001), while CRP and SAA showed no significant differences. Correlation analysis revealed a strong positive correlation between galectin-3 and presepsin (r = 0.860, p < 0.001) in FMF patients, with neither correlating with other acute-phase reactants. Conclusions: Galectin-3 and presepsin were found to serve as novel biomarkers reflecting alternative inflammatory pathways in FMF, even during remission. These results, obtained during the attack-free period, indicate the need for further studies to determine the relationship between galectin-3 and presepsin levels and disease activity in FMF. Full article

Galectin-1 and -9 (Gal1/9) are essential mediators of immune-inflammatory responses, which makes these proteins potential biomarkers for immune-mediated diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis (PS), psoriatic arthritis (PsA), inflammatory bowel disease, and systemic lupus erythematosus (SLE). Our aim was to evaluate plasma Gal1/9 differences between IMID patients and healthy donors (HD). We analyzed 980 plasma samples divided into two analytical cohorts (600 discovery group and 380 validation group). Generalized linear models estimated Gal1/9 levels, adjusting for sex, age, storage time, and plate variability. In the overall IMID group, plasma Gal1 levels were comparable to those of HD, while Gal9 levels were significantly elevated. Levels varied across individual diseases: SLE patients consistently showed the highest Gal1/9 levels compared to both HD and other IMIDs, and RA patients had elevated Gal9 levels versus HD. Both Gal1 and Gal9 plasma levels correlated positively with higher disease activity, and Gal1 was higher in patients with longer disease duration. After adjustment for these confounders, SLE and RA patients maintained the highest Gal9 levels compared to HD. Our study demonstrates that Gal1 and Gal9 are differentially expressed across IMIDs, with particularly elevated levels in SLE, and both galectins are associated with disease activity. Full article

Right ventricular (RV) dysfunction is common and linked to poor outcomes across conditions such as heart failure (HF), acute coronary syndromes, pulmonary embolism, and pulmonary hypertension. While imaging, electrocardiogram (ECG), and invasive tests remain central to RV assessment, circulating biomarkers offer a rapid, non-invasive, and reliable alternative. These biomarkers reflect key pathophysiological processes, including myocardial injury, stress, fibrosis, inflammation, congestion, and multiorgan involvement. High-sensitivity troponins and natriuretic peptides (BNP, NT-proBNP) are already widely used, while emerging biomarkers—such as CA125, copeptin, galectin-3, and others—may enhance diagnostic accuracy and risk stratification. Some, like CA125 and NT-proBNP, have shown promise in guiding post-discharge therapy. However, challenges remain regarding the specificity of biomarkers for RV dysfunction and their role across different clinical contexts. This review provides an integrated overview of RV dysfunction, with a focus on the diagnostic and therapeutic potential of both established and novel biomarkers. Full article

Lichen sclerosus (LS) is a chronic, relapsing skin disease that predominantly affects the perineal and genital regions, although extragenital manifestations can occur. Despite its significant impact on patients’ quality of life, particularly affecting sexual and urinary function, LS remains underdiagnosed. Multiple factors, including genetic predisposition, hormonal changes, immunological abnormalities, trauma, and urine irritation, contribute to its development and persistence. This review aims to clarify the complex pathophysiology of LS by exploring three main mechanisms: autoimmune dysregulation, sclerotic tissue formation, and oxidative stress. Autoimmune dysregulation involves T-cell infiltration and the roles of miR-155 and extracellular matrix protein 1 dysfunction, leading to chronic inflammation. miR-155 contributes to sclerotic tissue formation alongside galectin-7, promoting fibroblast proliferation and collagen synthesis. Oxidative stress results in tissue damage, autoimmunity, chronic inflammation, and an increased risk of carcinogenesis. Understanding these mechanisms is crucial for developing targeted therapies and improving LS management. Further research is needed to unravel the genetic basis, immune responses, and interactions between key mediators, ultimately advancing innovative therapeutic strategies and precision medicine in LS. Full article

Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. In contrast, HPV-negative tumours typically have a worse prognosis and are often linked to mutations in tumour suppressor genes. HNSCCs exist within a complex environment known as the tumour microenvironment (TME). The TME includes tumour cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM), blood vessels, and various signalling molecules. These components support tumour progression, invasion, metastasis, and resistance to treatment. Intercellular signalling within the TME—mediated by cytokines such as IL-6, TGF-b, and galectins—further promotes tumour growth and systemic effects like cachexia. Notably, the TME shares features with granulation tissue during wound healing, supporting the concept of cancer as a chronic, non-resolving wound. Effective therapy must target not only tumour cells but also the dynamic TME. Full article