Melatonin epigenetic potential on testicular functions and fertility profile in varicocele rat model is mediated by silent information regulator 1.

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 ß-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.

Unique Novel Role of Adropin in a Gastric Ulcer in a Rotenone-Induced Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, frequently associated with a gastric ulcer. We aimed to investigate the adropin neuroprotective/gastroprotective potential in the indomethacin (IND)-induced gastric ulcer in a rotenone-induced PD model. Rats were randomly divided into four groups: normal control group, rotenone/IND treated (PD /Ulcer) group, adropin treated PD/Ulcer group, and l-dopa/omeprazole (Om) treated PD/Ulcer group. There were ten rats selected for the normal control group. Striatal dopamine (DA), apoptosis/redox status, and motor/behavioral impairments were evaluated. Gastric oxidative stress, H+/K+-ATPase activity, prostaglandin E2, mucin content, and von Willebrand factor were measured. Gastric/striatal phosphatidylinositol 3-kinase (PI3K)/phosphorylated Akt and gastric vascular endothelial growth factor (VEGF)/striatal P53 immunoreactivities were checked. Striatal P53 upregulated modulator of apoptosis (Puma)/gastric vascular endothelial growth factor receptor-2 (Vegfr-2) expressions were evaluated. Adropin successfully restored striatal DA and attenuated rotenone-induced motor/behavior deficits along with strong gastroprotective potential, possibly through antioxidant activity via reduction in malondialdehyde level and upregulated superoxide dismutase, catalase activities, and serum ferric reducing antioxidant power. Adropin restored the delicate balance between the defective pro-survival PI3K/Akt/murine double minute 2 signals and apoptotic P53/Puma pathways. Adropin can be considered as a uniquely attractive therapeutic target in PD and its associated gastric ulcer.

Significance of Expression of Cancer Stem Cell Markers CD133 and Nestin in Pancreatic Intraepithelial Carcinoma-invasive Adenocarcinoma Sequence.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and one of the most leading causes of cancer related deaths. It has a very poor prognosis with high recurrence rate. We investigated the expression of CSC markers (CD133 and nestin) in 100 patients [30 pancreatic intraepithelial tumor cases (PanIN) and 70 PDAC cases] and correlate the expression levels of these markers with clinicopathological data with the aid of Ki67 expression. Our findings showed that both cancer stem markers are related to the grade, stage, metastasis of PDAC and to the grade of PanIN cases and revealed that both markers are associated with PanIN-PDAC sequence with inverse relation between them. Both markers may contribute to proliferation, differentiation, invasiveness, and histologic types of PDAC. Sothey may also be useful for developing new therapeutic modalities for PDAC.

Assessment of the potential therapeutic effects of omeprazole in Schistosoma mansoni infected mice.

Schistosomiasis is a neglected chronic parasitic disease with a significant lasting morbidity. Currently, praziquantel (PZQ) is the most efficient drug for schistosomiasis worldwide. However, the possibility of the occurrence of resistance to PZQ is increasing. Therefore, there is a vital need to find new antischistosomal drugs or to increase the efficacy of the existing ones. Omeprazole is a proton pump inhibitor which is reported to have antiparasitic properties. Thus, the aim of this study was to assess the potential therapeutic effects of omeprazole in experimental Schistosoma mansoni infection either alone or in combination with PZQ. For this aim, 80 laboratory bred mice were divided into 3 groups; uninfected control, infected untreated control, and infected and treated at tenth week P.I. The last group was divided into three subgroups that received either PZQ alone, omeprazole alone, or both drugs. The effectiveness of treatment was assessed by adult worm counts, liver egg count, scanning electron microscopy of adult worms, histopathological, and immunohistochemical (GFAP) examination. There was significant reduction of adult worm counts, liver egg counts, size, diameter of hepatic granulomas, hepatic fibrosis, and GFAP expression in the group that received combined treatment as compared to PZQ group. Moreover, the tegumental changes were more evident in the group that received combined treatment. In conclusion, the administration of omeprazole with PZQ improved the efficacy of PZQ in the treatment of Schistosomiasis mansoni.

Glucose transporter-1 (GLUT-1) expression in psoriasis: correlation with disease severity.

BACKGROUND: Epidermal hyperproliferation with abnormal differentiation, inflammation, and angiogenesis are the key features of psoriasis. Glucose transporter-1 (GLUT-1) is a member of facilitative sugar transporters that are integral membrane glycoproteins moving sugar across cell membrane. OBJECTIVE: The objective of this study was to study the GLUT-1 expression in psoriasis. PATIENTS AND METHODS: Forty patients with psoriasis vulgaris and 20 healthy individuals were included in the study. Skin biopsies were taken from lesional and nonlesional skin of psoriasis patients as well as normal skin of control subjects. All were examined for GLUT-1 antibody expression by immunohistochemistry and GLUT-1 mRNA expression by real-time polymerase chain reaction (RT-PCR). In addition, specimens of psoriasis lesions were stained by hematoxylin and eosin and CD31 for morphometric analysis of histopathological parameters. RESULTS: The intensity of GLUT-1 immunohistochemical expression and the relative levels of GLUT-1 mRNA expression in psoriasis lesions were upregulated in lesional skin of psoriasis patients in comparison with their nonlesional skin as well as normal control skin. GLUT-1 expression in psoriasis lesions showed significant positive correlations with Psoriasis Area and Severity Index (PASI) score, mean of epidermal thickness, inflammatory cell density, and microvessel density. CONCLUSION: Glucose transporter-1 could play a role not only in the onset of psoriasis but also in the progression and severity of the disease. It may participate in the pathogenesis of psoriasis through the facilitation of epidermal hyperproliferation, inflammation, and angiogenesis.

Napsin-A, a Possible Diagnostic Marker for Differentiating Clear Cell Ovarian Carcinoma From Other High-grade Ovarian Carcinomas.

Ovarian clear cell carcinoma (CCC) is divergent from other types of epithelial ovarian carcinoma in terms of clinicopathologic and molecular features. It should be separated from other high-grade carcinomas of the ovary for appropriate treatment. Napsin A is a reliable marker for adenocarcinoma of the lungs, but its role in ovarian epithelial carcinomas is vague. We investigated the expression of a panel of TTF-1, paired box 8, estrogen receptor, Wilms tumor 1, and Napsin A in 100 cases of high-grade ovarian carcinomas. All the examined cases were TTF-1 negative and paired box 8 positive. The 2 biomarkers estrogen receptor together with Wilms tumor 1 can separate CCC from endometriod carcinoma, yet this cannot be carried out in the case of serous and mucinous carcinomas of high grade. Napsin A can differentiate CCC with high sensitivity and specificity. It can be concluded that Napsin A is a sensitive and specific marker for CCC of the ovary. However, an entire marker panel may be useful for distinguishing ovarian CCC from other mimics.

Role of inducible nitric oxide synthase and interleukin-6 expression in estimation of skin burn age and vitality.

Estimation of age and vitality of burn injury both in the living and dead is essential in forensic practice. Nitric oxide and interleukin-6 (IL-6) play an important role in skin burn healing. In this study, the expression of inducible nitric oxide synthase (iNOS) and IL-6 proteins during skin burn healing in rats was studied for purposes of burn dating and to differentiate between ante-mortem and post-mortem burn. Ante-mortem skin burns were created on forty five rats. Normal and burnt skin samples were taken at 1, 3, 5, 7, 9, 11, 13, 15 and 21 days following burn induction (5 rats for each stage). Post-mortem burn was inflicted 6 h after scarification in another five rats. There was a statistically significant difference in both iNOS and IL-6 expression between the different time intervals of the ante-mortem burn. Expression of both iNOS and IL-6 decreased remarkably in the post-mortem burn with a statistically significant difference from ante-mortem intervals. A statistically significant positive association between the two markers was found. These results indicate that both iNOS and IL-6 expression in ante-mortem burnt skin was time dependent and significantly differed from post-mortem burn. Further research on humans is recommended.

Diagnostic utility of vimentin, CD117, cytokeratin-7 and caveolin-1 in differentiation between clear cell renal cell carcinoma, chromophobe renal cell carcinoma and oncocytoma.

Overlapping morphological characteristics pose some difficulties in making a proper diagnosis of clear cell renal cell carcinoma (CCRCC), chromophobe renal cell carcinoma (ChRCC), and oncocytoma, on the basis of hematoxylin-eosin-stained tissue sections. Our objective was to find out a fast, reliable panel of immunohistochemical markers for differentiation between them. The study was carried out on 55 selected renal tumor specimens: 36 cases of CCRCC, seven cases of ChRCC, and 12 cases of oncocytoma. The specimens were stained immunohistochemically for vimentin, CD117, cytokeratin (CK)7, and caveolin (Cav)-1. Sensitivity and specificity for each marker were calculated. Vimentin expression was exclusively observed in CCRCC (100%) and negative in ChRCC and oncocytoma. CD117 was absent in CCRCC, but it was strongly expressed in ChRCC (85.5%) and oncocytoma (91.7%), with high sensitivity and specificity. Most CCRCCs and oncocytomas were negative for CK7 (91.7% and 83.3%, respectively), in contrast to ChRCCs, which showed positivity in nearly 86% of the cases. Good sensitivity and specificity were calculated for CK7 in differentiating studied oncocytic tumors. Cav-1 was positive in ~78% of the CCRCCs and in all ChRCCs, whereas the vast majority of oncocytomas were negative. So the immunoprofile of CCRCC was vimentin+/CD117-/CK7-/Cav-1±, ChRCC was vimentin-/CD117+/CK7+/Cav-1+, and oncocytoma was vimentin-/CD117+/CK7±/Cav-1-. So, by using combination of four markers (vimentin, CD117, CK7, and Cav-1), we achieved excellent sensitivity and specificity for differential diagnosis of CCRCC, ChRCC and oncocytoma.