bims-supasi 2026-06-14 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–06–14
nine papers selected by
Jonathan Wolf Mueller, University of Birmingham

csRNA and heparan sulfate : cell surface ribonucleoproteins regulate HS-mediated signaling.
Chondroitin sulfate and chondroitinase ABC: emerging roles in drug delivery and wound healing applications.
Deep Learning-Driven Saccharide Online Sequencing for Elucidating the Pathological Alterations of Heparan Sulfate in APAP-Induced Acute Liver Injury.
Structural characterization, in vitro anticoagulant, and antiplatelet activities of a Distolasterias nipon dermatan sulfate-like polymer with a distinctive sulfation pattern.
Fully Synthetic, Biomimicking Polysulfates With Tunable Anticoagulant and Endothelial Cell-Selective Bioactivity.
Effect of short-term of vaginal therapy with prasterone before urogynecological surgery in woman.
Heparin-binding enhances extracellular listeriolysin O activity, overcoming cholesterol inhibition and pH dependence.
Total Synthesis of Conjugation-Ready Sulfated Red Algae Carrageenan Oligosaccharides for Sensing Applications.
Chondroitin Sulfate-Based MPDA@MnO2 Nanocomposite Hydrogels: A Smart Drug Delivery System with pH/ROS Responsiveness and Photothermal-Enhanced Therapeutic Effects.

Signal Transduct Target Ther. 2026 Jun 12. pii: 231. [Epub ahead of print]11(1):

csRNA and heparan sulfate : cell surface ribonucleoproteins regulate HS-mediated signaling.

Jinlin Li, Jiaxin Ling.

DOI: https://doi.org/10.1038/s41392-026-02727-z
J Biomater Sci Polym Ed. 2026 Jun 10. 1-51

Chondroitin sulfate and chondroitinase ABC: emerging roles in drug delivery and wound healing applications.

Bassam M Abualsoud, Majid Alhomrani, Abdulhakeem S Alamri, Walaa F Alsanie, Rekha M M, Yash Sharma, Shivang Mishra, Pooja Rani, Pankaj Nainwal, Deepak A.

  Chondroitin sulfate (CS), a naturally occurring glycosaminoglycan, is renowned for its biocompatibility, biodegradability, and considerable role in wound healing and drug delivery applications. In wound healing, CS fosters tissue regeneration by augmenting cell signaling, extracellular matrix remodeling, and accelerating tissue repair. As a drug delivery system, CS acts as an adaptable carrier, improving stability, bioavailability, and controlled release of therapeutic agents. Its ability to form hydrogels and nanoparticles enables prolonged, site-specific drug delivery, ensuring targeted therapeutic action at injury sites. Recent advancements have focused on CS-based formulations for chronic wound treatment, emphasizing its role in tissue regeneration and faster healing. The integration of CS with biomaterials like collagen and hydroxyapatite further optimizes therapeutic outcomes. In addition to CS, chondroitinase ABC (chABC) has gained attention for its potential in wound healing and drug delivery. chABC, an enzyme that degrades chondroitin sulfate chains, promotes tissue repair by breaking down inhibitory extracellular matrix components and promoting cell migration. The combination of CS and chABC could offer synergistic effects, enhancing wound healing and drug delivery efficiency. Challenges remain in optimizing formulations for clinical use, including stability, scalability, and regulatory issues, but the future potential for CS and chABC in therapy is significant.

Keywords:  Chondroitin sulphate; biomaterial; chABC; drug delivery; natural polymer; wound healing

DOI:  https://doi.org/10.1080/09205063.2026.2676163
Anal Chem. 2026 Jun 10.

Deep Learning-Driven Saccharide Online Sequencing for Elucidating the Pathological Alterations of Heparan Sulfate in APAP-Induced Acute Liver Injury.

Zizhe An, Lexin Chen, Changkai Bu, Deling Shi, Bin Zhang, Lan Jin, Lianli Chi.

Heparan sulfate (HS), one of the mostly negatively charged biomacromolecules anchored on the membrane surface of nearly all mammal cells, plays critical regulatory roles through interacting with a variety of proteins. However, there is still no method capable to directly sequence the domain alterations of HS in pathological states. In the current study, the pathological alterations of HS were elucidated for the first time in APAP-induced acute liver injury by a deep learning-driven chemical derivatization-tandem mass spectrometry strategy, and the sequence changes up to octasaccharides within the bioactive domain "GlcA-GlcNS6S" were successfully decoded. GAG-Explorer, a software incorporated with a comprehensive deep learning model capable of predicting the fragmentation patterns of HS oligomers under actual MS/MS condition was developed to facilitate large-scale sequencing of natural HS structures. The HS alterations in the sequence aspect were elucidated thoroughly in APAP-induced acute liver injury, rather than their compositional changes, which is of great significance for the applications of HS-based therapeutic agents in the biomedical field.

DOI: https://doi.org/10.1021/acs.analchem.6c00995
Carbohydr Polym. 2026 Sep 01. pii: S0144-8617(26)00609-0. [Epub ahead of print]387 125492

Structural characterization, in vitro anticoagulant, and antiplatelet activities of a Distolasterias nipon dermatan sulfate-like polymer with a distinctive sulfation pattern.

Alina P Filshtein, Vlada S Belova, Ilya V Taran, Maxim S Kokoulin.

  A novel dermatan sulfate-like polysaccharide (DNP) was isolated from the body walls of the starfish Distolasterias nipon. Its structure was elucidated using chemical methods and 2D NMR spectroscopy, revealing a backbone of →4)-α-L-IdopA-(1→3)-β-D-GalpNAc-(1→, with the α-L-iduronic acid residues predominantly 2,3-di-O-sulfated, alongside 2-O- and 3-O-monosulfated variants, and the β-D-GalpNAc residues 4-O-sulfated. Functional assays showed that DNP prolongs thrombin time (TT) comparable to heparin and more potently than enoxaparin (Clexane®), whereas its effect on activated partial thromboplastin time (APTT) is less pronounced. The anticoagulant activity of DNP is characterized by antithrombin-dependent thrombin inhibition and moderate suppression of factor Xa. Furthermore, the polysaccharide does not induce platelet aggregation nor interfere with physiological ADP-mediated pathways, but it inhibits ristocetin-induced aggregation. These findings identify D. nipon as a source of a dermatan sulfate structurally distinct from those found in other starfishes and invertebrates, and characterized by an antithrombin-dependent anti-IIa/anti-Xa profile and additional antiplatelet properties.

Keywords:  Anticoagulant activity; Dermantan sulfate; Distolasterias nipon; Starfish; Structure

DOI:  https://doi.org/10.1016/j.carbpol.2026.125492
Macromol Biosci. 2026 Jun;26(6): e70201

Fully Synthetic, Biomimicking Polysulfates With Tunable Anticoagulant and Endothelial Cell-Selective Bioactivity.

Andrea Cosimi, Roxana Pollehn, Andrea De Martino, Scarlett Manzke, Yannic Kerkhoff, Philip Nickl, Theresa Lohmann, Eriselda Keshi, Cornelia Lee-Thedieck, Marie Weinhart.

  We present a versatile method for fabricating glycosaminoglycan (GAG)-inspired polyelectrolyte brush coatings from fully synthetic sulfated PHEMA block copolymers. Using a bioinert backbone enables evaluation of sulfation effects independently of natural GAGs' carbohydrate backbone. A degree of sulfation above 70% imparted anticoagulant activity, extending plasma coagulation times beyond 500 s at 0.1 mg mL- 1. Controlled self-assembly enabled fabrication and photoimmobilization of uniform, nanometer-thin brushes on polystyrene substrates. The polysulfate brushes exhibited molecular weight-dependent properties: under serum-free conditions, endothelial cells (HUVECs) selectively proliferated on longer P2-OSO3-BP (65 kDa) compared to shorter P1-OSO3-BP (15 kDa) brushes, while smooth muscle cells (SMCs) remained quiescent. Despite comparable VEGF and bFGF surface densities (0.5 ng cm-2), P2-OSO3-BP coatings better preserved VEGF bioactivity, likely due to higher chain flexibility. In co-culture under serum conditions (5%), HUVEC/SMC ratios remained near unity with persistent colocalization, indicating restrained SMC overgrowth and stabilized vascular co-culture relevant to preventing neointimal hyperplasia. These findings highlight synthetic polysulfate brush coatings as a platform for studying sulfation-driven growth factor interactions and vascular cell competition at biomaterial interfaces, promoting reendothelialization in vitro. The system therefore represents a functional mimetic of GAGs, reproducing key electrostatic features while avoiding the structural complexity of native polysaccharides.

Keywords:  GAG‐mimetic; growth factor sequestration; in vitro reendothelialization; polyelectrolyte brushes; sulfated PHEMA

DOI:  https://doi.org/10.1002/mabi.70201
J Physiol Pharmacol. 2026 Apr;77(2): 279-287

Effect of short-term of vaginal therapy with prasterone before urogynecological surgery in woman.

K Tomczyk, M Kampioni, M Muszynska, P Piekarski, M Wilczak, K Chmaj-Wierzchowska.

  Among many different types of vaginal therapy for women suffering from urogynecological disorders, we may distinguish hormonal vaginal treatment with oestrogens. Lately, there has been a new option of treatment- prasterone. It is prohormone which can be further metabolized and acts like both estrogens and androgens. The purpose of the study is to analyze the effect of short-term vaginal application of prasterone. We checked 39 women of age 28-85 suffering from prolapse or stress incontinence that consented to surgical treatment and hadn't used vaginal estrogens before. We analyzed vaginal maturation index (VMI), biocenosis, endometrial thickness, and blood level of estradiol and dehydroepiandrosterone sulfate (DHEA-S) The analyses were performed before and after eight weeks of vaginal preparation with prasterone 6.5 mg once daily, administered intravginally. Results of the main variables before and after treatment were as follows: estradiol [pg/mL] 63.25±101.85 vs. 49.62±99.85 (p=0.94); DHEA-S [µmol/L] 3.93±2.19 vs. 4.28±2.55 (p=0.02); endometrial thickness [mm] 3.65±3.79 vs. 3.97±3.42 (p=0.97); biocenosis score [1-4] 2.95±0.94 vs. 2.50±0.76 (p=0.02). The study showed a significant increase in the DHEA-S levels after treatment and decrease in the degree of biocenosis. No substantial differences were found in relation to estradiol levels, or endometrium size. Moreover, a notable increase in the VMI was observed. Prasterone preparation has the effect of improving vaginal maturation and bacterial flora in both patients with stress urinary incontinence and female organ prolapse. In addition, these parameters are improved in both reproductive and menopausal women.

Keywords:  biocenosis; dehydroepiandrosterone sulfate; endometrium; estradiol; prasterone; prolapse; urogynecology; vaginal atrophy

DOI:  https://doi.org/10.26402/jpp.2026.2.09
J Bacteriol. 2026 Jun 12. e0052625

Heparin-binding enhances extracellular listeriolysin O activity, overcoming cholesterol inhibition and pH dependence.

Luigi La Pietra, Helena Pillich, Martina Hudel, Besim Berisha, Mobarak Abu Mraheil, Andreas Geissner, Peter H Seeberger, Trinad Chakraborty.

  The membranolytic toxin listeriolysin O (LLO), a member of the family of bacterial cholesterol-dependent cytolysins (CDC), is a key virulence factor of Listeria monocytogenes (Lm). Current evidence indicates that LLO is primarily a unique site-specific intracellular CDC, as it is highly active at the acidified pH of phagosomes but exhibits reduced activity and is prone to irreversible denaturation at physiological pH. Here, we demonstrate that LLO binds heparin and exploit this finding to affinity-purify the toxin in a single step. Heparin-binding increases LLO hemolytic activity at neutral pH manifold, and further amplifies the increased activity conferred by treatment with the thiol-reducing reagent DTT. Heparin-activated LLO is insensitive to inhibition by cholesterol, and its activity is not pH-dependent. We localized heparin binding to the C-terminal D4 membrane-interacting domain of LLO and used glycan arrays to define the minimal sulfated ligand engaged. Molecular docking studies suggest a heparin-binding site within this domain, and a LLO variant carrying a mutation (N508A) in this region no longer exhibited heparin-enhancing hemolytic activity. Engaging heparin enhances hemolysis and provides an additional layer of regulation of toxin function that ensures its optimal activity at physiological pH. As LLO is known to promote bacterial entry, and the sulfated heparin substructure recognized is present in many members of the family of cell surface heparan sulfates, our data suggest that this targeted tropism could contribute to the transition of the bacterium from extracellular compartments to intracellular niches.IMPORTANCEBacterial pore-forming cytolysins act extracellularly to disrupt host cell membranes. Listeriolysin (LLO), a cholesterol-dependent cytolysin (CDC) and a key virulence factor of Listeria monocytogenes, is distinguished by its site-specific intracellular activity, exhibiting maximal function at the acidic pH of phagosomes where the bacteria reside after uptake. At physiological pH and temperature, LLO exhibits reduced activity and susceptibility to denaturation. Here, we show that LLO binds heparin, a property that greatly enhances its hemolytic activity at neutral pH and overcomes cholesterol-dependent inhibition. We identified both the heparin binding site in LLO and the structure of the minimal interacting ligand engaged. The affinity of LLO for heparin enabled direct purification of highly active toxin from diverse naturally occurring isolates in a single step.

Keywords:  D4 domain; LLO purification; Listeria monocytogenes; core ligand; heparan sulfate; heparin-binding proteins; listeriolysin (LLO)-heparin interaction

DOI:  https://doi.org/10.1128/jb.00526-25
J Am Chem Soc. 2026 Jun 10.

Total Synthesis of Conjugation-Ready Sulfated Red Algae Carrageenan Oligosaccharides for Sensing Applications.

Yonatan Sukhran, Roey G Meir, Israel Alshanski, Shlomo Yitzchaik, Mattan Hurevich.

Carrageenans are versatile sulfated marine galactans that possess attractive modification-dependent bulk properties, making them prime candidates for various cosmetic, drug delivery, and food-related applications. The structural diversity and intrinsic complexity of carrageenans hamper access to homogeneous polysaccharides, limiting the development of many carrageenan-based applications. We devised a synthetic strategy for the acquisition of a panel of γ-carrageenan-derived oligosaccharides with varying sulfation profiles and chain length. To that end, we synthesized a set of specialized building blocks with an elaborate multilevel protecting group hierarchy, tailor-made to specifically accommodate the structural complexity of carrageenans. In doing so, we uncovered interdependent protecting group and reactivity constraints, which we resolved strategically to adapt the synthetic route across the panel of carrageenans and minimize trade-offs. Assembly of di-, tri-, and tetrasaccharides with precise control over monomer connectivity and regiodefined sulfation on a conjugation-ready linker showcased the first total synthesis of homogeneous carrageenan oligogalactans. We demonstrated that the application of the curated panel enabled elucidation of the effect of γ-carrageenan molecular features on IL-8 binding preferences via electrochemical sensing and surface analyses.

DOI: https://doi.org/10.1021/jacs.6c09827
Polymers (Basel). 2026 May 29. pii: 1351. [Epub ahead of print]18(11):

Chondroitin Sulfate-Based MPDA@MnO2 Nanocomposite Hydrogels: A Smart Drug Delivery System with pH/ROS Responsiveness and Photothermal-Enhanced Therapeutic Effects.

Xu Wang, Qin Ding, Rui Ran, Qiangguo Chen, Xian Li, Xu Ye.

  Chronic wounds, particularly those complicated by infection, present significant challenges in clinical management. The microenvironment of these wounds is typically characterized by the accumulation of reactive oxygen species (ROS) and abnormal local pH levels, both of which impede the healing process. Baicalin (BA), a natural flavonoid, exhibits anti-inflammatory activity, ROS-scavenging capability, and pro-healing effects. In this study, hydrogels were synthesized through photoinitiated radical polymerization of methacrylic anhydride (MAA) and dopamine (DA)-modified chondroitin sulfate (ChSMA-DA), grafting degrees of MA and DA were 58%, 23%, MPDA@MnO2 nanoparticles (NPs), and methacrylated gelatin (GelMA). The gelation time, microtopography, swelling behavior, and water retention of the hydrogels were investigated, along with their degradation, rheological properties, and photothermal effects. The results indicate that swelling ratio (SR) and water retention (WR) of optimal HG-MPDA@MnO2-M sample were 5.7, 82.42%, exhibited responsive behavior upon weakly acidic environment with pH 6.5 and elevated ROS levels, and exhibited a stable photothermal effect (photothermal conversion efficiency was 22.7%) under 808 nm near-infrared (NIR) light. Following the incorporation of the drug model BA, the cumulative release percentage over 24 h under the combined stimulation of pH 6.5, 1 mmol·L-1 H2O2, and 808 nm NIR was 81.1%, significantly higher than either factor alone. These hydrogels show promise as an injectable dressing for chronic wounds, effectively integrating the internal microenvironment of the wound tissue with external NIR to modulate drug release.

Keywords:  ROS; drug delivery; environmental stimulus response; hydrogels

DOI:  https://doi.org/10.3390/polym18111351