bims-supasi 2025-03-23 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–03–23
nine papers selected by
Jonathan Wolf Mueller, University of Birmingham

Synthesis of Sulfated Carbohydrates - Glycosaminoglycans.
A chondroitin sulfate/chitosan composite coating for anticoagulation on cardiovascular implants.
Heparan sulfate chains in hepatocellular carcinoma.
Cell surface heparan sulfate is an attachment receptor for grass carp reovirus.
CHPF2 as a novel biomarker and ponicidin as a potential therapeutic agent in hepatocellular carcinoma.
Assessment of androgenic hormones and other risk factors in Egyptian males with early onset androgenetic alopecia: a case control study.
Cholesterol Sulfate as a Negative Regulator of Cellular Cholesterol Homeostasis.
Viscoelasticity Can Be Tuned Through Covalent Incorporation of Chondroitin Sulphate in Allylated Gelatin Hydrogels.
Efficacy of novel activated bamboo charcoal in reducing uremic toxins and enhancing kidney function in chronic kidney disease patients: a pilot randomized controlled trial.

Handb Exp Pharmacol. 2025 Mar 19.

Synthesis of Sulfated Carbohydrates - Glycosaminoglycans.

Rakesh Raigawali, Sharath S Vishweshwara, Saurabh Anand, Raghavendra Kikkeri.

  Glycosaminoglycans (GAG) are polysaccharides that are ubiquitous on the surface of all mammalian cells, interacting with a multitude of proteins and orchestrating essential physiological and pathological processes. Among various GAG structures, heparan sulfate (HS) stands out for its intricate structure, positioning it as a significant cell-surface molecule capable of regulating wide range of cellular functions. Consequently, investigating the structure-activity relationships (SARs) with well-defined HS ligands emerges as an attractive avenue advancing drug discovery and biosensors. This chapter outlines a modular divergent strategy for synthesizing HS oligosaccharides to elucidate SARs. Here, we provide a literature overview on the synthesis of disaccharide building blocks, employing different orthogonal protecting groups, promoters, and optimization conditions to improve their suitability for subsequent oligosaccharide synthesis. Further, we highlight the synthesis of universal disaccharide building blocks derived from natural polysaccharides. We also provide insights of one-pot method and automated solid-phase synthesis of HS oligosaccharides. Finally, we review the status of SARs of popular heparan sulfate binding proteins (HSBPs).

Keywords:  Glycosaminoglycan; Glycosylation; Heparan sulfate; Orthogonal protection; Sulfation

DOI:  https://doi.org/10.1007/164_2025_742
Int J Biol Macromol. 2025 Mar 19. pii: S0141-8130(25)02897-1. [Epub ahead of print] 142345

A chondroitin sulfate/chitosan composite coating for anticoagulation on cardiovascular implants.

Bin Chu, Yibin Huang, Yifan Chen, Song Wang, Xiaoli Li.

  Developing durable anticoagulant coatings for cardiovascular implants remains a major research challenge. Heparin, the current gold-standard anticoagulant, faces challenges due to rapid elution from coated surfaces. This article reports a new heparin-alternative anticoagulant coating system engineered through rational design of a dual-functional chondroitin sulfate derivative (methacrylated/aldehyde-modified chondroitin sulfate, CSMAO) and sulfonated chitosan (SCS). The hierarchical architecture was constructed via sequential layer-by-layer (LbL) assembly on polydopamine (PDA)-functionalized 316 L stainless steel substrates. The material characterization methods included Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR), and X-ray photoelectron spectroscopy (XPS). The grafting rate of glycidyl methacrylate was 20.05 %, with an aldehyde substitution degree of 48.61 %, and the sulfonation degree of SCS reached 46.96 %. The composite coating exhibited excellent biocompatibility and anticoagulant properties. Coagulation profiling indicated comparable extrinsic pathway regulation to that of heparin controls along with superior intrinsic pathway inhibition (P < 0.01). This rationally designed coating system shows translational promise for improving the hemocompatibility of cardiovascular implants.

Keywords:  Anticoagulant coating; Blood compatibility; Chitosan; Chondroitin sulfate

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.142345
Gastroenterol Rep (Oxf). 2025 ;13 goaf023

Heparan sulfate chains in hepatocellular carcinoma.

Erwan Guyot.

  Hepatocellular carcinoma (HCC) corresponds to the vast majority of liver cancer cases, with one of the highest mortality rates. Major advances have been made in this field both in the characterization of the molecular pathogenesis and in the development of systemic therapies. Despite these achievements, biomarkers and more efficient treatments are still needed to improve its management. Heparan sulfate (HS) chains are polysaccharides that are present at the cell surface or in the extracellular matrix that are able to bind various types of molecules, such as soluble factors, affecting their availability and thus their effects, or to contribute to interactions that position cells in their environments. Enzymes can modify HS chains after their synthesis, thus changing their properties. Numerous studies have shown HS-related proteins to be key actors that are associated with cellular effects, such as tumor growth, invasion, and metastasis, including in the context of liver carcinogenesis. The aim of this review is to provide a comprehensive overview of the biology of HS chains and their potential importance in HCC, from biological considerations to clinical development, and the identification of biomarkers, as well as therapeutic perspectives.

Keywords:  biomarkers; heparan sulfate; hepatocellular carcinoma; praoteoglycans

DOI:  https://doi.org/10.1093/gastro/goaf023
iScience. 2025 Mar 21. 28(3): 112033

Cell surface heparan sulfate is an attachment receptor for grass carp reovirus.

Qian Wang, Hanyue Wang, Xuyang Wang, Cheng Yang, Yongming Li, Lanjie Liao, Zuoyan Zhu, Yaping Wang, Libo He.

  Grass carp reovirus (GCRV) causes hemorrhagic disease in grass carp, leading to significant economic losses in China's aquaculture. However, the cellular receptors responsible for the initiation of GCRV infection remain unclear. This study reveals that cell surface heparan sulfate (HS) acts as a crucial attachment receptor for GCRV. Removing HS with heparinase significantly reduces GCRV attachment and infection. Both HS and its homologue, heparin, inhibit the attachment of GCRV to cells. Altering HS levels in cells affects GCRV attachment and infection accordingly. GCRV outer capsid proteins VP5, VP56, and VP35, as well as purified GCRV virions, directly bind to HS. Pretreating GCRV with heparin or feeding grass carp with feed containing heparin significantly reduces mortality caused by GCRV infection. Collectively, these results highlight the crucial role of HS as an attachment receptor for GCRV and therefore provide a promising target for the prevention and control of this virus.

Keywords:  Aquaculture; Aquaculture diseases; Biochemistry; Cell biology; Virology

DOI:  https://doi.org/10.1016/j.isci.2025.112033
Pharmacol Res. 2025 Mar 17. pii: S1043-6618(25)00123-9. [Epub ahead of print] 107698

CHPF2 as a novel biomarker and ponicidin as a potential therapeutic agent in hepatocellular carcinoma.

Zuhui Liang, Yingyi Ye, Zhihong Deng, Huan Lan, Caihong Liu, Yuanhang Xu, Minqi Fan, Zhongqiu Liu, Peng Wu, Lin An, Caiyan Wang.

  Hepatocellular carcinoma (HCC) was associated with high morbidity and mortality, representing a significant health challenge. Chondroitin sulfate (CS), a glycosaminoglycan composed of glucuronic acid and N-acetylgalactosamine, is implicated in HCC progression through its role in cancer cell migration and proliferation as well as interactions with cell surface receptors integrin β-1 and CD44. Chondroitin polymerization factor 2 (CHPF2), the key to CS synthesis, has an undefined role in HCC. Our study aims to demonstrate that decreasing CHPF2 enzyme activity can inhibit the migration and proliferation of HCC cells. Bioinformatics analysis and in vitro experiments on clinical HCC samples confirmed the knockdown of CHPF2 inhibited HCC cell proliferation and migration. We further explored Rabdosia rubescens, a plant used in cancer therapy, for its potential to modulate CHPF2. Structural biology and ligand fishing identified ponicidin, a compound that significantly suppresses HCC cell growth and migration in both in vitro and in vivo models. These findings propose CHPF2 as a novel biomarker and ponicidin as a potential therapeutic agent for HCC management.

Keywords:  chondroitin polymerizing factor 2; chondroitin sulfate; hepatocellular carcinoma; ligand fishing; ponicidin

DOI:  https://doi.org/10.1016/j.phrs.2025.107698
Arch Dermatol Res. 2025 Mar 12. 317(1): 552

Assessment of androgenic hormones and other risk factors in Egyptian males with early onset androgenetic alopecia: a case control study.

Manal A Sharara, Esraa M Elfeki, Naziha H Khafagy.

  Early-onset androgenetic alopecia (AGA) is a common, hereditary hair loss condition in men, often starting in the early twenties. It involves gradual thinning of hair, influenced by genetics, hormones, and other factors like smoking and family history. Early identification of these risks could support timely intervention. This case control study aimed to evaluate androgen levels, specifically the free androgen index(FAI) and dehydroepiandrosterone sulfate ( DHEA-S), in males with early-onset AGA versus healthy age and sex matched controls. It also determined risk factors contributing to premature AGA in Egyptian males. This study included 40 male patients between 18 and 30 years with early-onset AGA and 40 age-matched healthy male controls. Risk factors and hormonal profiles including sex hormone binding globulin (SHBG), total testosterone (TS), DHEA-S as well as calculated FAI were compared between both groups using ELISA kit. Our study found that early-onset AGA is linked to a strong family history, smoking, coffee intake, hair straightener use, fast-food diets, and recent weight gain. Early-onset AGA patients also showed statistically significant lower SHBG levels and higher TS, DHEAS and FAI compared to healthy controls. These findings suggest that early-onset AGA is shaped by a complex interaction of different factors, highlighting the importance of a comprehensive approach and advice to patients as regards different risk factors.

Keywords:  Androgenetic alopecia; DHEA-S; Risk factors; SHBG; TS

DOI:  https://doi.org/10.1007/s00403-025-04041-0
Mol Cells. 2025 Mar 13. pii: S1016-8478(25)00033-0. [Epub ahead of print] 100209

Cholesterol Sulfate as a Negative Regulator of Cellular Cholesterol Homeostasis.

Le Ba Nam, Sung-Jin Kim, Tan Khanh Nguyen, Chang-Yun Jeong, June-Yong Lee, Jun-Seok Lee, Jeong Taeg Seo, Seok Jun Moon.

  Cholesterol sulfate (CS), one of the most abundant cholesterol derivatives, recently emerged as a key regulatory molecule in several physiological processes. Here, we demonstrate multiple mechanisms by which CS reduces intracellular cholesterol levels. CS promotes the proteasomal degradation of HMG-CoA reductase (HMGCR) by enhancing INSIG-mediated ubiquitination, thereby inhibiting cholesterol synthesis. In addition, CS blocks low-density lipoprotein (LDL) receptor endocytosis, reducing LDL cholesterol (LDL-C) uptake. CS further suppresses the proteolytic activation of sterol regulatory element-binding protein 2 (SREBP2), a master transcription factor governing cholesterol synthesis and uptake. Using in vitro and in vivo models, we show that CS lowers cholesterol by targeting both the cholesterol synthesis and uptake pathways, while also modulating an important feedback loop via SREBP2. These findings highlight the potential of CS as a modulator of cholesterol metabolism, offering new therapeutic insights into cholesterol-related disorders.

Keywords:  Cholesterol; Cholesterol homeostasis; Cholesterol sulfate; HMGCR; LDLR; SREBP2

DOI:  https://doi.org/10.1016/j.mocell.2025.100209
Macromol Biosci. 2025 Mar 19. e2400422

Viscoelasticity Can Be Tuned Through Covalent Incorporation of Chondroitin Sulphate in Allylated Gelatin Hydrogels.

Manuela A Boos, Khoon S Lim, Shireen R Lamandé, Kathryn S Stok.

  Cartilage is a slow-remodeling tissue with limited healing capacity. This has led to decades of tissue engineering efforts where the goal is biomaterials with regenerative capacity to restore functional integrity. Achieving full functional and mechanical integrity has proven difficult as cartilage has distinct mechanical properties. Glycosaminoglycans (GAGs) play a crucial role in cartilage mechanics due to their swelling behavior, contributing to viscoelasticity. The aims of this study are to covalently incorporate thiolated chondroitin sulphate (CSSH) in allylated gelatin (gelAGE) hydrogels at different concentrations to mimic GAG-rich regions in cartilage and create platforms to study subsequent cellular behavior. Hydrogels are evaluated for soluble fraction, swelling ratio, chondroitin sulphate (CS) retention, mechanical and viscoelastic properties, and cytocompatibility. ≈80% of CSSH is retained, and samples containing CSSH has an increased swelling ratio, indicating the incorporation of GAGs. Samples containing CSSH has an increased relaxation amplitude compared to gelAGE controls with a more elastic response. The addition of CSSH has no adverse effects on cytocompatibility. In conclusion, this study demonstrates the incorporation of thiolated CS in gelAGE hydrogels at different concentrations with no adverse effects on cytocompatibility. This allows for viscoelastic tuning which is important to consider when engineering new biomaterials.

Keywords:  biomaterials; cartilage; glycosaminoglycans; mechanics; stiffness; tissue engineering; viscoelastic

DOI:  https://doi.org/10.1002/mabi.202400422
PeerJ. 2025 ;13 e19007

Efficacy of novel activated bamboo charcoal in reducing uremic toxins and enhancing kidney function in chronic kidney disease patients: a pilot randomized controlled trial.

Kuo-Chin Hung, Mei-Yueh Lee, Shih-Yuan Hung, Chiao-Yin Sun, Chau-Chung Wu, Cheng-Jui Lin.

   Background: The role of uremic toxins in the progression of chronic kidney disease (CKD) and novel treatments to mitigate their effects are critical areas of research. This pilot study investigated the efficacy of a novel activated bamboo charcoal and/or probiotics in reducing uremic toxins and improving renal function in CKD patients.
Methods: This prospective, randomized, open, blinded end-point (PROBE) study included patients with stage 3 CKD. Patients were randomly assigned to one of four groups: activated bamboo charcoal (ABC), probiotics, ABC with probiotics, or standard treatment for 3 months.
Results: A total of 46 patients were enrolled (mean age 66.7 ± 11.5 years, 71.7% male). The ABC and ABC with probiotics groups showed a significant reduction in serum levels of the uremic toxins trimethylamine N-oxide (TMAO), p-cresyl sulfate (PCS), indoxyl sulfate (IS), and phenyl sulfate (PS) after 3 months of treatment (all p < 0.05). There was a particularly pronounced decrease in the percentage of IS in both the ABC group (-23.9 ± 28.9% vs. 33.9 ± 63.4%, p = 0.005) and the ABC with probiotics group (-29.3 ± 30.6% vs. 33.9 ± 63.4%, p = 0.009). The eGFR change ratio also significantly improved in the ABC group compared to the control group (4.6 ± 10.2% vs. -8.6 ± 12.5%, p = 0.011). However, the probiotics group did not exhibit a similar reduction in uremic toxins or an improvement in the eGFR.
Conclusion: This study suggested that ABC significantly reduced uremic toxins and might have potential in improving eGFR in CKD stage 3 patients over a 3-month period. These findings suggest a potential protective effect of ABC on kidney function, highlighting the need for further large-scale, long-term randomized controlled trials to confirm these results.

Keywords:  Activated bamboo charcoal; Chronic kidney disease; Indoxyl sulphate; Phenyl sulfate; Probiotics; TMAO; p-Cresyl sulfate

DOI:  https://doi.org/10.7717/peerj.19007