Methanol poisoning can cause severe and irreversible optic neuropathy, for which effective neuroprotective strategies remain limited. Mitochondrial dysfunction is important contributors to methanol-induced neuronal injury. Therefore, this study evaluated whether systemic mitochondrial injection could attenuate methanol-induced optic nerve injury. Adult rats were randomly assigned to control, methanol, methanol + single mitochondrial injection, and methanol + double mitochondrial injection groups. Following methanol intoxication, freshly isolated functional mitochondria (250 µg/kg) were administered intravenously. Motor and visual functions were evaluated using the beam walking and visual cliff tests. Mitochondrial dysfunction was assessed by flow cytometric analysis of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. Oxidative stress was assessed by measuring reduced glutathione (GSH) and malondialdehyde (MDA), and optic nerve histopathology was also examined. Methanol exposure impaired motor coordination and visual performance (P < 0.05) and was associated with increased ROS formation (P < 0.001), lipid peroxidation (P < 0.01), MMP collapse (P < 0.001), and GSH depletion (P < 0.05), accompanied by histopathological alterations in the optic nerve. Mitochondrial injection attenuated these changes (P < 0.05) and improved functional and histopathological outcomes. Overall, the double mitochondrial injection was associated with a relatively greater improvement than the single administration in some of the evaluated parameters. Systemic mitochondrial injection attenuated methanol-associated mitochondrial and oxidative disturbances and was accompanied by improved behavioral and histopathological outcomes in this experimental model. Obtained finding in the current study support further investigations of mitochondrial-based approaches as potential strategies for methanol-induced optic neuropathy, while additional works are required to establish their underlying mechanisms, durability, and translational potential.
Prurigo nodularis (PN) is a chronic, intensely pruritic inflammatory skin disease. Multiple targeted biologic therapies have shown efficacy against placebo, but no randomized trial has directly compared these agents, leaving their relative efficacy and safety uncertain. To compare the efficacy and safety of dupilumab, nemolizumab, vixarelimab, and serlopitant for PN using network meta-analysis. PubMed, Embase, Cochrane and ClinicalTrials.gov were searched for randomized trials enrolling adults with PN that evaluated dupilumab, nemolizumab, vixarelimab, or serlopitant against placebo or one another. Risk of bias was assessed with RoB 2. A frequentist network meta-analysis was performed, with treatment effects expressed as risk ratios (RR) or standardized mean differences (SMD) with 95
Monosodium glutamate (MSG) is a widely used food additive associated with neurotoxicity through excitotoxicity, oxidative stress, neuroinflammation, and apoptosis. The present study investigated the neuroprotective effects of hydroxytyrosol (HT), a naturally occurring phenolic compound with antioxidant and anti-inflammatory properties, against MSG-induced brain and cerebellar injury in rats. Thirty-two male Wistar albino rats were randomly assigned to four groups (Control, MSG, HT, and MSG + HT). MSG (2 g/kg) and HT (10 mg/kg) were administered intraperitoneally for 21 days. Oxidative stress markers, inflammatory cytokines, myelin basic protein (MBP), histopathological alterations, and immunohistochemical markers of glial activation and apoptosis were evaluated. MSG administration significantly increased malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels while decreasing glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and MBP levels in both brain and cerebellar tissues. Histopathological examination revealed marked neuronal degeneration, whereas immunohistochemical analyses demonstrated increased GFAP, S100β, and Bax expression together with reduced Bcl-2 immunoreactivity. HT treatment markedly attenuated these biochemical, histopathological, and immunohistochemical alterations by restoring antioxidant defenses, suppressing inflammatory responses, preserving MBP expression, reducing glial activation, and improving the Bax/Bcl-2 balance. These findings demonstrate that HT exerts neuroprotective effects against MSG-induced brain and cerebellar injury through coordinated antioxidant, anti-inflammatory, myelin-preserving, and anti-apoptotic mechanisms. The integrated evaluation of biochemical, histopathological, and immunohistochemical alterations highlights HT's potential as a promising candidate for preventing oxidative and inflammatory neurotoxicity.
Panax ginseng (PG) is a traditional herbal medicine widely used for the treatment of cardiovascular disorders in East Asia. Although PG has been reported to attenuate cardiomyocyte hypertrophy, the molecular mechanisms underlying its cardioprotective effects remain incompletely understood. In this study, we investigated whether modulation of the endothelin-1 (ET-1)–angiotensin II (AngII) signaling axis contributes to the anti-hypertrophic action of PG. Neonatal rat ventricular myocytes (NRVMs) were used to evaluate ET-1-induced hypertrophy, and pharmacological experiments using receptor antagonists were performed to examine the signaling pathways involved. Extracellular AngII levels were quantified by ELISA, intracellular Ca2+ accumulation was assessed in AT1AR-overexpressing NRVMs, and whole-cell patch-clamp recordings were performed in HEK293T cells co-expressing AT1AR and TRPC6. PG significantly attenuated ET-1-induced cardiomyocyte hypertrophy without altering ETAR or ETBR expression. Pharmacological experiments with the ETAR antagonist BQ-123 suggested that the anti-hypertrophic effect of PG could not be explained solely by direct inhibition of ETAR signaling. PG markedly suppressed ET-1-induced extracellular AngII production, and interaction studies with losartan further implicated the AngII–AT1AR pathway in the anti-hypertrophic action of PG. Moreover, PG inhibited AngII-induced intracellular Ca2+ accumulation in AT1AR-overexpressing NRVMs and attenuated AngII-evoked TRPC6-mediated membrane currents without affecting basal channel activity. These findings demonstrate that PG suppresses ET-1-induced cardiomyocyte hypertrophy by inhibiting both ET-1-induced AngII production and downstream AT1AR-dependent signaling, identifying suppression of the AngII–AT1AR signaling axis as a key mechanism underlying its cardioprotective effects.
The intestinal epithelium maintains immune and metabolic homeostasis at the host–microbiota interface, and its disruption contributes to inflammatory bowel disease (IBD). Microbial metabolites such as short-chain fatty acids (SCFAs) and indole derivatives are known to regulate epithelial and immune functions, but their roles in cholinergic signaling and aryl hydrocarbon receptor (AhR) pathways remain incompletely understood. Caco-2 intestinal epithelial cells were stimulated with lipopolysaccharide (LPS; 10 µg/mL) and co-treated with SCFAs (acetate, propionate, butyrate) or indole derivatives (IAA, IPA, IBA; 1000 µM). The AhR antagonist CH223191 was used to assess receptor involvement. Inflammatory markers (TNF-α, IL-6, COX-2), barrier integrity (FITC-dextran permeability, ZO-1 and occludin), cholinergic components (CHAT, ACHE, BCHE, α7nAChR, mAChR1, mAChR3), and AhR activation (nuclear localization, CYP1A1 expression) were analyzed using qPCR, ELISA, immunostaining, and enzymatic assays. Molecular docking was performed to predict metabolite–protein interactions. LPS induced inflammatory cytokine expression and barrier disruption, whereas SCFAs and indole derivatives significantly reduced inflammation, restored tight-junction organization, and decreased permeability. These metabolites enhanced CHAT and muscarinic receptor expression while suppressing ACHE upregulation, indicating restoration of cholinergic balance. Both groups reactivated AhR signaling, and AhR inhibition disrupted cholinergic regulation, supporting an AhR-dependent mechanism. Butyrate and indole-3-butyric acid exhibited the strongest protective effects. These findings identify a novel AhR–cholinergic axis in intestinal epithelial regulation and highlight microbial metabolites as promising therapeutic candidates for IBD.
