Background/Objectives: Rutin (RT), a promising bioflavonoid, faces clinical limitations due to its poor solubility and bioavailability. In this study, we formulated RT-loaded phytosome nanoparticles (RT-PNPs) via thin-layer hydration and characterized their morphology, size distribution, and zeta potential. Methods: We established a mouse model of Ehrlich ascites carcinoma (EAC), randomly allocating ninety female Swiss albino mice into six groups: untreated controls, RT-treated, RT-PNP-treated, EAC, EAC + RT, and EAC + RT-PNPs. Tumor induction and treatment protocols were controlled, with the oral administration of 25 mg/kg/day of RT or RT-PNPs for 20 days. We comprehensively assessed survival, body weight, ascitic fluid/tumor volume, and cell viability and performed detailed hematological, serum biochemical, and tumor marker analyses. Multiorgan (liver and kidney) function and redox homeostasis were evaluated through enzymatic assays for SOD, CAT, GSH-Px, and GSH, as well as lipid peroxidation assessment. Proinflammatory cytokines and tumor markers (AFP, CEA, CA19-9, CA125, and CA15-3) were quantified via ELISA. Results: Gene expression profiling (TP53, Bax, and Bcl-2) and flow cytometry (p53 and Ki-67) elucidated the modulation of apoptosis. Histopathological scoring documented organ protection, while advanced multivariate (heatmap and principal component) analyses revealed distinct treatment clusterings. The RT-PNPs demonstrated potent anti-tumor, antioxidant, anti-inflammatory, and apoptosis-inducing effects, outperforming free RT in restoring physiological markers and tissue integrity. Conclusions: The current results underscore the potential of RT-PNPs as a multifaceted therapeutic approach to EAC, leveraging nanoparticle technology to optimize efficacy and systemic protection.

This study aimed to examine the efficacy of Doppler and B-mode sonography in evaluating the impact of maternal temperament on hemodynamic alterations in both the fetus and uterus during ovine gestation in addition to alteration of the angiogenic protein expression and fetal biometry. Twenty Ossimi ewes were divided into two groups, more reactive (MR: 12 sheep) and less reactive (LR: 8 sheep). Several endpoints were assessed every 2 weeks (wk) from breeding to wk 20 of pregnancy. Blood samples were taken to evaluate the expression of angiogenic proteins at parturition. The resistance (RI) and pulsatility (PI) indexes of the uterine (UtA) and fetal umbilical arteries (UMA) were measured. Biometry includes: diameter of amniotic vesicles (AVD), umbilicus (UMD), fetal thoracic diameter (FTD) and metacarpal length (MCL). The UtA-PI was higher in MR compared to LR ewes between 6-12 wks of gestation (P>0.01), while a tendency was recognized at wk 14 (P=0.054). The same was true for UtA-RI during the first 8 wk of pregnancy (P < 0.03) when MR and LR animals were compared. Similarly, UMA-RI was higher in fetuses of MR than LR ewes at wk 14 (P<0.0003) and 20 (P<0.02) of pregnancy. The differences in UMA-PI reached significance at wk 6, 8, 10, and 20 (P<0.0 -0.003). Furthermore, significant changes in fetal biometry were investigated. The expressions of VEGF, NOS3 and HIF 1α were increased in the less reactive sheep (P<0.001). In conclusion, the maternal temperaments affect the Doppler, B mode as well as the expressions of mRNAs for VEGF, NOS3 and HIF 1α genes at time of parturition.

Colon cancer (CC) is a leading cause of cancer-related mortality globally. Although chemotherapy remains the primary treatment, its toxicity and drug resistance highlight the need for alternative therapeutic strategies. Silymarin (Sily), a natural compound, and zinc oxide nanoparticles (ZnO-NPs) have shown potential antitumor activity. This study evaluated Sily and/or ZnO-NPs against DMH-induced CC in rats. Thirty male Sprague-Dawley rats were divided into five groups (n = 6): control, CC (DMH 20 mg/kg/16-week S.C.), and three groups receiving Sily (40 mg/kg orally), ZnO-NPs (10 mg/kg IP), or their combination daily for 4 weeks. In comparison to the CC group, Sily or ZnO-NPs significantly decreased CEA levels, restored mucin synthesis, and improved colonic histology, with the combination treatment producing the most pronounced antitumor effects. Treatments attenuated oxidative stress, with Sily restoring SOD and GSH levels, whereas ZnO-NPs primarily reduced lipid peroxidation, as reflected by decreased MDA levels. Mechanistically, the combined therapy decreased inhibitory GSK-3β phosphorylation and β-catenin expression, consistent with restoration of GSK-3β-mediated suppression of β-catenin. The combination also restored PKCα and miR-192 expression and reduced the expression of the proliferation- and metastasis-associated markers MMP-9, c-Myc, and Cyclin-D1. CD133 expression was significantly reduced, suggesting an effect on the cancer stem cell-associated phenotype. Sily and ZnO-NPs demonstrated therapeutic effects against CC, particularly when administered in combination. Their antitumor effects were associated with modulation of miR-192/PKCα and GSK-3β/β-catenin signaling, supporting further investigation of their combined multitargeted potential in CC.

Thymoquinone (TQ), the principal bioactive constituent of Nigella sativa , possesses potent antioxidant and anticancer properties but suffers from poor aqueous solubility and limited bioavailability. This study evaluates the therapeutic efficacy of TQ encapsulated within poly(lactic-co-glycolic acid) nanoparticles (TQ-PNPs), synthesized via solvent evaporation and physicochemically characterized by dynamic light scattering, zeta potential measurement, and transmission electron microscopy. 90 female Swiss albino mice were allocated to 6 groups: control, TQ, TQ-PNPs (10 mg/kg, oral), EAC, EAC + TQ, and EAC + TQ-PNPs. Endpoints included tumor viability, hematological and biochemical indices, antioxidant enzyme activity, pro-inflammatory cytokines, oxidative stress biomarkers, and hepatorenal histopathology. Molecular docking assessed TQ binding affinities toward key antioxidant enzymes. Compared to free TQ, TQ-PNPs was associated with significantly greater reductions in tumor burden, inflammatory cytokines (IL-2, IL-6, TNF-α), and oxidative stress markers, with concurrent restoration of antioxidant defenses and enhanced hepatorenal protection. Molecular docking indicated high-affinity interactions between TQ and catalase, superoxide dismutase, and glutathione peroxidase, supporting a plausible mechanistic basis for its antioxidative activity but requiring experimental confirmation. These findings suggest that PLGA-based nanoencapsulation can enhance TQ’s bioavailability and therapeutic index in this murine EAC model, positioning TQ-PNPs as a promising platform for phytochemical delivery in cancer management.