ABSTRACT
Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Galectins , Mutation , Humans , Breast Neoplasms/genetics , Breast Neoplasms/blood , Breast Neoplasms/pathology , Female , Galectins/genetics , Galectins/blood , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Galectin 1/genetics , Galectin 1/blood , Middle Aged , Galectin 3/genetics , Galectin 3/blood , Adult , Blood ProteinsABSTRACT
OBJECTIVES: Experimental studies indicate a role for galectin-1 and galectin-3 in metabolic disease, but clinical evidence from larger populations is limited. METHODS: We measured circulating levels of galectin-1 and galectin-3 in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study, participants (n = 502, all aged 50 years) and characterized the individual association profiles with metabolic markers, including clinical measures, metabolomics, adipose tissue distribution (Imiomics) and proteomics. RESULTS: Galectin-1 and galectin-3 were associated with fatty acids, lipoproteins and triglycerides including lipid measurements in the metabolomics analysis adjusted for body mass index (BMI). Galectin-1 was associated with several measurements of adiposity, insulin secretion and insulin sensitivity, while galectin-3 was associated with triglyceride-glucose index (TyG) and fasting insulin levels. Both galectins were associated with inflammatory pathways and fatty acid binding protein (FABP)4 and -5-regulated triglyceride metabolic pathways. Galectin-1 was also associated with several proteins related to adipose tissue differentiation. CONCLUSIONS: The association profiles for galectin-1 and galectin-3 indicate overlapping metabolic effects in humans, while the distinctly different associations seen with fat mass, fat distribution, and adipose tissue differentiation markers may suggest a functional role of galectin-1 in obesity.
Subject(s)
Galectin 1 , Galectin 3 , Humans , Galectin 1/blood , Galectin 1/metabolism , Middle Aged , Male , Cross-Sectional Studies , Female , Galectin 3/blood , Galectin 3/metabolism , Prospective Studies , Obesity/metabolism , Obesity/blood , Blood Proteins/metabolism , Biomarkers/blood , Biomarkers/metabolism , Metabolomics/methods , Insulin Resistance/physiology , Galectins/metabolism , Galectins/blood , Adipose Tissue/metabolism , Body Mass Index , MultiomicsABSTRACT
PURPOSE: The number of studies conducted on the role of neuroinflammation in the etiopathogenesis of bipolar disorder has been increasing in recent years. The role of Galectin-1, Galectin-9, and YKL-40, which are considered to play roles in neuroinflammation and the etiopathogenesis of bipolar disorder, and the relationship of these parameters with cognitive functions were investigated in the present study. METHOD: Serum Galectin-1, Galectin-9, and YKL-40 levels were measured with the ELISA Method in 64 bipolar euthymic patients and 64 healthy controls. The Stroop and trail-making tests were administered to assess cognitive functions in all participants. RESULTS: Serum Galectin-1, Galectin-9, and YKL-40 levels were statistically and significantly lower in the patient group when compared to the healthy control group. The scores of the Stroop test and trail-making tests were statistically higher in the patient group than in the healthy control group. There was a weak and positive correlation between serum Galectin-1, Galectin-9, and YKL-40 levels and cognitive performance in all participants. DISCUSSION AND CONCLUSION: Statistically significant low levels of serum Galectin-1, Galectin-9, and YKL-40 detected in the patient group suggest that these parameters have important roles in neuroinflammation. The statistically higher Stroop and trail-making test scores of the patient group compared to the control group indicates that the cognitive performance of the patient group was weaker. Also, the positive correlation between Galectin-1, Galectin-9, and YKL-40 levels and cognitive performance suggests that these molecules may have a neuroprotective role. We think that the present study will contribute to this field where there is very limited data in the literature.
Subject(s)
Bipolar Disorder , Chitinase-3-Like Protein 1 , Cognition , Galectin 1 , Galectins , Humans , Bipolar Disorder/blood , Bipolar Disorder/psychology , Chitinase-3-Like Protein 1/blood , Galectin 1/blood , Neuroinflammatory Diseases , Neuropsychological Tests , Galectins/bloodABSTRACT
A new virus from the group of coronaviruses was identified as the cause of atypical pneumonia and called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and disease called Corona Virus Disease (COVID-19). During the cytokine storm, the main cause of the death, proinflammatory cytokines are released which stimulate further tissue destruction. Galectin-1 (Gal-1) is a pleiotropic cytokine involved in many immune and inflammatory processes and its role in COVID-19 is still unknown. The aim of this study was to determine systemic values of Gal-1 and correlations between Gal-1 and proinflammatory cytokines and clinical parameters during COVID-19 progression. This is observational and cross-sectional study. 210 COVID-19 patients were included and divided into mild, severe or critical group according to COVID-19 severity. Serum levels of IL-1ß, IL-6, IL-10, IL-23, IL-33 and Gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Systemic levels of IL-1ß, IL-6, IL-10, IL-23, IL-33 and Gal-1 were significantly higher in stage III of COVID-19 patients compared to stage I and II. There were no significant differences in the ratio between Gal-1 and IL-10 with proinflammatory cytokines. Positive correlation was detected between Gal-1 and IL-1ß, IL6, IL-10, IL-23 and IL-33. Gal-1 positively correlated with chest radiographic finding, dry cough and headache and negatively correlated with normal breathing sound. Linear regression model and ROC curve analysis point on Gal-1 as significant predictor for COVID-19 severity. Presented results implicate on Gal-1 and IL-10 dependent immunomodulation. The precise mechanism of Gal-1 effect in COVID-19 and its potential as a stage marker of disease severity is still to be clarified.
Subject(s)
COVID-19/blood , Galectin 1/blood , SARS-CoV-2/metabolism , Biomarkers/blood , COVID-19/diagnosis , Cytokines/blood , Female , Humans , Male , Middle Aged , Prognosis , Severity of Illness IndexABSTRACT
AIM: There is an urgent need to set up a useful biomarker for ovarian cancer. Galectin-1 is a promising carbohydrate-binding protein which plays a remarkable role in various malignancies yet its clinical significance is questionable. In this study, we have tested the clinical implications of serum Galectin-1 levels in patients with ovarian tumours. MAIN METHODS: Serum Galectin-1 levels were quantified in 84 newly diagnosed ovarian tumour patients and 20 healthy controls by Enzyme Linked Immuno Sorbent Assay during the course of the disease. Therefore the samples were taken at diagnosis, after surgery and after chemotherapy. KEY FINDINGS: The Galectin-1 levels were found to be associated with various variables of Ovarian Cancer patients. The levels were found to be prominently high in postmenopausal patients. Galectin-1 levels were raised in epithelial ovarian tumours with significantly high levels in serous subtype. A decrease in Galectin-1 levels post-surgical intervention and after receiving chemotherapy was found. Galectin-1 levels evidently distinguished between normal, benign, malignant and metastatic cases as compared to CA125 levels. Galectin-1 demonstrated to be a better biomarker than CA125 according to the Receiver Operating Characteristic (ROC) curve analysis. SIGNIFICANCE: The study emphasizes that serum Galectin-1 may serve as a better surrogate biomarker in Ovarian Cancer for early detection, discriminating between malignant and benign abdominal masses and monitoring the progression of the disease and response to treatment.
Subject(s)
Galectin 1/blood , Ovarian Neoplasms/blood , Adolescent , Adult , Aged , Biomarkers, Tumor/blood , Female , Humans , Middle Aged , Young AdultABSTRACT
It is important to determine the inflammatory biomarkers in the severity of coronavirus disease 2019 (COVID-19) with the emergence of the pandemic. Galectins and prostaglandins play important roles in the regulation of immune and inflammatory responses. Therefore, this study aimed to investigate Galectin-1 (Gal-1), Galectin-3 (Gal-3), and prostaglandin E2 (PGE2) levels in patients with COVID-19. Serum concentrations of Gal-1, Gal-3, and PGE2 were measured using enzyme-linked immunosorbent assay on 84 patients with COVID-19 (severe = 29 and nonsevere = 55) and 56 healthy controls. In this study, increased levels of Gal-1 (median, 9.86, 6.35, and 3.67 ng/mL), Gal-3 (median, 415.31, 326.33, and 243.13 pg/mL), and PGE2 (median, 193.17, 192.58, and 124.62 pg/mL) levels were found in patients with COVID-19 than in healthy controls (P < 0.001 for all). In the severe disease group, Gal-3 levels were higher, while no differences were noted in Gal-1 and PGE2 levels (P = 0.011, P = 0.263, and P = 0.921, respectively). Serum levels of Gal-1 were positively correlated with those of Gal-3 (P = 0.871 and P < 0.001). Gal-3, C-reactive protein, lymphocyte count, and age were found as independent predictors of disease severity (P = 0.002, P = 0.001, P = 0.007, and P = 0.003, respectively). With the emergence of effective drug needs in the COVID-19 pandemic, differentiation of severe disease is important. Therefore, Gal-3 could be a potential prognostic biomarker of COVID-19.
Subject(s)
COVID-19 , Dinoprostone/blood , Galectin 1/blood , Galectin 3/blood , Biomarkers/blood , COVID-19/blood , Case-Control Studies , Humans , PandemicsABSTRACT
Tropheryma whipplei, is an actinobacterium that causes different infections in humans, including Whipple's disease. The bacterium infects and replicates in macrophages, leading to a Th2-biased immune response. Previous studies have shown that T. whipplei harbors complex surface glycoproteins with evidence of sialylation. However, the exact contribution of these glycoproteins for infection and survival remains obscure. To address this, we characterized the bacterial glycoprofile and evaluated the involvement of human ß-galactoside-binding lectins, Galectin-1 (Gal-1) and Galectin-3 (Gal-3) which are highly expressed by macrophages as receptors for bacterial glycans. Tropheryma whipplei glycoproteins harbor different sugars including glucose, mannose, fucose, ß-galactose and sialic acid. Mass spectrometry identification revealed that these glycoproteins were membrane- and virulence-associated glycoproteins. Most of these glycoproteins are highly sialylated and N-glycosylated while some of them are rich in poly-N-acetyllactosamine (Poly-LAcNAc) and bind Gal-1 and Gal-3. In vitro, T. whipplei modulates the expression and cellular distribution of Gal-1 and Gal-3. Although both galectins promote T. whipplei infection by enhancing bacterial cell entry, only Gal-3 is required for optimal bacterial uptake. Finally, we found that serum levels of Gal-1 and Gal-3 were altered in patients with T. whipplei infections as compared to healthy individuals, suggesting that galectins are also involved in vivo. Among T. whipplei membrane-associated proteins, poly-LacNAc rich-glycoproteins promote infection through interaction with galectins. T. whipplei modulates the expression of Gal-1 and Gal-3 both in vitro and in vivo. Drugs interfering with galectin-glycan interactions may provide new avenues for the treatment and diagnosis of T. whipplei infections.
Subject(s)
Blood Proteins/metabolism , Galectin 1/metabolism , Galectins/metabolism , Tropheryma/pathogenicity , Whipple Disease/metabolism , Bacterial Proteins/metabolism , Galactose/metabolism , Galectin 1/blood , Galectins/blood , Glycoproteins/metabolism , Glycosylation , Humans , Macrophages/metabolism , Macrophages/microbiology , Polysaccharides, Bacterial/metabolism , Tropheryma/metabolism , Virulence , Whipple Disease/microbiologyABSTRACT
Inflammatory caspase sensing of cytosolic lipopolysaccharide (LPS) triggers pyroptosis and the concurrent release of damage-associated molecular patterns (DAMPs). Collectively, DAMPs are key determinants that shape the aftermath of inflammatory cell death. However, the identity and function of the individual DAMPs released are poorly defined. Our proteomics study revealed that cytosolic LPS sensing triggered the release of galectin-1, a ß-galactoside-binding lectin. Galectin-1 release is a common feature of inflammatory cell death, including necroptosis. In vivo studies using galectin-1-deficient mice, recombinant galectin-1 and galectin-1-neutralizing antibody showed that galectin-1 promotes inflammation and plays a detrimental role in LPS-induced lethality. Mechanistically, galectin-1 inhibition of CD45 (Ptprc) underlies its unfavorable role in endotoxin shock. Finally, we found increased galectin-1 in sera from human patients with sepsis. Overall, we uncovered galectin-1 as a bona fide DAMP released as a consequence of cytosolic LPS sensing, identifying a new outcome of inflammatory cell death.
Subject(s)
Alarmins/metabolism , Endotoxemia/immunology , Galectin 1/metabolism , Inflammation Mediators/metabolism , Inflammation/immunology , Intracellular Signaling Peptides and Proteins/metabolism , Macrophages/metabolism , Phosphate-Binding Proteins/metabolism , Adult , Aged , Aged, 80 and over , Alarmins/deficiency , Alarmins/genetics , Animals , Case-Control Studies , Disease Models, Animal , Endotoxemia/chemically induced , Endotoxemia/metabolism , Endotoxemia/pathology , Female , Galectin 1/blood , Galectin 1/deficiency , Galectin 1/genetics , HeLa Cells , Humans , Inflammation/chemically induced , Inflammation/metabolism , Inflammation/pathology , Intracellular Signaling Peptides and Proteins/deficiency , Intracellular Signaling Peptides and Proteins/genetics , Leukocyte Common Antigens/metabolism , Lipopolysaccharides , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Necroptosis , Phosphate-Binding Proteins/deficiency , Phosphate-Binding Proteins/genetics , RAW 264.7 Cells , Sepsis/blood , Sepsis/diagnosis , Signal Transduction , Up-RegulationABSTRACT
BACKGROUND: This study aims to investigate galectin-1 (Gal-1) expression in the serum and placenta of pregnant women with fetal growth restriction (FGR) and its significance. METHODS: Thirty-one pregnant women with single-birth FGR but without comorbidities, eight pregnant women with FGR and preeclampsia (PE), and eight pregnant women with FGR and gestational diabetes mellitus (GDM) were enrolled as the study group, while 20 pregnant women with normal singleton pregnancy in the same period were enrolled as the control group. The serum Gal-1 level was detected using an enzyme-linked immunosorbent assay (ELISA), and Gal-1 expression in the placenta was detected by western blot. RESULTS: The results revealed that, compared with the control group, the serum Gal-1 level decreased in the women with FGR without comorbidities, and the difference was statistically significant (P < 0.001). Compared with the control group, the difference in serum Gal-1 expression in the FGR-PE group was not statistically significant (P = 0.29). The peripheral serum Gal-1 level decreased in the FGR-GDM group compared with the control group, and the difference was statistically significant (P < 0.001). The serum Gal-1 level was positively correlated with birth weight (r2 = 0.172, P < 0.01). Compared with the control group, the Gal-1 expression level decreased in the placenta of the pregnant women with FGR without comorbidities (P < 0.05). CONCLUSIONS: Gal-1 exhibits low expression in the serum and placenta of pregnant women with FGR. In addition, Gal-1 may be involved in the pathogenesis of FGR and could represent a new diagnostic marker of the disease.
Subject(s)
Fetal Growth Retardation/metabolism , Galectin 1/analysis , Galectin 1/blood , Placenta/chemistry , Adult , Comorbidity , Diabetes, Gestational/epidemiology , Female , Fetal Growth Retardation/epidemiology , Humans , Infant, Newborn , Pre-Eclampsia/epidemiology , PregnancyABSTRACT
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a vascular degenerative disease causing sudden rupture of aorta and significant mortality in elders. Nevertheless, no prognostic and therapeutic target is available for disease management. Gal-1 (galectin-1) is a ß-galactoside-binding lectin constitutively expressed in vasculature with roles in maintaining vascular homeostasis. This study aims to investigate the potential involvement of Gal-1 in AAA progression. Approach and Results: Gal-1 was significantly elevated in circulation and aortic tissues of Ang II (angiotensin II)-infused apoE-deficient mice developing AAA. Gal-1 deficiency reduced incidence and severity of AAA with lower expression of aortic MMPs (matrix metalloproteases) and proinflammatory cytokines. TNFα (tumor necrosis factor alpha) induced Gal-1 expression in cultured vascular smooth muscle cells and adventitial fibroblasts. Gal-1 deletion enhanced TNFα-induced MMP9 expression in fibroblasts but not vascular smooth muscle cells. Cysteinyl-labeling assay demonstrated that aortic Gal-1 exhibited susceptibility to oxidation in vivo. Recombinant oxidized Gal-1 induced expression of MMP9 and inflammatory cytokines to various extents in macrophages, vascular smooth muscle cells, and fibroblasts through activation of MAP (mitogen-activated protein) kinase signaling. Clinically, serum MMP9 level was significantly higher in both patients with AAA and coronary artery disease than in control subjects, whereas serum Gal-1 level was elevated in patients with AAA but not coronary artery disease when compared with controls. CONCLUSIONS: Gal-1 is highly induced and contributes to AAA by enhancing matrix degradation activity and inflammatory responses in experimental model. The pathological link between Gal-1 and AAA is also observed in human patients. These findings support the potential of Gal-1 as a disease biomarker and therapeutic target of AAA.
Subject(s)
Aorta, Abdominal/metabolism , Aortic Aneurysm, Abdominal/metabolism , Aortitis/metabolism , Galectin 1/metabolism , Vascular Remodeling , Adventitia/metabolism , Adventitia/pathology , Angiotensin II , Animals , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/pathology , Aortitis/chemically induced , Aortitis/pathology , Case-Control Studies , Cells, Cultured , Cytokines/metabolism , Disease Models, Animal , Disease Progression , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Fibroblasts/metabolism , Fibroblasts/pathology , Galectin 1/blood , Galectin 1/deficiency , Galectin 1/genetics , Humans , Inflammation Mediators/metabolism , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/pathology , Male , Matrix Metalloproteinase 9/metabolism , Mice, Inbred C57BL , Mice, Knockout, ApoE , Mitogen-Activated Protein Kinases/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Signal Transduction , Up-RegulationABSTRACT
BACKGROUND: Galectins are a family of proteins that have recently emerged as regulators of cancer biology. OBJECTIVES: To investigate the impact of peritumoral and tumoral galectin expression on ovarian cancer prognosis. SEARCH STRATEGY: We searched Medline, Cochrane, and EMBASE databases from inception until March 22, 2020. SELECTION CRITERIA: All studies correlating galectins and ovarian cancer prognosis were selected. DATA COLLECTION AND ANALYSIS: The literature search presented 11 studies, which contained 1034 patients. Meta-analysis was performed with RevMan 5.3 software. MAIN RESULTS: Studies were stratified into two groups depending on the location of galectin expression (peritumoral stroma or nucleus/cytoplasm of tumor cells). Tumoral galectin-7 and galectin-9 expression was significantly associated with poor overall survival (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.32-3.21, P = 0.001; OR 1.71, 95% CI 1.27-2.30, P < 0.001, respectively). The total effect of high tumoral expression of galectins in overall survival and progression-free survival was significant (OR 1.51, 95% CI 1.02-2.23, P = 0.04; OR 2.76, 95% CI 1.73-4.40, P < 0.001, respectively). CONCLUSIONS: Our results suggest that galectins are implicated in ovarian cancer prognosis; however, further research is needed to ascertain their actual importance as well as their diagnostic accuracy.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Ovarian Epithelial/mortality , Galectins/blood , Ovarian Neoplasms/mortality , Carcinoma, Ovarian Epithelial/blood , Female , Galectin 1/blood , Galectin 3/blood , Humans , Ovarian Neoplasms/blood , Predictive Value of Tests , PrognosisABSTRACT
Galectin 1 (Gal1) is a lectin with a wide cellular expression that functions as a negative regulator of the immune system in several animal models of autoimmune diseases. Identification of patients with rheumatoid arthritis (RA) has improved during the last decade, although there is still a need for biomarkers allowing an early diagnosis. In this regard, it has been recently proposed that Gal1 serum levels are increased in patients with RA compared to the general population. However, this topic is controversial in the literature. In this work, we provide additional information about the potential usefulness of Gal1 serum levels as a biomarker for RA diagnosis. We studied Gal1 serum and synovial fluid levels and clinical parameters in samples from 62 patients with early arthritis belonging to the PEARL study. In addition, 24 healthy donors were studied. We found that both patients fulfilling RA criteria and patients with undifferentiated arthritis showed higher Gal1 levels than healthy donors. Similar findings were observed in synovial fluid, which showed even higher levels than serum. However, we did not find correlation between Gal1 levels and disease activity or disability. Therefore, our results suggest that Gal1 could be a diagnostic but not a severity biomarker.
Subject(s)
Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , Galectin 1/blood , Osteoarthritis/diagnosis , Adult , Aged , Early Diagnosis , Female , Humans , Male , Middle Aged , Synovial Fluid/metabolismABSTRACT
INTRODUCTION: Galectins are proteins that bind ß-galactosides such as N-acetylactosamine present in N-linked and O-linked glycoproteins and that seem to be implicated fibrotic mechanisms. Here we aimed to define the role of serum galectins in idiopathic pulmonary fibrosis and idiopathic non-specific interstitial pneumonia (NSIP) by comparison with other chronic interstitial lung diseases (ILDs) and healthy subjects. METHODS: Forty-one fibrotic ILD patients (median age (IQR), 65 years (20); 50 % male) were enrolled in the study. Peripheral blood concentrations of galectins-1, 3 and 9 were determined with commercial ELISA kits. RESULTS: Galectin-1 and 9 concentrations were higher in the ILD group than in healthy controls (p = 0.0318 and p < 0.0001, respectively). Galectin-3 was also higher in ILD patients (borderline significant p = 0.0617). In particular, significantly higher Gal-1 concentrations were found in sarcoidosis and NSIP patients (p = 0.0418 and p = 0.0015, respectively), while Gal-9 concentrations were significantly higher in all ILD subgroups. Specific cut-offs for all galectins were calculated by receiver operating curve (ROC) analysis. Several correlations with lung function parameters were found. DISCUSSION: Galectins 1, 3 and 9 concentrations were found altered in serum of ILD patients suggesting their potential utility as clinical, diagnostic and prognostic biomarkers. Inhibition of galectins may be useful in the therapeutic management of pulmonary fibrosis. Further studies on larger case series would be worthwhile.
Subject(s)
Galectin 1/blood , Galectin 3/blood , Galectins/blood , Idiopathic Pulmonary Fibrosis/blood , Idiopathic Pulmonary Fibrosis/diagnosis , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Humans , Male , Middle Aged , PrognosisABSTRACT
Although melanoma is considered one of the most immunogenic malignancies, spontaneous T-cell responses to melanoma antigens are ineffective due to tumor cell-intrinsic or microenvironment-driven immune evasion mechanisms. For example, oncogenic BRAF V600E mutation in melanoma cells fosters tumor immune escape by modulating cell immunogenicity and microenvironment composition. BRAF inhibition has been shown to increase melanoma cell immunogenicity, but these effects are transient and long-term responses are uncommon. For these reasons, we aimed to further characterize the role of BRAF-V600E mutation in the modulation of PD-L1, a known immunoregulatory molecule, and galectin-1 (Gal-1), a potent immunoregulatory lectin involved in melanoma immune privilege. We report herein that vemurafenib downregulates IFN-γ-induced PD-L1 expression by interfering with STAT1 activity and by decreasing PD-L1 protein translation. Surprisingly, melanoma cells exposed to vemurafenib expressed higher levels of Gal-1. In coculture experiments, A375 melanoma cells pretreated with vemurafenib induced apoptosis of interacting Jurkat T cells, whereas genetic inhibition of Gal-1 in these cells restored the viability of cocultured T lymphocytes, indicating that Gal-1 contributes to tumor immune escape. Importantly, Gal-1 plasma concentration increased in patients progressing on BRAF/MEK inhibitor treatment, but remained stable in responding patients. Taken together, these results suggest a two-faceted nature of BRAF inhibition-associated immunomodulatory effects: an early immunostimulatory activity, mediated at least in part by decreased PD-L1 expression, and a delayed immunosuppressive effect associated with Gal-1 induction. Importantly, our observations suggest that Gal-1 might be utilized as a potential biomarker and a putative therapeutic target in melanoma patients.
Subject(s)
B7-H1 Antigen/metabolism , Galectin 1/genetics , Immunomodulation , Interferon-gamma/metabolism , Melanoma/immunology , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Up-Regulation/genetics , Apoptosis , Cell Line, Tumor , Galectin 1/blood , Humans , Immunomodulation/drug effects , Melanoma/blood , Melanoma/drug therapy , Protein Biosynthesis/drug effects , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/metabolism , STAT1 Transcription Factor/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Vemurafenib/pharmacology , Vemurafenib/therapeutic useABSTRACT
Many hypothesis suggest that inflammation plays an important role in schizophrenia. Galectins can regulate inflammatory response in central nervous system. The relation between galectins and neuropsyhchiatric diseases and schizophrenia is unclear. The present study compared levels of Gal-1 and Gal-3 of patients with schizophrenia to that of first-degree relatives without the disease and healthy controls in order to evaluate any possible association. Sixty-two patients with schizophrenia, fifty-five unaffected siblings and fifty-eight age- and sex-matched healthy controls enrolled. Serum Gal-1, Gal-3 and CRP levels were measured. PANNS and CGI-S were used to evaluate the severity of disease. There was a statistically significant difference in serum Gal-1 levels among the patient, sibling, and control groups. There were no statistically significant correlations between serum CRP ââand serum Gal-1 or Gal-3 levels. Gal-1 values were significantly higher in the unaffected siblings compared to both the patient group and the healthy control group. Gal-3 levels were elevated in the sibling group relative to the patient group. In the literature, the relationship between galectins and schizophrenia is very limited and appears to be a new field of study. Future studies are needed to evaluate the protective roles of galectins.
Subject(s)
Galectin 1/blood , Galectins/blood , Schizophrenia/blood , Schizophrenia/immunology , Adult , Blood Proteins , C-Reactive Protein , Female , Humans , Male , Middle Aged , Schizophrenia/physiopathology , Severity of Illness Index , SiblingsABSTRACT
The inflammatory bowel diseases (IBD), which include mainly Crohn's disease (CD) and ulcerative colitis (UC), are common chronic inflammatory conditions of the digestive system. The diagnosis of IBD relies on the use of a combination of factors including symptoms, endoscopy and levels of serum proteins such as C-reactive protein (CRP) or faecal calprotectin. Currently there is no single reliable biomarker to determine IBD. Galectins are a family of galactoside-binding proteins that are commonly altered in the circulation of disease conditions such as cancer and inflammation. This study investigated serum galectin levels as possible biomarkers in determining IBD and IBD disease activity. Levels of galectins-1, -2, -3, -4, -7 and -8 were analysed in 208 samples from ambulant IBD patients (97 CD, 71 UC) patients and 40 from healthy people. Disease activity was assessed using Harvey-Bradshaw Index for CD and simple clinical colitis activity index for UC. The relationship of each galectin in determining IBD and IBD disease activity were analysed and compared with current IBD biomarker CRP. It was found that serum level of galectin-1 and -3, but not galectins-2, -4, -7 and -8, were significantly higher in IBD patients than in healthy people. At cut-off of 4.1ng/ml, galectin-1 differentiated IBD from healthy controls with 71% sensitivity and 87% specificity. At cut-off of 38.5ng/ml, galectin-3 separated IBD from healthy controls with 53% sensitivity and 87% specificity. None of the galectins however were able to distinguish active disease from remission in UC or CD. Thus, levels of galectins-1 and -3 are significantly elevated in both UC and CD patients compared to healthy people. Although the increased galectin levels are not able to separate active and inactive UC and CD, they may have the potential to be developed as useful biomarkers for IBD diagnosis either alone or in combination with other biomarkers.
Subject(s)
Colitis, Ulcerative/blood , Crohn Disease/blood , Galectin 1/blood , Galectin 3/blood , Adult , Biomarkers/blood , Blood Proteins , C-Reactive Protein/metabolism , Colitis, Ulcerative/pathology , Crohn Disease/pathology , Female , Galectins/blood , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/pathology , Humans , Inflammatory Bowel Diseases/blood , Inflammatory Bowel Diseases/pathology , Male , Middle AgedABSTRACT
Galectin-1 modulates acute and chronic inflammation, and is associated with glucose homeostasis and chronic renal disease. Whether the serum galectin-1 level can predict short-term and long-term renal outcomes after contrast exposure in patients undergoing coronary angiography (CAG) remains uncertain. This study aimed to evaluate the relationship between the serum galectin-1 level and the incidence of contrast-induced nephropathy (CIN), and to investigate the predictive role of the circulating galectin-1 level for renal function decline in patients undergoing CAG. In total, 798 patients who had undergone CAG were enrolled. Baseline creatinine and serum galectin-1 levels were determined before CAG. CIN was defined as an increase in the serum creatinine level of 0.5 mg/dl or a 25% increase from baseline within 48 h after the procedure, and renal function decline was defined as > 30% reduction of the estimated glomerular filtration rate from baseline. All patients were followed for at least 1 year or until the occurrence of death after CAG. Overall, CIN occurred in 41 (5.1%) patients. During a median follow-up period of 1.4 ± 1.1 years, 80 (10.0%) cases showed subsequent renal function decline. After adjustment for demographic characteristics, kidney function, traditional risk factors, and medications, higher galectin-1 levels were found to be associated independently with a greater risk of renal function decline [tertile 2: hazard ratio (HR) 5.56, 95% confidence interval (CI) 1.79-17.22; tertile 3: HR 5.56, 95% CI 1.97-16.32], but not with CIN, regardless of the presence of diabetes. In conclusion, higher baseline serum galectin-1 levels were associated with a greater risk of renal function decline in patients undergoing CAG, but were not associated independently with CIN.
Subject(s)
Contrast Media/adverse effects , Coronary Angiography/adverse effects , Galectin 1/blood , Kidney Diseases/diagnosis , Kidney/diagnostic imaging , Aged , Disease Progression , Female , Humans , Incidence , Kidney/pathology , Kidney Diseases/chemically induced , Kidney Diseases/epidemiology , Male , Middle Aged , Prognosis , Risk , Taiwan/epidemiologyABSTRACT
Heart failure (HF) is a serious disease syndrome characterized by elevated pro-inflammatory cytokines and inflammatory mediators presume to have significant contribution on disease progression. Galectins are carbohydrate-binding proteins responsible of various physiological functions. Role of galectins in heart failure has been ill-defined. In the present case-controls study, 136 patients clinically diagnosed with heart failure and 125 healthy Chinese controls were recruited. Levels of galectins (Gal-1, 3 and 9) and cytokines (IFN-γ, IL-17A, IL-4 and TGF-ß) were quantified by ELISA. Increased levels of galectin-1 and 3 was observed in HF patients and associated with clinical severity. In addition, pro-inflammatory cytokines such as IFN-γ and IL-17A were increased in patients whereas, anti-inflammatory TGFß was decreased. Galectin-3 was positively correlated with IFN-γ, IL-17A and inversely with TGF-ß. Furthermore, ROC curve analysis suggested galectin-3 as a promising biomarker for diagnosis and HF and clinical severity. Interestingly, a two-year follow-up indicated significant association of elevated galectin-3 with mortality due to HF. In conclusion, galectin-3 associated with HF and clinical manifestations possibly by inducing pro-inflammatory cytokines and could be a possible biomarker of HF and severe clinical conditions.
Subject(s)
Biomarkers , Galectin 3/blood , Heart Failure/blood , Heart Failure/mortality , Adult , Aged , Blood Proteins , Case-Control Studies , China/epidemiology , Cytokines/blood , Disease Susceptibility , Galectin 1/blood , Galectins , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Function Tests , Hospitalization , Humans , Middle Aged , Prognosis , Public Health Surveillance , Severity of Illness IndexABSTRACT
Objective: To investigate maternal serum galectin-1 and galectin-3 levels in pregnancies complicated with preterm prelabor rupture of membranes (PPROM) and to compare with pregnancies delivered at term.Materials and methods: In this cross-sectional study, 40 women with singleton pregnancies complicated with PPROM between 24 and 34 weeks of gestation were compared with gestational age-matched 40 pregnant women with no obstetrics complications, who delivered at term. The maternal serum galectin-1 and galectin-3 levels were measured.Results: Patients complicated with PPROM had significantly higher levels of galectin-1 (p = .001) and galectin-3 (p = .003) than the control group. Maternal serum galectin-3 levels were found significantly negatively correlated with the gestational age at delivery and birth weight.Conclusion: Maternal serum galectin-1 and galectin-3 levels were significantly higher in pregnancies complicated with PPROM. Galectin-1 and galectin-3, with their regulatory effects in key biological processes, may be both an initiating factor in the pathophysiology of PPROM, a marker in the prediction, and a target of preventing strategies of PPROM.
Subject(s)
Fetal Membranes, Premature Rupture/blood , Galectin 1/blood , Galectin 3/blood , Adult , Cross-Sectional Studies , Female , Humans , Pregnancy , Young AdultABSTRACT
AIMS: Both progenitor and differentiated cells were previously shown to secrete cardioprotective substances, but so far there has been no direct comparison of the paracrine effects of the two cell types on heart failure. The study sought to compare the paracrine effect of selected progenitors and the corresponding non-progenitor mononuclear cardiac cells on the cardiac function of transgenic heart failure mice. In addition, we aimed to further enhance the paracrine effect of the cells via pretreatment with the heart failure mediator aldosterone. METHODS AND RESULTS: Transgenic heart failure mice were injected with the supernatant of murine cardiac stem cell antigen-1 positive (Sca-1+) and negative (Sca-1-) cells with or without aldosterone pretreatment. Cardiac function was determined using small animal magnetic resonance imaging. In addition, heart failure markers were determined using enzyme-linked immunosorbent assay, RT-PCR, and bead-based multiplexing assay. While only the secretome of aldosterone pretreated Sca-1+ cells led to a significant improvement in cardiac function, N-terminal pro brain natriuretic peptide plasma levels were significantly lower and galectin-1 levels significantly higher in mice that were treated with either kind of secretome compared with untreated controls. CONCLUSION: In this first direct comparison of the paracrine effects of progenitor cells and a heterogeneous population of mononuclear cardiac cells the supernatants of both cell types showed cardioprotective properties which might be of great relevance for endogenous repair. During heart failure raised aldosterone levels might further increase the paracrine effect of progenitor cells.