Testicular torsion (TT) is the most common urological emergency in children and young adults that can lead to infertility in many cases. The ischemia-reperfusion (IR) injury due to TT has been implicated in the pathogenesis of testicular damage. The main pathological mechanisms of contralateral injury after ipsilateral TT are not fully understood. In the presented study, we investigated the molecular and microscopic basis of ipsilateral and contralateral testicular injury following ipsilateral testicular torsion detorsion (T/D) and explored the possible protective role of vitamin D3. The biochemical analysis indicated that IR injury following T/D significantly decreased the activity of testicular glutathione peroxidase (GPx) enzyme, level of serum testosterone, serum inhibin B, and expression of testicular miRNA145, while increased the activity of testicular myeloperoxidase (MPO) enzyme, level of testicular malondialdehyde (MDA), level of serum antisperm-antibody (AsAb), and expression of ADAM-17. The histological and semen analysis revealed that torsion of the testis caused damages on different tissues in testis. Interestingly, administration of vitamin D3 prior to the IR injury reversed the deterioration effect of IR injury on the testicular tissues as indicated by biochemical and histological analysis which revealed normal appearance of the seminiferous tubules with an apparent decrease in collagen fiber deposition in both ipsilateral and contralateral testes. Our results revealed that the protective effect of vitamin D3 treatment could be attributed to target miRNA145 and ADAM17 protein. To further investigate these findings, we performed a detailed molecular modelling study in order to explore the binding affinity of vitamin D3 toward ADAM17 protein. Our results revealed that vitamin D3 has the ability to bind to the active site of ADAM17 protein via a set of hydrophobic and hydrophilic interactions with high docking score. In conclusion, this study highlights the protective pharmacological application of vitamin D3 to ameliorate the damages of testicular T/D on the testicular tissues via targeting miRNA145 and ADAM17 protein.

Alzheimer’s disease (AD) is a worldwide chronic progressive neurodegenerative disease. We aimed to investigate and compare the neuroprotective impact of acetyl-l-carnitine and caloric restriction (CR) on AlCl₃-induced AD to explore the pathogenesis and therapeutic strategies of AD. Sixty-seven adult male Wistar rats were allocated into Control, AlCl₃, AlCl₃–acetyl-l-carnitine, and AlCl₃–CR groups. Each of AlCl₃ and acetyl-l-carnitine were given by gavage in a daily dose of 100 mg/kg and CR was conducted by giving 70% of the daily average caloric intake of the control group. Rats were subjected to behavioral assessment using open field test, Y maze, novel object recognition test and passive avoidance test, biochemical assay of serum phosphorylated tau (pTau), hippocampal homogenate phosphorylated adenosine monophosphate-activated protein kinase, Beclin-1, Bcl-2-associated X protein, and B cell lymphoma 2 (Bcl2) as well as hippocampal Ki-67 and glial fibrillary acidic protein immunohistochemistry. AlCl₃-induced cognitive and behavioral deficits coincident with impaired autophagy and enhanced apoptosis associated with defective neurogenesis and defective astrocyte activation. Acetyl-l-carnitine and CR partially protect against AlCl₃-induced behavioral, cognitive, biochemical, and histological changes, with more ameliorative effect of acetyl-l-carnitine on hippocampal apoptotic markers, and more obvious behavioral and histological improvement with CR.

Background: Aging is associated with cardiovascular and metabolic changes, increasing the susceptibility to acute myocardial infarction (AMI). Intermittent fasting (IF) has a beneficial effect on the age-associated cardiovascular diseases. The present study was planned to investigate the possible protective effect of IF against acute AMI induced by isoproterenol (ISO) in old rats and its possible underlying mechanisms mediated by heart and pancreatic autophagy. Thirty Male Wistar rats were divided into four groups: adult; old; Old-ISO (rats subjected to AMI by ISO) and Old-F-ISO groups (rats were subjected to IF for 4 weeks and AMI by ISO). Results: IF significantly increased the mRNA expression of cardiac Atg-5 and pancreatic Atg-7 in Old-F-ISO versus old and adult groups. This was associated with a significant decrease in serum troponin-I, serum creatine kinase (CK-MB), cardiac malondialdehyde and cardiac TNF-α, fasting plasma glucose, and HOMA-IR in Old-F-ISO compared to Old-ISO group. Also, IF significantly decreased the age-related overall and visceral obesity in Old-F-ISO versus old and Old-ISO groups. Histological studies revealed attenuation of the local inflammatory response in Old-F-ISO versus Old-ISO group. Pancreatic Atg-7 and heart Atg-5 were significantly increased in Old-ISO versus old rats. Conclusions: IF protects against acute AMI in old rats, possibly, via chronic activation of heart Atg-5 and pancreatic Atg-7, and alleviation of age-related overall and visceral obesity. Thus, IF could be a dietary lifestyle modification for attenuation of the susceptibility to acute AMI in aged population. On the other hand, acute activation of heart and pancreatic autophagy by ISO might augment cardiac injury.

Background: Responses to stress could range from homeostatic variations to life-threatening effects. Gender is accompanied by variations in oxidative stress that are implicated in the development of metabolic diseases. Females were found to be less susceptible to oxidative stress. Aim: to clarify the differences in metabolic responses to chronic immobilization stress in both rat sexes, and to elucidate the possible underlying mechanism. Methods: 40 adult albino rats of both sexes were divided into 2 main groups: control and stressed groups, each was subdivided into male and female groups. Stressed groups were exposed to immobilization for 4 weeks. All rats were subjected to estimation of body mass index percentage change (BMI%), visceral fat weight (VFW), glycemic parameters, lipid profile, plasma insulin, leptin, sex hormones, malondialdehyde (MDA), total antioxidant capacity (TAC) and nitrite. HOMA-B and HOMA-IR were calculated, Caspase-3 was assessed in pancreas by immunohistochemistry. Results: Stressed male rats showed lower BMI%, VFW, dyslipidemia, hyperglycemia, higher glucose output by kidneys, lower glucose uptake by diaphragm, HOMA-B, plasma insulin, testosterone and TAC, with higher plasma estrogen and MDA levels compared to control male group. Compared to control females, stressed females exhibited lower VFW, hyperglycemia, hypoinsulinemia, dyslipidemia, lower plasma TAC and HOMA-B, with higher nitrite and sex hormones. Compared to stressed males, stressed females showed higher BMI%, plasma TAC and estrogen, but lower glucose output by kidneys, dyslipidemia and testosterone. Conclusion: Chronic immobilization stress imposes greater metabolic derangement in males than in females. The altered sex hormones and lowered antioxidants could be contributory mechanisms.