Hepatocellular carcinoma (HCC) is the most common form of malignancy in the liver. Autophagy was found to have a significant effect in controlling HCC. Anthocyanins, which are naturally occurring pigments in a variety of fruits and vegetables, have been thoroughly documented to be involved in a variety of bioactive activities and are widely employed for their antioxidant capabilities. Cyanidin-3-glucoside (C3G) extracted from Morus alba L. has promising antioxidant and anti-tumour activities. The current study aims to examine the protective action of C3G against hepatocellular carcinoma through the investigation of the autophagy protein ATG16L1 expression along with its related RNA molecules (hsa_circ_0001345 and miRNA106b) in Wistar rats. In vivo precancerous lesions (PCL) were induced using diethylnitrosamine (DEN) and acetamidofluorene (2-AAF). Rats were treated with C3G (10, 15, and 20 mg/kg; 4 times weekly) for 112 days (16 weeks). Liver function tests, alfa fetoprotein, ATG16L1 expression, hsa_circ_0001345, and miRNA106b differential expression were examined. Liver sections were examined by histological and immunohistochemical approaches. The current study’s findings indicated that C3G administration protects against the negative effects of DEN-2-AAF on liver functions and liver histopathological sections, which nominated C3G as a potential prophylactic agent against HCC.

Acute kidney injury (AKI) is defined as a quick and often reversible decline in renal performance, as shown by elevated creatinine or reduced urine volume. AKI is a common illness, particularly among hospitalized cases, and can be observed in up to 7% of hospital admissions and 30% of ICU admissions. This study was designed to explore the nephroprotective potential of eco-synthesized quercetin–selenium nanoparticles (QUR-SeNPs) against experimentally glycerol-induced rhabdomyolysis leading to AKI. Forty healthy adult male albino rats were employed in the experiment. Animals were randomly distributed equally into five groups: Control: orally administered with normal saline solution. GLY: orally administered with normal saline (0.9% NaCl) for 15 consecutive days, at day 14, animals of this group received a single dose of intramuscular (im.) injection of 50% glycerol (GLY) (10 mg/kg/day). GLY and quercetin (GLY&QUR): orally administered with quercetin daily for 15 days (50 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). GLY&Na₂SeO₃: orally administered with sodium selenite daily for 15 days (0.5 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). GLY&QUR-SeNPs: orally administered with selenium nanoparticles synthesized using quercetin daily for 15 days (0.5 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). Oxidative stress, inflammatory, and apoptotic markers, in addition to histopathological, gene expression, and immunohistochemical analysis, were assessed for all groups. The results demonstrated that QUR-SeNPs effectively ameliorated renal functional, biochemical, and molecular disturbances through their synergistic antioxidant, anti-inflammatory, and anti-apoptotic potential, surpassing the effects of either quercetin or selenium alone. Biosynthesized selenium nanoparticles using QUR-SeNPs demonstrated remarkable nephroprotective activity by normalizing renal biomarkers, restoring antioxidant capacity, inhibiting inflammatory cytokines, and preventing apoptotic damage. The nanoparticle formulation exhibited superior efficacy to either QUR or Se alone, highlighting the synergistic interplay between selenium and quercetin through enhanced bioavailability, redox stability, and molecular targeting.

Paracetamol overdose is a major cause of drug-induced acute kidney injury (AKI), driven by oxidative stress, inflammation, mitochondrial dysfunction, and tubular apoptosis. This study evaluated the nephroprotective efficacy of pH-responsive carboxymethyl cellulose-encapsulated hesperidin-stabilized selenium nanoparticles (CMC@HES-SeNPs) against paracetamol-induced AKI in rats. HES-SeNPs were synthesized using hesperidin as a reducing/stabilizing agent and further coated with CMC. The nanoparticles were characterized by DLS, zeta potential, TEM, and in vitro release kinetics at pH 7.4 and 5.5. 42 Male rats were allocated into groups of control, paracetamol (PAR), paracetamol treated with sodium selenite (PAR&Se), paracetamol treated with hesperidin (PAR&HES), paracetamol treated with hesperidin-loaded selenium nanoparticles (PAR&HES-SeNPs), and paracetamol treated with carboxy methyl cellulose-coated hesperidin-loaded selenium nanoparticles (PAR&CMC@HES-SeNPs). Paracetamol markedly impaired renal function, increasing creatinine, urea, NGAL, KIM-1, and cystatin-C, and induced oxidative/nitrosative stress, Keap-1 upregulation, Nrf2 suppression, NF-κB-mediated inflammation, cytochrome-C release, Bax/Bcl-2 imbalance, caspase-3 activation, and severe renal histopathological injury. CMC@HES-SeNPs displayed sustained, pH-enhanced hesperidin release and produced the strongest renoprotective response, restoring renal biomarkers, associated with restoration of Keap-1/Nrf2-related antioxidant markers, reduction in TNF-α, IL-6, NF-κB, and caspase-3, increased IL-10, and preservation of renal architecture. Collectively, these results indicate that CMC@HES-SeNPs represent a promising multifunctional nanoplatform for mitigating paracetamol-induced AKI in association with coordinated modulation of redox, inflammatory, and mitochondrial apoptotic markers, and highlight CMC encapsulation as a rational strategy to enhance selenium–flavonoid delivery and efficacy for future drug-induced AKI management and translation.

Cisplatin is an effective chemotherapeutic agent whose clinical use is limited by dose-dependent off-target toxicities, particularly hepatic and cardiac injury. The present study investigated the protective efficacy of rutin-mediated selenium nanoparticles (RUT-SeNPs) against cisplatin-induced hepato-cardiotoxicity in rats and compared their effects against those of free rutin and sodium selenite. RUT-SeNPs were characterized using dynamic light scattering, zeta potential analysis, transmission electron microscopy, X-ray diffraction, and UV–visible spectroscopy. Thirty-five male rats were randomly assigned to five groups: control (CON), cisplatin (CIS), CIS + Rutin, CIS + selenium, and CIS + RUT-SeNPs. Cisplatin administration caused marked hepatic and cardiac injury, as evidenced by altered liver-function indices, elevated cardiac injury biomarkers, oxidative stress, inflammatory activation, endoplasmic reticulum stress, and apoptosis. These effects were associated with increased lipid peroxidation, depletion of endogenous antioxidants, KEAP1 upregulation, Nrf2 suppression, activation of the TLR4/MAPK/NF-κB inflammatory axis, elevated TNF-α, IL-6, and COX-2 levels, and increased mRNA expression of the ER stress-related genes PERK, ATF4, ATF6, and CHOP. Cisplatin also promoted mitochondrial apoptosis, as indicated by increased Bax expression and cytochrome c release together with reduced Bcl-2 levels. Although rutin and sodium selenite partially mitigated these alterations, RUT-SeNPs produced the most pronounced protective effects by restoring redox homeostasis, suppressing inflammatory signaling, reducing the elevated expression of ER stress-related genes, and limiting mitochondrial apoptotic activation. These molecular improvements were accompanied by substantial preservation of the hepatic and cardiac histoarchitecture. Collectively, these results indicate that RUT-SeNPs may represent a promising nanoformulation for reducing cisplatin-induced hepato-cardiac toxicity through coordinated modulation of oxidative stress, inflammation, endoplasmic reticulum stress, and apoptosis.

BackgroundDiabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus (DM) that often results in end-stage renal disease (ESRD). The global DM epidemic has made DN a public and clinical medical concern. It was shown that the age-standardized DN global prevalence was 15.48/1000 among men while in women was 16.50/1000. In Egypt, hypertension followed by DM are the primary causes of ESRD. Cross-sectional and longitudinal investigations revealed hyperglycemia, age, male gender, race, genetic susceptibility, hypertension, hyperfiltration, and smoking as DN risk factors. The earliest DN clinical evidence is microalbuminuria. Since structural damage could increase albumin excretion, there are several limitations to its diagnostic efficacy. Thus, specific and sensitive DN biomarkers are requried. The pathogenesis of DN is complex and poorly understood, resulting in poor treatment outcomes. The treatment of DN includes glycemic management, hypertension and hyperlipidemia treatment, protein restriction, and renal replacement therapy. Understanding the pathogenic mechanisms of DN is crucial for the development of new DN treatments. Aim of the ReviewThe review aims to empower researchers with a comprehensive and contemporary understanding of DN, facilitating early risk stratification, timely diagnosis, and the development of more effective and targeted therapeutic interventions.