The resistance to therapy and relapse in hepatocellular carcinoma (HCC) is highly attributed to hepatic cancer stem cells (HCSCs). HCSCs are under microenvironment control. This work aimed to assess the systemic effect of ellagic acid (EA) on the HCC microenvironment to decline HCSCs. Fifty Wistar rats were divided into six groups: negative control (CON), groups 2 and 3 for solvents (DMSO), and (OVO). Group 4 was administered EA only. The (HCC-M) group, utilized as an HCC model, administered CCL4 (0.5 mL/kg in OVO) 1:1 v/v, i.p) for 16 weeks. HCC-M rats were treated orally with EA (EA + HCC) 50 mg/kg bw for five weeks. Biochemical, morphological, histopathological, and immunohistochemical studies, and gene analysis using qRT-PCR were applied. Results revealed elevated liver injury biomarkers ALT, AST, ALP, and tumor biomarkers AFP and GGT, and marked nodularity of livers of HCC-M. EA effectively reduced the biomarkers and restored the altered structure of the livers. At the mRNA level, EA downregulated the expression of TGF-α, TGF-β, and VEGF, and restored p53 expression. This induced an increase in apoptotic cells immunostained with caspase3 and decreased the CD44 immunostained HCSCs. EA could modulate the tumor microenvironment in the HCC rat model and ultimately target the HCSCs.

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Context: Many congenital malformations are seen increasingly, due to diabetic mothers causing a burden on health systems. Corn silk (CS) extract has been used as a natural hypoglycemic treatment. However, its teratogenic safety was not studied. Aims: Therefore, in this study, we examine the effect of CS aqueous extract on fetuses, offspring of normal and diabetic female mice treated with CS aqueous extract. Settings and Design: Pregnant female mice were divided into two groups diabetic and nondiabetic. Then, each of these groups was divided into control and treated. Subjects and Methods: A daily dose of 4 g/kg of CS aqueous extract was given orally to the treated groups, control groups were given distilled water. The collection of samples was at day 16.5 of pregnancy, and neonates. Brown adipose tissue (BAT) in the sections of the preserved sample was examined. Statistical Analysis Used: BAT areas were measured from 10 samples of each treatment age group in 2 sections. Data were analyzed with one-way ANOVA, then, two-independent sample test (Mann–Whitney) was done to test the significance of differences between groups. Results: The BAT areas were negatively affected by diabetes and the extract. Both the extract and diabetes caused an increase in fat accumulation in the adipocytes with varying degrees. Conclusions: This study showed for the first time to our knowledge that the use of CS aqueous extract during pregnancy affected BAT organization and area, and that the used dose did not decrease the malformations caused by diabetes. More studies with different doses should be investigated.