High-fat diet (HFD)-induced hyperlipidemia is an experimental metabolic condition characterized primarily by dysregulated serum lipid levels and hepatic lipid accumulation, with associated oxidative, inflammatory, mitochondrial, and cardiovascular alterations. This study investigated the therapeutic efficacy of epigallocatechin gallate (EGCG)-functionalized selenium nanoparticles (EGCG-SeNPs) against HFD-induced metabolic and hepatic injury, in comparison with free EGCG, sodium selenite (Na₂SeO₃), and Lipanthyl. EGCG-SeNPs were characterized by dynamic light scattering, zeta potential analysis, transmission electron microscopy, X-ray diffraction, and UV–visible spectrophotometry. Forty-two adult male rats were allocated into six groups: control, HFD, HFD/Lipanthyl, HFD/EGCG, HFD/Na₂SeO₃, and HFD/EGCG-SeNPs. High-fat diet (HFD) feeding induced pronounced dyslipidemia, elevated hepatic enzymes, increased cardiac injury biomarkers, enhanced lipid peroxidation and nitrosative stress, depletion of antioxidant defenses, and disruption of the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) regulatory axis. HFD also increased nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while altering mitochondrial apoptotic markers, including B-cell lymphoma 2 (Bcl-2), cytochrome c, and caspase-3. At the transcriptional level, HFD increased lipogenic gene expression and reduced the expression of genes related to fatty-acid oxidation, metabolic regulation, and mitochondrial homeostasis. EGCG-SeNPs showed the greatest overall improvement among the tested interventions, as indicated by an improved lipid profile, hepato-cardiac injury biomarkers, antioxidant status, inflammatory markers, apoptotic markers, hepatic architecture, and Nrf2 immunoreactivity. Collectively, EGCG-SeNPs may mitigate HFD-induced hepatic lipotoxicity and associated cardiac stress through coordinated modulation of lipid metabolism, redox balance, inflammation, and mitochondrial homeostasis.

Rhabdomyolysis-associated acute kidney injury is driven by myoglobin-mediated oxidative stress, inflammation, mitochondrial impairment, and tubular cell death. This study evaluated the nephroprotective activity of green-synthesized Withania somnifera-functionalized selenium nanoparticles (Ws-SeNPs) in glycerol-induced renal injury and compared their efficacy with native W. somnifera extract and sodium selenite. The chemical profile of the plant extract was characterized by LC–MS/MS, and Ws-SeNPs were evaluated using dynamic light scattering, zeta potential analysis, transmission electron microscopy, and FTIR spectroscopy. Thirty-five male rats were assigned to Control, ARF, ARF & Ws, ARF & selenium, and ARF & Ws-SeNPs. ARF was induced by intramuscular injection of 50% glycerol. Glycerol administration induced marked skeletal muscle injury, renal dysfunction, tubular damage, oxidative stress, inflammation, mitochondrial dysregulation, pyroptosis, apoptosis, and histopathological alterations. Both Ws and sodium selenite provided partial protection, whereas Ws-SeNPs produced the greatest improvement in renal function and tissue architecture. Their protective effect was associated with restoration of Nrf2-dependent antioxidant defenses, suppression of NF-κB/NLRP3/GSDMD-associated inflammatory and pyroptotic signaling, preservation of mitochondrial regulatory pathways, and attenuation of apoptosis. These findings indicate that Ws-SeNPs provide multi-target protection against glycerol-induced rhabdomyolysis-associated renal injury and may represent a promising phytochemical-based selenium nanoformulation for further preclinical investigation.

Antimicrobial resistance (AMR) remains one of the most critical global health challenges, demanding innovative therapeutics beyond conventional antibiotics. In this study, Pseudomonas aeruginosa strain KAEH25, isolated from rhizospheric soil in Menoufia, Egypt, was identified as a potent producer of 1-hydroxyphenazine (1-HPZ), a redox-active phenazine derivative exhibiting broad-spectrum antimicrobial activity. The compound was extracted, purified, and characterized by ultraviolet–visible (UV–Vis) spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), high-performance liquid chromatography (HPLC), nuclear magnetic resonance spectroscopy (NMR), and gas chromatography–mass spectrometry (GC–MS), confirming its molecular identity and purity. To overcome its poor solubility and instability, 1-HPZ was encapsulated into mesoporous silica and magnetic Fe _₃ O _₄ nanoparticles. Nanomaterials were synthesized and characterized using dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM), confirming nanoscale uniformity, high surface area, and successful drug loading. Molecular docking studies (Schrödinger 2023-4) revealed strong binding affinities of 1-HPZ toward key bacterial enzymes including topoisomerase IV (–7.909 kcal/mol), DNA gyrase (–6.650 kcal/mol), and RNA polymerase (–6.750 kcal/mol), implying multitarget inhibition of DNA replication, cell wall biosynthesis, and protein synthesis. Molecular dynamics simulations (Materials Studio 2024, COMPASS III) demonstrated favorable insertion energies (≈–4.8 × 10⁶ kcal/mol) for both free and nanoformulated 1-HPZ into 1 -palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers, indicating strong membrane affinity and potential for enhanced cellular uptake. Experimentally, the 1-HPZ-loaded mesoporous nanoparticles showed the most potent antibacterial effect, producing inhibition zones up to 25 mm against Listeria monocytogenes and Escherichia coli , surpassing free 1-HPZ. Time-kill and minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) assays confirmed bactericidal activity at low concentrations (MIC 4–16 µg/mL; MBC 8–32 µg/mL), outperforming both magnetic formulations and free 1-HPZ. These findings validate that mesoporous nanocarriers significantly enhance the solubility, stability, and antibacterial potency of 1-HPZ while maintaining biocompatibility. This integrated experimental and computational investigation demonstrates that coupling a microbial natural product with nanotechnology offers a promising route to overcome multidrug resistance. The 1-HPZ–mesoporous system provides a robust platform for next-generation antimicrobial therapies and magnetically guided drug delivery applications.

This study establishes an integrated genome-to-structure-to-process framework that significantly enhances 1-hydroxyphenazine (1-OH-PHZ) biosynthesis in Pseudomonas aeruginosa KAEH25. Nanopore long-read sequencing completely resolved the 10,358 bp phenazine biosynthetic locus, confirming intact organization of core ( phzB–phzG ) and tailoring ( phzH , phzS ) genes. AlphaFold modeling and InterProScan analysis validated conserved catalytic domains across all pathway enzymes, confirming functional coherence. Plackett–Burman screening identified temperature, pH, glucose, peptone, inoculum size, and incubation time as significant production determinants, while response surface methodology optimized these factors to achieve a maximum 1-OH-PHZ titre of 24.85 µg mL⁻ ¹ under refined conditions (37 °C, pH 6.5–7, 1% glucose, 2 g L⁻ ¹ peptone, 10 mL inoculum, 48 h). The statistical model demonstrated exceptional explanatory power (R ² = 0.9605; Adeq Precision = 19.11). Preliminary antimicrobial assays demonstrated selective activity of 1-hydroxyphenazine (1-OH-PHZ), with inhibition zones of 20 ± 1 mm against Escherichia coli , 13 ± 0.5 mm against Salmonella enterica serovar Typhimurium, 13 ± 0.7 mm against Klebsiella pneumoniae , and 8 ± 0.3 mm against Staphylococcus aureus , while no inhibition was observed against Enterococcus faecalis or Listeria monocytogenes . Collectively, this systems-guided approach provides a transferable platform for optimizing microbial secondary metabolites and validates 1-OH-PHZ as a promising lead for antimicrobial development.