bims-supasi 2026-02-01 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–02–01
seventeen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Structural Basis of Chemokine CXCL8 Monomer and Dimer Binding to Chondroitin Sulfate: Insights into Specificity and Plasticity.
Composites Based on Collagen, Chondroitin Sulfate, and Sage Oil with Potential Use in Dentistry.
GlycoRNA complexed with heparan sulfate regulates VEGF-A signalling.
Preclinical profiling of antibody drug conjugates targeting oncofetal chondroitin sulfate.
Injectable Chondroitin Sulfate Methacrylate Hydrogel Microspheres Co-Loaded with GLPM Nanozyme, Dexamethasone, and Stem Cells for Synergistic Osteoarthritis Therapy.
The Uremic Toxin p-Cresyl Sulfate Is a New Predictor of Major Adverse Cardiovascular Events in Patients with ST-Elevation Myocardial Infarction.
β-CD-polyethyleneimine hybrid alginate macrospheres for the efficient removal of indoxyl sulfate.
Sulfated poly(aspartic acid) coatings as next-generation biomimetic interfaces for blood-contacting devices.
A Sulfated Polysaccharide from Red Seaweed Gracilaria caudata Exhibits Antioxidant and Antiadipogenic Activities In Vitro.
Electroacupuncture Modulation of Chondroitin Sulfate Glycosaminoglycan Promotes the Repair of Damaged Spinal Cord in Rats.
Optimization of Ibuprofen Route and Dosage to Enhance Protein-Bound Uremic Toxin Clearance During Hemodialysis.
Direct Relationship Between Heparin Binding to Midkine and Pleiotrophin and the Development of Acute Deep Vein Thrombosis.
Differential expression of sulfate transporters under selenium supply identifies OsSULTR1;1 as a candidate for nutritional enhancement in super basmati rice.
The relationship between sex hormones, metabolic markers, and cognitive linguistic functions in women with PCOS.
Probiotic Supplementation in Chronic Kidney Disease: Outcomes on Uremic Toxins, Inflammation, and Vascular Calcification from Experimental and Clinical Models.
Interaction of Lysozyme with Sulfated β-Cyclodextrin: Dissecting Salt and Hydration Contributions.
Proteomics and acetyl-proteomics reveal the antibacterial mechanism of berberine sulfate against methicillin-resistant Staphylococcus aureus.

Biomolecules. 2026 Jan 12. pii: 124. [Epub ahead of print]16(1):

Structural Basis of Chemokine CXCL8 Monomer and Dimer Binding to Chondroitin Sulfate: Insights into Specificity and Plasticity.

Bryon P Mahler, Balaji Nagarajan, Nehru Viji Sankaranarayanan, Prem Raj B Joseph, Umesh R Desai, Krishna Rajarathnam.

  Chemokines play a central role in orchestrating neutrophil recruitment from the bloodstream and determining their effector functions at sites of infection. Chemokine activity is determined by three key properties: reversible monomer-dimer equilibrium, binding to glycosaminoglycans (GAGs), and signaling through the GPCR class of receptors CXCR1 and CXCR2. In this study, we investigated the structural basis of CXCL8 monomer and dimer binding to GAG chondroitin sulfate (CS) using nuclear magnetic resonance (NMR) spectroscopy, docking, and molecular dynamics (MD) measurements. Our studies reveal that both the monomer and dimer use essentially the same set of basic residues for binding, that the interface is extensive, that the dimer is the high-affinity CS ligand, and that the CS-binding residues form a contiguous surface within a monomer. Several of these residues also participate in receptor interactions, suggesting that CS-bound CXCL8 is likely impaired in its ability to bind receptors. Notably, we observe that the same basic residues are involved in binding CS and heparin/heparan sulfate, even though these GAGs differ in backbone structures and sulfation patterns. We conclude that the strategic distribution and topology of basic residues on the CXCL8 scaffold enable engagement with diverse GAG structures, which likely allows fine-tuning receptor signaling to regulate neutrophil trafficking and effector functions.

Keywords:  CXCL8; chemokine; chondroitin sulfate; glycosaminoglycan; heparan sulfate; heparin; interleukin-8; molecular dynamics; neutrophil; nuclear magnetic resonance; proteoglycan

DOI:  https://doi.org/10.3390/biom16010124
Biomimetics (Basel). 2025 Dec 24. pii: 8. [Epub ahead of print]11(1):

Composites Based on Collagen, Chondroitin Sulfate, and Sage Oil with Potential Use in Dentistry.

Bogdan Valeriu Sorca, Ana-Maria Rosca, Durmuş Alpaslan Kaya, Sergiu-Marian Vatamanu, Mădălina Georgiana Albu Kaya, Cristina Elena Dinu-Pîrvu, Mihaela Violeta Ghica, Alina Elena Coman, Laura Cristina Rusu, Irina Titorencu.

  Osseointegration in dental implants involves the use of materials that mimic the bone tissue, with special properties such as biocompatibility and biodegradability. In this study, we describe the preparation and characterization of composites based on collagen, chondroitin sulfate, and sage oil obtained by freeze-drying method. Their morphological structures were determined by water uptake and scanning electron microscopy, the physical-chemical interactions between components by FT-IR, the stability by in vitro collagenase degradation, and the results indicate that the samples' properties are highly influenced by the hydrophobic and hydrophilic character of sage essential oil and chondroitin sulfate, respectively, concluding that we can design a formulation with certain properties. The composite spongious forms were evaluated for cytocompatibility using the MG63 osteoblast cell line and subjected to histological observation. The results showed that the samples with sage essential oil were most resistant to enzymatic degradation, and the ones with chondroitin sulfate promoted the deposition of an abundant extracellular matrix. Taken together, the results suggest that incorporating chondroitin sulfate and sage oil in a controlled manner into collagen scaffolds represents a promising approach for enhancing bone tissue regeneration.

Keywords:  bone tissue regeneration; cell biocompatibility; collagen–chondroitin–sage composite; sponge form

DOI:  https://doi.org/10.3390/biomimetics11010008
Nature. 2026 Jan 28.

GlycoRNA complexed with heparan sulfate regulates VEGF-A signalling.

Peiyuan Chai, Sina Kheiri, Andrew Kuo, Jessica Shah, Lauren Kageler, Ruiqi Ge, Jonathan Perr, Jennifer Porat, Charlotta G Lebedenko, Joao M L Dias, Eliza Yankova, Sandeep K Rai, Christopher P Watkins, Petar Hristov, Konstantinos Tzelepis, Timothy Hla, Ritu Raman, Eliezer Calo, Jeffrey D Esko, Ryan A Flynn.

Heparan sulfate proteoglycans (HSPGs) have been recognized as key plasma membrane-tethered co-receptors for a broad range of growth factors and cytokines containing cationic heparan-binding domains1,2. However, how HSPGs mechanistically mediate signalling at the cell surface-particularly in the context of cell surface RNA-remain poorly understood. During developmental and disease processes, vascular endothelial growth factor (VEGF-A), a heparan sulfate-binding factor, regulates endothelial cell growth and angiogenesis3. The regulatory paradigm for endothelial cell-mediated selectively of VEGF-A binding and activity has largely been focused on understanding the selective sulfation of the anionic heparan sulfate chains4-8. Here we examine the organizational rules of a new class of anionic cell surface conjugates, glycoRNAs9,10, and cell surface RNA-binding proteins (csRBPs11,12). Leveraging genome-scale knockout screens, we discovered that heparan sulfate biosynthesis and specifically the 6-O-sulfated forms of heparan sulfate chains are critical for the assembly of clusters of glycoRNAs and csRBPs (cell surface ribonucleoproteins (csRNPs)). Mechanistically, we show that these clusters antagonize heparan sulfate-mediated activation of ERK signalling downstream of VEGF-A. We demonstrate that the heparan sulfate-binding domain of VEGF-A165 is responsible for binding RNA, and that disrupting this interaction enhances ERK signalling and impairs vascular development both in vitro and in vivo and is conserved across species. Our study thus uncovers a previously unrecognized regulatory axis by which csRNPs negatively modulate heparan sulfate-mediated signalling in the context of angiogenesis driven by VEGF-A.

DOI: https://doi.org/10.1038/s41586-025-10052-8
Cell Death Dis. 2026 Jan 24.

Preclinical profiling of antibody drug conjugates targeting oncofetal chondroitin sulfate.

Ann Skafte, Elena Ethel Vidal-Calvo, Swati Choudhary, Joana Mujollari, Robert Dagil, Anne Martin-Salazar, Htoo Zarni Oo, Lara Duvnjak, Thor G Theander, Mads Daugaard, Tobias Gustavsson, Ali Salanti.

Antibody-drug conjugates (ADC) offer a targeted cancer treatment approach by delivering cytotoxic payloads directly to tumor cells. However, resistance mechanisms, poor tumor penetration, and off-target toxicity often limit clinical efficacy. Vartumab targets oncofetal chondroitin sulfate (ofCS), a pan-cancer target present on tumor cells and in the malignant stroma, with low expression in normal tissues. As part of transitioning Vartumab to clinical evaluation, two linker-payloads known to mediate bystander effects, valine-citrulline (vc)-monomethyl auristatin E (MMAE) and glycine-glycine-phenylalanine-glycine (ggfg)-Deruxtecan (DXd), were investigated for design of Vartumab ADCs. We show that the ADCs maintain specificity to ofCS proteoglycans, cancer cells, and tissue biopsies, exhibiting specific binding to a wide range of malignant and metastatic tissues. Biodistribution assessment of Vartumab ADCs in mice shows strong and specific tumor uptake, with minimal accumulation in other organs. Both ADCs induced bystander killing of antigen-negative cells in the presence of antigen-positive cells and displayed potent anti-tumor activities in a cell-derived xenograft melanoma model. Furthermore, we show that Vartumab conjugates with bystander-capable linker-payloads exhibit greater in vivo potency compared to those with payloads lacking significant bystander effect. Finally, toxicity assessment in rats indicates that the ADC-MMAE is well-tolerated upon repeated doses, with similar dose-limiting toxicities as reported for clinically approved MMAE-conjugated ADCs. Our data support further clinical development of Vartumab-based ADCs.

DOI: https://doi.org/10.1038/s41419-026-08420-x
Adv Sci (Weinh). 2026 Jan 30. e17083

Injectable Chondroitin Sulfate Methacrylate Hydrogel Microspheres Co-Loaded with GLPM Nanozyme, Dexamethasone, and Stem Cells for Synergistic Osteoarthritis Therapy.

Xiaochen Feng, Ying Fang, Hongwei Yu, Yicheng Wang, Yunze Xu, Chunxiao Shi, Haike Xia, Ranjith Kumar Kankala, Aizheng Chen, Shibin Wang, Chaoping Fu.

  Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, chronic inflammation, and subchondral bone remodeling. Conventional intra-articular therapies provide limited relief and fail to address its multifactorial pathogenesis. Here, we present an injectable hydrogel microsphere platform that integrates antioxidative, anti-inflammatory, and regenerative functions for localized OA management. Uniform (∼125 µm) chondroitin sulfate methacrylate (ChSMA)-based microspheres are fabricated via microfluidic photocross-linking. Manganese dioxide nanoparticles provided catalytic reactive oxygen species (ROS) scavenging, while dexamethasone sodium phosphate enabled sustained release, reducing TNF-α and IL-6 levels by ∼30%. Bone marrow mesenchymal stem cells (BMSCs) are co-delivered to promote cartilage repair. In vitro, the microspheres reduce intracellular ROS, induce M2 macrophage polarization, and suppress inflammatory cytokines by 60-70%, with IL-10 levels increased by ∼90%. 3D co-culture supports chondrocyte/BMSC viability and matrix production. In vivo, intra-articular injection in a rat OA model markedly reduces cartilage erosion, decreases osteophyte volume by 80%, and improves subchondral bone microarchitecture. Histological staining confirms matrix restoration and structural preservation, with Osteoarthritis Research Society International (OARSI) scores reduced by 88%. Collectively, this injectable hydrogel microsphere system offers a minimally invasive and integrated strategy, simultaneously delivering antioxidative, anti-inflammatory, and regenerative effects for comprehensive OA management.

Keywords:  chondroitin sulfate; hydrogel microspheres; injection microspheres; manganese dioxide; osteoarthritis

DOI:  https://doi.org/10.1002/advs.202517083
Toxins (Basel). 2025 Dec 20. pii: 4. [Epub ahead of print]18(1):

The Uremic Toxin p-Cresyl Sulfate Is a New Predictor of Major Adverse Cardiovascular Events in Patients with ST-Elevation Myocardial Infarction.

Laure-Anne Raillon, Thomas Bochaton, Griet Glorieux, Fitsum Guebre-Egziabher, Christophe Olivier Soulage.

  ST-elevation myocardial infarction (STEMI) remains a major health concern despite advances in care. Indoxyl sulfate (IS) and p-cresyl-sulfate (p-CS) are gut-derived uremic toxins linked to higher morbidity and mortality in patients with chronic kidney disease (CKD). IS has been identified as an independent predictor of major adverse cardiovascular events (MACE) after STEMI, but data on p-CS are lacking. This study assessed the predictive value of IS and p-CS in STEMI patients with preserved renal function (cohort # NCT03070496). Plasma IS and p-CS were measured in 260 patients with STEMI who underwent primary coronary angiography. Samples collected 4 h after inclusion were analyzed using ultra-performance liquid chromatography with fluorescence detection. Optimal cut-offs were determined by the Youden index, and associations with MACE were evaluated by log-rank tests and Cox regression. Among 234 analyzed patients, 11.5% experienced MACE within one year. IS and p-CS levels were higher in the MACE group (IS: 3.14 vs. 2.19 µmol/L, p < 0.05; p-CS: 6.76 vs. 2.70 µmol/L, p < 0.01). Elevated p-CS independently predicted MACE (HR 3.79, 95% CI 1.29-11.17, p < 0.05), whereas IS lost significance after adjusting for kidney function. In STEMI patients, plasma p-CS is a stronger independent predictor of MACE than IS, highlighting its potential role in the gut-heart axis.

Keywords:  ST-elevation myocardial infarction (STEMI); gut–heart axis; indoxyl sulfate (IS); major adverse cardiovascular events (MACE); p-cresyl sulfate (p-CS); predictive biomarkers; uremic toxins

DOI:  https://doi.org/10.3390/toxins18010004
Biomed Mater. 2026 Jan 28.

β-CD-polyethyleneimine hybrid alginate macrospheres for the efficient removal of indoxyl sulfate.

Yukuan Lou, Jiaolun Li, Zhenkai Wu, Yifeng Wang, Suhua Zhang.

  Indoxyl sulfate (IS), one of protein bound uremic toxins (PBUTs), is associated with various complications in chronic kidney disease (CKD) patients and could partially be removed through hemodialysis and hemoperfusion due to its high affinity to HSA. Many studies have demonstrated the potential for blood purification, such as poly-β-cyclodextrin (PCD) and metal-organic frameworks (MOFs), providing new possibilities for the efficient removal of IS. Here, we utilized β-cyclodextrin (β-CD)-grafted polyethyleneimine (PEI), which is referred to as βP, as a scavenger for IS and sodium alginate (SA) as the matrix material to prepare alginate-based hybrid macrospheres (MS). The surface polydopamine (PDA) and argatroban (AG) modification resulted in enhanced biocompatibility and anticoagulation. The results indicated that the hybrid MS demonstrated effective absorption and removal capacity (79.96 %) of IS. Moreover, the lower hemolysis rate (0.36 %) and longer anticoagulation-related factors (APTT: 161.5 s; TT, 35.6 s) also revealed favorable biocompatibility and anticoagulation. This study presents a new way to designate blood purification materials and highlights their potential in clinical hemoperfusion treatment.

Keywords:  Indoxyl sulfate; argatroban; polydopamine; β-cyclodextrin

DOI:  https://doi.org/10.1088/1748-605X/ae3ec3
Biomater Adv. 2026 Jan 19. pii: S2772-9508(26)00021-X. [Epub ahead of print]182 214723

Sulfated poly(aspartic acid) coatings as next-generation biomimetic interfaces for blood-contacting devices.

Cuong Hung Luu, Akriti Nepal, Nam-Trung Nguyen, Hang Thu Ta.

  The increasing reliance on blood-contacting medical devices underscores the need for materials that minimise thrombosis and inflammation. Devices such as stents and dialysis membranes often face complications related to clot formation and microbial colonisation. To address these challenges, this study explored the development of sulfated poly(aspartic acid) (sPASP) coatings aimed at improving haemocompatibility and reducing infection risk. PASP, a biodegradable, biocompatible polymer, and calcium chelator, served as the base material, with sulfation introduced to enhance its antithrombotic, antibacterial, and anti-inflammatory properties. Sulfate groups mimic natural anticoagulants such as heparin, potentially promoting antithrombin activity and inhibiting clot development. The coatings were fabricated via a simplified one-pot process on polydopamine-modified substrates. The degree of sulfation was systematically varied from 10% to 80% to optimise the material's performance and thoroughly evaluated across multiple dimensions of blood compatibility. Assessments included surface physicochemical properties, protein adsorption, platelet adhesion, antithrombotic efficacy, cellular compatibility, and antibacterial activity, under static and dynamic conditions. Notably, sPASP with a sulfation degree of 40% exhibited the most favourable blood compatibility, demonstrating strong potential compared to heparin-mimicking polysaccharide coatings. In addition, the material exhibited excellent in vivo biocompatibility in implantation models, further underscoring its promise as a high-performance, multifunctional biomimetic interface for blood-contacting biomedical applications.

Keywords:  Antibacterial; Antithrombogenic; Biomimetic surface coating; Poly(aspartic acid); Sulfated

DOI:  https://doi.org/10.1016/j.bioadv.2026.214723
Mar Drugs. 2025 Dec 26. pii: 15. [Epub ahead of print]24(1):

A Sulfated Polysaccharide from Red Seaweed Gracilaria caudata Exhibits Antioxidant and Antiadipogenic Activities In Vitro.

Maxsuell Lucas Mendes Marques, Leandro Silva Costa, Mariana Santana Santos Pereira Costa, Hugo Alexandre Oliveira Rocha.

  This study investigated the antioxidant and antiadipogenic activities of sulfated polysaccharide (SPs) from the red seaweed Gracilaria caudata. First, sulfated polysaccharide-rich extracts (SPREs) from fifteen tropical seaweeds were screened to evaluate both their chemical composition and antioxidant potential. Among all samples, G. caudata exhibited the highest total antioxidant capacity, which justified its selection for detailed characterization. Sequential acetone precipitation produced three SPs (F1.5, F2.0, and F3.0), differing in sulfate content, monosaccharide composition, and molecular weight. In vitro assays revealed that F1.5 had the highest total antioxidant capacity and strong iron-chelating activity, while F2.0 exhibited the most effective hydroxyl radical scavenger. Importantly, F1.5 was the only SP that was non-cytotoxic to non-tumor cell lines. In 3T3-L1 preadipocytes, F1.5 attenuated H2O2-induced oxidative stress by reducing ROS and MDA levels and restoring GSH and SOD activity, achieving effects comparable to those of quercetin. Moreover, F1.5 inhibited adipogenic differentiation in a dose-dependent manner, as evidenced by decreased Oil Red O staining and reduced glycerol release. Collectively, these findings indicate that F1.5 exerts both antioxidant and antiadipogenic activities, highlighting G. caudata as a promising natural source of bioactive polysaccharides with potential nutraceutical applications. Nonetheless, further studies are required to elucidate the molecular mechanisms underlying these effects, validate the efficacy in vivo, and assess bioavailability and safety before clinical translation can be considered.

Keywords:  3T3-L1 cells; anti-obesity; oxidative stress; sulfated galactan; sulfated polysaccharide

DOI:  https://doi.org/10.3390/md24010015
J Integr Neurosci. 2026 Jan 22. 25(1): 46448

Electroacupuncture Modulation of Chondroitin Sulfate Glycosaminoglycan Promotes the Repair of Damaged Spinal Cord in Rats.

Bowen Chen, Rong Hu, Xingying Wu, Mengting Shi, Yi Chen, Jieqi Zhang, Yi Huang, Xihan Ying, Dexiong Han, Ruijie Ma.

   BACKGROUND: The perineuronal net (PNN) is an important extracellular environment around parvalbumin interneuron (PV IN) in the spinal cord. Chondroitin sulfate proteoglycan (CSPG) serves as a key factor mediating PNN effects on the spinal cord, primarily formed by covalently linked chondroitin sulfate glycosaminoglycan (CS-GAG) chains and diverse core proteins. Extensive research suggests that degradation of CS-GAG following nerve injury may contribute to severe spinal cord damage. Inhibiting CS-GAG degradation could enhance PNN stability and plasticity, thereby promoting recovery from nerve injury. Electroacupuncture (EA) intervention demonstrates significant neuroprotective effects, facilitating restoration of spinal cord nerve function and axonal regeneration. This study aims to observe the changes in CS-GAG and the expression of PV IN after spinal cord injury (SCI) in rats and explore the effect.
METHODS: An SCI model was established in Sprague-Dawley rats using an Infinite Horizon (IH) impactor, and EA was applied to the Jia-ji acupoints (EX-B2). The Basso-Beattie-Bresnahan (BBB) score of SCI rats was evaluated, and electromyography (EMG) of the gastrocnemius muscle of the hind limbs was performed. The protein expression levels of CS-GAG and glutamic acid decarboxylase (GAD) were detected using western blotting, and perineuronal nets (PNN) and PV IN were observed using immunofluorescence (IF). Fiber-optic calcium imaging was used to detect and analyze PV IN activity. Adeno-associated virus containing carbohydrate sulfotransferase 11 (Chst11) was injected into T9 and T10 spinal cord spaces using a microneedle, and changes in CS-GAG in the spinal cord of SCI rats before and after EA intervention were observed.
RESULTS: CS-GAG and GAD expression levels were significantly decreased after SCI and PNN stability was reduced. Chondroitinase ABC (ChABC) treatment increased PV IN activity and GAD expression. EA effectively promoted an increase in CS-GAG and GAD, improved PNN stability and PV IN activity, and reversed the inhibitory effect of Chst11, thereby facilitating the rehabilitation of rats with SCI.
CONCLUSION: The mechanisms and effects of EA on SCI repair were investigated. The results revealed that EA can regulate the recovery of PNN structure and function via CS-GAG and GAD, improve PV IN activity, and reverse the inhibitory effect of Chst11 to promote SCI rehabilitation in rats.

Keywords:  chondroitin sulfate glycosaminoglycan; electroacupuncture; glutamic acid decarboxylase; parvalbumin interneuron; spinal cord injury

DOI:  https://doi.org/10.31083/JIN46448
Toxins (Basel). 2026 Jan 11. pii: 37. [Epub ahead of print]18(1):

Optimization of Ibuprofen Route and Dosage to Enhance Protein-Bound Uremic Toxin Clearance During Hemodialysis.

Víctor Joaquín Escudero-Saiz, Elena Cuadrado-Payán, María Rodríguez-García, Gregori Casals, Lida María Rodas, Néstor Fontseré, María Del Carmen Salgado, Carla Bastida, Nayra Rico, José Jesús Broseta, Francisco Maduell.

  Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT clearance by competing for albumin-binding sites, but the optimal dose and route of administration remain unclear. The aim of this study was to evaluate the effect of different ibuprofen doses, infusion durations, and routes of administration on the removal of IS and pCS during on-line hemodiafiltration (OL-HDF). In this prospective, single-centre, crossover study, 21 chronic haemodialysis patients receiving intradialytic analgesia underwent nine OL-HDF sessions. Ibuprofen was administered at two doses (400 or 800 mg) either in the arterial pre-filter line (infusion over 1 h, 2 h, or 3 h) or in the venous post-filter line (30 min). Reduction ratios (RR) of total IS and pCS were determined by LC-MS and corrected for haemoconcentration. Statistical analysis included repeated-measures ANOVA with post-hoc testing. Baseline RR for IS and pCS were 53.7 ± 9.9% and 47.1 ± 10.9%, respectively. The highest RR was achieved with 800 mg ibuprofen infused via the arterial line over 2 h (IS: 60.8 ± 8.6%; pCS: 57.8 ± 9.7%). All arterial-line 800 mg regimens and the 3-h 400 mg infusion significantly improved pCS clearance versus baseline; IS clearance improved significantly only with arterial-line 800 mg regimens and with the 400 mg 3-h infusion. Infusion rate (1-3 h) had no significant effect on RR within the same dose group. Pain scores decreased significantly after dialysis regardless of ibuprofen regimen. Arterial-line administration of ibuprofen enhances total IS and pCS removal during OL-HDF, with higher doses yielding greater clearance. Prolonged low-dose infusion appears similarly effective for pCS and may reduce systemic exposure, potentially lowering toxicity risk. These findings support the arterial line as the preferred route for displacer administration in clinical practice.

Keywords:  arterial line infusion; displacer; ibuprofen; indoxyl sulphate; online hemodiafiltration; p-cresyl sulphate; protein-bound uremic toxins

DOI:  https://doi.org/10.3390/toxins18010037
Biomedicines. 2026 Jan 21. pii: 242. [Epub ahead of print]14(1):

Direct Relationship Between Heparin Binding to Midkine and Pleiotrophin and the Development of Acute Deep Vein Thrombosis.

Suna Aydin, İsmail Polat, Kevser Tural, Nurullah Duger, Kader Ugur, İbrahim Sahin, Suleyman Aydin, Do-Youn Lee.

  Background/Objectives: The underlying molecular mechanisms of deep vein thrombosis (DVT), which continues to be a major global public health concern, remain unclear. A key component of anticoagulant therapy, heparin (HP) interacts with heparin-binding growth factors including pleiotrophin (PTN) and midkine (MK), both of which have basic amino acid-rich domains that have a strong affinity for HP. The purpose of this study was to determine if changes in the levels of circulating HP, MK, and PTN are linked to the onset of acute DVT. Methods: Thirty patients diagnosed with acute DVT by venous Doppler ultrasonography (VDU) and 28 healthy controls with normal VDU findings were enrolled. Serum HP, MK, and PTN concentrations were measured using ELISA. In DVT patients, blood samples were obtained before and after routine subcutaneous low-molecular-weight heparin treatment; controls provided a single blood sample. ROC curve analysis was used to assess diagnostic performance. Results: Prior to treatment, patients with acute DVT exhibited significantly lower serum HP levels (p < 0.05) and significantly higher MK and PTN levels compared with healthy controls (both p < 0.05). Following heparin administration, serum HP levels increased significantly (p < 0.05), while MK and PTN levels showed a decreasing trend that did not reach statistical significance (p > 0.05). ROC curve analysis demonstrated limited diagnostic performance for HP (sensitivity 10.3%, specificity 68.8%), PTN (62.1%, 54.2%), and MK (82.8%, 35.4%). Conclusions: Decreased circulating HP and increased MK and PTN levels are characteristics of acute DVT that may indicate endogenous HP sequestration through binding to these growth factors. This imbalance could lead to less free HP being available, which would encourage the formation of thrombus. Therapeutic approaches that target MK- and PTN-mediated HP interactions may constitute a unique approach for the therapy of acute DVT, as evidenced by the partial normalization seen after exogenous heparin delivery.

Keywords:  deep vein thrombosis; heparin; heparin-binding; low-molecular-weight heparin; midkine; pleiotrophin

DOI:  https://doi.org/10.3390/biomedicines14010242
Mol Biol Rep. 2026 Jan 28. 53(1): 333

Differential expression of sulfate transporters under selenium supply identifies OsSULTR1;1 as a candidate for nutritional enhancement in super basmati rice.

Noreen Alsam, Muhammad Sameeullah, Songul Gurel, Ekrem Gurel.

   BACKGROUND: Selenium (Se) is an essential micronutrient for humans, yet its dietary availability largely depends on plant-based foods. In rice, Se uptake occurs mainly via sulfate transporters due to the chemical similarity between sulfate and selenate. While the role of transporters such as OsSULTR1;2 has been described in japonica rice, little is known about their regulation in indica aromatic cultivars like Super Basmati, which are naturally enriched in Se and widely consumed across Asia. This study aimed to characterize the transcriptional regulation of OsSULTR genes in Basmati rice under selenate exposure to identify candidate transporters contributing to Se biofortification.
METHODS AND RESULTS: Super Basmati seedlings were hydroponically grown under varying sulfate and selenate concentrations, and gene expression was analyzed in roots, shoots, and developing grains by qRT-PCR. Se accumulation was quantified using ICP-MS. Among high-affinity transporters, OsSULTR1;1 showed strong induction in root tissues under selenate supply and was persistently expressed in developing grains, indicating dual roles in uptake and grain loading. In contrast, OsSULTR1;2 and OsSULTR1;3 were shoot-specific with minimal induction. Group 3 transporters exhibited variable shoot-specific expression, with OsSULTR3;2 and OsSULTR3;3 showing notable induction during grain development. Se accumulation increased dose-dependently in roots and shoots, with efficient translocation to shoots and progressive enrichment in grains. Uptake was strongly pH-dependent, with maximal absorption at acidic pH (3.5).
CONCLUSIONS: Our findings highlight OsSULTR1;1 as the primary transporter mediating Se uptake and seed loading in Basmati rice, contrasting with OsSULTR1;2 in japonica rice. This study provides new molecular insights into Se accumulation in aromatic indica rice and identifies OsSULTR1;1 as a promising target for Se biofortification strategies to improve dietary nutrition.

Keywords:  Basmati rice; Expression profile; OsSULTR1;1; SULTRs; Selenium

DOI:  https://doi.org/10.1007/s11033-026-11494-7
Ginekol Pol. 2026 Jan 28.

The relationship between sex hormones, metabolic markers, and cognitive linguistic functions in women with PCOS.

Agnieszka Adamczak, Izabela Dymanowska, Aleksandra Glowinska, Wlodzimierz Plotek, Karolina Frankowska, Julia Spaczynska, Ewa Wysocka, Beata Banaszewska.

   OBJECTIVES: Polycystic ovary syndrome (PCOS) is a chronic endocrinopathy associated with a wide range of psychological disorders. Recent literature suggests a correlation between PCOS and cognitive linguistics disorders. This study aimed to analyze the relationship between sex hormones, metabolic markers, and cognitive linguistic performance in patients with PCOS.
MATERIAL AND METHODS: 48 women with PCOS and 56 healthy control women were included in the study. Standardized questionnaires were used to assess depressive symptoms [the Beck Depression Inventory (BDI-II)] and linguistic capability [the Wechsler Vocabulary Subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) test and "Łatysz" non-word reading test]. Baseline cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Laboratory tests included measurements of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin (SHBG), glucose, insulin, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC). Oral glucose tolerance test (OGTT) results were also obtained.
RESULTS: We observed significant differences in testosterone, DHEA-S, SHBG, insulin, insulin measured in 120-minute post-OGTT, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) values between women with and without PCOS. A negative correlation was found between the Wechsler Vocabulary Subtest of the WAIS-R test and testosterone, LDL, insulin, and HOMA-IR. Our study revealed a negative correlation between "Łatysz" non-word reading test and testosterone and a positive correlation between "Łatysz" non-word reading test and 120-minute post-OGTT blood glucose concentrations.
CONCLUSIONS: Our results suggest that there is a relationship between hormonal, metabolic markers, and cognitive functions in patients suffering from PCOS.

Keywords:  cognitive disorders; linguistic functions; metabolic markers; polycystic ovary syndrome; sex hormones

DOI:  https://doi.org/10.5603/gpl.105502
Toxins (Basel). 2025 Dec 20. pii: 6. [Epub ahead of print]18(1):

Probiotic Supplementation in Chronic Kidney Disease: Outcomes on Uremic Toxins, Inflammation, and Vascular Calcification from Experimental and Clinical Models.

Teresa Obrero, María Victoria Pendón-Ruiz de Mier, Jose E Gordillo-Arnaud, María José Jiménez Moral, Victoria Vidal, Fátima Guerrero, Andrés Carmona, María Encarnación Rodríguez-Ortiz, Ana Isabel Torralbo, Raquel Ojeda, Cayetana Moyano, Mercedes Sanchez-Ramade, Juan Mesa, Daniel J López-Ruiz, Karen Valdés-Díaz, Raquel María García-Sáez, Daniel Jurado-Montoya, Cristian Rodelo-Haad, María Álvarez-Benito, Griet Glorieux, Mariano Rodríguez, Sagrario Soriano-Cabrera, Juan Rafael Muñoz-Castañeda.

  Chronic kidney disease (CKD) is associated with gut microbiota alterations that contribute to increased inflammation and the generation of uremic toxins and may worsen the disease progression. While probiotics may improve the pro-inflammatory cytokine profile, their effects on mineral metabolism, vascular calcification (VC), and CKD progression remain unclear. We aimed to evaluate the impact of a commercial probiotic (Probimel) supplementation on kidney function, mineral metabolism, inflammation and VC in both an experimental rat model and patients with advanced CKD and VC. The experimental model of VC was performed through 5/6 nephrectomy (Nx), a high-phosphate diet, and calcitriol. Animals were divided into three groups: Sham, Nephrectomy, and Nephrectomy + Probiotic. In the exploratory clinical study, 23 patients with advanced stage 5 CKD and VC were randomized and either received or did not receive daily probiotics for 6 months. Kidney function, mineral metabolism, uremic toxins, inflammation, VC, and fecal microbiota were evaluated. Probiotic supplementation decreased interleukin-6 (IL-6) and interpheron-γ (IFN-γ) and levels of the uremic toxin, indoxyl sulfate (IS), in the experimental model. However, no clear evidence of improvement in kidney function or vascular calcification was observed in either rats or patients with this probiotic. Under our experimental and clinical conditions, the selected probiotic did not modify key parameters related to CKD progression or VC.

Keywords:  chronic kidney disease; inflammation; microbiota; probiotics; uremic toxins; vascular calcification

DOI:  https://doi.org/10.3390/toxins18010006
Molecules. 2026 Jan 20. pii: 372. [Epub ahead of print]31(2):

Interaction of Lysozyme with Sulfated β-Cyclodextrin: Dissecting Salt and Hydration Contributions.

Jacek J Walkowiak.

  This article investigates the thermodynamic driving force of the interaction between lysozyme (Lys) and sulfated β-cyclodextrin (β-CDS), with a particular emphasis on the elusive role of hydration during polyelectrolyte-protein binding. Using isothermal titration calorimetry (ITC), the binding affinity was quantified across varying temperatures and salt concentrations, employing a recently developed thermodynamic framework that explicitly separates the contributions from counterion release and hydration effects. The study reveals that while counterion release is minimal in the Lys/β-CDS system, hydration effects become a dominant factor influencing the binding free energy ΔGb, especially as experimental temperature deviates from the characteristic temperature T0. It demonstrates that hydration contributions can substantially weaken binding at increased salt concentration cs. The high characteristic temperature T0 and the salt-dependent heat capacity change indicate a complex interplay of water structure and ion association-significantly departing from commonly linear interpretations of ΔGb vs. log cs based solely on counterion release effects. This work advances the understanding of polyelectrolyte-protein interactions by providing the first direct quantification of the hydration effect in such complexes and may have an impact on the rational design of biomolecular assemblies and therapeutic carriers.

Keywords:  cyclodextrin; hydration; isothermal titration calorimetry (ITC); protein; thermodynamic analysis

DOI:  https://doi.org/10.3390/molecules31020372
Front Microbiol. 2025 ;16 1732962

Proteomics and acetyl-proteomics reveal the antibacterial mechanism of berberine sulfate against methicillin-resistant Staphylococcus aureus.

Zunli Hu, Huiling Liu, Mengying Chen, Jiafu Zhou, Yunxu Bian, Chuyao Lin, Shuming Liu, Yewen Sun, Minjia Tan, Jun-Yu Xu.

   Introduction: The rising prevalence of methicillin-resistant Staphylococcus aureus (MRSA) underscores an urgent need for novel antibacterial strategies. Although the natural antibacterial agent berberine sulfate exhibits inhibitory effects against MRSA, its precise molecular targets and mechanisms of action remain unclear.
Methods: To elucidate its mechanism, this study employed quantitative proteomics to analyze protein expression changes in MRSA before and after drug treatment. Acetylomics was further applied to investigate the impact on post-translational modifications. Key findings were functionally validated using site-directed mutagenesis and electrophoretic mobility shift assays (EMSA).
Results: Quantitative proteomics identified 255 differentially expressed proteins. Acetylomic analysis further revealed 38 differentially acetylated sites, among which berberine sulfate specifically induced acetylation at the K82 site of the global regulator SarA. Functional experiments demonstrated that the K82-mutated SarA protein showed significantly reduced binding affinity to the promoter of the virulence gene cluster agr.
Discussion: These results indicate that berberine sulfate mediates a comprehensive stress response in MRSA through extensive alterations in protein expression and post-translational modifications. Specifically, the acetylation of SarA at K82 and the consequent impairment of its DNA-binding capacity represent a potential core mechanism by which berberine sulfate suppresses MRSA virulence and adaptability.

Keywords:  Berberine sulfate; SarA; lysine acetylation; methicillin-resistant Staphylococcus aureus; proteomic analysis

DOI:  https://doi.org/10.3389/fmicb.2025.1732962