bims-supasi 2025-11-02 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–11–02
seventeen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Characterization of YKL-40 Binding to Extracellular Matrix Glycosaminoglycans.
Structure-Function Relationships of Heparan Sulfate-Based Neoproteoglycans as Selective Immunostimulatory Scaffolds.
Comprehensive Insights into the Role of Hydrogen Bonds in the Anaerobic Fermentation of Insoluble Exopolysaccharides in Waste Activated Sludge: Taking Chondroitin Sulfate as an Example.
Cyclo-glycylproline, a food-derived diketopiperazine, inhibits bacterial indole production: Implications for diabetic nephropathy prevention.
A Sulfated Polysaccharide from the Green Alga Caulerpa taxifolia: Characteristics of Its Structure and Anti-Diabetic Activity.
Chondroitin Sulfate as a New Profibrinolytic-Like Agent: A Preclinical Proof of Concept in a Model of Thromboembolic Stroke in Mice.
Structural Variants of Dermatan Sulfate Can Affect the Expression of Proteins Involved in Breast Cancer Cell Survival.
The Role of the Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 in Breast Cancer Pathophysiology.
Spatial Raman Spectroscopy to Characterize (Sulfated) Glycosaminoglycans in Human Articular Cartilage.
Adsorption Removal of Protein-Bound Uremic Toxins: Material Strategies, Dissociation Mechanisms, and Clinical Challenges.
Near-infrared responsive nanozyme-carboxymethyl chitosan/chondroitin sulfate composite hydrogel: Multicomponent synergy optimizes bone defect microenvironment to enhance repair.
Renal Effects of Sulfated Polysaccharides from the Seaweed Gracilaria cornea.
The ExPAND Study: A Prospective Association Study into Endometriosis-Associated Pain, Neurosteroid Synthesis, and TRPM3.
Low molecular weight sulfated galactan attenuates imiquimod-induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation.
Androgen-Secreting Adrenal Adenoma in a Postmenopausal Woman as a Cause of Hirsutism.
A Sulfated Polysaccharide from Gelidium crinale Suppresses Oxidative Stress and Epithelial-Mesenchymal Transition in Cultured Retinal Pigment Epithelial Cells.
Sulfated hyaluronic acid for wound repair: Mechanisms, materials, and translational challenges.

Mar Drugs. 2025 Sep 26. pii: 379. [Epub ahead of print]23(10):

Characterization of YKL-40 Binding to Extracellular Matrix Glycosaminoglycans.

Unnur Magnusdottir, Yiming Yang Jonatansdottir, Kristinn R Oskarsson, Jens G Hjorleifsson, Jon M Einarsson, Finnbogi R Thormodsson.

  YKL-40 is a chitinase-like glycoprotein implicated in various pathological processes, yet its glycosaminoglycan (GAG) binding profile beyond heparin has not been examined. In this study, we performed a Microscale Thermophoresis (MST) analysis on the heparin-binding glycoprotein YKL-40 using low molecular weight GAG oligosaccharides. We identified two new GAG ligands, dermatan sulfate (DS) and hyaluronan (HA), while chondroitin sulfate (CS) showed no detectable binding affinity. The results show that heparin is bound with the strongest affinity, followed by DS and HA. To further investigate these differences, molecular docking was used to evaluate possible binding modes. Molecular docking results indicated that both heparin and DS interacted with the same site on YKL-40, the heparin-binding site at residues 143-149, suggesting a multifunctional binding region that may act as a competitive switch or integration hub for spatially regulated signaling. Together, these findings expand the known ligand profile of YKL-40 and offer new insights into its ECM-context-dependent roles, with implications for targeting YKL-40 in diseases involving chronic inflammation, fibrosis, and cancer progression.

Keywords:  Microscale Thermophoresis (MST); YKL-40; binding affinity; cancer; extracellular matrix (ECM); fibrosis; glycosaminoglycans (GAGs); inflammation; molecular docking

DOI:  https://doi.org/10.3390/md23100379
Chemistry. 2025 Oct 30. e02735

Structure-Function Relationships of Heparan Sulfate-Based Neoproteoglycans as Selective Immunostimulatory Scaffolds.

Ankita Chandra, Marco Maccarana, Sharath S Vishweshwara, Sandhya Mardhekar, Saurabh Anand, Preeti Ravindra Bhoge, Jin-Ping Li, Raghavendra Kikkeri.

  Heparan sulfate proteoglycans (HSPGs) play a critical role in regulating inflammatory responses. Their diverse functions arise from the distinct structural heterogeneity of heparan sulfate (HS) side chains. Deciphering these structural determinants offers a promising strategy for developing novel vaccine adjuvants and immunotherapeutic agents. Herein, we evaluated a panel of neoproteoglycans (neoPGs) functionalized with structurally defined HS oligosaccharides to identify ligands that selectively trigger cytokine responses in immune cells. Our results demonstrate that highly sulfated, L-iduronic acid-containing, N-sulfated HS-conjugated neoPGs, specifically H7 and H12 induced pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in human peripheral blood mononuclear cells (PBMCs), compared to their D-glucuronic acid analogs. Notably, cotreatment with lipopolysaccharide (LPS) did not result in a synergistic increase in cytokine levels, indicating that these HS neoPGs likely activate immune signaling independently of the LPS-mediated pathway. In contrast, similar experiments with murine macrophage cell line PMJ2-PC showed only modest cytokine induction, particularly with the H6 ligand, further supporting a cell-type specific and Toll-like receptor (TLR) independent mechanism of action. Collectively, these data identify structurally distinct HS domains that can function as cell-specific immunomodulators, offering new opportunities for the rational design of glycan-based adjuvants and therapeutic immune regulators.

Keywords:  cytokines; glycocalyx; heparan sulfate; immune response; proteoglycan

DOI:  https://doi.org/10.1002/chem.202502735
Environ Sci Technol. 2025 Oct 30.

Comprehensive Insights into the Role of Hydrogen Bonds in the Anaerobic Fermentation of Insoluble Exopolysaccharides in Waste Activated Sludge: Taking Chondroitin Sulfate as an Example.

Xing-Chen Huang, Si-Jie Zheng, Yan-Lin Hu, Yu-Er Cao, Ying-Ying Liu, Kun Dai, Raymond Jianxiong Zeng, Fang Zhang.

  The hydrogen bond confers the structural recalcitrance of insoluble exopolysaccharides, but its role in the anaerobic fermentation of waste activated sludge (WAS) is seldom reported. As a typical high-molecular-weight exopolysaccharide with poor solubility, chondroitin sulfate (CS) was used to elucidate the role of hydrogen bonds in WAS fermentation. The chondroitin sulfate-degrading consortium (CSDC) was enriched for 180 days, but the methane production was limited (∼18%). The methane production was significantly improved by 88.2%, and extracellular enzyme activity increased by 11.8% after the fast acidic pretreatment of CS. The disruption of the hydrogen bond was confirmed by combining 41.6% reduction of particle size, 46.7% decrease of surface height, blue shifts in the O-H vibrational spectra, and 38.1% decline of interfacial free energy. The molecular dynamics simulation further showed that the hydrogen bond number after the fast acidic pretreatment was reduced from 51.4 ± 2.7 to 44.9 ± 2.1. Co-occurrence network analysis identified Thermovirga as a keystone taxon to facilitate microbial cooperation. The metagenomics and metaproteomics analyses revealed that Proteiniphilum and Mariniphaga served as key producers of extracellular CS-degrading enzymes, primarily CS lyase (EC 4.2.2.5). Above all, these findings demonstrate that the hydrogen bond represents a non-negligible structural constraint on the degradability of insoluble exopolysaccharides.

Keywords:  chondroitin sulfate; co-occurrence network analysis; hydrogen bond; insoluble exopolysaccharides; metagenomics and metaproteomics

DOI:  https://doi.org/10.1021/acs.est.5c11116
Biosci Biotechnol Biochem. 2025 Oct 27. pii: zbaf152. [Epub ahead of print]

Cyclo-glycylproline, a food-derived diketopiperazine, inhibits bacterial indole production: Implications for diabetic nephropathy prevention.

Daiki Oikawa, Toru Nakayama.

  Diabetic nephropathy is a kidney disease aggravated by the uremic toxin indoxyl sulfate, which is produced from indole by the gut microbiota. Targeting the bacterial enzyme tryptophan indole-lyase (TIL), which produces indole from L-tryptophan, could be a promising therapeutic strategy. This study investigates diketopiperazines, particularly cyclo-glycylproline [cyclo(Gly-Pro)], as potential TIL inhibitors. Cyclo(Gly-Pro) and other diketopiperazines moderately inhibited indole production from L-tryptophan in crude bacterial extracts. Cyclo(Gly-Pro) was not metabolized by the bacteria and did not affect their viability. Cyclo(Gly-Pro) inhibited the Escherichia coli TIL with a Ki value of 17 μM through a mixed-type mechanism. Computational docking studies supported this finding, showing that cyclo(Gly-Pro) binds near the active site of TIL. Additionally, cyclo(Gly-Pro) significantly reduced indole production in bacterial cultures and human fecal samples. These findings suggest that cyclo(Gly-Pro) could be a promising dietary supplement or a lead compound for developing new therapeutics to prevent or treat diabetic nephropathy.

Keywords:  cyclo-glycylproline; diabetic nephropathy; enzyme inhibition; indoxyl sulfate; tryptophan indole-lyase

DOI:  https://doi.org/10.1093/bbb/zbaf152
Mar Drugs. 2025 Sep 25. pii: 374. [Epub ahead of print]23(10):

A Sulfated Polysaccharide from the Green Alga Caulerpa taxifolia: Characteristics of Its Structure and Anti-Diabetic Activity.

Shan Liu, Ling Qin, Dan Li, Fang Lu, Mengdi Liang, Jiejie Hao.

  Polysaccharides derived from green algae have garnered significant attention owing to their distinctive structural characteristics and biological activities. In particular, sulfated polysaccharides from these algae represent a promising frontier in the discovery of novel therapeutic agents. In this present study, a sulfated galactan from Caulerpa taxifolia, designated SGC, was obtained by dilute alkali extraction and chromatographic purification. On the basis of chemical and spectroscopic analyses, the backbone of SGC was constituted by a backbone of →3)-β-d-Galp-(1→ with sulfate substitution at the C-2 and a branch on C-6. The side chains contained →6)-β-d-Galp(2SO4)-(1→, →6)-β-d-Galp(3OMe)-(1→ and →3)-β-d-Galp(4,6-Pyr)-(1→ units. SGC possessed strong hypoglycemic activity in vitro, as evaluated by an assay of α-amylase inhibition. The anti-diabetic activity of SGC in vivo was further investigated using T2DM mice induced by high-fat diet combined with streptozotocin. The results indicated that SGC markedly restored body weight, reduced fasting blood glucose and possessed a significant glucose-regulating effect. Furthermore, SGC effectively increased insulin sensitivity and mitigated insulin resistance. Additionally, SGC effectively regulated lipid metabolism and alleviated oxidative stress. Notably, SGC ameliorated liver and pancreas damage induced by high-fat diet combined with streptozotocin. The investigation demonstrates that SGC is a unique sulfated galactan and has potential as a novel anti-diabetic agent.

Keywords:  Caulerpa taxifolia; anti-diabetic activity; structural characterization; sulfated galactan

DOI:  https://doi.org/10.3390/md23100374
Arterioscler Thromb Vasc Biol. 2025 Oct 30.

Chondroitin Sulfate as a New Profibrinolytic-Like Agent: A Preclinical Proof of Concept in a Model of Thromboembolic Stroke in Mice.

Nakougou Moï-Bohm Biatougou, Audrey Picot, Myriam Abiou-Mourgues, Matthieu Bourdin, Yohann Repesse, Geneviève Contant, Denis Vivien, Richard Macrez.

   BACKGROUND: Ischemic stroke requires effective reperfusion therapies to limit brain injury, yet rtPA (recombinant tissue-type plasminogen activator) efficacy is limited, particularly in platelet-rich thrombi. Neutrophil extracellular traps (NETs) and their components, especially histones and DNA, contribute to thrombolysis resistance. Chondroitin sulfate (CS), a glycosaminoglycan with high affinity for extracellular histones, may neutralize their prothrombotic effects and improve outcomes. This study aimed to evaluate the effects of CS in preclinical ischemic stroke models and its impact on components of neutrophil extracellular traps.
METHODS: Two mouse models of middle cerebral artery occlusion were used: a fibrin-rich thromboembolic stroke model (rtPA-sensitive) and a platelet-rich aluminum chloride model (rtPA-resistant). Mice received intravenous CS (30-120 mg/kg), rtPA (10 mg/kg), or a combination of both. Lesion volume, tissue recanalization/reperfusion, hemorrhagic transformation, and functional connectivity were assessed via 7T magnetic resonance imaging and ultrafast Doppler imaging. In vitro coagulation-fibrinolysis assays examined the effects of neutrophil extracellular trap components on fibrin polymerization and fibrinolysis, and their modulation by CS±rtPA.
RESULTS: In the fibrin-rich model, CS alone reduced lesion volume by 36% and improved recanalization, comparable to rtPA (43%), without increasing hemorrhagic transformation. CS enhanced functional connectivity recovery at 24 hours, whereas combined CS+rtPA lost these benefits. In the platelet-rich model, CS did not affect lesion size, recanalization, or hemorrhage. In vitro, histones promoted clot stabilization and altered fibrinolysis, effects fully neutralized by equimolar CS in the absence of rtPA. With rtPA, CS's neutralizing capacity was reduced, and histone-driven profibrinolysis was accentuated at higher CS doses. DNA produced opposite effects to histones, and combined DNA+histones masked histone activity, resisting inhibition by CS+DNase.
CONCLUSIONS: CS mitigates histone-mediated prothrombotic effects, improves reperfusion and network recovery in fibrin-rich stroke, but loses efficacy in platelet-rich thrombi and when combined with rtPA. These findings support CS as a potential adjunct or alternative therapy, particularly for patients with contraindications to rtPA.

Keywords:  contraindications; fibrin; hemorrhage; histones; ischemic stroke

DOI:  https://doi.org/10.1161/ATVBAHA.125.323525
Cells. 2025 Oct 11. pii: 1581. [Epub ahead of print]14(20):

Structural Variants of Dermatan Sulfate Can Affect the Expression of Proteins Involved in Breast Cancer Cell Survival.

Grzegorz Wisowski, Monika Paul-Samojedny, Katarzyna Komosińska-Vassev, Adam Pudełko, Ewa M Koźma.

  Dermatan sulfate (DS) is an animal glycosaminoglycan with significant structural heterogeneity and a high, but variable density of negative electric charge. Owing to these characteristics DS displays a high degree of biological reactivity that is subject to regulation. We previously demonstrated that structural variants of DS rapidly induce moderate necroptosis in luminal breast cancer cells. In the present study, we investigated the intracellular molecular mechanism(s) that may underlie this effect, focusing on the expression of key regulators of intrinsic (BCL-2A1) and extrinsic (cFLIP) apoptosis, autophagy (Beclin-1), and oxidative stress protection (heme oxygenase-1 (HO-1)). Using RT-qPCR, Western blotting, immunofluorescence, and pharmacological inhibition, we have shown for the first time that DS, depending on its structure and the cancer cell line, can rapidly, albeit transiently, upregulate either the long or short cFLIP splicing variant and also reduce the level of HO-1. These effects are mediated via DS-triggered PI3K and/or NFκB signaling. Moreover, DS can also influence the intracellular distribution of these proteins. In contrast, this glycan did not affect the expression of BCL-2A1 and BECN1. These findings indicate that DS induces coordinated molecular remodeling in luminal breast cancer cells that creates an intracellular environment favorable for necroptosis induction.

Keywords:  cFLIP; dermatan sulfate; heme oxygenase-1; luminal breast cancer

DOI:  https://doi.org/10.3390/cells14201581
Cells. 2025 Oct 17. pii: 1612. [Epub ahead of print]14(20):

The Role of the Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 in Breast Cancer Pathophysiology.

Lena Habenicht, Nourhan Hassan, Nancy A Espinoza-Sànchez, Jessica Oyie Sousa Onyeisi, Balázs Győrffy, Lars Hanker, Burkhard Greve, Martin Götte.

  The heparan sulfate proteoglycan syndecan-3 (SDC3) is a critical regulator of cell-matrix interactions. While other syndecan family members contribute to the progression of multiple cancers, SDC3's functional contributions to tumor biology remain largely unexplored. This study investigates the potential role of SDC3 in the pathogenesis of breast cancer. By conducting an in-silico analysis of publicly available datasets, including TNM-plot, The Human Protein Atlas, and Kaplan-Meier Plotter, we observed that SDC3 is upregulated in breast cancer tissue. Notably, high SDC3 expression correlates with improved relapse-free survival in breast cancer patients. In vitro experiments revealed that SDC3 depletion significantly impairs cell viability, cell-cycle progression, cell migration, and 3D-spheroid-formation in MDA-MB-231 and MCF-7 breast cancer cells. Furthermore, SDC3 depletion results in upregulated gene expression of matrix metalloproteinases (MMP1, MMP9), downregulation of E-cadherin (CDH1), and altered levels of vascular endothelial growth factor A (VEGFA). Activation of proto-oncogene tyrosine-protein kinase Src was inhibited when SDC3 depletion was combined with tissue factor pathway inhibitor treatment. These findings demonstrate that breast cancer cell-derived SDC3 plays a pivotal role in tumor progression.

Keywords:  MMP; TFPI; breast cancer; cell proliferation; extracellular matrix; heparan sulfate; prognosis; proteoglycan; syndecan-3

DOI:  https://doi.org/10.3390/cells14201612
Int J Mol Sci. 2025 Oct 10. pii: 9875. [Epub ahead of print]26(20):

Spatial Raman Spectroscopy to Characterize (Sulfated) Glycosaminoglycans in Human Articular Cartilage.

Andrea Schwab, Jannik Jahn, Kerstin Sitte, Christoph H Lohmann, Jessica Bertrand, Sonja Gamsjaeger.

  Raman spectroscopy allows for analyzing local molecular matrix components while preserving spatial resolution in tissue samples. The aim of this study was to use Raman line scans to discriminate between healthy and diseased cartilage tissue based on the depth-dependent sulfated glycosaminoglycans (sGAG) and total GAGs distribution. Full-thickness articular cartilage tissue was harvested from human individuals at different maturation stages (skeletally immature, skeletally mature) and from patients with diagnosed osteoarthritis. Raman spectroscopic line scans (30 µm step size) were utilized to analyze the sub-zonal sGAG (1062 cm-1) and total GAG (1370-1380 cm-1) distribution relative to the organic matrix (CH2 band 1430-1480 cm-1). We found a linear trend of the sGAG/CH2 ratio over the tissue depth in all samples (p < 0.0001). The total GAG/CH2 ratio of the skeletally immature and mature cartilage showed a characteristic non-linear behavior over the tissue distance. The elderly osteoarthritic cartilage exhibited lower total GAG/CH2 ratios compared to the ratios of the skeletally immature and mature samples, without a pronounced increase in the superficial area. Raman spectroscopic line scans are a fast and representative method allowing us to identify the local and tissue depth-dependent distribution of GAGs at higher specificity and resolution compared to histological staining.

Keywords:  Raman spectroscopy; articular cartilage; glycosaminoglycans; osteoarthritis; skeletal development; sulfation

DOI:  https://doi.org/10.3390/ijms26209875
ACS Appl Mater Interfaces. 2025 Oct 29.

Adsorption Removal of Protein-Bound Uremic Toxins: Material Strategies, Dissociation Mechanisms, and Clinical Challenges.

Shujing Wang, Yu Chen, Dongmei Tong, Yupei Li, Baihai Su, Weifeng Zhao.

  Chronic kidney disease (CKD) is a highly prevalent condition that is associated with an increased burden of cardiovascular diseases and mortality. Between 7% and 12% of the general population are affected by CKD. In patients with end-stage renal disease (ESRD), the most severe form of CKD, large amounts of uremic toxins are retained in the blood due to impaired kidney function, leading to uremic symptoms and functional as well as biochemical alterations. Currently, extracorporeal blood purification techniques, including hemodialysis, hemofiltration, hemodiafiltration, and hemoperfusion, are widely used to remove small- to medium-sized uremic toxins, maintain homeostasis, and sustain the lives of ESRD patients. However, the available blood purification methods do not efficiently eliminate protein-bound uremic toxins (PBUTs), such as indoxyl sulfate (IS), hippuric acid (HA), p-cresyl sulfate (PCS), and indole-3-acetate (IAA), due to their strong affinity for albumin. The accumulation of PBUTs unfortunately contributes to kidney fibrosis, oxidative stress, cardiovascular events, and poor long-term survival. Therefore, the development of novel blood purification techniques to improve PBUT elimination is of considerable clinical significance. In this review, we first discuss the limitations of current blood purification modalities of PBUT removal and then summarize recent advances in hemoperfusion adsorbents, adsorptive hemodialysis membranes, and dialysate regeneration systems with enhanced PBUT clearance. Finally, we discuss potential challenges and future research directions in this field, with the aim of providing opportunities for more personalized and targeted blood purification therapies for ESRD patients.

Keywords:  adsorption; end-stage renal disease; hemodialysis; hemoperfusion; protein-bound uremic toxins

DOI:  https://doi.org/10.1021/acsami.5c18435
Int J Biol Macromol. 2025 Oct 29. pii: S0141-8130(25)09203-7. [Epub ahead of print] 148646

Near-infrared responsive nanozyme-carboxymethyl chitosan/chondroitin sulfate composite hydrogel: Multicomponent synergy optimizes bone defect microenvironment to enhance repair.

Dan Sun, Chuanbo Ding, Ning Wang, Qiteng Ding, Wencong Liu, Xinglong Liu, Hewei Wei, Junran Yang, Zhiqiang Cheng, Shujie Zhao, Bo Hong, Ting Zhao.

  Bone defects currently face great challenges in clinical practice. Even traditional treatments, such as allogeneic bone grafting or autologous bone grafting, often have specific drawbacks. To address issues such as donor shortages and the need for secondary surgery in traditional surgical procedures, this study employed carboxymethyl chitosan and oxidized chondroitin sulfate as hydrogel matrices, preparing hydrogels through the Schiff base reaction. At the same time, Fe3+-taxifolin nanoparticles with dual functions of near-infrared photothermal effect and enzyme-like activity were encapsulated in the hydrogels. Experiments have shown that the addition of nanoparticles enhances the antibacterial and antioxidant activities of the hydrogels. In vitro experiments have shown that the hydrogels can promote osteoblast proliferation and upregulate the expression of osteogenesis-related proteins. In vivo studies have demonstrated that the hydrogels can promote bone healing through the BMP/Smad signaling pathway. This study provides new insights into the application of flavonoid natural products in regenerative medicine, bone tissue engineering, and other related fields, offering a simple and promising strategy for treating joint bone defects.

Keywords:  Bone defects; Enzyme activity; Hydrogel; Photoresponse; Polyphenol complex

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.148646
Toxins (Basel). 2025 Oct 09. pii: 499. [Epub ahead of print]17(10):

Renal Effects of Sulfated Polysaccharides from the Seaweed Gracilaria cornea.

Terentia Batista Sá Norões, Sophia Moinhos, Helena Serra Azul Monteiro, Alice Maria Costa Martins, Ricardo Parente Garcia Vieira, Claudio Gleidiston Silva.

  Sulfated polysaccharides (SPs) are abundant in seaweed and have several industrial and biomedical applications, but their renal effects remain unclear. This study evaluated the effects of total sulfated polysaccharides (TSPs) from Gracilaria cornea using an isolated rat kidney perfusion model. TSP at 3 µg/mL increased perfusion pressure and renal vascular resistance at 90-120 min, while 4.5 µg/mL induced earlier and more pronounced changes (from 60 min). Urinary flow decreased at 1 µg/mL (90 min) but increased at 4.5 µg/mL (90-120 min). Sodium transport was reduced at all concentrations, whereas potassium and chloride transport remained unchanged. Histological analysis revealed protein deposits in tubules and urinary space, indicating tubular injury. In vitro, TSP reduced MDCK cell viability in a concentration-dependent manner and induced apoptosis, with some cells progressing to secondary necrosis. In conclusion, TSP altered renal physiology and morphology and triggered apoptotic pathways in renal cells, highlighting the need for further mechanistic and translational studies.

Keywords:  Gracilaria cornea; MDCK cells; apoptosis; isolated kidney perfusion; sulfated polysaccharides

DOI:  https://doi.org/10.3390/toxins17100499
Biomolecules. 2025 Sep 23. pii: 1352. [Epub ahead of print]15(10):

The ExPAND Study: A Prospective Association Study into Endometriosis-Associated Pain, Neurosteroid Synthesis, and TRPM3.

Eleonora Persoons, Celine Bafort, Pilar Van Mechelen, Martina Ciprietti, Katrien Luyten, Melissa Benoit, Arne Vanhie, Thomas Voets, Carla Tomassetti, Joris Vriens.

  Endometriosis-associated pain has debilitating effects on the quality of life of patients. Despite its high prevalence in reproductive-aged women, the pathophysiology is still unknown, impeding the development of targeted treatment approaches. The prospective ExPAND study proposes the neurosteroids pregnenolone sulphate (PS) and dehydroepiandrosterone sulphate (DHEAS) as potential contributors to endometriosis-associated pain, due to their agonistic action at the pain-related ion channel TRPM3. To this end, endometrium, deep endometriosis lesions, and peritoneal fluid were prospectively collected in four demarcated patient groups, which were characterised based on their pain symptoms, as scored via the WERF-EPHect questionnaire, i.e., (1) control (n = 44), (2) endometriosis patients with no pain symptoms (n = 24), (3) with only severe dysmenorrhea (n = 54), or (4) with both severe dysmenorrhea and non-cyclic pelvic pain (n = 78). Tissue mRNA expression levels of steroidogenic enzymes were investigated and showed significantly increased levels of CYP17A1 in the endometrium of patients with severe pain symptoms compared to control tissue. In addition, liquid chromatography with tandem mass spectrometry (LC-MS/MS) was performed to investigate neurosteroid concentrations in the peritoneal fluid. Both neurosteroids PS and DHEAS were present in the peritoneal fluid at concentrations that are known to stimulate TRPM3 activity in vitro. Finally, using microfluorimetric Ca2+ imaging, we demonstrate that both DHEAS and PS stimulate human stem-cell-derived sensory neurons in a TRPM3-dependent manner. Taken together, these data indicate a potential contribution of steroidogenesis and TRPM3 in endometriosis-associated pain.

Keywords:  DHEAS; PS; TRPM3; endometriosis; pain; steroidogenesis

DOI:  https://doi.org/10.3390/biom15101352
Biomed Rep. 2025 Dec;23(6): 190

Low molecular weight sulfated galactan attenuates imiquimod-induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation.

Kamonwan Jongsomchai, Arnon Pudgerd, Laorrat Phuapittayalert, Sataporn Jamsuwan, Teera Chanmanee, Kanokpan Wongprasert, Phennapa Promthale, Tawut Rudtanatip.

  Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation and immune cell infiltration. Low molecular weight sulfated galactan (LSG), derived from the red seaweed Gracilaria fisheri, has immunomodulatory potential relevant to psoriasis pathogenesis. The present study investigated the therapeutic potential of LSG using an imiquimod (IMQ)-induced murine model of psoriasis. BALB/c mice received intraperitoneal administration of LSG once daily, 2 h prior to IMQ application, for 7 consecutive days. Clinical severity was assessed using the Psoriasis Area and Severity Index (PASI). Histopathological and immunohistochemical analyses were performed to evaluate epidermal architecture, vascular change and immune cell infiltration. Expression of keratinocyte proliferation and differentiation markers, proinflammatory cytokines and JAK/STAT pathway components was analyzed using reverse transcription-quantitative PCR, ELISA and western blotting. Systemic inflammation was assessed by spleen and lymph node size. LSG significantly decreased PASI scores, neovascularization, epidermal thickness and dermal inflammation. LSG downregulated keratinocyte proliferation and differentiation markers (Ki67, keratin 6, 16 and 17, involucrin) and decreased proinflammatory cytokine expression (TNF-α, IL-1β, IL-17A, IL-23, IL-6), accompanied by decreased CD4+ T and mast cell infiltration. LSG downregulated JAK2/STAT2/STAT3 signaling and downstream genes (BCL2, CCND1). Furthermore, LSG alleviated systemic inflammation without inducing hepatic or renal toxicity. These findings indicated that LSG effectively ameliorates IMQ-induced psoriatic inflammation via coordinated reduction of keratinocyte hyperproliferation, cytokine production and immune cell activity. LSG represents a promising marine-derived therapeutic candidate for psoriasis management.

Keywords:  Gracilaria fisheri; intraperitoneal administration; low molecular weight sulfated galactan; psoriasis; skin inflammation

DOI:  https://doi.org/10.3892/br.2025.2068
JCEM Case Rep. 2025 Dec;3(12): luaf250

Androgen-Secreting Adrenal Adenoma in a Postmenopausal Woman as a Cause of Hirsutism.

Laura Natalia Bermúdez-Silva, Julieth Daniela Buell-Acosta, Luz Andrea León-Cárdenas, Jhon Jairo Peralta-Franco.

  Androgen-secreting adrenal adenomas are an exceptionally rare cause of hyperandrogenism, particularly in postmenopausal women. Hirsutism is a frequent clinical manifestation and warrants a comprehensive evaluation to distinguish between ovarian and adrenal sources. We present the case of a postmenopausal woman with a history of progressive hirsutism and virilization. Biochemical evaluation revealed elevated dehydroepiandrosterone sulfate (DHEAS) and total testosterone. Pelvic lesions were ruled out but abdominopelvic tomography revealed a 41 × 30 mm left adrenal mass. The remaining hormonal profile was unremarkable. The patient underwent left adrenalectomy, with immunohistopathological analysis confirming an adrenal adenoma. Postoperatively, her androgen levels significantly decreased, accompanied by clinical improvement in hirsutism. Although the vast majority of hyperandrogenic states in postmenopausal women are secondary to ovarian pathology, adrenal etiologies must be ruled out. Androgen-producing adrenal adenomas represent a rare cause of hyperandrogenism, and this case contributes further evidence regarding the clinical and biochemical behavior of these benign lesions.

Keywords:  adrenal adenoma; androgens; hirsutism; hyperandrogenism; postmenopausal woman; virilization

DOI:  https://doi.org/10.1210/jcemcr/luaf250
Mar Drugs. 2025 Sep 26. pii: 381. [Epub ahead of print]23(10):

A Sulfated Polysaccharide from Gelidium crinale Suppresses Oxidative Stress and Epithelial-Mesenchymal Transition in Cultured Retinal Pigment Epithelial Cells.

Yurong Fang, Haiyan Zheng, Yizhu Chen, Bomi Ryu, Zhong-Ji Qian.

  Age-related macular degeneration (AMD) progresses to vision-threatening dry and wet forms, with no effective dry AMD treatments available. The sulfated polysaccharide (GNP, 25.8 kDa) derived from Gelidium crinale exhibits diverse biological activities and represents a potential source of novel therapeutic agents. This study employed a hydrogen peroxide (H2O2)-induced oxidative stress and epithelial-mesenchymal transition (EMT) model in retinal pigment epithelial (RPE) cells to investigate GNP's protective mechanisms against both oxidative damage and EMT. The results demonstrated that GNP effectively suppressed oxidative stress, with the 600 μg/mL dose significantly inhibiting excessive reactive oxygen species (ROS) generation to levels comparable to untreated controls. Concurrently, at concentrations of 200-600 μg/mL, GNP inhibited NF-κB signaling and increased the Bax/Bcl-2 ratio, effectively counteracting H2O2-induced oxidative damage and cell apoptosis. Furthermore, in H2O2-treated ARPE-19 cells, 600 μg/mL GNP significantly reduced the secretion of N-cadherin (N-cad), Vimentin (Vim), and α-smooth muscle actin (α-SMA), while increasing E-cadherin (E-cad) expression, consequently inhibiting cell migration. Mechanistically, GNP activated the Nrf2/HO-1 pathway, thereby mitigating oxidative stress. These findings suggest that GNP may serve as a potential therapeutic agent for dry AMD.

Keywords:  Gelidium crinale; antioxidant; epithelial-mesenchymal transition; sulfated polysaccharide

DOI:  https://doi.org/10.3390/md23100381
Regen Ther. 2025 Dec;30 956-968

Sulfated hyaluronic acid for wound repair: Mechanisms, materials, and translational challenges.

Min Lin, Danni Zhou, Kaixuan Chen, Hankang Jiang, Wenjie Chen, Jing Wu, Guizhi Zhu, Kailei Xu, Peng Wei.

  Sulfated hyaluronic acid (sHA) is emerging as a promising biomaterial for advanced wound dressings because it combines the intrinsic biocompatibility and extracellular matrix (ECM)-like hydration of hyaluronic acid (HA) with added chemical functionality that enhances stability and bioactivity. Chronic wounds, particularly diabetic ulcer, -remain a major clinical challenge due to persistent inflammation, protease/reactive oxygen species (ROS)-rich microenvironments, impaired angiogenesis, and poor growth-factor retention; native HA is limited by rapid enzymatic degradation, low protein affinity, and potentially pro-inflammatory low-molecular fragments, motivating strategies to introduce sulfate groups onto HA to tune its interactions with cells and proteins. In this review, we performed a comprehensive literature review of the biological functions and applications of sHA in wound healing. Key results demonstrate that sHA significantly enhances anti-inflammatory responses, promotes sustained release of cationic therapeutics, improves angiogenesis, and reduces fibrosis. Furthermore, sHA-functionalized hydrogels accelerate diabetic wound healing by modulating macrophage polarization, enhancing re-epithelialization, and supporting vascularization. In further, we also offered a practical roadmap for researchers and clinicians to rationally design next-generation sHA-based dressings with improved reproducibility, controlled release, and safety.

Keywords:  Angiogenesis; Anti-inflammation; Biomaterials; Chronic wound; Diabetic wound

DOI:  https://doi.org/10.1016/j.reth.2025.10.006