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Cancer stem cells (CSCs) significantly contribute to heterogeneity, malignancy, and therapy resistance in ovarian cancer. Recent studies emphasize the role of the vitamin D receptor (VDR) in regulating cell differentiation and stemness in various types of cancer. This study aims to determine the expression levels of CD44, CD133, and VDR in epithelial ovarian tumors (EOTs) and to compare these levels across different tumor types, including benign, atypical proliferative tumors, and five types of malignant phenotypes, in order to evaluate their potential as diagnostic tools for malignancy. Tissue samples from 218 patients diagnosed with EOT were analyzed. Clinical and histopathologic parameters were recorded. Quantitative immunohistochemical tissue microarray analysis was used to assess the expression levels of CD44, CD133, and VDR using two different scoring systems. Comparisons were made between benign tumors (n = 45), atypical proliferative tumors (n = 42), and ovarian carcinomas (n = 131), including high-grade serous (HGSC) and non-HGSC subtypes. Ovarian cancer, especially HGSC, showed a significantly higher expression of CD44 and VDR (p < 0.05) compared to atypical proliferative tumors and benign tumors. The expression of CD133 was highest in atypical proliferative tumors (p < 0.05). A moderate positive correlation was found between CD44, CD133, and VDR in all groups, with significant correlations with tumor grade and FIGO stage in ovarian cancer (p < 0.05). The increased expression of CD44 and VDR in aggressive ovarian cancer, along with elevated CD133 levels in atypical proliferative tumors, highlights the complexity of tumor biology. These markers may serve as valuable targets for the diagnosis of ovarian cancer.

Glucagon-like peptide-1 receptor agonists and lifestyle interventions effectively treat overt obesity, but the benefits/risks of their combined early intervention during middle age remain unclear. This study investigated whether submaximal-dose liraglutide combined with strength-endurance training improves metabolic and liver health, focusing on hepatic oxidative stress and lipid metabolism. Male Wistar rats (16 months old) received liraglutide (L; 0.186 mg/kg/day, s.c.), training (ladder climbing with weights, 3 times/week), both (L+E) or saline for control middle-aged (C) and young adults (CY; 3-4 months old) for 7 weeks (n = 8/group). Middle-aged rats exhibited age-related changes including higher body and visceral fat, increased hepatic and serum cholesterol, hepatic ALT and glutathione imbalance, and decreased soleus muscle ( < 0.05, vs. CY). Exercise increased hepatic glycogen and oxidative stress markers and downregulated lipogenic genes, consistent with liver adaptation to training. L+E synergistically reduced body and visceral fat, hepatic and serum triglycerides, and the triglyceride-glucose index, while reducing oxidative stress ( < 0.05 vs. E, C) and lipogenic gene expression ( < 0.05 vs. C), without affecting pancreas histopathology and function parameters, muscle mass or exercise load volume. In conclusion, submaximal liraglutide safely synergized with training to enhance metabolic health, improve hepatic redox balance and triglyceride metabolism in middle-aged rats, without mitigating cholesterol rise.

As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta’s morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p < 0.05) in female placentas. The volume density of PCNA-immunopositive nuclei was reduced (p < 0.05) in both sexes. The reduced (p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects.

The effects of multiple somatostatin (SRIH-14) administration on the pituitary–ovarian axis were examined in peripubertal rats. Female Wistar rats received subcutaneously, two daily doses of 20 μg SRIH-14 per 100 g body weight (b.w.) for five consecutive days (from the 33rd to the 37th day of life). Follicle-stimulating (FSH), luteinizing (LH) and somatotropic (GH) cells were examined by the peroxidase–anti-peroxidase immunocytochemical method. Changes in cell volumes, volume densities and number per unit area (mm 2 ) of FSH-, LH- and GH-immunoreactive cells were evaluated by stereology and morphometry. Serum FSH and LH levels were determined by RIA. Ovaries were analyzed by simple point counting of follicles. The volumes and volume densities of FSH-, LH- and GH-immunoreactive cells were significantly decreased while their numbers per mm 2 remained unchanged. SRIH-14 induced a significant decrease in serum FSH and LH levels. In the ovary, SRIH-14 induced an increase in the number of primordial follicles, followed by a reduction in the number of small healthy growing follicles and absence of preovulatory follicles. The number of atretic follicles was unchanged. We concluded that treatment with SRIH-14 during the peripubertal period markedly inhibited pituitary FSH, LH and GH cells. In the ovary, SRIH-14 acted by inhibiting folliculogenesis without affecting atretic processes.

Somatopause, the complex aspect of andropause, is recognizable by reduced growth hormone - GH/insulin-like growth factor 1 axis function in the ageing male. Soy isoflavones (usually genistein and daidzein), which are known for their beneficial effects in the treatment of ageing symptoms, are active in the pituitary, as well. The immunohistomorphometric and -fluorescent characteristics of pituitary growth hormone secreting cells, in an animal model of andropause, were examined after a treatment with genistein or daidzein. Andropausal Wistar rats were divided into sham operated, orchidectomized and genistein or daidzein treated orchidectomized groups. Genistein or daidzein (30 mg/kg/day) were administered subcutaneously for three weeks, while sham operated and orchidectomized groups received the vehicle alone. Growth hormone secreting cells were identified by the peroxidase-antiperoxidase immuno-histochemical, and immuno-fluorescent procedure. The main characteristic of growth hormone secreting cells in soy isoflavones treated groups is a weaker immuno-histochemical staining and immuno-fluorescent signal compared to sham operated and orchidectomized groups. The growth hormone secreting cell volume in orchidectomized +genistein or +daidzein groups is by 13.8% and 11.9% (p<0.05) smaller respectively, in comparison with the orchidectomized group. In orchidectomized +genistein or +daidzein groups, the growth hormone secreting cells relative volume density is by 62.5% and 61.0% lower (p<0.05) respectively than for the sham operated group, and decreased by 65.4% and 64.0% (p<0.05) respectively, compared to the orchidectomized group. It can be concluded that chronic genistein or daidzein treatment, in an animal model of andropause, attenuates immunohistomorphometric and -fluorescent characteristics of growth hormone secreting cells.

Background: Breast cancer is the most common form of cancer in women. It arises from multiple genetic changes in oncogenes and tumor suppressor genes. Among so far studied oncogenes relatively few, including epdermal growth factor receptor (EGfR), cyclinD1 (CCNDİ)and c-myc, have been found to play an important role in progression of this type of human malignancy. The aim of this study was to examine the prognostic potential of CCND1, c-myc and EGFR amplification and their possible cooperation in breast carcinogenesis. Methods: Copy number analyses of CCND1 and c-myc genes were done by TaqMan based quantitative real time PCR. Amplification status of EGFR was determined by differential Pcr. Results: Amplification of CCND1, c-myc and EGFR oncogene has been found in 20.4%, 26.5% and 26.5% of breast cancer cases, respectively. Analysis showed that amplification of CCND1 oncogene was significantly associated with the stage II of disease while amplification of EGFR gene was significantly associated with overexpression of HER-2/neu. Tumour stage and expression of HER-2/neu appeared to be significant predictors of patient's outcome. Stage I patients lived significantly longer then stage III patients (p=0.04) while patients with HER-2/neu overexpression had worse prognoses and lived significantly shorter (p=0.001). Finally, survival of patients who underwent hormone therapy only was significantly longer (p=0.001) then survival of the rest of patients. Conclusions: Amplification of CCND1 or EGFR oncogene is associated with the progression of breast cancer and bad prognosis. No co-ordination in amplification of CCND1, c-myc and EGFR oncogenes were established in this cohort of breast cancer patients.

Elevated glucocorticoid level in the gravid female circulation affects number of endocrine functions in fetuses and offspring. In this research female rats were injected with dexamethasone (Dx) in three consecutive daily doses of 1.0, 0.5, 0.5 mg/kg body weight, starting from day 16 of pregnancy. The influence of this treatment on the pituitary adrenocorticotrophic (ACTH) cells and adrenal glands of 19-day-old fetuses was examined immunocytochemically and by morphometric analysis. Moreover, the proliferative activity of adrenocortical cells was estimated after application of the mitotic inhibitor Oncovine. Administration of Dx to pregnant rats induced a decline of fetal ACTH cell immunopositivity and significant decreases of ACTH cell volume (23%, p < 0.05), volume density (41%, p < 0.05), and its number per unit area (17%, p < 0.05) in comparison to the control 19-day-old fetuses. Reduced proliferative activity of adrenocortical cells (31%; p < 0.05) in zona glomerulosa, as well as the volume of this zone were detected. The volume and number of fetal adrenocortical cells in the inner zone and chromoblasts were not significantly reduced after Dx treatment of pregnant rats. These results show that maternal Dx administration in the period when the fetal hypothalamo-pituitary-adrenal (PA) axis begins its function inhibited the PA axis. Reduced ACTH cell function and mitotic activity led to suppression of adrenocortical cell multiplication in zona glomerulosa, the region of the adrenal cortex where most proliferating cells were found in control 19-day-old fetuses. Thus, increased glucocorticoid levels during late pregnancy caused developmental modifications involving the fetal PA axis, which could be the basis of the altered endocrine responsiveness in adult life.

A decrease of erythrocyte membrane fluidity can contribute to the pathophysiology of hypertension. Soy products, which are used as alternative therapeutics in some cardiovascular conditions, contain various isoflavones (genistein, daidzein, and their glucosides, genistin and daidzin), which can incorporate cellular membrane and change its fluidity. The aim of this study was to examine the effects of soy extract (which generally corresponds to the soy products of isoflavone composition) on erythrocyte membrane fluidity at graded depths. We used electron paramagnetic resonance spectroscopy and fatty acid spin probes (5-DS and 12-DS), the spectra of which are dependent on membrane fluidity. After being treated with soy extract, erythrocytes showed a significant (P = 0.016) decrease of membrane fluidity near the hydrophilic surface, while there were no significant changes of fluidity in deeper hydrophobic membrane regions. These results suggest that soy products containing high levels of genistein and isoflavone glucosides may not be suitable for use in hypertension because they decrease erythrocyte membrane fluidity.

Body weight depends on the balance between energy intake and consumption. An interaction between ghrelin and thyroid function has been reported only in pathophysiological states. We examined whether intracerebroventricular (ICV) administration of ghrelin affects the structure and function of the pituitary-thyroid axis in young adult male rats. Ghrelin (0.3 nmol/5 μl PBS) or an equal volume of PBS were injected every 24 h into the lateral cerebral ventricle for 5 days. Two hours after the last treatment the animals were killed, their pituitaries and thyroids excised and prepared for further histological, immunohistochemical and morphometric investigation. Serum TSH levels were measured by RIA, while the total T 4 and T 3 levels were examined by ECLIA. Ghrelin treatment increased pituitary weight (p < 0.05) when compared to the controls, with no effect on the thyroid weight. Smaller, degranulated TSH-immunopositive cells were noticed within the pituitaries of ghrelin-treated animals; their cellular and nuclear volume as well as the relative volume density of thyrotrophs decreased (p < 0.05) in comparison to the control values. The level of serum TSH was reduced (p < 0.05). In the thyroid parenchyma of ghrelin-treated rats, an increased number of hypofunctioning follicles was noticed, characterized by flattened, weakly Tg-immunoreactive epithelium and colloid distension. The relative volume densities of the follicles and colloid increased (p < 0.05), while the thyroid index of activation rate and the serum level of total T 4 decreased (p < 0.05). In conclusion, centrally applied ghrelin modulated the immunohistomorphometric features of pituitary TSH cells and decreased the level of serum TSH, consequently changing thyroid morphology and function, by reducing the T 4 hormone level in the serum.