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Background and Purpose Varicocele is a leading cause of male infertility. Melatonin is a highly pleiotropic neurohormone. We aimed to characterize the melatonin epigenetic potential in varicocele and the involved molecular mechanisms. Experimental Approach Fifty‐two male albino rats were randomly divided into four groups (13 rats each): control (I), melatonin (II), varicocele (III) and melatonin treated varicocele (IV) groups. Left varicocele was induced by partial left renal vein ligation. Reproductive hormones, epididymal sperm functional parameters, testicular 3/17 β‐hydroxysteroid dehydrogenases, antioxidant enzymes, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, 8‐hydroxy‐2′‐deoxyguanosine and histopathological/Johnsen's score were evaluated. Flow cytometry and Comet were carried out to explore extent of sperm and testicular DNA damage. Testicular expression of silent information regulator 1 (SIRT1), forkhead transcription factors‐class O (type1) (FOXO1), tumour suppressor gene, P53, cation channels of sperm (CatSper) and steroidogenic acute regulatory protein was evaluated by western blot technique. Testicular expression of Bcl‐2 and its associated X protein and nuclear factor kappa‐light‐chain‐enhancer of activated B cells were assayed by immunohistochemical staining. Testicular miR‐34a expression was quantified by quantitative reverse transcription‐polymerase chain reaction. Key Results The varicocele induced testicular histological injury, enhanced oxidative stress, P53‐mediated apoptosis, DNA damage and increased testicular miR‐34a expression paralleled with down‐regulated SIRT1/FOXO axis. Melatonin treatment of varicocele rats displayed antioxidant/anti‐apoptotic efficacy and improved reproductive hormones axis, CatSper expression and fertility parameters. MiR‐34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele. Conclusion and Implications Melatonin can be used as an adjuvant therapy to improve varicocele and its complication.

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With extensive production and various applications of silica nanoparticles (SiNPs), there is a controversy regarding the ecotoxicological impacts of SiNPs. Therefore, the current study was aimed to assess the acute toxicity of silica nanoparticles in male Rattus norvegicus domestica after 24 and 96 h. Hematological, serum biochemical, stress biomarker, and immune-antioxidant parameters were addressed. Chemical composition, crystal structure, and the particle shape and morphology of SiNPs were investigated using XRD, FTIR, BET, UV-Vis, and SEM, while TEM was used to estimate the average size distribution of particles. For the exposure experiment, 48 male rats were divided into four groups (12 rat/group) and gavaged daily with different levels of zero (control), 5, 10, and 20 mg of SiNPs corresponding to zero, 31.25, 62.5, and 125 mg per kg of body weight. Sampling was carried out after 24 and 96 h. Relative to the control group, the exposure to SiNPs induced clear behavioral changes such as inactivity, lethargy, aggressiveness, and screaming. In a dose-dependent manner, the behavior scores recorded the highest values. Pairwise comparisons with the control demonstrated a significant (p < 0.05) decrease in hematological and immunological biomarkers [lysozymes and alternative complement activity (ACH50)] with a concomitant reduction in the antioxidant enzymes [catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)] in all exposed groups to SiNPs. On the contrary, there was a noticeable increase in biochemical parameters (glucose, cortisol, creatinine, urea, low-density lipoproteins (LDL), high-density lipoproteins (HDL), total protein, and albumin) and hepato-renal indicators, including alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), of all SiNP-exposed groups. It was observed that SiNPs induced acute toxicity, either after 24 h or 96 h, post-exposure of rats to SiNPs evidenced by ethological changes, hepato-renal dysfunction, hyperlipemia, and severe suppression in hematological, protein, stress, and immune-antioxidant biomarkers reflecting an impaired physiological status. The obtained outcomes create a foundation for future research to consider the acute toxicity of nanoparticles to preserve human health and sustain the environment.

The prevalence of obesity and its associated metabolic disorders, along with their healthcare costs, is rising exponentially. Irisin, an adipomyokine, may serve as a critical cross-organ messenger, linking skeletal muscle with adipose tissue and the liver to integrate the energy homeostasis under diet-induced obesity. We aimed to explore the putative role of irisin in the protection against obesity in a postmenopausal rat model by modulating energy expenditure (EE). Bilateral ovariectomy (OVX) was performed. After 3 weeks of recovery, the OVX rats were classified according to their dietary protocol into rats maintained on normal diets (ND) (OVX) or high-fat diet (HFD) groups. The HFD-fed animals were equally divided into OVX/HFD, or irisin-treated OVX/HFD groups. Sham rats, maintained on ND, were selected as the control group. We evaluated anthropometric, EE, and molecular biomarkers of browning and thermogenesis in inguinal white adipose tissue and skeletal muscle, and the activity of the proteins related to mitochondrial long chain fatty acid transport, oxidation, and glycolysis. HFD of OVX further deteriorated the disturbed glucose homeostasis, lipid profile, and the reduced irisin, thermogenic parameters in adipose tissue and skeletal muscle, and EE. Irisin treatment improved the lipid profile and insulin resistance. That was associated with reduced hepatic gluconeogenic enzyme activities and restored hepatic glycogen content. Irisin reduced ectopic lipid infiltration. Irisin augmented EE by activating non-shivering thermogenesis in muscle and adipose tissues and decreasing metabolic efficiency. Our experimental evidence suggests irisin’s use as a potential thermogenic agent, therapeutically targeting obesity in postmenopausal patients. Graphical abstract Irisin modulates the non-shivering thermogenesis in skeletal muscle and adipose tissue in postmenopausal model

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Many studies have demonstrated that osteopontin (OPN) contributes functionally to aggressive behaviour in many tumours including breast cancer.This study aims to investigate its role as a simple biochemical marker easily measured in plasma of breast cancer patients to give an early signal for metastases and to detect its relationship to clinicopathological findings and survival.We measured plasma OPN, CA15.3 and serum alkaline phosphatase (ALP) activity in 55 patients, 28 with early stage breast cancer and 27 with bone metastasis out of whom 20 had metastasis in other sites. The median age at diagnosis for non-metastatic cases was 60 years (range 35-85) and for metastatic cases was 45.5 years (range 32-59). In the non-metastatic group, 78.57% of the patients were histologically graded as grades I and II and 21.43% as grade III tumours. In the metastatic group, 81.48% of the patients had grades I and II and 18.52% had grade III tumours; 54% of patients in the non-metastatic group were at stage II and 46% were at stage III at presentation. All patients of group II had bone metastasis, 33% had liver metastases, 25.9% had lung metastasis and 14.8% had lymph node metastasis.Patients with non-metastatic disease had a median OPN level of 55 ng/ml (range 54-150 ng/l), while those in the metastatic group had a median of 148.0 ng/l (range 56.0-156.0 ng/l), a difference which was statistically significant (P = 0.001). There was no statistically significant difference in the median levels of CA15.3 and ALP between both groups.The median OPN level was significantly higher with serum ALP level above 90, progesterone receptor (PR) status, bone and visceral metastasis. Median OPN was not affected significantly by menopausal status (P-value 0.3), tumour grade (P-value 0.3), estrogen receptor (ER) status (P-value 0.7), pathological type (P-value 0.42) or serum CA15.3 level (P-value 0.6).At the end of 12-year follow-up, 83% of the patients survived (92.3% in the non-metastatic versus 74.1% in the metastatic group). The estimated median survival for the whole study population at 12 years was 13 years (95% CI 8.144-17.856). The estimated median survival was 13 years (95% CI 0) and 12 years (95% CI 4.893-19.11) in patients with median OPN levels of <142 and ≥142, respectively, a difference which was not statistically significant (P = 0.343). No statistically significant difference in overall survival OS was noticed in relation to menopausal status (P = 0.7), pathological type (P = 0.4) and hormone receptor status (P = 0.3). At 6-year follow-up, it was found that OS was affected by the presence of visceral metastasis, tumour grade, serum plasma level of ALP and the serum level of CA15.3 (P = 0.0006, 0.007, 0.001 and 0.03, respectively). However, the presence of bone metastasis did not affect OS (P = 0.6).Osteopontin level can be a simple biochemical marker easily measured in plasma of breast cancer patients to give early signals for metastases, but not a prognostic factor for survival.

A chronic low-grade inflammation is one of etiologic conditions closely associated with obesity. The study aims to examine the effect of lycopene on obesity inflammatory conditions in rats. 20 adult male albino rats were divided into four groups (n=5) and for 30-day treatment they were divided into the control group received corn oil as a vehicle, lycopene control group received lycopene extract (10 mg/kg) daily with gavage, obese control group subjected to high fat (HF) diet and received corn oil and obese/lycopene group subjected to HF diet and daily received lycopene extract by the same dose. Bodyweight, weight of thymus and spleen, cytokines [Resistin, Interleukin-1β (IL-1β), Tumor Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6)], lipid profile, and immunohistochemical assay for the Nuclear Factor kappa-B receptors (NF-κB) expression were measured and analyzed. The results revealed that the induced obesity caused a remarkable increase in bodyweight, relative weight of thymus and spleen, levels of serum cytokines, total cholesterol and triglycerides and NF-κB receptors expression, but decreased high-density lipid (HDL) level significantly. Administration of lycopene to obese rats caused a significant depletion in the levels of serum cytokines, total cholesterol (TC) and triglycerides (TG) with a significant increase in HDL level and caused no change in bodyweight, while the relative weight of the spleen and thymus was improved. Also, lycopene caused a marked decline in NF-κB receptors expression in thymus and spleen. These results supported the importance of lycopene as a beneficial carotenoid in combating obesity and companied disturbed fat index and metabolism.