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Apart from its potent antioxidant property, recent studies have revealed that melatonin promotes PI3K/Akt phosphorylation following focal cerebral ischemia (FCI) in mice. However, it is not clear (i) whether increased PI3K/Akt phosphorylation is a concomitant event or it directly contributes to melatonin's neuroprotective effect, and (ii) how melatonin regulates PI3K/Akt signaling pathway after FCI. In this study, we showed that Akt was intensively phosphorylated at the Thr308 activation loop as compared with Ser473 by melatonin after FCI. Melatonin treatment reduced infarct volume, which was reversed by PI3K/Akt inhibition. However, PI3K/Akt inhibition did not inhibit melatonin's positive effect on brain swelling and IgG extravasation. Additionally, phosphorylation of mTOR, PTEN, AMPK?, PDK1 and RSK1 were increased, while phosphorylation of 4E-BP1, GSK-3?/ß, S6 ribosomal protein were decreased in melatonin treated animals. In addition, melatonin decreased apoptosis through reduced p53 phosphorylation by the PI3K/Akt pathway. In conclusion, we demonstrated the activation profiles of PI3K/Akt signaling pathway components in the pathophysiological aspect of ischemic stroke and melatonin's neuroprotective activity. Our data suggest that Akt phosphorylation, preferably at the Thr308 site of the activation loop via PDK1 and PTEN, mediates melatonin's neuroprotective activity and increased Akt phosphorylation leads to reduced apoptosis. © 2017

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Cisplatin is one of the effective chemotherapeutics in the treatment of several types of cancers. However, in addition to the efforts against to its toxicity, the amelioration of cisplatin sensitivity is an important point in treatment of cervical cancer. To do so, additional substances such as epigallocatechin gallate (EGCG), a polyphenol in green tea, have been used in combination with chemotherapeutics. We aimed to investigate the possible molecular pathways to potentiate cervical cancer cell (HeLa) growth inhibition by combination therapy of cisplatin and EGCG. HeLa cells were treated with EGCG (25 µM), cisplatin (250 nM), and their combination for 24 h. Cell viability was determined by MTS Assay. We analyzed the expressions of NF-?B p65, COX-2, Nrf2, HO-1, p-mTOR, p-p70S6K1, p-4E-BP1, and p-Akt by Western blot analysis. Herein, we have demonstrated that EGCG works synergistic with cisplatin in inhibiting growth of cervical cancer cells. EGCG improved efficacy of cisplatin treatment in HeLa cells by regulating NF?B p65, COX-2, p-Akt, and p-mTOR pathways, whereas it increased the expression levels of Nrf2/HO-1 in combined therapy. Our observations revealed that EGCG increases the sensitization of cisplatin to cervical cancer cells by inhibiting cell survival and inducing apoptosis. © Copyright © 2015 Kilic, Sahin, Tuzcu, Basak, Orhan, Elibol-Can, Kilic, Sahin and Kucuk. Türkiye Bilimler Akademisi This study was supported by grants from Turkish Academy of Sciences (TUBA).

Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene. © 2015 Kilic et al.

Objectives: To develop a new parathyroid allotransplant method for the treatment of permanent hypoparathyroidism. Materials and methods: Parathyroid cells 50 × 10(6) derived from a parathyroid hyperplasia patient were transferred to a 61-year-old patient who had thyroidectomy 17 years earlier, allowing to papillary thyroid cancer; he was admitted to our outpatient clinic with symptomatic chronic hypocalcemia. Cell isolation, cryopreservation, and culturing were conducted according to a new protocol. Results: During a follow-up of 5 months, the patient had no complications that could indicate rejection, and clinical symptoms completely resolved without requiring any drug supplementation. Conclusions: Here, we report a new method, enabling fast and cost-effective parathyroid allotransplant with maintained tissue viability sufficient to treat persistent hypocalcemia.

Joint Congress of European Neurology -- MAY 31-JUN 03, 2014 -- Istanbul, TURKEY WOS: 000337563600191 … European Federat Neurol Soc

Joint Congress of European Neurology -- MAY 31-JUN 03, 2014 -- Istanbul, TURKEY WOS: 000337563600219 … European Federat Neurol Soc

Joint Congress of European Neurology -- MAY 31-JUN 03, 2014 -- Istanbul, TURKEY WOS: 000337563600554 … European Federat Neurol Soc

Joint Congress of European Neurology -- MAY 31-JUN 03, 2014 -- Istanbul, TURKEY WOS: 000337563601023 … European Federat Neurol Soc

WOS: 000335621800008, PubMed ID: 25050020, The aim of this study was to determine the nutritive value of some legume species in salt-affected soils of South-East Anatolian region using chemical composition and in vitro gas production kinetics. In this study, Lotus corniculatus, Trifolium alexandrinum, Medicago sativa were sown and tested in four different locations. A 3 by 4 factorial design with 3 legume species and 4 salt levels (non salty electrical conductivity (EC)ECECEC) was used in the study. Results indicated that salinity and plants had no significant effect on ash and ether extract. Dry matter (DM), acid detergent fiber, digestible dry matter, dry matter intake (DMI) were affected by plant, salinity and plantxsalinity interaction. On the other hand neutral detergent fiber, relative feed value (RFV), and DMI were affected by salinity and plantxsalinity interaction. Mineral contents were affected by plant species, salinity and salinityxplants interactions. In vitro gas production, their kinetics and estimated parameters such as were not affected by salinity whereas the gas production up to 48 h, organic matter digestibility, metabolizable energy (ME), and net energy lactation (NEL) were affected by plant and plantxsalt interaction. Generally RFVs of all species ranged from 120 to 210 and were quite satisfactory in salty conditions. Current results show that the feed value of Medicago saliva is higher compared to Lotus corniculatus and Trifolium alexandrinum.

Background: Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side-effects such as nephrotoxicity and ototoxicity. Cisplatin chemotherapy induces a reduction in the antioxidant status, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drugs. Cisplatin-induced oxidative stress in the kidney was partially prevented by antioxidant treatments using superoxide dismutase, glutathione, selenium and flavonoids. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. However, the mechanism of the protective effects of melatonin against cisplatin-induced nephrotoxicity is still essentially unknown. We therefore designed this study to investigate the underlying mechanism of the protective effect of melatonin against cisplatin-induced renal damage in a rat nephrotoxicity model in vivo. Methods: Twenty eight 8-week-old male Wistar rats were divided into four groups of control, melatonin treatment (4 mg/kg b.w i.p. for 10 days), cisplatin treatment (7 mg/kg b.w., i.p.) and melatonin and cisplatin combination treatment. Serum urea nitrogen (urea-N) and creatinine levels were measured. Histopathological changes were evaluated. In addition, we analyzed the expression levels of HO-1, Nrf2, NF-?B and AP-1 in Western blot analysis. Results: Both serum creatinine and urea nitrogen increased significantly following cisplatin administration alone; these values decreased significantly with melatonin co-treatment of cisplatin-treated rats. Histological analysis showed that cisplatin caused damage in the proximal tubular cells in the kidneys of cisplatin-treated rats; these changes were reversed by melatonin co-treatment. Upon Western blot analysis, melatonin treatment increased Nrf2 accumulation in the nuclear fraction, and increased the expression of HO-1 in the cytosolic fraction as compared to the cisplatin-treated rats. Expressions of NF-?B p65 and AP-1 were increased significantly in the kidneys of rats treated with cisplatin compared with the expression in the kidneys from the control, melatonin-only-treated and melatonin co-treated rats. Conclusion: Our present data suggest that melatonin attenuates cisplatin-induced nephrotoxicity possibly by modulating Nrf2/HO-1 signaling. © 2013 Kilic et al.; licensee BioMed Central Ltd. European Molecular Biology Organization Türkiye Bilimler Akademisi This work was supported by EMBO (European Molecular Biology Organization) installation grant and The Turkish Academy of Sciences (TUBA).

WOS: 000298971200013, The aim of this study was to determine the effect of essential oils (EO) of oregano, ORE (Origanum vulgare); black seed, BSD (Nigella sativa); laurel, LAU (Laurus nobilis); cumin, CUM (Cumminum cyminum); garlic, GAR (Allium sativum); anise, ANI (Pimpinella anisum), and cinnamon, CIN (Cinnamomum verum) on in vitro gas production (IVGP) and IVGP kinetics of barley, wheat straw and soyabean meal. IVGP values were determined by using rumen liquor from three dry Holstein cows. The findings of this study indicate that the effects of EO, doses, and EO x dose interactions were significant. IVGP was decreased by ANI, GAR and ORE, and only CUM increased IVGP. These EO and their different doses or combinations in diets could be used to improve the performance of ruminants. Moreover, EO may act at different levels in energy and protein metabolic pathways, thus their careful selection and combination may be a useful tool to effectively manipulate rumen fermentation.

Introduction Erythropoietin, which is a hematopoietic growth factor, has been found to play a role in various physiologic processes within the body including testicular steroidogenesis and spermatogenesis. However, it is not known whether erythropoietin is also essential for the normal physiology of mature sperm cells. In this study, the effects of recombinant human erythropoietin beta (rEPO) on sperm motility were investigated. Materials and methods Samples of 37 volunteers (with total motile sperm count >5 × 106/ml and a total motility of >50% according to WHO criteria) were collected by masturbation following a 3-5 days period of abstinence. After morphometric analysis before and just after washing, samples were either used as control or treated with rEPO at concentrations of 0.1, 1, 10 or 100 mIU/ml, respectively. Control and treated tubes were incubated for 4 h at 37°C. Results Total motility, total progressive motility, slow forward and nonmotile sperm counts of 1, 10 and 100 mIU/ml rEPO groups were signiWcantly improved. This effect was dose independent. Conclusion No signiWcant effect was found at 0.1 mIU/ml concentration. These results suggest that supplementation of media used for sperm preparation techniques with erythropoietin might be beneWcial. Further studies are needed to clarify the mechanism of action of erythropoietin on mature sperm cells. © Springer-Verlag 2009.

The pattern recognition receptor toll-like receptor (TLR)-4 mediates innate danger signaling in the brain, being activated in response to lipopolysaccharide. Until now, its role in the degenerating brain remained unknown. We here examined effects of a loss-of-function mutation of TLR-4 in mice submitted to transient focal cerebral ischemia and retinal ganglion cell (RGC) axotomy, which are highly reproducible and clinically relevant in vivo models of acute and subacute neuronal degeneration. We show that TLR-4 deficiency protects mice against ischemia and axotomy-induced RGC degeneration. Decreased phosphorylation levels of the mitogen-activated kinases ERK-1/-2, JNK-1/-2 and p38 together with reduced inducible NO synthase levels in injured neurons of TLR-4 mutant mice suggests that TLR-4 deficiency downscales parenchymal stress responses, thereby enhancing neuronal survival. At the same time, densities of MPO+ neutrophils and Iba1+ microglial cells were increased in the brains of TLR-4 mutant animals, pointing towards a futile inflammatory response aiming to compensate lost functions. Our data indicate that innate immunity may represent an attractive target for neuroprotective treatments in stroke and neurodegeneration. © 2008 Elsevier Inc. All rights reserved. nccr â?? on the move Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung: 3200B0-112056/1 Hartmann Müller-Stiftung für Medizinische Forschung This research was supported by the Swiss National Center of Competence (NCCR) ‘Neural plasticity’, the Center for Integrative Human Physiology (CIHP), the Swiss National Science (3200B0-112056/1), the Baasch-Medicus, Hermann-Klaus, David-and-Betty-Koetser and Hartmann-Müller Foundation (all to D.M.H.).

Epigenetics including small, noncoding RNAs, DNA modifications and histone modifications is heritable changes in gene expression. It refers to functional modifications of the genome, but does not involve any changes in the nucleotide sequence. Cancer is the uncontrolled growth of abnormal cells in the body. Both genetic and epigenetic alterations play a key role in cancer development. Epigenetic modifications influence gene silencing, which is important virtually for all steps in carcinogenesis including cancer initiation, progression, invasion and metastatis. Epigenetic modifications as molecular markers are being extensively explored for cancer risk evaluation, early detection, prognosis stratification, and treatment response prediction in urooncology, including prostate, bladder, renal, ovarian and endometrial cancers. Due to epigenetic alterations are pharmacologically reversible, which makes them an attractive target in cancer therapeutics. For cancer screening and detection, tumor methylation biomarkers are useable at predicting prognosis via the assessment of markers in body fluids such as ascites, serum or plasma. In this chapter, we discuss the main epigenetic changes related to carcinogenesis and urogenital cancer biomarkers. © 2013 by Nova Science Publishers, Inc. All rights reserved.

This study was carried out to investigate whether cafeteria feeding affects behaviour of newborn milk fed dairy calves. Twenty Holstein Fnesian calves were divided into two treatment groups single (TMR) and cafeteria feeding. Each calf was observed once a week for a period of 1 h at 5 min intervals at different times of a day after the initiation of daily feeding to monitor eating, ruminating, drinking, licking objects, playing, resting, body care and idle standing activities. The proportional count of eating, ruminating, drinking, licking objects, playing, resting, body care and idle standing were determined as 5.33, 6.52; 5.56, 8.89; 1.36,1.09; 5.61, 5.14; 2.19, 1.60; 64.00, 62.58; 2.89, 3.59, 12.82 and 10.14%, respective to feeding systems TMR and cafeteria. There were not any statistically significant difference between cafeteria and TMR calves with respect to growth performance and blood parameters, except urea concentration, which was higher in cafeteria calves. In conclusion, cafeteria feeding increased welfare status of calf by decreasing idle standing behaviour and increasing body care without affecting growth performance significantly. Also, pre-ruminant calves in cafeteria feeding are able to make their own diet, more nitrogenous and less fibrous, as more appropriate to their digestive physiology. © Medwell Journals, 2009.

The aim of study was to determine the potential nutritive value of some forages using chemical composition, in vitro gas production kinetics and some estimated parameters. In this study, maize hay-MH, grass hay-GH, alfalfa hay-AH and vetch hay-VH were used. There are significant differences among forages in terms of chemical composition. Crude protein (CP) content ranged from 9.17 to 21.89 %. Neutral detergent fiber (NDF) and acid detergent fiber (ADF) contents ranged from 45.40 to 57.86% and 28.07 to 36.07%. There are also significant differences among forages in terms of in vitro gas production, kinetics and some estimates of parameters such as metabolizable energy (ME), net energy lactation (NEL) and organic matter digestibility (OMD). The ME, NEL and OMD values of MH, AH and VH were significantly higher than that of GH. The potential nutritive of alfalfa and vetch hay had a significantly higher than those for maize and grass hay when chemical composition, gas production kinetics and some estimated parameters such as ME, NEL and OMD of forages were taken into consideration.

In this work, the neural performance data sheets of the transistor are employed to determine the feasible design target space in the optimization of a microwave amplifier. In order to obtain these data sheets the ANN model of the active device is utilized to approximate the small-signal [S] and noise [N] parameter functions in the operation domain. Inputting of these characterization parameters into the performance characterization of the device results in the triplet of gain G(T), noise F, and input VSWR V-i and its source (Z(S)) and load (Z(L)) termination functions in the operation domain, from which the neural performance data sheets can be obtained. The memetic algorithm with the decimal mode is utilized in the multi-objective optimization process for the global minimum of the objective function which is expressed as a function only gain of a matching circuit, in the negative exponential form to ensure the rapid convergence. Here optimization of a microwave amplifier with the matching circuits is given as a worked example and its resulted performance ingredients are compared with the design targets.