Investigation of survivin gene polymorphism in patients with gastric carcinoma

Objectives: Despite decreasing incidence of gastric cancerin worldwide, it is still a major health problem. Everyyear, 30.000 new gastric cancer cases emerging, and itis the second most common cancer in Turkey. Gastriccancer is a complex multifactorial disease, emerging byinteraction between genetic and environmental factors.Survivin, apoptosis inhibitory protein is over-expressed incancer tissue. In this study, association between Survivin-31G/C polymorphism and gastric carcinoma was investigated.Materials and Methods: 46 gastric carcinoma patientswho had been admitted at Düzce University Researchand Practice Hospital, Laboratory of Pathology and 42healthy individuals have been included in the study. Sampleshave been subjected to genetic analysis by PCRRFLPmethod in Medical Genetics Department laboratoryat Düzce University.Results: GG genotype was found in 16 (34.8%), GCgenotype in 21 (45.7%), CC genotype in 9 (19.6%) in patientgroup. In control group, genotype distribution werefound 13 (31%), 26 (61.9%) and 3 (7.1%) respectively.The statistically significant difference was not found whencompared between patient and control groups. However,we observed the increased occurrence of gastric cancerassociated with CC genotype (OR=1.52).Conclusions: In our knowledge, this study is the first toevaluate the relationship between gastric carcinoma andSurvivin -31G/C polymorphism in Turkish population. Ourresults show that there is no any association betweengastric carcinoma and Survivin -31G/C polymorphismin the community which is represented by our study andcontrol groups. However, it was concluded that CC genotypemay create the susceptibility to gastric cancer.Key words: Polymorphism, gastric carcinoma, survivinggene, apoptosi

The evaluation of omentin level in rheumatoid arthritis patients

YÖK Tez No: 412759Romatoid artrit (RA), nüfusun yaklaşık % 1 ini etkileyen inflamatuvar ve otoimmun olan bir hastalıktır. Eklem kıkırdağında geri dönüşü olmayan hasarlar ile karakterizedir. Yakın zaman önce tanımlanan omentinin çeşitli inflamatuvar hastalıklarda rol aldığı bilinmektedir. Bu çalışmanın amacı; omentinin RA'in patogenezindeki muhtemel rolünü hem genetik hemde protein düzeyde değerlendirmekdir. Bu çalışma, Düzce Üniversitesi Tıp Fakültesi Fiziksel Tıp ve Rehabilitasyon kliniğine başvurmuş 87 hastayı içermektedir. Serum omentin seviyesi ELISA, Val109Asp genotipleri ise PZR-RFLP yöntemleriyle analiz edildi. Serum omentin seviyesi ve Val109Asp polimorfizmi açısından hasta ve kontrol grubu arasında anlamlı bir fark bulunamadı. Bu çalışma, omentin adipokininin RA'in pathogenezindeki muhtemel rolünü inceleyen ilk araştırmadır. RA ile omentin arasında anlamlı bir ilişki bulunamamıştır. Çalışmada kullandığımız hastalarımız önceden tanısı konulmuş ve ilaç kullanan bireyler olması çalışmamızın başlıca kısıtlayıcı faktörü olarak düşünülebilir. Fakat omentinin RA'in patogenezindeki muhtemel rolünü açıklığa kavuşturmak için bu çalışma, ilaç kullanmamış hastalardan meydana gelen daha büyük popülasyonlarla tekrarlanmalıdır.Rheumatoid arthrisit (RA) is an inflammatory and autoimmune disease, affecting approximately 1% population. It is characterized by irreversible destruction of articular cartilage. Omentin has been recently identified as involved in several inflammatory diseases. The aim of this study is to evaluate the potential role of omentin in pathogenesis of RA both genetic and protein levels. 87 patients who applied to Düzce University School of Medicine, Physical Medicine and Rehabilitation Clinic were included in this study. Serum omentin level and Val109Asp genotypes were determined by ELISA and PCR-RFLP methods respectively. There was no significant difference between patient and control groups in terms of serum omentin level and Val109Asp polymorphism. This study is unique cause is the first study to investigate the possible role of omentin adipokine in the pathogenesis of RA in Turkish population. There was no significant relationship between omentin and RA disease. Our patients had been diagnosed previously and they started to use medicine. This can be considered to be a major limitation of our study. However, to elucidate the putative role of the omentin in the pathogenesis of RA, this study should be conducted on a larger population with more appropriate subjects

Omentin Val/Val genotype increases predisposition to acne vulgaris without changing omentin serum level

Yaykasli, Kursat/0000-0001-7550-6370WOS: 000449068700016PubMed: 30301508Acne vulgaris is the most frequent and multifactorial inflammatory skin disorder in all races. Obesity is considered to be a risk factor for acne due to its contribution to inflammation. The involvements of inflammatory (leptin and resistin) and anti-inflammatory (adiponectin) adipokines in the pathogenesis of acne were reported. Omentin resembles adiponectin in terms of having inhibitory effect on tumor necrosis factor-alpha (TNF-alpha) induced inflammation, a vital process in the acne formation. This study was designed to investigate the putative involvement of omentin in acne formation. The genotyping was performed by restriction fragment length polymorphism (RFLP) method. Serum omentin protein levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Serum omentin level was not significantly changed between groups. However, the decreased serum omentin level was observed as the mean value of BMI increased. The Asp/Asp, Val/Asp and Val/Val genotypes distributions for control and patient groups (19[17.4%], 22[20.2%], and 3[2.8%] respectively, vs. 31[28.4%], 25[22.9%], and 9[8.3%], respectively) were obtained. The Val/Val (mutant homozygote) genotype was found nearly 1.8 times more in the patient group (p=0.403, OR=1.839 (0.442-7.653)). This is the first time to clarify a linkage between anti-inflammatory omentin and acne vulgaris. Omentin Val109Asp polymorphism affects the overall function of the protein. In conclusion, omentin Val/Val (mutant homozygote) genotype increases predisposition to acne vulgaris by probably disrupting overall protein function of omentin.Duzce University Research FundDuzce University [2012.04.HD.043]This project is supported by Duzce University Research Fund, Project Number 2012.04.HD.04

Leptin increases ADAMTS9 gene expression in human chondrocytes

European Biotechnology Congress -- MAY 16-18, 2013 -- Comenius Univ, Bratislava, SLOVAKIAYaykasli, Kursat/0000-0001-7550-6370; Yaykasli, Emine/0000-0001-6471-0106WOS: 000323298100276…European Biotechnol Themat Network Assoc (EBTNA), Comenius Univ, Fac Nat Sc

Epigenetic Mechanisms and Cancer

İlk defa 1940ların başında Condrad Hal Waddington tarafından ortaya atılan epigenetik kavramı, DNA dizilimini değiştirmeden gen ifadesini etkileyen kalıtılabilir değişiklikler olarak tanımlanabilir. Yapılan araştırmalarla epigenetik mekanizmaların birçok biyolojik olayda ve kanser gibi hastalıklarda önemli görevler ifa ettiği bulunmuştur. Bu derlemede literatürdeki epigenetik mekanizmalar ve bunların kanserle olan ilişkileri hakkında bilgiler özetlenmiştir.Epigenetics, proposed by Condrad Hal Waddington at the begining of the 1940 describes heritable changes that affect gene expression without changing DNA sequencing. After researches, it has been found that the epigenetics modifications perform important task in many biological processes and diseases like cancer. In this review we summarize the information in literature related with epigenetic mechanisms and their relationship with cancer

Production of High Purity Beta Amanitin

Amaç: Beta amanitin nadiren bilimsel araştırmalarda kullanılmakta ve kullanımı gün geçtikçe artmaktadır. Piyasada bu ürün %90 saflıkta ticari olarak satılmaktadır. Bu araştırmada yüksek saflıkta beta amanitin üretme yöntemi tanımlanmıştır. Yöntem: Saflaştırma işlemi Amanita phalloides mantarlarından ekstraksiyonla yapılmıştır. Öncelikle bu mantarlar toplanmış, ekstrakte edilmiş, 2 defa preparatif HPLC ile saflaştırma işlemi uygulanmıştır. Toksinin karşılaştırması, analitik HPLC sisteminde tutulma zamanı ve ultraviyole spektrumu karşılaştırılması yöntemleriyle yapılmıştır. Bulgular: İlk saflaştırma sonucunda elde edilen beta amanitin saflık oranı %91(2,36) olarak ölçülmüştür. İkinci saflaştırma sonucunda elde edilen beta amanitin saflık oranı %99,2(0,38) olarak ölçülmüştür. Saflaştırma sonucu elde ettiğimiz toksin ile beta amanitin standardın UV spektrumlarında her ikisinde de 303 nmde maksimum, 263 nmde minimum absorbans verdiği ve spektrum yapısının aynı olduğu görülmüştür. Sonuç: Tanımladığımız bu yöntemle, %99 saflıkta beta amanitinin üretilmesi mümkündür.Objective: Beta amanitin has been used in experiment and has been purified only around 90% purity using existing methods. In this study, it has been aimed to describe the method in order to produce high-purity beta amanitin using preparative HPLC. Methods: Amanita phalloides mushrooms hve been collected, extracted and purified 2 times using preparative HPLC. Validation of the toxin has been performed by comparison of retention time at HPLC and ultraviolet spectrum. Results: Beta amanitin was obtained with 91% (±2.36) purity after first purification process. Beta amanitin was obtained with 99,2% (±0.38) purity after second purification process. It seemed that purified toxin and standard were given maximum absorbance at 303 nm and minumum absorbans at 263 nm, and the structure of the spectrums for both was similar. Conclusion: Beta amanitin with >%99 purity can be produced by this method

Dose-dependent effects of adiponectin on ADAMTS-9 gene expression in human chondrocytes

Yaykasli, Emine/0000-0001-6471-0106; Yaykasli, Kursat/0000-0001-7550-6370; Hatipoglu, Omer Faruk/0000-0002-1012-001XWOS: 000407091600002PubMed: 28766346OBJECTIVE: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), comprising of 19 members is a family of peptidases. They have several vital functions in physiological and pathological processes in organisms. ADAMTS-9 has aggrecanolytic activity and is responsible for degradation of aggrecan mainly in articular cartilage. It is known that adiponectin is the most abundantly secreted adipokine (adipocytokines), and the characteristics of adiponectin have not been elucidated yet. It was assumed that adiponectin has anti-inflammatory effect before. However, an inflammatory feature of adiponectin was shown in researches. In our study, the effect of adiponectin on ADAMTS-9 gene expression in primary human chondrocytes was investigated. METHODS: Primary human chondrocytes were exposed to adiponectin at 1, 4, 8 and 12 mu g/ml doses for certain time period. Total RNA was isolated and reverse-transcribed by random primer after incubation. ADAMTS-9 and beta-actin genes expression levels were determined using real-time polymerase chain reaction (qRT-PCR). RESULTS: The highest upregulation of ADAMTS-9 gene expression level was found at 12 mu g/ml dose of adiponectin and 48 h incubation. CONCLUSION: Adiponectin is the key element in the maintenance of cartilage homeostasis. Similarly, the involvement of adiponectin in articular inflammatory diseases was demonstrated in detail. These findings bring adiponectin into central place in the research to develop adiponectin based new therapy methods for arthritic diseases. Together with these findings, our results suggest that adiponectin may be involved in the degradation of articular cartilage by increasing ADAMTS-9 gene expression (Tab. 1, Fig. 3, Ref. 35). Text in PDF www.elis.sk.TUBITAK (The Scientific and Technical Research Council of Turkey)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [SBAG/111S218]This study was supported by TUBITAK (The Scientific and Technical Research Council of Turkey), (Project Number: SBAG/111S218)

NF-kappa B and MAPKs are involved in resistin-caused ADAMTS-5 induction in human chondrocytes

Yaykasli, Emine/0000-0001-6471-0106; Yaykasli, Kursat/0000-0001-7550-6370; Bender, Onur/0000-0003-0691-3508WOS: 000359119100021Purpose: Chronic inflammation is an important etiological factor in the development of arthritic diseases. Several factors contribute to aggregation of chronic inflammation, including the presence of excess adipose tissue. Methods: The putative induction mechanisms of ADAMTS-5 by resistin were investigated in normal primary human articular chondrocytes. Expression levels of the ADAMTS-5 gene were determined at several resistin doses and durations. Results: Human chondrocytes were activated and associated with upregulated ADAMTS-5 gene expression after exposure to resistin (also known as adipose tissue-specific secretary factor, ADSF). Release of ADAMTS-5 leads to joint cartilage degradation, a key event in the development of arthritic diseases rheumatoid arthritis (RA) and osteoarthritis (OA). Activation of chondrocytes was associated with upregulated NF-kappa B protein levels in a time-dependent fashion. Co-incubation of human chondrocytes with JNK and p38 inhibitors lead to abrogated levels of NF-kappa B, indicating that these MAPKs are important in the activation of chondrocytes after stimulation with resistin. Similarly, ADAMTS-5 expression levels were abrogated when co-incubated with p38, NF-kappa B, JNK, MEK and PI3K inhibitors. Our results demonstrate that resistin, released from adipose tissue, may be involved in the development of RA and OA in obese patients through degradation of joint cartilage via ADAMTS-5 released from activated chondrocytes

Visfatin increases the activity of aggrecanases-1 and-2 in human chondrocytes

Yaykasli, Emine/0000-0001-6471-0106; Yaykasli, Kursat/0000-0001-7550-6370WOS: 000209765003171