bims-supasi 2026-02-08 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–02–08
fourteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Heparan sulfate promotes autoactivation of pro-Cathepsin K by destabilizing the propeptide-catalytic domain interaction.
Persulfate-driven free radical depolymerization of fucosylated chondroitin sulfate and intrinsic Xase inhibition of the resulting oligosaccharides.
Plasma chondroitin sulfate predicts the effectiveness of fluid resuscitation strategies in patients with sepsis.
Design and synthesis of novel fucosylated chondroitin sulfate derivatives as intrinsic FXase inhibitors and evaluation of their antithrombotic activities.
A non-canonical EZH2/TRIM28 epigenetic axis drives heparan sulfate remodeling and melanoma metastasis.
Engineered mesenchymal stem cells-laden chondroitin sulfate hydrogel promotes diabetic wound healing through ROS scavenging and macrophage polarization.
Fucoidan as a renal protectant: mechanistic insights and therapeutic implications of endothelial glycocalyx targeting.
Curcumin nanoparticles functionalized with chondroitin sulfate for ulcerative colitis treatment: Enhanced efficacy and mechanism exploration.
Smart hypoxia-responsive sulfated polysaccharides liposomes for controlled and targeted urokinase delivery in thrombotic therapy.
Capillary electrophoresis in glycosaminoglycan analysis.
Endothelial glycocalyx of equine intestinal vessels: electron microscopic and immunohistochemical imaging.
Reprogramming Immunogenicity of Iron Oxide Nanoparticles through Sulfated Glycan Presentation.
BIOCHEMICAL INVESTIGATION OF THE ANTICOAGULANT ACTIVITY OF SULFONATED POLYMERS.
Prevalence & predictors of sexual functioning & sex hormone profiles among men with opioid dependence: A community-based, cross-sectional study.

bioRxiv. 2026 Jan 20. pii: 2026.01.18.700217. [Epub ahead of print]

Heparan sulfate promotes autoactivation of pro-Cathepsin K by destabilizing the propeptide-catalytic domain interaction.

Huanmeng Hao, Xiaoxiao Zhang, Jian Liu, Ding Xu.

Pro-cathepsin-K (pro-CtsK) is the zymogen of cathepsin-K (CtsK), a collagenase that is essential for bone resorption. pro-CtsK is known to bind heparan sulfate (HS), but the biological significance of the interaction remains unclear. Here we report that HS accelerates the autoprocessing of pro-CtsK in a manner dependent on both sulfation pattern and oligosaccharide length. We discovered a previously unknown electrostatic interaction between the propeptide and the catalytic domain, which stabilizes the conformation of the propeptide and prevents it from intermolecular proteolytic activation. HS accelerates autoprocessing of pro-CtsK by disrupting this critical electrostatic interaction. Mechanistically, HS competes with two glutamic acids in the propeptide for binding to three basic residues on the catalytic domain, thereby substantially alters the conformation of the propeptide and making it more labile for autoprocessing. We further discovered that HS is highly enriched in secretory lysosomes of osteoclasts and might be directly involved in autoactivation of CtsK.

DOI: https://doi.org/10.64898/2026.01.18.700217
Carbohydr Res. 2026 Jan 29. pii: S0008-6215(26)00033-9. [Epub ahead of print]563 109844

Persulfate-driven free radical depolymerization of fucosylated chondroitin sulfate and intrinsic Xase inhibition of the resulting oligosaccharides.

Jiaying Sun, Le Sha, Guangyu Zhu, Linquan Li, Pengfei Li, Mengran Chen, Junhao Wang, Xueying Jiao, Na Gao, Jinhua Zhao.

  Free radical depolymerization has been widely employed for polysaccharide structural and functional studies. However, H2O2-induced depolymerization of the unique sea cucumber derived fucosylated chondroitin sulfate (FCS) generated diverse fragments with oxidation at their reducing ends, thus limiting preparation of well-defined oligosaccharides. Here, a thermal dissociation initiator, potassium persulfate (KPS), was utilized to induce radical depolymerization of FCS, leading to depolymerized products that maintained their basic structural units and sulfate substituents. Structural analysis of the resulting oligosaccharides revealed that the reducing ends were uniformly GalNAc4S6S acid, distinct from those generated by H2O2-induced FCS depolymerization. The major components, tetrasaccharide (FIIIa), heptasaccharide (FVa) and decasaccharide (FVIa) possessed GalNAc4S6S residues at their non-reducing ends, demonstrating that the D-GlcA-β1,3-D-GalNAc4S6S linkage was preferentially cleaved. A free radical depolymerization mechanism of FCS by KPS was proposed. The regular aldonic acid terminal formation was attributed to the strong oxidative capacity of the sulfate radical for extensive oxidation of the newly formed GlcA residue after β1,3 glycosidic linkage cleavage, and further oxidation of C-1 of GalNAc. KPS was thermally dissociated to generate sulfate radicals, which subsequently attacked FCS chains and led to their fragmentation. Moreover, biological activity assay showed that heptasaccharide FVa and decasaccharide FVIa demonstrated strong anticoagulant activity, primarily via iXase inhibition mediated by high-affinity interaction with FIXa. Intriguingly, the unique oxidized reducing end exhibited enhanced iXase inhibitory activity. Hence, our findings expanded the free radical depolymerization of FCS and enriched structure-activity relationship information for iXase inhibition.

Keywords:  FIXa; Free radical; Fucosylated chondroitin sulfate; Oligosaccharides; Persulfate; iXase

DOI:  https://doi.org/10.1016/j.carres.2026.109844
J Clin Invest. 2026 Feb 03. pii: e202480. [Epub ahead of print]

Plasma chondroitin sulfate predicts the effectiveness of fluid resuscitation strategies in patients with sepsis.

Kaori Oshima, Bailu Yan, Ran Tao, Gustavo Amorim, Chiara Di Gravio, Sarah A McMurtry, Ryan C Burke, Yunbi Nam, Ina Nikolli, Max S Kravitz, Daniel Stephenson, Aaron Issaian, Kirk C Hansen, Angelo D'Alessandro, Ivor S Douglas, Wesley H Self, Christopher J Lindsell, Carolyn Leroux, Angelika Ringor, Michael A Matthay, Jonathan S Schildcrout, Nathan I Shapiro, Eric P Schmidt.

   BACKGROUND: Plasma heparan sulfate, a glycosaminoglycan released during endothelial glycocalyx degradation, predicts sepsis mortality. Chondroitin sulfate is a circulating glycosaminoglycan not specific to glycocalyx degradation; its relevance to sepsis is unknown.
METHODS: We studied the associations of plasma chondroitin sulfate with (a) mortality in patients with sepsis-associated hypotension and (b) the relative effectiveness of a randomly-assigned liberal versus restrictive intravenous fluid resuscitation strategy. We selected 574 patients enrolled in the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis trial using an outcome-enriched sampling strategy. We used liquid chromatography-mass spectrometry to quantify plasma chondroitin sulfate. In comparison, we measured hyaluronic acid as a glycocalyx degradation marker and IL-6 as an inflammatory biomarker. We conducted Cox proportional hazards regression analyses to examine associations of baseline biomarker concentrations with mortality and resuscitation strategy effectiveness. We used inverse probability of selection weights and generalized raking to account for the non-representative sampling design.
RESULTS: Plasma chondroitin sulfate, hyaluronic acid, and IL-6 were associated with mortality within 90 days. As baseline chondroitin sulfate increased, subsequent randomization to a restrictive strategy was increasingly beneficial (p = 0.022): treatment effect hazard ratio (restrictive versus liberal) for mortality was estimated as 1.49 (95% CI 0.98-2.27), 1.30 (1.00-1.69), 1.09 (0.82-1.44), 0.88 (0.66-1.16), and 0.71 (0.52-0.97) for 10th, 25th, 50th, 75th and 90th percentiles of baseline chondroitin sulfate.
CONCLUSIONS: Plasma chondroitin sulfate predicts sepsis mortality and may modify the response to a subsequent liberal vs. restrictive intravenous fluid resuscitation strategy.
TRIAL:
CLINICALTRIALS: gov NCT03434028.

Keywords:  Biomarkers; Clinical Research; Glycobiology; Infectious disease; Inflammation

DOI:  https://doi.org/10.1172/JCI202480
Carbohydr Polym. 2026 Apr 01. pii: S0144-8617(25)01623-6. [Epub ahead of print]377 124839

Design and synthesis of novel fucosylated chondroitin sulfate derivatives as intrinsic FXase inhibitors and evaluation of their antithrombotic activities.

Dongliang Xu, Xi Gong, Lisha Lin, Hang Dong, Yijian Wen, Yingnian Li, Gang Fu, Yuanhang Ma, Weicheng Xiong, Tianyu Guan, Ao Sun, Xiangbao Meng, Xudong Dong, Zhongtang Li, Mingyi Wu, Zhongjun Li.

  Thrombotic disease is a major threat to human health, underscoring the urgent need for novel anticoagulants. Fucosylated chondroitin sulfate (FuCS) oligosaccharides, have emerged as promising anticoagulant drug candidates owing to their selective inhibition of the intrinsic factor Xase complex (iFXase). However, elucidation of their structure-activity relationship (SAR) has been hindered by structural complexity and synthetic challenges. This work aims to fill this gap by systematically investigating the effects of terminal modifications on their anticoagulant properties. Here, we established a modular synthetic platform that enables the preparation of sixteen FuCS nonasaccharide derivatives via click chemistry-mediated terminal. All FuCS derivatives exhibited significant and selective intrinsic anticoagulant activity. Among them, compounds A-3 and B-1 demonstrated the highest potency and pronounced selectivity toward iFXase, while showing minimal effects on FXa and thrombin (FIIa). Both compounds further displayed favorable pharmacodynamic properties, characterized by rapid onset of action (Tmax = 30 min) and sustained anticoagulant effects. In vitro and in vivo tests further revealed that selective iFXase inhibition by FuCS oligosaccharide derivatives effectively suppressed thrombus formation, validating iFXase as a promising antithrombotic target. Collectively, this work provides a practical framework for the rational design and evaluation of FuCS oligosaccharide-based anticoagulants.

Keywords:  Anticoagulation; Click reaction; Fucosylated chondroitin sulfate; Intrinsic tenase complex; Structure-activity relationship

DOI:  https://doi.org/10.1016/j.carbpol.2025.124839
bioRxiv. 2026 Jan 22. pii: 2026.01.21.700969. [Epub ahead of print]

A non-canonical EZH2/TRIM28 epigenetic axis drives heparan sulfate remodeling and melanoma metastasis.

Neil G Patel, Alexandra Drakaki, Farhan Valummel, Jack C Moore, Amrita Basu, Bin Hu, Xiaolin Dong, Peng Zhao, Mees Botman, Emily Spector, Mark C Mochel, Lance Wells, Jennifer E Koblinski, Marten A Hoeksema, Ryan J Weiss.

Melanoma progression and metastasis are driven not only by oncogenic alterations but also by epigenetic programs that dynamically remodel the tumor microenvironment. Heparan sulfate (HS) proteoglycans are key extracellular matrix components that integrate growth factor signaling, cell-matrix interactions, and migratory behavior by controlling ligand availability and receptor engagement, yet how chromatin-associated factors regulate HS remodeling in cancer remains poorly defined. Here, we identify the histone methyltransferase EZH2 as a key regulator of HS biosynthesis in melanoma. Integrated bioinformatic and genomic analyses revealed enrichment of EZH2 and additional Polycomb Repressive Complex (PRC) factors at regulatory regions of HS biosynthetic genes. CRISPR-mediated loss of EZH2 altered expression of multiple HS-modifying enzymes, most notably the secreted endosulfatases SULF1 and SULF2, resulting in enhanced HS 6- O sulfation and altered ligand binding at the cell surface. Unexpectedly, EZH2 promoted SULF1 expression through a methyltransferase-independent mechanism via a non-canonical interaction with TRIM28, whereas SULF2 was regulated through canonical PRC2-mediated repression. Functionally, SULF1 depletion impaired melanoma cell migration and invasion in vitro and reduced spontaneous metastasis in an orthotopic xenograft model. Together, these findings define an epigenetic axis linking chromatin regulation to extracellular glycan remodeling and identify HS-modifying enzymes as candidate targets to limit melanoma metastasis.

DOI: https://doi.org/10.64898/2026.01.21.700969
Mater Today Bio. 2025 Dec;35 102271

Engineered mesenchymal stem cells-laden chondroitin sulfate hydrogel promotes diabetic wound healing through ROS scavenging and macrophage polarization.

Xi Cao, Ziqi Shen, Xiaohua Wang, Yuanyuan Chu, Runkong Wang, Liyang Zhu, Ruixue Zhong, Zhong Zhang, Mingquan Wu, Xu Zhou, Lei Zhang.

  The treatment of diabetic wound complications has long been a formidable challenge in the clinic, and a multifunctional biomaterial dressing holds great promise as an ideal approach for promoting diabetic wound healing. In this study, we designed a crosslinked chondroitin sulfate (CS) and polyethylene glycol (PEG) hydrogel (CS gel) as a reservoir via a Michael addition reaction. To further enhance the biological functions, surface-engineered mesenchymal stem cells (MSCs) modified with bilirubin-modified chondroitin sulfate-mediated mixed micellar backpacks possessing ROS scavenging/responsive and CD44-targeting abilities (DCMMs) were incorporated into the hydrogel system. The hydrogel served as a physical carrier, providing a sustained-release platform that ensured the long-term presence and controlled delivery of MSCs-tethered micellar backpacks at the wound site. In vitro experiments revealed the remarkable capacity of the hydrogel for ROS scavenging and regulating macrophage polarization. In vivo investigations in diabetic mouse models further confirmed the therapeutic potential, revealing a significant acceleration of wound closure, attenuation of inflammation, and augmentation of angiogenesis. Overall, this innovative hydrogel system that encapsulates surface-engineered mesenchymal stem cells (MSCs-DCMMs) represents a promising remedy and a framework for stem-cell-based therapeutic systems to treat diabetic wounds.

Keywords:  Diabetic wound healing; Hydrogel; Micellar backpacks; ROS-Responsive; Surface-engineered mesenchymal stem cells

DOI:  https://doi.org/10.1016/j.mtbio.2025.102271
Front Pharmacol. 2026 ;17 1749109

Fucoidan as a renal protectant: mechanistic insights and therapeutic implications of endothelial glycocalyx targeting.

Ping Xin, Chengqiao Ge, Yufan Tang, Yifan He, Bin Fu.

  The progression of chronic kidney disease (CKD) is closely associated with damage to the endothelial glycocalyx (eGC) of the renal microvasculature. The eGC, particularly its heparan sulfate (HS) components, is crucial for maintaining the charge-selective barrier and microenvironmental homeostasis. Modern pharmacological investigations of marine brown algae (e.g., Saccharina japonica), traditionally used in medicine for conditions such as "edema," reveal that their principal active component, fucoidan, is a sulfated polysaccharide with marked physicochemical similarities to endogenous HS. This review systematically posits that the core mechanism underlying the nephroprotective effects of fucoidan, as a natural product, lies in its direct targeting and repair of the damaged eGC. Through a systematic literature search up to November 2025, this review elucidates that fucoidan, especially its low-molecular-weight fractions, can consolidate and reconstitute the glycocalyx structure via dynamic integration, competitive substitution, and activation of intracellular signaling pathways. This central action not only directly restores the renal charge barrier and reduces proteinuria but also, by stabilizing endothelial function, systemically inhibits the inflammation and fibrosis cascades triggered by glycocalyx injury. The efficacy of fucoidan in diverse preclinical models, coupled with clinical trial evidence for fucoidan-based drugs in human CKD patients, collectively supports the validity of a glycocalyx-targeted therapeutic strategy. We conclude that fucoidan represents a natural product derived from traditional wisdom, with a defined molecular mechanism and translational potential, offering a promising complementary strategy for the comprehensive management of CKD.

Keywords:  charge barrier; chronic kidney disease; endothelial glycocalyx; fucoidan; glycosaminoglycan; heparan sulfate; proteinuria

DOI:  https://doi.org/10.3389/fphar.2026.1749109
Food Res Int. 2026 Mar 01. pii: S0963-9969(25)02562-1. [Epub ahead of print]227 118222

Curcumin nanoparticles functionalized with chondroitin sulfate for ulcerative colitis treatment: Enhanced efficacy and mechanism exploration.

Dan Zhang, Li-Hang Chen, Tao Chen, Di Wu, Yinan Du, Jiangning Hu.

  Ulcerative colitis (UC) is a chronic condition that causes inflammation and damage to the intestines. Curcumin (CUR) offers anti-inflammatory benefits, but its low bioavailability limits its effectiveness. In this study, CUR-loaded nanoparticles (OCC NPs) were developed using oleanolic acid and chondroitin sulfate (CS). The nanoparticles had a size of 238.9 ± 0.794 nm and showed good stability in gastrointestinal fluids. CS modification improved targeting to macrophages, enhancing anti-inflammatory and antioxidant effects. In a UC mouse model, OCC NPs alleviated UC symptoms, reduced inflammation, and repaired mucosal barrier function by upregulating ZO-1 and Claudin. The anti-inflammatory effects were driven by the TLR4/MyD88/NF-κB pathway, inhibiting pro-inflammatory cytokine levels and macrophage activation.

Keywords:  Chondroitin sulfate; Curcumin; Nanoparticles; Ulcerative colitis

DOI:  https://doi.org/10.1016/j.foodres.2025.118222
J Control Release. 2026 Jan 30. pii: S0168-3659(26)00070-2. [Epub ahead of print]392 114669

Smart hypoxia-responsive sulfated polysaccharides liposomes for controlled and targeted urokinase delivery in thrombotic therapy.

Dingfu Wang, Dan Li, Xiaolin Liu, Shixin Wang, Yile Fan, Ling Lu, Chuanbin Shen, Chunxia Li.

  Thrombosis remains a leading cause of cardiovascular and cerebrovascular mortality worldwide. Plasminogen activators, notably urokinase and alteplase, have been established as standard thrombolytic agents in clinical practice. However, their therapeutic potential is severely compromised by rapid metabolic clearance, non-specific biodistribution, and associated hemorrhagic complications. Here, we designed a dual-functional nano drug delivery platform that leverages P-selectin overexpression on activated platelets and the characteristic hypoxic microenvironment at thrombotic sites for precision thrombolytic intervention. Specifically, we developed a hypoxia-responsive block (PAC) by conjugating polyguluronate sulfate (PGS, P-selectin targeting motif) with azobenzene-modified cholesterol, enabling urokinase encapsulation within PAC@UK liposomes. Under hypoxic conditions that mimic the thrombotic microenvironment, the reductive cleavage of azobenzene moieties initiated sustained urokinase release (96.41% cumulative release), while maintaining exceptional biocompatibility and demonstrating preferential targeting of activated platelets. Comprehensive in vivo validation across zebrafish, murine mesenteric, and carotid artery thrombosis models revealed markedly enhanced thrombolytic efficacy compared to free UK. This biomimetic nanoplatform represents a paradigm shift toward intelligent, site-specific thrombolytic intervention, offering substantial clinical promise for safer and more effective treatment of thrombotic disorders.

Keywords:  Hypoxia-responsive; P-selectin targeting; Targeted delivery; Thrombolytic therapy; Urokinase

DOI:  https://doi.org/10.1016/j.jconrel.2026.114669
Talanta. 2026 Jan 18. pii: S0039-9140(26)00084-6. [Epub ahead of print]303 129429

Capillary electrophoresis in glycosaminoglycan analysis.

Rachma Dessidianti, Márkó Grabarics, Dávid Virág, Guinevere S M Lageveen-Kammeijer, Éva Szökő, Lilla Turiák.

Glycosaminoglycans (GAGs) are structurally complex, highly acidic polysaccharides that are produced by virtually all animal cells and play essential roles in cell communication, tissue organization, and disease processes. As key components of proteoglycans and as free saccharides, GAGs are abundant on cell surfaces and in the extracellular matrix, where they interact with a wide range of proteins such as growth factors and cytokines. Their interactions with proteins are fine-tuned by extensive structural variations of the polysaccharide chains, most importantly the attachment of sulfate modifications leading to distinct sulfation patterns. The resulting extraordinary structural complexity, however, poses significant challenges to the analysis of GAGs. Capillary electrophoresis (CE) offers distinct advantages for tackling these challenges, including exceptional resolution for charged analytes, low sample requirements, and compatibility with various detection methods. In this review, we highlight recent advances in the application of CE for GAG analysis, addressing key sample preparation steps, derivatization strategies, detection methods, and various CE modes to improve resolution and sensitivity. Challenges and benefits associated with coupling CE to mass spectrometry are addressed explicitly. Selected applications across the GAG families are presented to illustrate the utility of CE in biomedical and glycomic research. Finally, the strengths and current limitations of CE for the wider GAG analysis field are evaluated, and directions for further progress and future developments are outlined.

DOI: https://doi.org/10.1016/j.talanta.2026.129429
Am J Vet Res. 2026 Jan 30. 1-8

Endothelial glycocalyx of equine intestinal vessels: electron microscopic and immunohistochemical imaging.

Theresa A Schnelten, Sabine B R Kästner, Wencke Reineking, Marion Hewicker-Trautwein, Philipp Sauter, Stephan Neudeck.

   Objective: To visualize the endothelial glycocalyx in equine intestinal vessels using electron microscopy and immunohistochemistry and to evaluate the impact of induced endotoxemia on its integrity.
Methods: 6 healthy horses free of gastrointestinal disease were anesthetized with dexmedetomidine, ketamine, and diazepam and mechanically ventilated under isoflurane anesthesia. Jejunal venous tissue samples were collected after perfusion fixation with lanthanum nitrate before and 120 minutes after endotoxemia induced by IV administration of 30 ng·kg-1 Escherichia coli lipopolysaccharide. For transmission electron microscopy, samples were fixed in lanthanum nitrate solution and embedded in epoxide resin. Additional samples were fixed in formaldehyde, embedded in paraffin, and sectioned for indirect immunohistochemistry to assess heparan sulfate, syndecan-1, catalase, and superoxide dismutase-2 expression.
Results: The endothelial glycocalyx ultrastructure was successfully visualized in 3 of 6 horses. Morphological variations, particularly in glycocalyx thickness (up to 2.5 µm), were observed. Endotoxemia-related alterations indicating structural disruptions were evident in these horses. Immunohistochemical staining for syndecan-1 and superoxide dismutase-2 showed no assessable immunoreactivity, whereas heparan sulfate and catalase immunolabelling were detected on the endothelium.
Conclusions: The endothelial glycocalyx of intestinal vessels was visualized for the first time in horses. Among the tested antibodies, only those against heparan sulfate and catalase demonstrated endothelial reactivity, confirming their presence as components of the equine glycocalyx. Lipopolysaccharides may cause structural disintegrity and loss of glycocalyx.
Clinical Relevance: Visualization of the equine endothelial glycocalyx enhances understanding of vascular pathophysiology in endotoxemic horses. Investigation of the glycocalyx remains technically demanding.

Keywords:  endothelium; equine; glycocalyx; immunohistochemistry; transmission electron microscopy

DOI:  https://doi.org/10.2460/ajvr.25.11.0399
Small. 2026 Feb 01. e08613

Reprogramming Immunogenicity of Iron Oxide Nanoparticles through Sulfated Glycan Presentation.

Negin Pournoori, Heela Sarlus, Dick J Sjöström, Rohith Pavan Parvathaneni, Oommen P Varghese, Vesa P Hytönen, Robert A Harris, Per H Nilsson, Oommen P Oommen.

  Heparin (HP) and dextran sulfate (DS) are well-known for their anti-thrombotic and immunomodulatory properties; however, a direct comparison of their immunological responses when used in drug delivery applications is lacking. This study addresses this gap by evaluating the immunological behavior of superparamagnetic iron oxide nanoparticles (SPIONs) coated with HP or DS in human whole blood, primary immune cells, endothelial cells, and in vivo. Both HP-SPIONs and DS-SPIONs effectively suppressed complement activation, as shown by reduced C3bc, C3bBbP, and TCC levels. Notably, HP-SPIONs activated monocytes (CD11b) and endothelial cells (ICAM-1, CD62P/E), whereas DS-SPIONs suppressed endothelial activation. DS-SPIONs were preferentially internalized by myeloid cells (∼50% neutrophils, ∼42% macrophages, ∼55% dendritic cells), while HP-SPIONs showed significantly lower uptake (<25% dendritic cells, ∼5% neutrophils). DS-SPIONs induced an immunosuppressive, pro-healing phenotype in murine and human macrophages, whereas HP-SPIONs drove a pro-inflammatory, M1-like response. In healthy mice, intravenous DS-SPIONs elicited a modest increase in splenic immune cell populations compared to HP-SPIONs, indicating early immune engagement. Collectively, both SPIONs attenuate complement activation, indicating high biocompatibility. Based on the early immunological responses, DS-SPIONs display a pro-healing immune profile suitable for regenerative drug delivery, whereas HP-SPIONs induce pro-inflammatory responses that may be leveraged for anticancer immunotherapy.

Keywords:  dextran sulfate; heparin; immunomodulatory effects; macrophage polarization; superparamagnetic iron oxide nanoparticles

DOI:  https://doi.org/10.1002/smll.202508613
J Undergrad Chem Res. 2025 ;24(3): 45-49

BIOCHEMICAL INVESTIGATION OF THE ANTICOAGULANT ACTIVITY OF SULFONATED POLYMERS.

Rami A Al-Horani, Kholoud F Aliter, Elias Al-Horani.

Venous thrombotic disorders are a leading cause of mortality in the US. While anticoagulants are the primary treatment, their use is limited by bleeding risks. This highlights the critical need for safer alternatives. In this study, we investigated eight sulfonated polymers for anticoagulant potential using human plasma clotting assays. Nonacetylated lignosulfonate (NALS) emerged as the most promising candidate, doubling clotting times at 309-980 μg/mL concentrations. We also performed chromogenic assays targeting key coagulation factors (thrombin, factor Xa, and factor XIa) to elucidate its mechanism of action. NALS exhibited a potent and selective inhibition of factor XIa, with an IC50 of ~8 μg/mL, while showing minimal effects on thrombin or factor Xa. Factor XIa inhibition is particularly advantageous, as it may reduce thrombosis while preserving hemostasis, addressing a major drawback of current therapies. Our findings position NALS as a novel, targeted anticoagulant lead with a mechanistically improved safety profile. Future studies will explore its efficacy in vivo and structure-activity relationships to optimize therapeutic potential. This work opens new avenues for developing safer antithrombotic drugs.

Keywords: Anticoagulant; Factor XIa; Factor Xa; Heparin; Sulfonated Polymer; Thrombin; Thrombosis
Indian J Med Res. 2026 Dec;pii: 10.25259/IJMR_1525_2025. [Epub ahead of print]162(6): 754-763

Prevalence & predictors of sexual functioning & sex hormone profiles among men with opioid dependence: A community-based, cross-sectional study.

Vinit Patel, Ravindra Rao, Roshan Bhad, Ashwani Kumar Mishra, Rizwana Quraishi, Yashdeep Gupta.

  Background & objectives Though sexual dysfunction are common in individuals with opioid dependence, the relative contribution of hormonal and psychological determinants remains unclear. Studies assessing sexual functioning and sex hormone levels together in this population remain limited. This study aimed to evaluate self-reported sexual dysfunction and sex hormone alterations, and their association with demographic, psychosocial, and hormonal factors in men with opioid dependence, primarily using heroin. Methods In this cross-sectional study, 143 sexually active males (aged 18-50 yr) with opioid dependence were recruited. Sexual functioning was assessed using the international index of erectile function (IIEF-15). Hormonal assays included total testosterone, prolactin (PRL), luteinising hormone (LH), follicle-stimulating hormone (FSH), gonadotropin-releasing hormone (GnRH), sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEA-S). Descriptive statistics, Spearman's rank correlation with FDR (false discovery rate) correction, and hierarchical multiple regression with bootstrapped confidence intervals (1000 samples) were conducted. A sensitivity analysis restricted to married participants (n=78) allowed inclusion of intimate partner violence as predictor. Results The median age of participants (n=143) was 26 yr [Interquartile range (IQR):24-30], with 93 per cent identifying as heterosexual. Erectile dysfunction (93.7%, n=134), orgasmic dysfunction (95.1%, n=136), low sexual desire (94.4%, n=135), dissatisfaction with sexual intercourse (99.3%, n=142), and premature ejaculation (72%, n=103) were highly prevalent. Hormonal analysis showed low testosterone in 7.7 per cent (n=11), high PRL in 8.4 per cent (n=12), and elevated GnRH in 57.3 per cent (n=82) of participants. Median hormone levels were: Testosterone 20.5 (15.0-27.3) nmol/L, PRL 5.8 (3.5-11.2) ng/mL, and GnRH 160.3 (132.2-178.1) pg/mL. No significant correlations were observed between hormone levels and sexual function. In regression analysis, demographic and psychosocial variables predicted sexual functioning, while hormonal measures did not contribute independently. The final model explained 17 per cent of variance (adjusted R2 = 0.17). Interpretation & conclusion Sexual dysfunction in men with opioid dependence primarily using heroin was driven more by psychosocial and demographic determinants than by hormonal changes. Endocrine alterations were not sufficient to explain the high burden of dysfunction. Addressing sexual health in opioid dependence requires a multifactorial approach, with attention to social and psychological contributors alongside biological assessment.

Keywords:  Erectile dysfunction; gonadotropin releasing hormone; heroin dependence; sex hormones; sexual dysfunction, physiological; testosterone

DOI:  https://doi.org/10.25259/IJMR_1525_2025