Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairment, with no definitive cure currently available. Neuroinflammation, oxidative stress, and amyloid-beta accumulation play central roles in disease progression. While curcumin shows therapeutic promise, its clinical efficacy is limited due to poor bioavailability. This study investigates the neuroprotective effects of chitosan-curcumin nanoparticles in a streptozotocin (STZ)-induced rat model of AD, focusing on cognitive performance, hippocampal integrity, and molecular markers of neurodegeneration. Sixty male Wistar rats were randomly divided into five groups: control, AD, AD + chitosan, AD + curcumin, and AD + chitosan-curcumin. AD was induced via intraventricular injection of STZ (3 mg/kg). Two weeks’ post-induction, cognitive function was assessed using the Morris water maze (MWM). At the end of the treatment period, oxidative stress parameters, inflammatory cytokines, and gene expression levels (IL-1β, IL-6, IL-10, NRF2, PPARγ, BDNF) were measured via real-time PCR. Data were analyzed using one-way ANOVA with Tukey’s post hoc test (p < 0.05). Rats treated with chitosan-curcumin nanoparticles exhibited significantly improved memory and learning compared to all other groups (p < 0.001). There was a marked downregulation of IL-1β and IL-6, along with increased expression of NRF2, PPARγ, and BDNF (p < 0.05). Histological analysis confirmed reduced neuronal damage and increased neuronal density. Chitosan-curcumin nanoparticles demonstrated potent neuroprotective effects, enhancing cognitive performance, reducing inflammation and oxidative stress, and preserving neuronal structure. These multifaceted effects highlight the therapeutic potential of CS–CUR nanoparticles in targeting the core pathological mechanisms of AD. Future studies should focus on long-term safety and efficacy assessments, dose–response optimization, and mechanistic pathway analyses to further elucidate the neuroprotective actions of CS–CUR nanoparticles. Additionally, translational and clinical investigations are warranted to validate the therapeutic potential of this nanocarrier system for Alzheimer’s disease management.
Drug abuse can impact the function of immune cells, leading to a compromised immune system response. This study aimed to investigate the immunomodulatory effects of Methamphetamine and its detoxification agents on peripheral blood dendritic cells. A total of 60 participants were enrolled, including 30 individuals with Methamphetamine addiction and 30 matched healthy controls. Participants were assessed at three time points: at the beginning of detoxification, at the end of detoxification, and one-month post-detoxification. Flow cytometry was employed to analyze dendritic cell subsets (CD11c + myeloid dendritic cells and CD123 + plasmacytoid dendritic cells) and surface marker expression (HLA-DR, CD11c, CD123). The percentages of both CD11c + and CD123 + dendritic cells in peripheral blood were significantly lower in Methamphetamine addicts compared to the control group. Detoxification with Risperidone corrected this reduction, while the combination of Risperidone and Methylphenidate failed to produce any change in the percentage of dendritic cells. The expression of HLA-DR, CD11c, and CD123 markers was downregulated in the dendritic cells of Methamphetamine addicts. Treatment with Risperidone restored these markers, whereas the combination therapy further exacerbated the downregulation of these markers. The findings suggest that detoxification with Risperidone may help ameliorate the immunological disorders associated with Methamphetamine use.
Netrin-1, a central axonal guidance molecule discovered for its role in neuronal development, is also essential in neurodegenerative diseases. Netrin-1 inhibits leukocyte migration and inflammation-related tissue damage outside the central nervous system. Therefore, it can be viewed as a potential biomarker for inflammatory activity in neurodegenerative diseases. Recent studies highlight the dual roles of Netrin-1 in neuroinflammation and neurodegenerative diseases. In the context of neurodegeneration, Netrin-1 demonstrates both protective and harmful effects. This review highlights recent advancements in research regarding the dual roles of Netrin-1 in neuroinflammation and neurodegeneration. We discuss its involvement in protecting the blood–brain barrier (BBB) and regulating immune cell migration and its effects on various neurodegenerative diseases. A greater understanding of the multifunctionality of Netrin-1 could potentially be employed in developing new treatment modalities.
BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, and oxidative stress. Current treatments are largely symptomatic, necessitating novel neuroprotective strategies.ObjectiveThis study aimed to investigate the anti-inflammatory and antioxidant effects of chitosan-cannabidiol (CS-CBD) nanoparticles in a streptozotocin (STZ)-induced rat model of AD.MethodsSixty male Wistar rats were randomly divided into five groups: control, AD model (STZ-induced), chitosan-treated, cannabidiol-treated, and CS-CBD-treated. AD was induced by intracerebroventricular injection of STZ (3 mg/kg). Treatments were administered intranasally for 21 days. Cognitive performance was assessed using the Morris water maze. After treatment, oxidative stress markers (NO, FRAP), liver enzymes (ALT, AST), and the expression of inflammatory and neuroprotective genes (IL1β, IL6, IL10, iNOS, PPARγ, BDNF) were evaluated by real-time PCR. Histological analysis of the hippocampus was also performed. Data were analyzed using one-way ANOVA and Tukey's post hoc test (p < 0.05).ResultsThe AD group showed significant impairments in memory and learning (p < 0.0001), increased oxidative stress, and upregulation of pro-inflammatory genes (IL1β, iNOS), with decreased neuroprotective markers (BDNF, PPARγ). CS-CBD treatment significantly improved cognitive function (p < 0.001), restored oxidative balance, reduced IL1β and iNOS expression, and elevated BDNF and PPARγ expression (p < 0.05). Histological analysis confirmed reduced neuronal degeneration and increased neuronal density in the CS-CBD group.ConclusionsCS-CBD nanoparticles exerted potent neuroprotective, antioxidant, and anti-inflammatory effects in an STZ-induced rat model of AD. These findings support the potential of CS-CBD nanoparticles as a promising adjunctive therapy for AD, warranting further investigation.
Liver fibrosis is a progressive pathological condition that results from chronic liver injuries, including viral infections, alcohol abuse, and metabolic-associated fatty liver disease. Although curcumin, a polyphenolic compound from turmeric, exhibits potent antioxidant and anti-inflammatory properties, its clinical utility is limited by poor solubility and low bioavailability. To address this, chitosan-based curcumin nanoparticles (CUR-CS NPs) have been developed to enhance curcumin’s therapeutic potential. CUR–CS NPs were synthesized by ionic gelation and characterized by DLS, FE-SEM, and zeta potential analyses. Encapsulation efficiency (EE
Background & aims Pneumosepsis is a global healthcare challenge associated with substantial morbidity and mortality rates. Its pathogenesis involves intricate interactions among host factors, pathogens, and immune dysregulation. Vitamins A and D are crucial for immune function, acting as regulators and cofactors in immune cell development and function. Given these roles, this study aimed to assess the impact of combined vitamin D and A supplementation on T cell levels in pneumosepsis patients. Methods This double-blind clinical trial enrolled 84 pneumosepsis patients who were randomly assigned to four groups after demographic data collection. Intervention: Group 1 received standard treatment plus 300,000 IU of vitamin D and 50,000 IU of vitamin A. Group 2 received standard treatment plus 300,000 IU of vitamin D. Group 3 received standard treatment plus 50,000 IU of vitamin A. Group 4 received only standard treatment. Main outcome measures: Vital signs were monitored every 6 hours, and T-cell count, ESR, CRP, creatinine, urea, and uric acid levels were assessed at 0, 24, 48, and 72 hours. Results Initially and one day post-intervention, vital signs and blood factors showed no significant differences among the groups. However, on days two and three post-intervention, the combined vitamin D and A group exhibited significantly lower levels compared to other groups. Lymphocytes expressing CD3+, CD4+, CD25+, CD3,4+, and CD3,4,25+ markers significantly differed in the combined vitamin A + D group versus the control. No significant differences were noted in lymphocyte percentages between the combined vitamin A + D group and those receiving only vitamin D or A. Conclusion This study underscores the potential benefits of concurrent vitamin D and A supplementation in reducing symptoms among pneumosepsis patients, particularly in modulating key physiological parameters and immune responses. Trial registration This study is registered on Iranian Registry of Clinical Trials (IRCT) under identifieron IRCT20130424013110N10 . (The registration date: Jul 6, 2020).