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Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole‐induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid‐PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle‐stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor‐α (TNF‐α), interleukin‐1β, monocyte chemotactic protein‐1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF‐α and caspase‐3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole‐induced PCOS through its anti‐inflammatory and antiangiogenesis effects. Significance Statement: Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age.Letrozole's efficacy in inducing PCOS in rats is extensively proven.Rosmarinic acid enhances folliculogenesis and gonadotropin production.Rosmarinic acid's efficacy in PCOS appears to be owing to its antiangiogenesis and anti‐inflammatory effects. [ABSTRACT FROM AUTHOR]

The chemotherapeutic drug methotrexate (MTX) is utilized to treat various malignancies. MTX exposure during pregnancy causes miscarriages, abnormalities in newborns, and developmental delays. The current study examined the placenta's sequential histopathological alterations following exposure to the MTX in pregnant rats. Twenty-four pregnant rats were assigned into; the control group and MTX group (0.2 mg/kg). MTX was given intraperitoneally on gestational days 11–12. Oxidative stress parameters were measured in placental homogenates. The placental specimens were evaluated by light, immunohistochemical (caspase-3 and vascular endothelial growth factor (VEGF)), and electron microscopic study. Malondialdehyde levels were significantly elevated by MTX, whereas glutathione peroxidase and superoxide dismutase levels were significantly reduced. The MTX group showed a marked reduction in the thickness of both the basal and labyrinth zones. Degeneration of the labyrinth zone was demonstrated. Also, giant trophoblast cells and the spongiotrophoblasts of the basal zone showed vacuolations with dark nuclei. Up-regulation of caspase-3 and down-regulation of VEGF immunoexpression were demonstrated. Ultrastructurally, disintegration of the interhemal membrane, spongiotrophoblasts with vacuolated cytoplasm and small condensed nuclei, and the giant trophoblasts with irregular nuclear outlines and vacuolated cytoplasm were demonstrated. In conclusion, MTX has profoundly altered the structure of the placenta. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with highrisk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProEx™C, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProEx™C, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProEx™C was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProEx™C is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC. [ABSTRACT FROM AUTHOR]

Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant. Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high postimplantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001). Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects. [ABSTRACT FROM AUTHOR]