Amoxicillin/clavulanate (Co-Amox), a commonly used antibiotic for the treatment of bacterial infections, has been associated with drug-induced liver damage. Quercetin (QR), a naturally occurring flavonoid with pleiotropic biological activities, has poor water solubility and low bioavailability. The objective of this work was to produce a more bioavailable formulation of QR (liposomes) and to determine the effect of its intraperitoneal pretreatment on the amelioration of Co-Amox-induced liver damage in male rats. Four groups of rats were defined: control, QR liposomes (QR-lipo), Co-Amox, and Co-Amox and QR-lipo. Liver injury severity in rats was evaluated for all groups through measurement of serum liver enzymes, liver antioxidant status, proinflammatory mediators, and microbiota modulation. The results revealed that QR-lipo reduced the severity of Co-Amox-induced hepatic damage in rats, as indicated by a reduction in serum liver enzymes and total liver antioxidant capacity. In addition, QR-lipo upregulated antioxidant transcription factors SIRT1 and Nrf2 and downregulated liver proinflammatory signatures, including IL-6, IL-1β, TNF-α, NF-κB, and iNOS, with upregulation in the anti-inflammatory one, IL10. QR-lipo also prevented Co-Amox-induced gut dysbiosis by favoring the colonization of Lactobacillus, Bifidobacterium, and Bacteroides over Clostridium and Enterobacteriaceae. These results suggested that QR-lipo ameliorates Co-Amox-induced liver damage by targeting SIRT1/Nrf2/NF-κB and modulating the microbiota.

Background: Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats. Methods: Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs’ antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis. Results: According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration. Conclusion: The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy. Graphical

Background: Vancomycin (VCM)-induced hepatotoxicity is a significant clinical concern due to its association with oxidative stress, apoptosis, and inflammatory responses. This study investigated the formulation and potential preclinical application of rutin-loaded nanocapsules (RUT-NC) as a hepatoprotective agent against VCM-induced liver injury. Methods: Hepatotoxicity was induced in rats through VCM administration, followed by oral treatment with RUT-NC. Liver function, oxidative stress markers, apoptotic proteins, lipid metabolism regulators, and inflammatory cytokines were subsequently evaluated. Results: RUT-NC treatment significantly improved liver function parameters, attenuated oxidative stress, and modulated apoptotic pathways by downregulating the expression of p38 , p53 , caspase-8 , miR-122 , miR-7 , and beclin-1. Furthermore, RUT-NC restored lipid metabolism homeostasis by regulating the expression of PPAR-α, FASN, and SREBP-1. Notably, it exerted potent anti-inflammatory effects by suppressing NF-κB , TNF-α , IL-1β , IL-6 , IL-17 , and Gasdermin-D , thereby mitigating chronic liver inflammation. The pathological effects of VCM administration on hepatocytes were effectively counteracted by RUT-NC. Conclusion: RUT-NC demonstrates promising hepatoprotective properties by enhancing antioxidant defenses, inhibiting apoptosis, regulating lipid metabolism, and reducing inflammation. These findings highlight its potential as a therapeutic intervention for drug-induced liver injury (DILI) and warrant further investigation for clinical application.

Metabolic dysfunction associated fatty liver disease (MAFLD) is a rapidly growing global health burden characterized by hepatic lipid accumulation, insulin resistance, oxidative stress, and inflammation. Phyllanthus niruri (PHYLN) is rich in polyphenols and lignans with known antioxidant and anti-inflammatory properties; however, its therapeutic efficacy is limited by poor bioavailability. This study investigated the protective potential of PHYLN extract loaded into niosomal nanocarriers (PHYLN-NIO) against obesity-induced hepatic steatosis and explored its mechanistic similarity to glucagon-like peptide-1 receptor agonists (GLP-1RAs). Rats were divided into seven groups: control, PHYLN-NIO, HFD, HFD + Semaglutide, HFD + Semaglutide + exendin 9–39, HFD + PHYLN-NIO, and HFD + PHYLN-NIO + exendin 9–39. PHYLN-NIO markedly reduced body weight and body mass index, hepatic steatosis, and inflammation, while enhancing antioxidant status, insulin sensitivity, and lipid profiles. Mechanistically, PHYLN-NIO modulated the lncRNA-MALAT1/miR-206 axis, restored GLP-1/GLP-1R signaling, and downregulated key hepatic lipogenic regulators (LXR-α, SREBP-1c, FASN, ACC-1), while upregulating genes involved in fatty acid oxidation and metabolic homeostasis (FXR, PPAR-α, FOXA2). Notably, co-administration of exendin 9–39 reversed these effects, confirming a GLP-1R-dependent mechanism. These findings suggest that PHYLN-NIO effectively targets MALAT1/miR-206/GLP-1R signaling pathways, demonstrating its potential as a promising nanotherapeutic candidate for MAFLD management.

Bovine papillomatosis virus (BPV) is a prevalent cutaneous oncogenic viral disease in cattle, causing economic losses due to reduced milk production, poor carcass quality, and hide damage. Despite BPV’s economic significance, molecular information on current strains, genetic relationships, and origins in Egypt is limited, with most studies focusing on electron microscopy and histopathological analysis. The study aimed to genetically analyze BPV‐1 circulation in Al‐Sharkia, Egypt, and characterize viral strains compared with local and global papillomaviruses isolates. A total of 27 crossbred cattle with clinical symptoms of papillomatosis, such as wart‐like lesions on various body parts, were examined. The collected tissue samples underwent histological analysis, revealing typical benign neoplasms such as hyperkeratosis and koilocytes. Polymerase chain reaction (PCR) confirmed the presence of BPV‐1 in all samples, with partial amplification of the L1 gene. Sequencing and phylogenetic analysis of three representative samples indicated high similarity to BPV‐1 strains from Egypt, Iraq, Turkey, and Belgium, suggesting livestock trading may play a role in disease transmission. The isolates were found to be linked to equine Delta papillomavirus 4 (DPV4) strains, indicating cross‐species transmission between cattle and equines. The study marks one of the first reports of BPV‐1 infection in cattle in Al‐Sharkia, providing crucial molecular insights into Egypt’s circulating strains and emphasizing the need for stronger biosecurity protocols in animal trading.