bims-supasi 2026-05-17 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–05–17
nineteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Sulfation of Chondroitin Sulfate Regulates Neuronal Morphology via Src-Family Signaling with Likely Contribution from Fyn.
Dye displacement on a GO-like cationic porphyrin polymer for heparin sensing and quality control.
Threonine sulfation: a rare post translational modification in insect adipokinetic hormones.
Multivalency influences virus dynamics at the glycocalyx: a study of glycosaminoglycan binding in HPV16 entry.
Targeting Protein-Bound Uremic Toxins: A Dual Approach with Medium Cut-Off Membrane Dialysis and a Dietary Intervention-A Randomized Controlled Study.
Salivary Free Testosterone as a Potential Biomarker for Pelvic Organ Prolapse in Postmenopausal Women: A Prospective Case-Control Study.
Engineering, Expression, Purification, and Application of Glycosaminoglycan-Specific Antibodies.
Influence of the Adsorption Time on the Growth of Bovine Serum Albumin-Chondroitin Sulfate Multilayer Films: A Surface Plasmon Resonance Spectroscopy Study.
Engineering Chondroitinase-Free Baculovirus-Insect Cell Expression System for Efficient Synthesis of Chondroitin Sulphates.
Cost-Effectiveness of Chondroitin Sulphate (with or without Glucosamine) Prescription in the Treatment of Knee Osteoarthritis Compared to NSAIDs and COXIBs.
Separation of sulfated fucose-containing isomers found in polysaccharides from brown seaweed using cyclic ion mobility mass spectrometry.
Biomimetic control of hydroxyapatite crystallization by chondroitin sulfate for enamel remineralization.
Structural characterization and anticancer enhancement of selenized squid ink glycosaminoglycan nanoparticles.
Association of Serum P-Cresyl Sulfate Level with Peripheral Artery Disease in Kidney Transplantation Patients.
Heparan Sulphate Glycosaminoglycan Chains Contribute to the Tethering of Coronal Factors and Are Important for Extracellular Vesicle-Mediated Fibroblast Activation.
Comprehensive analysis of the skeletal phenotype in Chst14 -/- mice: implications for dermatan sulfate in bone structure and strength.
Targeting the Gut-Kidney-Heart Axis in Chronic Kidney Disease: The Mediterranean Diet as a Strategy to Reduce Uremic Toxins and Cardiovascular Risk.
Sustainable enzymatic approach for recovery of potential bioactive peptides and chondroitin sulphate from bovine trachea.
Sulfation Attenuates Mitigating Effects of 25-Hydroxycholesterol on Postmenopausal Bone Loss.

Cells. 2026 Apr 22. pii: 747. [Epub ahead of print]15(9):

Sulfation of Chondroitin Sulfate Regulates Neuronal Morphology via Src-Family Signaling with Likely Contribution from Fyn.

Saya Kubosaka, Tadahisa Mikami, Hiroshi Kitagawa.

  Chondroitin sulfate (CS) chains are major components of the extra- and pericellular matrix in the central nervous system (CNS), and their sulfation patterns influence CNS development and function. Highly sulfated CS preparations, including CS-D- and CS-E-enriched forms, have been shown to facilitate neurite outgrowth in cultured mouse hippocampal neurons. Notably, neurons cultured on CS-D- or CS-E-enriched substrates exhibited the following distinct morphological characteristics: CS-D promoted the extension of multiple short neurites, whereas CS-E induced the formation of a single elongated neurite with a polarization-like morphology. These features are consistent with early stages of neuronal polarization. However, the specific roles of these highly sulfated CS forms in polarization-like morphology remain unclear. In this study, we demonstrate that polarization-like morphological transitions in hippocampal neurons can be modulated on mixed CS-D/CS-E substrates by varying their ratios. Compared with CS-D-enriched substrates, CS-E-enriched substrates more effectively promoted polarization-like neuronal morphology, accompanied by enhanced activation of Src-family kinases. Furthermore, forced activation of Fyn kinase induced morphological changes resembling polarization-like features in a neuroblastoma cell line, even in the absence of CS-D/CS-E mixed substrates. In conclusion, highly sulfated CS subtypes may function as extracellular cues that regulate neuronal morphology via Src-family signaling, with likely involvement of Fyn.

Keywords:  Src-family kinases; chondroitin sulfate; glycan-binding receptors; neuronal morphology

DOI:  https://doi.org/10.3390/cells15090747
Anal Chim Acta. 2026 Jul 15. pii: S0003-2670(26)00490-3. [Epub ahead of print]1407 345540

Dye displacement on a GO-like cationic porphyrin polymer for heparin sensing and quality control.

Yusheng Fan, Yanlin Fu, Chunfei Bao, Weihua Zhang, Yubin Ding.

   BACKGROUND: It is meaningful but challenging to develop convenient and accurate analytical methods for heparin sensing, owing to its complex and heterogeneous chemical structure. Although indicator displacement assay offers a promising alternative, the number of suitable host molecules capable of accommodating heparin remains limited.
RESULTS: Two positively charged porphyrin-based polymers, A30 and A32, are synthesized via alkylation reactions between 5,10,15,20-tetra(4-pyridyl)porphyrin and corresponding linkers of 1,2-diiodoethane and p-Xylylene dibromide, respectively. These polymers are designed to interact effectively with heparin through multiple hydrogen bonding and electrostatic interactions. Especially, A30 and A32 exhibit graphene oxide-like fluorescence quenching behavior, enabling their use as a general platform for constructing non-fluorescent polymer-dye ensembles. Therefore, a four-component sensor array named PSA is constructed by simple mixing A30 and A32 with representative dyes for heparin sensing.
SIGNIFICANCE: The PSA sensor array demonstrates satisfactory performance in discriminating common glycosaminoglycans, including heparin, chondroitin sulfate, and hyaluronic acid. Furthermore, it has been successfully applied for quantifying heparin concentration in diluted serum samples, detecting glycosaminoglycan contaminants in heparin, and accurately identifying unknown glycosaminoglycan samples in an accurate and convenient way.

Keywords:  Glycosaminoglycan; Heparin; Pattern recognition; Sensor array; Serum sample

DOI:  https://doi.org/10.1016/j.aca.2026.345540
Sci Rep. 2026 May 15.

Threonine sulfation: a rare post translational modification in insect adipokinetic hormones.

Gerd Gäde, Simone König, Sameer S Kulkarni, Richard J Payne, Heather G Marco.

  Peptides of the adipokinetic hormone family are responsible for metabolic roles in insects, regulating release of energy metabolites from the fat body. We report on adipokinetic hormone octapeptide sequences bearing a rarely identified post-translational modification (sulfation of a threonine residue) in two beetle subfamilies (Cetoniinae and Dynastinae) of the large superfamily of Scarabaeoidea (dung beetles, rhinoceros beetles and flower beetles), and in a bug species (family Coreidae). In the cetonids Pachnoda sinuata, Dicronorhina derbyana derbyana, Tropinota hirta, Protaetia cuprea, Cetonia aurata and Oxytherea funesta sulfated Pacsi-AKH is found (pQINLTsTGW amide), while sulfated Penid-AKH (pQVNISsTGW amide) occurs in the dynastid beetles Pentodon idiota, Xylotrupes gideon and Syrichthodontus spurius. Sulfated Schgr-AKH-II (pQLNFSsTGW amide) is found in the twig wilter Holopterna alata. Sequence elucidation was achieved by mass spectrometry, however, due to the labile nature of the sulfate group under mass spectrometric conditions, the modified amino acid could not be easily identified. Edman degradation and comparative mass spectrometry evaluations with synthetic sulfopeptide standards were therefore employed for sequence validation. This type of sulfation was previously only reported present on the protein backbone of very few proteins from vertebrates (including humans), a mollusc and a protozoan parasite.

Keywords:  Adipokinetic hormone; Insect; Mass spectrometry; Post-translational modifications; Solid-phase peptide synthesis; Threonine sulfation

DOI:  https://doi.org/10.1038/s41598-026-50205-x
Biophys J. 2026 May 12. pii: S0006-3495(26)00354-1. [Epub ahead of print]

Multivalency influences virus dynamics at the glycocalyx: a study of glycosaminoglycan binding in HPV16 entry.

Dario Valter Conca, Fouzia Bano, Yara Abidine, Laura Soria Martinez, Kerstin Seier, Justas Svirelis, Andreas Dahlin, Mario Schelhaas, Marta Bally.

Virus attachment at the cell surface often involves the establishment of multiple ligand-receptor interactions between viral capsid proteins and glycans in the glycocalyx. Multivalency likely contributes to strengthening and fine-tuning virus dynamics at the cell surface to optimize entry. Here, we present experimental and theoretical frameworks to describe how virus attachment, detachment and diffusion at the cell surface is modulated by multivalency. We focus on human papillomavirus 16 (HPV16), a leading cause of cervical cancer and its multivalent interactions with heparan sulfate (HS), a ubiquitous cell-surface glycan. Using single particle tracking microscopy, we investigate the dynamic behavior of HPV16 particles interacting with multiple HS chains through a glycocalyx mimic consisting of end-tethered heparin chains which were selectively desulfated. We further establish a theoretical framework to predict the dynamic behavior of individual virus particles interacting with multiple cellular receptors and apply it to the HPV16-HS binding system using previously published association and dissociation rates of the individual capsomer-glycan bonds. Our experiments reveal that N-sulfation is essential to ensure HPV16 association and validate our theoretical prediction that at biologically relevant time scales, the lifetime of monovalent interaction primarily influences the apparent particle attachment behaviour. Conversely, the nature of the sulfate group had a marginal effect on particle dissociation in the experiments, due to the great influence of multivalency on the particle's interaction lifetime. Experiments and simulations also indicate that the mobility of HPV16 particles on heparin surfaces is highly restricted due to the relatively high affinity of the monovalent interactions, suggesting that particle motion due to the creation and rupturing of individual bonds is unlikely key in HPV16 recruitment. Together, these findings provide quantitative mechanistic insights into how virus-glycan interactions are modulated. They highlight the importance of HS chemistry in modulating early HPV16 engagement and suggest new targets against viral binding.

DOI: https://doi.org/10.1016/j.bpj.2026.05.014
J Clin Med. 2026 Apr 23. pii: 3228. [Epub ahead of print]15(9):

Targeting Protein-Bound Uremic Toxins: A Dual Approach with Medium Cut-Off Membrane Dialysis and a Dietary Intervention-A Randomized Controlled Study.

Tjaša Herič, Tjaša Vivoda, Špela Bogataj, Aljoša Kuzmanovski, Joško Osredkar, Joanna Giebułtowicz, Jernej Pajek.

  Background/Objectives: Protein-bound uremic toxins (PBUTs), particularly p-cresyl sulfate (PCS) and indoxyl sulfate (IS), are associated with cardiovascular toxicity and increased mortality. Conventional hemodialysis (HD) removes PBUTs poorly, and the efficacy of medium cut-off (MCO) dialyzer membranes remains uncertain. Furthermore, PBUT production is influenced by gut microbial metabolism and can be modified through diet. We hypothesized that MCO dialysis would provide superior clearance of PCS and IS compared with online hemodiafiltration (OL-HDF), and that combining MCO dialysis with increased dietary fiber and short-chain fatty acid (SCFA) intake would further reduce PBUT levels. Methods: In this prospective randomized trial, 62 maintenance HD patients underwent a 2-week wash-in period with high-flux HD (HF-HD) and were then randomized to MCO-HD (EXP) or OL-HDF (CON). After a 4-week intervention with the assigned dialysis modality, both groups continued with the same dialysis treatment and received an 8-week dietary intervention consisting of 19 g/day fiber and 1 g/day sodium propionate. The study concluded with a 4-week wash-out period on HF-HD. Primary outcomes were total serum PCS and IS levels measured at four timepoints. Results: Fifty-two patients completed the study. No significant changes in PCS or IS were observed after the dialysis-only intervention. PCS levels remained stable throughout the study. When the aligned dialysis regimen was combined with the dietary intervention, IS levels were significantly lower in the CON than in the EXP group (31.5 ± 10.3 vs. 42.0 ± 15.8 µmol/L; p = 0.006), with a partial rebound after wash-out in the CON group (39.6 ± 20.9 µmol/L; p = 0.003). Conclusions: While MCO-HD and OL-HDF had a similar effect on serum PCS and IS concentrations, only OL-HDF combined with the dietary intervention significantly reduced IS levels.

Keywords:  fiber supplementation; indoxyl sulfate; medium cut-off dialyzer; p-cresyl sulfate; protein-bound uremic toxins

DOI:  https://doi.org/10.3390/jcm15093228
Int J Urol. 2026 May;33(5): e70473

Salivary Free Testosterone as a Potential Biomarker for Pelvic Organ Prolapse in Postmenopausal Women: A Prospective Case-Control Study.

Maki Kawasaki, Kei Nagase, Minika Yukimoto, Yukako Yamaguchi, Akihiro Maeda, Shuhei Kusano, Yuka Kakinoki, Hiroaki Kakinoki, Kazuma Udo, Shohei Tobu, Mitsuru Noguchi.

   OBJECTIVE: Pelvic organ prolapse (POP) is a common pelvic floor disorder in postmenopausal women, yet no biomarkers currently exist to predict its development. This study aimed to investigate the relationship between sex hormone levels, particularly androgens, and the severity of POP in postmenopausal women.
METHODS: We conducted a prospective observational study including 109 postmenopausal women with POP and 66 age-matched women without POP (control group) at Saga University Hospital. POP severity was classified using the Pelvic Organ Prolapse Quantification (POP-Q) system. Salivary free testosterone and 17β-estradiol were measured, along with serum dehydroepiandrosterone sulfate (DHEA-S), using enzyme-linked immunosorbent assays. Clinical characteristics and lower urinary tract symptoms were also assessed. Statistical comparisons were performed using t-tests, Chi-square tests, and Pearson correlation analysis.
RESULTS: The POP group had significantly higher BMI and parity and reported more severe lower urinary tract symptoms than the control group. Salivary free testosterone levels were significantly decreased, and serum DHEA-S levels were significantly increased in the POP group (p = 0.0157 and p = 0.0082, respectively), while estradiol levels showed no significant difference. Advanced POP (stages III-IV) was associated with further reductions in free testosterone. DHEA-S levels were unexpectedly higher in POP stages II and III compared to controls.
CONCLUSION: Reduced levels of circulating androgens, particularly Salivary free testosterone, may be associated with POP development and severity. Salivary free testosterone could serve as a non-invasive biomarker for POP risk stratification. Further longitudinal and multi-institutional studies are needed to clarify the role of androgens in POP pathophysiology.

Keywords:  Dehydroepiandrosterone sulfate (DHEA‐S); enzyme‐linked immunosorbent assay; estradiol; pelvic organ prolapse; salivary free testosterone

DOI:  https://doi.org/10.1111/iju.70473
Curr Protoc. 2026 May;6(5): e70358

Engineering, Expression, Purification, and Application of Glycosaminoglycan-Specific Antibodies.

Kheerthana Duraivelan, Sriram Sundaravel, Esther N Njoroge, Robert A Townley, Ulrich G Steidl, Hannes E Bülow, Steven C Almo, Scott J Garforth.

  Cluster of differentiation markers have been transformative for defining cell populations and their functional states, but recent work indicates that finer granularity can be achieved by considering the diverse heparan sulfate structures presented on proteoglycans. Heparan sulfates (HSs) are long, unbranched polysaccharides of a repeating disaccharide composed of hexuronic acid and N-acetylglucosamine. HS is attached to core proteins via serine residues. Owing to multiple modifications of the sugar moieties by a set of specific Golgi-resident modification enzymes, HSs exhibit extraordinary variations in modification patterns. Because these patterns are non-template based, they display substantial heterogeneity, yet are expressed reproducibly with high spatiotemporal and tissue-specific selectivity. This complexity of HS modification is, in turn, believed to control extracellular receptor:ligand interactions in a cell-specific fashion. Conventional methods to study HS structure require specialized expertise and instrumentation, and remain challenging due to the considerable heterogeneity of even tissue-specific HSs. Here, we describe protocols for the production and implementation of a panel of anti-HS single-chain variable fragments (scFvs) based on scFvs originally reported in the 1990s and early 2000s. This panel is an attractive resource for detailed study of HS modification patterns in various physiological processes. Rather than determining HS structure by analytical means, we use this panel to define cells based on the scFvs they bind. We detail practical considerations, strategies, and protocols for the construction, development, expression, purification, and application of the anti-HS scFv panel from bacterial and mammalian expression systems. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Expression and purification of anti-HS scFvs from bacterial expression systems Basic protocol 2: Expression and purification of anti-HS scFvs from mammalian expression systems Basic Protocol 3: Sortase-mediated site-specific labeling of anti-HS scFvs Basic Protocol 4: In vitro HS detection by ELISA Basic Protocol 5: In vitro HS detection by flow cytometry using indirect labeling in live Jurkat E6-1 cells Alternate Protocol 1: In vitro HS detection by flow cytometry using indirect labeling in fixed Vero cells Alternate Protocol 2: In vitro HS detection by flow cytometry using direct labeling in live Vero cells Basic Protocol 6: In vitro HS detection by immunofluorescence in fixed adherent cells Alternate Protocol 3: In vitro HS detection by immunofluorescence in suspension cells prior to fixation.

Keywords:  glycosaminoglycan; heparan sulfate; heterologous protein expression and purification; scFv; single chain variable fragment

DOI:  https://doi.org/10.1002/cpz1.70358
Biopolymers. 2026 May;117(3): e70104

Influence of the Adsorption Time on the Growth of Bovine Serum Albumin-Chondroitin Sulfate Multilayer Films: A Surface Plasmon Resonance Spectroscopy Study.

Angelos Pavlopoulos, Nikolitsa Katsenou, Aristeidis Papagiannopoulos, Dimitrios L Anastassopoulos, Nikolaos Spiliopoulos.

  Multilayer films of bovine serum albumin (BSA) and chondroitin sulfate (CS) were assembled on gold substrates at pH 4.2 using the layer-by-layer (LbL) method, and their structural evolution was investigated via surface plasmon resonance (SPR) spectroscopy. To elucidate the role of adsorption kinetics in multilayer buildup, BSA adsorption times of 15, 30, 60, and 120 min (for each BSA adsorption cycle) were examined, while the CS adsorption time was kept constant at 15 min. Analysis of SPR reflectivity curves revealed two distinct growth regimes for all cases, an initial exponential followed by a linear regime. Longer BSA adsorption time promoted deeper chain infiltration, extending the exponential region and shifting the exponential-to-linear transition to higher bilayer numbers. In parallel, evaluation of the average dielectric constant of the polymer layer enabled quantification of the film volume fraction, which initially increased linearly before reaching a saturation plateau. The evolution of the adsorbed mass was inferred from the combined analysis of film thickness and volume fraction, revealing two distinct growth cases depending on the adsorption time. These cases reflect different relationships between the transition from exponential to linear growth and the saturation of the volume fraction. These findings demonstrate that BSA adsorption time is a key kinetic parameter governing chain diffusion, film compaction, and overall multilayer architecture. The results provide insight into the physicochemical mechanisms that dictate biopolymer film growth and offer a route for tuning the structural and optical properties of protein-polysaccharide coatings.

Keywords:  layer‐by‐layer; multilayer; protein‐polysaccharide; surface plasmon; transition point

DOI:  https://doi.org/10.1002/bip.70104
Microb Biotechnol. 2026 May;19(5): e70365

Engineering Chondroitinase-Free Baculovirus-Insect Cell Expression System for Efficient Synthesis of Chondroitin Sulphates.

Junyue Li, Yuqing Tian, Lihe She, Zhangliang Liu, Yingying Zhou, Yanyan Wang, Jihui Zhang, Leilei Zhu, Huarong Tan, Jine Li.

  Owing to the high expression levels, proper protein folding and post-translational modifications, baculovirus-insect cell expression system is an ideal platform for producing active chondroitin sulfotransferases, which specifically catalyse the synthesis of chondroitin sulphate (CS). However, the CS can be degraded by the endogenous chondroitinase derived from the viral envelope protein ODV-E66, thus requiring elaborate purification, which is impractical for large-scale production. To address this issue, a chondroitinase-free baculovirus was constructed by deleting the odv-e66 gene from bacterial artificial chromosomes (BACs). Through the engineered baculovirus, highly active chondroitin sulfotransferases (CS-4OST, CS-6OST and GalNAc4S-6OST) were successfully expressed and secreted into the culture supernatant. Of note, the culture supernatant can be directly employed for CS synthesis. Using the cultures harbouring the corresponding sulfotransferases, CS-A, CS-C and CS-E were successfully prepared at the gram-scale, thus obviating the need for laborious and costly purification. Collectively, this work overcomes the inherent limitation of CS degradation in baculovirus-insect cell expression system, thereby providing a robust and reliable platform for the expression of chondroitin sulfotransferases.

Keywords:  chondroitin sulphate; chondroitin sulphotransferases; engineered baculovirus; enzymatic synthesis

DOI:  https://doi.org/10.1111/1751-7915.70365
Clinicoecon Outcomes Res. 2026 ;18 577731

Cost-Effectiveness of Chondroitin Sulphate (with or without Glucosamine) Prescription in the Treatment of Knee Osteoarthritis Compared to NSAIDs and COXIBs.

Carlos Rubio-Terrés, Miguel Bernad Pineda, Josep Vergés.

   Background: Chondroitin sulfate, alone or associated with glucosamine (CS/CS+GLU), is an effective knee osteoarthritis (KOA) treatment, with fewer adverse effects (AEs) than non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase 2 inhibitors (COXIBs).
Purpose: To estimate the CS/CS+GLU cost-effectiveness versus NSAIDs/COXIBs, due to the avoidance of mild-moderate or severe gastrointestinal AEs (GIAE), ischemic heart disease (IHD), acute kidney insufficiency (AKI), chronic kidney failure (CKF) and ischemic stroke (IS) from the Spanish National Health System (NHS) perspective.
Methods: Two analyses were considered: 1) savings to the NHS from current CS/CS+GLU treatment; and 2) maximum savings that could be achieved by the NHS if all patients with KOA currently treated with NSAIDs/COXIB would be switched to CS/CS+GLU. AEs frequency, associated utilities loss and managing cost were obtained from medical literature and Spanish sources. A probabilistic model (second-order Monte Carlo simulation) was carried out for a 3-year time horizon. Treatment duration: 180 days (base case); 90 and 240 days (sensitivity analysis).
Results: First analysis: 45,087 mild-moderate GIAE, 3,217 severe GIAE, 211 IHD, 1,087 AKI, 746 CKF and 3,359 IS, would be avoided with CS/CS+GLU. Discounting drugs cost, the three-year savings would be 57.1 million euros (savings probability: 80.7%). The savings per patient treated with CS/CS+GLU would amount to €38.02 (95% CI 14.06; €75.69), with a mean gain of 0.0023 (95% CI 0.0018-0.0027) QALY. The probability that CS/CS+GLU treatment was dominant (lower costs and QALY gain) or cost-effective (cost per QALY gained less than €25,000) was 80.7% and 98.1%, respectively. In the second analysis, savings for the NHS would amount to 387 million euros, with the CS/CS+GLU-only option being dominant and cost-effective in 100% of the analyses.
Conclusion: The improved tolerability of CS/CS+GLU versus NSAIDs/COXIBs is expected to prevent thousands of AEs and generate considerable savings for the NHS, making it cost-effective treatment.

Keywords:  budgetary impact; chondroitin sulfate; cost-effectiveness; glucosamine; health impact; knee osteoarthritis

DOI:  https://doi.org/10.2147/CEOR.S577731
RSC Adv. 2026 May 08. 16(27): 24650-24658

Separation of sulfated fucose-containing isomers found in polysaccharides from brown seaweed using cyclic ion mobility mass spectrometry.

Olivia M Wyper, Karl J Jobst, Francesca M Kerton.

Brown seaweeds and some marine invertebrates contain bioactive polysaccharides, including fucoidan, with antimicrobial, antibacterial, and antifungal properties. Improved characterization of their structures would be valuable. To our knowledge, fucoidan extracted from the macroalga Laminaria digitata grown in the North Atlantic has not been structurally determined. We show that both singly and doubly sulfated fucose units, and singly sulfated galactose species present within fucoidan exist as isomers. These were identified via analysis of the biopolymer using Cyclic Ion Mobility Mass Spectrometry (cIM-MS), which has not been used to determine isomeric species present in fucoidan-derived structures previously. Along with using cIM, tandem MS (MS/MS) provided unique fragmentation related to differing sulfate locations and glycosidic linkages. Connectivity positions between both sulfated fucose and galactose trimers and dimers were identified using Collisional Cross Section (CCS) modelling via a machine-learning approach (AllCCS2 prediction software) and drift times from cIM. Previous studies determined that the linkage between the sulfated galactose dimer ([Gal2SO3]-) was 1 → 4 due to the presence of m/z = 361. Herein, both fragmentation and drift time suggest glycosidic linkages between the monomer units at 1 → 4 and 1 → 3 positions. Ions of high m/z were identified, e.g. [Fuc3(SO3)2-H2O]2-, along with smaller, lighter ions such as a dehydrated sulfated fucose, [FucSO3-H2O]-. A major ion seen in this work appears at m/z = 357, which we hypothesize as a galactose dimer where one unit has ring-opened to yield a deprotonated glycolic acid ion. The presence of this species has not been reported in earlier structural investigations and speaks to the structural complexity of fucoidan present in Laminaria digitata harvested in Atlantic Canada.

DOI: https://doi.org/10.1039/d6ra00238b
Dent Mater. 2026 May 13. pii: S0109-5641(26)00319-2. [Epub ahead of print]

Biomimetic control of hydroxyapatite crystallization by chondroitin sulfate for enamel remineralization.

Changyu Shao, Tong Shi, Dayu Wang, Chang Liu, Zhenhang Tang, Yuanyu Zhou, Haihua Pan, Zhijian Xie, Ruikang Tang, Zhuo Chen.

   OBJECTIVES: This study aims to develop a biomimetic mineralization strategy using chondroitin sulfate (CS) to reconstruct the intricate hierarchical structure of enamel and restore its mechanical properties.
METHODS: Demineralized enamel was remineralized in a CS-containing artificial saliva (AS). The crystallization of hydroxyapatite (HAP) in AS was investigated using transmission electron microscopy (TEM) and atomic force microscopy (AFM)-infrared spectroscopy. Enamel repair efficacy was systematically evaluated via scanning electron microscopy (SEM) and AFM to characterize the microstructure and repair thickness, while nanoindentation was employed to quantify the mechanical properties. In addition, acid resistance was evaluated using a 50 mM HCl solution. Furthermore, an AS-hydrogel mineralization system was developed to evaluate its efficacy in restoring demineralized enamel under biologically relevant conditions.
RESULTS: The results demonstrate that CS-modified ACP successfully assembles into chain-like precursors via anisotropic forces, which simultaneously regulate the oriented crystallization of HAP. This strategy resulted in a newly formed mineralized layer that effectively reconstructs the hierarchical architecture and recovers mechanical properties, including hardness, elastic modulus, and coefficient of friction, to near-native levels. In addition, the repaired enamel exhibits an acid resistance level comparable to that of native enamel.
SIGNIFICANCE: This study establishes a new, mechanism-driven strategy for enamel remineralisation that is mediated by CS, and a corresponding hydrogel mineralization system, which can be translated into practice, offering a promising approach to future clinical enamel restoration.

Keywords:  Agarose hydrogel; Chondroitin sulfate; Dental enamel; Hydroxyapatite; Remineralization

DOI:  https://doi.org/10.1016/j.dental.2026.05.008
Int J Biol Macromol. 2026 May 12. pii: S0141-8130(26)02431-1. [Epub ahead of print] 152504

Structural characterization and anticancer enhancement of selenized squid ink glycosaminoglycan nanoparticles.

Yipeng Gu, Xiaomei Yang, Ling Yang, Siqi Yao, Huazhong Liu.

  Squid ink polysaccharide 4 (SIP4), a marine-derived sulfated glycosaminoglycan with favorable biocompatibility and coordination capacity, was employed as a functional template and stabilizing matrix for the synthesis of selenized nanoparticles (SIP4-SeNPs). The optimal SIP4 concentration (0.4 mg/mL) yielded nanoparticles with the highest selenium incorporation (23.88%, ICP-MS), smallest particle size (130.57 nm), and a negative zeta potential (-24.23 mV). Spectroscopic and microscopic analyses (UV-Vis, FT-IR, SEM, DSC, TGA, XRD) confirmed selenium-induced structural reorganization and the formation of uniform, semi-crystalline SIP4-SeNPs stabilized by hydroxyl, carboxyl, and sulfate groups. The nanoparticles exhibited improved stability at 4 °C for up to 14 days. Biological evaluations showed that SIP4-SeNPs significantly enhanced antiproliferative activity against MDA-MB-231 cells with a markedly lower IC₅₀ than SIP4, while maintaining low cytotoxicity toward MCF-10 A cells. Apoptosis analysis and ROS detection indicated that SIP4-SeNPs promote cancer cell death through oxidative stress-mediated pathways. This study demonstrates that SIP4-based selenium nanoparticles are promising candidates for breast cancer therapy with improved efficacy and safety.

Keywords:  Anticancer activity; Selenized polysaccharide; Structural characterization

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.152504
J Clin Med. 2026 Apr 26. pii: 3302. [Epub ahead of print]15(9):

Association of Serum P-Cresyl Sulfate Level with Peripheral Artery Disease in Kidney Transplantation Patients.

Hsiao-Hui Yang, Yen-Cheng Chen, Chin-Hung Liu, Bang-Gee Hsu.

  Background: p-Cresyl sulfate (PCS) has been linked to vascular dysfunction through endothelial injury and vascular remodeling. Peripheral artery disease (PAD), identified by a low ankle-brachial index (ABI), is associated with increased mortality in kidney transplant (KT) recipients. This study investigated the association between serum PCS levels and PAD (as defined by ABI) in KT recipients. Methods: This cross-sectional, single-center study included 90 KT recipients. Serum total PCS levels were quantified using liquid chromatography-mass spectrometry. ABI was measured using an automated oscillometric device, and PAD was defined as ABI < 0.9. Results: Among the 90 KT recipients, 20 (22.2%) met the ABI for PAD. Patients with ABI-defined PAD had a significantly higher prevalence of diabetes mellitus (p = 0.036) and serum PCS levels (p = 0.001). Multivariate logistic regression analysis adjusting for potential confounders revealed that serum PCS levels remained independently associated with PAD (odds ratio 1.254, 95% confidence interval 1.108-1.419; p < 0.001). PCS levels were inversely correlated with both left (r = -0.339, p = 0.001) and right (r = -0.357, p < 0.001) ABIs. The association remained consistent in penalized regression models. Conclusions: Higher serum PCS levels were independently associated with ABI-defined PAD in KT recipients. The findings indicate that residual uremic toxin burden may contribute to peripheral vascular disease despite the restoration of renal function following transplantation.

Keywords:  ankle-brachial index; kidney transplantation; p-cresyl sulfate; peripheral artery disease

DOI:  https://doi.org/10.3390/jcm15093302
J Extracell Biol. 2026 May;5 e70146

Heparan Sulphate Glycosaminoglycan Chains Contribute to the Tethering of Coronal Factors and Are Important for Extracellular Vesicle-Mediated Fibroblast Activation.

Sara Veiga, Alex P Shephard, Kate Milward, Alex Cocks, Félix Royo, Juan M Falcon-Perez, Aled Clayton, Jason P Webber.

Extracellular vesicles (EVs) play a critical role in intercellular communication, yet the contribution of the EV corona and associated surface structures, such as heparan sulphate glycosaminoglycan (HS GAG) chains, to EV function remains poorly understood. In this study, we highlight a hitherto unknown requirement of HS GAG chains for the simultaneous delivery of a myriad assortment of growth factors by EVs. We demonstrate an attenuated function following enzymatic removal of HS GAG chains from the surface of prostate cancer (PCa)-derived EVs, using heparinase III (HepIII). Our results confirm that digestion of HS GAG chains is specific and does not compromise EV integrity regarding size or tetraspanin expression. Enzymatic removal of HS GAG chains did, however, substantially altered the vesicular protein profile, reducing the expression of factors such as midkine, CYR61 and TFPI implicating HS GAG chains as a mode of tethering these factors to the EV surface. Importantly, EV-associated HS GAG chains are required for functional delivery of such factors, resulting in successful activation of cellular signalling pathways for SCF, IGF-1, midkine and VEGF in recipient fibroblasts. Furthermore, HS GAG chain removal attenuated EV-induced fibroblast production of pro-angiogenic factors VEGF and angiogenin as well as inflammatory factors VCAM-1 and IL-1α alpha/IL-1F1, underscoring the role of vesicular HS GAG chains in mediating functional outcomes. These findings highlight the importance of EV surface HS GAG chains in growth factor delivery and signalling, providing new insights into the EV corona and its relevance in pathological processes relating to modulation of the tissue microenvironment.

DOI: https://doi.org/10.1002/jex2.70146
Glycobiology. 2026 May 15. pii: cwag037. [Epub ahead of print]

Comprehensive analysis of the skeletal phenotype in Chst14 -/- mice: implications for dermatan sulfate in bone structure and strength.

Yuki Takahashi, Takahiro Yoshizawa, Shuji Mizumoto, Fumiko Ono, Masashi Uehara, Takafumi Watanabe, Shin Shimada, Yuko Nitahara-Kasahara, Shuhei Yamada, Jun Takahashi, Takashi Okada, Tomoki Kosho.

  Dermatan sulfate (DS) is a glycosaminoglycan known to contribute to tissue strength through collagen fibril assembly. Musculocontractural Ehlers-Danlos syndrome (mcEDS) caused by pathogenic variants in the gene that encodes carbohydrate sulfotransferase 14 (CHST14) (mcEDS-CHST14) is a representative disorder of DS deficiency. Skeletal lesions, such as progressive spinal deformity and osteoporosis/osteopenia, are significant manifestations of mcEDS-CHST14, which can lead to deterioration in quality of life. To characterize skeletal alterations associated with DS deficiency, we performed comprehensive analyses of the skeletal phenotypes in Chst14 gene-deleted (Chst14-/-) mice. Chst14-/- mice exhibited progressive kyphosis, proximal femoral deformities, and decreased bone strength, as well as reduced trabecular bone mass and structural parameters, from a young age. Qualitative ultrastructural alterations of collagen fibrils in cortical bone were observed in middle-aged Chst14-/- mice by transmission electron microscopy. In addition, cortical bone showed increased expression of receptor activator of NF-κB (Rank), a gene involved in osteoclast differentiation, in middle age. Histomorphometric analyses of cancellous bone demonstrated reduced trabecular structural parameters in Chst14-/- mice, including decreases in bone volume and trabecular number. These findings indicate age-dependent alterations in both cortical and cancellous bone compartments that may contribute to progressive skeletal deformation. The present study provides insight into skeletal alterations associated with mcEDS-CHST14 and highlights a broader role of DS in maintaining bone structure and strength.

Keywords:  bone metabolism; carbohydrate sulfotransferase 14 (CHST14); dermatan sulfate; musculocontractural Ehlers–Danlos syndrome (mcEDS)

DOI:  https://doi.org/10.1093/glycob/cwag037
Nutrients. 2026 Apr 30. pii: 1451. [Epub ahead of print]18(9):

Targeting the Gut-Kidney-Heart Axis in Chronic Kidney Disease: The Mediterranean Diet as a Strategy to Reduce Uremic Toxins and Cardiovascular Risk.

Josipa Radić, Tina Bečić, Marijana Vučković, Ivana Jukić, Jonatan Vuković, Damir Fabijanić, Mislav Radić.

  Chronic kidney disease (CKD) is associated with a markedly increased risk of cardiovascular (CV) morbidity and mortality that cannot be fully explained by traditional risk factors. Emerging evidence highlights the central role of the gut-kidney-heart axis, whereby gut microbiota dysbiosis promotes the generation and systemic accumulation of uremic toxins, including indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO). These metabolites contribute to endothelial dysfunction, oxidative stress, inflammation, and vascular remodeling, thereby accelerating CV disease progression in CKD. Dietary patterns represent a key modifiable factor influencing gut microbiota composition and metabolic activity. The Mediterranean diet, characterized by high intake of plant-based foods, dietary fiber, and polyphenols, and low consumption of red and processed meats, has emerged as a promising microbiota-targeted strategy. It promotes saccharolytic fermentation, enhances short-chain fatty acid production, and reduces proteolytic pathways responsible for uremic toxin generation. Accumulating evidence from observational studies, meta-analyses, and dietary intervention trials suggests that adherence to Mediterranean and plant-based dietary patterns is associated with reduced uremic toxin burden, improved renal outcomes, and lower CV risk in CKD populations. However, direct interventional evidence linking Mediterranean diet adherence to changes in specific uremic toxin levels remains limited. This narrative review summarizes current evidence on diet-microbiota interactions in CKD and highlights the Mediterranean diet as a biologically plausible strategy for targeting the gut-kidney-heart axis. Future well-designed randomized controlled trials (RCTs) are needed to confirm causal relationships and support clinical implementation.

Keywords:  Mediterranean diet; TMAO; cardiovascular risk; chronic kidney disease; gut microbiota; gut–kidney–heart axis; indoxyl sulfate; p-cresyl sulfate; short-chain fatty acids; uremic toxins

DOI:  https://doi.org/10.3390/nu18091451
Food Res Int. 2026 Jul 31. pii: S0963-9969(26)00822-7. [Epub ahead of print]236 119145

Sustainable enzymatic approach for recovery of potential bioactive peptides and chondroitin sulphate from bovine trachea.

Marta Gallego, Leticia Mora, Fidel Toldrá.

  The valorisation of cartilaginous meat by-products as a source of compounds such as chondroitin sulphate (CS) and bioactive peptides offers a sustainable alternative for nutraceutical or pharmaceutical applications. This study developed a mild and sustainable approach, integrating enzymatic hydrolysis and ultrasounds (US) pre-treatments, to obtain extracts from bovine tracheal cartilage. The extracts were purified, fractionated by molecular weight, and characterised both qualitatively and quantitatively for CS and peptide content. Results showed that the combination of papain with US improved extraction yield, while further purification increased the CS content to approximately 40%. Bioactivity assays revealed the highest antioxidant, antihypertensive, and antidiabetic activities generally in fractions <30 kDa, particularly in extracts obtained through US-assisted enzymatic hydrolysis. The composition and bioactivity of the extracts varied with the pre-treatment applied, allowing process adaptation for specific applications. These findings highlight the potential to achieve high CS purity and bioactive peptide content from cartilaginous meat by-products.

Keywords:  Bioactive extracts; Meat by-products; Multifunctional activity; Sequential enzymatic hydrolysis; Ultrasounds

DOI:  https://doi.org/10.1016/j.foodres.2026.119145
FASEB J. 2026 May 15. 40(9): e71882

Sulfation Attenuates Mitigating Effects of 25-Hydroxycholesterol on Postmenopausal Bone Loss.

He Liu, Wenrui Ma, Yichen Niu, Xiaodan Ji, Liangjie Huang, Jingyan Hu, Chengxiang Zhao, Liu Yang, Chao Zheng.

  Postmenopausal osteoporosis is a prevalent skeletal disorder with an unmet need for safer therapeutic strategies. While certain oxysterols show osteoinductive potential, the role of 25-hydroxycholesterol (25HC) in bone homeostasis remains unclear. Furthermore, 25HC can undergo sulfation, a largely underexplored chemical modification, to form 25HC3S. This study aimed to investigate the effects of 25HC and 25HC3S on bone loss and the underlying mechanisms. We found that treatment with 25HC, but not 25HC3S, ameliorated bone loss in an ovariectomized (OVX) mouse model of osteoporosis, as evidenced by increased bone mass and expression of type I collagen, alongside decreased osteoclast numbers. Transcriptomic analysis revealed that 25HC regulated genes related to cell cycle and Rho GTPase signaling in bone tissue and osteoblastic lineage cell cultures, while 25HC3S had attenuated effects. In vivo and in vitro experiments demonstrated that 25HC promoted pre-osteoblast proliferation and enhanced osteocyte survival. Mechanistically, 25HC inhibited Rho GTPase signaling in pre-osteoblasts but activated it in osteocytes, which was largely abolished by sulfation. Collectively, this study identifies 25HC as a protective regulator against postmenopausal bone loss and unveils sulfation as a critical switch that negates its benefit, supporting 25HC supplementation as promising therapeutic strategies for osteoporosis.

Keywords:  25‐hydroxycholesterol; bone loss; osteoblast; osteocyte; rho GTPase; sulfation

DOI:  https://doi.org/10.1096/fj.202600557R