Search Results (727)

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

Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p < 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p < 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p < 0.05), and between RRI and suPAR (r = 0.331, p < 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients. Full article

Aedes aegypti, a crucial vector mosquito that transmits many diseases that cause millions of deaths worldwide, can be controlled with Bacillus thuringiensis subsp. israelensis (Bti). The larvicidal activity of Bti against Ae. aegypti is due primarily to Cry4Aa, Cry4Ba, and Cry11Aa, and Cyt1Aa, a protein that synergizes the activity of the Cry proteins. Interestingly, Galectins-6 and Galectins-14, members of a family of β-galactoside-binding proteins that play a role in immune responses insects, have been shown to decrease the activity of Bti toxins. The activity of other Galectins, particularly Galectin-8A, against the Cry proteins is not known. Toward this end, we cloned the gene coding for galactin-8A and expressed the recombinant protein and purified protein. The bioassay results indicated that Galectin-8A can also reduce the toxicity of Cry11Aa, but it was much stronger than Galectin-6. To investigate the interactions among Galectin-8A, Cry11Aa, and toxin receptors, Octet Red System analysis, Western blot, far-Western blot, and ELISA assay were also performed. The Octet Red System result showed that Galectin-8A could also bind to BBMVs of Ae. aegypti, with a lower kDa value than that of Galectin-6, indicating that Galectin-8A had a stronger binding affinity to BBMVs than Galectin-6. Western blot, far-Western blot, and ELISA assay analyses also demonstrated that Galectin-8A bound to Ae. aegypti receptor ALP1 and APN2, consistent with the protein docking simulation results. These findings support the conclusion that Galectin-8A blocks with ALP1 and APN2 more effectively than Galectin-6, which may subsequently reduce the toxicity of Cry11Aa in Ae. aegypti. Full article

Doxorubicin (Dox) is not a first-line treatment for melanoma due to limited antitumor efficacy and dose-dependent cardiotoxicity. However, sublethal doses may trigger adaptive cellular responses that influence tumor progression and systemic toxicity. Small extracellular vesicles (EVs) are key mediators of intercellular communication and can carry bioactive molecules that modulate both the tumor microenvironment and distant tissues. This study investigates how sublethal Dox exposure alters EV biogenesis and cargo in A375 melanoma cells and explores the potential implications for cardiovascular function. We treated human A375 melanoma cells with 10 nM dox for 96 h. EVs were isolated using differential ultracentrifugation and size exclusion chromatography. Vesicle characterization included Immunocytochemistry for CD63, CD81, CD9, Rab7 and TSG101, scanning electron microscopy (SEM) Nanoparticle Tracking Analysis (NTA), and Western blotting for CD81 and CytC. We analyzed cytokine content using cytokine membrane arrays. Guinea pig cardiomyocytes were exposed to the isolated vesicles, and mitochondrial activity was evaluated using the MTT assay. Statistical analysis included t-tests, ANOVA, Cohen’s d, and R² and η². Dox exposure significantly increased EV production (13.6-fold; p = 0.000014) and shifted vesicle size distribution. CD81 expression was significantly upregulated (p = 0.0083), and SEM (microscopy) confirmed enhanced vesiculation. EVs from treated cells were enriched in TGF-β (p = 0.0134), VEGF, CXCL1, CXCL12, CCL5, IL-3, IL-4, IL-10, Galectin-3, and KITLG. Cardiomyocytes exposed to these vesicles showed a 2.3-fold reduction in mitochondrial activity (p = 0.0021), an effect absent when vesicles were removed. Bioinformatic analysis linked EV cargo to pathways involved in cardiac hypertrophy, inflammation, and fibrosis. As conclusion, sublethal Doxorubicin reprograms melanoma-derived EVs by enhancing their production and enriching their cargo with profibrotic and immunomodulatory mediators. These vesicles may contribute to tumor progression and cardiovascular physiopathology, suggesting that targeting EVs could improve therapeutic outcomes in cancer and cardiovascular disease. Full article

We investigated the impact of liver damage on systemic inter-organ communication in an extensive observational case–control study of 923 patients with severe obesity and biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH) undergoing bariatric surgery. Using a comprehensive panel of circulating organokines, including fibroblast growth factor (FGF) 19, FGF21, adiponectin, galectin-3, irisin, and leptin, along with choline metabolites, we characterized metabolic signaling patterns associated with liver disease severity. Compared to controls, patients with MASLD/MASH exhibited significantly lower levels of FGF19, choline, and trimethylamine, while FGF21, galectin-3, irisin, and leptin were elevated. Sex-specific alterations in leptin and adiponectin were observed in patients with severe obesity but not in controls. Network analysis revealed a complex and individualized interplay among organokines, shaped by age, sex, and anthropometric factors. Despite this complexity, a dysregulation of the FGF21–adiponectin axis was associated with more advanced liver involvement. The large cohort and comprehensive organokine profiling studied provide valuable insights into the role of the FGF21–adiponectin axis on systemic metabolic alterations in severe obesity and their potential clinical implications. Full article

Surgery and anesthesia induce a stress response that provokes increased sympathetic stimulation, secretion of cortisol, hypercoagulability, and systemic inflammatory response. All these homeostatic deteriorations, especially systemic inflammation, represent a risk for organ damage. Perioperative cardiac complications have an increasing impact on morbidity and mortality, not only in cardiovascular but also in non-cardiac surgery. Surgical procedures represent a potential trigger for systemic inflammation that causes secretion of proinflammatory cytokines, activation of neutrophils, and tissue damage. Also, increased levels of preoperative inflammatory markers predict perioperative cardiovascular events. Systemic inflammatory biomarkers increase during the first days after surgical procedures and decline within a few weeks. Besides contemporary traditional biomarkers (CRP, BNP), newer biomarkers, such as galectin-3, TNF-α, and various MiRNAs, can predict inflammatory response and related cardiac injury. Determination of inflammatory markers in the perioperative period could help identify patients at risk for cardiovascular events. The reduction in perioperative inflammatory response may improve surgical outcomes. Prevention and treatment of systemic inflammation can be achieved by optimization of surgical procedures, anesthetic regimen, and pharmacological agents, especially interleukin inhibitors. Determination of inflammatory biomarkers, along with prevention and treatment of inflammation, can improve perioperative cardiac risk reduction strategies. Full article