Objective: Free radical production is implicated in the pathogenesis of diabetes mellitus, in which several pathways and different mechanisms are shown to involve in the pathophysiology of the complications. Through the administration of nicotinamide(NA) and streptozotocin(STZ), a model of human type II diabetes can be induced in rats. The aim of this study was to determine the effects of Stevia rebaudiana (SrB) and L-NNA (N-nitro-L-arginine) in the formation of free radicals in STZ-NA induced type II diabetic rats. Material and Methods: In this study, rats were treated with SrB and L-NNA 5-8 weeks after the induction of diabetes. The levels of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were determined in the liver homogenate and erythrocyte hemolysate. The nitric oxide synthase (NOS) levels were also measured in the liver homogenate and serum. To study the histological changes in diabetes, the liver tissue samples stained with hematoxylein-eosin and were investigated under light microscope. Results: Although fasting and postprandial blood sugar levels were high in diabetic groups, blood sugar levels were significantly reduced in diabetic treated groups. While the erythrocyte MDA levels of stevia-treated diabetic group decreased, lipid peroxidation increased with L-NNA treatment in both control and diabetic groups. There was no significant difference for the tissue CAT, NOS, and erythrocyte SOD and CAT activities between. Liver samples in control group had a normal structure. Normal histological arrangement was noticed in the livers of control group. In hepatocytes of the diabetic control group, necrotic cells with pycnotic nucleus and eosinophylic cytoplasm as well as sinusoidal dilatation were seen. The hepatocyte structure was more protected in diabetic LNNA group than in diabetic group. The maximum protection was seen in hepatocytes of diabetic stevia L-NNA group. Conclusion: SrB and L-NNA reduced blood glucose levels in diabetic rats and had some beneficial effects on oxidative and histological changes. However, a NOS inhibitor, L-NNA was less effective than SrB treatment in type II diabetes.

Association of PTEN Gene Polymorphisms, Protein Levels and Endometrial Cancer: A Hospital-Based Case-Control Study Emine Yagci1, Hikmet Melike Ozturk1, Tufan Oge2, Cansu Ozbayer3, Hulyam Kurt1 0000-0003-2179-1318, 0000-0002-1951-9713,0000-0002-1120-1874, 0000-0003-2433-9925 1Eskisehir Osmangazi University, Faculty of Medicine, Department of Medical Biology, Eskisehir, Turkey. 2 Eskisehir Osmangazi University, Faculty of Medicine, Department of Gynecology, Eskisehir, Turkey. 3 Kutahya Health Sciences University, Medical Faculty, Department of Medical Biology, Kutahya, Turkey. Corresponding Author: Emine Yagci, Telephone: +90 (222) 2392979/4598, e-mail adress: eminetsci@gmail.com Abstract Endometrial cancer is a type of cancer that develops in the inner lining of the uterus, called the endometrium. After breast, lung, and colon cancer, endometrial cancer is the most prevalent malignancy of the female genital system in industrialized nations like North America and Europe. Phosphatase and Tensin homolog (PTEN), deleted on chromosome 10, is a tumor suppressor gene located on chromosome 10q23.31, which encodes a 403 amino acid protein with both lipid and protein phosphatase activities. One of the most common genetic abnormalities identified in human malignancies are somatic mutations in the PTEN gene. The tumor suppressor activity of the PTEN enzyme is reduced or completely lost as a result of PTEN gene mutations. Considering this information, it is thought that PTEN gene polymorphisms may be associated with the pathogenesis of the disease. The purpose of our study is to determine the relationship between functional PTEN polymorphisms IVS4 (–/+) and -9 C/G and endometrial cancer. DNAs belonging to 63 endometrial cancer patients and 63 control individuals were genotyped by PCR-RFLP method for 2 genetic variants of PTEN IVS4 (–/+) and -9 C/G gene. The expression level of PTEN protein was measured by the Elisa method from serum samples. Our results were evaluated with appropriate statistical methods. As a result of our study, no statistically significant difference was found in the risk of endometrial cancer and genotype frequencies of –9 C/G and IVS4 (-/+) variants (p> 0.05). It was detected that the serum level of PTEN lessened significantly in patients with endometrial cancer in comparison to the control (p

Lung cancer is a malignant lung tumor characterized by uncontrolled cell growth in lung tissue. Genetic and epigenetic abnormalities can be seen in lung cancer. These abnormalities can lead to activation of oncogene and inactivation of tumor suppressor genes. Inflammation is a powerful mediator of cancer development. Pulmonary inflammation may play a role in the initiation or progression of cancer. The main mediator of inflammation is inducible nitric oxide synthase (iNOS), which synthesizes nitric oxide from L-arginine. Monocyte chemoattractant protein-1 (MCP-1) is one of the important chemokines that regulate the migration and infiltration of monocytes/macrophages. It has been determined that MCP-1 plays an important role in lung allergic inflammation, lung leukocyte infiltration and bronchial hyperresponsiveness in the pathogenesis of asthma. Cyclooxygenases (COX) are responsible for prostaglandin production from arachidonic acid. They contribute to inflammation-induced carcinogenesis. COX2 is the enzyme responsible for inflammation induced by inflammatory stimuli, hormones and growth factors. In line with the information given, in this study, serum levels of COX2, iNOS and MCP-1 were determined using the ELISA method in 90 (36 adenocarcinoma, 36 squamous cell, 18 small cell carcinoma) lung cancer patients and 90 healthy control individuals. It was determined that COX2, iNOS and MCP-1 serum concentrations in lung cancer patients were significantly higher than in control individuals (p0.05). It is thought that our findings may contribute to early diagnosis and development of new treatments for lung cancer.

Özet: Osteoartrit (OA) yaygın olarak görülen önemli bir eklem hastalığıdır ve klinik olarak tedavisi tam olarak mümkün değildir. Eklem kıkırdağındaki doku homeostazının bozulması sonucu ortaya çıkan OA’nın moleküler patofizyolojisinde biyokimyasal, metabolik ve genetik faktörlerin rol oynadığı düşünülmekte ancak etki mekanziması halen tam olarak bilinmemektedir. Kıkırdak homeostazını kontrol eden ekstrasellüler düzenleyicilerin ve intrasellüler sinyal mekanizmaların anlaşılması OA için yeni terapötik hedeflerin tanımlanmasına katkı sağlayacaktır. Son zamanlarda, küçük kodlamayan RNA’ların bir sınıfı olan mikroRNA (miRNA)’ların gelişim, homeostaz ve bağışıklık fonksiyonlarında önemli rol oynadığı ve miRNA’ların kanserden inflamasyona kadar çoğu hastalıkla ilişkili olduğu gösterilmiştir. mRNA yıkılması veya translasyon baskılanması ile gen ekspresyonunu düzenleyen miRNA’ların, çeşitli hastalıklardaki rollerinin öğrenilmesi onların yeni bir biyobelirteç olarak değerlendirilmesine yol açmaktadır. miRNA’ların ekpresyonlarının hücre kaderinin belirlenmesindeki önemli rolü dışında, özel immün cevabı ve inflamatuar uyarıyı da düzenledikleri belirlenmiştir. Eklem kıkırdağında miRNA ekspresyonlarının araştırılması OA gibi hastalıklarda hedeflerin tanımlanmasına imkan sağlayabilecektir. Eklem hasarı veya tamiri sırasında çeşitli biyobelirteçler menisküs ve ligamentler, eklem kıkırdağı, kemik doku, osteofitler ve sinoviyal zardan salınarak sinoviyal sıvı havuzuna ve buradan da lenfatik dolaşıma ve sistemik dolaşıma katılmaktadır. Bu biyobelirteçlerin serum, idrar veya kanda belirlenmesi, OA’nın erken dönemde saptanması, hastalığın seyrinin ve tedaviye cevabının izlenmesi için önemlidir. Bu nedenlerle yapılan çalışmalarda, OA mekanizmasının anlaşılmasına katkı sağlamak için yeni bir terapötik hedef olan miRNA’ların OA patofizyolojisindeki rollerinin belirlenmesi amaçlanmaktadır. Bu derlemede post-transkripsiyonal düzenlemede görevli miRNA’ların, OA’nın moleküler mekanizmasındaki rolleri incelenmektedir. Özet olarak, miRNA’ların tanı ve tedavide önemli potansiyele sahip olabileceği ve OA’nın tedavi edilmesi için yeni bir yol sağlayabileceği önerilmektedir. Anahtar kelimeler: Osteoartrit, mikroRNA MicroRNAs and OSTEOARTHRITIS Abstract: Osteoarthritis (OA) is most common musculoskeletal disorder and its full treatment is not possible clinically. The pathogenesis of OA involves the degradation of tissue homeostasis in articular cartilage, but many of the underlying biochemical, metabolic and genetic factors remain largely unknown. Understanding the extracellular regulators and the intracellular signaling mechanisms controlling the cartilage homeostasis will contribute to the identification of new therapeutic targets for OA. Recently, it is shown that microRNAs (miRNAs), which are a sub-group of small non-coding RNAs, play an important role in terms of development, homeostasis and immunity functions; and that miRNAs are connected to several diseases from cancer to inflammation. miRNAs regulating gene expression with mRNA degradation or suppression of translation have roles in various diseases causes them to be evaluated as a new biomarker. It was found out that miRNAs regulate specific immune response and inflammatory stimuli, in addition to their important role in determination of a cell’s fate. Investigation of miRNA expression in the articular cartilage can make the identification of targets in diseases such as OA possible. During joint’s damage and repair, various biomarkers from meniscus and ligaments, articular cartilage, bone tissue, osteophytes and synovial membrane are secreted into the synovial fluid pool and are passed from there to lymphatic and systemic circulations. Identification of these biomarkers in serum, urine or blood is important for early detection of OA and for monitoring the course of the disease and its response to treatment. For these reasons, it was aimed to determine miRNAs’ role, in the pathophysiology of OA as a new therapeutic target in order to contribute to the understanding of OA’s mechanism of action in the studies carried out. In this review, the current evidence of the role of miRNAs in charge of post-transcriptional regulation, which is playing in molecular mechanisms underlying development and progression of OA, has been summarized. In summary, it is proposed that miRNAs have an important potential in terms of diagnosis and treatment of OA and that they can provide a new way for treatment of OA. Keywords: Osteoarthritis, microRNA