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Protein glycosylation is a post-translational modification involved in wide range of biological processes. In mammalian spermatozoa this modification has been identified in numerous proteins, and membrane glycoproteins are involved in the fertilization process. The objective of the present study was to identify changes in protein glycosylation after acrosome reaction (AR) induction using the 4-Br-A23187 ionophore. Our results showed that treatment with 10 μM of 4-Br-A23187 for 20 min significantly increased the percentage of live acrosome-reacted spermatozoa compared to the control (69.8 ± 0.8 vs. 6.4 ± 0.5; mean % ± SEM, respectively). Also, we observed an increase in 32 kDa tyrosine-phosphorylated protein (p32) and a decrease in serine/threonine phosphorylation of the protein kinase A substrates (phospho-PKA-substrates) after ionophore treatment. Furthermore, changes in glycosylated proteins following AR induction were analyzed using different HRP-conjugated lectins (GNA, DSA, and SNA), revealing changes in mannose and sialic acid residues. Proteomic analysis of isolated proteins using GNA lectin revealed that 50 proteins exhibited significantly different abundance (q-value < 0.01). Subsequent analysis using Uniprot database identified 39 downregulated and 11 upregulated proteins in the presence of 4-Br-A23187. Notably, six of these proteins were classified as transmembrane proteins, namely LRRC37A/B like protein 1 C-terminal domain-containing protein, Membrane metalloendopeptidase like 1, VWFA domain-containing protein, Syndecan, Membrane spanning 4-domains A14 and Serine protease 54. This study shows a novel protocol to induce acrosome reaction in boar spermatozoa and identifies new transmembrane proteins containing mannose residues. Further work is needed to elucidate the role of these proteins in sperm-oocyte fusion. • Incubation with 4-Br-A23187 for 20 min induces acrosome reaction in boar spermatozoa. • Glycosylated protein profile changes after acrosome reaction induction. • 50 proteins containing mannose residues showed regulation after acrosome reaction. • 6 transmembrane proteins containing mannose residues were regulated. [ABSTRACT FROM AUTHOR]

Dioclea violacea seed mannose-binding lectin (DvL) has attracted considerable attention because of its interesting biological activities, including antitumor, antioxidant, and anti-inflammatory activities. This study evaluated the cytotoxic effect of DvL on tumor and normal cells using the mitochondrial activity reduction (MTT) assay, the carcinogenic and anti-carcinogenic activity by the epithelial tumor test (ETT) in Drosophila melanogaster , and the anti-angiogenic effect by the chick embryo chorioallantoic membrane (CAM) assay. Data demonstrated that DvL promoted strong selective cytotoxicity against tumor cell lines, especially A549 and S180 cells, whereas normal cell lines were weakly affected. Furthermore, DvL did not promote carcinogenesis in D. melanogaster at any concentration tested, but modulated DXR-induced carcinogenesis at the highest concentrations tested. In the CAM and immunohistochemical assays, DvL inhibited sarcoma 180-induced angiogenesis and promoted the reduction of VEGF and TGF-β levels at all concentrations tested. Therefore, our results demonstrated that DvL is a potent anticancer, anti-angiogenic, and selective cytotoxic agent for tumor cells, suggesting its potential application as a prototype molecule for the development of new drugs with chemoprotective and/or antitumor effects. • Dioclea violacea lectin (DvL) promoted high selective cytotoxicity against A549 and S180 tumor cells. • DvL associated with α- d -mannose partially reversed the inhibitory effect of the lectin on A549 cell and S180 cell. • DvL modulated doxorubicin-induced tumorigenesis in Drosophila melanogaster. • DvL inhibits sarcoma 180-tumor angiogenesis and reduced VEGF and TGF-β expression in CAM assay. [ABSTRACT FROM AUTHOR]

Lectins are proteins capable of binding specifically and reversibly to carbohydrates, allowing several biotechnological applications. In the present study, the lectin from Libidibia ferrea var. ferrea pod (LifePL) was purified and the cytotoxic and genotoxic potentials were evaluated through cell viability and micronucleus in vitro assays. LifePL was isolated by chitin column chromatography followed by elution with 1 M acetic acid. The hemagglutinating activity (HA) of LifePL was determined in the presence of carbohydrates or divalent cations, as well as after heating and incubation at different pH values. In the cytotoxic assay using MTT, human peripheral blood mononuclear cells (PBMCs) were exposed to 10 concentrations of the lectin (ranging from 5 to 200 µg/mL) for 24 h. Genotoxicity was tested using the micronucleus assay at concentrations of 120, 160, and 200 µg/mL to evaluate a previous safety use of lectin. The purified LifePL showed a single band of 8 kDa on SDS-PAGE in the presence or absence of 2-mercaptoethanol or by gel filtration using an AKTA purification system. LifePL agglutinated erythrocytes from humans and rabbits and was inhibited by glycoproteins (e.g. , fetal bovine serum). The HA of LifePL remained stable and resistant at temperatures of 30–100 °C. The HA of the lectin was stimulated by ions (Ca2+ and Mg2+), as well as at different pH values ​​ (pH 4.5, 5.0, 5.5 and 7.5). There was no cytotoxicity for the concentrations tested. However, all concentrations increased cell viability (p < 0.05). Regarding genotoxicity, no concentration induced statistically significant changes (p < 0.05). In conclusion, the lectin isolated from L. ferrea var. ferrea pod revealed a good safety profile, since it did not show cytotoxic or genotoxic potential under used conditions. [Display omitted] • LifePL lectin was purified from libidibia ferrea var. ferrea pod;. • This lectin presented a single band of 8 kDa on SDS-PAGE;. • The hemagglutinating activity of LifePL was stimulated by Ca2+ and Mg2+ ions;. • LifePL remained stable at different temperatures and pH values;. • LifePL did not present cytotoxicity and genotoxicity according to in vitro assays. [ABSTRACT FROM AUTHOR]

Fibroblast growth factors (FGFs) and their receptors (FGFRs) constitute plasma-membrane localized signaling hubs that transmit signals from the extracellular environment to the cell interior, governing pivotal cellular processes like motility, metabolism, differentiation, division and death. FGF/FGFR signaling is critical for human body development and homeostasis; dysregulation of FGF/FGFR units is observed in numerous developmental diseases and in about 10% of human cancers. Glycosylation is a highly abundant posttranslational modification that is critical for physiological and pathological functions of the cell. Glycosylation is also very common within FGF/FGFR signaling hubs. Vast majority of FGFs (15 out of 22 members) are N-glycosylated and few FGFs are O-glycosylated. Glycosylation is even more abundant within FGFRs; all FGFRs are heavily N-glycosylated in numerous positions within their extracellular domains. A growing number of studies points on the multiple roles of glycosylation in fine-tuning FGF/FGFR signaling. Glycosylation modifies secretion of FGFs, determines their stability and affects interaction with FGFRs and co-receptors. Glycosylation of FGFRs determines their intracellular sorting, constitutes autoinhibitory mechanism within FGFRs and adjusts FGF and co-receptor recognition. Sugar chains attached to FGFs and FGFRs constitute also a form of code that is differentially decrypted by extracellular lectins, galectins, which transform FGF/FGFR signaling at multiple levels. This review focuses on the identified functions of glycosylation within FGFs and FGFRs and discusses their relevance for the cell physiology in health and disease. [Display omitted] • FGF/FGFR signaling plays a pivotal role in establishing and maintaining the cell and organism homeostasis. • Vast majority of FGF proteins and all FGFRs are N-glycosylated. • N- and O-glycosylation of FGFs affects their secretion, stability and function. • N-glycosylation of FGFRs facilitates intracellular trafficking of FGFRs to the cell surface and regulates FGFRs interaction with FGFs and co-receptors. • N-glycosylation of FGFs and FGFRs constitutes a layer of information differentially read by galectins and transformed into specific modulatory activities. [ABSTRACT FROM AUTHOR]

A lectin was isolated from the hepatopancreas of freshwater prawn, Macrobrachium rosenbergii by affinity chromatography using mucin-sepharose matrix. The purity of the isolated lectin was confirmed in native gradient PAGE that showed a single protein band of ∼37.9 kDa. In SDS-PAGE also one band of ∼43.3 kDa molecular weight was observed that indicated the protein to be a monomer. The band from the SDS-PAGE gel was identified through mass spectrometry as chitinase 1. The purified chitinase (50 μg/ml) hemagglutinated rabbit RBCs and, mucin and glucose inhibited hemagglutination with minimum concentrations of 0.1 mg/ml and 100 mM, respectively. Bacterial agglutination with Gram –ve Vibrio harveyi , Aeromonas sobria and Escherichia coli was also observed by this protein. Thus, chitinase 1 showed lectin-like properties besides its chitin hydrolytic activity. In western blot with hepatopancreas sample, rabbit antiserum against chitinase 1 cross-reacted to two additional proteins namely, chitinase 1C and obstructor E (a chitin-binding protein, CBP), besides its specific reactivity. An indirect ELISA was developed with the antiserum to quantify chitinases/CBP in hepatopancreas and serum samples of M. rosenbergii. The assay was used in samples from juvenile prawns following V. harveyi challenge. At 72 h post-challenge, significantly higher levels of chitinases/CBP were quantified in the hepatopancreas of the challenged group (1.8 ± 0.2 mg/g tissue) compared to the control (1.2 ± 0.1 mg/g tissue). This study suggests that the chitinase 1 protein with lectin-like properties is possibly induced at the protein level and can be putatively involved in the innate immune response of M. rosenbergii. • A ∼43.3 kDa Chitinase 1 was purified from the hepatopancreas of M. rosenbegii. • It possesses chitinolytic, hemagglutinating and bacterial agglutinating properties. • Antiserum to chitinase 1 cross-reacted to chitinase 1C and obstructor E proteins. • ELISA was developed to quantify chitinases/CBP in hepatopancreas and serum samples. • Vibrio harveyi challenge revealed chitinases/CBP to be inducible in nature. [ABSTRACT FROM AUTHOR]

Toll-like receptor 2 (TLR2) and galectin-3 (Gal-3) are involved in the pathological process of asthma, but the underlying mechanism is not fully understood. We hypothesized that TLR2 pathway may regulate expression of Gal-3 in allergic airway inflammation. Wild-type (WT) and TLR2−/− mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14–21 to establish a model of allergic airway inflammation, and were treated with a specific ERK inhibitor U0126. Histological changes in the lungs were analyzed by hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining; cytokines and anti-OVA immunoglobulin E (IgE) were tested by ELISA; and related protein expression in lung tissues was measured by western blot. We found that the expression levels of TLR2 and Gal-3 markedly increased concomitantly with airway inflammation after OVA induction, while TLR2 deficiency significantly alleviated airway inflammation and reduced Gal-3 expression. Moreover, the expression levels of phosphorylated mitogen-activated protein kinases (p-MAPKs) were significantly elevated in OVA-challenged WT mice, while TLR2 deficiency only significantly decreased phosphorylated extracellular signal-regulated kinase (p-ERK) levels. Furthermore, we found that U0126 treatment significantly alleviated allergic airway inflammation and decreased Gal-3 levels in OVA-challenged WT mice, but had no further effect in OVA-challenged TLR2−/− mice. These above results suggested that TLR2 is an upstream signal molecule of ERK. We further demonstrated that TLR2 regulates Gal-3 expression through the ERK pathway in LTA-stimulated macrophages in vitro. Our findings showed that the TLR2-ERK signaling pathway regulates Gal-3 expression in a murine model of allergic airway inflammation. • TLR2 and MAPKs signal pathways were activated concomitantly with increased Galectin-3 expression in OVA-induced allergic mice. • TLR2 deficiency significantly reduced airway inflammation, ERK phosphorylation and -Galectin-3 expression in allergic mice. • TLR2 signaling regulated airway inflammation and Galectin-3 expression through ERK pathway in allergic mice. [ABSTRACT FROM AUTHOR]

Integrin-mediated activation of the profibrotic mediator transforming growth factor-β1 (TGF-β1), plays a critical role in idiopathic pulmonary fibrosis (IPF) pathogenesis. Galectin-3 is believed to contribute to the pathological wound healing seen in IPF, although its mechanism of action is not precisely defined. We hypothesized that galectin-3 potentiates TGF-β1 activation and/or signaling in the lung to promote fibrogenesis. We show that galectin-3 induces TGF-β1 activation in human lung fibroblasts (HLFs) and specifically that extracellular galectin-3 promotes oleoyl-L-α-lysophosphatidic acid sodium salt–induced integrin-mediated TGF-β1 activation. Surface plasmon resonance analysis confirmed that galectin-3 binds to αv integrins, αvβ1, αvβ5, and αvβ6, and to the TGFβRII subunit in a glycosylation-dependent manner. This binding is heterogeneous and not a 1:1 binding stoichiometry. Binding interactions were blocked by small molecule inhibitors of galectin-3, which target the carbohydrate recognition domain. Galectin-3 binding to β1 integrin was validated in vitro by coimmunoprecipitation in HLFs. Proximity ligation assays indicated that galectin-3 and β1 integrin colocalize closely (≤40 nm) on the cell surface and that colocalization is increased by TGF-β1 treatment and blocked by galectin-3 inhibitors. In the absence of TGF-β1 stimulation, colocalization was detectable only in HLFs from IPF patients, suggesting the proteins are inherently more closely associated in the disease state. Galectin-3 inhibitor treatment of precision cut lung slices from IPF patients’ reduced Col1a1, TIMP1, and hyaluronan secretion to a similar degree as TGF-β type I receptor inhibitor. These data suggest that galectin-3 promotes TGF-β1 signaling and may induce fibrogenesis by interacting directly with components of the TGF-β1 signaling cascade. [ABSTRACT FROM AUTHOR]

Receptor-mediated cellular uptake of specific ligands constitutes an important step in the dynamic regulation of individual protein levels in extracellular fluids. With a focus on the inflammatory lung, we here performed a proteomics-based search for novel ligands regulated by the mannose receptor (MR), a macrophage-expressed endocytic receptor. WT and MR-deficient mice were exposed to lipopolysaccharide, after which the protein content in their lung epithelial lining fluid was compared by tandem mass tag-based mass spectrometry. More than 1200 proteins were identified in the epithelial lining fluid using this unbiased approach, but only six showed a statistically different abundance. Among these, an unexpected potential new ligand, thrombospondin-4 (TSP-4), displayed a striking 17-fold increased abundance in the MR-deficient mice. Experiments using exogenous addition of TSP-4 to MRtransfected CHO cells or MR-positive alveolar macrophages confirmed that TSP-4 is a ligand for MR-dependent endocytosis. Similar studies revealed that the molecular interaction with TSP-4 depends on both the lectin activity and the fibronectin type-II domain of MR and that a closely related member of the TSP family, TSP-5, is also efficiently internalized by the receptor. This was unlike the other members of this protein family, including TSPs −1 and −2, which are ligands for a close MR homologue known as urokinase plasminogen activator receptor-associated protein. Our study shows that MR takes part in the regulation of TSP-4, an important inflammatory component in the injured lung, and that two closely related endocytic receptors, expressed on different cell types, undertake the selective endocytosis of distinct members of the TSP family. [ABSTRACT FROM AUTHOR]

Recombinase-aided polymerase chain reaction (RAP) is a sensitive, single-tube, two-stage nucleic acid amplification method. This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Acinetobacter baumannii (AB) in the bloodstream based on recombinant human mannan-binding lectin protein (M1 protein)-conjugated magnetic bead (M1 bead) enrichment of pathogens combined with RAP. Recombinant plasmids were used to evaluate the assay sensitivity. Common blood influenza bacteria were used for the specific detection. Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR (M-RAP) and quantitative PCR (qPCR) assays. Kappa analysis was used to evaluate the consistency between the two assays. The M-RAP method had sensitivity rates of 1, 10, and 1 copies/μL for the detection of SA, PA, and AB plasmids, respectively, without cross-reaction to other bacterial species. The M-RAP assay obtained results for < 10 CFU/mL pathogens in the blood within 4 h, with higher sensitivity than qPCR. M-RAP and qPCR for SA, PA, and AB yielded Kappa values of 0.839, 0.815, and 0.856, respectively (P < 0.05). An M-RAP assay for SA, PA, and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia. [ABSTRACT FROM AUTHOR]

CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals remains unclear. Herein, we reported the crystal structure of the human CLEC12A-C-type lectin-like domain (CTLD) and identified a unique "basic patch" site on CLEC12A-CTLD that is necessary for the binding of MSU crystals. Meanwhile, we determined the interaction strength between CLEC12A-CTLD and MSU crystals using single-molecule force spectroscopy. Furthermore, we found that CLEC12A clusters at the cell membrane and seems to serve as an internalizing receptor of MSU crystals. Altogether, these findings provide mechanistic insights for understanding the molecular mechanisms underlying the interplay between CLEC12A and MSU crystals. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests an association between schizophrenia and atherosclerosis. We conducted a systematic review and meta-analysis of cell adhesion molecules, critically involved in early atherosclerosis, in schizophrenia. We searched electronic databases from inception to 11 November 2023 for case-control studies assessing vascular cell, VCAM-1, intercellular, ICAM-1, platelet endothelial cell, PECAM-1, neural cell, NCAM, and Down syndrome cell, DSCAM, adhesion molecules, selectins (E-, L-, and P-selectin), integrins, and cadherins in patients with schizophrenia and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively. In 19 eligible studies, there were non-significant between-group differences in the concentrations of cell adhesion molecules, barring higher P-selectin in patients with schizophrenia (standard mean difference, SMD = 2.05, 95 % CI 0.72 to 3.38, p = 0.003; I2 = 97.2 %, p<0.001; very low certainty of evidence). Limited or no information was available regarding PECAM-1, DSCAM, ESAM, integrins, and cadherins. In meta-regression and subgroup analysis, there were significant associations between the SMD of ICAM-1 and matrix used (plasma or serum) and pharmacological treatment of schizophrenia, and between the SMD of VCAM-1 and pharmacological treatment, but not with other study and patient characteristics. The results of our systematic review and meta-analysis do not support a significant role of immunoglobulin-like adhesion molecules, selectins, integrins, or cadherins in mediating the associations between schizophrenia, atherosclerosis, and cardiovascular disease. Further studies are warranted to investigate these associations in patients with different cardiovascular risk and the effects of antipsychotic treatments on cell adhesion molecules and surrogate markers of atherosclerosis (PROSPERO registration number: CRD42023463916). [ABSTRACT FROM AUTHOR]

Galectins, a family of evolutionarily conserved glycan-binding proteins, play key roles in diverse biological processes including tissue repair, adipogenesis, immune cell homeostasis, angiogenesis, and pathogen recognition. Dysregulation of galectins and their ligands has been observed in a wide range of pathologic conditions including cancer, autoimmune inflammation, infection, fibrosis, and metabolic disorders. Through protein-glycan or protein-protein interactions, these endogenous lectins can shape the initiation, perpetuation, and resolution of these processes, suggesting their potential roles in disease monitoring and treatment. However, despite considerable progress, a full understanding of the biology and therapeutic potential of galectins has not been reached due to their diversity, multiplicity of cell targets, and receptor promiscuity. In this article, we discuss the multiple galectin-binding partners present in different cell types, focusing on their contributions to selected physiologic and pathologic settings. Understanding the molecular bases of galectin-ligand interactions, particularly their glycandependency, the biochemical nature of selected receptors, and underlying signaling events, might contribute to designing rational therapeutic strategies to control a broad range of pathologic conditions. [ABSTRACT FROM AUTHOR]

Osteolectin is a secreted glycoprotein of the C-type lectin domain superfamily, expressed in bone tissues and is reported as a novel osteogenic factor that promotes bone regeneration. However, the effect of osteolectin on human dental pulp cells (hDPCs) has not been reported. Therefore, we aimed to investigate the odontoblastic differentiation of osteolectin in hDPCs and further attempt to reveal its underlying mechanism. Cytotoxicity assays were used to detect the cytotoxicity of osteolectin. The odontoblastic differentiation of hDPCs and its underlying mechanisms were measured by the alkaline phosphatase (ALP) activity, mineralized spots formation, and the gene and protein expression of odontoblastic differentiation through ALP staining, Alizarin red S staining, quantitative real-time polymerase chain reaction, and Western blot analysis, respectively. WST-1 assay showed osteolectin at concentrations below 300 ng/ml was noncytotoxic and safe for hDPCs. The following experiment demonstrated that osteolectin could increase ALP activity, accelerate the mineralization process, and up-regulate the odontogenic differentiation markers in both gene and protein levels (P <.05). Osteolectin stimulated the phosphorylation of ERK, JNK, and Protein kinase B (AKT) in hDPCs. Extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and AKT inhibitors decreased ALP activity and mineralization capacity and suppressed the expression of dentin sialophosphoprotein and dentin matrix protein-1. Osteolectin can promote odontoblastic differentiation of hDPCs, and the whole process may stimulate ERK, JNK, and AKT signaling pathways by increasing p-ERK, p-JNK, and p-AKT signals. [ABSTRACT FROM AUTHOR]

Lectins presents the ability to interact with glycans and trigger varied responses, including the inhibition of the development of various pathogens. Structural studies of these proteins are essential to better understand their functions. In marine sponges, so far only a few lectins have their primary structures completely determined. Thus, the objective of this work was to structurally characterize and evaluate antibacterial potential, in association with different antibiotics, of the lectin isolated from the marine sponge Aplysina lactuta (ALL). ALL is a homotetramer of 60 kDa formed by four 15 kDa-subunits. The lectin showed affinity only for the glycoproteins fetuin, asialofetuin, mucin type III, and bovine submaxillary mucin type I. The complete amino acid sequences of two isoforms of ALL, named ALL-a and ALL-b, were determined by a combination of Edman degradation and overlapped peptides sequenced by tandem mass spectrometry. ALL-a and ALL-b have 144 amino acids with molecular masses of 15,736 Da and 15,985 Da, respectively. Both structures contain conserved residues typical of the galectin family. ALL is a protein with antibacterial potential, when in association with ampicillin and oxacillin the lectin potentiates its antibiotic effect, included Methicillin-resistant Staphylococcus strains. Thus, ALL shows to be a molecule with potential for the development of new antibacterial drugs. • ALL conserves structural motifs and carbohydrate-binding residues of galectins. • The predicted 3-D structure of ALL is a typical galectin β-sandwich. • ALL in association with ampicillin potentiates the effect of the antibiotic. • ALL in association with tetracycline confers an additive effect to the antibiotic. [ABSTRACT FROM AUTHOR]

In multicellular organisms, a variety of lipid-protein particles control the systemic flow of triacylglycerides, cholesterol, and fatty acids between cells in different tissues. The chemical modification by oxidation of these particles can trigger pathological responses, mediated by a group of membrane proteins termed scavenger receptors. The lectin-like oxidized lowdensity lipoprotein (LOX-1) scavenger receptor binds to oxidized low-density lipoprotein (oxLDL) and mediates both signaling and trafficking outcomes. Here, we identified five synthetic proteins termed Affimers from a phage display library, each capable of binding recombinant LOX-1 extracellular (oxLDL-binding) domain with high specificity. These Affimers, based on a phytocystatin scaffold with loop regions of variable sequence, were able to bind to the plasma membrane of HEK293T cells exclusively when human LOX-1 was expressed. Binding and uptake of fluorescently labeled oxLDL by the LOX-1-expressing cell model was inhibited with subnanomolar potency by all 5 Affimers. ERK1/2 activation, stimulated by oxLDL binding to LOX-1, was also significantly inhibited (p < 0.01) by preincubation with LOX-1-specific Affimers, but these Affimers had no direct agonistic effect. Molecular modeling indicated that the LOX-1-specific Affimers bound predominantly via their variable loop regions to the surface of the LOX-1 lectin-like domain that contains a distinctive arrangement of arginine residues previously implicated in oxLDL binding, involving interactions with both subunits of the native, stable scavenger receptor homodimer. These data provide a new class of synthetic tools to probe and potentially modulate the oxLDL/LOX-1 interaction that plays an important role in vascular disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pretreatment with AKK or pAKK modulates S. Typhimurium infection. • AKK enhances the gut barrier and increases RegIII lectins secretion after infection. • pAKK stimulates antimicrobial activity, ROS production, and inflammasome activation in macrophages and mice. • AKK-altered gut microbiota plays a partial role in attenuating infection. The gut microbiome is vital for providing resistance against colonized pathogenic bacteria. Recently, specific commensal species have become recognized as important mediators of host defense against microbial infection by a variety of mechanisms. To examine the contribution of live and pasteurized A. muciniphila to defend against the intestinal pathogen Salmonella Typhimurium in a streptomycin-treated mouse model of infection. C57B6J mice were pretreated with phosphate-buffered saline (PBS), live Akkermansia muciniphila (AKK), and pasteurized A. muciniphila (pAKK) for two weeks, then mice were infected by S. Typhimurium SL 1344. 16S rRNA-based gut microbiota analysis was performed before and after infection. Bacterial counts in feces and tissues, histopathological analysis, gut barrier-related gene expression, and antimicrobial peptides were examined. Co-housing was performed to examine the role of microbiota in the change of susceptibility of mice to infection. AKK and pAKK markedly decrease d Salmonella fecal and systemic burdens and reduced inflammation during infection. Notably, further characterization of AKK and pAKK protective mechanisms revealed different candidate protective pathways. AKK promoted gut barrier gene expression and the secretion of antimicrobial peptides, and co-housing studies suggested that AKK-associated microbial community played a role in attenuating infection. Moreover, pAKK had a positive effect on NLRP3 in infected mice. We verified that pretreatment of pAKK could promote the expression of NLRP3, and enhance the antimicrobial activity of macrophage, likely through increasing the production of reactive oxygen (ROS), nitric oxide (NO), and inflammatory cytokines. Our study demonstrates that live or pasteurized A. muciniphila can be effective preventive measures for alleviating S. Typhimurium-induced disease, highlighting the potential of developing Akkermansia-based probiotics or postbiotics for the prevention of Salmonellosis. [ABSTRACT FROM AUTHOR]

The expression of trophoblast cell surface antigen-2 (Trop-2) is enhanced in many tumor tissues and is correlated with increased malignancy and poor survival of patients with cancer. Previously, we demonstrated that the Ser-322 residue of Trop-2 is phosphorylated by protein kinase Cα (PKCα) and PKCδ. Here, we demonstrate that phosphomimetic Trop-2 expressing cells have markedly decreased E-cadherin mRNA and protein levels. Consistently, mRNA and protein of the E-cadherin– repressing transcription factors zinc finger E-Box binding homeobox 1 (ZEB1) were elevated, suggesting transcriptional regulation of E-cadherin expression. The binding of galectin-3 to Trop-2 enhanced the phosphorylation and subsequent cleavage of Trop-2, followed by intracellular signaling by the resultant C-terminal fragment. Binding of β-catenin/transcription factor 4 (TCF4) along with the C-terminal fragment of Trop-2 to the ZEB1 promoter upregulated ZEB1 expression. Of note, siRNA-mediated knockdown of β-catenin and TCF4 increased the expression of E-cadherin through ZEB1 downregulation. Knockdown of Trop-2 in MCF-7 cells and DU145 cells resulted in downregulation of ZEB1 and subsequent upregulation of E-cadherin. Furthermore, wild-type and phosphomimetic Trop-2 but not phosphorylation-blocked Trop-2 were detected in the liver and/or lung of some nude mice bearing primary tumors inoculated intraperitoneally or subcutaneously with wild-type or mutated Trop-2 expressing cells, suggesting that Trop-2 phosphorylation, plays an important role in tumor cell mobility in vivo, too. Together with our previous finding of Trop-2 dependent regulation of claudin-7, we suggest that the Trop-2–mediated cascade involves concurrent derangement of both tight and adherence junctions, which may drive metastasis of epithelial tumor cells. [ABSTRACT FROM AUTHOR]

Galectin (Gal)-3 is a multifunctional lectin present in biological fluids and tissues with a widespread distribution within the cell, the plasma membrane, and extracellular matrix. Gal-3 binds hundreds of ligands with preferential affinity for those possessing β-galactoside motifs, through its carbohydrate recognition domain. The still poorly understood mode of action of Gal-3 must be regarded with respect to the variety of its binding partners. Gal-3 modulates biological processes depending on its own levels, but also on those of its ligands, each possessing its own function. Increased Gal-3 levels are associated with inflammation and fibrosis, highlighting its value as a biomarker and/or therapeutic target in many related diseases. The identification of selective and potent Gal-3 inhibitors is challenging. Novel generation compounds capable of alleviating pathogenic events emphasize the role of Gal-3 as a direct disease target. Galectin (Gal)-3 is a β-galactoside-binding lectin emerging as a key player in cardiac, hepatic, renal, and pulmonary fibrosis and inflammation, respiratory infections caused by COVID-19, and neuroinflammatory disorders. Here, we review recent information highlighting Gal-3 as a relevant therapeutic target in these specific disease conditions. While a causal link was difficult to establish until now, we discuss how recent strategic breakthroughs allowed us to identify new-generation Gal-3 inhibitors with improved potency, selectivity, and bioavailability, and report their usefulness as valuable tools for proof-of-concept studies in various preclinical models of the aforementioned diseases, with emphasis on those actually in clinical stages. We also address critical views and suggestions intended to expand the therapeutic opportunities provided by this complex target. [ABSTRACT FROM AUTHOR]

Endotheliochorial cat (Felis catus) and lion (Panthera leo) term placentae and one 6 week placenta (term 60–63 days) from a dog (Canis familiaris) were stained with a panel of 24 lectins to compare glycosylation at the feto-maternal interface. Glycan expression in lion and cat placentae was very similar apart from the occurrence of terminal α-galactose in the lion trophoblast. The dog differed in several respects, particularly in the trophoblast, consistent with species-specific glycotypes differing according to the degree of their evolutionary divergence. The data suggest that evolutionary effects on the glycotype are most readily observed in trophoblast. • Endotheliochorial placental glycosylation in cat, lion and dog was examined with 24 lectins. • Cat and lion glycans were similar apart from terminal α-galactose expression in lion trophoblast. • Glycans in dog placenta differed with respect to several classes of glycan, mainly in trophoblast. • This suggests the presence of a glycocode diverging with evolutionary distance between species. [ABSTRACT FROM AUTHOR]

Spontaneous preterm birth (sPTB) is a global health issue. Studies suggest infections are chiefly associated with sPTB and galectins (gals) play a role in regulation of innate and adaptive maternal immune response against pathogens during sPTB. The aim of this study was to describe the gene expression of gal -1, -3, -8, -9, -13 in relation to gene expression of cyclooxygenase-2 (COX-2) and the cytokines IL-8, IL-10, TNF-α, IFN-ϒ in the setting of sPTB and confirmed infection with Chlamydia trachomatis , Mycoplasma hominis , and Ureaplasma urealyticum. Placental samples were collected from 120 term control and 120 sPTB pregnancies. PCR was used to detect specific pathogens. Gene expression of galectins, cytokines, and COX-2 was performed using real time qPCR. Fold-change expression of gal -1, -3, -8, -9, -13 was 5.13, 6.11, 1.14, 5.23 and 7.16 (p<0.001), respectively; while IL-10, IL-8, TNF-α, IFN-ϒ and COX-2 was 6.29, 6.55, 6.35, 6.36 and 2.73-fold upregulated (p<0.05), respectively in infected sPTB. Gal-1 was positively correlated with IL-10 (r=0.49, p=0.003) while gal-3 showed significant correlation with IL-8 (r=0.42, p=0.0113), TNF-α (r=0.65, p=< 0.001) and COX-2 (r=0.72, p=0.001). However, gal-8 was not significantly correlated with any cytokine. Gal-9, -13 were negatively correlated with IFN-ϒ (r=-0.45, p=0.006) and IL-8 (r=-0.39, p=0.018). Gal-1, -9, -13 are anti-inflammatory and might play role in immune-tolerance while gal-3 is pro-inflammatory and possibly responsible for immunogenic response, having potential to anticipate the clinical beginning of preterm labour during infection. • Gals were significantly upregulated with maximum fold-change in gal-13 (7.16). • Significant upregulation of cytokines, i.e. IL-10, IL-8, TNF-α, IFN-ϒ and COX-2. • Gal-1 was positively correlated with IL-10 while gal-3 with IL-8/TNF-α/COX-2. • Gals-9, -13 were negatively correlated with IFN-ϒ and IL-8. • Gal-3 associated with pre-mature labour; gal-1,-9,-13 involved in immunotolerance. [ABSTRACT FROM AUTHOR]

• M. urundeuva lectins were potentially toxic to human lymphocytes and non-hemolytic. • M. urundeuva lectins showed weak genotoxicity to human lymphocytes. • MuHL and MuLL were moderately active against cancer cell lines. • MuHL non-cytotoxic or genotoxic doses were fungicidal against Cryptococcus. • MuHL acted synergistically with fluconazole and inhibited C. neoformans biofilm. This study evaluated the lectins from bark (MuBL), heartwood (MuHL) and leaf (MuLL) of Myracrodruon urundeuva for cytotoxicity on cancer and normal cells; hemolytic activity; genotoxicity using comet and micronucleus tests; and antifungal activity against Cryptococcus through determination of minimal inhibitory (MIC) and minimal fungicidal (MFC) concentration, antibiofilm formation effect and evaluation of synergism with other drugs. MuBL, MuHL and MuLL showed IC 50 on mononuclear peripheral blood cells of 58.41, 43.19 and 62.28 µg/mL, respectively. MuHL and MuLL (25 µg/mL) were moderately active on the cancer cell lines HL-60 (promyelocytic leukemia), NCI-H292 (lung mucoepidermoid carcinoma) and MCF-7 (breast adenocarcinoma). The percentage of hemolysis promoted by lectins ranged from 0 to 11.6%. Data from comet assay revealed that MuBL (100 µg/mL), MuHL and MuLL (50 µg/mL) showed frequency of damage of 33.5%, 35.67% and 65.2%, respectively. On micronucleus test, the number of micronuclei was 7.91, 7.41 and 8.91 to MuBL (100 µg/mL), MuHL and MuLL (50 µg/mL), and did not differ from the negative control. Only MuHL exhibited fungistatic and fungicidal activity with MIC of 6.25 and 12.5 µg/mL and MFC of 12.5 and 25 µg/mL against Cryptococcus neoformans and Cryptococcus gattii , respectively. MuHL also potentialized antibiotic action and reduced in 80% biofilm formation by C. neoformans. In conclusion, lectins from M. urundeuva did not promote damage to erythrocytes and presented low cytotoxicity and absence of genotoxicity on lymphocytes. Nontoxic concentrations of MuHL and MuLL showed moderate cytotoxicity on cancer cell lines. MuHL presented antifungal activity against Cryptococcus isolates. [ABSTRACT FROM AUTHOR]

• OA patients have higher gal-1 and 4 serum levels than healthy controls. • Gal-1 levels are associated to joint edema in OA patients. • There is no difference of Gal-3 and Gal-7 serum levels between OA patients and healthy controls. Although immunostaining of galectins is associated with cartilage damage, the serum levels of these lectins in osteoarthritis (OA) are not fully understood. Therefore, we evaluate the concentrations of galectins-1, 3, 4, and 7 in patients with osteoarthritis and correlate them with clinical parameters. This cross-sectional study involved 60 osteoarthritis patients and 43 healthy volunteers, who had serum samples collected for galectins titration by Enzyme-Linked Immunosorbent Assay (ELISA). Our finds showed that the median values of gal-1 and 4 serum levels in patients were statistically higher (13,990 and 969.1 pg/mL, respectively) than in healthy controls (1,798 and 519.5 pg/mL) with p < 0.001. Further, gal-1 expressed higher levels in patients who had joint edema at the time of collection with a median value of 14,970 pg/mL. Surprisingly, galectin-4 appears to be involved in the osteoarthritis inflammation process as the well-known galectin-1. [ABSTRACT FROM AUTHOR]

Poor lifestyle choices and genetic predisposition are factors that increase the number of cancer cases, one example being breast cancer, the third most diagnosed type of malignancy. Currently, there is a demand for the development of new strategies to ensure early detection and treatment options that could contribute to the complete remission of breast tumors, which could lead to increased overall survival rates. In this context, the glycans observed at the surface of cancer cells are presented as efficient tumor cell markers. These carbohydrate structures can be recognized by lectins which can act as decoders of the glycocode. The application of plant lectins as tools for diagnosis/treatment of breast cancer encompasses the detection and sorting of glycans found in healthy and malignant cells. Here, we present an overview of the most recent studies in this field, demonstrating the potential of lectins as: mapping agents to detect differentially expressed glycans in breast cancer, as histochemistry/cytochemistry analysis agents, in lectin arrays, immobilized in chromatographic matrices, in drug delivery, and as biosensing agents. In addition, we describe lectins that present antiproliferative effects by themselves and/or in conjunction with other drugs in a synergistic effect. • Aberrant glycosylations in breast cancer cells. • Diagnostic strategies against breast cancer based in lectins. • Plant lectins as a therapeutic target against breast cancer. • Proposed anticancer mechanism of lectins. [ABSTRACT FROM AUTHOR]

The lung airway epithelial surface is heavily covered with sialic acids as the terminal carbohydrate on most cell surface glycoconjugates and can be removed by microbial neuraminidases or endogenous sialidases. By desialylating the lung epithelial surface, neuraminidase acts as an important virulence factor in many mucosal pathogens, such as influenza and S. pneumoniae. Desialylation exposes the subterminal galactosyl moieties – the binding glycotopes for galectins, a family of carbohydrate-recognition proteins playing important roles in various aspects of immune responses. Galectin-1 and galectin-3 have been extensively studied in their roles related to host immune responses, but some questions about their role(s) in leukocyte recruitment during lung bacterial infection remain unanswered. In this study, we found that both galectin-1 and galectin-3 bind to polymorphonuclear leukocytes (PMNs) and enhance the interaction of endothelial intercellular adhesion molecule-1 (ICAM-1) with PMNs, which is further increased by PMN desialylation. In addition, we observed that in vitro galectin-1 mediates the binding of PMNs, particularly desialylated PMNs, onto the endothelial cells. Finally, in a murine model for LPS-mediated acute lung injury, we observed that galectin-1 modulates PMN infiltration to the lung without altering the expression of chemoattractant cytokines. We conclude that galectins, particularly galectin-1, may function as adhesion molecules that mediate PMN-endothelial cell interactions, and modulate PMN infiltration during acute lung injury. • Desialylation of endothelial cells and PMNs increases galectin binding. • Galectins mediates ICAM-1 binding onto PMNs, which is increased by PMN desialylation. • Galectin-1 mediates PMN adhesion more effectively than Galectin-3. • Galectin-1, expressed in LPS-challenged mouse lung, promotes LPS-mediated ALI. • Diverse galectin functions complicate the analysis and warrant further investigation. [ABSTRACT FROM AUTHOR]

Placental glycosylation has been examined on eight feline placentae ranging from approximately 15 to 60 days post-conception as little is known about changes in glycan distribution in this species. Specimens were resin embedded and lectin histochemistry was applied to semi-thin sections using a panel of 24 lectins and an avidin-biotin revealing system. Abundant tri-tetraantennary complex N-glycan and α-galactosyl residues found in the syncytium in early pregnancy were greatly reduced in mid-pregnancy, though retained at the invasion front in the syncytium (N-glycan) or cytotrophoblast layer (αGal). Some other glycans were also uniquely present in invading cells. Abundant polylactosamine was found in the infolding basal lamina of syncytiotrophoblast and the apical villous cytotrophoblast membrane. Syncytial secretory granules often clustered near the apical membrane abutting maternal vessels. Decidual cells selectively expressed β-galactosyl residues throughout pregnancy and highly branched N-glycan levels increased over time. Glycan distribution changes significantly over pregnancy, probably relating to the development of transport and invasive properties of trophoblast which in the endotheliochorial placenta reaches the level of the maternal vessels. Highly branched complex N-glycans, often associated with invasive cells, N-Acetylgalactosamine and terminal α-galactosyl residues are present at the invasion front abutting the junctional zone of the endometrium. Abundant polylactosamine on the syncytiotrophoblast basal lamina may reflect the presence of specialised adhesive interactions, while clustering of glycosylated granules apically is probably associated with secretion and absorption of material via maternal vasculature. It is suggested that lamellar and invasive cytotrophoblast represent distinct differentiation pathways. 246 words. • Glycan profiling demonstrates distinct phenotypes in trophoblast subpopulations. • The invasive cytotrophoblast phenotype persists at the distal tips of lamellae. • Stepped maturational changes are evident in syncytiotrophoblast. • A glycan marker profile is derived for maternal decidual cells. [ABSTRACT FROM AUTHOR]

Lectins or agglutinins are mainly proteins or glycoproteins, reported to uphold an ability to agglutinate the red blood cells (RBCs) with a known sugar specificity in a diverse group of organisms. In the present study, we purified a hemocyanin (named as MmHc) from a shrimp, Metapenaeus monoceros by size-exclusion chromatography. Further characterization revealed that the purified MmHc showed hemagglutination activity that was found to be specifically inhibited by Lewis B and Lewis Y tetrasaccharides. The MmHc displayed two oligomers of molecular weight approximately ∼78 and ∼85 kDa in SDS-PAGE. The native molecular mass of MmHc was found to be ∼457 kDa as determined by size-exclusion chromatography which indicated that the purified MmHc is an oligomeric protein. MmHc showed a maximum activity within pH 7.0–8.0, while a wide range of temperature stability was observed between 4 to 55 °C, however, it did not show any dependency on metal ions for binding. Subsequently, the analysis of the peptides by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) identified the purified MmHc as shrimp hemocyanin showing significant similarity to the hemocyanin of Penaeus vannamei. The results of multiple sequence alignment and detailed analysis of the molecular interactions predicted by AutoDock suggested that besides the oxygen carrier function, this MmHc may have multiple roles and can interact well with the Lewis Y antigen through a typical sugar binding motif containing the similar hydrophilic amino acids as the conserved residues. • A hemocyanin from a shrimp, Metapenaeus monoceros (named as MmHc), was purified by size-exclusion chromatography. • SDS- and native-PAGE analysis indicated MmHc as an oligomeric protein that was specifically inhibited by Lewis Y and B sugars. • MALDI-TOF/MS analysis revealed it as hemocyanin and showed sequence similarity with hemocyanin of shrimp. • MSA and molecular docking study revealed the presence of a typical sequence motif, whose hydrophilic amino acid residues involved in Lewis sugar interaction. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus and Staphylococcus epidermidis are frequently associated with medical device infections that involve establishment of a bacterial biofilm on the device surface. Staphylococcal surface proteins Aap, SasG, and Pls are members of the Periscope Protein class and have been implicated in biofilm formation and host colonization; they comprise a repetitive region ("B region") and an N-terminal host colonization domain within the "A region," predicted to be a lectin domain. Repetitive E-G5 domains (as found in Aap, SasG, and Pls) form elongated "stalks" that would vary in length with repeat number, resulting in projection of the Nterminal A domain variable distances from the bacterial cell surface. Here, we present the structures of the lectin domains within A regions of SasG, Aap, and Pls and a structure of the Aap lectin domain attached to contiguous E-G5 repeats, suggesting the lectin domains will sit at the tip of the variable length rod. We demonstrate that these isolated domains (Aap, SasG) are sufficient to bind to human host desquamated nasal epithelial cells. Previously, proteolytic cleavage or a deletion within the A domain had been reported to induce biofilm formation; the structures suggest a potential link between these observations. Intriguingly, while the Aap, SasG, and Pls lectin domains bind a metal ion, they lack the nonproline cis peptide bond thought to be key for carbohydrate binding by the lectin fold. This suggestion of noncanonical ligand binding should be a key consideration when investigating the host cell interactions of these bacterial surface proteins. [ABSTRACT FROM AUTHOR]

The mushroom Hericium erinaceus expresses isolectins with different glycan binding specificities; of these, the ricin B-like lectin HEL1 and HEL2 (HEL2a and HEL2b) can bind fucosylated N-glycans and core 1 O-glycans, respectively. However, other lectin-like protein-coding transcripts detected in the H. erinaceus transcriptome, named HEL3, remain to be characterized. Therefore, in this study, the expression levels of all these isolectins genes were compared to characterize the molecular and biochemical properties of these carbohydrate-binding proteins. Low expression genes encoding putative cytolysin proteins, HEL3a and HEL3b, were identified. Bioinformatics analyses revealed that these proteins shared highly homologous structures and carbohydrate-binding residues with other mushroom lectins. Further, their recombinant proteins, rHEL3a and rHEL3b showed an octamer composed of identical 17 kDa subunits under non-denaturing conditions and a slightly basic isoelectric point value of approximately 8.3. The hemagglutination activity of these isolectins was strongly inhibited by glycoproteins rather than free glycans. Interestingly, glycan-binding profiles showed that rHEL3 isolectins interacted with most polylactosamine (poly-LacNAc)-extended N-glycans with relatively low binding activity. Isothermal titration calorimetry also revealed that these recombinant lectins have different binding capacities toward N-glycan-containing glycoproteins. Further, treatment with different concentrations of rHEL3 lectins showed cytotoxic effects in K562, UACC62, and CHO model cell lines, which express poly-LacNAc glycans, confirmed by inhibition of proliferation. Overall, these biochemical properties indicate that rHEL3 isolectins may be used as unique lectins for detecting poly-LacNAc-extended glycans, which are known to be over-expressed in leukemia or metastatic melanoma cells, in cancer diagnostic assays and anti-cancer therapies. [ABSTRACT FROM AUTHOR]

Blocking the signaling activated by the plasma membrane receptor CD93 has recently been demonstrated a useful tool in antiangiogenic treatment and oncotherapy. In the proliferating endothelium, CD93 regulates cell adhesion, migration, and vascular maturation, yet it is unclear how CD93 interacts with the extracellular matrix activating signaling pathways involved in the vascular remodeling. Here for the first time we show that in endothelial cells CD93 is structured as a dimer and that this oligomeric form is physiologically instrumental for the binding of CD93 to its ligand Multimerin-2. Crystallographic X-ray analysis of recombinant CD93 reveals the crucial role played by the C-type lectin-like and sushi-like domains in arranging as an antiparallel dimer to achieve a functional binding state, providing key information for the future design of new drugs able to hamper CD93 function in neovascular pathologies. [ABSTRACT FROM AUTHOR]

Objective: Accumulated studies have revealed that oxidative stress and inflammation play important roles in the development of OSA related cognitive dysfunction. Galectin-3, a member of the galectin family, has been reported to be involved in the neuroinflammatory diseases. However, the relationship between Galectin-3 and cognitive impairment in OSA remains ambiguous.Materials and Methods: 47 new diagnosed OSA patients and 18 age-, gender-, education- and body mass index-matched healthy control subjects were enrolled in the present study. All subjects underwent whole-night in-laboratory polysomnography (PSG). Montreal Cognitive Assessment (MoCA) was used to evaluated the cognitive function of OSA patients. Serum Galectin-3, interleukin (IL)-1β and IL-8 were examined by enzyme-linked immunosorbent assay (ELISA). The levels of malonaldehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were measured to evaluate oxidative stress. Protein level of Galectin-3 and NLRP3 in peripheral blood mononuclear cells (PBMCs) and human microglial clone 3 (HMC3) cells were measured by Western Blot.Results: Serum Galectin-3 level in severe OSA patients (2.31 ± 0.43 ng/m) was higher than those in mild-moderate OSA patients (1.87 ± 0.32 ng/m, p < 0.001) and those in the healthy controls (1.56 ± 0.22 ng/ml, p < 0.001). Similarly, Galectin-3 level in PBMCs was increased with disease severity (p < 0.01). In addition, OSA patients also showed higher levels of inflammation and oxidative stress (p < 0.01). Patients with OSA scored significantly lower than healthy controls on the MoCA test after controlling for age, gender, education, and BMI. CPAP treatment for 12 weeks effectively reduced the levels of Galectin-3, inflammation and oxidative stress, as well as improved cognitive function of severe OSA patients. Closed correlations were observed between Galectin-3 with sleep respiratory parameters and cognitive dysfunction. In addition, we explored the underlying mechanism of Galectin-3 in neuroinflammation and oxidative stress. We treated HMC3 cells with LPS to mimic neuroinflammatory response in vitro. The results showed that LPS treatment led to a dose-dependent increase in Galectin-3 expression, meanwhile induced inflammation and oxidative stress. Inhibiting Galectin-3 with a specific Galectin-3 inhibitor, TD139, significantly ameliorated LPS-induced neuroinflammation and oxidative stress via suppressing NLRP3.Conclusion: Current findings suggest that increased Galectin-3 might be involved in the cognitive impairment of OSA patients by promoting neuroinflammation and oxidative stress via regulating NLRP3. These results suggested that Galectin-3 inhibition may exert a protective role against the neurocognitive dysfunction associated with OSA. [ABSTRACT FROM AUTHOR]

Because of the apparent stasis in antibiotic discoveries and the growth of multidrug resistance, Helicobacter pylori -associated gastric infections are difficult to eradicate. In the search for alternative therapy, the reductive amination of chitosan with mannose, followed by ionic gelation, produced mannose functionalized chitosan nanoparticles. Then, molecular docking and molecular dynamics (MD) simulations were conducted with H. pylori lectin (HPLectin) as a target protein involved in bacterium adherence to host cells, biofilm formation, and cytotoxicity. Changes in zeta potential and FTIR spectroscopy revealed that chitosan was functionalized with mannose. Time-kill, polystyrene adherence, and antibiofilm studies were utilized to assess nanoparticles as an alternative antibacterial treatment against a resistant gastric pathogen. Man-CS-Nps were discovered to have effective anti-adherence and biofilm disruption characteristics in suppressing the development of resistant H. pylori. In addition, bioimaging studies with CLSM, TEM, and SEM illustrated that Man-CS-Nps interacted with bacterial cells and induced membrane disruption by creating holes in the outer membranes of the bacterial cells, resulting in the leakage of amino acids. Importantly, molecular docking and 20 ns MD simulations revealed that Man-CS-Nps inhibited the target protein through slow-binding inhibition and hydrogen bond interactions with active site residues. As a consequence of the findings of this study, the Man-CS-Nps is an excellent candidate for developing alternative therapies for the increasing incidences of resistant gastric infections. [ABSTRACT FROM AUTHOR]

Mannose/glucose-binding lectin from Canavalia ensiformis seeds (Concanavalin A - ConA) has several biological applications, such as mitogenic and antitumor activity. However, most of the mechanisms involved in the in vivo toxicity of ConA are not well known. In this study, the Drosophila melanogaster model was used to assess the toxicity and genotoxicity of different concentrations of native ConA (4.4, 17.5 and 70 μg/mL) in inhibited and denatured forms of ConA. The data show that native ConA affected: the survival, in the order of 30.6 %, and the locomotor performance of the flies; reduced cell viability to levels below 50 % (4.4 and 17.5 μg/mL); reduced nitric oxide levels; caused lipid peroxidation and increased protein and non-protein thiol content. In the Comet assay, native ConA (17.5 e 70 μg/mL) caused DNA damage higher than 50 %. In contrast, treatments with inhibited and denatured ConA did not affect oxidative stress markers and did not cause DNA damage. We believe that protein-carbohydrate interactions between ConA and carbohydrates of the plasma membrane are probably the major events involved in these activities, suggesting that native ConA activates mechanisms that induce oxidative stress and consequently DNA damage. • The Lectin ConA induces ROS production. • ConA causes oxidative stress in Drosophila melanogaster. • The toxic effect of ConA results in damage to DNA and membranes. • The toxic effect of ConA is related to its CRD. [ABSTRACT FROM AUTHOR]

Biomimetic mineralization of enzymes for enhanced stability and activity is an important area of research due to its potential applications. Inorganic materials with enzymes coated and or embedded in them, viz., protein-inorganic hybrid nanomaterials with distinctive morphology and surface characteristics are promising candidates for exploring their elevated enzymatic activity. In this work, we have developed two different types of protein inorganic nanohybrid materials using a 120 kDa lectin purified from bitter gourd seeds (Momordica charantia lectin, MCL), and (i) copper phosphate nanoflowers to result in a protein – inorganic nano hybrid material CuPNF_MCL and (ii) encapsulating the protein in zeolitic imidazole framework, ZIF8_MCL. While CuPNF_MCL showed floral morphology, the ZIF8_MCL mostly showed hexapod morphology as noticed from the microscopy data. Both the nanomaterials showed a distinctive trend of decrease in size with increase in the protein concentration used during the preparation. The nanoflowers also showed an increase in the tightness of the packing of petals with increase in the protein concentration. Powder X-Ray diffraction studies confirmed the crystallinity of the inorganic frameworks. The Fourier Transform infrared spectroscopy studies coupled with confocal imaging of the fluorophore tagged MCL embedded hybrids confirmed the presence of the protein. The MCL protein was examined for its ability to cleave DNA, i.e., nuclease activity using pBR322, wherein the form I plasmid is completely transformed into the form II / III at 2 mg/mL concentration of the protein. However, both the hybrids showed a superior nuclease activity as compared to the protein, wherein the CuPNF_MCL showed a threefold greater nuclease activity as compared to the ZIF8_MCL. The greater nuclease activity of CuPNF_MCL is attributable to its mesoporous nature with higher pore size and pore volume as compared to that in case of ZIF8_MCL, which is microporous in nature. Thus, in this paper, we have purified a nuclease like lectin from bitter gourd seeds and improved its nuclease property by converting it into inorganic hybrid nanomaterial of two types wherein higher activity was observed in the material having better porosity and surface area characteristics. [Display omitted] • Purification and characterization of Momordica charantia lectin (MCL) from bitter gourd seeds. • Preparation and characterization of protein-inorganic hybrids CuPNF_MCL and ZIF8_MCL. • Study the DNA nuclease activity of MCL protein using agarose gel electrophoresis and pBR322 plasmid DNA. • Study the higher nuclease activity of CuPNF_MCL/ ZIF8_MCL compared to MCL protein. • Understand the higher activity of CuPNF_MCL compared to ZIF8_MCL using BET surface area experiments. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a long-term chronic disease characterized by abnormal high level blood glucose (BG). An artificial closed-loop system that mimics pancreatic β-cells and releases insulin on demand has potential to improve the therapeutic efficiency of diabetes. Herein, a lectin Concanavalin A modified oxidized starch nanogel was designed to regulate glucose dynamically according to different glucose concentrations. The nanogels were formed by double cross-linking the Concanavalin A and glucose units on oxidized starch via specific binding and amide bonds to achieve the high drug loading and glucose responsiveness. The results showed that oxidized starch nanogels prolonged the half-life of antidiabetic peptide drug exenatide and released it in response to high BG concentrations. It could absorb BG at a high level and maintain glucose homeostasis. Besides, the oxidized starch nanogels performed well in recovering regular BG level from hyperglycemia state and maintaining in euglycemia state that fitted in a biological rhythm. In addition, the nanogels showed high biocompatibility in vivo and could improve plasma half-life and therapeutic efficacy of exenatide. Overall, the nanogels protected peptide drugs from degradation in plasma as a glucose-responsive platform showing a high potential for peptide drugs delivery and antidiabetic therapy. A lectin Concanavalin A (Con A) modified oxidized starch (OS) nanogels was developed through inverse-emulsion method by double cross-linking via Con A-glucose unit specific affinity binding and amide bonds between Con A and carboxyl groups on the TEMPO-oxidized starch. Peptide drug exenatide (EX) with extremely short half-life was effectively loaded into the nanogels due to its excellent swelling capacity. The EX-loaded nanogels showed a glucose-responsive controlled release property and could maintain glucose homeostasis. At low glucose concentration, the nanogels showed an interesting swelling and deswelling behavior as an "on-off" effect in response to adding glucose and removing glucose in the media. However, at high glucose concentration, glucose could competitively bind to Con A on nanogels, disrupting the nanogels and releasing the loaded EX to adjust the blood glucose level. The EX-loaded nanogels with a high biocompatibility showed a long-term therapeutic effect in diabetic mice. [Display omitted] • OS-Con A Ngels were prepared by double cross-linking via affinity and amide bonds. • OS-Con A Ngels showed a high biocompatibility and glucose stimuli-responsive property. • OS-Con A Ngels could responsively release EX and regulate glucose hemostasis. • The Ngels prolonged the half-life of EX and improved the glucose regulating property. • Ngels-EX showed both short and long-term therapeutic efficacy in diabetes mice. [ABSTRACT FROM AUTHOR]

Fibrosis, stiffening and scarring of an organ/tissue due to genetic abnormalities, environmental factors, infection, and/or injury, is responsible for > 40% of all deaths in the industri-alized world, and to date, there is no cure for it despite extensive research and numerous clinical trials. Several bio-markers have been identified, but no effective therapeutic targets are available. Human galectin-3 is a chimeric gene product formed by the fusion of the internal domain of the collagen alpha gene [N-terminal domain (ND)] at the 5'-end of galectin-1 [C-terminal domain (CRD)] that appeared during evolution together with vertebrates. Due to the overlapping structural similarities between collagen and galectin-3 and their shared susceptibility to cleavage by matrix metal-loproteases to generate circulating collagen-like peptides, this review will discuss present knowledge on the role of collagen and galectin-3 as biomarkers of fibrosis. We will also highlight the need for transformative approaches targeting both the ND and CRD domains of galectin-3, since glycoconjugate binding by the CRD is triggered by ND-mediated oligomerization and the therapies targeted only at the CRD have so far achieved limited success. [ABSTRACT FROM AUTHOR]

The macrophage mannose receptor (MR, CD206) is a transmembrane endocytic lectin receptor, expressed in selected immune and endothelial cells, and is involved in immunity and maintaining homeostasis. Eight of the ten extracellular do-mains of the MR are C-type lectin domains (CTLDs) which mediate the binding of mannose, fucose, and GlcNAc in a calcium-dependent manner. Previous studies indicated that self-glycosylation of MR regulates its glycan binding. To further explore this structure-function relationship, we studied herein a recombinant version of mouse MR CTLD4-7 fused to human Fc-portion of IgG (MR-Fc). The construct was expressed in different glycosylation-mutant cell lines to study the influence of differential glycosylation on receptor glycan- binding properties. We conducted site-specific N- and O-glycosylation analysis and glycosylation site characterization using mass spectrometry by which several novel O-glycosylation sites were identified in mouse MR and confirmed in human full-length MR. This information guided experiments evaluating the receptor functionality by glycan microarray analysis in combination with glycan-modifying enzymes. Treatment of active MR-Fc with combinations of exoglycosidases, including neuraminidase and galactosidases, resulted in the loss of trans-binding (binding of MR CTLDs to non-MR glycans), due to unmasking of terminal, nonreducing GlcNAc in N-glycans of the MR CTLDs. Regalactosylation of N-glycans rescues mannose binding by MR-Fc. Our results indicate that glycans within the MR CTLDs act as a regulatory switch by masking and unmasking self-ligands, including terminal, nonreducing GlcNAc in N-glycans, which could control MR activity in a tissue- and cell-specific manner or which potentially affect bacterial pathogenesis in an immunomodulatory fashion. [ABSTRACT FROM AUTHOR]

Viscumin, a lectin used in anti-cancer therapy, was originally considered as βGal recognizing protein; later, an ability to bind 6′-sialyl N-acetyllactosamine (6′SLN) terminated gangliosides was found. Here we probed viscumin with a printed glycan array (PGA) containing a large number of mammalian sulfated glycans, and found a strong binding to glycans with 6-O-SuGal moiety as lactose, N-acetyllactosamine (LN), di-N-acetyllactosamine (LacdiNAc), and even 6- O -SuGalNAcα (but not SiaTn). Also, the ability to bind some of αGal terminated glycans, including Galα1-3Galβ1-4GlcNAc, was observed. Unexpectedly, only weak interaction was detected with parent neutral β-galactosides including LN-LN-LN and branched (LN) 2 LN oligolactosamines; in the light of these data, one should not confidently classify viscumin as a β-galactoside-binding lectin. Carrying out PGA in the presence of neutral or sulfated/sialylated glycan, together with sequential elution from lactose-sepharose and consideration of the protein structure, lead to the conclusion that two glycan-binding sites of viscumin have different specificities, one of which prefers charged sulfated and sialylated moieties. • Viscumin specificity is broader than what was commonly believed to be galactose-ended glycans. • Two glycan-binding sites of viscumin have different specificities. • Viscumin has high affinity to glycans with 6-O-SuGal moiety. [ABSTRACT FROM AUTHOR]

Since the early discovery of plant lectins at the end of the 19th century, and the finding that they could agglutinate erythrocytes and precipitate glycans from their solutions, many applications and biological roles have been described for these proteins. Later, the observed erythrocytes clumping features were attributed to the lectin-cell surface glycoconjugates recognition. Neoplastic transformation leads to various cellular alterations which impact the growth of the cell and its persistence, among which is the mutation in the outer surface glycosylation signatures. Quite a few lectins have been found to act as excellent biomarkers for cancer diagnosis while some were presented with antiproliferative activity that initiated by lectin binding to the respective glycocalyx receptors. These properties are blocked by the hapten sugar that is competing for the lectin affinity binding site. In vitro investigations of lectin-cancer cell's glycocalyx interactions lead to a series of immunological reactions that result in autophagy or apoptosis of the transformed cells. Mistletoe lectin, an agglutinin purified from the European Viscum album is the first plant lectin employed in the treatment of cancer to enter into the clinical trial phases. The entrapment of lectin in nanoparticles besides other techniques to promote bioavailability and stability have also been recently studied. This review summarizes our up-to-date understanding of the future applications of plant lectins in cancer prognosis and diagnosis. With the provision of many examples of lectins that exhibit anti-neoplastic properties. Tumor-associated glycan antigen structures. [Display omitted] • Lectins (agglutinin) are carbohydrate-binding proteins of non-immune origin. • Neoplastic transformation leads to various cellular alterations, including outer surface glycosylation signatures mutation. • Many plant lectins can recognize changes in tumor cells and are thus useful tools in tumor diagnosis and prognosis. • Many plant lectins have been endowed with the capacity to either cause a cytotoxic effect or apoptosis to tumor cells. • Mistletoe lectin is the first agglutinin to enter into clinical trials and produce promising outcomes. [ABSTRACT FROM AUTHOR]

Photosynthetic microorganisms, specifically cyanobacteria and microalgae, can synthesize a vast array of biologically active molecules, such as lectins, that have great potential for various biotechnological and biomedical applications. However, since the structures of these proteins are not well established, likely due to the presence of intrinsically disordered regions, our ability to better understand their functionality is hampered. We embarked on a study of the carbohydrate recognition domain (CRD), intrinsically disordered regions (IDRs), amino acidic composition, as well as and functional motifs in lectins from cyanobacteria of the genus Arthrospira and microalgae Chlorella and Dunaliella genus using a combination of bioinformatics techniques. This search revealed the presence of five distinctive CRD types differently distributed between the genera. Most CRDs displayed a group-specific distribution, except to C. sorokiniana possessing distinctive CRD probably due to its specific lifestyle. We also found that all CRDs contain short IDRs. Bacterial lectin of Arthrospira prokarionte showed lower intrinsic disorder and proline content when compared to the lectins from the eukaryotic microalgae (Chlorella and Dunaliella). Among the important functions predicted in all lectins were several specific motifs, which directly interacts with proteins involved in the cell-cycle control and which may be used for pharmaceutical purposes. Since the aforementioned properties of each type of lectin were investigated in silico , they need experimental confirmation. The results of our study provide an overview of the distribution of CRD, IDRs, and functional motifs within lectin from the commercially important microalgae. • Cyanobacteria and microalgae lectins are few characterized structurally. • Most of carbohydrate recognition domains seems to be microalgae group-specific. • Lectins from Dunaliella and Chlorella contain higher levels of IDR than Artrhospira. • C. sorokiniana is lectin source with higher number and types of functional motifs. [ABSTRACT FROM AUTHOR]

Plant bioactive compounds are extensively used in traditional medicine to treat diabetes, inflammation, hypertension, liver disease, and microbial infections. In this context, plant proteins are promising molecules in the treatment of candidiasis, being an alternative to the classical antifungals currently in use. This study aimed to better understand the structural characteristics of Mo -CBP 2 , a chitin-binding protein isolated from Moringa oleifera seeds. Its mode of action against Candida spp. was investigated, evaluating protein oligomerization, pore formation, secondary structure, cell wall interaction, and biofilm inhibition. Mo -CBP 2 has a trimeric and hexameric structure, which may explain its aggregation effect against Candida albicans cells. Both yeast aggregation and anti-candida activity were depleted in the presence of N,N,N′-acetylchitotriose and laminarin, indicating that Mo -CBP 2 interacts with the fungal cell wall. Mo -CBP 2 showed high stability at extreme temperatures (100 ºC) and pH (2, 4 and 10). Furthermore, treatment with Mo -CBP 2 caused pores, severe morphological damage, and the release of cytoplasmic material in Candida. Mo -CBP 2 also showed a synergistic effect with azole, polyene, and echinocandin antifungals. Finally, Mo -CBP 2 strongly inhibited biomass production in both mature and non-mature biofilms of C. albicans. This study highlights the biotechnological potential of Mo -CBP 2 as a promising anti-candida molecule against planktonic and sessile C. albicans cells. [Display omitted] • Mo -CBP2, a protein from M. oleifera , has antifungal activity against Candida sp. • Mo- CBP2 presents a trimeric and hexameric structure, and it is highly stable. • The treatment with Mo- CBP2 caused severe damages in C. albicans cells. • The protein showed synergistic effect with antifungal drugs. • Mo- CBP2 was also active against biofilm formation and preformed biofilm. [ABSTRACT FROM AUTHOR]

Siglec-3, also known as CD33, is a type of sialic acid binding immunoglobulin-like lectin that plays a role in regulating cellular activation in the innate immune system and subsequent inflammatory responses. In this study, we cloned the cDNA encoding OnSiglec3-like ORF sequence (1170 bp) in Nile tilapia, contained two Ig-like domains in the extracellular region and one inhibitory ITIM-like motif in the intracellular region. Through qRT-PCR analysis, we found that the mRNA of OnSiglec3-like lectin was highly expressed in the brain and head kidney. When challenged with Streptococcus agalactiae both in vivo and in vitro , we observed a significant up-regulation in the expression of OnSiglec3-like lectin in the head kidney tissues and leukocytes, respectively. Additionally, we investigated the interaction between a recombinant extracellular region protein (referred to as (r)exSiglec3-like protein) and three different phenotypes of S. agalactiae : WT (wild type), ∆cps (cps-deficient mutant), and ∆neuA (sia-deficient mutant) using ELISA. We found that the exOnSiglec3-like protein, when combined with RNA interference and bacterial infection, significantly enhanced the phagocytic ability against S. agalactiae. Furthermore, the expression of four common inflammatory factors (OnIL-6, OnIL-10, OnTNF-α, and OnTGF-β) showed a significant up-regulation. Overall, this study suggests that OnSigelc3-like lectin may play a role in host defence against bacterial infection and mediate immune escape in Nile tilapia. • A Siglec3-like lectin was identified and characterized in Nile tilapia. • The recombinant exOnSiglec3-like bound the three different phenotypes of S. agalactiae. • The (r)exOnSiglec3-like protein could enhance the phagocytic ability to S. agalactiae significantly. • Siglec3-like could regulate the expression of the inflammatory factors in head kidney leukocytes. [ABSTRACT FROM AUTHOR]

The Araceae family boasts >3000 species of flowering plants that thrive across the tropics. Among the focal points of study within this family are lectins, proteins with affinity for binding carbohydrates. This review endeavors to gather data gleaned from numerous studies conducted over the past three decades on lectins extracted from Araceae plants. Our examination spans their extraction and purification methods, their specific interactions with carbohydrates, their molecular structures, and various physicochemical characteristics. Furthermore, we investigated the biological activities of these lectins and investigated the outcomes of cloning their genes. Despite their apparent similarities, these lectins exhibit notable distinctions, particularly regarding their unique preferences in interacting with erythrocytes from animals and humans, their sugar affinities, the critical amino acids for their functionality, the molecular weights of their subunits and their respective topologies, and ultimately, their dimerization and 3D β-prism-II structure, which reportedly diverge from those observed in other GNA-related lectins. These discrepancies not only deepen our understanding of monocot lectins but also render these proteins inherently captivating. This review marks the inaugural attempt at consolidating almost all published reports on lectins from the Araceae family, with the aim of furnishing glycobiology scientists with essential insights into potential laboratory challenges, the characteristics of these lectins, and avenues for future research. [Display omitted] • Reviews three decades of Araceae lectin research. • Covers extraction, purification, structures, and properties. • Investigates biological activities and gene cloning. • Examines unique interactions and 3D structures. • First comprehensive review for glycobiology. • Provides insights into challenges and future research. [ABSTRACT FROM AUTHOR]

Plant lectins, a diverse group of carbohydrate-binding proteins, have garnered significant interest for their potential biomedical applications. This review explores their multifaceted functionalities, highlighting their historical significance, unique carbohydrate recognition properties, and therapeutic potential in various medical conditions. We discuss their efficacy against microbes, cancer cells, and inflammation, as well as their roles in blood typing, diagnostics, wound healing, and neuroprotection. Additionally, we explored the potential of lectin-based drug delivery systems and lectin-nanoparticle conjugates for targeted therapeutic interventions. However, challenges such as lectin specificity, toxicity, production methods, and clinical validation are acknowledged. Overcoming these hurdles is crucial to unlocking the full potential of plant lectins and paving the way for advancements in medicine. [ABSTRACT FROM AUTHOR]

Galectins are glycan-binding proteins translating the sugar-encoded information of cellular glycoconjugates into physiological activities, including immunity, cell migration, and signaling. Galectins also interact with non-glycosylated partners in the extracellular milieu, among which the pre-B cell receptor (pre-BCR) during B cell development. How these interactions might interplay with the glycan-decoding function of galectins is unknown. Here, we perform NMR experiments on native membranes to monitor Gal-1 binding to physiological cell surface ligands. We show that pre-BCR interaction changes Gal-1 binding to glycosylated pre-B cell surface receptors. At the molecular and cellular levels, we identify α2,3-sialylated motifs as key targeted epitopes. This targeting occurs through a selectivity switch increasing Gal-1 contacts with α2,3-sialylated poly- N -acetyllactosamine upon pre-BCR interaction. Importantly, we observe that this switch is involved in the regulation of pre-BCR activation. Altogether, this study demonstrates that interactions to non-glycosylated proteins regulate the glycan-decoding functions of galectins at the cell surface. [Display omitted] • The pre-BCR (λ5-UR) modifies Gal-1 binding to cell surface glycoconjugates • Gal-1 targets cell surface α2,3-sialylated glycoconjugates upon pre-BCR binding • Gal-1 selectivity switch occurs by increased contacts with α2,3-sialylated glycans • Targeting of α2,3-sialylated glycoconjugates by Gal-1 regulates pre-BCR signaling Touarin et al. report NMR monitoring of Gal-1 binding to cell surface ligands. They find that interaction with the pre-BCR changes Gal-1 binding to specifically target α2,3-sialylated glycoconjugates at the pre-B cell surface. This targeting regulates pre-BCR signaling, a key checkpoint during B cell development. [ABSTRACT FROM AUTHOR]

Leishmaniases, caused by Leishmania parasites, are widespread and pose significant health risks globally. Visceral leishmaniasis (VL) is particularly prevalent in Brazil, with high morbidity and mortality rates. Traditional treatments, such as pentavalent antimonials, have limitations due to toxicity and resistance. Therefore, exploring new compounds like lectins is crucial. Concanavalin A (ConA) has shown promise in inhibiting Leishmania growth. This study aimed to evaluate its leishmanicidal effect on L. infantum promastigotes and understand its mechanism of action. In vitro tests demonstrated inhibition of promastigote growth when treated with ConA, with IC 50 values ranging from 3 to 5 μM over 24–72 h. This study suggests that ConA interacts with L. infantum glycans. Additionally, ConA caused damage to the membrane integrity of parasites and induced ROS production, contributing to parasite death. Scanning electron microscopy confirmed morphological alterations in treated promastigotes. ConA combined with the amphotericin B (AmB) showed synergistic effects, reducing the required dose of AmB, and potentially mitigating its toxicity. ConA demonstrated no cytotoxic effects on macrophages, instead stimulating their proliferation. These findings reinforce that lectin exhibits promising leishmanicidal activity against L. infantum promastigotes, making ConA a potential candidate for leishmaniasis treatment. • ConA has anti-promastigote activity. • ConA interacts with leishmania glycans. • ConA induces membrane and cell wall damage and ROS overproduction. • ConA increases the action of amphotericin B. [ABSTRACT FROM AUTHOR]

Lectins are proteins or glycoproteins of non-immune origin with carbohydrate-binding properties. They are found both prokaryotic and eukaryotic organisms. The most abundant source of the lectins are plants. Many lectins have anticancer effects by directly exerting cytotoxic effects on malignant cells or indirectly activating the immune system. Lectins also have antiviral activities. These proteins can recognise glycoproteins on the surface of enveloped viruses and bind to them. This creates a physical barrier between them and the corresponding receptors on the surface of the host cell, which prevents the virus from entering the cell and can thus effectively inhibit the replication of the virus. In this review, we focus on the anticancer activities of selected lectins and the underlying mechanisms. We also discuss different types of lectins with antiviral activity. We have paid special attention to lectins with inhibitory activity against SARS-CoV-2. Finally, we outline the challenges of using lectins in therapy and suggest future research directions. [ABSTRACT FROM AUTHOR]

Exosomes, as emerging biomarkers in liquid biopsies in recent years, offer profound insights into cancer diagnostics due to their unique molecular signatures. The glycosylation profiles of exosomes have emerged as potential biomarkers, offering a novel and less invasive method for cancer diagnosis and monitoring. Colorectal cancer (CRC) represents a substantial global health challenge and burden. Thus there is a great need for the aberrant glycosylation patterns on the surface of CRC cell-derived exosomes, proposing them as potential biomarkers for tumor characterization. The interactions of 27 lectins with exosomes from three CRC cell lines (SW480, SW620, HCT116) and one normal colon epithelial cell line (NCM460) have been analyzed by the lectin microarray. The result indicates that Ulex Europaeus Agglutinin I (UEA-I) exhibits high affinity and specificity towards exosomes derived from SW480 cells. The expression of glycosylation related genes within cells has been analyzed by high-throughput quantitative polymerase chain reaction (HT-qPCR). The experimental result of HT-qPCR is consistent with that of lectin microarray. Moreover, the limit of detection (LOD) of UEA-I microarray is calculated to be as low as 2.7 × 105 extracellular vehicles (EVs) mL−1 (three times standard deviation (3σ) of blank sample). The UEA-I microarray has been successfully utilized to dynamically monitor the progression of tumors in mice-bearing SW480 CRC subtype, applicable in tumor sizes ranging from 2 mm to 20 mm in diameter. The results reveal that glycan expression pattern of exosome is linked to specific CRC subtypes, and regulated by glycosyltransferase and glycosidase genes of mother cells. Our findings illuminate the potential of glycosylation molecules on the surface of exosomes as reliable biomarkers for diagnosis of tumor at early stage and monitoring of cancer progression. [Display omitted] • The aberrant glycosylation patterns of CRC cell-derived exosomes have been analyzed. • UEA-I has been found as a biorecognition molecule for SW480 CRC subtype. • The expression of glycosylation related genes has been analyzed by HT-qPCR. • UEA-I has been utilized to monitor the progression of SW480 tumor. [ABSTRACT FROM AUTHOR]

Non-enzymatic cascade reactions between amines and reducing sugars are known as Maillard reaction. The late phase of these reactions consists of advanced glycation end products (AGEs), which have been implicated in the pathogenesis of numerous human diseases. Recent evidence suggests that galectin-3 acts as a receptor for AGEs and some early products of the Maillard reaction. The early phase of the Maillard reaction, which consists of 1-amino-1-deoxyketoses (Amadori compounds) and 2-amino-2-deoxyaldoses (Heyns compounds), was the subject of our study. The binding interactions between galectin-3 and the Amadori and Heyns compounds of leucine-enkephalin (YGGFL), leucine-enkephalin methyl ester (YGGFL-OMe), truncated enkephalin (YGG and Y) and tetrapeptide (LSKL) were measured using the AlphaScreen competitive binding assay. The affinity of galectin-3 for Amadori and Heyns compounds depends on both the sugar moiety and the amino acid sequence of the model compounds. The best results were obtained with Leu-enkephalin derivatives of Amadori (IC 50 = 6.06 μm) and Heyns (IC 50 = 8.6 μm) compound, respectively. [Display omitted] • The interactions between Amadori and Heyns compounds of Leu-enkephalin and the tetrapeptide Leu-Ser-Lys-Leu with galectin-3 were investigated. • The AlphaScreen competitive binding assay was used to study the interactions of Amadori and Heyns compounds with galectin-3. • The Heyns compounds showed a higher affinity for galectin-3 compared to Amadori compounds. • The lack of the aromatic residues within the peptide sequence, showed a significantly lower affinity for galectin-3. [ABSTRACT FROM AUTHOR]

Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin, has been implicated in the progression of preeclampsia (PE). This heterogeneous syndrome (defined by hypertension with or without proteinuria after 20 weeks of pregnancy) remains a major global health burden with long-term consequences for both mothers and child. Previously, we showed that in vivo systemic human (hsFLT1) overexpression led to reduced placental efficiency and PE-like syndrome in mice. Galectins (gal-1, −3 and −9) are critical determinants of vascular adaptation to pregnancy and dysregulation of the galectin-glycan circuits is associated with the development of this life-threatening disease. In this study, we assessed the galectin-glycan networks at the maternal-fetal interface associated with the hsFLT1-induced PE in mice. We observed an increase on the maternal gal-1 expression in the decidua and junctional zone layers of the placenta derived from hs FLT1high pregnancies. In contrast, placental gal-3 and gal-9 expression were not sensitive to the hsFLT1 overexpression. In addition, O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation were down-regulated in hsFLT1 high placentas. Thus, the gal-1-glycan axis appear to play an important role counteracting the anti-angiogenic status caused by sFLT1, becoming critical for vascular adaptation at the maternal-fetal interface. • Anti-angiogenic milieu induced by human soluble fms-like tyrosine kinase-1 (hsFLT1) alters the galectin-glycan circuits during pregnancy. • Decidual gal-1 is upregulated in hsFLT1 induced Preeclampsia (PE)-like syndrome in mice. • hsFLT1 exerts a strong influence on the O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation at the maternal-fetal interface. [ABSTRACT FROM AUTHOR]

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 μg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 μg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC 50 = 3.5 μg/mL), KG1 (IC 50 = 18.6 μg/mL) and K562 (102.0 μg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 μg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte – HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells. [Display omitted] [ABSTRACT FROM AUTHOR]