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Supplementation of feed with organic zinc (Zn) has long been discussed as an alternative to inorganic Zn in pigs, but its effects on growth performance are mixed. This meta-analysis was conducted to provide a comprehensive evaluation of the influence of organic Zn on the growth performance of weanling pigs, on the basis of average daily gain (ADG), average daily feed intake (ADFI), and feed to gain ratio (F/G). We screened the PubMed and Web of Science databases (published before December 31, 2022; limited to English) systematically and contrasted organic Zn supplementation with inorganic Zn supplementation. There were 680 retrievals of studies, of which 16 (1389 pigs, 37 records) were eligible to analyze. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. The subgroup analysis was classified as organic Zn source (Zn-amino acid (Zn-AA), Zn-glycine (Zn-Gly), Zn-methionine (Zn-Met), Zn-Lysine (Zn-Lys), proteinate complex Zn (Zn-Pro), chitosan-Zn (Zn-CS) or Zn-lactate (Zn-Lac)) and Zn additive dose (low, medium, or high, i.e., lower than, equal to or higher than the requirement of NRC). Organic Zn addition in the weaning phase increased the ADG (P < 0.001) and the ADFI (P = 0.023) and decreased the F/G (P < 0.001). Specifically, for the organic sources, only Zn-CS supplementation presented significant effects on the ADG (P < 0.001), ADFI (P = 0.011), and F/G (P < 0.001). Moreover, medium-dose organic Zn supplementation had positive effects on ADG (P = 0.012), ADFI (P = 0.018), and F/G (P < 0.001). Our results indicate that organic Zn added to diets greatly improves the growth performance of weanling pigs. © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

There is no research on the comparative effects of nutraceuticals on weight loss in adults with overweight or obesity. This study aimed at quantifying and ranking the effects of different nutraceuticals on weight loss. We searched PubMed, Scopus, and Web of Science to November 2022. We included randomized trials evaluating the comparative effects of two or more nutraceuticals, or compared a nutraceutical against a placebo for weight loss in adults with overweight or obesity. We conducted random-effects network meta-analysis with a Frequentist framework to estimate mean difference [MD] and 95% confidence interval [CI] of the effect of nutraceuticals on weight loss. One hundred and eleven RCTs with 6171 participants that investigated the effects of 18 nutraceuticals on body weight were eligible. In the main analysis incorporating all trials, there was high certainty of evidence for supplementation of spirulina (MD: -1.77 kg, 95% CI: -2.77, -0.78) and moderate certainty of evidence that supplementation of curcumin (MD: -0.82 kg, 95% CI: -1.33, -0.30), psyllium (MD: -3.70 kg, 95% CI: -5.18, -2.22), chitosan (MD: -1.70 kg, 95% CI: -2.62, -0.78), and Nigella sativa (MD: -2.09 kg, 95%CI: -2.92, -1.26) could result in a small improvement in body weight. Supplementations with green tea (MD: -1.25 kg, 95%CI: -1.68, -0.82) and glucomannan (MD: -1.36 kg, 95%CI: -2.17, -0.54) demonstrated small weight loss, also the certainty of evidence was rated low. Based on our findings, supplementations with nutraceuticals can result in a small weight loss in adults with overweight or obesity.

Despite various strategies, overweight and obesity problems are still increasingly prevalent worldwide with serious health outcomes. Consequently, the continuous demand for more effective, safe and acceptable therapies for reducing body weight is also escalating-including complementary and alternative therapies (CATs). The aim of this review is to provide a summary of the most commonly- and recently-used CATs, with evaluation of their safety and efficacy for weight loss. Electronic scientific databases such as Scopus, PubMed and EBSCO Host were explored for articles that reported CATs for overweight and obesity treatment from 2015 to December 2019. Only systematic reviews, meta-analysis and randomized controlled trials (RCTs) published in English were included. Studies whereby CATs were not utilized for reducing body weight were excluded. Eight systematic reviews and meta-analyses and 11 additional RCTs with 765 participants (50.2% overweight and 49.8% obese) related to hypnotherapy, acupuncture and dietary supplements met the inclusion criteria. Their results suggested that spirulina, chitosan, probiotic, EPA + DHA, vitamin D, fiber, and herbal extract supplementation may all provide small reductions in body weight (ranging from 1-10 kg). Interestingly, hypnotherapy and acupuncture reported significantly greater reduction in body weight compared with placebo (p < 0.001 and p < 0.0001, respectively). Nonetheless, the evidence is still relatively limited and not encouraging to provide a definitive conclusion due to the methodological shortcomings and the presence of adverse events in chitosan and fiber supplementation. Hence, studies of this nature need to be further replicated and improved to corroborate the efficacy and safety of the CATs to combat weight issues.

BACKGROUND/OBJECTIVES: A systematic review with meta-analysis was conducted to synthesise evidence on the efficacy of dietary supplements containing isolated organic compounds for weight loss. SUBJECTS/METHODS: Four electronic databases (Medline, Embase, Web of Science, Cinahl) were searched until December 2019. Sixty-seven randomised placebo-controlled trials of dietary supplements containing isolated organic compounds for weight loss were included. Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid and fructans, comparing mean weight difference post-intervention between participants receiving the dietary supplement or placebo. RESULTS: Statistically significant weight differences compared to placebo were observed for chitosan (-1.84 kg; 95% confidence interval [CI] -2.79, -0.88; p < 0.01), glucomannan (-1.27 kg; 95%CI -2.45, -0.09; p = 0.04), and conjugated linoleic acid (-1.08 kg; 95%CI -1.61, -0.55; p < 0.01). None met our threshold for clinical significance (≥2.5 kg). There was no statistically significant effect on weight for fructans compared to placebo (p = 0.24). For dietary supplements with an inadequate number of trials for meta-analysis, a statistically and borderline clinically significant weight difference compared to placebo was found for modified cellulose, manno-oligosaccharides (in males), blood orange juice extract, and three multiple-ingredient dietary supplements. These were only reported in one trial of each. Thus, more evidence is needed before recommending them for weight loss. CONCLUSIONS: While some dietary supplements containing isolated organic compounds warrant further investigation to determine efficacy and safety, there is currently insufficient evidence to recommend any of these dietary supplements for weight loss. © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran's Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger's linear regression test. Among the items evaluated, blood triglyceride and HDL-cholesterol showed the highest heterogeneity, respectively. Other than blood HDL-cholesterol, total cholesterol, and triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for serum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in reducing the risk of cholesterol related metabolic disorder.

BACKGROUND: Chitosan supplementation has been shown to modulate glycemic levels; however, studies have reported conflicting results. The present meta-analysis with trial sequential analysis was conducted to verify the overall influence of chitosan on glycemic levels in patients with metabolic syndrome. METHODS: The PubMed, Cochrane library, and EMBASE databases were systematically searched for randomized controlled studies of chitosan intake and glycemic levels. RESULTS: A total of ten clinical trials including 1473 subjects were included in this meta-analysis. Pooled effect sizes were determined by random-effects meta-analysis. Subgroup analysis was performed to analyze the sources of heterogeneity and their influence on the overall results. The results revealed a significant reduction in fasting glucose levels (SMD: - 0.39 mmol/L, 95% CI: - 0.62 to - 0.16) and hemoglobin A1c (HbA1c) levels (SMD: -1.10; 95% CI: - 2.15 to - 0.06) following chitosan supplementation but no effect on insulin levels (SMD: - 0.20 pmol/L, 95% CI: - 0.64 to 0.24). Subgroup analyses further demonstrated significant reductions in fasting glucose levels in subjects administered 1.6-3 g of chitosan per day and in studies longer than 13 weeks. Trial sequential analysis of the pooled results of the hypoglycemic effect demonstrated that the cumulative Z-curve crossed both the conventional boundary and trial sequential monitoring boundary for glucose and HbA1c. CONCLUSIONS: The glucose level of patients who are diabetic and obese/overweight can be improved by supplementation with chitosan for at least 13 weeks at 1.6-3 g per day. Additional clinical research data are needed to confirm the role of chitosan, particularly in regulating glycosylated hemoglobin and insulin.

The use of dietary supplements for weight loss has gained significant momentum. Polyglucosamine, a chitosan derivative, is a dietary supplement increasingly used for weight loss. In this meta-analysis, we systematically summarized and quantified the key findings of four randomized, placebo-controlled clinical trials examining the effects of polyglucosamine supplementation and caloric restriction, and physical activity on body weight, body mass index (BMI), and waist circumference in subjects with overweight and obesity. The control group was set with a physical activity from 6-7 MET-h/week activity and up to 21 MET-h/week activity with caloric restriction. Compliance in the latter trials was reported via a follow-up questionnaire with the individual participants. The analysis included 399 subjects followed for a period ranging from 12 weeks to one year. Subjects' age ranged from 21-75 years, BMI from 26-45 kg/m2, and all were white European or Caucasian in ethnicity. The meta-analyzed mean differences for random effects showed that polyglucosamine supplementation improves weight loss by -1.78 kg [-2.78, -0.79], BMI by -1.52 kg/m2 [-3.58, 0.54], and improves waist circumference reduction by -1.45 cm [-2.77, -0.12]. In conclusion, the use of polyglucosamine supplementation in conjunction with lifestyle behavioral therapies can be effective for weight reduction. Further studies are needed to examine the long-term effects of polyglucosamine supplementation on weight loss and other metabolic parameters.

Although several clinical trials studied the efficacy of chitosan on weight loss, controversial results have been found. Herein, we evaluated randomized controlled trials (RCTs) of chitosan consumption in adult participants on body weight and body composition through a meta-analysis with trial sequential analysis (TSA). We searched EMBASE, MEDLINE, Web of Science, and CENTRAL databases. The primary body composition indices including body weight, body mass index (BMI), waist circumference, body fat, and hip circumference were extracted. The quality of included articles was assessed according to the Cochrane risk of bias tool. Data were pooled using the random-effects models and calculated as weighted mean difference (WMD) with 95% confidence intervals (CI). Heterogeneity investigated using I2 statistics. TSA, subgroup analyses, sensitivity analysis, meta-regression and publication bias were also evaluated. Overall, 15 eligible trials (18 treatment arms) with 1130 subjects were included. The pooled analyses revealed a significant reduction in body weight (WMD, -0.89 kg; 95% CI, -1.41 to -0.38; P = 0.0006), BMI (WMD, -0.39 kg/m2; 95% CI, -0.64 to -0.14; P = 0.002) and body fat (WMD, -0.69%; 95% CI, -1.02 to -0.35; P = 0.0001) receiving chitosan supplementation. Subgroup analyses also showed that consuming chitosan in dose (>2.4 g/d), shorter-term (<12 weeks), studies with parallel design and studies including participants with obese or overweight had positive effects on body composition. TSA provided conclusive evidence for the benefit of chitosan supplementation. Our findings provided evidence that chitosan consumption might be a useful adjunctive pharmacological therapeutic tool for body weight management particularly in overweight/obese participants. Further well-constructed clinical trials that target body weight and body composition as their primary outcomes are needed.

Background and objectives: Erratic results have been published concerning the influence of the dietary supplement chitosan used as a complementary remedy to decrease the body weight of overweight and obese people. The published articles mention as secondary possible benefits of usage of chitosan the improvement of blood pressure and serum lipids status. We performed a meta-analysis evaluating body weight, body mass index, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure among overweight and obese patients. Materials and Methods: Searching MEDLINE, Cochrane up to December 2017 on clinical trials that have assessed the influence of chitosan used as a dietary supplement on overweight and obese patients. An additional study was identified in the References section of another meta-analysis. A total of 14 randomised control trials (RCT) were used to assess the effect on body weight, serum lipids and blood pressure. Results: The usage of chitosan as a dietary supplement up to 52 weeks seems to slightly reduce the body weight (-1.01 kg, 95% CI: -1.67 to -0.34). Considering the other parameters studied, the most significant improvement was observed in systolic and diastolic blood pressure: -2.68 mm Hg (95% CI: -4.19 to -1.18) and -2.14 mm Hg (95% CI: -4.14 to -0.14) in favour of chitosan versus a placebo. Conclusions: Based on the meta-analysis realized with 14 RCT we concluded that the usage of chitosan as a dietary supplement can lead to a slight short- and medium-term effect on weight loss and to the improvement of serum lipid profile and cardiovascular factors.

BACKGROUND: Chitosan is a popular dietary fiber often used to reduce dietary fat absorption to control weight and blood lipids. However, its effects on blood pressure (BP) have not been fully elucidated. We evaluated the effects of chitosan administration on systolic blood pressure (SBP) and diastolic blood pressure (DBP) through a pooled analysis of available randomized controlled trials (RCTs). MATERIALS AND METHODS: Electronic searches were conducted in Medline, Cochrane Library, Scopus, and EMBASE to identify relevant human placebo-control RCTs. Trials that reported BP changes from baseline to study endpoint in patients receiving treatment of chitosan were included for analysis. Weighted mean difference (WMD) and 95% CIs were pooled using fixed-effects or random-effects models. Statistical heterogeneity, prespecified subgroup, publication bias, sensitivity analysis, and meta-regression assessments were also tested. RESULTS: Six hundred and seventeen participants from eight trials with 10 arms were included. Overall, chitosan administration did not significantly lower SBP (WMD: -1.41 mmHg, 95% CI: -3.29 to 0.47; P=0.14) and DBP (WMD: -0.61 mmHg, 95% CI: -1.75 to 0.52; P=0.29). However, our subgroup analyses indicated that chitosan consumption significantly reduced DBP in shorter-term (<12 weeks) and higher-dose (>2.4 g/day) arms. Funnel plots or Egger's tests analysis (P=0.36 and 0.43 for SBP and DBP, respectively) demonstrated that there was no significant publication bias in this study. CONCLUSION: This meta-analysis indicates that chitosan consumption significantly decreases DBP at higher dosage and in shorter-term interventions, while chitosan has no significant effects on SBP. However, these results should be interpreted cautiously because of the limited eligible RCTs included in this meta-analysis; further large-scale, well-designed RCTs on this topic are urgently needed.

INTRODUCTION: Fixed orthodontic appliances can serve as a breeding ground for bacterial accumulation and colonization, which are responsible for the development of white spot lesions (WSLs). OBJECTIVE: This study evaluated and compared the antibacterial activity of chitosan nanoparticle-coated and uncoated nickel-titanium (NiTi) orthodontic archwires against Streptococcus mutans (S. mutans) and Lactobacillus acidophilus (L. acidophilus). MATERIAL AND METHODS: Thirty patients received 0.016-in NiTi archwires, using a split-mouth design. Sixty archwires were randomized into two groups: Group A, nanochitosan-coated (n = 30, experimental), and Group B, uncoated (n = 30, control). Allocation was determined using sequentially numbered, opaque, sealed envelopes prepared by an independent researcher, with assignments concealed until allocation. The ionic gelation technique was used for coating. After six weeks in the oral cavity, archwires were retrieved, and bacterial presence was evaluated as Colony Forming Units (CFUs), through culture formation. RESULTS: A statistically significant difference was observed in the mean CFU counts of S. mutans and L. acidophilus between the experimental and control groups (p < 0.001). The mean CFU values for S. mutans were 0.12 × 106 CFU/ml (SD ± 0.38; experimental) and 1.82 × 106 CFU/ml (SD ± 0.69; control). For L. acidophilus, mean CFUs were 0.036 × 106 CFU/ml (SD ± 0.06; experimental) and 1.96 × 106 CFU/ml (SD ± 0.65; control). CONCLUSION: Orthodontic archwires coated with nanochitosan demonstrated significantly greater antimicrobial activity against S. mutans and L. acidophilus compared with uncoated archwires. INTRODUÇÃO: Os aparelhos ortodônticos fixos podem servir como um ambiente propício para o acúmulo e colonização bacteriana, responsáveis pelo desenvolvimento de lesões de mancha branca (LMBs). OBJETIVO: Este estudo avaliou e comparou a atividade antibacteriana de fios ortodônticos de níquel-titânio (NiTi), revestidos e não revestidos com nanopartículas de quitosana, contra bactérias Streptococcus mutans (S. mutans) e Lactobacillus acidophilus (L. acidophilus). MATERIAL E MÉTODOS: Trinta pacientes receberam arcos ortodôntico

BACKGROUND: Periodontitis is a chronic inflammatory condition marked by progressive attachment loss and bone destruction. Traditional therapy includes mechanical debridement; however, subgingival pathogens persist in complex biofilms. Hence photodynamic therapy using photosensitizers for elimination of subgingival pathogens is being widely studied. Indocyanine green is one such photosensitizer which when used along with lasers has shown promising results. Photosensitizer bioavailability is found to be better when used in the form of nanoparticles. OBJECTIVE: This study aimed to evaluate the efficacy of photodynamic therapy (PDT) using indocyanine green (ICG) loaded chitosan nanoparticles (CS-NPs) as an adjunct to scaling and root planing (SRP) in patients with chronic periodontitis. METHODS: In this randomized controlled interventional study, 40 patients with moderate to severe periodontitis were randomly allocated into test (SRP + PDT) and control (SRP alone) groups. ICG-CS-NPs were applied locally and activated with 810 nm diode laser. Clinical parameters (plaque index-PI, gingival index-GI, probing pocket depth-PPD, and clinical attachment level-CAL) were recorded at baseline and 3 months. Subgingival plaque samples were analysed for colony forming units (CFU). RESULTS: In both the treatment groups there was a significant improvement in all the clinical parameters from baseline to 3 months. When intergroup comparisons were made the test group showed a statistically significant improvements in probing pocket depth, clinical attachment level as well as colony forming units (CFU) of Porphyromonas gingivalis (Pg) & Aggregatibactor actinomycetemcomitans (Aa) at 3 months post therapy. CONCLUSION: Chitosan (CS) encapsulated ICG- Nanoparticles mediated PDT when used as an adjunct to SRP in the treatment of chronic periodontitis patients can render improvements in clinical as well as microbiological parameters. CS-ICG-NP can be considered as an alternative to conventional photosensitizers used in PDT for the treatment of chronic periodontitis.

OBJECTIVE: This study compared the efficacy of continuous chelation with etidronate and sequential chelation with chitosan to traditional chelation with EDTA in reducing bacterial levels in teeth with necrotic pulp. METHODS: Sixty patients with single-rooted and single-canalled teeth with pulp necrosis were randomly divided into three groups based on the irrigation protocol with passive ultrasonic activation (PUI). G1 (Control): NaOCl/EDTA+PUI, G2: NaOCl/etidronate+PUI, and G3: NaOCl/chitosan+PUI. Microbiological samples were taken before (S1) and after the root canal preparation and irrigation protocol (S2). Total bacterial counts were measured using 16S ribosomal RNA gene-based real-time quantitative polymerase chain reaction. Statistical analysis was performed using the Wilcoxon signed rank test and the Kruskal-Wallis test (P<0.05). RESULTS: All S1 samples tested positive for bacteria, and total bacterial counts from S1 to S2 were significantly reduced across all three groups (p<0.001), with a mean reduction of 97.7% in G1, 96.3% in G2, and 96.8% in G3. No significant differences were observed among the groups (p=0.345). Bivariate and multivariate analyses revealed that none of the patient-related or tooth-related variables had a significant effect on bacterial reduction (p>0.5). CONCLUSION: All three irrigation protocols, including continuous chelation with etidronate, sequential chelation with chitosan, and traditional chelation with EDTA, significantly reduced bacterial levels in teeth with primary endodontic infections.Etidronate and chitosan may serve as alternatives to EDTA; however, further prospective clinical studies are required to validate and recommend their use in clinical practice.(EEJ-2025-07-114).

BACKGROUND: Although effective for atrophic acne scars, ablative fractional CO₂ laser (AFCL) causes unavoidable downtime and carries the potential for post-inflammatory hyperpigmentation (PIH). OBJECTIVES: To evaluate the efficacy and safety of hydroxybutyl chitosan (HBC) in wound healing and to investigate the possible molecular mechanisms of HBC. METHODS: Eighteen participants were enrolled in a split-face study, with each hemiface randomly assigned to receive either HBC or positive control therapy (PC: desonide cream, epidermal growth factor gel, and fusidic acid cream in combination) following AFCL. Clinical assessments included erythema, edema, pain, the time to decrustation, the skin barrier function, and melanin were assessed. In parallel, a mouse skin wound healing model was employed to investigate the effects of HBC. The expression of interferon regulatory factor 7 (IRF7) and cathepsin S (Ctss), as well as M1 and M2 macrophage polarization, was evaluated by immunohistochemistry and Western blot analysis of mouse skin tissues. RESULTS: Although HBC exhibited a slightly delayed onset of wound healing compared to the PC protocol, it achieved comparable outcomes by Days 7 and 28 between the groups. HBC showed more early pain but no steroid-related irritation and better moisturization. In mice, HBC demonstrated effects comparable to PC drugs, promoting macrophage M2 polarization and upregulating IRF7 and Ctss expression. CONCLUSIONS: HBC is effective and safe for promoting wound healing post AFCL. HBC upregulates IRF7 and Ctss expression and promotes macrophage M2 polarization. The expression of IRF7/CTSS may be correlated with M2 polarization of macrophages. CLINICAL TRIAL REGISTRATION NO: ChiCTR2200063765. © 2026 Wiley Periodicals LLC.

AIM: To compare non-surgical subgingival re-instrumentation with an oscillating chitosan brush (OCB), with and without a novel chitosan hydrogel (LGX), in residual or recurrent pockets in step 3 or 4 of stage III-IV periodontitis patients. MATERIALS AND METHODS: Patients presenting with residual 5-8 mm probing pocket depth (PPD) and modified bleeding on probing (mBOP) scores of 2 or 3 at 3-8 teeth were randomly assigned to treatment with either an OCB alone or OCB combined with LGX gel. Treatment was repeated at 3 months. Examinations took place at baseline (BL) and at 1 (Tp1), 3 (Tp2) and 6 months (Tp3) thereafter. Primary outcomes comprised changes in PPD, mBOP and pocket closure (PC). RESULTS: Thirty-eight patients were included in the analysis. Both treatments resulted in significant PPD and mBOP reductions at all follow-ups. However, sites treated with adjunctive LGX resulted in significantly greater PPD reductions and higher rates of PC compared to OCB alone (Tp2: PPD reductions 1.55 vs. 1.04, p < 0.001; PC: 67.1% vs. 46.4%, p < 0.001; Tp3: PPD reductions 1.73 vs. 1.33, p = 0.001; PC: 76.8% vs. 60.8%, p < 0.01). CONCLUSION: Adjunctive LGX gel application enhanced the efficacy of repeated subgingival re-instrumentation with OCB, reducing the need for additional step 3 interventions. TRIAL REGISTRATION: ClinicalTrials.gov identification number: NCT05773911, first submitted: 2022-09-15 (https://clinicaltrials.gov/study/NCT05773911). © 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

OBJECTIVES: To clinically evaluate the effectiveness of phosphorylated nano chitosan (Pchi-ACP), a novel biomimetic scaffold, and self-assembling peptide P11-4 (SAP-P11-4) in treating white spot lesions (WSLs) compared to a conventional remineralizing agent. METHODS: Thirty-three patients with 101 WSL-affected teeth, either post-orthodontic or early enamel caries, were randomly allocated to Pchi-ACP, SAP-P11-4, or casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). Materials were professionally applied twice weekly for 1.5 months. Assessments were performed at baseline (T0), immediately after the first in-office application (T1), six weeks after the final application (T2), and at 1, 3, 6, 9, and 12 months (T3-T7) using ICDAS scoring, computer-assisted surface area analysis of standardized photographs, and DIAGNOdent measurements. All participants received standardized oral hygiene instructions. Generalized linear mixed models (GLMMs) were applied to account for repeated measures and clustering, with treatment group, time, and their interaction as fixed effects (p < 0.05). RESULTS: All groups showed significant improvements in ICDAS and DIAGNOdent values over 12 months (p < 0.05). Pchi-ACP achieved the greatest improvement, reducing median ICDAS scores (0.00 [1.00]), followed by SAP-P11-4 (1.00 [2.00]) and CPP-ACP (2.00 [1.00]) (p = 0.004-0.046). The WSL surface area was reduced to 1.14 [1.93] of the tooth surfaces for Pchi-ACP, significantly smaller than 6.39 [3.54] for SAP-P11-4 and 20.41 [26.85] for CPP-ACP (p1 < 0.001, p2 < 0.001, p3 = 0.0004). GLMM analysis confirmed a significant time effect and group-by-time interaction, validating the superior and sustained performance of Pchi-ACP over 12 months. Pairwise comparisons confirmed Pchi-ACP's superiority at all time points. CONCLUSIONS: Pchi-ACP demonstrated superior clinical effectiveness in remineralizing early enamel lesions compared to SAP-P11-4 and CPP-ACP, supporting its potential as a promising preventive and regenerative treatment option. CLINICAL SIGNIFICANCE: Pchi-ACP represents a valuable non-invasive treatment for WSLs, enabling effective enamel repair through a biomimetic approach. TRIAL

OBJECTIVE: To explore the role of intraoperative implantation modified chitosan medical membrane (MCMM) in postoperative inflammation and recurrence for primary pterygium excision with adjunctive amniotic membrane transplantation (AMT). DESIGN: Prospective, randomized, controlled, single-center clinical trial. METHODS: We included 54 patients (54 eyes) with primary pterygium scheduled for pterygium excision. They were randomly divided into two groups. The cryopreserved amniotic membrane (AM) group accepted pterygium excision with adjunctive AMT, and the MCMM group received AMT with adjunctive subconjunctival MCMM implantation during surgery. A follow-up of 3 years was conducted to observe pterygium recurrence. Primary outcomes included recurrence rate and tear cytokine levels after surgery. Secondarily, epidemiological data, visual acuity change, intraocular pressure (IOP), and ocular surface score were also collected. Data were analyzed using SPSS software version 26.0. The χ2 test and Student t test were used to compare qualitative and continuous quantitative variables, respectively. RESULTS: A total of 54 subjects with 54 eyes were included, 26 in the AM group and 28 in the MCMM group. Corneal recurrence of pterygium occurred in 3 cases (11.5%), whereas 2 cases (7.7%) showed conjunctival recurrence in the AM group. Two cases (7.1%) experienced corneal recurrence, and 2 cases (7.1%) had conjunctival recurrence in MCMM group. Nonetheless, there was no significant difference in the recurrence rate of pterygium between the AM and the MCMM group (P = .903). In the 1-month and 3 to 6-month groups postoperatively, the MCMM group showed a significant reduction in the levels of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) in the tear fluid compared to the AM group, respectively (IL-8: P = .003, TNF-α: P = .044, for 1 month; IL-8: P = .016 for 3 to 6 months, respectively), indicating that MCMM has a significant inhibitory effect on ocular surface inflammation after surgery. When comparing the patients with recurrent and non-recurrent conditions within each group after the surgery, both TNF-α and IL-8 showed an increase 1 month after the operation (AM group:

BACKGROUND: To investigate if chitosan nanoparticles (ChNPs), incorporated into three-dimensional-printed clear aligners (CAs), retain their antibiofilm activity against Streptococcus mutans after extended use in the oral environment. Additionally, to measure the impact of the aligners on patient-reported outcomes. METHODS: Participants were randomly assigned to two groups: conventional CA and CA containing 3% ChNPs. They were instructed to wear their aligners for either one week (N = 16) or two weeks (N = 16) before CAs were retrieved. Clinical parameters, including plaque index (PI) and bleeding on probing (BOP), were measured, and the devices were weighed at baseline and at endpoints. A self-reported questionnaire was also completed. Samples from the retrieved devices underwent antibiofilm assays against S. mutans (American Type Culture Collection strain and a clinical isolate). RESULTS: After two weeks, the experimental group exhibited significantly lower PI and BOP scores compared to the control group (4.61 ± 1.22 vs 16.16 ± 5.26, and 3.83 ± 1.03 vs 5.35 ± 3.03, respectively). The number of colony-forming units was significantly reduced in the ChNPs-containing CAs (effect size > 0.9), with a greater effect against the American Type Culture Collection strain than the clinical isolate at both time points (effect size week 1: 0.953, week 2: 0.621). The ChNPs did not affect the device weight after in vivo aging, and the participants reported higher satisfaction levels. CONCLUSIONS: Three-dimensional-printed CAs with ChNPs retained strong antibiofilm activity against S. mutans after two weeks of in vivo use. This was clinically reflected by lower PI and BOP scores and improved self-reported outcomes.

BACKGROUND: Antifungals are the standard treatment for onychomycosis. However, oral antifungals present contraindications and potential drug-drug interactions, while topical antifungals suffer from limited efficacy and penetration. Recently, researchers have explored physical therapies, including laser and photodynamic therapy. OBJECTIVE: To evaluate the clinical efficacy of combining diode laser therapy with photodynamic therapy and ciclopirox 8% hydroxypropyl chitosan (HPCH) nail lacquer in treating onychomycosis. METHODS: We conducted a randomised controlled clinical trial involving patients with onychomycosis. A total of 26 patients were enrolled and followed for 12 months. Participants received either eight sessions of laser treatment combined with three sessions of photodynamic therapy, or daily treatment with ciclopirox 8% HPCH. RESULTS: The clinical cure rate was 94.1% in the group treated with laser and photodynamic therapy, compared to 53.3% in the group treated with ciclopirox 8% HPCH (p = 0.008). All patients who achieved clinical cure with either treatment also reached mycologic and complete cure, with a rate of 100%. The average time to healing was significantly shorter for the group receiving laser and photodynamic therapy (3.6 ± 1.2 months) than for those treated with ciclopirox 8% HPCH nail lacquer (9.2 ± 1.6 months) (p < 0.001). In the laser and photodynamic therapy group, adverse events, specifically subungual hematoma and blisters, occurred in 11.4% of patients, with a recurrence rate of 33.3%. No adverse events or recurrence were observed in patients treated with ciclopirox 8% HPCH. CONCLUSIONS: Treatment of onychomycosis using diode laser and photodynamic therapy results in higher clinical cure rates and shorter healing times compared to the reference treatment with 8% ciclopirox HPCH. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05809297. © 2025 The Author(s). Mycoses published by Wiley‐VCH GmbH.

Oral lichen planus (OLP) is a chronic inflammatory disorder with limited topical treatment options and long-term corticosteroid dependency. This study investigates a novel atorvastatin-loaded hyalurosomal gel (ATV-Hyalugel) as a topical adjuvant to reduce systemic corticosteroid use in severe OLP. The objective of the study is to develop, optimize, characterize ATV-Hyalugel and evaluate its clinical efficacy in a randomized controlled clinical trial. ATV-loaded hyalurosomes (ATV-HAs) were prepared via thin-film hydration and optimized using an I-optimal mixture design (independent variables: phospholipid, Tween 80, and hyaluronic acid; responses: entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimal formulation was incorporated into a chitosan gel, which was characterized for its pH, rheological behavior, and in-vitro drug release. Four weeks randomized controlled trial (n = 90) compared: group one received standard prednisolone (40 mg/day) while group two received half-dose prednisolone (20 mg/day) in combination with ATV-Hyalugel (topically, three times daily). Pain and ulcer scores were recorded weekly. Between-group comparisons were performed using the Mann-Whitney U test (non-parametric; α = 0.05), and within-group improvement from baseline to Week 4 was assessed using the Kruskal-Wallis test. Optimized ATV-HAs demonstrated high EE% (79.1 ± 0.4%), uniform PS (221.2 ± 5.1 nm), and stable ZP (-31.6 ± 0.2 mV). ATV-Hyalugel exhibited mucosa-compatible pH (6.48 ± 0.2), pseudoplastic rheology, and a sustained release profile dominated by diffusion-driven kinetics. Clinically, group two achieved therapeutic equivalence to group one by Week 2 (p > 0.05), despite receiving 50% less corticosteroid. Both groups showed significant symptom reduction from baseline to Week four (p < 0.0001, Kruskal-Wallis). No adverse events were reported with ATV-Hyalugel. ATV-Hyalugel enables a 50% corticosteroid dose reduction while maintaining clinical efficacy. Its favorable release kinetics and safety profile support its use as an innovative adjuvant therapy for severe OLP. © 2025. The Author(s).

BACKGROUND: The rise of multidrug-resistant (MDR) Gram-negative bacterial infections, particularly those caused by Pseudomonas aeruginosa and Acinetobacter baumannii, necessitates innovative treatment strategies. Usnic acid (UA), a natural compound with antimicrobial properties, has limited clinical use due to poor solubility and toxicity. This study evaluated the antibacterial, antibiofilm, and hemocompatibility profiles of UA encapsulated in chitosan-coated liposomes (Lipo-UA-Chi), alone and in combination with polymyxin B (PMB). METHODS: UA, PMB, Lipo-UA-Chi, and their combinations were tested in vitro against MDR clinical strains of P. aeruginosa and A. baumannii. Antibacterial activity was assessed via broth microdilution and checkerboard assays. Antibiofilm inhibition and eradication were evaluated using the crystal violet method. Hemolytic activity was measured to assess cytotoxicity. RESULTS: The Lipo-UA-Chi + PMB combination demonstrated additive or synergistic interactions in all tested strains, with MIC reductions of up to 128-fold for PMB and 4-fold for Lipo-UA-Chi. This combination also achieved superior biofilm inhibition, reaching up to 100% in specific P. aeruginosa strains, and eradication of up to 81.3%. CONCLUSION: These findings highlight Lipo-UA-Chi combined with PMB as a promising and biocompatible strategy to improve antimicrobial efficacy and biofilm control in MDR infections. Although limited to in vitro evaluation, these findings support the potential of this formulation as a promising alternative to current polymyxin-based regimens.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder that impairs motor function in humans. This research explores the combined neuroprotective effects of carboxymethyl chitosan (CMC) and phloroglucinol (PGL) in a zebrafish (ZF) model of PD induced by rotenone (ROT). The structural features of the CMC-PGL conjugate were analysed using UV-visible, Fourier Transform Infrared (FT-IR), and fluorescence spectroscopy. The phenolic content of conjugated sample was estimated and confirmed the conjugation of CMC with PGL. The LD50 of CMC-PGL was determined as 8 μg/mL in ZF embryo (ZFE). In vivo experiments revealed that ROT exposure decreased locomotor activity, while CMC-PGL 4 mg/L treated ZF exhibits improved was confirmed by the ToxTrac analysis. Behavioural parameters improvements were also seen in Novel tank test (NTT) and light/dark tests with CMC-PGL 4 mg/L (LD) and CMC-PGL 8 mg/L (HD) treated ZF. RP- HPLC showed the significant (P < 0.0001) restoration of dopamine (DA) levels post-treatment. Histological analysis showed ROT-induced brain damage in ZF, including necrosis, cytoplasmic vacuolisation, and neuronal degeneration, whereas in the CMC-PGL 4 mg/L showed a decrease in neuronal loss and vacuolisation. These findings suggest that CMC-PGL conjugates may hold promise as therapeutic agents for managing neurodegeneration (ND) associated with PD.

The soil-borne pathogen Sclerotium rolfsii presents a significant challenge to global agricultural productivity due to its persistent sclerotia and resistance to conventional fungicidal treatments. In this study, chitosan‑zinc oxide nanocomposites (CS-ZnO NCs) were synthesized and comprehensively characterized using UV-Vis spectroscopy, FTIR, XRD, DLS, zeta potential analysis, SEM, and EDX. The results confirmed the successful incorporation of ZnO nanoparticles into a chitosan matrix, forming a stable nanocomposite with a positive zeta potential of +41 mV and an average particle size of 204 nm. Structural imaging revealed a compact network with well-distributed ZnO particles. In vitro antifungal assays demonstrated that CS-ZnO NCs significantly inhibited the radial growth of S. rolfsii (87% inhibition) compared to the commercial fungicide Iprodione (Rovral) (70%), and completely suppressed sclerotia formation and reduced mycelial biomass by 98%. Biochemical analysis further revealed marked reductions in fungal total phenolics (77%) and key defense-related enzymes, including peroxidase, phenylalanine ammonia lyase, and polyphenol oxidase (up to 76%). FTIR spectral analysis revealed substantial alterations in fungal protein and membrane structures, indicating that the enhanced antifungal activity results from the synergistic action of chitosan-induced membrane disruption and ZnO-mediated oxidative stress. These findings highlight CS-ZnO NCs as a highly effective and environmentally sustainable alternative to chemical fungicides for the management of S. rolfsii.

Articular cartilage injury often leads to progressive degeneration, necessitating advanced strategies that integrate immunomodulation, stem cell recruitment, and microenvironment regulation. Traditional hydrogels face limitations in spatiotemporal drug release and mechanical adaptability for dynamic joint environments. This study introduces an injectable, self-healing nanocomposite hydrogel engineered through dynamic boronate ester bonds between carboxymethyl chitosan and polyvinyl alcohol, synergizing macrophage-targeted curcumin nanomicelle and chondroinductive icariin. The hydrogel's reversible network enables shear-thinning injectability and reactive oxygen species (ROS)-responsive degradation, ensuring localized anti-inflammatory and pro-regenerative drug release. Curcumin-loaded mannose-functionalized micelles enhance macrophage uptake, polarizing macrophages toward an anti-inflammatory phenotype, while icariin promotes bone marrow mesenchymal stem cell (BMSC) migration and chondrogenic differentiation via Wnt/β-catenin and BMP/Smad pathway activation. In vitro studies demonstrated the hydrogel's capacity to scavenge ROS, suppress pro-inflammatory cytokines, and enhance BMSC recruitment and cartilage-specific matrix synthesis. In vivo evaluation in a rat full-thickness cartilage defect model revealed accelerated repair with organized neocartilage formation, reduced inflammation, and restored subchondral bone architecture. Histological and immunohistochemical analyses confirmed significant collagen II deposition and M2 macrophage polarization, aligning with native tissue regeneration. The hydrogel's biocompatibility and absence of systemic toxicity were validated through hematological and organ histopathology assessments. By dynamically coupling early-stage immunomodulation with sustained chondroinductive signaling, this dual-drug hydrogel disrupts the inflammation-degeneration cycle, offering a cell-free therapeutic platform for functional cartilage restoration. Its design principles provide a blueprint for intelligent biomaterials addressing complex tissue repair challenges.

Cutaneous candidiasis remains a therapeutic challenge owing to limited skin penetration of anti-fungal agents, high recurrence, and increasing resistance to azoles. In this work, a chitosan-based film-forming gel (FFG) was developed incorporating luliconazole (LUL) and carvacrol (CAR) to improve dermal delivery and therapeutic performance. A 3² factorial design was employed to optimize polymer and plasticizer concentrations, with drying time, spreadability, and viscosity as key formulation attributes. The optimized gel exhibited rapid in situ film formation, suitable viscosity, and mechanical resilience. FTIR and DSC confirmed the absence of drug-excipient interactions. In vitro diffusion and ex vivo permeation studies revealed higher drug release, enhanced skin penetration, and greater retention compared with drug suspensions. The synergistic activity of pure LUL and CAR was demonstrated by checkerboard (FICI = 0.5) and well diffusion assays, confirming a fourfold reduction in minimum inhibitory concentrations. Anti-fungal testing of the CAR-LUL gel showed larger inhibition zones than marketed formulations, while time-kill studies validated faster and more sustained fungicidal activity. Safety was confirmed through skin irritation and histopathological evaluations, and stability analysis demonstrated robustness for six months. These findings establish CAR-LUL FFG as a promising topical platform for effective management of resistant Candida infections.

BACKGROUND: The alarming rise of multidrug-resistant (MDR) bacteria, particularly Salmonella spp., has prompted an urgent search for alternative and synergistic antimicrobial strategies. In this study, a novel, green, and multicomponent nanocomposite was synthesized by integrating zinc oxide nanoparticles (ZnO NPs), chitosan (CS), the β-lactam antibiotic ceftazidime (CAZ), and the antidiabetic agent metformin (MTF) straightforward and economical manner. METHODS AND RESULTS: Bacillus subtilis strain ATCC 6633 was used to biosynthesize ZnO NPs, acting as a reliable bio-nanofactory. Various characterization techniques such as FTIR, XRD, TEM, and zeta potential analysis verified the successful integration and structural integrity of the ZnO NPs within the CS nanocomposite containing CAZ and MTF (ZnO/CS/CAZ/MTF). The FTIR spectra confirmed the presence of proteins that act as binding and supportive agents during the biosynthesis process. The produced nanomaterials have a significant positive surface charge of +28.61 mV, which enhances their stability. The particle sizes of the NPs ranged from 9.93 to 17.44 nm. The nanocomposite exhibited strong antibacterial activity against MDR Salmonella enterica subsp., enterica serovar Typhi ATCC 19214, showing a significantly increased inhibition zone of 42 mm and a greatly reduced minimum inhibitory concentration (MIC) value of 8 µg/ml, compared to the separate components. The minimum bactericidal concentration (MBC) value was found to be consistent with the MIC result, emphasizing the potent bactericidal action of the prepared nanocomposite. In silico molecular docking further supported these findings by revealing favorable interactions between the nanocomposite constituents and the outer membrane proteins (OMPs) of Salmonella enterica serovar Typhimurium (PDB ID: 4W4M) and S. typhi (PDB ID: 3UU2). Key interactions included hydrogen bonding, ionic forces, and metal coordination with critical residues. Cytotoxicity assessment using WI-38 lung fibroblast cells revealed an IC₅₀ of 84.26 µg/ml, indicating acceptable preliminary biocompatibility. CONCLUSIONS: The present study demonstrates the novelty of a ZnO-based multicomponent

Quaternized chitosan derivatives conjugated with naturally occurring medicinal compounds have emerged as promising drug-delivery vehicles, exhibiting properties such as site-specificity, enhanced permeation into cancer cells, and reduced efflux of encapsulated drugs. In this study, ferulic acid (FA) was conjugated with quaternized chitosan (QCS) and used for the encapsulation of dimethoxycurcumin (DMC). The resulting nanomicelles were evaluated for activity against colorectal adenocarcinoma. The conjugates were obtained in 74% yield and structurally characterized by FTIR, proton NMR, DSC, and XRD. The DMC-loaded FA-QCS nanomicelles exhibited a spherical morphology under transmission electron microscopy, an average size of approximately 224.63 ± 2.49 nm to 270.6 ± 8.45 nm with a positive surface charge around +30 mV and an entrapment efficiency of 65.57%. The nanomicelles exhibited pH-responsive drug release, with maximum release at pH 5.5, which mimics the tumor microenvironment. In anticolorectal adenocarcinoma evaluations, the DMC-loaded micelles showed selective cytotoxicity and enhanced internalization in the colorectal adenocarcinoma cell lines (HT-29), with a significantly lower IC50 value (0.99 ± 0.16 μg/mL) than that of free DMC (5.43 ± 0.86 μg/mL), inducing cell cycle arrest at the G2/M phase and promoting apoptosis. Notably, the DMC-loaded nanomicelles exhibited reduced toxicity toward the normal fibroblast cell line (L929) compared to pure DMC. Furthermore, cotreatment of DMC-loaded nanomicelles and 5-fluorouracil (5-FU) significantly enhanced anticancer efficacy through synergism (combination index < 1). Overall, this study supports quaternized chitosan and ferulic acid conjugates as potential drug-delivery vehicles that can encapsulate anticancer drug candidates and facilitate combination treatment strategies with chemotherapeutic agents such as 5-FU. However, further mechanistic anticancer and cytotoxic studies are warranted using tumor-bearing animal models and chemotherapy-resistant cell lines.

A vitamin K3 (VK3)-loaded metal-organic framework (Cu/ZIF-8/VK3) was synthesized by a one-pot method. After the coencapsulation of Cu/ZIF-8/VK3 and 5-fluorouracil (5-FU) in the hyaluronate acid (HA)/carboxymethyl chitosan (CMCS) hydrogels formed via an amidation reaction, a drug-controlled release system (Cu/ZIF-8/VK3/5-FU/HA/CMCS) was obtained. In the weakly acidic media, the amide bonds in the HA/CMCS hydrogels are prone to be hydrolyzed, resulting in the release of 5-FU and Cu/ZIF-8/VK3; and the Cu/ZIF-8/VK3 is further degraded in the acidic environment, leading to the release of VK3 and Cu2+. The released Cu2+ can be reduced by glutathione (GSH) to Cu+, which can react with intracellular H2O2 to produce cytotoxic hydroxyl radicals (·OH) for chemodynamic therapy (CDT). On the other hand, H2O2 can be replenished through the redox cycling of VK3 in the presence of NAD(P)H: quinone oxidoreductase-1 (NQO1), generating stable ·OH for enhanced CDT. Cytotoxicity assay demonstrates that the developed drug-controlled release system has excellent biocompatibility, which can effectively inhibit the growth of mouse breast tumor cells 4T1 due to the synergistic chemotherapy and enhanced CDT.

OBJECTIVE: This study aimed to encapsulate calcium ions in mesoporous silica coated with a polyelectrolyte multilayer, incorporate these particles into an experimental mouthrinse, and evaluate their potential to control dental erosion-abrasion. METHODS: Bovine enamel and dentin specimens were assigned to five groups: NaF (225 ppmF⁻), Ca²⁺ (encapsulated calcium), Ca+F (encapsulated calcium + NaF), F+Sn (225 ppmF⁻; 800 ppmSn²⁺), and Control (distilled water). Fluoride availability was measured using an ion-selective electrode. Specimens underwent a 5-day erosive-abrasive cycling model with citric acid challenges, brushing, and treatment with the assigned solutions. Surface loss (µm) was quantified by optical profilometry. Data were analyzed using one-way ANOVA and Tukey's test (α = 5 %). RESULTS: Fluoride-containing solutions exhibited the expected ion availability, and no interaction between fluoride and encapsulated calcium was detected. In enamel, only F+Sn (4.81±0.13) significantly reduced surface loss compared to the Control (9.91±0.06) (p < 0.001). In dentin, Ca+F (10.39±0.48) significantly reduced surface loss relative to the Control (12.07±1.33) (p = 0.014) and did not differ from F+Sn (9.10±1.29) (p = 0.095). NaF and Ca alone showed no significant protective effect for either substrate. CONCLUSIONS: Mesoporous silica loaded with calcium, when combined with NaF, provided protection against dentin erosive wear but did not reduce enamel loss. Tin-containing formulations remained the most effective option for enamel. CLINICAL SIGNIFICANCE: A fluoride mouthrinse containing calcium encapsulated in mesoporous silica demonstrated protective potential for dentin under erosive-abrasive conditions, offering a promising tin-free alternative for individuals with dentin exposure requiring management of erosive tooth wear.

Mastitis is one of the major diseases affecting dairy cattle worldwide. Antibiotic therapy remains the most widely used treatment. However, its effectiveness has been compromised due to the selection of antibiotic-resistant and biofilm-producing pathogenic bacteria. This promotes the search for alternatives that increase the antibacterial and antibiofilm efficacy of antibiotics such ceftiofur (CFT). Nisin (N) and chitosan (CH) may possess these properties. The aim of this study was to evaluate whether N + CFT and CH + CFT combinations enhance the antibacterial activity of the antibiotic on Staphylococcus aureus associated with bovine mastitis, as well as its antibiofilm effect. Two clinical isolates of S. aureus (AMC-43 and AMC-48) and the reference strain ATCC 27543 resistant to CFT were used. Through the microdilution method in 96-well microplates, the combination of sub-inhibitory concentrations of N (320 µg/mL) and CH (400 µg/mL) with CFT (1, 2, 4, and 8 µg/mL) significantly reduced bacterial growth; however, the CH + CFT mixtures were the most efficient. The crystal violet staining method and live cell plating showed antibiofilm activity in biofilm synthesis and in the reduction in living bacterial cells located inside this preformed structure. These results highlight N and CH as potential agents for the prevention or control of bovine mastitis.