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Postoperative adhesion often develops as a natural physiological response following abdominal and pelvic surgeries. Although existing resorbable adhesion barriers have reduced the incidence of postoperative adhesion formation, their clinical efficacy requires improvement. In this study, we generated a novel cross-linked, powder-formed chondroitin sulfate (SI-449) as an effective postoperative anti-adhesion barrier. We evaluated its anti-adhesion effect in animal models of abdominal and pelvic surgeries and elucidated its mechanism of action. Rats in the cecum-abraded adhesion and uterine horn adhesion models were treated with SI-449 and Seprafilm, and adhesion frequency and scores were evaluated. The mechanisms underlying this anti-adhesion effect were examined histopathologically using a cecum-abraded adhesion model. In the cecum-abraded adhesion model, SI-449 reduced the adhesion frequency and total adhesion score to 30% and 1.6, respectively, compared with 100% and 8.1 in the control group and 50% and 2.5 in the Seprafilm group. We observed an SI-449-like substance between the cecum and abdominal wall and no fibrin net structure connecting the invasive tissues after surgery, as observed in the control group. In the rat uterine horn adhesion model, SI-449 reduced the adhesion frequency to 40%, compared with 100% in the control. SI-449 exhibits anti-adhesion activity in animal models of postoperative adhesion. The mechanism of action of SI-449 during wound healing suggests mechanical obstruction of fibrin net structure formation, which is a key step in the development of adhesions at surgical sites. SI-449 is a promising candidate for preventing postoperative adhesions in clinical practice. [ABSTRACT FROM AUTHOR]

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General strategies for synthesizing sulfated oligosaccharides employ the protection of sulfate groups for glycosylation or post‐sulfation after the synthesis of oligosaccharides. However, the chemical behavior of free sulfate groups in glycosylation reactions has not been thoroughly studied. We examined several glycosyl donors with free sulfate groups, but neither glycosyl imidates nor thioglycosides achieved products. Conversely, activating 6‐sulfated GalNAc donors with either a 2‐NTroc group or 2‐O‐acetyl group using an ortho‐hexynylbenzoate group at the anomeric position yielded β‐glycosides in good yield. These results indicate that glycosylations with a free sulfate group can be performed and that the neighboring group participation of 2‐NHTroc and 2‐O‐acetyl groups works even with an unprotected sulfate group at the 6‐position. Ab initio calculations supported the formation of acyloxonium‐cation via 2‐O‐acyl participation. Additionally, glycosylation reactions under various counter cations of the sulfate group, such as Na+, Li+, K+, Ba2+, and pyridinium were examined. Results showed that sodium and lithium salt donors yielded the products in good yield. These results were also supported by ab initio calculations. Practical glycosylation reactions between disaccharide donor‐acceptor pairs with free sulfate groups successfully yielded the sulfated tetrasaccharides. This study also discusses how a sodium salt acts as a protecting group during glycosylation. [ABSTRACT FROM AUTHOR]

Mutations in IDH1 and TP53 have a significant impact on glioma prognosis and progression; however, their roles in tumor cell invasion in terms of interactions with particular components of the extracellular matrix (ECM) are still unclear. Using gene editing protocol based on CRISPR-Cas 9 with cytidine deaminase, we introduced point mutations into U87MG glioblastoma cells to establish modified cell lines with heterozygous IDH1 R132H, homozygous TP53 R248Q and heterozygous IDH1 R132H, homozygous TP53 R248Q genotypes. A comparative study of cell migration on major ECM components was carried out by high-content microscopy. IDH1 R132H mutation introduced to U87MG glioblastoma cells was shown to decrease the migration speed on Matrigel and collagen IV substrates compared to the wild-type. This data were supported by cell adhesion quantification via the lateral shift assay performed by atomic force microscopy (AFM). TP53 R248Q mutation increased cell adhesion to various substrates and significantly promoted cell migration on hyaluronic acid and chondroitin sulfate but did not change the migration rates on laminin and collagens IV and I. A double-mutant genotype produced by consequently introducing IDH1 R132H and TP53 R248Q to parental glioblastoma cells was characterized by the highest migration among all the cell lines, with particularly faster motility on chondroitin sulfate. These findings underscore the complex interactions between glioma cells, with the most important driver mutations and specific ECM components regulating cancer cell migration, offering valuable insights for potential therapeutic targets in glioma treatment. [ABSTRACT FROM AUTHOR]

Glycosaminoglycans are often deprioritized as targets for synthetic immunotherapy due to the complexity of glyco-epitopes and limited options for obtaining specific subtype binding. Solid tumors express proteoglycans that are modified with oncofetal chondroitin sulfate (CS), a modification normally restricted to the placenta. Here, we report the design and functionality of transient chimeric antigen receptor (CAR) T cells with selectivity to oncofetal CS. Following expression in T cells, the CAR could be "armed" with recombinant VAR2CSA lectins (rVAR2) to target tumor cells expressing oncofetal CS. While unarmed CAR T cells remained inactive in the presence of target cells, VAR2-armed CAR T cells displayed robust activation and the ability to eliminate diverse tumor cell types in vitro. Cytotoxicity of the CAR T cells was proportional to the concentration of rVAR2 available to the CAR, offering a potential molecular handle to finetune CAR T cell activity. In vivo, armed CAR T cells rapidly targeted bladder tumors and increased the survival of tumor-bearing mice. Thus, our work indicates that cancer-restricted glycosaminoglycans may be exploited as potential targets for CAR T cell therapy. Synopsis: Transient VAR2-[SpyT][SpyC]-CAR T cells targeting oncofetal chondroitin sulfate (CS) show high specificity and activity against solid tumor cells, adding glycosaminoglycans to the list of potential actionable targets for CAR T cell therapy in solid tumors. Transient CAR T cells were developed to target oncofetal CS, unique to cancer cells. VAR2-[SpyT]-armed CAR T cells demonstrated robust activation, cytokine production, and cytotoxicity in vitro. The targeting mechanism offers high specificity and potential broad applicability across various solid tumors. VAR2-[SpyT][SpyC]-CAR T cells inhibited tumor growth and increased survival in vivo. The VAR2-[SpyT][SpyC]-CAR T cell system provides proof-of-concept for oncofetal CS as a potential target for CAR T cell approaches. Transient VAR2-[SpyT][SpyC]-CAR T cells targeting oncofetal chondroitin sulfate (CS) show high specificity and activity against solid tumor cells, adding glycosaminoglycans to the list of potential actionable targets for CAR T cell therapy in solid tumors. [ABSTRACT FROM AUTHOR]

Morbidities associated with natural bone have highlighted the need of advanced bioactive implants for the replacement of damaged bone. Known for their beneficial bioactivity and biocompatibility, Nigella sativa seeds (kalonji/black seed) are traditionally used in many medications. This research focuses on the positive impact of black seed extract on the chondroitin sulfate‐based hydroxyapatite nanocomposite for bone tissue regeneration applications. Novel nanocomposites with varied concentrations of black seed extract (0, 1, 2, and 3 wt%) were fabricated through a coprecipitation approach and analyzed for physicochemical and biological applications. The results of X‐ray diffraction and FTIR spectroscopy revealed that the HCSK3 nanocomposite was successfully developed with appreciably strong molecular interactions among their components. HCSK3 nanocomposite exhibits higher rough surface morphology (Ra −1.13 µm and Rz −4.8 µm), uniform particle distribution (average particle size −9.9 nm), and good thermal stability with total weight loss of 13%. It also provides better nucleation sites for apatite formation and protein adsorption stimulating cell attachment, proliferation, and differentiation. Moreover, HCSK3 nanocomposite showed excellent cell viability, higher ARS/ALP activities, better antibacterial property, and nonhemolytic property (below 3%). Thus, it can be concluded that HCSK3 nanocomposite manifested the highest biocompatibility and negligible cell toxicity. Therefore, it can be employed as an ideal bone implant in the bone tissue restoration phenomenon. [ABSTRACT FROM AUTHOR]

For the non-invasive treatment of rheumatoid arthritis (RA), a chondroitin sulfate C (CSC)-based dissolving microneedles (cMN) was prepared to deliver human adipose stem cell-derived extracellular vesicles (hASC-EV) into inflamed joints. Owing to their anti-inflammatory function, the hASC-EV-bearing cMN (EV@cMN) significantly suppressed activated fibroblast-like synoviocytes (aFLS) and M1 macrophages (M1), which are responsible for the progression of RA. In addition, EV@cMN facilitated the chondrogenic differentiation of bone marrow-derived stem cells. In mice with collagen-induced arthritis, EV@cMN efficiently delivered both hASC-EV and CSC to inflamed joints. Interestingly, pro-inflammatory cytokines in the inflamed joints were remarkably downregulated by the synergistic effect of CSC and hASC-EV. Consequently, as judged from the overall clinical score and joint swelling, EV@cMN showed an outstanding therapeutic effect, even comparable to the wild-type mice, without significant adverse effects. Overall, EV@cMN might have therapeutic potential for RA by efficiently delivering CSC and hASC-EV into the inflamed joints in a non-invasive manner. [Display omitted] • Macrophages and synoviocytes contribute significantly to the progression of rheumatoid arthritis. • Stem cell-derived extracellular vesicle (hASC-EV) inhibits M1 polarization of macrophages. • We discovered that chondroitin sulfate (CSC) reduces the invasiveness of synoviocytes. • Co-delivery of hASC-EV and CSC via microneedle effectively inhibits the progression of RA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF‐associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6‐O‐sulfated CS‐binding peptide (C6S‐p) on blocking CS functions were tested in vitro and in vivo. Results indicated that the expression of CHPF and SDC1 was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF‐β) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS–SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient‐deprived conditions. Furthermore, C6S‐p demonstrated the ability to bind CS‐SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth in vivo. Although other PGs may also be involved in CHPF‐regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells. [ABSTRACT FROM AUTHOR]

Background: Cartilage is an avascular and alymphatic tissue that lacks the intrinsic ability to undergo spontaneous repair and regeneration in the event of significant injury. The efficacy of conventional therapies for invasive cartilage injuries is limited, thereby prompting the emergence of cartilage tissue engineering as a possible alternative. In this study, we fabricated three‐dimensional hydrogel films utilizing sodium alginate (SA), gelatin (Gel), and chondroitin sulfate (CS). These films were included with Wharton's jelly mesenchymal stem cells (WJ‐MSCs) and intended for cartilage tissue regeneration. Methods: The hydrogel film that were prepared underwent evaluation using various techniques including scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, assessment of the degree of swelling, degradation analysis, determination of water vapor transmission rate (WVTR), measurement of water contact angle (WCA), evaluation of mechanical strength, and assessment of biocompatibility. The rabbit ear cartilage regeneration by hydrogel films with and without of WJ‐MSCs was studied by histopathological investigations during 15, 30, and 60 days. Results: The hydrogel films containing CS exhibited superior metrics compared to other nanocomposites such as better mechanical strength (12.87 MPa in SA/Gel compared to 15.56 in SA/Gel/CS), stability, hydrophilicity, WVTR (3103.33 g/m2/day in SA/Gel compared to 2646.67 in nanocomposites containing CS), and swelling ratio (6.97 to 12.11% in SA/Gel composite compared to 5.03 to 10.90% in SA/Gel/CS). Histopathological studies showed the presence of chondrocyte cells in the lacunae on the 30th day and the complete restoration of the cartilage tissue on the 60th day following the injury in the group of SA/Gel/CS hydrogel containing WJ‐MSCs. Conclusions: We successfully fabricated a scaffold composed of alginate, gelatin, and chondroitin sulfate. This scaffold was further enhanced by the incorporation of Wharton's jelly mesenchymal stem cells. Our findings demonstrate that this composite scaffold has remarkable biocompatibility and mechanical characteristics. The present study successfully demonstrated the therapeutic potential of the SA‐Gel‐CS hydrogel containing WJ‐MSCs for cartilage regeneration in rabbits. [ABSTRACT FROM AUTHOR]

In this work, capillary electrophoresis with Gaussian distribution‐based peak fitting for improved peak resolution for simultaneous quantitative analysis of chondroitin sulfate (CS) and dermatan sulfate (DS) was developed for the first time. The effects of different pH, voltage, and peak shapes on the peak fitting were investigated. The results indicate that separation conditions that affect peak shape have a significant impact on peak fitting. Under optimized separation conditions, the peak fitting achieves high accuracy and precision, the relative standard deviation (n = 5) of peak area and migration time of CS and DS were 1.1%, 1.8% and 0.94%, 0.84%, respectively. Furthermore, the results obtained by peak fitting were close to real values. The developed method was used to analyze the purity of CS. The results had a high consistency with the labeled value; furthermore, the peak fitting could point out the number of possible impurities. The developed method has good potential for the analysis of other glycosaminoglycans with peak overlap. [ABSTRACT FROM AUTHOR]

El uso de un grupo de fármacos conocidos como SYSADOA (SYmptomatic Slow-Acting Drugs for Osteoarthritis) en el tratamiento de la osteoartritis (OA) ha sido fuente de debate en la comunidad científica y en entidades públicas con relación a su financiación pública en España. El objetivo principal de este estudio fue describir y analizar las principales posiciones de los medios de comunicación y las entidades públicas frente al uso y la financiación de SYSADOA en España. Se realizó un análisis cualitativo y cuantitativo del contenido respecto al uso y a la financiación de SYSADOA en medios generalistas (El País , El Mundo , La Vanguardia , ABC y 20minutos), comunicados de organismos públicos y publicaciones en Twitter®. Se identificaron 15 artículos en medios generalistas, 872 tweets y 7 comunicados de organismos públicos. Mayoritariamente, los datos obtenidos en medios de comunicación (91%) y redes sociales (78%) respaldaron la financiación de SYSADOA. A pesar de la controversia en la comunidad científica, este estudio destaca un consenso en los medios de comunicación y asociaciones a favor de la financiación pública de SYSADOA en los pacientes de OA. The use of SYmptomatic Slow-Acting Drugs for Osteoarthritis (SYSADOA) in the treatment of osteoarthritis (OA) has been a topic of debate in the scientific community and public entities regarding their public financing in Spain. The objective of this study was to describe and analyze the main positions of media outlets, public entities, regarding the use and financing of SYSADOA in Spain. A qualitative and quantitative analysis of the content regarding the use and financing of SYSADOA was conducted in general media outlets (El País , El Mundo, La Vanguardia, ABC, and 20minutos), public statements, and Twitter® publications. A total of 15 articles in general media outlets, 872 tweets, and 7 public entity statements were identified. Mostly, media outlets (91%) and social media platforms (78%) exhibited a favorable trend towards funding. The use of SYSADOA in OA patients continues to be controversial in the scientific community. However, there is consensus among patient associations in favor of public funding and use as a treatment for OA patients. [ABSTRACT FROM AUTHOR]

Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. In vitro characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS in vitro and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair. Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects. [Display omitted] [ABSTRACT FROM AUTHOR]

The metachromatic dye dimethylmethylene blue is used to quantify total glycosaminoglycans in urine. Understanding the interaction of dimethylmethylene blue with glycosaminoglycans is pertinent to optimize the assay procedure depending on the type of sample and interpret the findings meaningfully. The present spectrophotometric study determined the optimum sample-to-dye ratio, primary wavelength for measuring absorbance, after studying the interaction of two different chondroitin sulfate species (unfractionated chondroitin sulfate from bovine trachea vs. chondroitin sulfate oligosaccharide with degree of polymerization of 12, from shark cartilage) with dimethylmethylene blue. Respective dye-glycosaminoglycan complexes of the two chondroitin sulfate species showed significantly different absorbance maxima, while that of the chondroitin sulfate oligosaccharide was closer to absorbance maxima of urine glycosaminoglycans. The chondroitin sulfate oligosaccharide showed relatively less stable absorbance readings at higher concentrations in the reaction volume. Furthermore, the chondroitin sulfate reference materials exhibited differences in the linearity of standard curves and hence parallelism. Based on the findings, the method was semiautomated on Beckman Coulter D✕C 700 biochemistry analyzer using the chondroitin sulfate oligosaccharide as the standard. The urine glycosaminoglycan concentration obtained was slightly lower but reasonably close to that obtained through the External Quality Assurance (EQA) scheme administrated by ERNDIM (European Research Network, Inherited Disorders of Metabolism). The findings of the present study can be used to guide the dimethylmethylene blue assay optimization, redevelopment efforts, and harmonization across laboratories. The chondroitin sulfate oligosaccharide is better than the unfractionated chondroitin sulfate from bovine trachea due to its absorbance maxima closer to urine glycosaminoglycans. On the other hand, unfractionated chondroitin sulfate exhibit poor parallelism leading to falsely lower urine glycosaminoglycan levels. [ABSTRACT FROM AUTHOR]

In this study, RAW 264.7 cells and immunosuppressive models were used to investigate the immunostimulatory activity of tilapia-head chondroitin sulfate (CS) through in vitro and in vivo experiments. The results showed that tilapia-head chondroitin sulfate (CS) could induce the produce of NO, IL-1β, IL-6, IL-10 and TNF-α in RAW 264.7 cells. Cyclophosphamide (CTX) induced thymic atrophy in mice (thymic index 0.11%±0.01%), while thymic index was significantly up-regulated by low-dose CS (thymic index (0.17%±0.03%) and high-dose CS (thymic index (0.18%±0.02%) interventions (P

Abstract Glycosaminoglycans are often deprioritized as targets for synthetic immunotherapy due to the complexity of glyco-epitopes and limited options for obtaining specific subtype binding. Solid tumors express proteoglycans that are modified with oncofetal chondroitin sulfate (CS), a modification normally restricted to the placenta. Here, we report the design and functionality of transient chimeric antigen receptor (CAR) T cells with selectivity to oncofetal CS. Following expression in T cells, the CAR could be “armed” with recombinant VAR2CSA lectins (rVAR2) to target tumor cells expressing oncofetal CS. While unarmed CAR T cells remained inactive in the presence of target cells, VAR2-armed CAR T cells displayed robust activation and the ability to eliminate diverse tumor cell types in vitro. Cytotoxicity of the CAR T cells was proportional to the concentration of rVAR2 available to the CAR, offering a potential molecular handle to finetune CAR T cell activity. In vivo, armed CAR T cells rapidly targeted bladder tumors and increased the survival of tumor-bearing mice. Thus, our work indicates that cancer-restricted glycosaminoglycans may be exploited as potential targets for CAR T cell therapy.

Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF‐associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6‐O‐sulfated CS‐binding peptide (C6S‐p) on blocking CS functions were tested in vitro and in vivo. Results indicated that the expression of CHPF and SDC1 was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF‐β) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS–SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient‐deprived conditions. Furthermore, C6S‐p demonstrated the ability to bind CS‐SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth in vivo. Although other PGs may also be involved in CHPF‐regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells.

The paper presents the results of developing a fish culinary product (thorny skate meat mixed with Atlantic cod meat, baked with potatoes and mushrooms in a cream sauce) enriched with chondroitin sulfate contained in the meat and cartilage of the wings of thorny skate. Atlantic cod, more familiar to the Russian consumer and successfully complementing the skate's meat with amino acid composition, has been chosen as an additional fish raw material. Thorny skate belongs to the underutilized fishing facilities of the Northern Basin. The meat of its wings contains up to 1.5 % urea, which worsens its organoleptic properties. To solve this problem, it was previously proposed to use short-term preliminary heat treatment (PHT) of skate's wings by blanching them in water at a temperature from 93 to 96 °C for 1–3 minutes, which guarantees a fourfold decrease in the mass fraction of urea in the meat, relative to the initial content, below the organoleptic perception of the consumer. PHT also facilitates the cutting of the skate's meat. The formulation and technology of a combined fish culinary product is proposed, packaged and completely ready for consumer's use. To prolong the shelf life up to 120 days, it is proposed to subject the product to shock freezing with subsequent storage at a temperature no higher than minus 18 °C. To solve the problem of delamination of cream sauce during storage and to improve the consumer properties of the product, an experimentally based technological solution is proposed – the introduction of oat flour in the composition of the sauce formulation as a thickener and structure-forming agent in an amount of 3.5 % per total mass of sauce.

Osteoarthritis (OA) is one of the leading causes of disability in the world, but the efficacy and safety of its treatment remain extremely low. This review presents epidemiology of OA, mechanism of its development and modern possibilities of pharmacological regulation of immune-mediated inflammation in OA. We analyze the immunological aspects of oral tolerance phenomenon and the prospects for its use to suppress autoinflammation in OA using combined pharmaconutraceutical preparation Chondroguard® TRIO as an element of nutritional support for patients with this disease. It is emphasized that it is advisable to develop a scientifically based rational approach to the treatment of OA that alleviates symptoms, reduces autoinflammatory affection of articular cartilage and improves its regeneration with the involvement of extracellular matrix components.

Osteoarthritis (OA) is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage. Traditional treatments for OA are limited to alleviating various OA symptoms. There is a lack of drugs available in clinical practice that can truly repair cartilage damage. Here, we developed the chondroitin sulfate analog CS-semi5, semi-synthesized from chondroitin sulfate A. In vivo, CS-semi5 alleviated inflammation, provided analgesic effects, and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model. A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats, revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment. Binding prediction revealed that miR-122-5p acted on the 3′-untranslated region of p38 mitogen-activated protein kinase, which was related to MMP13 regulation. Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis, which was further validated in the articular cartilage of OA rats. This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5, revealing its cartilage-protecting, anti-inflammatory, and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.

Abstract Most of the conditions involving cartilaginous tissues are irreversible and involve degenerative processes. The aim of the present study was to fabricate a biocompatible fibrous and film scaffolds using electrospinning and casting techniques to induce chondrogenic differentiation for possible application in cartilaginous tissue regeneration. Polycaprolactone (PCL) electrospun nanofibrous scaffolds and PCL film were fabricated and incorporated with multi-walled carbon nanotubes (MWCNTs). Thereafter, coating of chondroitin sulfate (CS) on the fibrous and film structures was applied to promote chondrogenic differentiation of human dental pulp stem cells (hDPSCs). First, the morphology, hydrophilicity and mechanical properties of the scaffolds were characterized by scanning electron microscopy (SEM), spectroscopic characterization, water contact angle measurements and tensile strength testing. Subsequently, the effects of the fabricated scaffolds on stimulating the proliferation of human dental pulp stem cells (hDPSCs) and inducing their chondrogenic differentiation were evaluated via electron microscopy, flow cytometry and RT‒PCR. The results of the study demonstrated that the different forms of the fabricated PCL-MWCNTs scaffolds analyzed demonstrated biocompatibility. The nanofilm structures demonstrated a higher rate of cellular proliferation, while the nanofibrous architecture of the scaffolds supported the cellular attachment and differentiation capacity of hDPSCs and was further enhanced with CS addition. In conclusion, the results of the present investigation highlighted the significance of this combination of parameters on the viability, proliferation and chondrogenic differentiation capacity of hDPSCs seeded on PCL-MWCNT scaffolds. This approach may be applied when designing PCL-based scaffolds for future cell-based therapeutic approaches developed for chondrogenic diseases.

In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Purpose: The study explored the enhanced skin moisturizing capabilities and moisture retention effects achieved by forming a polyion complex using sulfated glycosaminoglycan (GAG), specifically chondroitin sulfate (CS), and amino acids (AA) such as glutamine (Q) and arginine (R). The overall hydration effect of this CS‐AA complex was examined. Methods: After analyzing the CS‐AA polyion complex structure using spectroscopic methods, the ex vivo moisture retention ability was assessed under dry conditions using porcine skin samples. Additionally, the efficacy of the CS‐AA polyion complex in reducing transepidermal water loss (TEWL) and improving skin hydration was evaluated on human subjects using a digital evaporimeter and a corneometer, respectively. Results: Validating a systematic reduction in particle size, the following order was observed: CS > CS/AA simple mixture > CS‐AA complex based on dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. Furthermore, observations revealed that the CS‐AA complex exhibits negligible surface charge. Additionally, Fourier‐transform infrared spectroscopy (FT‐IR) analysis demonstrated a distinct peak shift in the complex, confirming the successful formation of the CS‐AA complex. Subsequently, the water‐holding effect through porcine skin was assessed, revealing a notable improvement in moisture retention (weight loss) for the CS‐Q complex: 40.6% (1 h), 20.5% (2 h), and 18.7% (4 h) compared to glycerin. Similarly, the CS‐R complex demonstrated enhancements of 50.2% (1 h), 37.5% (2 h), and 33% (4 h) compared to glycerin. Furthermore, TEWL improvement efficacy on human skin demonstrated approximately 25% improvement for both the CS‐Q complex and CS‐R complex, surpassing the modest 12.5% and 18% improvements witnessed with water and glycerin applications, respectively. Finally, employing a corneometer, hydration changes in the skin were monitored over 4 weeks. Although CS alone exhibited nominal alterations, the CS‐Q complex and CS‐R complex showed a significant increase in moisture levels after 4 weeks of application. Conclusion: In this study, polyion complexes were successfully formed between CS, a sulfated GAG, and AA. Comparisons with glycerin, a well‐known moisturizing agent, confirmed that the CS‐AA complex exhibits superior moisturizing effects in various aspects. These findings suggest that the CS‐AA complex is a more effective ingredient than CS or AA alone in terms of efficacy. [ABSTRACT FROM AUTHOR]

Chondroitin sulfate (CS) is a linear polysaccharide chain of alternating residues of glucuronic acid (GlcA) and N -acetylgalactosamine (GalNAc), modified with sulfate groups. Based on the structure, CS chains bind to bioactive molecules specifically and regulate their functions. For example, CS whose GalNAc is sulfated at the C4 position, termed CSA, and CS whose GalNAc is sulfated at both C4 and C6 positions, termed CSE, bind to a malaria protein VAR2CSA and receptor type of protein tyrosine phosphatase sigma (RPTPσ), respectively, in a specific manner. Here, we modified CSA and CSE chains with phosphatidylethanolamine (PE) at a reducing end, attached them to liposomes containing phospholipids and generated CSA and CSE liposomes. The CS-PE was incorporated into the liposome particles efficiently. Inhibition ELISA revealed specific interaction of CSA and CSE with recombinant VAR2CSA and RPTPσ, respectively, more efficiently than CS chains alone. Furthermore, CSE liposome was specifically incorporated into RPTPσ-expressing HEK293T cells. These results indicate CS liposome as a novel and efficient drug delivery system, especially for CS-binding molecules. [ABSTRACT FROM AUTHOR]

Presently, the clinical treatment of intervertebral disc degeneration (IVDD) remains challenging, but the strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) has become an effective way to alleviate IVDD. IL-1ra, a natural antagonist against IL-1β, can mitigate inflammation and promote regeneration in IVDD. Chondroitin sulfate (CS), an important component of the NP, can promote ECM synthesis and delay IVDD. Thus, these were chosen and integrated into functionalized microspheres to achieve their synergistic effects. First, CS-functionalized microspheres (GelMA-CS) with porous microstructure, good monodispersion, and about 200 µm diameter were efficiently and productively fabricated using microfluidic technology. After lyophilization, the microspheres with good local injection and tissue retention served as the loading platform for IL-1ra and achieved sustained release. In in vitro experiments, the IL-1ra-loaded microspheres exhibited good cytocompatibility and efficacy in inhibiting the inflammatory response of NP cells induced by lipopolysaccharide (LPS) and promoting the secretion of ECM. In in vivo experiments, the microspheres showed good histocompatibility, and local, minimally invasive injection of the IL-1ra-loaded microspheres could reduce inflammation, maintain the height of the intervertebral disc (IVD) and the water content of NP close to about 70 % in the sham group, and retain the integrated IVD structure. In summary, the GelMA-CS microspheres served as an effective loading platform for IL-1ra, eliminated inflammation through the controlled release of IL-1ra, and promoted ECM synthesis via CS to delay IVDD, thereby providing a promising intervention strategy for IVDD. The strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in nucleus pulposus (NP) has shown great potential prospects for alleviating intervertebral disc degeneration (IVDD). From the perspective of clinical translation, this study developed chondroitin sulfate functionalized microspheres to act as the effective delivery platform of IL-1ra, a natural antagonist of interleukin-1β. The IL-1ra loading microspheres (GelMA-CS-IL-1ra) showed good biocompatibility, good injection with tissue retention, and synergistic effects of inhibiting the inflammatory response induced by lipopolysaccharide and promoting the secretion of ECM in NPCs. In vivo , they also showed the beneficial effect of reducing the inflammatory response, maintaining the height of the intervertebral disc and the water content of the NP, and preserving the integrity of the intervertebral disc structure after only one injection. All demonstrated that the GelMA-CS-IL-1ra microspheres would have great promise for the minimally invasive treatment of IVDD. [Display omitted] [ABSTRACT FROM AUTHOR]

AbstractOsteoarthritis (OA) is a prevalent joint disorder characterized by cartilage and bone degradation. Medical therapies like glucosaminoglycan (GAG), chondroitin sulfate (CS), and hyaluronic acid (HA) aim to preserve joint function and reduce inflammation but may cause side effects when administered orally or via injection. Microneedle arrays (MNAs) offer a localized drug delivery method that reduces side effects. Thus, this study aims to demonstrate the feasibility of delivering GAG, CS, and HA using microneedles in vitro. An optimal needle geometry is crucial for the successful application of MNA. To address this, here we employ a multi-objective optimization framework using the non-dominated sorting genetic algorithm II (NSGA-II) to determine the ideal MNA design, focusing on preventing needle failure. Then, a three-step fabrication approach is followed to fabricate the MNAs. First, the master (male) molds are fabricated from poly(methyl methacrylate) using mechanical micromachining based on optimized needle geometry. Second, a micro-molding with Polydimethylsiloxane (PDMS) is used for the fabrication of production (female) molds. In the last step, the MNAs were fabricated by microcasting the hydrogels using the production molds. Light microscopy (LIMI) confirms the accuracy of the MNAs manufactured, and in vitro skin insertion tests demonstrate failure-free needle insertion. Subsequently, we confirmed the biocompatibility of MNAs by evaluating their impact on the L929 fibroblast cell line, human chondrocytes, and osteoblasts. [ABSTRACT FROM AUTHOR]

AbstractPolyetheretherketone (PEEK) implants have emerged as a clinically favored alternative to titanium alloy implants for cranial bone substitutes due to their excellent mechanical properties and biocompatibility. However, the biological inertness of PEEK has hindered its clinical application. To address this issue, we developed a dual-functional surface modification method aimed at enhancing both osteogenesis and antibacterial activity, which was achieved through the sustained release of chondroitin sulfate (CS) and levofloxacin (LVFX) from a biomimetic polydopamine (PDA) coating on the PEEK surface. CS was introduced to promote cell adhesion and osteogenic differentiation. Meanwhile, incorporation of antibiotic LVFX was essential to prevent infections, which are a critical concern in bone defect repairing. To our delight, experiment results demonstrated that the SPKD/CS-LVFX specimen exhibited enhanced hydrophilicity and sustained drug release profiles. Furthermore, in vitro experiments showed that cell growth and adhesion, cell viability, and osteogenic differentiation of mouse calvaria-derived osteoblast precursor (MC3T3-E1) cells were significantly improved on the SPKD/CS-LVFX coating. Antibacterial assays also confirmed that the SPKD/CS-LVFX specimen effectively inhibited the growth of Escherichia coli and Staphylococcus aureus, attributable to the antibiotic LVFX released from the PDA coating. To sum up, this dual-functional PEEK implant showed a promising potential for clinical application in bone defects repairing, providing excellent osteogenic and antibacterial properties through a synergistic approach. [ABSTRACT FROM AUTHOR]

Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (n  = 81) and mouse (n  = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-glycosaminoglycans and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress impacts these PNN features discovered that although early-life stress increases WFL+ PNN density, the CS-glycosaminoglycan sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage. Traditional treatments for OA are limited to alleviating various OA symptoms. There is a lack of drugs available in clinical practice that can truly repair cartilage damage. Here, we developed the chondroitin sulfate analog CS-semi5, semi-synthesized from chondroitin sulfate A. In vivo , CS-semi5 alleviated inflammation, provided analgesic effects, and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model. A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats, revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment. Binding prediction revealed that miR-122-5p acted on the 3′-untranslated region of p38 mitogen-activated protein kinase, which was related to MMP13 regulation. Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis, which was further validated in the articular cartilage of OA rats. This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5, revealing its cartilage-protecting, anti-inflammatory, and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway. Semi-synthesized chondroitin sulfate CS-semi5 effectively alleviated inflammation, provided analgesic effects and protected cartilage via miR-122-5p/p38/MMP13 axis. [Display omitted] [ABSTRACT FROM AUTHOR]

Pregnant women with chronic kidney disease (CKD) face increased risks of adverse outcomes in their adult offspring. Offspring rats born to dams fed an adenine diet develop hypertension, coinciding with dysregulated hydrogen sulfide (H2S) and nitric oxide (NO) pathways, as well as alterations in gut microbiota. Chondroitin sulfate (CS) is a multifunctional food known for its diverse bioactivities. As a sulfate prebiotic, CS has shown therapeutic potential in various diseases. Here, we investigated the protective effects of maternal CS supplementation against hypertension in offspring induced by an adenine diet. Mother rats were administered regular chow, 0.5% adenine, 3% CS, or a combination throughout gestation and lactation. Maternal CS supplementation effectively protected offspring from hypertension induced by the adenine diet. These beneficial effects of CS were connected with increased renal mRNA and protein levels of 3-mercaptopyruvate sulfurtransferase, an enzyme involved in H2S production. Furthermore, maternal CS treatment significantly enhanced alpha diversity and altered beta diversity of gut microbiota in adult offspring. Specifically, perinatal CS treatment promoted the abundance of beneficial microbes such as Roseburia hominis and Ruminococcus gauvreauii. In conclusion, perinatal CS treatment mitigates offspring hypertension associated with maternal adenine diet, suggesting that early administration of sulfate prebiotics may hold preventive potential. These findings warrant further translational research to explore their clinical implications. [ABSTRACT FROM AUTHOR]

Most of the conditions involving cartilaginous tissues are irreversible and involve degenerative processes. The aim of the present study was to fabricate a biocompatible fibrous and film scaffolds using electrospinning and casting techniques to induce chondrogenic differentiation for possible application in cartilaginous tissue regeneration. Polycaprolactone (PCL) electrospun nanofibrous scaffolds and PCL film were fabricated and incorporated with multi-walled carbon nanotubes (MWCNTs). Thereafter, coating of chondroitin sulfate (CS) on the fibrous and film structures was applied to promote chondrogenic differentiation of human dental pulp stem cells (hDPSCs). First, the morphology, hydrophilicity and mechanical properties of the scaffolds were characterized by scanning electron microscopy (SEM), spectroscopic characterization, water contact angle measurements and tensile strength testing. Subsequently, the effects of the fabricated scaffolds on stimulating the proliferation of human dental pulp stem cells (hDPSCs) and inducing their chondrogenic differentiation were evaluated via electron microscopy, flow cytometry and RT‒PCR. The results of the study demonstrated that the different forms of the fabricated PCL-MWCNTs scaffolds analyzed demonstrated biocompatibility. The nanofilm structures demonstrated a higher rate of cellular proliferation, while the nanofibrous architecture of the scaffolds supported the cellular attachment and differentiation capacity of hDPSCs and was further enhanced with CS addition. In conclusion, the results of the present investigation highlighted the significance of this combination of parameters on the viability, proliferation and chondrogenic differentiation capacity of hDPSCs seeded on PCL-MWCNT scaffolds. This approach may be applied when designing PCL-based scaffolds for future cell-based therapeutic approaches developed for chondrogenic diseases. [ABSTRACT FROM AUTHOR]

The objective of the present study was to assess the effect of intra-articular Hyaluronic acid (HA) and Chondroitin sulfate (CS) supplementation (Hialurom® Hondro (HH)) on pain symptoms and joint mobility. In total, 60 mg/mL sodium hyaluronate and 90 mg/mL CS were administered to 21 patients (17 females and 4 males) respecting the in-force requirements, excluding patients with some specific comorbidities. In addition to the clinical study (where the pain intensity (severity) and joint mobility were assessed), rheological characterization was conducted evaluating the following parameters: elastic modulus (G′), loss modulus (G″) oscillatory frequency (fc) at 0.5 Hz and 2.5 Hz, crossover frequency (fc), relaxation time (λ) where it was noticed that the addition of chondroitin sulfate (CS) to sodium hyaluronate (SH) significantly enhances and improves the viscoelastic properties, particularly at higher shear frequencies. A significant decrease in pain intensity felt by the subjects was found, from 7.48 (according to Wong–Baker scale)—pain close to 8 (the patient is unable to perform most activities), to more reduced values of 5.86—at 6 weeks after injection, 4.81—at 3 months after injection, and 5.24—at 6 months after injection, improvements in symptoms was fast and durable. Data related to the evolution of joint mobility show that at 6 weeks after injection, the mobility of joints increased by 17.8% and at 6 months by 35.61%. No serious adverse events were reported with undesired effects so that they would impose additional measures. Better resistance to enzymatic degradation and free radicals could be expected from the synergic combination of sodium hyaluronate and chondroitin sodium sulfate, this having a special importance for the patients, granting them the ability to perform more ample movements and reducing dependency on attendants, thus increasing quality of life. [ABSTRACT FROM AUTHOR]

Cryogels represent a valid strategy as scaffolds for tissue engineering. In order to adequately support adhesion and proliferation of anchorage-dependent cells, different polymers need to be combined within the same scaffold trying to mimic the complex features of a natural extracellular matrix (ECM). For this reason, in this work, gelatin (Gel) and chondroitin sulfate (CS), both functionalized with methacrylic groups to produce CSMA and GelMA derivatives, were selected to prepare cryogel networks. Both homopolymer and heteropolymer cryogels were produced, via radical crosslinking reactions carried out at −12 °C for 2 h. All the scaffolds were characterized for their mechanical, swelling and morphological properties, before and after autoclave sterilization. Moreover, they were evaluated for their biocompatibility and ability to support the adhesion of human gingival fibroblasts and tenocytes. GelMA-based homopolymer networks better withstood the autoclave sterilization process, compared to CSMA cryogels. Indeed, GelMA cryogels showed a decrease in stiffness of approximately 30%, whereas CSMA cryogels of approximately 80%. When GelMA and CSMA were blended in the same network, an intermediate outcome was observed. However, the hybrid scaffolds showed a general worsening of the biological performance. Indeed, despite their ability to withstand autoclave sterilization with limited modification of the mechanical and morphological properties, the hybrid cryogels exhibited poor cell adhesion and high LDH leakage. Therefore, not only do network components need to be properly selected, but also their combination and ability to withstand effective sterilization process should be carefully evaluated for the development of efficient scaffolds designed for tissue engineering purposes. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the anti‐cervical cancer activity of chondroitin sulfate–functionalized selenium nanoparticles (SeCS) and to elucidate their action mechanism. Cytotoxic effect of SeCS on HeLa cells was assessed by MTT assay. Further molecular mechanism of SeCS was analyzed by flow cytometric assay and western blotting. The results showed that treatment with SeCS resulted in a dose‐ and time‐dependent inhibition in the proliferation of HeLa cells. The data obtained from flow cytometry demonstrated that SeCS inhibited HeLa cell growth via the induction of S‐phase arrest and cell apoptosis. Further mechanism analysis found that SeCS down‐regulated expression levels of cyclin A and CDK2 and up‐regulated p21 expression, which contributed to S arrest. Moreover, SeCS increased the level of Bax and decreased the expression of Bcl‐2, resulting in the release of cytochrome C from mitochondria and activating caspase‐3/8/9 for caspase‐dependent apoptosis. Meanwhile, intracellular reactive oxygen species (ROS) levels were elevated after SeCS treatment, suggesting that ROS might be upstream of SeCS‐induced S‐phase arrest and cell apoptosis. These data show that SeCS has anti‐tumor effects and possesses the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. Practical Application: In our previous study, we used chondroitin sulfate to stabilize nano‐selenium to obtain SeCS to improve the bioactivity and stability of nano‐selenium. We found that it possessed an inhibitory effect on HeLa cells. However, the molecular mechanism remains unclear. This study elucidated the mechanism of SeCS damage to HeLa cells. SeCS has the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. [ABSTRACT FROM AUTHOR]

Background Glycosaminoglycans (GAGs) are a family of polysaccharides found abundantly in the extracellular matrix (ECM) of tissues. Research has indicated that the dysregulation of ECM, including changes and disruptions in GAGs, contributes to various cancer hallmarks such as metabolic reprogramming, persistent growth signals, immunosuppression, angiogenesis, tumor invasion, and metastasis. Objective This systematic review aims to evaluate the diagnostic accuracy of GAGs, including heparan sulfate (HS), chondroitin sulfate (CS), and hyaluronic acid (HA), in early detection of cancer. Method Four databases (PubMed, Scopus, EBSCO, and Ovid) were searched for studies in English within the last 15 years, involving at least 50 human participants. Using a two-stage process: identification and screening, 11 articles were selected and critically appraised using Critical Appraisal Skills Programme (CASP) checklists and Newcastle-Ottawa Scale (NOS) appropriate for each study design. Result Eleven studies met the inclusion criteria, encompassing various cancers like renal cell carcinoma (RCC), upper GI cancer (UGI), ovarian cancer, prostate cancer, breast cancer, lung cancer, colorectal cancer and oral cancer. Methodological quality was assessed using two established tools, with no studies exhibiting a high risk of bias. Heparan sulfate levels showed diagnostic potential in renal cancer with a maximum accuracy of 98.9%, achieving 94.7% specificity and 100% sensitivity. Chondroitin sulfate disaccharides emerged as a promising diagnostic marker in ovarian cancer and showed potential as diagnostic markers in renal cancer. However, there were no statistically significant differences in urinary chondroitin sulfate levels between patients and controls in prostate cancer. In breast cancer, hyaluronic acid showed moderate accuracy (AUC = 0.792) in distinguishing metastatic from non-metastatic disease, and a composite score incorporating multiple markers, including HA, showed even higher accuracy (AUC = 0.901) in detecting metastatic breast cancer. HA demonstrated moderate diagnostic accuracy for UGI cancers. Serum HA levels were significantly elevated in patients with oral cancer and pleural malignant mesothelioma and associated with tumor progression in patients with lung cancer. Elevated low molecular weight form of hyaluronan (~6 k Da HA) levels were found in colorectal cancer tissues. Conclusion GAGs hold potential as early cancer detection biomarkers. Further validation with larger, diverse populations is needed to validate their diagnostic accuracy and clinical utility.

Background. The urgency of pain relief and patient improvement necessitates evaluating the most effective treatment approaches. This includes a comparative analysis of medications with different mechanisms of action, both taken individually and in combination while considering potential drug toxicity and individual patient intolerances. The study purposed to assess the efficacy of a bioactive concentrate derived from marine fish (BCMF), both alone and in combination with a non-steroidal anti-inflammatory drug (NSAID), for the treatment of back pain, in comparison to therapy involving solely oral sodium chondroitin sulfate (CS). Materials and methods. We examined four groups of patients, each comprising 30 male or female subjects with complaints of back pain. Each group was administered one of three medications: NSAIDs in a standard dosage, CS in a daily dose of 1 g (two capsules of 500 mg each), and BCMF in the form of intramuscular injections in a daily dose of 1 ml (0.2 ml per injection). The fourth group of patients received combined treatment, namely, 1 ml of BCMF and NSAIDs in a standard dosage daily. All parti­cipants underwent laboratory tests and instrumental examinations. ­Results. The administration of BCMF, both alone and in combination with NSAIDs resulted in an improved subjective assessment of patients’ psychoemotional well-being, marked by reduced back pain intensity, enhanced quality of life indices, and diminished le­vels of anxiety and depression. The combination of BCMF with NSAIDs demonstrated a more pronounced effect on redu­cing tumor necrosis factor α serum concentration than monothe­rapy with BCMF. The combination therapy positively impacted the condition of lower extremity vessels as indicated by Doppler ultrasonography. Conclusions. BCMF can be an effective addition to the standard therapy of back pain.

Aims: To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment. Methods: Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue. Results: This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as CHL1 (false discovery rate (FDR) = 2.11 × 10-11), RIC8A (FDR = 7.05 × 10-4), and SOX12 (FDR = 1.43 × 10-3). Additionally, RIC8A and CHL1 were hypermethylated in responders, while SOX12 was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in TESPA1 and ATP11A exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells. Conclusion: Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients. Cite this article: Bone Joint Res 2024;13(5):237–246.

Activated platelets (PLT) could adhere to tumor cells to promote tumor progression and metastasis. Therefore, inhibiting platelet activation and blocking the interaction between tumor cells and platelets are an effective approach to inhibit distal tumor metastasis. In this study, chondroitin sulfate (CS)–glycyrrhetinic acid (GA) dual ligand-modified liposomes (CS–GA–LIP) were prepared for codelivery of aspirin (ASP) and curcumin (CUR). In order to simulate the tumor microenvironment, we established the "HuH-7 + PLT" in vitro coculture cell model and the "H22 + NIH/3T3" coinjected mice model. Physicochemical analysis showed that the particle size of CUR&ASP/CS–GA–LIP was 133.27 nm with high stability. In vitro studies found that CUR&ASP/CS–GA–LIP could target both hepatocellular carcinoma cells and platelets, enhance drug retention in tumor cells, and effectively inhibit tumor proliferation and migration. In addition, in vivo antitumor results demonstrated that CUR&ASP/CS–GA–LIP could aggregate in tumor tissues, inhibit platelet activation and neoangiogenesis, and down-regulate the expression of matrix metalloproteinase 2 (MMP-2), exhibiting strong antiproliferative and antipulmonary metastatic abilities. Consequently, the combination therapy based on CS–GA–LIP might be a valuable antihepatocellular carcinoma strategy. [ABSTRACT FROM AUTHOR]

Aim: This study was aimed to assess the efficacy and safety of two oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs)—Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA). Methods: This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar, using the search terms—Glucosamine sulfate (GS), Chondroitin sulfate (CS), Knee osteoarthritis, Joint pain, Joint disease, and Joint structure, for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration's Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination. Results: Twenty-five randomized controlled trials (RCTs) were included in this systematic review. In short, exclusively 9 RCTs for GS, 13 RCTs for CS, and 3 RCTs for the combination of GS and CS. All these studies had their treatment groups compared with placebo. In the meta-analysis, CS showed a significant reduction in pain intensity, and improved physical function compared to the placebo; GS showed a significant reduction in tibiofemoral joint space narrowing. While the combination of GS and CS showed neither a reduction in pain intensity, nor any improvement in the physical function. However, the combination exhibited a non-significant reduction in joint space narrowing. In the safety evaluation, both CS and GS have shown good safety profile and were well tolerated. Conclusion: This meta-analysis revealed that the CS (with decreased pain intensity and improvement in the physical function), and GS (with significant reduction in the joint space narrowing) have significant therapeutic benefits. However, their combination did not significantly improve the symptoms or modify the disease. This may be due to the limited trials that are available on the combination of the sulfate forms of the intervention. Hence, there is a scope for conducting multicentric randomised controlled trials to evaluate and conclude the therapeutic role of CS and GS combination in the management of KOA. [ABSTRACT FROM AUTHOR]

Oil-core nanocapsules (NCs, also known as nanoemulsions) are of great interest due to their application as efficient carriers of various lipophilic bioactives, such as drugs. Here, we reported for the first time the preparation and characterization of NCs consisting of chondroitin sulfate (CS)-based shells and liquid oil cores. For this purpose, two amphiphilic CS derivatives (AmCSs) were obtained by grafting the polysaccharide chain with octadecyl or oleyl groups. AmCS-based NCs were prepared by an ultrasound-assisted emulsification of an oil phase consisting of a mixture of triglyceride oil and vitamin E in a dispersion of AmCSs. Dynamic light scattering and cryo-transmission electron microscopy showed that the as-prepared core–shell NCs have typical diameters in the range of 30–250 nm and spherical morphology. Since CS is a strong polyanion, these particles have a very low surface potential, which promotes their stabilization. The cytotoxicity of the CS derivatives and CS-based NCs and their impact on cell proliferation were analyzed using human keratinocytes (HaCaTs) and primary human skin fibroblasts (HSFs). In vitro studies showed that AmCSs dispersed in an aqueous medium, exhibiting mild cytotoxicity against HaCaTs, while for HSFs, the harmful effect was observed only for the CS derivative with octadecyl side groups. However, the nanocapsules coated with AmCSs, especially those filled with vitamin E, show high biocompatibility with human skin cells. Due to their stability under physiological conditions, the high encapsulation efficiency of their hydrophobic compounds, and biocompatibility, AmCS-based NCs are promising carriers for the topical delivery of lipophilic bioactive compounds. [ABSTRACT FROM AUTHOR]

The effects of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB), which removes the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate, on the expression of PD-L1 were determined, and the underlying mechanism of PD-L1 expression was elucidated. Initial experiments in human melanoma cells (A375) showed that PD-L1 expression increased from 357 ± 31 to 796 ± 50 pg/mg protein (p < 10−11) when ARSB was silenced in A375 cells. In subcutaneous B16F10 murine melanomas, PD-L1 declined from 1227 ± 189 to 583 ± 110 pg/mg protein (p = 1.67 × 10−7), a decline of 52%, following treatment with exogenous, bioactive recombinant ARSB. This decline occurred in association with reduced tumor growth and prolongation of survival, as previously reported. The mechanism of regulation of PD-L1 expression by ARSB is attributed to ARSB-mediated alteration in chondroitin 4-sulfation, leading to changes in free galectin-3, c-Jun nuclear localization, HDAC3 expression, and effects of acetyl-H3 on the PD-L1 promoter. These findings indicate that changes in ARSB contribute to the expression of PD-L1 in melanoma and can thereby affect the immune checkpoint response. Exogenous ARSB acted on melanoma cells and normal melanocytes through the IGF2 receptor. The decline in PD-L1 expression by exogenous ARSB may contribute to the impact of ARSB on melanoma progression. [ABSTRACT FROM AUTHOR]

Background: Condoliase is an enzyme used as a treatment for lumbar disc herniation (LDH). This enzyme degrades chondroitin sulfate (CS) in the nucleus pulposus of the intervertebral disc (IVD). However, there are cases in which symptoms do not improve, despite condoliase administration. This study reports histological analysis of lumbar disc tissue of LDH patients who underwent surgery because condoliase had no therapeutic effect. Methods: Between March 2019 and August 2019, 12 LDH patients who underwent full endoscopic spine surgery (FESS) discectomy at the Dezawa Akira PED Clinic were the subjects of the study. There are two study groups: six cases underwent FESS after condoliase administration, while six underwent FESS without condoliase administration. The average duration from drug administration to surgery was 152 days. Herniated disc removed at surgery was evaluated by histological staining including immunohistochemistry by anti‐CS antibodies. Results: Multiple large clusters (40–120 μm in diameter) were observed in the nucleus pulposus of those who received condoliase, but no clusters were observed in those who did not. The lumbar disc tissues, including the nucleus pulposus of recipients, were stained with anti‐CS antibodies that recognize the CS unsaturated disaccharide, but non‐administration tissue was not stained. These findings suggest that the enzyme acted on the nucleus pulposus, even in cases where symptoms were not improved by condoliase administration. Furthermore, there was no histological difference between stained images of the extracellular matrix in those who did or did not receive condoliase, suggesting that condoliase acted specifically on CS in the nucleus pulposus. Conclusions: We demonstrated that CS in the nucleus pulposus was degraded in patients in whom condoliase did not have a therapeutic effect. Moreover, condoliase acts in human IVD without causing necrosis of chondrocytes and surrounding tissues. [ABSTRACT FROM AUTHOR]

In the context of aging and age-associated neurodegenerative disorders, the brain's extracellular matrix (ECM) serves as a critical regulator for neuronal health and cognitive function. Within the extracellular space, proteoglycans and their glycosaminoglycan attachments play essential roles in forming, stabilizing, and protecting neural circuits throughout neurodevelopment and adulthood. Recent studies in rodents reveal that chondroitin sulfate-glycosaminoglycan (CS-GAG) containing perineuronal nets (PNNs) exhibit both structural and compositional differences throughout the brain. While animal studies are illuminating, additional research is required to translate these interregional PNN/CS-GAG variations to human brain tissue. In this perspective article, we first investigate the translational potential for interregional CS-GAG variances across species as novel targets for region-specific therapeutic development. We specifically focus on the observation that alterations in brain PNN-associated CS-GAGs have been linked with the progression of Alzheimer's disease (AD) neuropathology in humans, but these changes have not been fully recapitulated in rodent models of this disease. A second highlight of this perspective article investigates whether AD-associated shifts in CS-GAGs in humans may be dependent on region-specific baseline differences in CS-GAG sulfation patterning. The current findings begin to disentangle the intricate relationships between the interregional differences in brain PNN/CS-GAG matrices across species, while emphasizing the need to better understand the close relationship between dementia and changes in brain CS-GAG sulfation patterns in patients with AD and related dementias. [ABSTRACT FROM AUTHOR]

In this research, we demonstrated a chondroitin sulfate (CHS), polyvinylpyrrolidone (PVP), and 2-acrylamide-2-methylpropane sulphonic acid (AMPS)-based captopril-loaded mucoadhesive hydrogel that efficiently facilitated the sustained release of drug molecules and is developed by radical polymerization technique. The designed hydrogel network is initially analyzed for the influence of different formulation ingredients as well as their quantities on swelling behavior and mucoadhesion capacity. The physical interaction along with biocompatibility of CHS/PVP-co-poly (AMPS) hydrogels is illustrated by utilizing FT-IR and histopathological analysis. Thermal stability, conversion of crystalline nature ingredient to amorphous nature hydrogel matrix, prolonged and sustained in vitro released behavior at 1.2 pH, porous surface morphology, and enhanced mucoadhesive characteristics are ensured by thermal analysis, XRD, drug in vitro released profile, SEM, and ex-vivo mucoadhesive analysis. Interestingly, the findings suggest that CHS/PVP-co-poly (AMPS)-based hydrogel systems are viable candidates for sustained delivery of captopril by enhancing its adherence with the gastric mucus layer and decreasing its dose frequency. [ABSTRACT FROM AUTHOR]

Aim: Cell microenvironment contains a plethora of information that influences cell modulation. Indeed, the extracellular matrix plays a central role in tissue development. Reproducing the cell–extracellular matrix crosstalk able to recapitulate both physical and biochemical signals is crucial to obtain functional tissue models or regenerative strategies. Materials & methods: Here, a combined method is proposed to easily functionalize collagen surface films, tailoring morphological properties. Oxygen nonthermal plasma treatment and glyco-conjugation with chondroitin sulfate are used to modify surface properties. Results: It results in higher adhesion, proliferation and morphological organization of U87 glioblastoma cells. Conclusion: Our finding suggests new promising strategies for the development of collagen-based biomaterials, which can be employed for advanced in vitro models. [ABSTRACT FROM AUTHOR]

Background. The urgency of pain relief and patient improvement necessitates evaluating the most effective treatment approaches. This includes a comparative analysis of medications with different mechanisms of action, both taken individually and in combination while considering potential drug toxicity and individual patient intolerances. The study purposed to assess the efficacy of a bioactive concentrate derived from marine fish (BCMF), both alone and in combination with a non-steroidal anti-inflammatory drug (NSAID), for the treatment of back pain, in comparison to therapy involving solely oral sodium chondroitin sulfate (CS). Materials and methods. We examined four groups of patients, each comprising 30 male or female subjects with complaints of back pain. Each group was administered one of three medications: NSAIDs in a standard dosage, CS in a daily dose of 1 g (two capsules of 500 mg each), and BCMF in the form of intramuscular injections in a daily dose of 1 ml (0.2 ml per injection). The fourth group of patients received combined treatment, namely, 1 ml of BCMF and NSAIDs in a standard dosage daily. All participants underwent laboratory tests and instrumental examinations. Results. The administration of BCMF, both alone and in combination with NSAIDs resulted in an improved subjective assessment of patients’ psych-oemotional well-being, marked by reduced back pain intensity, enhanced quality of life indices, and diminished levels of anxiety and depression. The combination of BCMF with NSAIDs demonstrated a more pronounced effect on reducing tumor necrosis factor α serum concentration than monotherapy with BCMF. The combination therapy positively impacted the condition of lower extremity vessels as indicated by Doppler ultrasonography. Conclusions. BCMF can be an effective addition to the standard therapy of back pain. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a persistent joint condition resulting from the disturbance of joint homeostasis due to various systemic and biomechanical factors. This condition is marked by the deterioration of cartilage and other joint tissues, accompanied by low-grade inflammation that can lead to symptoms such as pain, diminished function, and disability. Objective. The study assessed the impact of frequently prescribed pharmacological treatments on structural changes in the knee among participants experiencing progressive OA using MRI. Material and Methods. The study was conducted on a number of 34 patients with bilateral knee OA (22 women and 12 men), aged between 35 and 78 years. Selected patients were evaluated at the initial visit, then 6 months after administration of glucosamine, chondroitin sulfate and Harpagophytum procumbens therapy. From a clinical point of view, morning stiffness and pain intensity (visual analogue scale – VAS), knee mobility and functionality were quantified with the help of the WOMAC and the quality-of-life questionnaire (HAQ – 20 items). In terms of imaging evaluation bilateral knee MRI was performed. Measurements of the cartilage thickness were performed both at the level of the lateral and medial condyles, as well as intercondylar. Outcomes. The average age of onset of OA was 55.06 ± 10.05 years. The mean duration of the disease at the time of inclusion was 6.32±3.45 years. The mean VAS value at baseline was 73 ± 9.90 mm. The degree of OA was quantified on the Kellgren-Lawrence scale up to grade III disease severity. The use of slow-acting symptomatic agents (SYSADOA) resulted in a reduced need for administration of analgesic and anti-inflammatory therapy, leading to diminished side effects associated with these drugs. Thus, spontaneous pain and assessed functionality improved significantly, with symptom improvement reaching up to 25%. In addition, SYSADOA therapy resulted in a delay in imaging progression of knee OA, with improvement in femoral hyaline cartilage thickness in all compartments. The MRI results did not show a statistically significant difference between the thickness of the femoral hyaline cartilage, between the first and the second imaging evaluation. Thus, between baseline and the 6-month visit, femoral cartilage thickness appears to be maintained, even showing a slight increase after SYSADOA treatment. Conclusions. SYSADOA administration delays the radiographic progression of knee OA, with preservation, even modest improvement in hyaline cartilage thickness, making MRI an important tool in the evaluation and monitoring of OA. An increase in patients’ quality of life in terms of both pain and functionality was also reported. [ABSTRACT FROM AUTHOR]

BACKGROUND: In this study, a biocompatible nano‐carrying platform using chitosan (ChI) and chondroitin sulfate (ChS) was developed for the encapsulation of cobia liver oil (CBLO) to prevent its oxidation and improve its absorption. An ionic gelation method was applied to encapsulate CBLO with different weight ratios (from 1.0 to 1.5) to obtain ChS‐ChI nano‐capsules (ChS‐ChI@CBLO NCs). RESULTS: Morphological observations of the nano‐capsules revealed a spherical shape and diameter around 267–381 nm. The maximum loading capacity (LC) and encapsulation efficiency (EE) for ChS‐ChI@CBLO NCs estimated by thermogravimetric analysis (TGA) and derivative thermogravimetric (DTG) analysis were 25.7% and 56.2%, respectively. The structural stability of ChS‐ChI@CBLO NCs was confirmed through differential scanning calorimetry (DSC) and X‐ray diffraction (XRD) analysis; moreover DSC also further confirmed the oxidative stability of ChS‐ChI@CBLO NCs. Fourier‐transform infrared (FTIR) spectra confirmed the excellent stability of ChS‐ChI@CBLO NCs against high temperature and sunlight exposure. Biocompatibility analysis also verified the non‐toxicity of ChS‐ChI@CBLO NCs, further indicating safety and potential application in complex‐nutritional supplements. CONCLUSION: Nano‐degree of ChS‐ChI@CBLO NCs has a loading capacity and encapsulation efficiency of around 16.5 ~ 25.7% and 33.4 ~ 56.2%, respectively, for encapsulation of CBLO. Characterization results also indicate that ChS‐ChI@CBLO NCs display high oxidative stability against long‐term, hyperthermal, and sunlight exposure. Bioassay results confirm that the ChS‐ChI@CBLO NCs are safe and non‐toxic. This study demonstrates that nano‐capsules are also beneficial in preventing sensitive compounds from metamorphosis, and are non‐toxic. These materials are suitable for use in the food and pharmaceutical industries. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]