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INTRODUCTION: There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. METHODS: We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry. RESULTS: The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I2 = 94%) and improved function (SMD: - 0.82; 95% CI: - 1.31, - 0.33; I2 = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: - 0.25; 95% CI: - 0.34, - 0.16; I2 = 75%) and function (SMD: - 0.33; 95% CI: - 0.47, - 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: - 0.08; 95% CI: - 0.19, + 0.02; I2 = 20%; SMDFunction: - 0.18; 95% CI: - 0.36, +0.01; I2 = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS = 0.93; LI: rS = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses. CONCLUSION: This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.

105. J Spec Oper Med. 2019 Spring;19(1):113-124. doi: 10.55460/JLSS-PG9B. Effects of Oral Chondroitin Sulfate on Osteoarthritis-Related Pain and Joint Structural Changes: Systematic Review and Meta-Analysis. Knapik JJ, Pope R, Hoedebecke SS, Schram B, Orr R. Osteoarthritis (OA) is a disorder involving the deterioration of articular cartilage and underlying bone and is associated with symptoms of pain and disability. In military personnel, the incidence of OA has increased between 2000 and 2012 and was the first or second leading cause of medical separations in this period. It has been suggested that consumption of chondroitin sulfate (CS) may reduce the pain and joint deterioration associated with OA. This article reports on a systematic review and meta-analysis of the effectiveness of CS on reducing OA-related pain and joint deterioration. PubMed and Ovid Embase databases and other sources were searched to find randomized, double-blind, placebo-controlled trials on the effects of orally consumed CS on pain and/or joint structure. The outcome measure was the standardized mean difference (SMD) which was the improvement in the placebo groups minus the improvement in the CS groups divided by the pooled standard deviation. There were 18 trials meeting the review criteria for pain with SMD -0.41, 95% confidence interval (95% CI) -0.57 to -0.25 (negative SMD favors CS). Six studies met the review criteria for joint space narrowing with SMD -0.30, 95% CI -0.61 to +0.00. Two studies meet the review criteria for cartilage volume with SMD -0.11, 95% CI -0.48 to +0.26. Larger dosages (1200mg/d) had greater pain reduction efficacy than lower dosages (≤ 1000mg/d). These data suggest that CS has small to moderate effectiveness in reducing OA-related pain but minimal effects on joint space narrowing and no effect on cartilage volume. It is important that clinicians recommend pharmaceutical-grade CS to their patients due to the variability in the amount of CS in dietary supplements purporting to contain CS. 2019.

Although glucosamine and chondroitin sulfate have showed beneficial effects on joint tissues in osteoarthritis (OA), their therapeutic use in the clinical setting is still debatable. Hence, a systematic review and meta-analysis of randomized placebo-controlled trials was conducted to investigate the efficacy of glucosamine and chondroitin sulfate on knee OA symptoms. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials evaluating the effect of orally administered glucosamine and/or chondroitin sulfate on OA symptoms using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and/or the Visual Analog Scale (VAS). Meta-analysis was conducted using a random-effects model and generic inverse-variance method. Heterogeneity was tested using the I2 statistic index. Treatments with glucosamine and chondroitin were found to significantly reduce pain in VAS [weighted mean difference (WMD) - 7.41 mm, 95% CI - 14.31, - 0.51, p = 0.04 and WMD - 8.35 mm, 95% CI - 11.84, - 4.85, p < 0.00001, respectively]. Their combination did not show this behavior (WMD - 0.28 mm, 95% CI - 8.87, 8.32, p = 0.95). None of the glucosamine, chondroitin or their combination had a significant positive effect on the total WOMAC index and its subscores. Oral supplementation with glucosamine or chondroitin sulfate reduces pain in knee OA. However, there is no additional effect using both therapeutic agents in combination for the management of symptomatic knee OA.

Erratum in Phys Sportsmed. 2010 Oct;38(3):128. Osteoarthritis (OA) is a common, painful, and debilitating condition that affects approximately 46.4 million individuals in the United States. By 2012, this number is expected to increase to 60 million. In addition, it is the leading cause of activity limitation in adults and represents a widely acknowledged economic burden. Although the ultimate goal is to slow or prevent OA progression, at present, medical management of OA is aimed primarily at controlling symptoms of pain and stiffness and maintaining joint mobility and quality of life. Because of the lack or perceived lack of response to many conventional therapies for OA as well as concerns regarding the long-term administration of drugs (eg, nonsteroidal anti-inflammatory drugs), oral joint health supplements (OJHSs) have become increasingly popular among patients with OA. This article briefly reviews pertinent molecular mechanisms involved in the development of OA and summarizes available in vitro and in vivo evidence supporting the use of avocado and soybean unsaponifiables (ASU) either alone or in combination with glucosamine and chondroitin sulfate in patients with OA. Basic scientific research studies and a systematic review and meta-analysis of the available high-quality randomized clinical trials indicate that 300 mg of ASU per day (with or without glucosamine and chondroitin sulfate) appears to be beneficial for patients with hip or knee OA. There is also some evidence that ASU or ASU/glucosamine/chondroitin sulfate combination products could be used prophylactically in even the earliest stages of OA. Considering concerns regarding inferior-quality OJHSs, consumers and physicians are encouraged to take an evidence-based approach when evaluating OJHSs to identify and recommend safe and effective products that meet label claims when tested independently, and are of the highest quality.

OBJECTIVE: To assess the structural and symptomatic efficacy of oral glucosamine sulfate and chondroitin sulfate in knee osteoarthritis through independent meta-analyses of their effects on joint space narrowing, Lequesne Index, Western Ontario MacMaster University Osteoarthritis Index (WOMAC), visual analog scale for pain, mobility, safety, and response to treatment. METHODS: An exhaustive systematic research of randomized, placebo-controlled clinical trials published or performed between January 1980 and March 2002 that assessed the efficacy of oral glucosamine or chondroitin on gonarthrosis was performed using MEDLINE, PREMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Contents, BIOSIS Previews, HealthSTAR, EBM Reviews, manual review of the literature and congressional abstracts, and direct contact with the authors and manufacturers of glucosamine and chondroitin. Inclusion, quality scoring, and data abstraction were performed systematically by 2 independent reviewers who were blinded to sources and authors. Conservative approaches were used for clear assessment of potential efficacy. RESULTS: Our results demonstrated a highly significant efficacy of glucosamine on all outcomes, including joint space narrowing and WOMAC. Chondroitin was found to be effective on Lequesne Index, visual analog scale pain, mobility, and responding status. Safety was excellent for both compounds. CONCLUSIONS: Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds. Regarding the relatively sparse data on glucosamine and joint space narrowing and the absence of data on structural effects of chondroitin, further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.

BACKGROUND AND OBJECTIVES: Whole grains are rich in nutrients and have multiple health benefits, playing an important role in the diet. This study aims to investigate the acute effects of different whole grain pancakes on cardiometabolic risk factors in healthy subjects. METHODS AND STUDY DESIGN: Twenty eligible healthy sub-jects (aged 19-24 years) were recruited, with baseline measurements including fasting blood glucose, insulin, C-reactive protein (CRP), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Then, the subjects were randomly allocated into four groups: the steamed bun (SB) group (control group), maize pancake (MP) group, buckwheat pancake (BP) group, and oat pancake (OP) group, with a serving size of 100g. Blood samples were collected at 0h, 0.5h, 1h, 2h, and 3h, respectively. After a one-week washout period, the volunteers consumed another type of pancake in a crossover manner until each volunteer had tried all four foods. Serum cardiometabolic risk factors were analyzed using standard methods. RESULTS: No significant differences in serum glucose, insulin, CRP, TG, and HDL-C concentrations were observed among the control group and three whole grain pancake groups. However, compared with the control group, the concentrations of serum TC and LDL-C in the oat pancake group were significantly reduced (p <0.05), which may be attributed to the presence of β-glucan and higher dietary fiber in oat pancakes. CONCLUSIONS: This study provides important dietary guidance for both pancake consumers and individuals with cardiometabolic risk factors.

BACKGROUNDPlasma heparan sulfate, a glycosaminoglycan released during endothelial glycocalyx degradation, predicts sepsis mortality. Chondroitin sulfate is a circulating glycosaminoglycan not specific to glycocalyx degradation; its relevance to sepsis is unknown.METHODSWe studied the associations of plasma chondroitin sulfate with (a) mortality in patients with sepsis-associated hypotension and (b) the relative effectiveness of a randomly assigned liberal versus restrictive intravenous fluid resuscitation strategy. We selected 574 patients enrolled in the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis trial using an outcome-enriched sampling strategy. We used liquid chromatography-mass spectrometry to quantify plasma chondroitin sulfate. In comparison, we measured hyaluronic acid as a glycocalyx degradation marker and IL-6 as an inflammatory biomarker. We conducted Cox proportional hazards regression analyses to examine associations of baseline biomarker concentrations with mortality and resuscitation strategy effectiveness. We used inverse probability of selection weights and generalized raking to account for the nonrepresentative sampling design.RESULTSPlasma chondroitin sulfate, hyaluronic acid, and IL-6 were associated with mortality within 90 days. As baseline chondroitin sulfate increased, subsequent randomization to a restrictive strategy was increasingly beneficial (P = 0.022): treatment effect hazard ratio (restrictive versus liberal) for mortality was estimated as 1.49 (95% CI, 0.98-2.27), 1.30 (95% CI, 1.00-1.69), 1.09 (95% CI, 0.82-1.44), 0.88 (95% CI, 0.66-1.16), and 0.71 (95% CI, 0.52-0.97) for 10th, 25th, 50th, 75th, and 90th percentiles of baseline chondroitin sulfate.CONCLUSIONPlasma chondroitin sulfate predicts sepsis mortality and may modify the response to a subsequent liberal versus restrictive intravenous fluid resuscitation strategy.TRIAL REGISTRATIONClinicalTrials.gov NCT03434028.FUNDINGNIH grants R01HL149422 and R01HL094786.

Knee osteoarthritis (KOA) is a chronic joint disease marked by cartilage degradation and inflammation. Probiotics exhibit anti-inflammatory properties and may influence the gut-joint axis. Thus, a 4-month human trial was conducted to assess the adjunctive effects of Bifidobacterium animalis subsp. lactis Probio-M8 on KOA in postmenopausal women. Sixty-five KOA patients were randomly allocated to the probiotic group (n = 37; Probio-M8 and chondroitin sulfate) or placebo group (n = 28; placebo and chondroitin sulfate). Following a 3-month intervention, participants from both groups entered a 1-month observation without probiotic supplementation. Our findings revealed that Probio-M8 co-administration significantly reduced Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at months 1, 3, and 4 compared to the placebo group (P < 0.001). The probiotic group showed a significant decrease in serum IFN-γ and increases in IL-4 and IL-10 (P < 0.05). Fecal metagenome analysis showed significant changes in the gut microbiota of the probiotic group, with increases in potentially beneficial species, including Agathobaculum butyriciproducens, Bacteroides stercoris, B. animalis, Roseburia hominis, and Ruminococcus bromii, while Dorea formicigenerans decreased (P < 0.05). Changes in B. animalis were strongly associated with WOMAC scores. The gut metabolic potential analysis showed elevated levels of N-oleoylethanolamine and decreased levels of cholesterol and hypoxanthine in probiotic receivers (P < 0.05). Metabolite analysis revealed post-interventional alternations in fecal prostaglandin E2, stearic acid, cholic acid, chenodeoxycholic acid, xanthine, testosterone, and serum bile acids (P < 0.05). Collectively, Probio-M8 enhances the effectiveness of chondroitin sulfate in KOA management through modulating the gut-joint axis, potentially via regulating multiple inflammatory pathways. IMPORTANCE: The pathogenesis of knee osteoarthritis (KOA) and its phenotypic expression have been associated with the human gut microbiota. Our study demonstrated that the co-administration of Probio-M8 with chondroitin sulfate significantly alleviates KOA symptoms. This

PURPOSE: To compare 2 dispersive ophthalmic viscosurgical devices (OVDs), Z-HYALCOAT (investigational) and HEALON EndoCoat (control), with a 3-month postoperative follow-up. SETTING: Multicenter study conducted in 11 sites across Europe. DESIGN: Prospective, randomized, masked, multicenter postmarket study. METHODS: Adult participants having clear intraocular media excluding the presence of cataract and scheduled for uneventful age-related cataract removal by phacoemulsification and intraocular lens implantation in the capsular bag with sole administration of either investigational or control device as per randomization scheme were included in this study. Primary endpoint was the incidence of intraocular pressure (IOP) ≥30 mm Hg. Other endpoints included slitlamp observations, corneal endothelial cell density (ECD), surgeon-reported device functionality, and rate of adverse events and device deficiencies. RESULTS: 242 participants were treated in this study (123 with the investigational OVD and 119 with the control OVD). In per-protocol population, 13 eyes (11.2%) from the investigational group and 19 (17.0%) from the control group reached an IOP equal to or higher than 30 mm Hg at 8 hours after device use. Slitlamp examinations performed up to 3 months did not reveal any relevant differences between the groups. ECD loss was also similar between the groups. Surgeon-reported OVD functionality was generally favorable and comparable for both devices. CONCLUSIONS: This investigation proved the noninferiority of Z-HYALCOAT to HEALON EndoCoat in IOP spikes and showed the 2 devices to be highly similar in all evaluated aspects.

BACKGROUND: Sensitive skin requires targeted care to improve barrier function, reduce inflammation, and manage neurovascular reactivity. OBJECTIVE: Encorelane, a novel ingredient blend of saccharide isomerate, ribose, and fructooligosaccharides, was evaluated for its efficacy in addressing sensitive skin and visible aging signs. METHODS: In vitro: A 3D epidermal model (EpiKutis) with Sodium Lauryl Sulfate (SLS) induction was used to assess cytokines (interleukin 1α [IL-1α], interleukin 6 [IL-6], interleukin 8 [IL-8], tumor necrosis factor α [TNF-α], prostaglandin E2 [PGE2]) and barrier markers (filaggrin [FLG], loricrin [LOR], transglutaminase 1 [TGM1]). Hydration was examined via aquaporin 3 (AQP3) expression levels. Anti-wrinkle efficacy was tested against UVA/UVB exposure, evaluating collagen synthesis and skin matrix components (Collagen types I, III, IV, VII, XVII, Laminin 5, hyaluronic acid [HA], Chondroitin sulfate [CS]). In vivo: A 6-week double-blind, half-face study in 23 sensitive-skin subjects evaluated the clinical effects of Encorelane versus placebo on repair, redness, firmness, and wrinkles. RESULTS: In vitro: Compared to the control group, Encorelane significantly reduced the levels of IL-1α, TNF-α, IL-6, IL-8, and PGE2 (p < 0.05), and significantly increased the levels of AQP3, FLG, LOR, TGM1, collagen types I, III, IV, VII, XVII, and laminin 5 (p < 0.05). In vivo: Compared to the placebo, Encorelane significantly improved TEWL, R2, F4, and crow's feet wrinkles (p < 0.05). CONCLUSION: Encorelane effectively targets both inflammation and aging signs, supporting its use as a dermocosmetic solution for sensitive, aging-prone skin. © 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

In individuals with irritable bowel syndrome (IBS), eliminating dietary triggers can alleviate symptoms but may lead to nutrient deficiencies and overall health decline. Although various nutritional supplements show promising results in relieving IBS symptoms due to their potential to alter the microbiome, conclusive scientific evidence remains lacking. This exploratory study aims to assess the bifidogenic properties of four nutritional supplement interventions and their impact on IBS-symptoms, faecal microbiota composition, faecal short-chain fatty acid (SCFA) concentrations, stool pattern, and quality of life (QoL), compared to a placebo control. Seventy subjects with IBS, meeting the ROME IV criteria, participated in this randomised, double-blind, placebo-controlled parallel intervention study. Subjects were assigned to one of the four treatment groups, receiving either resistant starch, pea fibre, chondroitin sulfate, protein hydrolysate, or placebo daily for four weeks. Daily reports on stool pattern and gastrointestinal complaints were collected. Stool samples and questionnaires on dietary intake, symptom severity, QoL, and anxiety and depression were collected at baseline and after the 4-week intervention. The results show no significant increase in Bifidobacterium abundance or faecal SCFA levels after the 4-week intervention with any of the four nutritional supplement interventions. While some improvements in symptom severity and QoL were observed within-groups, these were not significantly different from changes observed with placebo. In conclusion, the tested nutritional supplements did not increase Bifidobacterium abundance in subjects with IBS within four weeks. Furthermore, we conclude that future studies should consider a run-in period and a larger sample size to study improvements in IBS symptoms. © The Author(s) 2025.

Osteoarthritis (OA) is a prevalent degenerative joint disease, often affecting the elderly, characterized by cartilage degradation and bone remodelling, leading to pain, stiffness, and impaired movement. This 12-week, randomized, double-blind, placebo-controlled pilot study investigated the efficacy of a formulation containing collagen type II, glucosamine hydrochloride and chondroitin sulfate, in alleviating knee OA symptoms in subjects with mild to moderate knee pain. Fifty-four participants were enrolled, with 52 completing the study. Participants were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), performance-based physical function tests and global assessment tests. Results indicated significant improvements in the verum group compared to placebo. KOOS subscales showed improvements in symptoms (8.16%, p < 0.05), sport/recreation (25.25%, p < 0.01), and quality of life (27.66%, p < 0.001). Stiffness improved by 14.68% (p < 0.05) in the verum group. Both groups exhibited significant pain reduction (KOOS pain, p < 0.001 and p < 0.01 for verum and placebo, respectively). Performance-based measures, such as the Chair Stand test, improved significantly in both groups, though other metrics showed no significant differences. The verum group exhibited a linear improvement over 12 weeks, contrasting with the placebo group's initial response and subsequent plateau. SF-36 Physical Component scores improved in both groups (p < 0.05), but mental health scores remained unchanged. Global assessment favoured the verum group, with more participants reporting OA improvement and recommending the product (p < 0.01). Biomarkers hsCRP and COMP showed no significant changes, likely due to sample variability. While the study did not achieve its primary endpoint, the nutritional formulation demonstrated an excellent safety profile and encouraging improvements in patient-reported symptoms and quality of life, warranting larger confirmatory trials.Registration number: DRKS00029563 05/10/2022. © 2025. The Author(s).

AIM: To evaluate the efficacy of a combination therapy containing chondroitin sulfate (CS), glucosamine (GL), methylsulfonylmethane (MSM), hyaluronic acid (HA), and native/hydrolyzed collagen compared to collagen-free therapy in the initial management of knee osteoarthritis (OA) exacerbations. MATERIALS AND METHODS: A single-center, prospective, comparative phase IV study included 60 patients with knee OA (Kellgren-Lawrence stages 2-3). Participants were randomized into two groups: Group A (n=30) received CS/GL/MSM/HA, while Group B (n=30) received the same regimen supplemented with collagen. Pain dynamics (VAS, WOMAC), NSAID requirements, and functional outcomes (Timed Up-and-Go test, walking speed, muscle strength) were assessed at weeks 1, 2, 4, and 8. RESULTS: Group B demonstrated significant superiority: a 76% reduction in WOMAC pain scores (vs. 47% in Group A; p=0.04) and a 74% reduction in VAS scores (vs. 56%; p<0.05). NSAID use at week 8 was 2.6±0.5 days in Group B (vs. 4.3±1.8 in Group A; p=0.04). Functional improvements (12% increase in walking speed, 42% reduction in Timed Up-and-Go test duration) were also more pronounced in Group B (p<0.05). CONCLUSION: The combination of CS/GL/MSM/HA with collagen significantly outperforms collagen-free therapy in reducing pain, improving joint function, and decreasing symptomatic treatment needs in patients with knee OA exacerbations. These findings support the inclusion of collagen in OA combination therapy. Publisher: Цель. Оценка эффективности комбинации хондроитина сульфата (ХС), глюкозамина (ГГ), метилсульфонилметана (МСМ), гиалуроновой кислоты (ГК) с добавлением нативного и гидролизованного коллагена в сравнении с терапией без коллагена при стартовом лечении обострений остеоартрита (ОА) коленного сустава. Материалы и методы. Проведено одноцентровое проспективное сравнительное исследование (IV фаза) с участием 60 пациентов с ОА коленного сустава II–III стадии по Kellgren–Lawrence. Пациенты рандомизированы на две группы: группа А (n=30) получала ХС/ГГ/МСМ/ГК, а группа Б (n=30) – аналогичную терапию с добавлением коллагена. Оценка включала динамику боли (по Визуальной аналоговой шкале, валидизированной шкале о

OBJECTIVES: The double blind, multicentre, randomised, placebo-controlled GAG-therapy Efficacy Trial Solution for Bladder pain syndrome/Interstitial cystitis (GETSBI) study aims to evaluate the efficacy of intravesical glycosaminoglycans therapy with hyaluronic acid and chondroitin sulfate in symptomatic bladder pain syndrome/interstitial cystitis (BPS/IC) patients with Hunner lesions. This trial encompasses multiple methodologies, including a standard randomised controlled trial (RCT), a cross-over trial and an N-of-1 trial. An N-of-1 trial is a multiple crossover trial, usually randomised and often blinded, conducted in a single patient (1). The N-of-1 methodology is, however, only valid under the condition that there is no carry-over effect, meaning a carry-over of effect from an a-priori intervention period into the placebo period. Therefore, it is important to examine any potential carry-over effects to determine the validity of the study protocol concerning the N-of-1 trial part and thereby justifying recruitment. DESIGN: Interim analysis for potential carry-over effects. SETTING: Secondary care, 21 participants. PARTICIPANTS: 21 participants, participants concluded part one from the GETSBI study at time of this analysis (October 2023). OUTCOME MEASURE: The primary outcome of the study is the change from baseline in pain intensity, measured by visual analogue scale (VAS) pain. To assess for carry-over effects, the placebo responses on VAS pain were compared between groups with (n=10) and without (n=11) potential carry-over effects. The threshold for a clinically relevant carry-over effect was set at a difference on VAS pain >0.50 points. Data were analysed using descriptive statistics, T-tests, effect sizes and 95% CI. Statistical significance was set at α=0.05. RESULTS: The mean baseline VAS pain did not differ (p=0.12) between group A (n=10, VAS 7.52, SD=0.52) and group B (n=11, VAS 6.02, SD=2.47). The mean placebo responses on VAS pain for groups A and B were 0.97 (SD=1.85) and 1.47 (SD=1.81), respectively. The mean carry-over effect was 0.50 (SD=1.83), which was not statistically significant with a 95% CI of -1.17 to 2.17 and p=0.5369. CONCLUSIONS: Thi

BACKGROUND: To evaluate the efficacy of a new D-mannose dietary supplement containing D-mannose, Propolis-Quercetin, Bacillus Coagulans, Hyaluronic Acid and Chondroitin Sulfate with fosfomycin in reducing rUTI episodes and improving quality of life. RESEARCH DESIGN AND METHODS: Single-blind, randomized controlled trial conducted at tertiary-care hospital in Italy. Women aged 21-65 with a history of rUTIs were randomized into three groups: fosfomycin, the dietary supplement, and a combination of both treatments. Primary outcome was frequency of rUTI episodes per month. RESULTS: Combination therapy demonstrated greatest reduction in rUTI episodes per month at 12 months compared to fosfomycin or supplement monotherapy (0.23 ± 0.37 vs 0.58 ± 0.67 and 1.12 ± 0.96 for fosfomycin and supplement monotherapy respectively; p < 0.05) and to supplement monotherapy at 6 months (0.69 ± 1.03 vs 1.43 ± 1.33; p < 0.05), with significant improvement of ICIQ-FLUTS domains compared to other groups at 12 months (p < 0.05). Combination therapy had lower number of women matching rUTI criteria (55.32% vs 76.47% and 84%; p < 0.05) and symptoms remission at 12 months (89.36% vs 56.86% and 20%; p < 0.001). CONCLUSIONS: Combining fosfomycin and an integrated D-mannose supplement for managing rUTIs offers a potential reduction in antibiotic reliance. Further large-scale studies are recommended to confirm these findings. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT06659016).

Tumor stromal remodeling is an obstacle for immune checkpoint inhibitors (ICI). A stroma modifying small interfering RNA (siRNA) to carbohydrate sulfotransferase 15 (CHST15) was recently shown to enhance tumor-infiltrating T cells, yet its impact on antitumor response of ICI remains unexplored. In mouse pancreatic cancer KPC and Pan02 subcutaneous syngeneic tumor models, mice were divided into 4 groups for treatment; (1) control, (2) CHST15 siRNA monotherapy, (3) anti-programmed death receptor 1 (PD-1) monotherapy, and (4) combination therapy with CHST15 siRNA and anti-PD-1 antibody. Mice were sacrificed after 2 week-treatments and anti-tumor effects were evaluated by immunohistochemistry for KPC and flow cytometry for Pan02 model, respectively. In the KPC model, combination treatment with intratumoral CHST15 siRNA (0.9-1.0 mg/kg) and systemic anti-PD-1 antibody (5 mg/kg) synergistically and robustly suppressed tumor growth with a significant increase of tumor-infiltrating CD4+ and CD8+ T cells compared to anti-PD-1 monotherapy. In the Pan02 model, combination treatment with CHST15 siRNA and anti-PD-1 showed anti-tumor effect with significant increases in % necrosis area of the tumor, and tumor-infiltrating T cells compared to the control. Notably, the combination therapy dramatically diminishes Ly6C+Ly6G+ granulocytic myeloid-derived suppressor cells (MDSCs) compared to anti-PD-1 monotherapy. The present study demonstrated the robust synergy between systemic anti-PD-1 antibody and a single stroma modifying agent. Combination usage of intratumoral CHST15 siRNA would provide a novel therapeutic option to trigger the remarkable effect of ICI on this most hard-to-treat solid tumor. © 2025. The Author(s).

Targeted drug delivery strategy can accurately deliver multiple drugs to tumor cells by biocompatible materials, enhance the therapeutic effect and weaken adverse side effects. Chondroitin sulfate (CS) is a biodegradable material which has dual-targeting ability to CD44 receptors and Golgi apparatus. Flurbiprofen is a COX-2 inhibitor that can be used as an anticancer adjuvant in combination with docetaxel to enhance the antitumor effect. Herein, docetaxel and flurbiprofen were coupled to CS via disulfide bond and ester bond respectively to prepare polymer conjugates chondroitin sulfate-docetaxel (C-ss-D) and chondroitin sulfate-flurbiprofen (C-F). Then the reduction-sensitive micelles C-ss-D and the pH-sensitive micelles C-F were constructed by self-assembly respectively, and the dual-drug micelles C-F/C-ss-D were further prepared. C-F/C-ss-D displayed uniform spherical shape, negative surface charge, and achieved controlled drug release in slightly acidic and reductive tumor microenvironment. C-F/C-ss-D exhibited remarkable targeting ability towards tumor cells and Golgi apparatus, demonstrated potent cytotoxic effect on MCF-7 cells, and induced apoptosis by regulating the expression of COX-2 and apoptosis-related proteins. C-F/C-ss-D effectively inhibited tumor growth in MCF-7 xenograft mice with low toxicity to blood and major organs. Therefore, the environmental responsive dual-drug synergistic and dual-targeted micelles based on CS have great potential for the treatment of breast cancer.

According to the close association between cancer and inflammation demonstrated in clinical data, the strategy of synergistic anti-tumor and anti-inflammatory therapy shows promising potential. However, challenges remain in the synthesis and development of co-delivery systems for synergistic therapy. Herein, an amphiphilic chondroitin sulfate-rosmarinic acid polymeric prodrug was synthesized, and then combined with DSPE-PEG to encapsulate doxorubicin, forming a redox-responsive nanomicelle (PRSC/DOX) delivery system. PRSC/DOX exhibited a particle size of 188.6 nm and remained stable in PBS for at least 7 days. PRSC/DOX was internalized into tumor cells via CD44 receptor-mediated endocytosis, and degraded by intracellular glutathione to release the drugs. The released doxorubicin killed tumor cells through chemotherapy, and rosmarinic acid inhibited tumor cell growth by suppressing inflammation levels in the tumor microenvironment. In vivo experiments showed a statistically significant decrease in the inflammation levels in mice, along with a considerable reduction in tumor volume. Consequently, the PRSC/DOX significantly enhanced antitumor efficacy through a synergistic therapy of chemotherapy and inflammation suppression.

Rheumatoid arthritis, a chronic autoimmune disorder characterized by joint inflammation, is thought to be exacerbated by bacterial infections, notably Proteus mirabilis. This study explores the combined effects of quercetin, a potent antioxidant and anti-inflammatory flavonoid, and chondroitin sulfate, known for its cartilage-protective properties, as a potential therapeutic approach. Molecular docking analyses revealed favourable interactions between these compounds and key pro-inflammatory cytokines IL-6 and TNF-α, suggesting their potential to disrupt inflammation-related signaling pathways. In vitro assays demonstrated that the quercetin-chondroitin sulfate combination (1:1 ratio) significantly inhibited oxidative stress and hemolysis, highlighting its enhanced anti-inflammatory and membrane-protective effects. The free radical scavenging assays further confirmed the antioxidant potential of this combination, which demonstrated strong radical scavenging activity. Antimicrobial assays showed notable antibacterial effects, with an increased inhibition zone against P. mirabilis when quercetin and chondroitin sulfate were combined, suggesting a synergistic antimicrobial action. In vivo, zebrafish subjected to bacterial stress showed improved survival rates with the quercetin and chondroitin sulfate combination treatment, along with enhanced mineralization and significant modulation of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities, indicating its protective role in maintaining joint health. Furthermore, gene expression analysis revealed a substantial reduction in pro-inflammatory markers, including TNF-α and IL-6, demonstrating the quercetin and chondroitin sulfate combination's ability to mitigate inflammation. Together, these findings suggest that the quercetin and chondroitin sulfate combination hold significant therapeutic potential in reducing oxidative stress, inflammation, and microbial-induced RA exacerbations.

Rheumatoid arthritis (RA) progression involves multiple cell types, and sequential drug action on target cells is necessary for RA treatment. Nanocarriers are widely used for RA treatment; however, the targeted delivery and on-demand release of multiple drugs remains challenging. Therefore, in this study, a dual-sensitive polymer is developed using chondroitin sulfate (CS) for the co-delivery of the cartilage repair agent, glucosamine (GlcN), and anti-inflammatory drug, tofacitinib (Tof). In the joint cavity, acidic pH facilitates the cleavage of GlcN from CS polymer to repair the cartilage damage. Subsequently, macrophage uptake via CS-CD44 binding and intracellular reactive oxygen species (ROS) mediate conversion of (methylsulfanyl)propylamine to a hydrophilic segment jointly triggered rapid Tof/GlcN release via micelle disassembly. The combined effects of Tof, GlcN, and ROS depletion promote the M1-to-M2 polarization shift to attenuate inflammation. The synergistic effects of these agents against RA are confirmed in vitro and in vivo. Overall, the dual pH/ROS-sensitive CS nanoplatform simultaneously delivers GlcN and Tof, providing a multifunctional approach for RA treatment with synergistic drug effects. © 2024 Wiley‐VCH GmbH.

Osteoarthritis is one of the leading conditions that promote the consumption of these dietary supplements. Chondroitin sulfate, glucosamine, and methylsulfonylmethane are among the prominent alternative treatments for osteoarthritis. In this study, these dietary supplements were incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes, and the formation of marker metabolites was measured to investigate their inhibitory potential on cytochrome P450 enzyme activities. The results revealed no significant inhibitory effects on seven CYPs, consistent with established related research data. Therefore, these substances are anticipated to have a low potential for cytochrome P450-mediated drug interactions with osteoarthritis medications that are likely to be co-administered. However, given the previous reports of interaction cases involving glucosamine, caution is advised regarding dietary supplement-drug interactions. A chondroitin sulfate proteoglycan 4‑specific monoclonal antibody inhibits melanoma cell invasion in a spheroid model. Uranowska K(1), Samadaei M(2), Kalic T(1), Pinter M(2), Breiteneder H(3), Hafner C(1). Author information: (1)Department of Dermatology, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, A-3100 St. Poelten, Austria. (2)Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, A-1090 Vienna, Austria. (3)Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria. The overexpression of chondroitin sulfate proteoglycan 4 (CSPG4) is associated with several tumor types, including malignant melanoma, squamous cell carcinoma, triple‑negative breast carcinoma, oligodendrocytomas or gliomas. Due to its restricted distribution in normal tissues, CSPG4 has been considered a potential target for several antitumor approaches, including monoclonal antibody (mAb) therapies. The aim of the present study was to characterize the impact of the CSPG4‑specific mAb clone 9.2.27 on its own or in combination with the commonly used BRAF‑selective in

43. Int J Oncol. 2021 Sep;59(3):70. doi: 10.3892/ijo.2021.5250. Epub 2021 Jul 28. A chondroitin sulfate proteoglycan 4‑specific monoclonal antibody inhibits melanoma cell invasion in a spheroid model. Uranowska K(1), Samadaei M(2), Kalic T(1), Pinter M(2), Breiteneder H(3), Hafner C(1). Author

BACKGROUND: Osteoarthritis (OA) is a common worldwide disease induced by a wide range of biochemical processes, mainly inflammation and degradation of collagen. The aim of this study, was to describe the effect of a multistrain probiotic (PB) and chondroitin sulfate (CS), administered separately or in combination, on the expression of Ptgs2, Tgfb1 and Col2a1 during monoiodoacetate-induced OA in male rats. METHODS: OA was induced in male rats by injecting monoiodoacetate in right hind knee. Therapeutic groups received 3 mg/kg of CS for 28 days and/or 1.4 g/kg of multistrain PB for 14 days. Knee cartilage were taken 30 days after monoiodoacetate injection. RNA was extracted and the expression of Ptgs2, Tgfb1 and Col2a1 were analyzed using SYBR Green 1-step real-time quantitative polymerase chain reaction. RESULTS: Induction of OA caused an upregulation in Ptgs2, Tgfb1 expression, and downregulation of Col2a1. Separate administration of PB and CS reduced Ptgs2 and Tgfb1 expressions. Their combined administration significantly decreased the expression of these pro-inflammatory cytokines, comparable to controls. Expression of Col2a1 showed similar behavior, with upregulation in therapeutic group with separate administration and the cumulative effects in case of co-administration. CONCLUSIONS: The multistrain PB diet may offer a perspective to improve the standard treatment of OA and, necessitates further investigation with clinical trials.

Standard treatment, unfortunately, yields a poor prognosis for patients with primary or metastatic cancers in the central nervous system, indicating a necessity for novel therapeutic agents. Immunotoxins (ITs) are a class of promising therapeutic candidates produced by fusing antibody fragments with toxin moieties. In this study, we investigated if inherent resistance to IT cytotoxicity can be overcome by rational combination with pro-apoptotic enhancers. Therefore, we combined ITs (9.2.27-PE38KDEL or Mel-14-PE38KDEL) targeting chondroitin sulfate proteoglycan 4 (CSPG4) with a panel of Bcl-2 family inhibitors (ABT-737, ABT-263, ABT-199 [Venetoclax], A-1155463, and S63845) against patient-derived glioblastoma, melanoma, and breast cancer cells/cell lines. In vitro cytotoxicity assays demonstrated that the addition of the ABT compounds, specifically ABT-737, sensitized the different tumors to IT treatment, and improved the IC50 values of 9.2.27-PE38KDEL up to >1,000-fold. Mechanistic studies using 9.2.27-PE38KDEL and ABT-737 revealed that increased levels of intracellular IT, processed (active) exotoxin, and PARP cleavage correlated with the enhanced sensitivity to the combination treatment. Furthermore, we confirmed the synergistic effect of 9.2.27-PE38KDEL and ABT-737 combination therapy in orthotopic GBM xenograft and cerebral melanoma metastasis models in nude mice. Our study defines strategies for overcoming IT resistance and enhancing specific antitumor cytotoxicity in primary and metastatic brain tumors.

Axotomy results in permanent loss of function after brain and spinal cord injuries due to the minimal regenerative propensity of the adult central nervous system (CNS). To identify pharmacological enhancers of axon regeneration, 960 compounds were screened for cortical neuron axonal regrowth using an in vitro cortical scrape assay. Diltiazem, verapamil, and bromopride were discovered to facilitate axon regeneration in rat cortical cultures, in the presence of chondroitin sulfate proteoglycans (CSPGs). Diltiazem, an L-type calcium channel blocker (L-CCB), also promotes axon outgrowth in adult primary mouse dorsal root ganglion (DRG) and induced human sensory (iSensory) neurons.

BACKGROUND: Recently genome-wide association studies identified that NCAN rs2228603 polymorphism was associated with non-alcoholic fatty liver disease (NAFLD) mainly in subjects of European ancestry. While no research have been conducted to demonstrate the relationship between NCAN rs2228603 and NAFLD in Chinese Han adults. The aim of this study was to investigate whether NCAN rs2228603 is associated with NAFLD in Chinese population. METHODS: Gene NCAN rs2228603 was genotyped in 182 patients with NAFLD and 195 healthy controls. The expression of NCAN was tested according to polymerase chain reaction analysis (PCR) and serum lipids were performed by biology techniques. RESULTS: No significant difference was found in genotype and allele frequencies of NCAN rs2228603 between the NAFLD group and the controls (P > 0.05). Subjects with the NCAN rs2228603 CT genotype showed a higher level of alkaline phosphatase (AKP) (P = 0.017) and a higher high-density lipoprotein (HDL) (P < 0.05). CONCLUSIONS: Our study for the first time identified that the gene NCAN rs2228603 is not a risk factor for the incidence of NAFLD in Chinese population. Also we found the dual and opposite role of T variant in protecting liver with a higher level of HDL and conferring risk for liver damage with a higher level of AKP. TRIAL REGISTRATION: Chinese Clinical Trial Register.gov Identifier: ChiCTR-ROC-15006447 .

INTRODUCTION: Osteoarthritis (OA) is a chronic, progressive joint disease characterized by the degradation of articular cartilage, subchondral bone remodeling, synovial inflammation, and osteophyte formation. Despite being a leading cause of disability in older people, effective long-term management of OA remains a significant challenge. Current treatment strategies primarily focus on symptom control, with both non-pharmacological and pharmacological interventions. MATERIALS AND METHODS: A systematic literature review followed by a structured Delphi survey was conducted, involving an international Technical Expert Panel (TEP) of OA specialists. The panel evaluated the efficacy, safety, and clinical utility of combining low dose diclofenac and chondroitin sulfate in OA management. RESULTS: The analysis of expert consensus indicated that the combination of low dose diclofenac and chondroitin sulfate may be effective in reducing pain and improving joint function in patients with knee OA. Additionally, this combination could reduce the need for higher doses of NSAIDs, thereby minimizing systemic adverse effects. CONCLUSION: The combination of low dose diclofenac and chondroitin sulfate represents a promising therapeutic strategy for managing knee OA. Further studies are needed to confirm these findings and optimize therapeutic strategies to improve patient outcomes. © 2025. The Author(s).

OBJECTIVES: To establish French recommendations for the management of people living with hand osteoarthritis (OA) on behalf of the French Society of Rheumatology (SFR) and of the French Society of Physical and Rehabilitation Medicine (SOFMER). METHODS: A systematic review of the literature, including systematic reviews, meta-analyses, and randomized controlled trials on pharmacological and non-pharmacological treatments, was conducted from inception until November 24, 2023. Based on this review and expert consensus, a multidisciplinary group of 25 healthcare professionals-including rheumatologists, physical and rehabilitation medicine physicians, hand surgeons, general practitioner, geriatrician, occupational therapists, physiotherapists, and patients-formulated the recommendations. Each statement was assigned a level of evidence, a grade of recommendation, and a level of agreement based on EULAR standardized procedures for recommendations. RESULTS: The group established four general principles and 11 specific recommendations. The general principles emphasize treatment objectives, individualized management, patient education, and a multimodal approach combining non-pharmacological and pharmacological therapies. Four specific recommendations address non-pharmacological strategies, including exercise, ergonomic advice, assistive devices, orthoses and heat applications. The group advises against the use of electromagnetic waves, laser therapy, acupuncture, or kinesiotaping. Seven specific recommendations cover pharmacological treatments, advocating for topical and oral NSAIDs, acetaminophen, chondroitin sulfate for symptom relief, low-dose oral corticosteroids for inflammatory flares, and intra-articular steroid injections for inflammatory painful interphalangeal OA. Given the current data, the group advises against the use of conventional synthetic or biological disease-modifying anti-rheumatic drugs (DMARDs). CONCLUSIONS: These recommendations provide a structured approach for the management of people living with hand OA in France, aligning with national healthcare practices and patient needs.

The emergence of direct oral anticoagulants (DOACs) has revolutionized the landscape of anticoagulation, while emerging targeted inhibitors of endogenous coagulation pathways have introduced novel dimensions to anticoagulant therapy. This study aimed to systematically characterize the evolving research landscape through a comprehensive bibliometric analysis, elucidating historical development, research hotspots, and emerging trends in this field. A total of 1993 relevant publications (1990-2024) was systematically retrieved from the Web of Science Core Collection. The bibliometric tools including CiteSpace and HistCite were employed to perform the analysis of historical characteristics, evolution analysis of active topics, and identification of emerging trends. The number of articles in this field was growing rapidly, with the USA, China, and Canada emerging as predominant contributors. Moreover, four principal investigators demonstrated sustained academic dominance through high publication output: Zhao Jinhua, Lip Gregory Y.H., Weitz Jeffrey I., and Gao Na. Three distinct research frontiers were identified, including clinical application and medication safety of DOACs, therapeutic potential of factor XI inhibitors for thrombosis prevention with reduced bleeding risks, and the exploration of fucosylated chondroitin sulfate as a novel iXase-targeting anticoagulant. This study presents a systematic review of DOACs and inhibitors targeting endogenous coagulation pathways in antithrombotic therapy. By identifying current research priorities and emerging trends, this analysis serves as an invaluable resource to guide scholars in recognizing novel therapeutic targets and advancing the development of next-generation anticoagulant drugs. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Background and Objective: According to international guidelines, glucosamine and chondroitin, regarded as slow-acting drugs for osteoarthritis (SYSADOAs), have been first-line treatments for knee osteoarthritis (OA); however, their efficacies remain controversial. Additionally, the efficacies of plant extract cocktails, SKI306X, and its newer formulation, SKCPT, have not been well investigated. To evaluate the effectiveness and safety of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) in patients with knee OA. Materials and Methods: Electronic databases were systematically searched to identify randomized controlled trials (RCTs) assessing the effectiveness and safety of SYSADOAs, including chondroitin sulfate, glucosamine sulfate, and SKCPT/SKI306X. The outcomes included pain relief, functional improvements, and safety profiles. The outcome measurements were compared between the treatment and control groups, including placebo and non-placebo groups, within and after 3 months of follow-up. Results: Analysis of 21 RCTs showed significantly greater improvement in pain relief in the treatment group compared with the placebo group both within (standard mean difference [SMD], 0.38; 95% confidence interval [CI], 0.18-0.57; p < 0.001) and after 3 months of follow-up (SMD, 0.22; 95%CI, 0.03-0.42 p = 0.023). The treatment group also showed significantly greater functional improvements regardless of follow-up. Pain and functional improvement did not differ significantly between the treatment and non-placebo groups. Regarding the safety profile, the risk ratios did not differ significantly between the treatment and control groups, including the placebo and non-placebo subgroups. Conclusions: Glucosamine, chondroitin, and SKCPT/SKI306X improved the pain and function and were non-inferior to pharmacologic drugs for up to 12 months. These findings support the clinical use of these SYSADOAs to treat knee OA. Level of Evidence: Therapeutic Level II.