Colorectal adenomas represent precursor lesions in the adenoma-carcinoma sequence and are characterized by chronic low-grade inflammation. Chemokine CCL20/CCR6 signaling and metabolic hormone ghrelin have been implicated in colorectal tumorigenesis, while IgG glycosylation reflects systemic immune status. However, their interrelationship across different stages of adenoma dysplasia remains unclear. A total of 70 patients with histologically confirmed colorectal adenomas were stratified into low-grade (n = 36) and high-grade dysplasia (n = 34). Serum CCL20, CCR6, acylated and deacylated ghrelin concentrations were measured using enzyme immunoassay (ELISA), while IgG N-glycans were analyzed by hydrophilic interaction liquid chromatography-ultra performance liquid chromatography (HILIC-UPLC). Correlation analyses were performed to assess associations between inflammatory, metabolic, and glycomic parameters. No significant differences were observed between low- and high-grade dysplasia in circulating CCL20, CCR6, acylated or deacylated ghrelin, or IgG N-glycosylation profiles. A significant positive correlation between acylated and deacylated ghrelin was detected only in high-grade dysplasia. In low-grade dysplasia, CCL20 correlated significantly with deacylated ghrelin. Additional nominal associations between ghrelin, CCL20, and selected IgG glycan traits were identified but lost significance after Benjamini-Hochberg false discovery rate correction. These exploratory associations included bisecting glycans with deacylated ghrelin and CCL20 with GP20, GP21, GP1, and GP10. Although systemic inflammatory biomarkers, ghrelin isoforms, and IgG N-glycosylation did not differ between dysplasia grades, distinct correlation patterns suggest stage-specific relationships. The association between CCL20 and deacylated ghrelin in low-grade dysplasia and the strong correlation between ghrelin isoforms in high-grade dysplasia warrant further investigation.

GlycoRNAs are a newly identified class of post‑transcriptionally modified small non‑coding RNAs that carry covalently attached N‑ and O‑linked glycans. This discovery challenges the conventional view that glycosylation is exclusive to proteins and lipids, and places RNA at the interface of glycobiology and immune recognition. Emerging evidence implicates glycoRNAs in tumor biology, where they function as cell‑surface ligands for Siglecs and P‑selectin, thereby modulating three interconnected processes: immune escape and immune regulation, intercellular communication and adhesion, and tumor metastasis and metabolic crosstalk. Recent technological advances-including single‑cell imaging (ARPLA), FRET‑based sEV analysis, and chemoenzymatic profiling-have enabled sensitive detection and revealed aberrant glycoRNA patterns across malignancies. Notably, tumor‑specific glycoRNA signatures correlate with immune checkpoint glycosylation (such as PD‑1/PD‑L1) and metabolic reprogramming. This review synthesizes current understanding of glycoRNA biosynthesis, structure, and function, with an emphasis on its emerging roles in the tumor microenvironment. We also outline the potential of RNA‑centric glycobiology for developing liquid biopsy biomarkers and mechanism‑informed immunotherapeutic strategies.

Mucopolysaccharidoses (MPS) are heterogeneous group of disorders caused by the deficiency of lysosomal enzymatic activities. Deficiencies in these enzymes are required for proper degradation of glycosaminoglycans (GAGs), thus referred as inborn errors of lysosomal GAG metabolism. Arylsulfatase K (ARSK) has been recently characterized as lysosomal hydrolase involved in GAG degradation removing the 2-O-sulfate group from 2-sulfoglucuronate and has been associated with MPS X. A 12-year-old female presented with developmental delay, progressive musculoskeletal abnormalities, and skeletal dysplasia, with symptom onset at 2-3 years of age. Whole exome sequencing [WES], followed by bi-directional Sanger sequencing was performed to identify the culprit gene. As the three-dimensional structure of ARSK has not yet been experimentally resolved, an in silico predicted ARSK model was used for structural modeling, molecular dynamics simulations, and stability analyses to investigate the effect of the identified variant on protein structure and function. Biochemical and molecular analysis revealed likely pathogenic novel variant (c.238T > G; p.Cys80Gly) in the ARSK gene [NM_198150.3]. The identified sequence variant was screened in 2000 in-house exomes from the same ethnic population. Here, we report a novel variant in ARSK gene associated with MPS X, which will help in proper genetic counselling of the family.

Lectins are made with identical polypeptide subunits as homo-oligomers in various species of Canavalia. Their interaction with the structures of specific glycans is influenced greatly when many identical polypeptides are cooperatively involved in a homo-oligomeric state than when they interact as individual polypeptide subunits. In the present study, lectins characterised from various species of Canavalia available in the literature were identified, and their sequences were retrieved to conduct in-silico bioinformatic analyses to offer a structural insight into their interaction with specific glycans such as D-mannose and. D-glucose. Our results disclosed that one of the critical parameters on the characteristic feature of lectins, i.e. the number of amino acids contributing to carbohydrate recognition domains (CRD) by lectin homo-oligomers in their tertiary and quaternary conformations through. in-silico docking, was less than in reported experimental studies conducted using XRD. Further, the docking results revealed that the kind of amino acids involved in recognising the structures of glycans was significantly different among homo-oligomeric polypeptide chains of various lectins, indicating the unique nature of each protein in their functions. The nature of glycan binding by these lectins was observed with higher affinity scores, with their quaternary structures containing four homo-oligomeric polypeptide chains. It is thus recognised that the unique nature of homo-oligomers of lectins from various species of Canavalia that possess analogous structural features relies profoundly on the kind of amino acid residues for their interaction with glycans in accomplishing their diverse functions.

Sirtuins, as classic NAD[+]-dependent class III histone deacetylases (HDACs), have been the focus of extensive research since their discovery, primarily centered on the mechanisms by which their deacetylase activity mediates the pathogenesis of various diseases and regulates key biological processes. With the rapid advancement of epigenetics, numerous novel acylation modifications, including lysine malonylation (Kma), lysine β-hydroxybutyrylation (Kbhb), lysine succinylation (Ksucc), and have been identified to date. Notably, the recently discovered lysine lactylation (Kla) modification has fundamentally revised long-held perception of lactic acid as a mere "metabolic waste". Importantly, SIRT1-3 have been shown to possess robust delactylase activity. To date, SIRT1-7 have been discovered to exert over ten distinct novel enzymatic functions. Herein, we summarized the functions of SIRT1-7 and their associated metabolic regulatory pathways in the context of post-translational modifications.

Previous study demonstrated that Hypnea cervicornis lectin (HCA) reduces inflammation and nociception via interaction with the lectin carbohydrate-binding site, modulating gene expression of the interleukins IL-1β, TNF-α and of iNOS. This study evaluated the effect of HCA in the rat model of arthritis induced by zymosan in the tibiotarsal joint and the involvement of macrophage-derived mediators. In vitro, macrophages were stimulated with zymosan before being incubated with HCA and the supernatant was injected into the joint. In vivo, HCA was administered by intravenous route after intra-articular injection of zymosan, fMLP, or macrophages supernatant. Hypernociception, edema and leukocyte influx were evaluated in the joints, and inflammatory mediators in the macrophage supernatant or periarticular tissue. In vitro, HCA (100 µg/ml) reduced NO2[-] and IL-1β in the supernatant of macrophages. In vivo, HCA (3 mg/kg) reduced articular hypernociception, edema and leukocyte influx elicited by zymosan, fMLP or by the supernatant of zymosan activated macrophages, as well as the zymosan-induced rolling and adhesion, and gene expression of iNOS and IL-1. HCA attenuated edema and leukocyte influx in the periarticular tissue, revealing preserved chondrocytes in the cartilage. In conclusion, HCA exerts anti-inflammatory effect in the arthritis induced by zymosan in rat tibio-tarsal joints, involving NO and IL-1 released by resident macrophages.

Sialidase Neu4 is a glycosidase that removes sialic acids from nonreducing ends of sugar chains. Recently, Mexican tetra Neu4 (AmNeu4) was identified as a nuclear-localized sialidase. However, the subnuclear localization and biological functions of AmNeu4 have remained unclear. This study demonstrated that AmNeu4 localized in the nucleolus and investigated the significance of its nuclear localization signal (NLS) for the nucleolar localization. Green fluorescent protein (GFP) fused to NLS localized to the nucleolus. Additionally, deletion of the NLS in AmNeu4 abolished its nucleolar localization, and insertion of additional lysine/arginine residues into AmNeu4's NLS induced exclusive nucleolar localization. These results indicated that the nucleolar localization of AmNeu4 was mediated by its NLS. The proliferation of AmNeu4-overexpressing HeLa cells was significantly reduced compared with that of the mock-transfected cells. Moreover, enzymatically inactive AmNeu4 also suppressed cell growth, indicating that the enzymatic activity of AmNeu4 is not required for the suppression of cell growth. We hypothesized that the suppressed cell proliferation is mediated by protein-protein interactions involving AmNeu4. By immunoprecipitation assay, ribosomal proteins L5 and L11 (RPL5 and RPL11, respectively) were identified as AmNeu4 interacting partners. C-MYC protein levels were lower in AmNeu4-overexpressing cells than in mock cells, and these reduced levels were restored by RPL11 knockdown. Coimmunoprecipitation assay further revealed that RPL11 bound to C-MYC in AmNeu4-overexpressing cells. These results suggest that the interaction between AmNeu4 and RPL5/RPL11 delays cell growth through destabilizing C-MYC.

Malignant melanoma has a high mortality rate and is aggressive. The development, metastasis, and angiogenesis of melanoma have all been connected to toll-like receptor 4 (TLR4). However, signal transduction mediated by TLR4 for accelerating melanoma progression is fully unclear. Because of this, the current research has been carried out to explore drug candidate possibility using 3'-Sialyllactose (3'-SL). We investigated the inhibitory effect of 3'-SL on migration and invasion, which are associated with treatment difficulty and mortality. The suppression of matrix metalloproteinases 9 (MMP-9) expression and activity by 3'-SL in B16F10 murine melanoma cells and concurrently downregulated the MAPK signaling pathway involved in this regulation. Therefore, our results demonstrate that 3'-SL may be a good candidate for the development of therapeutic agents to suppress malignancy associated with metastasis and invasion.

Optimizing non-viral vectors for gene therapy requires elucidating the molecular mechanisms underlying vector uptake and intracellular delivery. In this study, cell transfection using pDNA/polysaccharide complexes was investigated to develop a gene delivery system specific for gastric tumor cells that express hyaluronic acid (HA) receptors such as CD44 variant 9 (CD44v9) and receptor for hyaluronan-mediated motility (RHAMM). pDNA/chitosan/HA complexes showed specific transgene expression activity in CD44v9(+) cells, mediated by CD44v9-dependent cell uptake and microtubule-dependent transport. Particularly, RHAMM was involved in intracellular transport of pDNA/chitosan/HA complexes. We demonstrated that HA drives CD44v9-mediated internalization, RHAMM-mediated, and microtubule-dependent intracellular transport, which are essential for enhanced pDNA complex-driven gene expression in gastric cancer cells co-expressing CD44v9 and RHAMM.

α-Gal syndrome (AGS) is a type of allergy to red meat and other mammalian products that develops after a tick bite. Symptoms may include urticaria, angioedema, gastrointestinal and respiratory symptoms, and, most dangerously, anaphylactic shock. Among food allergies, it is considered unusual because: (i) the major allergen is not a protein, but a carbohydrate moiety Galα-1,3-Gal, which humans do not synthesize; (ii) it is caused by α-Gal-containing glycoconjugates injected during a tick bite; (iii) the hypersensitivity is effected by IgE antibodies which arise after a class switch from IgG and IgM-class antibodies; (iv) it seems to be triggered by α-Gal-containing glycolipids present in red meat, with delayed onset. Here, we evaluate glycans that may cause AGS, review the data about glycosyltransferases that synthesize α-Gal and related antigens and describe the immune mechanism behind AGS: sensitization and host response to ticks' saliva. In addition, we consider future research avenues that may lead to a better understanding and management of AGS as a modern dietary affliction rooted in an old evolutionary trade-off.

Glycated hemoglobin (HbA1c) is a well-established biomarker reflecting chronic glycemic control in diabetes. It accumulates through non-enzymatic glycation of hemoglobin under sustained hyperglycemia and serves as a surrogate of metabolic memory. Emerging in parallel, glycosylated RNA (glycoRNA), small noncoding RNAs bearing covalently attached N-linked glycans, has revealed unexpected roles in immune signaling and glycoimmunomodulation. While glycation and glycosylation represent distinct biochemical processes, both are modulated by glucose availability and cellular stress. This opinion paper aimed to explore the conceptual parallels between HbA1c and glycoRNA, proposing that hyperglycemia-induced metabolic changes may simultaneously influence both processes. In light of these, glycoRNA represents an emerging biomarker as a functional effector in metabolic disease, mirroring the hyperglycemia-driven immunological dimensions of HbA1c with a further advantage of a defined metabolic sequence, which can deepen diagnostics towards disease progression patterns. Though direct experimental evidence is currently limited, we outline plausible mechanistic intersections and suggest methodological frameworks for future research. Therefore, this perspective aims to stimulate interdisciplinary investigation into glycoRNA biology within the broader context of glycemic dysregulation and immune modulation in diabetes.

Protein glycosylation has been implicated in the pathogenesis of cancer, with colorectal cancer (CRC) strongly associated with serum N-glycosylation and IgG N-glycosylation. However, the N-glycosylation profile of non-immunoglobulin serum proteins (IgS-D) in CRC progression remains largely unexplored. Serum IgS-D was isolated using affinity chromatography, followed by the release of N-glycans, methylamidation, and MALDI-MS analysis. The potential of the IgS-D N-glycome profile to reflect CRC progression was assessed through Mann-Whitney U tests and multivariate analysis. A total of 43 distinct N-glycans were identified in IgS-D. Notably, a significant reduction in serum IgS-D mannosylated N-glycans was observed in CRC patients compared to healthy controls. Further analysis of individual N-glycans revealed significant differences and diagnostic potential in five specific N-glycans: H5N2 (AUC = 0.868), H6N2 (AUC = 0.73), H5N4S1 (AUC = 0.800), H5N5S1F1 (AUC = 0.713), and H5N4S2F1 (AUC = 0.689). A panel comprising these five N-glycans demonstrated high diagnostic accuracy for CRC (AUC = 0.924). The N-glycosylation profile of serum IgS-D is closely associated with CRC progression. Specific N-glycan signatures provide robust discrimination between CRC patients and healthy controls, warranting further investigation into the underlying molecular mechanisms.

Avidities and intensities of the Structural units, Glycotopes and their polyvalencies in the LFuc Recognition Protein (FRP)-glycan interactions have not been well defined and organized. This is due to the absence of the special glycan reagents and insufficient experiences. In this report, one of the best LFuc Recognition Proteins (FRPs) was analyzed by the enzyme-linked lectinosorbent and inhibition assays. From the data provided, it is found that the polyvalencies of the Fucα1→2Gal related structural units and their glycotopes are the dominant ones, especially these units of the human blood group H, Leb/Ley-tetra saccharide and AB-Leb/Ley-penta active glycans, but not the Lea/Lex-tri ligands and Man related units. When their intensities are expressed by Mass Relative Potency (Mass R.P.), it can be up to 5.0×105 fold higher than their key monomer (LFuc). In addition to this FRP can be a used as a powerful tool to detect the presence of the H, Leb/Ley-tetra and AB-Leb/Ley-penta glycotopes in the mammalian glycoconjugates, the theme of this report is the first constructive work of its structural units and codes for the LFuc Recognition Protein (FRP) system. It is expected to expand to reveal more others in the future.