Extraction and characterization of valuable compounds from chicken sternal cartilage: Type II collagen and chondroitin sulfate.

Type II collagen (Col II) and chondroitin sulfate (CS) are the main macromolecules in the extracellular matrix. This study investigated the characteristics of Col II and CS obtained from chicken sternal cartilage (CSC) via enzymatic hydrolysis for various treatment times. For Col II and CS, the highest efficiency of enzymatic hydrolysis was achieved after 24 and 6 h of treatment, respectively. The average molecular weights were α1 chain-130 kDa, ß chain-270 kDa for Col II, and 80.27 kDa for CS. Fourier transform infrared spectroscopy revealed that the Col II samples maintained their triple-helical structure and that the predominant type of CS was chondroitin-4-sulfate. Scanning electron microscopy revealed that the Col II and CS samples possessed fibrillar and clustered structures, respectively. This study suggests that collagen and CS obtained from CSC can be used as promising molecules for application in food and pharmaceutical industries.

Transient CAR T cells with specificity to oncofetal glycosaminoglycans in solid tumors.

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.

Exploring the mechanism of chondroitin sulfate-selenium nanoparticles in improving Alzheimer's disease: Insights from intestinal flora evaluation.

In this study we have investigated the effect of chondroitin sulfate-selenium nanoparticles (CS@Se) on Alzheimer's disease (AD) mice using 16S rDNA technique. We randomly divided 30 SPF grade male C57BL/6 J mice into 6 groups according to random number table method. The AD mouse model was established by subcutaneous injection of D-galactose (D-gal) combined with gavage of AlCl3 for 30 consecutive days, and then drug intervention was performed in the administration group for 40 consecutive days. The findings demonstrated several positive effects of CS@Se on AD mice. Firstly, CS@Se improved spatial learning and memory problems and reduces anxiety in AD mice. It also significantly reduced pyramidal cell arrangement disorder and rupture, leading to an improvement in synaptic structure damage between hippocampal neurons. Furthermore, CS@Se reduced mitochondrial swelling and vacuolation while increasing neuron survival in AD mice. Moreover, CS@Se significantly impacted the diversity and richness of intestinal flora in AD mice. It increased the relative abundance of Firmicutes and Actinobacteria while reducing the relative abundance of Bacteroidetes and Proteobacteria. In conclusion, CS@Se effectively reduced the breakdown of hippocampal pyramidal cells, improved the superfiber structure of hippocampal neurons, and restored intestinal flora balance, ultimately contributing to improving learning and memory abilities and alleviating anxiety in AD mice.

Metabolomic analysis reveals the potential of fucosylated chondroitin sulfate from sea cucumber in modulating metabolic homeostasis.

In this study, we prepared four derivatives of fucosylated chondroitin sulfate (FCS): full-length FCS (flFCS) from Holothuria leucospilota, low molecular weight FCS (lmFCS) derived from flFCS, and their de-branched counterparts, de-branched flFCS (d-flFCS) and de-branched lmFCS (d-lmFCS) via controlled acid treatment. Following structural verification using various analytical techniques, we applied targeted metabolomics to examine the impact of FCS on nutritional efficacy and its structure-activity relationship. Analysis of 225 plasma and feces samples from 75 mice revealed a positive correlation between metabolomic shifts and increased weight gain, underscoring FCS's potential to enhance nutrient absorption and promote growth. The observed linear relationship between the levels of short-chain fatty acids in plasma and feces suggests that FCS may facilitate catabolic activities in the gastrointestinal tract. The comparative study of different FCS derivatives on mouse growth and metabolic homeostasis regulation led to the conclusion that FCS exhibits greater biological activity with a higher degree of branching and larger molecular weight.

Fine-tuning the cytotoxicity profile of N,N,N-trimethyl chitosan through trimethylation, molecular weight, and polyelectrolyte complex nanoparticles.

N,N,N-trimethyl chitosan (TMC) is a promising biopolymer for pharmaceutical applications due to its enhanced solubility and bioadhesive properties, though its cytotoxic limitations necessitate careful modification to ensure safety and efficacy. This study sought to investigate whether nanoparticle (NP) formation could reduce the anticipated cytotoxic effects of TMC, thus improving its applicability across a wider spectrum of pharmaceutical uses. TMC's capability to form NPs with anionic polyelectrolytes led to the application of chondroitin sulfate (ChS) in this study. Five TMC samples, varying in degree of trimethylation (DTM 23, 32, 46, 50 and 99 %) and molecular weight (Mw, 66-290 kDa) were synthesized, and their biocompatibility with human umbilical vein endothelial cells (HUVECs) was assessed. The results revealed a discernible impact of both DTM and Mw on cell viability, with higher DTM and lower Mw correlating with increased toxicity. Cytotoxicity studies against ovarian cancer cell lines SKOV-3 and OVISE showed a clear indication of a higher cytotoxic effect of TMC samples against cancer cells compared to healthy cells (HUVEC). The cytotoxicity against cancer cells also indicated an optimal DTM for maximum efficacy, deviating from a linear trend. The effects of Mw were cell-dependent, introducing complexity to the observed relationship. Additionally, TMC-ChS NPs were successfully prepared, demonstrating a substantial reduction in cytotoxicity compared to TMC alone in all tested cells. This promising outcome suggests the potential of NP formation to fine-tune the cytotoxicity profile of TMC, paving the way for the development of safer and more effective pharmaceutical formulations.

Dengue Envelope Protein as a Cytotoxic Factor Inducing Hemorrhage and Endothelial Cell Death in Mice.

Dengue virus (DENV) infection, prevalent in tropical and subtropical regions, can progress to dengue hemorrhagic fever (DHF), which increases mortality during secondary infections. DHF is characterized by endothelial damage and vascular leakage. Despite its severity, no specific antiviral treatments exist, and the viral factors responsible for endothelial damage remain unclear. This study examines the role of the DENV envelope protein domain III (EIII) in inducing endothelial apoptosis using a mouse model. Additionally, we aim to explore whether cell death-inducing pathways could serve as drug targets to ameliorate EIII-induced endothelial injury and hemorrhage. In vitro experiments using human endothelial HMEC-1 cells demonstrated that both recombinant EIII (rEIII) and DENV markedly induced caspase-3-mediated endothelial cell death, an effect that was attenuated by co-treatment with chondroitin sulfate B (CSB), N-acetyl cysteine (NAC), and the caspase-3 inhibitor z-DEVD-FMK. In vivo, sequential injections of rEIII and anti-platelet immunoglobulin in mice, designed to mimic the clinical phase of DHF with peak viremia followed by an increase in DENV-induced Ig, including autoantibodies, revealed that these dual treatments markedly triggered caspase-3-dependent apoptosis in vascular endothelial cells at hemorrhage sites. Treatments with z-DEVD-FMK effectively reduced DHF-like symptoms such as thrombocytopenia, hemorrhage, inflammation, hypercoagulation, and endothelial damage. Additionally, CSB and NAC alleviated hemorrhagic symptoms in the mice. These results suggest that targeting EIII, reactive oxygen species, and caspase-3-mediated apoptosis could offer potential therapeutic strategies for addressing EIII-induced hemorrhagic pathogenesis.

Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma.

Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody-drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape.

Local Sustained Dinutuximab Delivery and Release From Methacrylated Chondroitin Sulfate.

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. High-risk NB is a subset of the disease that has poor prognosis and requires multimodal treatment regimens, with a 50% rate of recurrence despite intervention. There is a need for improved treatment strategies to reduce high-risk patient mortality. Dinutuximab is an anti-GD2 antibody ideal for targeting GD2 expressing NB cells, but binding of the antibody to peripheral nerve fibers leads to severe pain during systemic administration. Intratumoral delivery of the anti-GD2 antibody would allow for increased local antibody concentration, without increasing systemic toxicity. Chondroitin Sulfate (CS) is a biocompatible glycosaminoglycan that can be methacrylated to form CSMA, a photocrosslinkable hydrogel that can be loaded with therapeutic agents. The methacrylation reaction time can be varied to achieve different degrees of substitution, resulting in different release and degradation profiles. In this work, 4 and 24 h reacted CSMA was used to create hydrogels at 10% and 20% CSMA. Sustained in vitro release of dinutuximab from these formulations was observed over a 24-day period, and 4 h reacted 10% CSMA hydrogels had the highest overall dinutuximab release over time. An orthotropic mouse model was used to evaluate in vivo response to dinutuximab loaded 4 h methacrylated 10% CSMA hydrogels as compared to bolus tail vein injections. Tumor growth was monitored, and there was a statistically significant increase in the days to reach specific tumor size for tumors treated with intratumoral dinutuximab-loaded hydrogel compared to those treated with dinutuximab solution through tail vein injection. This supports the concept that locally delivering dinutuximab within the hydrogel formulation slowed tumor growth. The CSMA hydrogel-only treatment slowed tumor growth as well, an interesting effect that may indicate interactions between the CSMA and cell adhesion molecules in the tumor microenvironment. These findings demonstrate a potential avenue for local sustained delivery of dinutuximab for improved anti-tumoral response in high-risk NB.

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

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.

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

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

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

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

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

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

In situ crosslinked injectable chondroitin sulfate hydrogel for preventing postoperative adhesion.

Postoperative adhesion is a common clinical disease caused by surgical trauma, accompanying serious subsequent complications. Current non-surgical drug therapy and biomaterial barrier administration have limited therapeutic effects due to their inherent deficiencies. Therefore, developing a simple, effective, and feasible method to effectively prevent postoperative adhesions after surgical procedures remains a challenge. An injectable chondroitin sulfate complex hydrogel was prepared based on aldehyde-modified chondroitin sulfate (ChS-CHO) and hydrazine-modified chondroitin sulfate (ChS-ADH). The hydrogel showed enhanced strength and good self-healing ability. By using the Schiff base reaction principle that aldehyde group reacts with hydrazide to form hydrazone bond, C-A hydrogel physical barrier is formed at the wound site to reduce the occurrence of postoperative adhesion. There is no use of chemical crosslinkers in the whole reaction system to prepare C-A hydrogel, which has excellent biocompatibility and is safe and non-toxic. The results showed that C-A hydrogel showed excellent mechanical properties, good self-healing, and biocompatibility. The cecal-abdominal wall adhesion model and hepatic adhesion model of rats were constructed respectively to evaluate its preventive effect on postoperative adhesion. The results showed that C-A hydrogel had a more significant preventive effect on postoperative adhesion, and appears to be a promising candidate for postoperative adhesion.

Chondroitin Sulfate from Halaelurus burgeri Skin Inhibits Hepatic Endoplasmic Reticulum Stress and Inflammation, and Regulates Gut Microbiota.

SCOPE: Previous study has demonstrated the chemical structure of chondroitin sulfate (CHS) from Halaelurus burgeri skin and its effects on insulin resistance. However, the precise impact of this phenomenon on endoplasmic reticulum (ER) stress and inflammation, which contribute to insulin resistance, remains unclear. This study is to investigate the impact of CHS on ER stress, inflammatory response and signaling, and gut microbiota in high-fat diet (HFD)-fed mice. METHODS AND RESULTS: HFD-fed C57BL/6J mice receive dietary gavage intervention of CHS for 18 weeks. Blood, liver tissue, and feces are harvested for further investigation. Results show that CHS inhibits ER stress, accompanied by lowered blood glucose, nitric oxide (NO), reactive oxygen (ROS), and free fatty acids (FFA) levels, and increases hepatic glycogen accumulation. Moreover, hepatic inflammation is improved by CHS treatment via inactivation of Toll-like receptor 4 (TLR4) signaling and its downstream c-jun N-terminal kinase (JNK) and nuclear factor kappa B (NFκB) pathways. Additionally, CHS regulates gut microbiota, particularly the decline in the Firmicutes to Bacteroidetes ratio. CHS also lowers fecal lipopolysaccharide and elevates several fecal short chain fatty acids. CONCLUSION: These findings suggest that CHS from H. burgeri skin may be an alternative functional food supplement for anti-ER stress, anti-inflammtion, and regulation of gut microbiota.

Novel Cosmetic Ingredient CS-AA Polyion Complex and Skin Moisturizing Effect.

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.

Controversy about the use and financing of SYSADOA for osteoarthritis in Spain: An analysis of the scientific-social debate in the media.

BACKGROUND AND OBJECTIVE: 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 analyse the main positions of media outlets, public entities, regarding the use and financing of SYSADOA in Spain. METHODS: 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. RESULTS: 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. DISCUSSION AND CONCLUSIONS: The use of SYSADOA in OA patients continues to be controversial in the scientific community. However, there is consensus among patient associations in favour of public funding and use as a treatment for OA patients.

Multifunctional natamycin modified chondroitin sulfate eye drops with anti-inflammatory, antifungal and tissue repair functions possess therapeutic effects on fungal keratitis in mice.

Fungal keratitis (FK) is recognized as a stubborn ocular condition, caused by intense fungal invasiveness and heightened immune reaction. The glycosaminoglycan chondroitin sulfate exhibits properties of immunomodulation and tissue regeneration. In prior investigations, oxidized chondroitin sulfate (OCS) ameliorated the prognosis of FK in murine models. To further improve the curative efficacy, we used the antifungal drug natamycin to functionalize OCS and prepared oxidized chondroitin sulfate-natamycin (ON) eye drops. The structure of ON was characterized by FTIR, UV-vis, and XPS, revealing that the amino group of natamycin combined with the aldehyde group in OCS through Schiff base reaction. Antifungal experiments revealed that ON inhibited fungal growth and disrupted the mycelium structure. ON exhibited exceptional biocompatibility and promoted the proliferation of corneal epithelial cells. Pharmacokinetic analysis indicated that ON enhanced drug utilization by extending the mean residence time in tears. In murine FK, ON treatment reduced the clinical score and corneal fungal load, restored corneal stroma conformation, and facilitated epithelial repair. ON effectively inhibited neutrophil infiltration and decreased the expression of TLR-4, LOX-1, IL-1ß, and TNF-α. Our research demonstrated that ON eye drops achieved multifunctional treatment for FK, including inhibiting fungal growth, promoting corneal repair, enhancing drug bioavailability, and controlling inflammatory reactions.

Evaluation of the protective effects of chondroitin sulfate oligosaccharide against osteoarthritis via inactivation of NLRP3 inflammasome by in vivo and in vitro studies.

Osteoarthritis (OA) is the most prevalent degenerative arthritis disease linked to aging, obesity, diet, and accumulation of octacalcium phosphate (OCP) crystals in joints. Current research has focused on inflammation and chondrocytes apoptosis as underlying OA mechanisms. Inflammatory cytokines like IL-1ß activate matrix metalloproteinase-13 (MMP-13) and aggrecanase (the member of A Disintegrin and Metalloproteinase with Thrombospondin motifs family, ADAMTS), leading to cartilage matrix degradation. The NLRP3 inflammasome also contributes to OA pathogenesis by maturing IL-1ß. Natural products like chondroitin sulfate oligosaccharides (oligo-CS) show promise in OA treatment by inhibiting inflammation. Our study evaluates the protective effects of oligo-CS against OA by targeting NLRP3 inflammation. Stimulating human SW1353 chondrocytes and human mononuclear macrophage THP-1 cells with OCP showed increased NLRP3 inflammation initiation, NF-κB pathway activation, and the production of inflammatory cytokines (IL-1ß, IL-6) and the metabolic index (MMP-13, ADAMTS-5), leading to cartilage matrix degradation. However, oligo-CS treatment significantly reduced inflammation. In a 28-day in vivo study with C57BL/6 female mice, OCP was injected into their right knee and oligo-CS was orally administered. The OCP group exhibited significant joint space narrowing and chondrocyte loss, while the oligo-CS group maintained cartilage integrity. Oligo-CS groups also regulated gut microbiota composition to a healthier state. Taken together, our findings suggest that oligo-CS can be considered as a protective compound against OA.

"Advancements in minimally invasive treatment for lumbar disc herniation: insights into condoliase and chondroitin sulfate ABC endolyase".

This study examines the efficacy and safety of condoliase chemonucleolysis (CC) in treating lumbar disc herniation (LDH) and highlights emerging alternatives like chondroitin sulfate ABC endolyase. Research indicates that condoliase, an enzyme used to degrade glycosaminoglycans in the nucleus pulposus, provides effective and prompt relief of leg pain, with significant reductions observed within a day of treatment. Studies reveal that a lower pretreatment straight leg raising (SLR) angle may predict early symptom relief, and condoliase is generally effective at doses up to 1.25 U, balancing efficacy and safety. Despite promising results, concerns about long-term safety, including disc height reduction and imaging changes, persist. Additionally, chondroitin sulfate ABC endolyase shows potential as a safer and more effective alternative, though further research is needed to optimize treatment protocols and assess long-term outcomes. Future investigations should address current limitations, such as small sample sizes and short follow-up periods, to better understand the long-term benefits and risks of these treatments.

Polydopamine-coated chondroitin sulfate methacryloyl multifunctional microspheres for wound treatment.

The disappearance of the protective barrier after skin injury leads to the overproduction of reactive oxygen species (ROS) in response to various stimuli. Oxidative stress is one of the most important causes of delayed wound healing, leading to negative outcomes, such as excessive inflammatory response and impaired angiogenesis. In this study, we used microfluidic technology to integrate Prussian blue nanozymes and vascular endothelial growth factor and constructed multifunctional microspheres that improved local oxidative stress. In order to enhance the adhesion of the microspheres on the wound surface and prolong the release of the drug, we coated them with dopamine, ensuring uniform encapsulation on their surface. The microspheres adhered well to the wound surface and promoted wound healing by scavenging ROS, reducing the inflammatory response, and promoting angiogenesis. This strategy of integrating nanozymes and growth factors can have a synergistic effect, which is significant for wound healing.