Tip 2 diabetes mellitus ve kognitif disfonksiyonu olan hastalarda uzun kodlamayan RNA'ların ekspresyon analizi

Tip 2 Diabetes Mellitus, artan mortalite ve morbidite oranlarıyla Dünya Sağlık Örgütü tarafından pandemi ilan edilmiş kronik metabolik bir hastalıktır. Bu kronik sendromda, çoklu metabolik yolakların ve moleküllerin etkileşimleri söz konusudur. Bu karmaşık etkileşimler çeşitli hücre tiplerini, dokuları ve sistemleri etkileyerek birçok komplikasyonu beraberinde getirmektedir. Glukoz homeostazının ve insülin sekresyonunun bozulması sonucu oluşan hiperglisemi ile karakterize bu hastalık; en büyük hasarı vasküler sistem ve beyin üzerinde gerçekleştirmektedir. Yüksek glukoz konsatrasyonları sonucu serebrovaskülatürde meydana gelen oksidatif stres ve enflamasyon; şiddetlenerek endotel hasarlarını ve aterosklerozu meydana getirir. Bu hasarlar sonucunda beynin kan perfüzyonunda aksamalar, nöronal hücrelerde deformasyonlar oluşur ve kognitif disfonksiyon’lar ortaya çıkar. Kognitif disfonksiyonlar, beynin sinaps oluşturmada ve nöronal etkileşimlerinde aksamalar yaşaması ve taleplere cevap veremeyecek kadar bilişsel işlev bütünlüğünün bozulması şeklinde tanımlanmaktadır. Hafif bilişsel bozukluk, demans ve Alzheimer prevalansı en yüksek olan kognitif disfonksiyonlardır. Tip 2 Diabetes Mellitus ve kognitif disfonksiyonların klinikte tanı, tedavi ve prognozda rutinleştirilmiş yöntemler içermesine rağmen, kanonik moleküler etkileşimleri, patofizyolojisinin altında yatan sinyal etkileşimleri ve düzenleyici elemanları henüz tam olarak aydınlatılamamıştır. Son on yılın popüler keşfi epigenetik, gen ifadesinin regülasyonu ve ürünlerinin işlevleri, hücresel gelişim ve survival gibi birçok hayati fonksiyonu modüle etme özelliğiyle Tip 2 Diabetes Mellitus ve komplikasyonlarına bakış açımızı değiştirmektedir. Epigenetik, hem glukoz homeostazı hem de bilişsel fonksiyonlar üzerinde etkin rollere sahip olma potansiyelindedir. Epigenetik düzenlemenin elemanları kodlamayan RNA transkriptlerinden oluşmaktadır. Kodlama yapmayan bu transkriptler, 200 nükleotit eşiği ile büyük ve küçük olmak üzere ikiye ayrılarak çeşitlenirler. 200 nükleotidten uzun olan grup, uzun kodlamayan RNA’lar (lncRNA) olarak adlandırılır. Bu tez çalışmasında, epigenetik regülatör lncRNA’ların kanonik etkileşimlere sahip Tip 2 Diabetes Mellitus ve kognitif disfonksiyon patogenezindeki modülatör etkilerinin belirlenmesi amaçlanmıştır. Bu amaç doğrultusunda, Tip 2 Diabetes Mellitus ve Kognitif Disfonksiyon tanısı olan (n=40), yalnızca Tip 2 Diabetes Mellitus tanısı olan (n=40) ve tamamen sağlıklı bireylerden oluşan (n=25) kontrol gruplarına dahil edilmiş tüm olguların serum örneklerinden serbest dolaşan totalRNA izolasyonları gerçekleştirilmiş ve 96 “hastalık spesifik” lncRNA’ nın nispi ekspresyonları qRT-PCR ile analiz edilmiştir. Tip 2 Diabetes Mellitus tanılı olgularda kontrol grubuna göre 25 lncRNA’nın ekspresyonunda azalış; 23 lncRNA’da artış gözlemlenmiştir. Tip 2 Diabetes Mellitus ve kognitif disfonksiyon tanılı olgulardan oluşan çalışma grubunun kontrol grubu ile kıyasında, 34 lncRNA’ da azalış; 1 lncRNA’ da artış; CCND ANCR, DD3, GOMAFU, LincRNA-VLDLR, MEG3, NEAT1, PANDA, PCAT-1, RMRP, SCA8 ve ST7OT4 lncRNA’larında anlamlı fark saptanmıştır. Tip 2 Diabetes Mellitus ve kognitif disfonksiyon tanılı olgu grubu, yalnızca Tip 2 Diabetes Mellitus tanısı olan olgu grubu ile kıyaslandığında ise, 24 lncRNA’ da azalış; 1 lncRNA’ da artış; AAA1, DLG2AS, HOTAIRM1, NDM29, PCAT-32, SAF ve Telomerase RNA’larında anlamlı fark tespit edilmiştir (kat değişimi >±2.0, p0.05). Çalışmamız sonuçlarına göre anlamlı fark elde ettiğimiz CCND-ANCR, DD3, GOMAFU, NEAT1, NDM29 ve DLG2AS lncRNA’larının, Tip 2 Diabetes Mellitus ve kognitif disfonksiyon patogenezinde rol alan moleküler etkileşimler üzerinde önemli regülatör etkilere sahip olabileceği düşünülmektedir. Bu lncRNA’ ların, hem Tip 2 Diabetes Mellitus hem de buna bağlı olarak oluşan komplikasyonların tanı ve tedavisinde etkin biyomarkerler olarak kullanılabilme potansiyeli, ileri çalışmalar ile gösterilmelidir.Diabetes Mellitus Type 2 is a chronic metabolic disease that has been declared a pandemic by the World Health Organization with increased mortality and morbidity rates. In this chronic syndrome, there are interactions of multiple metabolic pathways and molecules. These complex interactions affect many cell types, tissues, and systems, bringing many complications. This disease, which is characterized by hyperglycemia caused by impaired glucose homeostasis and insulin secretion; it does the biggest damage to the vascular system and the brain. Oxidative stress and inflammation occurring in cerebrovasculature as a result of high glucose concentrations; intensifies, causing endothelial damage and atherosclerosis. As a result of these damages, disruptions in the blood perfusion of the brain, deformations in neuronal cells, and cognitive dysfunctions occur. Cognitive dysfunctions are defined as the brain experiencing disruptions in synapse formation and neuronal interactions, and impaired cognitive function integrity to respond to demands. Mild cognitive impairment, dementia, and Alzheimer's are the most prevalent cognitive dysfunctions. Although Diabetes Mellitus Type 2 and cognitive dysfunctions contain routine methods in clinical diagnosis, treatment, and prognosis, canonical molecular interactions, underlying signal interactions and regulatory elements have not yet been fully elucidated. The popular discovery of the last decade is changing our perspective on Diabetes Mellitus Type 2 and its complications, with its ability to modulate many vital functions such as epigenetics, regulation of gene expression, and the functions of its products, cellular development, and survival. Epigenetics has the potential to have effective roles in both glucose homeostasis and cognitive functions. Elements of epigenetic regulation consist of RNA transcripts that do not encode. These non-coding transcripts are divided into two, namely large and small, with 200 nucleotide thresholds. The group that is longer than 200 nucleotides are called long-encoding RNAs (lncRNA). In this thesis, it is aimed to determine the modulating effects of epigenetic regulator lncRNAs in the pathogenesis of Type 2 Diabetes Mellitus and cognitive dysfunction which have canonical interactions; Free-circulating total RNA isolations were obtained from serum samples of all patients who were diagnosed with Type 2 Diabetes Mellitus and Cognitive Dysfunction (n=40), included only in the control groups who were diagnosed as Type 2 Diabetes Mellitus (n=40) and who were completely healthy (n=25). and relative expressions of 96 "disease-related" lncRNA were analyzed by qRT-PCR. The decrease in expression of 25 lncRNA in patients with Diabetes Mellitus Type 2 compared to the control group; An increase in 23 lncRNA was observed. Comparison of the study group consisting of cases diagnosed with Diabetes Mellitus Type 2 and cognitive dysfunction compared to the control group, decrease in 34 lncRNA; Increase in 1 lncRNA; There was a significant difference in CCND ANCR, DD3, GOMAFU, LincRNA-VLDLR, MEG3, NEAT1, PANDA, PCAT-1, RMRP, SCA8, and ST7OT4 lncRNAs. The case group diagnosed with Diabetes Mellitus Type 2 and cognitive dysfunction, compared with the case group diagnosed with Diabetes Mellitus Type 2 only, decreased in 24 lncRNA; Increase in 1 lncRNA; There was a significant difference in AAA1, DLG2AS, HOTAIRM1, NDM29, PCAT-32, SAF and Telomerase RNA (fold change >± 2.0, p 0.05). According to the results of our study, it is thought that CCND-ANCR, DD3, GOMAFU, NEAT1, NDM29 and DLG2AS lncRNAs, which we obtained a significant difference, may have important regulatory effects on the molecular interactions involved in the pathogenesis of Diabetes Mellitus Type 2 and cognitive dysfunction. The potential of these lncRNAs to be used as effective biomarkers in the diagnosis and treatment of both Diabetes Mellitus Type 2 and related complications needs to be demonstrated by further studies

SYNTHESIS OF DUAL PHASE CATHODE FOR IT SOFCs VIA THERMAL PLASMA

The combinatorial approach is particularly suitable for identification of suitable cathode materials. This involves a simultaneous deposition of thin film cathodes each with a different composition in a single experiment. The composition and microstructure of cathode materials has a large impact on the performance of solid oxide fuel cells (SOFCs). A main goal in SOFC research is the development of cathodes with a sufficiently low electrochemical resistance (- 0.15 Q.cm2) at operating temperatures significantly below 800°C. Focus has been shifted to particularly mixed conducting perovskites of the La I -xSncCo03-8 (LSC), Lal–xSniMnO3AZ (LSM), LaxSrl–xCoyFel–y03-8 (LSCF) family [1]. Since, Cnunl in et al.[2] and Sase et al. [3] exhibit improved electrochemical performance with hetero-structures [4]. Oxygen surface exchange was found to be enhanced at the heterointerface of LSC214/LSC113 [3]. It was recently shown that the sputter deposited (La0.8Sr0.2) Co03 (LSC-113) - (La0.5Sr0.5)2Co04 (LSC-214) dual phase cathode yield the best performance where the mixture had an amorphous-like structure [5]. In this study a composite cathodes LSC113- LSC214 and LSF-LSM were synthesized via thermal plasma using a large flow rate of quenching gas yielding non-equilibrium cathode powder. The purpose is to see if similar performance improvement could be obtained with plasma synthesized composite powders. The powders were screen printed onto suitable electrolytes and were characterized based on EIS responses using a symmetric cell under air. The typical EIS response at 500°C is given in Fig

Synthesis of Dual Oxide Cathode for IT-SOFCs via Th ermal Plasma

The composition and microstructure of cathode materials has a large impact on the performance of solid oxide fuel cells (SOFCs). It was recently shown that the sputter deposited (La0.8Sr0.2) CoO3 (LSC-113) - (La0.5Sr0.5)2CoO4 (LSC-214) dual phase cathode yield the best performance where the mixture had an amorphous-like structure. In this study a composite cathode of LSC-113: LSC-214 was synthesized via thermal plasma using a large flow rate of quenching gas yielding non-equilibrium cathode powder. The purpose is to see if similar performance improvement could be obtained with plasma synthesized powder. Powder obtained were then screen printed onto the gadolinium doped ceria (Gd0.1Ce0.9O1.95) electrolytes and were characterized based on EIS responses using a symmetric cell under air

Human APRIL and FGF-21 and adhesion molecules in relation to cognitive function in elderly diabetic patients

Savas, Sumru/0000-0003-4836-3786WOS: 000543270900001Aim A diverse combination of etiologies such as vascular and inflammatory factors and social and physical inactivity may take place in the etiology of cognitive dysfunction (CD). Diabetes mellitus (DM) may contribute to CD over insulin resistance, inflammation, and vascular risk factors. However, mechanisms included in the process are not very clear. We aimed to investigate serum levels of selected biomarkers as a proliferation-inducing ligand (APRIL), FGF-21, P-selectin, soluble vascular cell, and intercellular adhesion molecules-1 (sVCAM-1 and sICAM-1) in elderly patients with DM in relation to cognitive function. Methods A group of 80 elderly type 2 diabetic patients from the outpatient clinic, consisting of 40 patients with CD (mini-mental state examination (MMSE) score < 24) and 40 individuals without CD were enrolled in the study. Anthropometric, sociodemographic, and functional-glycemic evaluations were determined. Biomarker levels were determined by enzyme-linked immunosorbent assay. Results Median sICAM-1 and FGF-21 levels were higher, and P-selectin level, activities of daily living (ADL), instrumental ADL, MNA, and MMSE scores were lower in the CD group (p = 0.002,p = 0.010,p = 0.001,p = 0.001,p < 0.001,p = 0.005,p < 0.001, respectively). There was no significant difference between the groups regarding age, gender, living status, education, cigarette and alcohol consumption, antidiabetic therapy as well as comorbidities such as hypertension and other diseases, depression, body composition, sVCAM-1, APRIL levels, and related biochemical values. Conclusion Median sICAM-1 and FGF-21 levels were higher and P-selectin level was lower in older diabetic patients with CD than in patients with normal cognitive status. Understanding the mechanisms may lead to the prevention or delay of CD in those patients.Ege University Scientific Research ProjectsEge University [15-TIP-065]This study was supported by funding from the Ege University Scientific Research Projects (number: 15-TIP-065)

Assessment of In-vitro Antileishmanial Activities of Cynara scolymus Extracts Against Leishmania tropica

It was aimed to investigate in vitro antileishmanial activities of the receptacle, bractea, and stem leaves extracts of Cynara scolymus (artichoke) against Leishmania tropica. The Leishmania isolate, isolated from a cutaneous leishmaniasis patient from Manisa province, Turkey and stored in liquid nitrogen, was identified as L. tropica (MHOM/TR/2012/CBCL-LT) by genotyping. In vitro antileishmanial activities of C. scolymus plant extracts were examined by CelltTiter-glo and hemocytometry, and cytotoxic activities by MTT. IC50 values of receptacle water (WRC), aqueous ethanol (ARC) and ethanol (ERC), bractea leaf water (WBC), aqueous ethanol (ABC) and ethanol (EBC), and stem leaf water (WSC), aqueous ethanol (ASC) and ethanol (ESC) extracts were determined as 2.45 mg/mL, 1.52 mg/mL, 1.66 mg/mL, 3.45 mg/mL, 1.46 mg/mL and 0.58 mg/mL, 0.24 mg/mL, 0.21 mg/mL and 0.08 mg/mL, respectively. When these results are compared with the drug-free control group, it was determined that stem leaf aqueous ethanol (SI: 7.98), ethanol (SI: 4.96) and water (SI: 2.71) extracts with the highest selectivity index (SI) values showed antileishmanial activity (P0.05). Extracts of C. scolymus did not show cytotoxic activity except for WBC, WRC and ARC. In conclusion, the data presented in the current study indicated that C. scolymus stem leaf extracts (ESC, ASC and WSC) present effective antileishmanial activity. Future studies could focus on the identification and purification of the antileishmanial compounds within these extracts for analysis of their in vivo antileishmanial activity