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Endoplazmik Retikulum (ER) ökaryotik hücrelerde bulunan, hücre içi kalsiyum homoastasizi, lipid sentezi, proteinlerin işlenmesi ve katlanmasından sorumlu olan bir organeldir. Hatalı katlanmış veya katlanmamış proteinlerin artması durumunda ortaya çıkan hücresel cevap endoplazmik retikulum stresi olarak adlandırılır. Değişen çevre koşullarına adaptasyonu sağlamak amacıyla evrimsel süreçte korunmuş bir mekanizma olan Katlanmamış Protein Cevabı (UPR) ile uyum sağlanmaya çalışılmaktadır. Ancak endoplazmik retikulum stresi ile başa çıkılamadığı durumlarda apopitoz tetiği çekilerek hücre ölümü meydana gelmektedir. Endoplazmik retikulum stresinin indüklediği apopitoz yolağında; CCAAT/enhance binding protein (C/EBP) homolog protein (CHOP), Mitojen tarafından aktive edilmiş protein kinaz (MAP kinaz) kaskadı, Bcl-2-ilişkili X protein (Bax/Bak), İnozitol Gerektiren Kinaz 1 (IRE1) ve kaspaz-12 gibi birçok molekül görev almaktadır. Endoplazmik retikulum stresinin kanser hücresi proliferasyonu ve sağkalımı üzerinde büyük bir etkisi vardır. Son yapılan araştırmalar endoplazmik retikulum stresi ve katlanmamış protein cevabının, kanserde önemli rol oynadığını göstermiştir. Nitekim, tümör hücrelerinin büyümesinde ve çevresel değişikliklere adaptasyonda rol oynayan katlanmamış protein cevabının, genellikle kanser hücrelerinin lehine çalışan bir süreç olarak kullanıldığı bulunmuştur. Endoplazmik retikulum stresinin tetiklediği katlanmamış protein cevabında tam olarak aydınlatılamamış bazı mekanizmaların varlığı, tedaviye giden süreci olumsuz yönde etkilemekte olduğundan bu mekanizmaların tam olarak aydınlatılmasıyla birlikte; hastalıkların daha iyi anlaşılması ve yeni tedavi stratejilerinin geliştirilmesinin de önü açılacaktır. Bu derlemede; kanser hücrelerinin endoplazmik retikulum stres cevabı ile proliferasyonlarını nasıl sürdürebildikleri, katlanmamış protein cevabı ekseninde ele alınacak ve bunun altında yatan moleküler mekanizmalara genel bir bakış yapılacaktır.

Diabetes mellitus is a metabolic disease that causes increased morbidity and mortality in developed and developing countries. With recent advancements in technology, alternative treatment methods have begun to be investigated in the world. This study aims to evaluate the effect of pulsed magnetic field (PMF) on vascular complications and contractile activities of aortic rings along with Kir6.1 and Kir6.2 subunit expressions of ATP-sensitive potassium channels (KATP) in aortas of controlled-diabetic and non-controlled diabetic rats. Controlled-diabetic and non-controlled diabetic adult male Wistar rats were exposed to PMF for a period of 6 weeks according to the PMF application protocol (1 h/day; intensity: 1.5 mT; consecutive frequency: 1, 10, 20, and 40 Hz). After PMF exposure, body weight and blood glucose levels were measured. Then, thoracic aorta tissue was extracted for relaxation–contraction and Kir6.1 and Kir6.2 expression experiments. Blood plasma glucose levels, body weight, and aortic ring contraction percentage decreased in controlled-diabetic rats but increased in non-controlled diabetic rats. PMF therapy repressed Kir6.1 mRNA expression in non-controlled diabetic rats but not in controlled diabetic rats. Conversely, Kir6.2 mRNA expressions were repressed both in controlled diabetic and non-controlled diabetic rats by PMF. Our findings suggest that the positive therapeutic effects of PMF may act through (KATP) subunits and may frequently occur in insulin-free conditions. Bioelectromagnetics. 2018;9999:XX–XX. © 2018 Wiley Periodicals, Inc.

BACKGROUND: To evaluate clinical, genetic, and radiologic features of our patients with muscle-eye-brain disease. METHODS: The data of patients who were diagnosed with muscle-eye-brain disease from a cohort of patients with congenital muscular dystrophy in the Division of Pediatric Neurology of Dokuz Eylul University School of Medicine and Gaziantep Children’s Hospital between 2005 and 2013 were analyzed retrospectively. RESULTS: From a cohort of 34 patients with congenital muscular dystrophy, 12 patients from 10 families were diagnosed with muscle-eyebrain disease. The mean age of the patients was 9 � 5.5 years (2-19 years). Mean serum creatine kinase value was 2485.80 � 1308.54 IU/L (700-4267 IU/L). All patients presented with muscular hypotonia at birth followed by varying degrees of spasticity and exaggerated deep tendon reflexes in later stages of life. Three patients were able to walk. The most common ophthalmologic and radiologic abnormalities were cataracts, retinal detachment, periventricular white matter abnormalities, ventriculomegaly, pontocerebellar hypoplasia, and multiple cerebellar cysts. All of the patients had mutations in the POMGNT1 gene. The most common mutation detected in 66% of patients was c.1814 G > A (p.R605H). Two novel mutations were identified. CONCLUSIONS: We suggest that muscle-eye-brain disease is a relatively common muscular dystrophy in Turkey. It should be suspected in patients with muscular hypotonia, increased creatine kinase, and structural eye and brain abnormalities. The c.1814 G > A mutation in exon 21 of the POMGNT1 gene is apparently a common mutation in the Turkish population. Individuals with this mutation show classical features of muscle-eye-brain disease, but others may exhibit a milder phenotype and retain the ability to walk independently. Congenital muscular dystrophy patients from Turkey carrying the clinical and radiologic features of muscle-eye-brain disease should be evaluated for mutations in POMGNT1 gene.