Luteolin is an essential natural polyphenol found in a variety of plants. Numerous studies have supported its protective role in neurodegenerative diseases, yet the research for its therapeutic utility in D-galactose (D-gal)-induced brain ageing is still lacking. In this study, the potential neuroprotective impact of luteolin against D-gal-induced brain ageing was explored. Forty rats were randomly divided into four groups: control, luteolin, D-gal, and luteolin-administered D-gal groups. All groups were subjected to behavioural, cholinergic function, and hippocampal mitochondrial respiration assessments. Hippocampal oxidative, neuro-inflammatory, senescence and apoptotic indicators were detected. Gene expressions of SIRT1, BDNF, and RAGE were assessed. Hippocampal histopathological studies, along with GFAP and Ki67 immunoreactivity, were performed. Our results demonstrated that luteolin effectively alleviated D-gal-induced cognitive impairment and reversed cholinergic abnormalities. Furthermore, luteolin administration substantially mitigated hippocampus oxidative stress, mitochondrial dysfunction, neuro-inflammation, and senescence triggered by D-gal. Additionally, luteolin treatment considerably attenuated neuronal apoptosis and upregulated hippocampal SIRT1 mRNA expression. In conclusion, our findings revealed that luteolin administration attenuated D-gal-evoked brain senescence, improving mitochondrial function and enhancing hippocampal neuroregeneration in an ageing rat model through its antioxidant, senolytic, anti-inflammatory, and anti-apoptotic impacts, possibly due to upregulation of SIRT1. Luteolin could be a promising therapeutic modality for brain aging-associated abnormalities.

Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a life-threatening clinical issue with limited preventive approaches, posing a substantial challenge to cancer survivors. The anthraquinone diacerein (DCN) exhibits significant anti-inflammatory, anti-proliferative, and antioxidant actions. Its beneficial effects on DIC have yet to be clarified. Therefore, this study investigated DCN’s cardioprotective potency and its conceivable molecular targets against DIC. Twenty-eight Wister rats were assigned to CON, DOX, DCN-L/DOX, and DCN-H/DOX groups. Serum cardiac damage indices, iron assay, oxidative stress, inflammation, endoplasmic reticulum (ER) stress, apoptosis, ferritinophagy, and ferroptosis-related biomarkers were estimated. Nuclear factor E2-related factor 2 (NRF2) DNA-binding activity and phospho-p53 immunoreactivity were assessed. DCN administration effectively ameliorated DOX-induced cardiac cytomorphological abnormalities. Additionally, DCN profoundly combated the DOX-induced labile iron pool expansion alongside its consequent lethal lipid peroxide overproduction, whereas it counteracted ferritinophagy and enhanced iron storage. Indeed, DCN valuably reinforced the cardiomyocytes’ resistance to ferroptosis, mainly by restoring the NRF2/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling axis. Furthermore, DCN abrogated the cardiac oxidative damage, inflammatory response, ER stress, and cardiomyocyte apoptosis elicited by DOX. In conclusion, for the first time, our findings validated DCN’s cardioprotective potency against DIC based on its antioxidant, anti-inflammatory, anti-ferroptotic, and anti-apoptotic imprint, chiefly mediated by the NRF2/SLC7A11/GPX4 axis. Accordingly, DCN could represent a promising therapeutic avenue for patients under DOX-dependent chemotherapy.

Acetaminophen (APAP) is one of the most clinically relevant medications associated with acute liver damage. A prolific deal of research validated the hepatoprotective effect of empagliflozin (EMPA); however, its effect on APAP‐induced hepatotoxicity has still not been investigated. In this study, the prospective hepatoprotective impact of EMPA against APAP‐induced hepatotoxicity was investigated. Twenty‐eight Balb‐C mice were assigned to four groups: control, APAP, EMPA10/APAP, and EMPA25/APAP. At the end of the experiment, serum hepatotoxicity biomarkers, MDA level, and GSH content were estimated. Hepatic mitofusin‐2 (MFN2), optic atrophy 1 (OPA1), dynamin‐related protein 1 (Drp1), and mitochondrial fission 1 protein (FIS1) were immunoassayed. PGC‐1α, cGAS, and STING mRNA expression were assessed by real‐time PCR. Histopathological changes and immunohistochemistry of INF‐β, p‐NF‐κB, and iNOS were evaluated. APAP treatment caused significant hepatic functional impairment and increased hepatic MDA levels, as well as a concomitant decrease in GSH content. Marked elevation in Drp1 and FIS1 levels, INF‐ß, p‐NF‐κB, and iNOS immunoreactivity, and reduction in MFN2 and OPA1 levels in the APAP‐injected group, PGC‐1α downregulation, and high expression of cGAS and STING were also documented. EMPA effectively ameliorated APAP‐generated structural and functional changes in the liver, restored redox homeostasis and mitochondrial dynamics balance, and enhanced mitochondrial biogenesis, remarkably diminished hepatic expression of cGAS and STING, and elicited a reduction in hepatic inflammation. Moreover, the computational modeling data support the interaction of APAP with antioxidant system‐related proteins as well as the interactions of EMPA against Drp1, cGAS, IKKA, and iNOS proteins. Our findings demonstrated for the first time that EMPA has an ameliorative impact against APAP‐induced hepatotoxicity in mice via modulation of mitochondrial dynamics, biogenesis, and cGAS/STING‐dependent inflammation. Thus, this study concluded that EMPA could be a promising therapeutic modality for acute liver toxicity.

This study aimed to investigate the immune-epigenetic profile of pediatric immune thrombocytopenic purpura (ITP) and its association with disease chronicity. This case–control study included 93 participants: 33 children with newly diagnosed ITP, 28 with chronic ITP (> 12 months), and 32 age- and sex-matched healthy controls. We assessed platelet count, serum transforming growth factor-β (TGF-β), interleukin-10 (IL-10) levels, circulating CD4⁺CD25⁺FoxP3⁺ Treg frequency, and relative expression of miR-106b-5p and miR-146a-5p. ITP patients demonstrated significantly lower platelet counts, Treg frequency, and TGF-β levels, with elevated IL-10 levels compared to controls. miR-106b-5p expression was significantly upregulated in ITP, particularly in chronic cases, and negatively correlated with platelet count, Treg frequency, and TGF-β. Conversely, miR-146a-5p was significantly downregulated and positively correlated with platelet count and Treg frequency. Chronic ITP exhibited more pronounced miRNA dysregulation and Treg depletion. ROC analysis revealed high diagnostic accuracy of both miRNAs for chronic ITP, with miR-146a-5p demonstrating superior sensitivity. Conclusion: This study highlights the interplay between immune dysregulation and epigenetics in ITP. The opposing roles of miR-106b-5p and miR-146a-5p in Treg function and cytokine homeostasis suggest their potential contribution to disease chronicity and their potential as chronicity biomarkers. These findings provide a foundation for future research aimed at improving ITP patient stratification, identifying therapeutic targets, and advancing precision-based interventions. What is Known: • Despite extensive research, the aetiopathogenesis of immune thrombocytopenic purpura (ITP) remains incompletely understood, involving complex interactions between immune dysregulation, cytokine imbalance, and emerging epigenetic factors, such as microRNAs. • This work aimed to investigate the immunological and molecular mechanisms underlying ITP in the pediatric population, focusing on cytokine profiles (TGF-β, IL-10), regulatory T cells (Tregs), and the relative expression of miR-106b-5p and miR-146a-5p, and to assess their value as predictive tools for chronic ITP. What is New: • This study highlights the critical interplay between immune dysregulation and epigenetics in ITP. The opposing roles of miR-106b-5p and miR-146a-5p suggest their involvement in disease chronicity. These miRNAs may serve as non-invasive markers for ITP chronicity and as candidate targets for therapy to restore immune tolerance in ITP. Despite the cross-sectional nature of the current work, it provides a foundation for future research aimed at improving ITP patient stratification, identifying therapeutic targets, and advancing precision-based interventions.