Background: Obesity is a complex multifactorial disease characterized by excessive adiposity, and is linked to an increased risk of nonalcoholic fatty liver disease (NAFLD). Flavonoids are natural polyphenolic compounds that exert interesting pharmacological effects as antioxidant, anti-inflammatory, and lipid-lowering agents. In the present study, we investigated the possible therapeutic effects of the flavonoid chrysin on obesity and NAFLD in rats, and the role of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways in mediating these effects. Method: Thirty-two Wistar male rats were divided into two groups: the control group and the obese group. Obesity was induced by feeding with an obesogenic diet for 3 months. The obese rats were subdivided into four subgroups, comprising an untreated group, and three groups treated orally with different doses of chrysin (25, 50, and 75 mg/kg/day for one month). Results revealed that chrysin treatment markedly ameliorated the histological changes and significantly and dose-dependently reduced the weight gain, hyperglycemia, and insulin resistance in the obese rats. Chrysin, besides its antioxidant boosting effects (increased GSH and decreased malondialdehyde), activated the AMPK pathway and suppressed the mTOR and lipogenic pathways, and stimulated expression of the genes controlling mitochondrial biogenesis in the hepatic tissues in a dose-dependent manner. In conclusion, chrysin could be a promising candidate for the treatment of obesity and associated NAFLD, aiding in attenuating weight gain and ameliorating glucose and lipid homeostasis and adipokines, boosting the hepatic mitochondrial biogenesis, and modulating AMPK/mTOR/SREBP-1c signaling pathways.

Obesity has harmful consequences on reproductive outcomes and the rapid increase in obesity is assumed to be influenced by epigenetics and trans-generation effects. Our study aimed to explore the effect of maternal and/or paternal obesity on the ovarian tissues of the first-generation female offspring in rats. The study was conducted on 40 adult Wistar albino rats (20 males and 20 females). Obesity was induced by feeding them an obesogenic diet for 3 months. The pregnancy was induced in the females by mating with males in four combinations: healthy mother with healthy father (control parents, CP), healthy mother with obese fathers (OF), obese mothers with healthy father (OM), and obese mother with obese father (obese parents, OP). After delivery, the female offspring at two months were sacrificed, and the blood and ovarian tissues were collected to assess the studied parameters. Our result showed differential impacts of maternal and paternal obesity on the ovarian health of the female offspring. The female offspring of obese OM or OP showed early signs of obesity. These metabolic abnormalities were associated with signs of ovarian lesions, impaired folliculogenesis, and decreased oocyte quality and also showed significant alterations in mitochondrial biogenesis, redox status, inflammation, and microRNAs expression (miR-149 and miR-494). In conclusion, altered ovarian expression of microRNAs and associated impaired mitochondrial biogenesis pathways may be the root causes for the observed intergeneration transmission of the obesogenic phenotype.

(1) Background: Hepatitis C virus (HCV) infection is endemic in Egypt, with the highest prevalence rate worldwide. Sofosbuvir (SOF) is a nucleos(t)ide analog that specifically inhibits HCV replication. This study aimed to explore the possible effects of the therapeutic dose of SOF on the mitochondrial biogenesis and functions of the liver, muscle, and ovarian tissues of young normal female rats. (2) Methods: This study was conducted on 20 female Wistar rats, classified into two groups, the control group and the exposed group; the latter was orally supplemented with 4 mg/kg/day of SOF for 3 months. (3) Results: The exposure to SOF impairs mitochondrial biogenesis via mitochondrial DNA copy number decline and suppressed mitochondrial biogenesis-regulated parameters at mRNA and protein levels. Also, SOF suppresses the DNA polymerase γ (POLG) expression, citrate synthase activity, and mitochondrial NADH dehydrogenase subunit-5 (ND5) content, which impairs mitochondrial functions. SOF increased lipid peroxidation and oxidative DNA damage markers and decreased tissue expression of nuclear factor erythroid 2-related factor 2 (Nfe2l2). (4) Conclusions: The present findings demonstrate the adverse effects of SOF on mitochondrial biogenesis and function in different tissues of young female rats, which mostly appeared in ovarian tissues.

Sofosbuvir (SOF), a nucleos(t)ide polymerase inhibitor, has been used during the past decade for mass treatment of viral hepatitis C in endemic countries like Egypt, increasing the exposure of women at childbearing age to SOF. This study investigated the long-lasting consequences of the pre-conceptional exposure of young female rats to SOF on the ovarian tissues of F1 offspring and explored the possible molecular mechanisms of these intergenerational effects at various levels. The study was conducted on young female rats that were divided into control group and SOF-exposed group at a dose of 4 mg/kg/day for three months. After that, pregnancy was induced in both groups by mating with healthy male rats. After delivery, the female neonates were followed for 4 months, and the ovarian tissues were collected to assess the studied parameters. Pre-conceptional exposure to SOF affected the ovarian functions of F1 offspring through modulation of estrogen receptors, ovarian Kiss1 and its receptor, increased lipid peroxidation marker, DNA oxidation marker, and redox-sensitive nuclear factor kappa B, and decreased nuclear erythroid-2-related factor 2, mitochondrial function, and biogenesis. SOF affected the ovarian function of the F1 offspring by inducing oxidative stress and inflammation, leading to the modulation of mitochondrial functions and biogenesis.

Background: Breast cancer (BC) is the second most frequently diagnosed malignancy worldwide and the most common cancer among Egyptian women, accounting for 38.8% of female malignancies. Early diagnosis is critical for improving outcomes; however, conventional serum tumor markers such as CEA and CA15-3 show limited sensitivity and specificity in early-stage BC. Liquid biopsy has emerged as a promising non-invasive approach, enabling detection of circulating tumor-derived products, including non-coding RNAs (ncRNAs). This study aimed to evaluate the differential expression of circulating ncRNAs in the serum of female patients with early and metastatic BC prior to initiation of chemotherapy, and to assess their associations with clinicopathological characteristics and prognostic parameters. We also sought to determine their potential utility as prognostic biomarkers for early detection of metastasis. Method: A total of fifty female participants were enrolled following ethical approval and categorized into three groups: healthy controls ( n = 10), early-stage breast cancer patients ( n = 21), and metastatic breast cancer patients ( n = 19). All breast cancer cases were diagnosed with invasive disease and exhibited mixed hormone receptor status. Result: the results demonstrated that the studied ncRNAs (miRNAs and lncRNAs) effectively distinguished early BC patients from healthy controls, whereas CEA and CA15-3 did not. Conclusion: This pilot study provides preliminary evidence that PVT1, HOTAIR, miR-331, and miR-195 may represent potential diagnostic and prognostic biomarkers in BC. However, due to the limited sample size and exploratory nature of the analyses, validation in larger, independent, and prospectively collected cohorts is essential before clinical application can be established.

Objective Evaluate Melatonin, circadian clock genes; brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL-1), Period 2 (PER2) & nuclear factor kabba B (NF-Kb), sirtuin 1 (SIRT-1), Toll-like receptor 4 (TLR-4), tumor necrosis factor alpha (TNF-α) genes expression and vitamin D in Egyptian patients with Hashimoto thyroiditis (HT). Methods: 240 Egyptian volunteers (Egyptian healthy females and Egyptian females with HT). All participants were susceptible to laboratory investigations including and gene expressions. Results The current study revealed increased serum thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (anti TPO-Ab) and anti- thyroglobulin antibody (anti Tg-Ab) in the HT group. On the other hand, decreased serum concentration of melatonin, vitamin D, free tetraiodothyronine (FT4), free triiodothyronine (FT3), ionized calcium & blood hemoglobin in the HT group. Also, our results revealed that the gene expression of the BMAL-1, PER2 and SIRT-1 were downregulated in the HT group. On the contrary, the levels of gene expression of NF-kB, TLR-4,TNF-α genes were upregulated in the HT group. Conclusions We concluded that there is an association between HT and circadian rhythms approved by downregulation of Bmal-1 and PER2 genes expression Also, it may lead to an inflammatory response and oxidative stress. The significant decrease of serum melatonin levels in HT patients, strongly suggests an association between the melatonin pathway and HT. So, Melatonin may be recommended as supplementation for HT patients.