Serap Sancar-Bas

Male Reproductive System Morphology and Spermatophore Formation in Astacus Leptodactylus (Eschscholtz, 1823) (Decapoda: Astacidae)

Abstract We studied the morphology of the male reproductive system and spermatophore formation in Astacus leptodactylus. The testis has two anterior lobules and only one posterior lobule, which lie dorsal to the gut on the large hepatopancreas. Collecting tubule cells comprise a simple cuboidal epithelium with synthetic activity. Vasa deferentia are laterally connected with the testis and have three parts: proximal vas deferens (PVD), middle vas deferens (MVD) and distal vas deferens (DVD). While the PVD is off-white in color similar to the testis and has no convolutions, the MVD is intensely white in color and convoluted. On the other hand, the DVD is the widest of all and an intensely white structure. The spermatophore, which is non-pedunculate and tubular, extrudes an uninterrupted column and consists of a sperm mass covered with primary and secondary layers. The primary layer is stained with bromephenol blue, while secondary layer gives positive reaction with Alcian blue and aldehyde fuchsin. The histochemical results indicate that the functions of layers are different.

Exendin-4 attenuates renal tubular injury by decreasing oxidative stress and inflammation in streptozotocin-induced diabetic mice

Abstract In this study, we aimed to research the restorative effects of exendin-4, a GLP-1 analog, on renal tubular injury in streptozotocin-induced diabetes model. BALB/c male mice were divided into four groups: non-diabetic, non-diabetic + exendin-4 (3 μg/kg), diabetic and diabetic + exendin-4. In our diabetic model, we observed renal injury mainly in tubular area rather than glomeruli and exendin-4 decreased tubular injury with its glucose lowering effect. Besides, PCNA positive tubular cells, activities of LDH and Na+-K+-ATPase were also significantly declined by the administration of exendin-4. Furthermore, exendin-4 attenuated the levels of ROS, MDA, 8-OHdG, proinflammatory cytokines (TNF-α, IL-1β), chemokine MCP-1, ICAM-1, and fibrosis-related molecules (transforming growth factor β1 and fibronectin). In consistent with reducing tubular injury, macrophage infiltration and both MCP-1 and ICAM-1 production in tubular cells were decreased. These results indicate that exendin-4 may decrease renal tubular injury seen in the beginning of diabetic nephropathy by decreasing ROS production and inflammation.

Distribution of prolactin receptor in frog (Rana Ridibunda) dorsal skin during hibernation

The role of prolactin in the regulation of frog skin functions is still unclear particularly during environmental changes. In this study, prolactin receptor (PRLR) was detected in active and hibernating frog dorsal skin using immunohistochemical method. PRLR immunoreactivity in active frogs was observed in the epidermis, in the secretory epithelium of granular glands and the secretory channel cells of the glands. Myoepithelial cells of granular glands that started accumulating secretory material or those with a full lumen were PRLR immunoreactive, while some myoepithelial cells of empty granular glands were negative for PRLR. In hibernating frogs, this immunoreactivity was observed in the same regions; however, immunoreactivity was more intense than that in active frogs. PCNA was employed for detection of proliferative activity of PRL in the dorsal skin, and immunoreactivity was detected in the nuclei of a few epidermis cells and in the duct of glands of active frogs. The number of immunoreactive nuclei in these regions increased in hibernating and in prolactin injected groups. We conclude that prolactin provides morphological and functional integrity of skin stimulating the proliferation and regulating the function of granular glands and plays an important role in the adaptation of amphibians to the long winter period.

The immune system as a chronotoxicity target of the anticancer mTOR inhibitor everolimus

ABSTRACT The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing. C57BL/6J mice were synchronized with light-dark 12h:12h, with L onset at Zeitgeber Time (ZT) 0. Everolimus was administered orally to male (5 mg/kg/day) and female mice (15 mg/kg/day) at ZT1, during early rest span or at ZT13, during early activity span for 4 weeks. Body weight loss, as well as hematological, immunological and biochemical toxicities, were determined. Spleen and thymus were examined histologically. Everolimus toxicity was less severe following dosing at ZT13, as compared to ZT1, as shown with least body weight inhibition in both genders; least reductions in thymus weight both in males (p < 0.01) and females (p < 0.001), least reduction in female spleen weight (p < 0.05), and less severe thymic medullar atrophy both in males (p < 0.001) and females (p < 0.001). The mean circulating counts in total leukocytes, total lymphocytes, T-helper and B lymphocytes displayed minor and non-significant changes following dosing at ZT13, while they were decreased by 56.9% (p < 0.01), 45.5% (p < 0.01), 43.1% (p < 0.05) and 48.7% (p < 0.01) after everolimus at ZT1, respectively, in only male mice. Chronotherapy of everolimus is an effective way to increase the general tolerability and decrease toxicity on the immune system.

Exendin-4 partly ameliorates - hyperglycemia-mediated tissue damage in lungs of streptozotocin-induced diabetic mice

Graphical abstract Figure. No caption available. HighlightsExendin‐4 contributed to the healing of lung against hyperglycemia‐mediated oxidative stress, tissue damage and pulmonary edema.Exendin‐4 induced the cell proliferation in pulmonary epithelium and interstitium.Exendin‐4 results in the disruption of insulin signaling and increases at the protein level of collagen‐type‐I in the lung of diabetic mice.Exendin‐4‐mediated a critical reduction in the amount of fibronectin may result in excessive collagen accumulation in the lung of diabetic mice. ABSTRACT Glucagon‐like peptide‐1 (GLP‐1) stimulates insulin secretion, ‐ plays anti‐inflammatory role in atherosclerosis, and has surfactant‐releasing effects in lungs. GLP‐1 analogues are used in diabetes therapy. This is the first study to investigate the effects of exendin‐4, a GLP‐1 receptor agonist, on lung injury in diabetic mice. BALB/c male mice were divided into four groups. The first group was given only citrate buffer, the second group was given only exendin‐4, the third group was given only streptozotocin (STZ), and the fourth group was given both exendin‐4 and STZ. Exendin‐4 (3 &mgr;g/kg) was administered daily by subcutaneous injection for 30 days after mice were rendered diabetic with a single dose of STZ (200 mg/kg). Structural alterations, oxidative stress, apoptosis, insulin signaling and expressions of prosurfactant‐C, alpha‐smooth muscle actin, collagen‐I and fibronectin were evaluated in lung tissue. Diabetic mice lungs were characterized by induced oxidative stress, apoptosis, edema, and cell proliferation. They had honeycomb‐like alveoli, thicker alveolar walls, and hypertrophic pneumocytes. Although exendin‐4 treatment improved pulmonary edema, apoptosis, oxidative stress, and lung injury, it led to the disrupted insulin signaling and interstitial collagen accumulation in the lungs of diabetic mice. Exendin‐4 ameliorates hyperglycemia‐mediated lung damage by reducing glucose, ‐oxidative stress and stimulating cell proliferation. However, exendin‐4 led to increased lung injury partly by reducing insulin signaling ‐ and collagen accumulation around pulmonary vasculature in diabetic mice.

Involvement of Dying Beta Cell Originated Messenger Molecules in Differentiation of Pancreatic Mesenchymal Stem Cells Under Glucotoxic and Glucolipotoxic Conditions

Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type 2 diabetes mellitus. In this study, pancreatic islet derived mesenchymal stem cells (PI‐MSCs) were isolated from adult rats and characterized. Then, beta cells isolated from rats were co‐cultured with PI‐MSCs and they were exposed to glucotoxicity, lipotoxicity and glucolipotoxicity conditions for 72 hr. As the results apoptotic and necrotic cell death were increased in both PI‐MSCs and beta cells especially by the exposure of glucotoxic and glucolipotoxic conditions to the co‐culture systems. Glucotoxicity induced‐differentiated beta cells were functional due to their capability of insulin secretion in response to rising glucose concentrations. Moreover, beta cell proliferation was induced in the glucotoxicity‐treated co‐culture system whereas suppressed in lipotoxicity or glucolipotoxicity‐treated co‐culture systems. In addition, 11 novel proteins, that may release from dead beta cells and have the ability to stimulate PI‐MSCs in the direction of differentiation, were determined in media of glucotoxicity or glucolipotoxicity‐treated co‐culture systems. In conclusion, these molecules were considered as important for understanding cellular mechanism of beta cell differentiation and diabetes. Thus, they may be potential targets for diagnosis and cellular or therapeutic treatment of diabetes.

The effect of plant lectins on the survival and malignant behaviors of thyroid cancer cells

Altered or aberrant glycosylation is a common phenomenon in cancer cells and it originates from changes in the expression of the enzymes, glycosyltransferase, and glycosidase which up‐regulate in response to some oncogenes in the glycan synthesis pathway. In this present study, it has been aimed to determine the alteration of sialic acid and fucose expressions in the cell surface of human thyroid carcinoma cells and investigate the changes in tumorigenic and malignant characters after treating them with specific plant lectins. Our study showed that the cell surface glycan chains of anaplastic 8305C, follicular FTC‐133, and papillary K1 thyroid carcinoma cells were rich in α‐2,6, α‐2,3, sialic acid, and α‐1,6 fucose residues. When the cells were treated with specific doses of Maackia amurensis lectin II (MAL), Sambucus nigra agglutinin (SNA), and Aleuria aurantia lectin (AAL) which have specific binding capacity for the detected glycan residues, respectively their cancerous traits changed dramatically. Remarkable findings obtained from MAL treatment leading to necrosis in 8505C cells without any toxicity for normal thyroid epithelial cells but it had proliferative effect on K1 and FCT‐133 cells. Besides, MAL and SNA treatment decreased the mobility of 8505C and K1 cells. MAL and SNA lectins dramatically reduced the endothelial affinity of the cells and AAL significantly attenuated that of 8050C and K1 cells but not FTC‐133. These results suggest that altered cell surface glycosylation in thyroid cancer seems to be a strong candidate for developing new therapeutic strategies.

Tub and β-catenin play a key role in insulin and leptin resistance-induced pancreatic beta-cell differentiation

The aim of this study was to investigate the molecular mechanism of pancreatic islet-derived mesenchymal stem cell (PID-MSC) differentiation into beta-cells in the presence of insulin and leptin resistance stimulators. We determined that beta-cell differentiation was stimulated by glucose, insulin, and leptin. Co-administration of insulin and leptin resulted in greater, at a further stage of differentiation but non-functional beta-cell formation. The levels of p-AKT(Ser473) did not change; SOCS3, PTP1B, p-IRS1(Ser307), PTEN levels increased and p-IRS1(Try) levels decreased due to insulin and leptin co-administration. These findings suggest that co-administration of insulin and leptin to PID-MSCs results in the development of both insulin and leptin resistance together. We showed that this differentiation signaling is mainly mediated by AKT/GSK-3β/β-catenin and Tub. Moreover, β-catenin and Tub were linked to each other in the nucleus under this condition. Furthermore, we found that Tub and β-catenin contributes to insulin production by increasing the expression of transcription factors by binding to the promoter regions of ins1, ins2, and pdx1 genes. In addition, Tub is also bound to the promoter region of the MafA gene. These findings demonstrate that when insulin and leptin resistance develop together in rat PID-MSCs beta-cell differentiation increases markedly via β-catenin and Tub. New therapeutic agents that inhibit AKT/GSK-3β/β-catenin and in particular Tub may help prevent the development or retard the progression of type 2 diabetes.

Protective effect of Amaranthus lividus L. on carbon tetrachloride induced hepatotoxicity in rats / Karbon tetraklorür ile sıçanlarda oluşturulan karaciğer toksisitesi üzerine Amaranthus lividus L. bitkisinin koruyucu etkisi

Abstract Objective: Amaranthus lividus is consumed as popular vegetable in West Black Sea Region of Turkey. In this study, we aimed to evaluate the protective and antioxidant effects of A. lividus on carbon tetrachloride (CCl4) induced oxidative stress and acute liver injury in rats. Methods: Male albino Wistar rats were divided into 7 groups: Normal control, A. lividus control, silymarin control, CCl4, A. lividus (250 mg/kg)+CCl4, A. lividus (500 mg/kg)+CCl4, silymarin+CCl4. Rats were orally pretreated with A. lividus (250 and 500 mg/kg) or silymarin (25 mg/kg) daily for 9 days before administration of CCl4 (1.5 mL/kg, 1:1 in olive oil, i.p.). Results: Pretreatment of rats with A. lividus, significantly prevented the CCl4 induced elevation in the levels of serum alanine aminotransferase, aspartate aminotransferase, bilirubin and hepatic lipid peroxidation and myeloperoxidase. In addition, pretreatment with A. lividus significantly prevented the CCl4 induced depletion in the activities of antioxidant enzymes such as catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase and glutathione level in liver. It has been observed that the hepatoprotective effect of A. lividus was comparable to that of silymarin, a standard drug. Histopathological evaluation of the liver also revealed that A. lividus at 250 mg/kg dose partially suppressed the CCl4 induced liver damage in rats. Conclusion: Our results indicated that A. lividus has a protective effect against CCl4 induced acute hepatotoxicity in rats, and this effect might be related to its antioxidant activity. Özet Amaç: Amaranthus lividus, Türkiye’nin Batı Karadeniz Bölgesinde sebze olarak yaygın şekilde tüketilen bir bitkidir. Bu çalışmada A. lividus’un karbon tetraklorür (CCl4) ile sıçanlarda oluşturulan oksidatif stres ve akut karaciğer hasarı üzerine koruyucu ve antioksidan etkilerinin ölçülmesini amaçladık. Metod: Erkek albino Wistar cinsi sıçanlar 7 gruba ayrıldı: Normal kontrol, A. lividus kontrol, silimarin kontrol, CCl4, A. lividus (250 mg/kg)+CCl4, A. lividus (500 mg/kg)+CCl4, silimarin+CCl4. Sıçanlara CCl4 (1.5 mL/kg, 1:1 zeytin yağı içinde, i.p.) verilmeden önce 9 gün boyunca günde 1 kere ağızdan A. lividus (250 ve 500 mg/kg) veya silimarin (25 mg/kg)’in ön uygulaması yapıldı. Bulgular: Sıçanlara A. lividus ile ön uygulama yapılması, serumdaki alanin aminotrasferaz, aspartat aminotransferaz, bilirubin ve karaciğerdeki lipit peroksidasyonu ve miyeloperoksidaz düzeylerinde CCl4’ün neden olduğu artışı anlamlı şekilde önledi. İlave olarak A. lividus ile ön uygulama yapılması, karaciğerdeki katalaz, glutatyon-S-transferaz, glutatyon peroksidaz, glutatyon redüktaz ve süperoksit dismutaz gibi antioksidan enzim aktivitelerinde ve glutatyon düzeyinde CCl4’ün neden olduğu azalışı anlamlı şekilde önledi. A. lividus ve standart ilaç olarak kullanılan silimarinin karaciğer üzerinde benzer koruyucu etkiler gösterdiği gözlenmiştir. Ayrıca karaciğerin histopatolojik olarak değerlendirilmesi, 250 mg/kg dozda A. lividus’un CCl4 nedeni ile sıçanların karaciğerinde oluşan hasarı kısmen baskıladığını ortaya koymuştur. Sonuç: Bulgularımız, CCl4 ile sıçanlarda oluşturulan akut karaciğer toksisitesine karşı A. lividus’un koruyucu etkiye sahip olduğunu ve bu etkinin antioksidan aktivitesi ile bağlantılı olabileceğini göstermektedir.