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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., (© 2024. The Author(s).)

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.

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., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

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-1β, 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-1β, 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-1β, 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., (© 2022. The Author(s).)

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.

Background: Galectin-1 (Gal-1), a member of the β-galactoside binding protein family, is associated with inflammation and chronic kidney disease. However, the effect of Gal-1 on mortality and acute kidney injury (AKI) in critically-ill patients remain unclear., Methods: From May 2018 to March 2020, 350 patients admitted to the medical intensive care unit (ICU) of Taipei Veterans General Hospital, a tertiary medical center, were enrolled in this study. Forty-one patients receiving long-term renal replacement therapy were excluded. Serum Gal-1 levels were determined within 24 h of ICU admission. The patients were divided into tertiles according to their serum Gal-1 levels (low, serum Gal-1 < 39 ng/ml; median, 39-70 ng/ml; high, ≥71 ng/ml). All patients were followed for 90 days or until death., Results: Mortality in the ICU and at 90 days was greater among patients with elevated serum Gal-1 levels. In analyses adjusted for the body mass index, malignancy, sepsis, Sequential Organ Failure Assessment (SOFA) score, and serum lactate level, the serum Gal-1 level remained an independent predictor of 90-day mortality [median vs. low: adjusted hazard ratio (aHR) 2.11, 95% confidence interval (CI) 1.24-3.60, p = 0.006; high vs. low: aHR 3.21, 95% CI 1.90-5.42, p < 0.001]. Higher serum Gal-1 levels were also associated with a higher incidence of AKI within 48 h after ICU admission, independent of the SOFA score and renal function (median vs. low: aHR 2.77, 95% CI 1.21-6.34, p = 0.016; high vs. low: aHR 2.88, 95% CI 1.20-6.88, p = 0.017). The results were consistent among different subgroups with high and low Gal-1 levels., Conclusion: Serum Gal-1 elevation at the time of ICU admission were associated with an increased risk of mortality at 90 days, and an increased incidence of AKI within 48 h after ICU admission., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2021. The Author(s).)

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., (© 2020 International Federation of Gynecology and Obstetrics.)

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 β-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.

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 (r 2  = 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.

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 β-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, β-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.

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 β-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.

Introduction: Galectins are proteins that bind β-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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

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 ​​and 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.

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., (© 2020 Institute of Hematology and Transfusion Medicine. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

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-β) 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 TGFβ was decreased. Galectin-3 was positively correlated with IFN-γ, IL-17A and inversely with TGF-β. 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., (© 2019 The Scandinavian Foundation for Immunology.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

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.

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.

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., Competing Interests: TBY, SD, NM and JR declare no conflicts of interest. SS has received speaker fee from MSD, Actavis, Abbvie, Dr Falk pharmaceuticals, Shire and received educational grant from MSD, Abbvie. LGY is an Academic Editor of PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Galectins, a family of animal lectins, play central roles in immune system regulation, shaping both innate and adaptive responses in physiological and pathological processes. These include rheumatoid arthritis (RA), a chronic multifactorial autoimmune disease characterized by inflammatory responses that affects both articular and extra-articular tissues. Galectins have been reported to play central roles in RA and its experimental animal models. In this perspective article we present new data highlighting the regulated expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) in sera from RA patients under disease-modifying anti-rheumatic drugs (DMARDs) and/or corticoid treatment in the context of a more comprehensive discussion that summarizes the roles of galectins in joint inflammation. We found that Gal-1 levels markedly increase in sera from RA patients and positively correlate with erythrocyte sedimentation rate (ERS) and disease activity score 28 (DAS-28) parameters. On the other hand, Gal-3 is downregulated in RA patients, but positively correlates with health assessment questionnaire parameter (HAQ). Finally, by generating receiver-operator characteristic (ROC) curves, we found that Gal-1 and Gal-3 serum levels constitute good parameters to discriminate patients with RA from healthy individuals. Our findings uncover a differential regulation of Gal-1 and Gal-3 which might contribute to the anti-inflammatory effects elicited by DMARDs and corticoid treatment in RA patients.

Background: Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy., Procedure: A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma., Results: Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms., Conclusions: Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy., (© 2018 Wiley Periodicals, Inc.)

Purpose: To analyze the interaction between aflibercept and galectin-1 and evaluate the plasma levels of galectin-1 and vascular endothelial growth factor (VEGF)-A after intravitreal injection of aflibercept in patients with diabetic retinopathy (DR)., Methods: Interaction of galectin-1 with aflibercept was determined via immunoprecipitation. Seventeen patients with type 2 diabetes and diabetic macular edema (DME) were each treated with a single intravitreal injection of aflibercept (2.0 mg, 50 µL) monthly for three consecutive months. Plasma galectin-1 and VEGF-A levels were measured just before an injection was administered, 1 week after the first injection, and 2 months after the last injection. Nineteen age- and sex-matched healthy participants served as controls., Results: Irrespective of the tested galectin-1 concentration, 24% of added galectin-1 was precipitated by aflibercept. Baseline plasma concentrations of galectin-1 were 22.0 and 23.0 ng/mL in the control and aflibercept-treated groups, respectively. Systemic galectin-1 levels increased to 27.0 and 24.0 ng/mL at 7 days and 4 weeks, respectively, after treatment. At week 8, plasma galectin-1 levels significantly increased to 36.0 ng/mL. This level persisted for 20 weeks. Systemic VEGF-A levels significantly reduced to below the minimum detectable dose in 16 DME patients at 7 days after treatment. This level persisted for 4 weeks. Plasma VEGF-A levels were reduced at weeks 8 (p = 0.099) and 20 (p = 0.023). Decreased plasma VEGF-A levels were observed in all patients after treatment., Conclusion: We confirmed that physiological aflibercept levels precipitate galectin-1 in in vitro assays. Additionally, systemic upregulation of galectin-1 might be induced by intravitreal aflibercept, which may be relevant in the clinical outcomes of DR treatment.

Our aim was to evaluate whether the serum level of galectin-1 (Gal-1) at 18-24 and 27-31 weeks of gestation is a risk factor for predicting the later occurrence of not only preeclampsia (PE) but also gestational hypertension (GH). We measured serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and Gal-1 using an enzyme-linked immunosorbent assay in 81 and 73 normal pregnant women, 22 and 16 women with a later onset of GH, and 37 and 29 women with a later onset of PE at 18-24 and 27-31 weeks, respectively. We also measured Gal-1 in 33 women with GH and 78 women with PE after the onset. The levels of Gal-1 after the onset of GH, late-onset PE (onset at ⩾34 weeks), and early-onset PE (onset at <34 weeks) were significantly higher than those in normal pregnant women at 27-31 weeks. However, the low levels of Gal-1 (<8.1 ng ml -1 ) at 18-24 weeks, but not at 27-31 weeks, predicted the later occurrence of not only early-onset PE and late-onset PE but also GH. The low level of Gal-1 at 18-24 weeks was an independent risk factor for the later occurrence of GH and PE, after adjusting for the effects of a high BP and increased sFlt-1/PlGF ratio at 18-24 weeks. In conclusion, the serum level of Gal-1 is a novel risk factor for both GH and PE, specifically its expression at a low level in the second trimester and a high level after onset.

Background: Previous studies have reported that galectin-3 is involved in inflammatory processes in the central nervous system and that neuroinflammation may play a role in the pathogenesis of schizophrenia. However, the link between schizophrenia and various galectins is unclear., Objective: The objective of the present study is to determine whether galectin, a well-known lectin protein that binds to μ-galactoside, is associated with chronic schizophrenia., Methods: Thirty-six patients with schizophrenia and 36 healthy controls participated in this study. Schizophrenia symptoms were assessed using the Brief Psychiatry Rating Scale (BPRS). Serum galectin-1 and galectin-3 levels were evaluated using ELISA and compared between the participant groups. Correlation analyses were also performed to examine the relationship between BPRS scores and each galectin level., Results: Serum galectin-3 levels were significantly higher in patients with schizophrenia than they were in controls (p = 0.009, d = 0.640); however, serum galectin-1 levels were not significantly different between the groups (p = 0.513). No significant correlation was identified between serum galectin-3 level and the total BPRS score; however, a significant positive correlation was found between the serum galectin-3 level and the positive symptom score of the BPRS (ρ = 0.355; p = 0.033). Additionally, a significant negative correlation was identified between serum galectin-3 levels and the negative symptom score of the BPRS (ρ = -0.387; p = 0.020)., Conclusions: Given the high serum levels of galectin-3 found in patients with schizophrenia compared with that in controls, these findings may support the inflammation hypothesis of schizophrenia.

Galectin-1, a recently identified peptide, is primarily released from the adipose tissue. Although galectin-1 was shown to have an anti-inflammatory effect, its specific function is not clearly understood. We aimed to evaluate the relationship of serum galectin-1 levels with clinical and laboratory parameters in childhood obesity. A total of 45 obese children (mean age: 12.1±3.1years) and 35 normal-weight children (mean age: 11.8±2.2years) were enrolled. Clinical [body mass index (BMI), waist circumference (WC), percentage of body fat and blood pressure] and biochemical [glucose, insulin, lipids, galectin-1, high-sensitive C-reactive protein (hsCRP) and leptin levels] parameters were assessed. Serum galectin-1, hsCRP and leptin levels were significantly higher in obese children than those in normal-weight children (12.4 vs 10.2ng/mL, p<0.001; 3.28 vs 0.63mg/L, p<0.001; 8.3 vs 1.2ng/mL, p<0.001, respectively). In obese children, galectin-1 levels correlated negatively with fasting glucose (r=-0.346, p=0.020) and positively with fat mass (r=0.326, p=0.026) and WC standard deviation score (SDS) (r=0.451, p=0.002). The multivariate regression analysis demonstrated that serum galectin-1 levels were significantly associated with fasting glucose and WC SDS. This study showed that obese children had significantly higher galectin-1 levels in proportion to fat mass in obese cases than those in healthy children, which may be interpreted as a compensatory increase in an attempt to improve glucose metabolism., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Galectin-1 (Gal-1) is differentially expressed in normal and pathological tissues and regulates immune cell homeostasis. Restraint stress increases serum Gal-1 in rats. However, the function of stress-induced Gal-1 in serum is unknown. We determined if stress-induced Gal-1 in serum accumulates in immunocompetent organs as protection from physiological and/or psychological stress. Western blotting showed that the intensity of Gal-1 bands in stressed groups was significantly higher than that in controls. RT-PCR analysis indicated that the Gal-1 mRNA level did not increase after restraint stress. The numbers of Gal-1 immunoreactive cells in the splenic periarterial lymphatic sheath (PLS) and the thymus medulla of the stressed group were increased compared with those in controls. Furthermore, stress-induced Gal-1 immunoreactive cells corresponded to CD45 immunoreactive lymphocytes (CD45 + ) in the PLS of the spleen and the medulla of the thymus. Thus, stress-induced Gal-1 immediately accumulates in the spleen and thymus, and may modulate the immune response through apoptosis by binding to CD45 + lymphocytes in immune organs following physiological and/or psychological stress.

The aim of this study was to assess the expression patterns of serum galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-3 binding protein (Gal-3BP) and their associations with stroke outcome in large artery atherosclerotic (LAA) stroke. The serum levels of Gal-1, Gal-3, Gal-9, and Gal-3BP were measured by ELISA in 130 patients with LAA stroke and 130 age- and sex-matched controls. Serum samples were collected from the patients on day 1, day 6, and in the 4th week after ischaemic stroke (IS). An unfavourable outcome was defined as a modified Rankin Scale score of >2 on day 90 after IS. Our results indicated that the Gal-3 and Gal-9 levels were higher in patients with LAA stroke than in controls. A higher Gal-3 level was independently associated with an unfavourable outcome both on day 1 and day 6 after IS. In addition, Gal-9 and Gal-1 levels were upregulated on day 6 and in the 4th week after IS, respectively. For Gal-3BP, no difference was detected between patients and controls and no predictive value was found in patients. In conclusion, these findings suggest that the serum levels of Gal-1, Gal-3, and Gal-9 may be associated with LAA stroke.

Purpose: Eales' disease (ED), an enigmatic inflammatory disease, affects peripheral retinal veins and thereby vision in males. This study was aimed at identifying and deciphering the role of a novel 88-kDa protein reported in the serum and vitreous of patients with ED., Experimental Design: The purified 88-kDa protein was identified by UPLC coupled ESI-QTOF-MS. The identified proteins were quantified in the serum from 20 ED patients and controls (age and sex matched), respectively by ELISA. The interaction of these proteins was studied using co-immunoprecipitation, western blot, and MS analyses. N-glycosylation of protein was observed by MS and lectin blot., Results: The 88-kDa protein was identified to be a complex of haptoglobin, complement C3, and galectin-1. ELISA results showed a 1.5-fold increase in levels of haptoglobin (p = 0.008), with level of complement C3 unaltered and 1.2-fold decreased serum galectin-1 levels (p = 0.003) in ED patients compared to controls. Co-immunoprecipitation illustrated the interaction between haptoglobin and complement C3. Reduced sialylation and increased β-1, 6-N-acetyl-glucosamine branched N-glycans were observed in haptoglobin of ED patients., Conclusion: The 88-kDa protein, a complex of haptoglobin, complement C3, and galectin-1, may play a potential role in ED pathogenesis while levels galectin-1 and haptoglobin may serve as potential biomarker of ED., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Soluble Galectin-1 (sGal-1, also termed LGALS1), soluble CD163 (sCD163) and soluble CD30 (sCD30) have been reported to be elevated in plasma or serum of patients with classical Hodgkin lymphoma (cHL). We aimed to determine the clinical utility of these biomarkers for evaluation of treatment response compared to thymus and activation regulated chemokine (TARC, also termed CCL17). Plasma or serum samples were prospectively collected among 103 newly diagnosed cHL patients before and after treatment. Levels of sGal-1, sCD163, sCD30 and TARC were correlated with disease characteristics and clinical treatment response. Elevated plasma levels of sGal-1, sCD163, sCD30 and TARC were found in 67%, 21%, 91% and 93% of cHL patients respectively. Mean plasma levels of sGal-1 and sCD30 decreased after treatment but sCD163 did not decrease after treatment. There was no correlation with change of these markers and clinical treatment response in individual patients. TARC levels strongly correlated with disease characteristics and metabolic volume. TARC remained high in 6 out of 7 non-responsive patients and dramatically decreased in 95 out of 96 responsive patients. In summary, elevated pre-treatment levels of sGal-1, sCD163, sCD30 and TARC can be found in patients with cHL. However, only plasma TARC accurately reflects disease activity and correlates with clinical treatment response., (© 2016 John Wiley & Sons Ltd.)

Purpose: Galectins are modulators of many processes critical for tumor progression and metastasis but their clinical significance is still unclear. The objective of this study was to analyze the clinical significance of Galectin-1 and Galectin-3 in the tissue and sera of patients with colorectal carcinoma (CRC). Examined were also their association with serum CEA, IL-17 and IL-23 in CRC patients., Methods: One hundred and twenty patients with CRC were included in this study. The expression of Galectin-1 and Galectin-3 in biopsy samples of CRC was determined using immunohistochemistry (N=120). The concentrations of Galectin-1, Galectin-3, IL-17 and IL-23 in the sera of CRC patients (N=38) were determined by Enzyme Linked Immunosorbent Assay (ELISA)., Results: Serum Galectin-1 concentrations positively correlated with parameters of malignancy including perineural invasion (p=0.016), lymph node involvement and distant metastases (p=0.029). Higher expression of peritumoral Galectin-1 was associated with both presence of perineural invasion and poor differentiation of CRC. Serum CEA levels positively correlated with circulating Galectin-1, but inversely correlated with peritumoral Galectin-1 expression. There was no correlation between Galectin-3 and clinicopathological parameters of CRC, but it was found that Galectin-3 expression in the tumor tissue positively correlated with serum IL-17 and IL-23. Circulating Galectin-3 levels significantly correlated with IL-17 (p=0.042), but not with IL-23 in the sera of CRC patients., Conclusions: This study suggests that Galectin-1 and Galectin-3 exhibit protumorigenic activity in CRC by affecting different aspects of tumor progression. Galectin-1 facilitates tumor invasion and metastasis while Galectin-3 preferentially modulates tumor-associated inflammatory processes.

Aim: To determine serum galectin-1 levels and their clinical associations in patients with systemic sclerosis (SSc)., Method: Serum galectin-1 levels were examined by enzyme-linked immunosorbent assay in 66 patients with SSc and 24 healthy individuals., Results: No significant differences were observed in serum galectin-1 levels between patients with SSc (9.4 ± 5.6 ng/mL), and healthy individuals (8.9 ± 1.3 ng/mL). Among patients with SSc, no significant differences were seen in serum galectin-1 levels between those with diffuse cutaneous SSc (8.8 ± 5.7 ng/mL; n = 31) and those with limited cutaneous SSc (10.0 ± 5.4 ng/mL; n = 35). Patients with SSc who had increased galectin-1 levels less often had pitting scars/digital ulcers than those with normal galectin-1 levels (17% vs. 49%; P < 0.01). Consistently, galectin-1 levels were significantly lower in SSc patients with pitting scars/digital ulcers than in those without pitting scars/digital ulcers (6.9 ± 4.8 vs. 10.9 ± 5.5 ng/mL; P < 0.01)., Conclusion: These results suggest that galectin-1 is a protective factor against the development of digital vasculopathy in SSc. In addition, measurement of serum galectin-1 levels may be useful for risk stratification for the development of digital vasculopathy in the early phase of SSc., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Galectin-1 (gal-1), a member of a family of conserved β-galactoside-binding proteins, has been shown to exert a key role during gestation. Though gal-1 is expressed at higher levels in the placenta from HELLP patients, it is still poorly understood whether systemic gal-1 levels also differ in HELLP patients. In the present study, we evaluated the systemic expression of gal-1, together with the angiogenic factors, placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in conjunction with HELLP syndrome severity. Systemic levels of gal-1 and sFlt-1 were elevated in patients with both early- and late-onset HELLP syndrome as compared to healthy controls. In contrast, peripheral PlGF levels were decreased in early- and late-onset HELLP. A positive correlation between systemic gal-1 levels and sFlt-1/PlGF ratios was found in early onset HELLP patients. Our results show that HELLP syndrome is associated with increased circulating levels of gal-1; integrating systemic gal-1 measurements into the diagnostic analyses of pregnant women may provide more effective prediction of HELLP syndrome development., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Timely and accurate diagnosis of cancer is crucial to cancer treatment. However, serological diagnosis of cancer still faces great challenge because the conventional methodology based on the enzyme-linked immune sorbent assay (ELISA) is costly, time-consuming, and complicated, involving multiple steps. Herein, lactose-functionalized gold nanorods (Lac-GNRs) are fabricated as efficient biosensors to detect cancerous conditions based on the unique surface plasmon resonance properties of GNRs and high specificity of lactose to the galectin-1 cancer biomarker. A trace concentration of galectin-1 as small as 10(-13) M can be detected by Lac-GNRs. The comparative study among BSA, galectin-3, and galectin-1 demonstrates the good specificity of Lac-GNRs to galectin-1 either in aqueous solutions or in the complex and heterogeneous serum specimens. Clinical tests show that the Lac-GNRs biosensors can readily distinguish the serums of cancer patients from those of healthy persons simply by using a microplate reader or even direct visual observation. The Lac-GNRs biosensing platform is highly efficient and easy to use and have great potential in rapid screening of cancer patients.

Aims: Galectin-1 (GAL1) is an important member of the lectin family with a carbohydrate recognition domain and has recently been demonstrated to be involved in adipose metabolism. In the present study, we investigated the effects of targeted inhibition of GAL1 by its binding inhibitor lactulose under high fat diet (HFD)-induced obesity., Main Methods: Effects of targeted inhibition of GAL1 by lactulose on lipid metabolism were investigated in vitro and in vivo. Changes in lipogenic capacity in lactulose-treated adipocytes were demonstrated by Oil Red O staining, triglyceride quantification and major adipogenic marker expression patterns. After lactulose treatment in Sprague-Dawley rats, various important body weight parameters, food efficiency, plasma metabolic parameters (glucose, ALT, free fatty acid, triglycerides, leptin, and insulin) and metabolic protein expression patterns were evaluated., Key Findings: Lactulose treatment reduced adipogenesis and fat accumulation in vitro by down-regulation of major adipogenic transcription factors such as C/EBPα and PPARγ. In vivo treatment of lactulose to 5-week-old Sprague-Dawley male rats significantly alleviated HFD-induced body weight gain and food efficiency as well as improved plasma and other metabolic parameters. In addition, lactulose treatment down-regulated major adipogenic marker proteins (C/EBPα and PPARγ) in adipose tissue as well as stimulated expression of proteins involved in energy expenditure and lipolysis (ATP5B, COXIV, HSL, and CPT1)., Significance: In conclusion, reduced adipogenesis and increased energy expenditure mediated by lactulose treatment synergistically contribute to alleviation of HFD-induced body weight gain. Therefore, pharmaceutical targeting of GAL1 using lactulose would be a novel therapeutic approach for the treatment of obesity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Sorafenib has become the standard therapy for patients with advanced hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop acquired resistance. Therefore, it is important to identify potential biomarkers that could predict the efficacy of sorafenib. To identify target proteins associated with the development of sorafenib resistance, we applied stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomic approach to analyze differences in protein expression levels between parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7(R)) cells in vitro, combined with an isobaric tags for relative and absolute quantitation (iTRAQ) quantitative analysis of HuH-7 and HuH-7(R) tumors in vivo. In total, 2,450 quantified proteins were identified in common in SILAC and iTRAQ experiments, with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75 showing decreased expression (<0.5-fold). In silico analyses of these differentially expressed proteins predicted that 10 proteins were related to cancer with involvements in cell adhesion, migration, and invasion. Knockdown of one of these candidate proteins, galectin-1, decreased cell proliferation and metastasis in HuH-7(R) cells and restored sensitivity to sorafenib. We verified galectin-1 as a predictive marker of sorafenib resistance and a downstream target of the AKT/mTOR/HIF-1α signaling pathway. In addition, increased galectin-1 expression in HCC patients' serum was associated with poor tumor control and low response rate. We also found that a high serum galectin-1 level was an independent factor associated with poor progression-free survival and overall survival. In conclusion, these results suggest that galectin-1 is a possible biomarker for predicting the response of HCC patients to treatment with sorafenib. As such, it may assist in the stratification of HCC and help direct personalized therapy., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Galectin-1 (GAL-1) belongs to the family of β-galactoside-binding lectins. It regulates cell-cell and cell-matrix interactions, the immune response, apoptosis, cell cycle, RNA splicing and neoplastic transformation. We investigate the effect of heart manipulation secondary to cardiac surgery on the level of GAL-1 in murine heart and plasma. Male C57B6/J mice were used for adopted model of cardiac surgery. Heart samples were processed for immunohistochemical and immunofluorescent labeling, Enzyme linked immunosorbent assay and quantitative RT-PCR to identify GAL-1 levels in the heart and plasma during the first 24 hours following cardiac surgery. There is significant increase of GAL-1 in the LV at 30 minutes (P<0.000), 60 minutes (P<0.001), 4 hour (P<0.003), and 24 hour (P<0.003) time points of surgically operated groups compared to non-operated control group, while GAL-1 mRNA levels in any of the surgically operated groups are not significantly different from the non-operated group suggesting extracardiac origin of this raise of GAL-1. There is significant increase of GAL-1 in the plasma at 30 minutes (P<0.000), 60 minutes (P<0.009), 4 hour (P<0.043), and 24 hour (P<0.000) time points of surgically operated groups compared to non-operated control group. In conclusion, GAL-1 is valuable biomarker of surgical stress.

Objective: To determine levels of galectins (gal)-1 and -3 (implicated in angiogenesis/immunologic mechanisms) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies, as these groups differ in fat mass, angiogenic patterns and immune responses., Methods: Cord-blood (UC) gal-1 and -3 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA singleton full-term infants and their mothers (MS)., Results: IUGR, LGA and AGA groups did not differ in gal-1 and -3 concentrations. UC gal-1 levels were lower when mothers were older [b=-0.651, CI 95% -1.186 (-0.116), P=0.018] and UC gal-3 levels were increased when mothers presented gestational diabetes [b=9.836, CI 95% 3.833- (15.839), P=0.002]. In IUGRs MS gal-3 and in LGAs UC gal-1 were decreased in multiparas [b=-5.372, CI 95% -9.584- (-1.161), P=0.014], and [b=-7.540, CI 95% -14.606- (-0.473), P=0.037], respectively. No correlations were found between MS or UC gal-1 and gal-3 concentrations., Conclusions: Lower UC gal-1 levels, when mothers were older, and increased UC gal-3 levels in cases of gestational diabetes, possibly reflect angiogenic activity. In multiparas, decreased MS gal-3 and UC gal-1 levels in IUGR/LGA, respectively, might imply inflammatory response against immunosuppression expected in subsequent pregnancies, as compared to the first one.

Background: Galectins are a family of carbohydrate binding proteins that regulate several cellular functions such as growth, migration, adhesion and apoptosis., Methods: We investigated the expression of galectin (gal)-1 and galectin (gal)-3 in patients with oral squamous cell carcinoma (OSCC) and observed their effects on growth and survival of OSCC cell lines., Results: OSCC patients expressed significantly higher levels of gal-1 and gal-3 in circulation (p<0.0001) and at the tumour sites (p<0.01) as compared to controls. Patients with higher tumour load showed significantly higher expression of both galectins than those with lower tumour load. In ROC analysis, serum levels of gal-1 and gal-3 at cut-off values of 4.875 and 0.871ng/ml respectively, discriminated between healthy subjects and patients with more than 80% sensitivity and specificity. Similarly, logistic regression analysis revealed about 3-times higher risk of OSCC in subjects over expressing these proteins. Further, exogenous gal-1 and gal-3 significantly increased survival, proliferation and angiogenesis in OSCC cell lines., Conclusions: Serum levels of gal-1 and gal-3 may serve as plausible markers for oral squamous cell carcinoma and may be useful in screening population at a higher risk., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Enterovirus 71 (EV71) infection causes a myriad of diseases from mild hand-foot-and-mouth disease or herpangina to fatal brain stem encephalitis complicated with pulmonary edema. Several severe EV71 endemics have occurred in Asia-Pacific region, including Taiwan, and have become a serious threat to children's health. EV71 infection is initiated by the attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between viruses and cell surface receptors, soluble factors may also influence the binding of EV71 to host cells. Galectin-1 has been reported to participate in several virus infections, but is not addressed in EV71. In this study, we found that the serum levels of galectin-1 in EV71-infected children were higher than those in non-infected people. In EV71 infected cells, galectin-1 was found to be associated with the EV71 VP1 and VP3 via carbohydrate residues and subsequently released and bound to another cell surface along with the virus. EV71 propagated from galectin-1 knockdown SK-N-SH cells exhibited lower infectivity in cultured cells and less pathogenicity in mice than the virus propagated from parental cells. In addition, this galectin-1-free EV71 virus was sensitive to high temperature and lost its viability after long-term storage, which could be restored following supplement of recombinant galectin-1. Taken together, our findings uncover a new role of galectin-1 in facilitating EV71 virus infection.

Previous studies demonstrated that a subpopulation of cancer cells, which are CD133 positive (CD133+) feature higher invasive and metastatic abilities, are called cancer stem cells (CSCs). By using tumor cells derived from patients with lung adenocarcinoma, we found that galectin-1 is highly overexpressed in the CD133+ cancer cells as compared to the normal cancer cells (CD133-) from the same patients. We overexpressed galectin-1 in CD133- cancer cells and downregulated it in CSCs. We found that overexpression of galectin-1 promoted invasiveness of CD133- cells, while knockdown of galectin-1 suppressed proliferation, colony formation and invasiveness of CSCs. Furthermore, tumor growth was significantly inhibited in CSCs xenografts with knockdown of galectin-1 as compared to CSCs treated with scramble siRNAs. Biochemical studies revealed that galectin-1 knockdown led to the suppression of COX-2/PGE2 and AKT/mTOR pathways, indicating galectin-1 might control the phenotypes of CSCs by regulating these signaling pathways. Finally, a retrospective study revealed that galectin-1 levels in blood circulation negatively correlates with overall survival and positively correlates with lymph node metastasis of the patients. Taken together, these findings suggested that galectin-1 plays a major role on the tumorigenesis and invasiveness of CD133+ cancer cells and might serve as a potential therapeutic target for treatment of human patients with lung adenocarcinoma.

To investigate the changes of Galectin-1 and T-lymphocyte phenotypes in unexplained recurrent spontaneous abortion (URSA). Totally 60 participants were recruited and divided into 3 groups in average: pregnant patients with URSA (URSA group), normal early pregnant women with induced abortion (IA group) and normal non-pregnant women (control group). After the tissue and blood sample were collected, Galectin-1 was measured using enzyme-linked immunosorbent assay. Then the proportion of T regulatory cells was determined by flow cytometry. The expression levels of Galectin-1 in IA group and URSA group was significantly higher than that in the control group (24.30 ± 3.06 and 6.23 ± 2.41 vs. 1.30 ± 0.66, P < 0.05). Besides, the expression level of Galectin-1 in URSA group was lower than that in IA group (P < 0.05). The percentage of CD4(+)CD25(+)Foxp3(+) Tregs was lower in URSA group than IA group (0.77 ± 0.31 vs. 1.00 ± 0.35, P < 0.05) and the ratio of CD4(+)CD25(+)Foxp3(+)/CD4(+) in URSA group was also obviously lower than that in IA and control group (P < 0.05). Galectin-1 and CD4(+)CD25(+)Foxp3(+) may play essential roles in maintaining a normal pregnancy and their reduction may involve in the pathogenesis of URSA.

Background: The simultaneous correlation of serum galectin-1, galectin-3, and 90K/Mac-2BP levels with clinical stages of patients with colorectal cancer has not yet been clarified. We plan to measure the serum levels of galectin-1, galectin-3, and 90K/Mac-2BP of patients at different stages of colorectal cancer and analyze the correlation of these galectins with stages of colorectal cancers., Methods: 198 colorectal cancer patients (62 ± 13 (range 31-85) years old, 43.6% female) were recruited for this study. Subjects' blood samples were checked for serum galectin-1, galectin-3, 90K/Mac-2BP, and carcinoembryonic antigen by sandwich enzyme-linked immunosorbent assay. We determined the correlation between plasma concentrations with clinical tumor stages., Results: Colorectal cancer patients with larger cancer sizes (stages T3, T4 rather than T1, T2) have higher serum 90K/Mac-2BP (P = 0.014) and patients with lymph node metastasis have higher serum galectin-1 (P = 0.002) but there was not a significant correlation between galectin-3 and tumor staging of colon cancer. In colorectal cancer patients even with normal carcinoembryonic antigen, serum galectin-1 could predict more lymph node metastasis., Conclusions: We found 90K/Mac-2BP correlated with the size of colorectal cancer. Galectin-1 but not galectin-3 was associated with lymph node metastasis. Galectin-1 could predict more lymph node metastasis in colorectal cancer patients with normal serum carcinoembryonic antigen.

Introduction: The achievement of a state of tolerance and minimization of the immunosuppressive load form part of the "Holy Grail" in solid organ transplantation. Galectin-1 recently has been described to be involved in the maintenance of a tolerant environment, but there is no evidence of its role in human liver transplantation. The aim of our study was to measure the serum levels of galectin-1 in stable liver transplant recipients., Methods: Serum levels of galectin-1 were determined in 30 stable liver transplant recipients who had been free of rejection episodes for at least 8 years. Fifteen patients with an acute rejection episode and 34 healthy subjects were used as the control group., Results: The concentrations of galectin-1 were significantly higher in stable liver transplant recipients compared with healthy subjects and with the acute rejection group., Conclusions: These preliminary results indicate that galectin-1 is upregulated in stable liver transplant recipients. Thus, our results extend the recent findings that galectin-1 may play an immune-suppressive role in liver transplantation. It remains to be established whether it might help to induce tolerance in liver transplantation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The molecular mechanism of vascular pathology mediated by circulating lipoprotein(a) [Lp(a)] remains unknown. We examined the role of two distinguishing features of Lp(a) viz non-covalent complex formation with a low density lipoprotein (LDL) and heavy glycosylation as determinants of binding of this lipoprotein and its LDL complex to cell-surface receptors. LDL isolated from the Lp(a):LDL complex, free LDL and oxidized LDL were equally efficient in forming a reconstituted complex with pure Lp(a). Complexed LDL in healthy individuals was equal in oxidation status to free LDL. The number of LDL molecules associated with each Lp(a) molecule (LDL index) in plasma samples increased steadily with Lp(a) size (correlation coefficient r = 0.834). Complex reconstituted from purified plasma Lp(a) and LDL maintained the same LDL index as plasma in accordance with Lp(a) size. Consequently, the percentage of complex-free Lp(a) in the plasma decreased sharply with Lp(a) size (r = -0.887). Although O-glycosylation measured in terms of lectin binding increased with Lp(a) size, the LDL index increased significantly faster than O-glycosylation among Lp(a) phenotypes of different plasma samples. Complexes with varying stoichiometry existed in the same plasma. Extra LDL complex molecules were not recognized by LDL receptors on human macrophages or rat cardiac fibroblasts indicating attachment to Lp(a) involved LDL receptor-binding sites. However, unlike free LDL complex LDL could attach through Lp(a) to immobilized form of galectin-1, a lectin ubiquitous on mammalian cells. Results suggest that phenotype-dependence of the physiological and pathological functions of Lp(a) may operate through differential LDL-carrier activity.

Objectives: Galectins (gals), a growing family of β-galactoside-binding animal lectins, have been implicated in a variety of biological processes including fibrosis, angiogenesis, and immune activation, all of which are involved in hemodialysis (HD) and renal transplantation (RTx). In this study, we aimed to investigate serum gal levels in HD and RTx recipients., Design and Methods: 41 normal subjects, 41 RTx recipients and 32 HD patients were recruited for this study. RTx recipients were evaluated before transplantation as well as 3 months afterwards. Serum gals-1, 2, 3, 4, 8, and 9 were measured both at baseline and 3 months later in each group., Results: At baseline, there were no differences in gals-1, 2, 3, 4, 8, and 9 between the RTx and HD groups. However, the levels of gals-1, 2, 3, 8, and 9 in the RTx and HD groups were higher than that of normal subjects. In paired analyses, gals-1, 2, and 3 were significantly decreased in RTx patients (P<0.0001) at 3 months, while there was no change in the HD group. However, levels of gals-4, 8, and 9 did not significantly change in either the HD or RTx group., Conclusion: Gal-1, 2, and 3 levels were high in maintenance HD patients. Kidney transplantation improved gal-1, 2, and 3 levels., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)