Search Results (447)

The prevalence of obesity among elderly women is increasing, particularly in postmenopausal populations. This exploratory study investigated the associations between chondroitin sulfate (CS) supplementation and body weight control in ovariectomized (OVX) rats, a preclinical model for postmenopausal physiology. CS supplementation was associated with significantly reduced body weight gain and preserved adipocyte morphology. CS-treated OVX rats exhibited decreased gut microbiota diversity, with reduced abundance of Photobacterium and Rhodococcus and increased abundance of Turicibacter. Metabolomic analysis revealed elevated levels of carbohydrates, fatty acids, and their conjugates, some of which correlated with body weight parameters. Bioinformatic analysis identified enriched KEGG pathways including tyrosine metabolism, glucosinolate biosynthesis and thiamine metabolism. Collectively, these findings provide preliminary correlational evidence in an OVX rat model supporting the potential of CS as a food supplement for body weight control, although causal relationships and clinical applicability warrant further investigation in postmenopausal populations. Full article

Environmental stressors like low temperature, low relative humidity (RH), and particulate matter (PM2.5), promote tear film instability and dry eye disease. This study investigates how these conditions alter the interfacial behavior of meibomian gland secretion (MGS) films in vitro and evaluates the capacity of mucomimetic polymers (0.5% hyaluronic acid [HA], polyvinylpyrrolidone [PVP], and chondroitin sulfate [CHS]) to suppress these impacts. MGS films over polymer-containing aqueous subphases were analyzed using a Langmuir trough and Brewster angle microscopy under adverse conditions (20 °C subphase, 20% RH, PM2.5 exposure). A sophisticated analytical framework was developed to evaluate MGS duplex multilayers: (i) a Volmer equation-based 2D-VES model to probe interfacial molecular properties (limiting area, compressibility, cohesion pressure) and (ii) a combined Maxwell viscoelastic and diffusion-relaxation model to quantify the dilatational relaxation modulus. Results indicate that despite their distinct nature, environmental stressors similarly disrupt the multilayer structure, reorganization, and rheological properties of MGS layers during blink-like deformations. Polymer supplementation moderated these adverse effects, yielding partial recovery of film structure and isothermal reversibility. Distinct mechanisms of action for HA, PVP, and CHS at the film/aqueous interface are elucidated. Full article

In this study, a pH-responsive chondroitin sulfate–methotrexate (MTX) polymeric prodrug was synthesized through Schiff base formation between oxidized chondroitin sulfate and MTX. The resulting amphiphilic conjugate exhibited a conjugation degree of 184 mg MTX per g conjugate and spontaneously self-assembled into stable nanoparticles (CSMXPs) with a mean diameter of 120 ± 10 nm, a polydispersity index of 0.24, and a critical aggregation concentration of 4.7 × 10⁻⁴ mg mL⁻¹. Drug release studies demonstrated a marked pH-dependent behavior, with complete MTX release after 24 h at pH 5.0 and a sustained release profile under physiological conditions. The release mechanism followed reversible first-order kinetics and was accelerated by acid-catalyzed hydrolysis of the imine linkage. Biological evaluation revealed enhanced therapeutic selectivity of CSMXPs compared with free MTX. At 36 μM MTX-equivalent concentration, CSMXPs reduced HeLa cell viability to 37%, while maintaining MCF-10A viability above 88%, whereas free MTX decreased viability in both cell lines (51% and 65%, respectively). Fluorescence confocal microscopy confirmed efficient nanoparticle uptake by cancer cells. These findings demonstrate that CSMXPs represent a promising self-assembling nanoprodrug platform for selective and targeted cancer therapy. Full article

The escalating prevalence of bacterial infections has intensified the search for innovative antimicrobial strategies, particularly for infected wound management. Chondroitin sulfate (CS), a naturally occurring glycosaminoglycan with established biocompatibility, presents an attractive scaffold for developing metal ion-functionalized biomaterials. This study reports the fabrication of chondroitin sulfate–copper complex (CSCu) and chondroitin sulfate–zinc complex (CSZn) through an ion exchange method, wherein Cu²⁺ and Zn²⁺ ions bind to the groups of carboxylate, sulfate, or N-acetyl from the CS backbone. The resulting complexes exhibited copper or zinc loading capacities of about 6.6% and demonstrated potent antibacterial activity against E. coli and S. aureus. The integration of CSCu or CSZn with sodium alginate yielded a hydrogel system with a higher apparent viscosity, possessing injectability and spreadability on the skin surface and a porous three-dimensional internal structure conducive to wound healing applications. In a murine model of S. aureus-infected full-thickness wounds, topical application of CSCu and CSZn hydrogels substantially accelerated wound closure, achieving 97.46% and 98.11% healing, respectively, by day 10. Additionally, treatment with CSCu or CSZn hydrogels significantly attenuated systemic inflammatory responses, as reflected in lowered serum TNF-α, IL-1β, and IL-6 alongside increased IL-10. Histological evaluation confirmed enhanced re-epithelialization and stratum spinosum formation in treated wounds. These findings establish CSCu and CSZn as a promising bioactive agent for addressing bacterial wound infections through a dual mechanism of direct antibacterial action and immunomodulatory effects, offering a valuable alternative to conventional antibiotic therapies. Full article

Background: Rheumatoid arthritis (RA) is influenced by environmental exposures. High humidity has been clinically associated with worsened joint symptoms, but the microbial and metabolic mechanisms remain unclear. We investigated whether a gut microbiota–metabolism axis contributes to humidity-associated aggravation of collagen-induced arthritis (CIA). Methods: CIA mice were maintained under normal or high relative humidity. We integrated 16S rRNA and metagenomic sequencing, liquid chromatography–tandem mass spectrometry metabolomics, and intestinal barrier assessments. Fecal microbiota transplantation (FMT) was performed to evaluate microbiota dependency. Based on multi-omics findings, we quantified chondroitin sulfate (CS) and conducted functional experiments involving Prevotella stercorea (P. stercorea) supplementation, CS administration, and in vitro degradation assays. Results: High humidity aggravated arthritis severity and systemic inflammation, including increased interleukin-6, interleukin-17A, and granulocyte colony-stimulating factor, and was accompanied by impaired intestinal barrier integrity. FMT supported a microbiota-dependent contribution. Metagenomic analysis identified enrichment of P. stercorea and glycosaminoglycan degradation pathways under high humidity. CS abundance was reduced in articular cartilage, P. stercorea degraded CS in vitro and was associated with cartilage CS loss in vivo, and CS supplementation attenuated arthritis under high humidity and reduced the arthritis-promoting effects associated with P. stercorea. Conclusions: High humidity is associated with microbiota-dependent functional remodeling, enhanced CS degradation, and aggravated arthritis in CIA mice. These findings suggest that humidity-associated alterations in microbial CS metabolism may link environmental exposure to cartilage disruption and joint inflammation. Full article

Proteoglycans (PGs) and their glycosaminoglycan (GAG) chains play key roles in corneal epithelial physiology and host–microbe interactions. Although bacterial exposure has been shown to alter PG and GAG biosynthesis, the contribution of specific bacterial-derived signals remains unclear. In this study, reconstructed human corneal epithelia (QobuR) were exposed to bacterial extracellular vesicles (BEVs) from Pseudomonas aeruginosa and Staphylococcus epidermidis, as well as to lipopolysaccharide, peptidoglycan, and lipoteichoic acid. The expression of 72 genes involved in PG and GAG biosynthesis and remodeling was analyzed by quantitative real-time PCR. Only 22 genes showed significant transcriptional alterations, indicating a highly selective response. Most changes affected enzymes involved in the generation of heparan sulfate (HS) and chondroitin sulfate (CS) fine structure, particularly sulfotransferases. Notably, HS3ST4 and HS3ST5 were consistently upregulated under all experimental conditions, suggesting that modulation of HS 3-O-sulfation represents a conserved corneal epithelial response to bacterial-derived stimuli. Whereas microbial-associated molecular patterns induced broader transcriptional responses, BEVs elicited more restricted and species-dependent effects. Overall, these findings demonstrate that bacterial-derived signals selectively remodel GAG biosynthetic pathways and provide new insights into the molecular mechanisms underlying host–microbe interactions at the ocular surface. Full article

Glycosaminoglycans (GAGs) are the carbohydrate portion of proteoglycans (PGS), a family of complex biomacromolecules ubiquitously found in the extracellular matrix and on cell surfaces that play critical roles in a plethora of physiological and pathological processes. In the present work, chondroitin sulfate (CS) and dermatan sulfate (DS) were extracted and purified from the head (GCB) and skin (GDB) of blue runner fish (Caranx crysos) to explore their structural features and biological properties. GCB and GDB were purified by ion-exchange chromatography with yields of 0.82% and 0.61%, respectively. Chemical and structural analysis showed that GCB and GDD demonstrated quite similar sulfation degrees (4.45% and 4.24%, respectively). The molecular weight values obtained for GCB and GDB as estimated by high-performance size exclusion chromatography coupled with a triple detector array (HP-SEC-TDA) were 48.9 and 28.54 KDa, respectively. Structural features were elucidated using FT-IR and 2D NMR spectroscopy. GCB was mainly identified as chondroitin sulfate, containing 82% GlcA and minor proportions of IdoA and IdoA2S (scoring 18% dermatan-like structures). In contrast, GDB was predominantly dermatan sulfate, with a higher unsulfated IdoA content (54%) and a lower GlcA percentage (17%). In vitro anticoagulant activity, evaluated using APTT and PT assays, demonstrated that both GAGs exhibit significant anticoagulant potential. In addition, both fractions exhibited no antiplatelet activity, suggesting that the isolated glycosaminoglycans selectively target the coagulation cascade without affecting platelet aggregation. Furthermore, hemolytic assays confirmed that neither GCB nor GDB showed any hemolytic activity at the tested concentrations. Cytotoxicity assessment in HEK293 and HUVEK cell lines further confirmed the absence of detectable toxicity even at high concentration. Overall, these marine-derived GAGs present promising therapeutic potential as a source of anticoagulant drugs. Full article

Background and Objectives: Polyacrylamide hydrogel (PAAG) is still underresearched, and few human studies have validated its efficacy in knee osteoarthritis (OA), particularly in advanced stages. The aim of this study was to compare the efficacy of intra-articular PAAG with that of the widely used cross-linked chondroitin sulfate/hyaluronic acid (HA/CS) combination in treating knee OA in a retrospective trial. Materials and Methods: A total of 127 patients diagnosed with grade 3 or 4 knee OA according to the Kellgren–Lawrence scale were included. The first group received an intra-articular injection of the cross-linked HA (60 mg)/CS (90 mg) combination, whereas the second group was administered 6 mL of PAAG. The outcome measures, which were assessed at baseline, 3 months, and 12 months, were knee pain severity measured with the visual analog scale (VAS), range of motion (ROM), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale score, and the Pittsburgh Sleep Quality Index (PSQI). Results: At three months, the PAAG group demonstrated significantly lower pain and WOMAC scores than the HA/CS group, while ROM and sleep quality scores were not significantly different at either 3 or 12 months. Within-group comparisons revealed significant reductions in pain, WOMAC, and sleep scores in both groups over time, but no significant improvement in ROM was detected in either group. Conclusions: Compared with HA/CS injection, intra-articular PAAG injection significantly improved the VAS and WOMAC scores in advanced knee OA patients at three months. However, the outcomes for all the parameters were similar in the two groups at 12 months. Full article

NG2 glia, also known as oligodendrocyte progenitor cells, represent a unique population of glial cells characterized by dynamic morphology and the ability to extend branched processes that actively contact neurons and other cellular elements. These structural and functional interactions enable NG2 glia to contribute to the regulation of axonal excitability, electrical activity, and axonal architecture. Unlike most other glial cells, NG2 glia receive direct synaptic input from neurons and can generate action potentials, defining their distinctive physiological status. A particularly important feature of this cell population is the expression of the chondroitin sulfate proteoglycan NG2/CSPG4, which serves as a key molecular marker and plays an essential role in intercellular interactions. Following spinal cord injury (SCI), NG2 glia rapidly become activated, undergo phenotypic changes, and engage in extensive interactions with neurons, astrocytes, microglia, and endothelial cells. These interactions form a complex regulatory network that influences both the severity of secondary injury and the effectiveness of remodeling and repair processes. Mechanisms of particular importance include the secretion of chondroitin sulfate proteoglycans and alterations in extracellular matrix properties. Finally, this review highlights potential therapeutic approaches aimed at modulating NG2 glial activity and their intercellular interactions. The focus is on strategies designed to reduce the inhibitory effects of proteoglycans while enhancing the remyelinating and neuroprotective potential of these cells, thereby opening new perspectives for regenerative therapies after SCI. Full article

Chronic wounds, particularly those complicated by infection, present significant challenges in clinical management. The microenvironment of these wounds is typically characterized by the accumulation of reactive oxygen species (ROS) and abnormal local pH levels, both of which impede the healing process. Baicalin (BA), a natural flavonoid, exhibits anti-inflammatory activity, ROS-scavenging capability, and pro-healing effects. In this study, hydrogels were synthesized through photoinitiated radical polymerization of methacrylic anhydride (MAA) and dopamine (DA)-modified chondroitin sulfate (ChSMA-DA), grafting degrees of MA and DA were 58%, 23%, MPDA@MnO₂ nanoparticles (NPs), and methacrylated gelatin (GelMA). The gelation time, microtopography, swelling behavior, and water retention of the hydrogels were investigated, along with their degradation, rheological properties, and photothermal effects. The results indicate that swelling ratio (SR) and water retention (WR) of optimal HG-MPDA@MnO₂-M sample were 5.7, 82.42%, exhibited responsive behavior upon weakly acidic environment with pH 6.5 and elevated ROS levels, and exhibited a stable photothermal effect (photothermal conversion efficiency was 22.7%) under 808 nm near-infrared (NIR) light. Following the incorporation of the drug model BA, the cumulative release percentage over 24 h under the combined stimulation of pH 6.5, 1 mmol·L⁻¹ H₂O₂, and 808 nm NIR was 81.1%, significantly higher than either factor alone. These hydrogels show promise as an injectable dressing for chronic wounds, effectively integrating the internal microenvironment of the wound tissue with external NIR to modulate drug release. Full article

Bone repair is a complex and dynamic process that demands implanted scaffolds to provide temporal-specific functions: antibacterial activity in the early stage, followed by angiogenic and osteogenic stimulation in later stages. This study introduces a biomimetic scaffold composed of a filled Gel-OSA hydrogel and a 3D-printed PLA framework, enabling sequential multi-drug release for bone regeneration. Zero-dimensional arginine-derived carbon dots were incorporated into the hydrogel to achieve rapid release after implantation, conferring potent antibacterial activity and ROS regulation. Meanwhile, chondroitin sulfate (CS)-loaded mesoporous bioactive glass nanoparticles were immobilized onto the 3D-printed PLA surface via a polydopamine coating, allowing sustained release of CS and Ca/P ions to enhance the scaffold’s long-term osteoinductive capability. The composite scaffold further demonstrated combined effects in promoting cell proliferation and osteogenic differentiation in vitro. Collectively, these findings suggest that this biomimetic scaffold, designed for temporally controlled multi-drug release, represents a promising therapeutic strategy for the reconstruction of bone tissue. Full article

Hydrocolloids comprise a diverse class of high-molecular-weight polymeric carbohydrates associated with a wide range of physicochemical and functional properties. This review provides an integrated analysis of natural hydrocolloids derived from algal (agar, alginate, carrageenan, fucoidan, laminarin, and ulvan), animal (chitin, chitosan, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin, heparan sulfate, glycogen, and hyaluronan), and plant (pectin, starch, and locust bean gum) sources, together with semisynthetic cellulose-based derivatives. Emphasis is placed on the relationship between molecular structure, charge density, sulfation patter, and branching degree, and how these parameters modulate hydration, gelation, and rheological behavior. Comparative analyses are presented, establishing structure–function interactions that link molecular characteristics to functional properties, including thickening, gelling, emulsifying, stabilizing, film-forming, and controlled-release capacities. The review also discusses the biological activities and application potential of these hydrocolloids in pharmaceutical, biomedical, and advanced material systems. In addition, emerging modification strategies, including chemical functionalization, crosslinking, and nanostructuring are discussed as tools to adjust their action and diversify their application range. Special attention is given to structure–rheology–gelation relationships and to the influence of molecular organization on mechanical strength, stability, and delivery performance. Current challenges associated with scalability, processability, reproducibility, and long-term functional stability are also critically discussed. Overall, this review provides a comprehensive structure–function perspective on hydrocolloids as sustainable and multifunctional polymeric materials, supporting their rational design and continued development in pharmaceutical sciences, biomedical engineering, and advanced material applications. Full article

Objectives: Given that the structure-activity relationship between sturgeon chondroitin sulfate (S-CS) and the alleviation of osteoarthritis (OA) remains unclear, we characterized the structure of S-CS and explored the relationship between its structure and its effect in alleviating OA. Methods: Chondroitin sulfate was extracted from sturgeon cartilage by alcohol precipitation. Its structure was thoroughly characterized using infrared spectroscopy, pre-column derivatization, high-performance liquid chromatography with PMP (PMP-HPLC), nuclear magnetic resonance spectroscopy (NMR), and other techniques. A rat OA model was established to explore the mechanism underlying its alleviation of OA. In addition, 16S rRNA sequencing was performed to investigate the role of gut microbiota. Results: S-CS was identified as a sulfated polysaccharide with an average molecular weight of 68.81 kDa and a GlcUA-to-GalN molar ratio of approximately 1:1. NMR analysis confirmed its characteristic 6-/4-sulfation patterns. Oral administration of S-CS at 100 mg/kg/d significantly alleviated joint damage by inhibiting the NF-κB and p38 MAPK signaling pathways. Specifically, S-CS decreased the levels of p65 and p38 by 18.94% and 52.40% (p < 0.05), respectively, and decreased TNF-α concentration. Moreover, 16S rRNA sequencing showed that S-CS enhanced the diversity and richness of gut microbiota and reconstructed the microbial community structure. Conclusions: S-CS may be an effective supplement for OA. Full article

Background/Objectives: This investigation aims to assess the potential for repurposing nitazoxanide (NIT) as a treatment for COVID-19. NIT was loaded into terpene-enriched chondrosomes (TECs) to assess its anti-hCoV-19 activity through pulmonary delivery. Methods: NIT-TECs were then fabricated utilizing the ethanol injection method. Using a D-optimal design, the effects of factors on entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP) were determined, and the optimal formulation was selected. Results: The optimum TEC exhibited an EE% of 98.87 ± 0.69, a PS of 129.43 ± 5.43 nm, a polydispersity index (PDI) of 0.433 ± 0.022, and a ZP of −25.99 ± 0.99 mV. The optimum TEC was lyophilized to attain a dry powder. Further, the differential scanning calorimetry test confirmed that NIT was transformed from crystalline to amorphous form inside the optimum TEC. In addition, the mucoadhesion test confirmed the ability of the optimum TECs to adhere to pulmonary tissues. Additionally, NIT binding to the active site of SARS-CoV-2 enzymes was investigated using in silico analysis. When compared to NIT, the aerodynamic characteristics of the lyophilized optimum TECs employing the cascade impactor showed superior residence in the lungs. Conclusions: These findings suggest that loading NIT into TECs enhanced its antiviral activity, as indicated by the in vitro cytotoxicity study. Overall, the results point to NIT-loaded TECs as a potentially effective pulmonary delivery system for COVID-19 treatment. Full article

Targeted delivery systems offer a promising approach for selectively modulating cellular processes; yet the intracellular consequences of targeted nutrient delivery to trophoblast cells remain poorly defined. Here, we investigated a previously validated placenta-targeting peptide conjugated to liposomes encapsulating stable isotope-labelled L-arginine and L-lysine to examine cellular uptake and downstream molecular responses in a trophoblast-like cell model. Peptide-dependent uptake of fluorescently labelled liposomes was confirmed in BeWo cells, demonstrating selective internalisation compared with non-targeted controls. Encapsulation of isotope-labelled amino acids enabled direct quantification of intracellular delivery and incorporation into the cellular proteome using stable isotope labelling by amino acids in cell culture (SILAC). Quantitative proteomic analysis revealed coordinated changes in proteins associated with translation, metabolism, and nitric oxide synthase regulation following targeted liposomal uptake. Notably, V-type proton ATPase subunit G1 (ATP6V1G1) and large neutral amino acid transporter small subunit 1 (SLC7A5) showed increased incorporation of labelled amino acids and were independently validated by Western blotting. Together, these findings establish a proof-of-concept platform for targeted intracellular amino acid delivery to trophoblast-like cells and define the resulting proteomic responses. This work provides mechanistic insight into intracellular amino acid utilisation and a framework for future studies in placental cell biology. Full article