Mesenchymal-Stem Cell-Derived Conditioned Media Versus Exosomes in the Treatment of Rat Model of Polycystic Ovary: An Attempt to Understand the Underlying Mechanisms (Biochemical and Histological Study).

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and reproductive disorders throughout female reproductive age. Cell free therapy [conditioned media (CM) & exosomes (EXO)] is a promising approach in regenerative medicine. This study aimed to compare between the therapeutic effects of stem cell-derived CM and exosomes on induced animal model of polycystic ovary. Polycystic ovary (PCO) was induced in female rats (3-4 weeks old, weighing 70-80 g) by letrozole with a dose of 1 mg/kg/day dissolved in carboxymethylcellulose 1% orally once daily for 5 weeks. Animals were divided into four groups: control group, PCO group, EXO-treated group, and CM-treated group. Serum levels of testosterone hormone, leutinizing hormone, follicle stimulatimg hormone, and insulin hormone were estimated. Immunohistochemistry using anti-P53, anti-AMP-dependent protein kinase antibodies were done. Six rats/group were used for matting with adult male rats for testing fertility. The results showed that CM had significant superior therapeutic effects on exosomes in restoring the normal histological architecture of the ovary and fertility. In summary, cell free treatment is a safe approach for tissue regeneration. Stem cell-derived CM was more effective than exosomes in restoring normal histological structure of the ovaries and fertility in animal models of polycystic ovary.

Exercise ameliorates hippocampal damage induced by Wi-Fi radiation; a biochemical, histological, and immunohistochemical study.

INTRODUCTION: Nowadays, using electromagnetic devices (EMD) has been increased. However, the control of EMD hazards was poorly evaluated, especially those affected the hippocampus. Regular physical exercises are safe, easily, inexpensive, and acceptable for long-term use. It is reported that exercise protects against many health problems. AIM: is to investigate the hypothesis of the possible prophylactic effect of exercise on the hippocampal damage induced by electromagnetic waves of Wi-Fi. MATERIAL AND METHODS: Adult male albino rats were divided into four groups: group I (control), group II (exercise), group III (Wi-Fi), and group IV (exercise -Wi-Fi). Hippocampi were subjected to biochemical, histological, and immunohistochemical techniques. RESULTS: In group III, a significant increase in the oxidative enzymes as well as decrease in antioxidant enzymes were detected in rat hippocampus. Additionally, the hippocampus showed degenerated pyramidal and granular neurons. An evident decrease in both PCNA and ZO-1 immunoreactivity was also noticed. In group IV, physical exercise alleviates the effect of Wi-Fi on previously mentioned parameters. CONCLUSION: Regular physical exercise performance significantly minimizes the hippocampal damage and protects against the hazarders of chronic Wi-Fi radiation exposure.

Dose-Dependent Cardioprotective Effect of Hemin in Doxorubicin-Induced Cardiotoxicity Via Nrf-2/HO-1 and TLR-5/NF-κB/TNF-α Signaling Pathways.

Doxorubicin (DOX) is one of the most widely used chemotherapeutic drugs, but its cardiotoxicity has been shown to be a dose-restricting factor during therapy. Finding new agents for reducing these complications is still in critical need. The current study aimed to evaluate the possible cardioprotective effect of hemin (HEM) in DOX-induced cardiotoxicity and exploring the role of toll like receptor-5/nuclear factor kappa-B/tumor necrosis factor-alpha (TLR-5/NF-κB/TNF-α) and nuclear factor erythroid 2-related factor-2/hemeoxygenase-1 (Nrf-2/HO-1) signaling pathways in mediating such effect. Wistar albino rats were randomly divided into five groups. They were administered DOX by interaperitoneal (i.p.) injection (15 mg/kg) on the 5th day of the experiment with or without HEM in different doses (2.5, 5, 10 mg/kg/day) i.p. for 7 days. Results showed that the DOX group had cardiotoxicity as manifested by a significant increase in cardiac enzymes, malondialdehyde (MDA), TLR-5, NF-κB, TNF-α, and cleaved caspase-3 levels with toxic histopathological changes. Based on these findings, HEM succeeded in reducing DOX-induced cardiotoxicity in a dose-dependent effect by stimulation of Nrf-2/HO-1 and inhibition of TLR-5/NF-κB/TNF-α pathways with subsequent antioxidant, anti-inflammatory, and anti-apoptotic effects.

Amelioration of estrogen-induced endometrial hyperplasia in female rats by hemin via heme-oxygenase-1 expression, suppression of iNOS, p38 MAPK, and Ki67.

Although heme oxygenase-1 (HO-1) is part of an endogenous defense system implicated in the homeostatic response, its role in cell proliferation and tumor progression is still controversial. Endometrial hyperplasia (EH) is associated with high risk of endometrial cancer (EC). Therefore, we aimed to evaluate the effect of hemin, a HO-1 inducer, against EH. Thirty-two female rats (60-70 days old) were divided into 4 groups treated for 1 week: vehicle control group, hemin group (25 mg/kg; i.p. 3 times/week), estradiol valerate (EV) group (2 mg/kg per day, p.o.), and hemin plus EV group. Sera were obtained for reduced glutathione level. Uterine malondialdehyde, superoxide dismutase, total nitrite/nitrate, and interleukin-1ß levels were estimated. HO-1 and p38 mitogen-activated protein kinase expressions were obtained in uterine tissue. Uterine histological and immunohistochemical assessment of iNOS and Ki67 were also done. Results demonstrated that upregulation of HO-1 expression in hemin plus EV rats led to amelioration of EH which was confirmed with histological examination. This was associated with significant decrease in oxidative stress parameters, p38 mitogen-activated protein kinase expression, and interleukin-1ß level. Also, uterine iNOS and Ki67 expressions were markedly suppressed. In conclusion, upregulation of HO-1 expression via hemin has ameliorative effect against EH through its antioxidant, anti-inflammatory, and antiproliferative actions.

Physiological and structural changes of the lung tissue in male albino rat exposed to immobilization stress.

In case of a life-threatening, stressful event, the body prepares for an emergency. Indeed, the lung is unique in which alveolar cells are constantly exposed to physical and chemical stresses. This study aimed to study the impact of immobilization stress on the blood-air barrier and how it initiate and maintain an inflammatory response, plus determining the resolution of lung inflammation and repair. There was a significant increase in the plasma levels of stress markers "corticosterone and catecholamines" with a decrease in surfactant protein A (a lung-injury marker). Chronic stress produced a significant increase in the pulmonary oxidative and inflammatory markers malondialdehyde, tumor necrosis factor α, and induced nitric oxide synthase when compared with that of acute stress. Both stresses provoked marked pulmonary morphological and ultrastructural changes with a significant increase in caspase-3 immunoexpression. There was increasing evidence of lung's capacity for repair. This process involved edema resolution, cell proliferation, and tissue remodeling in improving the lung-injury, oxidative, and inflammatory markers.