RESUMO
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-1ß, 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.
Assuntos
Quimiocina CCL2 , Cinamatos , Depsídeos , Modelos Animais de Doenças , Letrozol , Síndrome do Ovário Policístico , Ácido Rosmarínico , Fator A de Crescimento do Endotélio Vascular , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Feminino , Cinamatos/farmacologia , Depsídeos/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos , Quimiocina CCL2/metabolismo , Letrozol/farmacologia , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Imuno-Histoquímica , Testosterona/sangue , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the anogenital distance from the upper verge of the anus to the posterior fourchette (AGDAF), FASL, and BCL2 combination as a reliable and non-invasive tool for the diagnosis of endometriosis. METHODS: This study included 100 women with endometriosis and 50 women without endometriosis as the control group. All cases underwent history taking, body mass index (BMI) measurement, AGD measurement, and FASL and BCL2 immunohistochemical staining of the eutopic endometrial tissue. RESULTS: This study included 150 women divided into endometriosis and control groups. Endometriosis cases significantly had shorter AGDAF, 22.9 ± 2.6 mm, compared with the control group, 27.3 ± 3.5 mm (P < 0.001). Lower FASL and higher BCL2 expression were associated with endometriosis (P < 0.001). The combined measurement of AGDAF (cut-off point 24.55 mm) with FASL and BCL2 was associated with endometriosis (P < 0.001). The combined diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of AGDAF, FASL, and BCL2 were 83%, 78%, 87.3%, and 69.6%, respectively. The area under the curve was greater for AGDAF, FASL, and BCL2 in combination than for individual measurements. CONCLUSION: Combining short AGDAF with high BCL2 and low FASL is a highly sensitive, non-invasive diagnostic tool for endometriosis.
Assuntos
Canal Anal , Endometriose , Endométrio , Proteína Ligante Fas , Proteínas Proto-Oncogênicas c-bcl-2 , Humanos , Feminino , Endometriose/diagnóstico , Endometriose/patologia , Adulto , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Endométrio/patologia , Endométrio/metabolismo , Canal Anal/patologia , Proteína Ligante Fas/metabolismo , Proteína Ligante Fas/análise , Estudos de Casos e Controles , Sensibilidade e Especificidade , Adulto Jovem , Valor Preditivo dos TestesRESUMO
Background & Objective: Cervical cancer spreads to the pelvic lymph nodes, leading to a high incidence of cancer recurrence and unfavorable survival rates. Therefore, there is an urgent need to detect new predictive biomarkers for the early assessment of pelvic lymph node status in patients with cervical cancer. The current study aimed to assess the expression of FABP4, GINS2, and CBX7 in cervical cancer tissue to detect their prognostic and predictive roles in developing lymph node metastases in patients with that cancer type. Methods: We collected the tissues from patients with cervical cancer and evaluated the expression of FABP4, GINS2, and CBX7 using immunohistochemistry. We evaluated the association between their expression and clinicopathological and prognostic parameters. Results: A high expression of FABP4 and GINS2 and a low expression of CBX7 were found to be positively associated with the old age group, large tumor size, high grade and lymphovascular involvement, para-uterine organ infiltration, advanced FIGO stage, chemotherapeutic resistance, and tumor recurrence. Conclusion: We demonstrated the oncogenic roles of FABP4 and GISN2 in addition to the on-co-suppressive roles of CBX7 in cervical cancer and their association with poor clinicopathological criteria and poor survival. Our results may indicate that FABP4, GISN2, and CBX7 could be considered predictive biomarkers of the occurrence of lymph node metastases in the cancer of the cervix preoperatively, which could be beneficial in the accurate preoperative design therapy.
RESUMO
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 post-implantation 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.
Assuntos
Inibidores da Aromatase , Letrozol , Placenta , Animais , Feminino , Gravidez , Ratos , Inibidores da Aromatase/farmacologia , Letrozol/farmacologia , Placenta/efeitos dos fármacos , Receptores de Estrogênio , Fator A de Crescimento do Endotélio VascularRESUMO
Pregnancy-related cardiovascular disease with stroke remains a considerable source of higher maternal morbidity and mortality occurs in periods of pregnancy, delivery, and postpartum. It is essential to counsel the mother before pregnancy by an expert cardiologist and obstetric team to discuss any event related to preexistent cardiac or past preeclampsia for estimation of maternal and fetal risks. In pregnancy, the cardiac state includes hypertensive disorders, ischemic heart disease, valvular disease, and postpartum stroke. The incidence of stroke is increasing in pregnancy, particularly in postpartum, and its strong relationship with hypertensive disorders of pregnancy (preeclampsia). The combined cardiologist and obstetrics team requires during pregnancy mainly due to the approach to the management of a cardiac disease that subsequently prevents stroke postpartum. Therefore, a general perception of cardiac disease during pregnancy, delivery, and postpartum should be a core knowledge extent for all cardiovascular and clinicians. Many studies provided linked that deregulation of microRNAs (miRNAs) in maternal circulation and placenta tissue may development of pregnancy complications including preeclampsia considered a diagnostic marker. The desire of this review provides a detailed outline of current knowledge and dealing in this field with strength on the physiological changes during pregnancy.