bims-supasi 2024-11-03 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2024‒11‒03
nine papers selected by
Jonathan Wolf Mueller, University of Birmingham

Chondroitin sulfate functionalized nanozymes inhibit the inflammation feedback loop for enhanced atherosclerosis therapy by regulating intercellular crosstalk.
Fabrication and Properties of Hydrogel Dressings Based on Genipin Crosslinked Chondroitin Sulfate and Chitosan.
Comprehensive Analysis of Sulfated Flavonoids in Eclipta prostrata for Quality Evaluation.
Cost-Effectiveness Analysis of Pharmaceutical-Grade Chondroitin Sulfate for Knee Osteoarthritis Based on Individual Patient Data from a Randomized Clinical Trial.
Phase behavior and interaction of strong polyelectrolyte dextran sulfate and whey protein isolation: Effects of pH, protein/polysaccharide ratio, and salt addition.
Mass Spectrometry Imaging with Trapped Ion Mobility Spectrometry Enables Spatially Resolved Chondroitin, Dermatan, and Hyaluronan Glycosaminoglycan Oligosaccharide Analysis In Situ.
Effect of Endogenous Hormone Levels on Basal Metabolic Rate in Men With Obesity.
The role of chondroitin sulphate as a potential biomaterial for hepatic tissue regeneration: A comprehensive review.
Multifaceted Heparin: Diverse Applications beyond Anticoagulant Therapy.

Int J Biol Macromol. 2024 Oct 28. pii: S0141-8130(24)07727-4. [Epub ahead of print]282(Pt 3): 136918

Chondroitin sulfate functionalized nanozymes inhibit the inflammation feedback loop for enhanced atherosclerosis therapy by regulating intercellular crosstalk.

Chenglong Wang, Yufeng He, Jun Tang, Jingying Mao, Xiaoya Liang, Maochang Xu, Zongquan Zhang, Ji Tian, Jun Jiang, Chunhong Li, Xiangyu Zhou.

  In the inflammatory microenvironment of atherosclerotic plaques, metabolic dysregulation of superoxide anion (O2-) and hydrogen peroxide (H2O2) leads to the activation of feedback mechanisms involving IL-1β, TNF-α, and MCP-1, which triggers inflammatory cascades between macrophages and vascular smooth muscle cells (VSMCs) in atherosclerosis (AS). To address this, a chondroitin sulfate (CS)-functionalized dual-targeted engineered nanozyme, CS-Lip/PB@Rap, was developed by encapsulating mesoporous Prussian blue nanoparticles (PBs) loaded with rapamycin (Rap) within CS-modified liposomes. CS functionalization endowed CS-Lip/PB@Rap with a specific targeting ability for CD44 receptors, thus enabling targeted delivery to inflammatory macrophages and VSMCs. Moreover, its enhanced multiple enzyme-like activities effectively modulated the imbalance of oxidative stress. The underlying mechanism of crosstalk regulation by these engineered nanozymes may inhibit the NF-κB pathway by restoring normal metabolism of O2- and H2O2, thereby blocking the TNF-α, IL-1β, and MCP-1 feedback loops between macrophages and VSMCs. This process reduced the production of inflammatory macrophages and inhibited the VSMC transformation from a contractile phenotype to a synthetic phenotype, preventing the formation of fibrous caps. Furthermore, the elimination of oxidative stress could decrease the production of oxygenized low-density lipoprotein (ox-LDL), which inhibited the formation of foam cells and alleviated the atherogenic progression.

Keywords:  Chondroitin sulfate functionalized nanozymes; Inflammation feedback loop; Intercellular crosstalk

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.136918
Polymers (Basel). 2024 Oct 11. pii: 2876. [Epub ahead of print]16(20):

Fabrication and Properties of Hydrogel Dressings Based on Genipin Crosslinked Chondroitin Sulfate and Chitosan.

Ling Wang, Xiaoyue Ding, Xiaorui He, Ning Tian, Peng Ding, Wei Guo, Oseweuba Valentine Okoro, Yanfang Sun, Guohua Jiang, Zhenzhong Liu, Armin Shavandi, Lei Nie.

  Multifunctional hydrogel dressings remain highly sought after for the promotion of skin wound regeneration. In the present study, multifunctional CHS-DA/HACC (CH) hydrogels with an interpenetrated network were constructed using hydroxypropyl trimethyl ammonium chloride modified chitosan (HACC) and dopamine-modified chondroitin sulfate (CHS-DA), using genipin as crosslinker. The synthesis of HACC and CHS-DA was effectively confirmed using Fourier transform infrared (FT-IR) analysis and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The prepared CH hydrogels exhibited a network of interconnected pores within the microstructure. Furthermore, rheological testing demonstrated that CH hydrogels exhibited strong mechanical properties, stability, and injectability. Further characterization investigations showed that the CH hydrogels showed favorable self-healing and self-adhesion properties. It was also shown that increasing HACC concentration ratio was positively correlated with the antibacterial activity of CH hydrogels, as evidenced by their resistance to Escherichia coli and Staphylococcus aureus. Additionally, Cell Counting Kit-8 (CCK-8) tests, fluorescent images, and a cell scratch assay demonstrated that CH hydrogels had good biocompatibility and cell migration ability. The multifunctional interpenetrated network hydrogels were shown to have good antibacterial properties, antioxidant properties, stable storage modulus and loss modulus, injectable properties, self-healing properties, and biocompatibility, highlighting their potential as wound dressings in wound healing applications.

Keywords:  chitosan; chondroitin sulfate; genipin; hydrogel; interpenetrated network; wound dressings

DOI:  https://doi.org/10.3390/polym16202876
Molecules. 2024 Oct 15. pii: 4888. [Epub ahead of print]29(20):

Comprehensive Analysis of Sulfated Flavonoids in Eclipta prostrata for Quality Evaluation.

Ryunosuke Sato, Yuto Nishidono, Ken Tanaka.

  Eclipta prostrata (Asteraceae) is employed as a hemostatic agent in many traditional medicines, owing to its sulfated flavonoid content. In this study, we obtained crude drug samples from three provinces collected in different years and analyzed their sulfated flavonoid contents using liquid chromatography-mass spectrometry (LC-MS) for quality evaluation. Because sulfated flavonoids are unstable and difficult to isolate from extracts, this study first synthesized a variety of sulfated flavonoids and accumulated spectral data in order to identify the compounds in E. prostrata. The LC-MS analysis of six crude drug samples revealed the presence of luteolin 7-sulfate, apigenin 7-sulfate, diosmetin 7-sulfate, and diosmetin 3'-sulfate. The samples without luteolin 3'-sulfate featured high apigenin 7-sulfate content. Although the samples were collected from the same locality, their compositions differed depending on the year of collection. Further, they were classified according to three patterns: (1) samples with luteolin 7-sulfate as the main component, (2) samples with apigenin 7-sulfate as the main component, and (3) samples with relatively high diosmetin sulfate content. Luteolin 7-sulfate typically exhibits relatively high erythrocyte aggregation efficiency and fibrinogen aggregation rate. These results demonstrate that the analysis of sulfated flavonoids is beneficial for the quality evaluation of E. prostrata for hemostatic applications.

Keywords:  Eclipta prostrata; LC–MS; sulfated flavonoids

DOI:  https://doi.org/10.3390/molecules29204888
Adv Ther. 2024 Oct 30.

Cost-Effectiveness Analysis of Pharmaceutical-Grade Chondroitin Sulfate for Knee Osteoarthritis Based on Individual Patient Data from a Randomized Clinical Trial.

Olivier Bruyère, Jean-Yves Reginster.

  INTRODUCTION: In a previously published randomised, placebo-controlled trial, 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was shown to be superior to placebo in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). The aim of the current post hoc analyses was to evaluate the cost-effectiveness of CS compared with placebo in a European perspective using individual patient data from this clinical trial.METHODS: Patients with knee OA randomised to CS or placebo were followed up at 1, 3 and 6 months. The algo-functional Lequesne index was used to derive the EuroQol Five-Dimension Five-Level (EQ-5D-5L) score based on a validated formula. The EQ-5D-5L scores at each time point were used to calculate the changes in quality-adjusted life years (QALYs) with the area under the curve method. Costs were assessed using the average price of CS in the countries where the original study took place and where CS is currently marketed. The costs of CS in three countries were then used (i.e. the Czech Republic, Italy and Switzerland). The incremental cost-effectiveness ratio (ICER) threshold for CS to be considered cost-effective was set at 91,870 EUR per QALY (equivalent to the usually recommended threshold of US $100,000). The study used an intention-to-treat population, i.e. patients who received one dose of the study drug, and imputed missing values using the basal observation carried forward method.
RESULTS: No significant differences in baseline characteristics were observed between the CS group (N = 199) and the placebo group (N = 205). The mean cost of CS for 6 months of treatment was 194.74 EUR. After 6 months of treatment, CS showed a mean ICER of 33,462 (95% CI 5130-61,794) EUR per QALY gained, indicating cost-effectiveness compared with placebo. The acceptability curve for cost-effectiveness shows that the CS treatment is likely to be cost-effective compared with placebo, with a 93% probability when the ceiling ratio is set at 91,870 EUR per QALY gained.
CONCLUSIONS: These results highlight the role of CS as a cost-effective therapeutic option in the management of OA. However, further studies taking into account the use of other healthcare resources are warranted for a more complete understanding.

Keywords:  Chondroitin sulfate; Health economics; Osteoarthritis; Quality-adjusted life years

DOI:  https://doi.org/10.1007/s12325-024-03007-4
Food Chem. 2024 Oct 28. pii: S0308-8146(24)03465-4. [Epub ahead of print]464(Pt 1): 141815

Phase behavior and interaction of strong polyelectrolyte dextran sulfate and whey protein isolation: Effects of pH, protein/polysaccharide ratio, and salt addition.

Liyuan Zheng, Qiushuo Chang, Xing Chen, Xuan Ding, Chunyu Xi.

  The strong polyelectrolyte dextran sulfate (DS) is an anionic polysaccharide with a high negative charge, characterized by high stability and pH independence. DS and whey protein isolate (WPI) were selected to study the specific effects of highly negatively charged polysaccharides on the phase behavior and interaction of WPI/DS complexes (1 % w/v) under varying external conditions (pH, WPI:DS ratio, and salt addition). The phase diagrams, zeta potential, and laser confocal scanning microscopy measurements indicated that the WPI/DS complexes did not dissociate even at pH 1 due to the pH independence of DS. The exclusion volume effect of DS promoted WPI self-aggregation at high salt concentrations, which inhibited acidification-induced dissociation. Isothermal titration calorimetry indicated that the WPI/DS interaction is a spontaneous exothermic reaction driven by both enthalpy and entropy changes due to electrostatic interactions. This study provides valuable information on the interactions between highly negatively charged polysaccharides and proteins.

Keywords:  Dextran sulfate; Electrostatic interaction; Isothermal titration calorimetry; Phase behavior; Strong polyelectrolyte; Whey protein isolate; pH

DOI:  https://doi.org/10.1016/j.foodchem.2024.141815
Anal Chem. 2024 Oct 30.

Mass Spectrometry Imaging with Trapped Ion Mobility Spectrometry Enables Spatially Resolved Chondroitin, Dermatan, and Hyaluronan Glycosaminoglycan Oligosaccharide Analysis In Situ.

Anthony Devlin, Felicia Green, Zoltan Takats.

Previously, spatially resolved analysis of glycosaminoglycans (GAGs), by type and sulfation state, was unobtainable. Here, we describe a mass spectrometry imaging (MSI) approach which enables the detection, identification, localization, and profiling of GAG oligosaccharides directly from retinal tissue. Through in situ treatment of tissues with relevant chondroitinase enzymes, we liberate and spatially resolve chondroitin, dermatan, and hyaluronan from disaccharides through to hexasaccharides, directly from tissue sections. We demonstrate the separation of isomeric GAG oligosaccharide ions at different histologically relevant regions using trapped ion mobility spectrometry (TIMS). This paper describes the first spatially resolved analysis of multiple GAGs and their oligosaccharide sulfation state(s) directly from tissues.

DOI: https://doi.org/10.1021/acs.analchem.4c02706
Clin Endocrinol (Oxf). 2024 Oct 27.

Effect of Endogenous Hormone Levels on Basal Metabolic Rate in Men With Obesity.

Van Cauwenberghe Jolijn, Van Dessel Kristof, De Block Christophe, Dirinck Eveline.

  OBJECTIVE: Basal metabolic rate (BMR) is an important factor in weight management and is influenced by fat-free mass (FFM), fat mass (FM) and age. Current knowledge of the influence of hormonal levels on BMR is based on studies with small populations, studies that investigate exogenous administration and studies frequently lacking correction for body composition.DESIGN: Cross-sectional study.
PATIENTS: All men (n = 457) who were referred to our centre for a metabolic work-up were eligible for inclusion. Median age was 47 (18-78) years and the vast majority had obesity (BMI ≥ 30 kg/m², 90.9%).
MEASUREMENTS: All men had a measurement of BMR, body composition and measurement of testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH) and free thyroxine (fT4). Men with low, normal and/or high levels of each of these hormones were compared. The association between hormone levels and BMR was assessed through linear regression models. All analyses were controlled for FFM, FM and age.
RESULTS: In men with obesity, testosterone (total or free) was not associated with BMR. Linear regression analysis showed that DHEAS was positively associated with BMR in a sample of men with obesity and normal endogenous DHEAS levels, with the following equation: BMR (adjusted R² = 0.72): (BMR [kcal/d] = 513.402 + 18.940 × FFM [kg] + 9.507 × FM [kg] - 3.362 × age [years] + 0.307 × DHEAS [µg/dL]) (p < 0.01). TSH, fT4 and IGF-1 were not associated with BMR.
CONCLUSION: In men with obesity, endogenous DHEAS is positively associated with BMR. Testosterone, TSH, fT4 and IGF-1 were not associated with BMR in men with obesity. Since we examined the specific population of men with obesity and only examined endogenous hormone levels, no extrapolation of results to other populations or the overall population can be made.

Keywords:  androgens; basal metabolism; body composition; dehydroepiandrosterone sulphate; insulin like growth factor; testosterone; thyrotropin

DOI:  https://doi.org/10.1111/cen.15157
Int J Biol Macromol. 2024 Oct 07. pii: S0141-8130(24)07141-1. [Epub ahead of print] 136332

The role of chondroitin sulphate as a potential biomaterial for hepatic tissue regeneration: A comprehensive review.

Saleha Faheem, Huma Hameed, Ana Cláudia Paiva-Santos, Mahtab Ahmad Khan, Shazia Akram Ghumman, Anam Hameed.

  Chondroitin sulphate is an anionic hetero-polysaccharide, having numerous structural affinities for building the bio-active components. In addition to biodegradable/biocompatible activities, chondroitin sulphate also possesses anti-coagulant/anti-thrombogenic, anti-inflammatory, anti-oxidant as well as anti-tumor activities. Chondroitin sulphate has an inherited affinity for glycosylation enzymes and receptors, which are overexpressed over degenerated cells and organelles. Because of this affinity, chondroitin sulphate is nominated as an active cellular/subcellular targeted biological macromolecule to assist in site-specific delivery. Chondroitin sulphate is mainly considered a promising biomaterial for drug targeting and tissue engineering due to its specific physicochemical, mechanical, bio-degradation, and biological characteristics. In this review, the fundamental applications of chondroitin sulphate in hepatic tissue engineering are discussed. Chondroitin sulphate along with mesenchymal stem cells (MSCs) based scaffold and hydrogels for biopharmaceuticals' delivery in hepatic tissue engineering are critically discussed. In addition, the manuscript also describes leading features and markers involved in hepatic damage, and the potential role of chondroitin sulphate-based delivery systems in hepatic tissue engineering.

Keywords:  Chondroitin sulphate; Liver regeneration; Tissue engineering

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.136332
Pharmaceuticals (Basel). 2024 Oct 12. pii: 1362. [Epub ahead of print]17(10):

Multifaceted Heparin: Diverse Applications beyond Anticoagulant Therapy.

Razia Sultana, Masamichi Kamihira.

  Heparin, a naturally occurring polysaccharide, has fascinated researchers and clinicians for nearly a century due to its versatile biological properties and has been used for various therapeutic purposes. Discovered in the early 20th century, heparin has been a key therapeutic anticoagulant ever since, and its use is now implemented as a life-saving pharmacological intervention in the management of thrombotic disorders and beyond. In addition to its known anticoagulant properties, heparin has been found to exhibit anti-inflammatory, antiviral, and anti-tumorigenic activities, which may lead to its widespread use in the future as an essential drug against infectious diseases such as COVID-19 and in various medical treatments. Furthermore, recent advancements in nanotechnology, including nano-drug delivery systems and nanomaterials, have significantly enhanced the intrinsic biofunctionalities of heparin. These breakthroughs have paved the way for innovative applications in medicine and therapy, expanding the potential of heparin research. Therefore, this review aims to provide a creation profile of heparin, space for its utilities in therapeutic complications, and future characteristics such as bioengineering and nanotechnology. It also discusses the challenges and opportunities in realizing the full potential of heparin to improve patient outcomes and elevate therapeutic interventions.

Keywords:  anticoagulant; bioengineering; glycosaminoglycan; heparin; nano-drug delivery systems; nanotechnology

DOI:  https://doi.org/10.3390/ph17101362