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In this work, twenty hydrazide-hydrazone and 4-thiazolidinone derivatives were synthesized starting from m-cresol. Antimicrobial evaluation was carried out by microdilution method against Enterococcus faecalis and Staphylococcus aureus as Gram-positive bacteria and Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria, and three pathogenic fungi Candida albicans, Candida parapsilosis and Candida krusei. Some compounds possessed considerable antimicrobial properties against the tested microorganisms, particularly against E. coli. 4-Thiazolidinones containing 3-methoxyphenyl and 3,5-dichlorophenyl moieties (4h and 4i) were found to be the most active derivatives with MICs of 2 μg/mL against E. coli. N'-[(3,5-dichlorophenyl)methylidene]-2-(3-methylphenoxy)acetohydrazide (3i) also displayed antifungal activity against Candida krusei that was comparable to fluconazole. Calculated drug-likeness and ADMET parameters of the most active compounds confirmed their potential as antimicrobial drug candidates. Molecular docking investigations were carried out in the thiamine diphosphate-binding site of pyruvate dehydrogenase multienzyme complex E1 component (PDHc-E1) to clarify the potential antibacterial mechanism against E. coli. The results showed the potential and importance of developing new hydrazones and 4-thiazolidinones that would be effective against microbial strains. Communicated by Ramaswamy H. Sarma

7th Brain Research School (2022-BRS) was performed in Isparta, Turkey between 27 June and 3 July 2022 (http://2022.brs.org.tr/). There were abstracts of 8 speakers, 11 oral presentations, and 3 poster presentations in the 2022-BRS. Titles of speakers; 1- Mustafa NAZIROĞLU. Fluorescent Ca2+ stains for imaging the mice microglia. 2- Beatrice Mihaela RADU. Low-energy accelerated protons irradiation inhibits DNA repair and diminishes cell proliferation, migration and calcium signaling in brain microvascular endothelial cells. 3- Nashat ABUMARIA. Behavioral assays and animal models of psychiatric disorders. 4- Ferah YILDIRIM. Mapping genome-wide DNA methylation changes in alcohol use disorder (No abstrcat). 5- Marco CANEPARI. Principles of Ca2+ imaging using low-affinity indicators. 6- Denis ROUSSEAU. Western blot analyses in the mitochondria. 7- Xinhua SHU. Protection of p-Coumaric acid against depression and memory impairment via inhibition of neuroinflammation 8- Simon HEBEISEN. State dependent block of voltage gated sodium and calcium channels as modern treatment for epilepsy. Titles of oral presentations (OPs); OP1. Bünyamin AYDIN. Diabetic neuropathic pain and TRPM2 Channel: Focus on selenium. OP2. Agomelatine attenuates calcium signaling and apoptosis via the inhibition of TRPV1 channel in the hippocampal neurons of rats with chronic mild stress depression model. OP3. Hatice DALDAL. An interaction between cisplatin-induced optic nerve injury and TRPM2 channel. OP4. Kemal ERTİLAV. Recent developments on the traumatic brain injury models in the experimental animals. OP5. Kaan ERBAKAN. Involvement of TRPV1 channel in the etiology of epilepsy. OP6. Ramazan ÇINAR. Does GSH depletion induce TRPM2 activation in neuronal cells? OP7. Esin AKBAY ÇETİN. TRP ion channels and approaches in COVID-19. OP8. Gülin ÖZDAMAR ÜNAL. Early life stress and neuroinflammation. OP9. Adem AHLATCI. Investigation of TRPM2 cation channel activation in PTZ-induced SH-SY5Y cells by patch-clamp technique: Regulatory role of valproic acid. OP10. Yener YAZĞAN. Orthodontic teeth movement-induced pain and TRPV1 channel. OP11. Evaluation of the role of Radish (Raphanus sativus) extract in movement tests in MPTP induced experimental Parkinson's model in Balb/C mice. Titles of poster presentations (P); P1- Esin AKBAY ÇETİN. Probable pathways of SARS-CoV-2 to central nervous system. P2. Yusuf DAL. Low molecular weight heparin treatment reduced apoptosis, oxidative stress, and calcium signaling in the thrombocytes of patients with recurrent pregnancy loss and thrombophilia: Involvements of TRPM2 and TRPV1 channels. P3. Ferruh KARAMANGİL. Investigation of frequency and diversity of experimental animal models of schizophrenia.

Objective: The frequencies of amino acids in proteins for different structural levels have been determined by many studies. However, due to the different content of data sets, findings from these studies are inconsistent for some amino acids. This study aims to eliminate the contradictions in the findings of the studies by determining the frequencies of the amino acids in all structural level of globular proteins. Methods: The frequencies of the amino acids in overall protein, in secondary structural elements (helix, sheet, coil) and in subtypes of secondary structural elements (α-, π-, and 310-helices, and first, parallel and anti-parallel strands) were calculated separately using a data set including 4.882 dissimilar globular peptides. The frequencies of the amino acids were calculated as the ratio of the total number of a specific residue in related structure to the total number of all residues in the related structure. Results: The frequencies of residues determined in this study is partially in consistent with the other studies. The differences are probably due to the data set contents of the studies. The frequencies of the amino acids in subtypes of secondary structural elements were determined for the first time in this study. Conclusions: Variations in the frequencies of PRO residue in 310-helix structure and of ILE, LEU, and VAL residues in strands of sheet structure are valuable findings for the improvement of secondary structure prediction methods, as they can be used as secondary structural elements markers.

© 2023 Elsevier B.V.Because of the brain\"s complexity, developing effective treatments for neurological disorders is a formidable challenge. Research efforts to this end are advancing as in vitro systems have reached the point that they can imitate critical components of the brain\"s structure and function. Brain-on-a-chip (BoC) was first used for microfluidics-based systems with small synthetic tissues but has expanded recently to include in vitro simulation of the central nervous system (CNS). Defining the system\"s qualifying parameters may improve the BoC for the next generation of in vitro platforms. These parameters show how well a given platform solves the problems unique to in vitro CNS modeling (like recreating the brain\"s microenvironment and including essential parts like the blood-brain barrier (BBB)) and how much more value it offers than traditional cell culture systems. This review provides an overview of the practical concerns of creating and deploying BoC systems and elaborates on how these technologies might be used. Not only how advanced biosensing technologies could be integrated with BoC system but also how novel approaches will automate assays and improve point-of-care (PoC) diagnostics and accurate quantitative analyses are discussed. Key challenges providing opportunities for clinical translation of BoC in neurodegenerative disorders are also addressed.

Chickpea (Cicer arietinum L.) is one of the important legume crops and is cultivated large-scale throughout Turkiye as well as the world. Ascochyta blight, caused by the fungal phytopathogen Ascochyta rabiei, is the leading reason for the highest yield losses among the diseases known for chickpea. The pathogen exhibits high genetic diversity in Turkiye. Therefore, resistancy using Sequence Tagged Microsatellite Site (STMS) markers related with the genes that provide resistance against Ascochyta blight was investigated for the 205 chickpea breeding lines grown in different parts of Turkiye. The analysis for Ascochyta blight resistance was performed using Ta2, Ta146 and Ts54. It was demonstrated that Ta2, Ts54 and Ta146 were the STMS markers having distinguishable features for the detection of Ascochyta blight resistance and were shown to be used in credible fashion for the selection of resistant chickpea breeding lines.

Deneysel çalışmalarda periferik sinirin akson çapı, miyelinli sinir lifi çapı ve miyelinli sinir için iç çap/dış çap oranı (g-ratio), demiyelinizasyon, remiyelinizasyon ve sinir onarımının değerlendirilmesinde görüntü analiz programlarından yararlanılmaktadır. Bu nedenle, morfometrik değerlendirmeye sıklıkla gereksinim duyulan periferik sinir çalışmaları hedeflenerek, laboratuvarımızda yarı otomatik bir görüntü analiz programı geliştirilmiştir. Çalışmamızda, geliştirdiğimiz görüntü analiz yazılımının performansının, serbest erişimli çok amaçlı diğer bir yazılım ile güvenilirlik yönünden karşılaştırılması amaçlanmıştır. Farelerin genel anestezi altında siyatik sinirlerinden alınan doku örnekleri gluteraldehit solüsyonuna alınmıştır. Rutin elektron mikroskop takip yöntemlerinden geçirilerek epoksi resin (epoxy resin) gömülen dokulardan yarı ince kesitler alınmış ve toluidin mavisi ile boyanmıştır. Kesitler dijital kameralı ışık mikroskopta incelenmiş ve X100’lük objektifte fotoğraflanmıştır. Mikrograflar laboratuvarımızda geliştirilen Tantuna Morfometrik Ölçüm Sistemi (TanTuna Morphometric Measuring System; TT-MMS) yazılımı ile analiz edilmiştir. Seçilen iki adet ışık mikrograftan rastgele seçilen 200 adet miyelinli akson kesitinin ölçümleri program kullanılarak yapılmıştır. Aynı ölçümler ImageJ programı ile tekrarlanmış ve her iki programla elde edilen veriler istatistiksel olarak karşılaştırılmıştır. Ek bir donanıma ihtiyaç duymadan her iki yazılımın da güvenilir olduğu ve birbirleriyle uyumlu ölçümler yaptıkları saptanmıştır (p, Image analysing programs are used in peripheral nerve studies to measure axon diameter, myelinated nerve diameter and the ratio of inner axonal diameter to outer diameter (g-ratio), demyelination, remyelination and nerve repair. So, a semi-automatic, image analysis program was developed in our laboratory by targeting peripheral nerve studies which morphometric evaluation is frequently required. It is aimed to compare the performance and reliability of this program with another free access multipurpose software. Tissue samples from sciatic nerves of mice were taken into gluteraldehyde solution under general anesthesia. After routine electron microscopic processing method, semi-thin sections were taken from epoxy resin embedded blocks and stained with toluidine blue. Sections were examined and photographed under the light microscope at X100 magnification. Micrographs were analyzed using the Tantuna Morphometric Measuring System (TT-MMS) software developed in our laboratory. Measurements of the randomly selected 200 myelinated axon sections from two selected light micrograph were performed using the program. The measurements were repeated with ImageJ program and data obtained using both programs were compared statistically. We determined that both softwares are reliable and measurements compatible with each other (p

Hepatocellular carcinoma is one of the deadly cancers with a significant incidence worldwide. In cancer cells, aerobic glycolysis increases with the Warburg effect. Glucose transport across the cell membrane becomes important at this stage. It has been found that there is an increase in GLUT1 expression in various cancers. BAY-876 is a new generation GLUT1 inhibitor. The affinity of BAY-876 for GLUT1 was found to be approximately 100 times higher than for other glucose transporters. HepG2 cells will be used in molecular analyzes to investigate the role of this novel GLUT1 inhibitor in GLUT1-mediated cell proliferation and glucose uptake into the cell.The effect of BAY-876 on glucose uptake was investigated in the case of bioenergetic stress by applying metformin, an insulin-sensitizing agent with strong antihyperglycemic properties, and in hypoxic environment by applying CoCl2 treatment. A steatosis cell model was created using oleic acid and palmitic acid. We aimed to investigate the effects of BAY-876 on cell proliferation and glucose uptake in HepG2 cell line and HepG2 steatosis cell model. Drugs were added to the culture medium. its effect on cell proliferation was investigated with the BrDU method. Cell proliferation, glucose uptake and colony formation were investigated in HepG2 cell line and HepG2 steatosis cell model in the presence and absence of BAY-876. BAY-876 inhibits cell proliferation and reduces glucose uptake in HepG2 cells and steatosis cell model. BAY-876 was also found to reduce glucose uptake in normal and steatosis cell models under bioenergetic and hypoxic stress conditions. It is predicted that our study will contribute to the literature, provide a different perspective to anticancer drug research studies of GLUT1 inhibitor and contribute to the elucidation of the signal transmission mechanism of hepatocellular carcinoma.

COVID-19 is known as the novel coronavirus disease and complications proceed from COVID-19 infection vary depending on various factors such as age, gender and comorbidities. COVID-19 infection which can affect all age groups may occur as a cause of serious illness and death in some of the confirmed cases, depending on the individual characteristics of the affected populations. Therefore, besides intrinsic factors such as the expression levels of tissue proteins, genetic factors such as genetic variations may also contribute to the pathogenesis of the infection. One of the most common complications in COVID-19 patients is ARDS (Acute Respiratory Distress Syndrome). In COVID-19, cytokines such as IL-10 are released in response to viral infection. Cytokine storm that develops during COVID-19 infection causes uncontrolled inflammation. Thus, multiple organ failure can develop and ARDS-related syndromes can be induced. Cytokine storm has been associated with significantly increased IL-10 levels in COVID-19 patients. Changes occur in IL-10 mRNA and protein levels as a result of genetic variations in the promoter regions of the IL-10 gene. It is thought that IL-10 can contribute to the reduction of mortality in COVID-19 infection by preventing pathological proinflammatory function. Determining IL-10 expression levels according to IL-10 (-1082G/A) gene variation genotype distributions defined in the promoter region of IL-10 gene in COVID-19 patients with ARDS very important in terms of better understanding of the pathological mechanisms and developing of therapeutic strategies. In this review, it is aimed to examine the role of IL-10 and IL-10 (-1082G/A) gene variation in ARDS complication of COVID-19 infection., COVID-19 yeni koronavirüs hastalığı olarak bilinmektedir ve COVID-19 enfeksiyonundan kaynaklanan komplikasyonlar yaş, cinsiyet ve komorbiditeler gibi çeşitli faktörlere bağlı olarak değişmektedir. Tüm yaş gruplarını etkileyebilen COVID-19 enfeksiyonu etkilenen popülasyonların bireysel özelliklerine bağlı olarak doğrulanmış vakaların bir kısmında ciddi rahatsızlık ve ölüm nedeni olarak ortaya çıkabilmektedir. Bu enfeksiyon özellikle yaşlı bireylerde ve hipertansiyon, diabetes mellitus, astım gibi komorbiditelere sahip kişilerde daha şiddetli seyretmektedir. Ancak COVID-19 enfeksiyonunun oldukça genç olan bireylerde de görülebileceği bildirilmiştir. Bu yüzden doku proteinlerinin ekspresyon düzeyleri gibi intrinsik faktörlerin yanısıra, genetik varyasyonlar gibi genetik faktörler de enfeksiyon patogenezine katkıda bulunabilmektedir. COVID-19 hastalarının yarısından fazlasında en sık görülen komplikasyonlardan biri yoğun bakım tedavisi gerektiren ARDS (Akut Solunum Sıkıntısı Sendromu) dir. COVID-19’da viral enfeksiyona yanıt olarak İnterlökin-10 (IL-10) gibi sitokinler salınmaktadır. COVID-19 enfeksiyonu sırasında gelişen sitokin fırtınası kontrolsüz inflamasyona neden olmaktadır. Böylece çoklu organ yetmezlikle-ri gelişebilmekte ve ARDS ile ilişkili sendromlar indüklenebilmektedir. Sitokin fırtınası COVID-19 hastalarında anlamlı derecede artmış IL-10 düzeyleri ile ilişkilendirilmiştir. ARDS patogenezinde inflamasyon önemli bir belirteçtir. Proinflamatuar ve antiinflamatuar sitokinler arasındaki dengesizlik sonucunda ARDS gelişebilmektedir. IL-10 geninin promotör bölgelerindeki genetik varyasyonlar sonucunda IL-10 mRNA ve protein düzeylerinde değişiklikler ortaya çıkmaktadır. IL-10’un patolojik proinflamatuar işlevi engelleyerek COVID-19 enfeksiyonundaki mortalitenin azalmasına katkı sağlayabileceği düşünülmektedir. ARDS gelişen COVID-19 hastalarında IL-10 geninin promotör bölgesinde tanımlanan IL-10 (-1082G/A) gen varyasyonu genotip dağılımlarına göre IL-10 ekspresyon düzeylerinin belirlenmesi, ARDS’nin patolojik mekanizmalarının daha iyi anlaşılabilmesi ve ARDS’ye yönelik terapötik stratejilerin geliştirilebilmesi bakımından oldukça önemlidir. Bu derlemede COVID-19 enfeksiyonunda gelişen ARDS komplikasyonunda IL-10 ve IL-10 (-1082G/A) gen varyasyonlarının rolünün incelenmesi amaçlanmıştır.

Diabetes, which causes oxidative stress-induced neuronal damage, is still one of the most important chronic health problems in the world. It can cause serious cellular loss and damage throughout the course of the disease. It is hypothesized that increased oxidative stress in this process increases free reactive oxygen species (ROS) and apoptotic markers and causes diabetic damage. Alpha-Lipoic acid (α-LA), which has a direct antioxidant effect in ROS reduction reactions, is also among the main components of the antioxidant system that works for free radical control and apoptosis. To understand the role of α-LA in reducing diabetes-induced oxidative damage, we examined the production of ROS in the brain cortex and erythrocytes of rats and their effects on markers of apoptosis. Forty adult Wistar albino rats were divided into four groups as control, α-LA, diabetic (DIA), and DIA+α-LA. For the induction of diabetes, the intraperitoneal injection of a dose of streptozotocin (STZ) (45 mg/kg) was used. α-LA (50 mg/kg) was applied to the groups of α-LA and DIA+α-LA for 14 days. At the end of the experiment, the brain cortex tissue and erythrocyte samples were taken from the rats. The levels of apoptosis, caspase 3, caspase 9, mitochondrial membrane potential, intracellular ROS, and lipid peroxidation were increased in the STZ group, although their levels were decreased in the DIA+α-LA group by the injection of α-LA. The STZ treatmentinduced decreases of cell viability, reduced glutathione, and glutathione peroxidase were increased in the brain and erythrocytes by the treatment of α-LA. In conclusion, diabetes acted a role in neuronal damage caused by increased ROS and apoptosis. We observed that α-LA induced a modulatory role on the apoptotic, oxidant, and antioxidant parameters in the brain and erythrocyte. The neuroprotective role of α-LA treatment may be explained by its modulating activity against increased oxidative stress and apoptosis.

In this study, the basics of optical system design are presented. It contains a series of formulations ordered by subject areas or topics representing typical lens design tasks and optical system design tasks. Different aspects are covered, such as the definition of starting systems and the creation, evaluation, and optimization of lenses and systems. The formulas of the most critical lens design equations are given in detail in the content of the study. It also provides an overview of basic mathematical models for calculating simple optical components such as single lenses, systems, and achromatic pairs. Such components represent the foundation of any optical system. The literature study on this study determined that studies on lens design in national publications are limited. The study differs in that it clearly articulates the fundamentals of lens design. It is thought that this study will contribute to the literature.

Alzheimer’s disease is a common neurodegenerative disease. Microglia induces oxidative stress in the brain for engulfing bacteria and viruses. The accumulating data indicate that oxidative stress and apoptosis are two main actors for the induction of microglia activation-induced Alzheimer’s Disease. Oxidative stress is one of many triggers that activate the transient receptor potential melastatin 2 (TRPM2) channel. Glutathione (GSH) is a main cytosolic antioxidant in the mammalian cells. The GSH depletion via the activation of TRPM2 induces oxidative stress and apoptosis in neuronal cells. It has not yet been researched how GSH depletion via activation of TRPM2 affects oxidative stress and apoptosis in microglial cells with the Alzheimer's disease model. The BV2 cells divided into 5 groups as control, buthionine sulphoximine (BSO and 0.5 mM for 6 h), amyloid beta (1 uM for 72 h), amyloid beta+BSO, and amyloid beta+BSO+GSH (10 mM for 2 h). In the BSO group, the levels of apoptosis, mitochondrial membrane potential, cytosolic free oxygen reactive species (cyROS), caspase (Casps) -3, Casps -8, and Casps -9 were increased as compared to the control group, although cell viability level was decreased. The expression levels of TRPM2, Casps -3, Casps -9, Bax, Bcl-2, and PARP-1 were also increased in the BSO group. In addition, their levels were further increased in the amyloid beta and BSO+amyloid beta groups as compared to the BSO group. However, the changes were modulated in the BSO+amyloid beta+GSH group by the incubation of GSH. In conclusion, the depletion of GSH increased apoptosis and cyROS levels via activation of caspases and TRPM2 in the amyloid beta-induced microglia cells. The treatment of GSH may be a potential target on the apoptosis and oxidative stress in the amyloid beta-induced microglia cells.

Amaç: Grafen yapının iç içe silindirler oluşturması ile elde edilen çok duvarlı karbon nanotüpler (ÇDNT), geniş yüzey alanları, hidrofobik yapıları, yüksek elektron iletkenlikleri ile geniş kullanım alanı bulmaktadırlar. İlaç taşıma özellikleri değerlendirilmekle birlikte, biyosensörlerde ve polimerlerle birlikte antibakteriyel malzeme sentezlenmesinde kullanılmaktadırlar. Farklı fizikokimyasal özelliklere sahip ÇDNT’lerin toksisitelerine dair çok sayıda veri vardır. Bunların yanında son yıllarda antibakteriyel etkilerinin değerlendirilmesi oldukça önemli hale gelmiştir. Buradaki araştırmada daha önce farklı hücre soylarına ve yuvarlak solucanlara uyguladığımız; yüksek konsantrasyonlara kadar oldukça sınırlı bir toksik etkiye sahip olduğunu bildiğimiz, literatürde bulunan ÇDNT çeşitlerinin çoğuna göre daha kısa ÇDNT’ lerin, E. coli K12 üzerindeki anti bakteriyel etkisi değerlendirilmek istenmiştir. Yöntem: ÇDNT’ lerden 20 - 100 µg/ml aralığında değişen farklı konsantrasyonlar hazırlanmış ve E. coli K12’ye uygulanmıştır. Koloni sayımı, bakteriyel konsantrasyon ve mikroskobik görüntüler değerlendirilmiştir. Bulgular: Kontrol ile karşılaştırıldığında 10 µg/ml’den 100 µg/ml’ye, her konsantrasyonda ÇDNT’lerin bakterilerin çoğalmasını etkilediği, 50 ve 100 µg/ml konsantrasyonlarda en çok antibakteriyel etkinin ortaya çıktığı görülmüştür. 10 ve 20 µg/ml arasında, inhibisyon dozu olarak belirgin bir fark izlenmemiştir. Yüksek dozlarda 90. dakikadan sonra çoğalma inhibisyonunun %20'den fazla olduğu görülmüştür. Sonuç: Sıvı ve katı besiyerinde çoğaltılan bakteriler düşük ve yüksek konsantrasyonlarda farklı inhibisyon özellikleri ortaya çıkarmıştır. Konsantrasyona bağlı olarak E. coli K-12’nin absorbans ve canlılık değerlerinde azalma olduğu her iki deneyde de tespit edilmiştir. Ayrıca DAPI boyama ile ÇDNT uygulanan bakteri aktivitesinde ve mikroskopta yapılan görüntü analizlerinde de, nanotüp miktarındaki artışa bağlı olarak bakteri kolonilerindeki azalmalar oldukça belirgindir., Objective: Multi-walled carbon nanotubes (MWNTs), obtained by the graphene structure forming multi-walled cylindrical structures, find wide usage areas in different areas with their large surface areas, hydrophobic structures, and high electron conductivity. Although their drug transport properties are evaluated, they are used in biosensors and in synthesizing antibacterial materials with polymers. There are many data on the toxicities of MWNTs with different physicochemical properties. In addition to these, evaluation of antibacterial effects has become very important in recent years. In this study, it was aimed to evaluate the antibacterial effect of MDNTs on E. coli K12 strain, which are shorter than most of the MWNTs in the literature, which we have previously applied to different cell lines, nematodes and which have a very limited toxic effect up to high concentrations. Methods: Different concentrations ranging from 20 to 1000 µg/ml were prepared from MDNTs and applied to E. coli K12 strain. Colony count, bacterial optical density and microscopic images were evaluated.Results: Compared with the control, it was observed that it affected the proliferation at every concentration from 10 µg/ml to 100 µg/ml, and the antibacterial effect was most pronounced at 50 and 100 µg/ml concentrations. There was no significant difference in inhibition dose between 10 and 20 µg/ml. Growth inhibition was observed to be greater than 20% after 90 minutes at high doses.Conclusion: Bacteria grown in liquid and solid agar revealed different inhibition properties at low and high concentrations. Depending on the concentration, it was determined that the absorbance and viability values of E. coli cells decreased in both experiments. In addition, decreases in bacterial colonies, and in bacterial activity performed with DAPI staining and image analyzes are quite evident.

Equisetum L. is the only genus of the Equisetaceae family, which commonly known as horsetails, in English and atkuyruğu or kırkkilit in Turkish. In traditional medicine, Equisetum telmateia Ehrh. is used in diseases of the urinary system, such as pyelonephritis, prostatic hypertrophy, and cystitis. Besides, this species is known to be used by humans to treat kidney stones or kidney sand. The extracts were obtained from the aerial parts of the E. telmateia using three different extraction methods (maceration, Soxhlet, ultrasonic bath) and their antioxidant (ABTS, CUPRAC), anti-urease and anticholinesterase activities were examined. Also, calcium oxalate anti-crystallization activity of Soxhlet methanol extract showing strong antioxidant activity was determined. Soxhlet methanol extract exhibited stronger ABTS radical scavenging (0.0676 mM Trolox/mg extract) and cupric ion reducing/antioxidant (4.351 mM Trolox/mg extract) activity than other extracts. Soxhlet methanol (65.528%) and maceration methanol (61.965%) extracts showed the strongest anticholinesterase activity. In the anti-urease assay, it was found that Soxhlet petroleum ether extract (15.302%) had the highest anti-urease activity. Furthermore, the data obtained showed that the Soxhlet methanol extract had high efficacy in the nucleation and aggregation phase of calcium oxalate crystals. These results prove that Soxhlet methanol extract has antioxidant, anticholinesterase and anti-crystallization capabilities. Therefore, this extract can be used in the future as an antioxidant and anticholinesterase agent as well as the treatment and / or prevention of stone formation.

The brain forms EEG waves due to mental processes. The aim of this study is to investigate the effectiveness of the EEG theta wave formed in the brain during different mathematical and verbal tasks. Twenty healthy medical students without any health problems were included in the study. The five questions were answered by the subjects via power point on the computer screen. Bipolar electrode positioning was performed. In this study, domain measurements, FFT and power spectral density were analyzed. As a result of the study, no statistically significant difference was found between EEG theta waves obtained as a result of both numerical and verbal correct and incorrect answers (p>0.05). An increase in mean amplitude was found in both the mathematical and verbal processes to respond incorrectly. As a result, no significant change was observed in the domain measurements, frequency and power analysis of EEG theta waves during numerical and verbal correct and incorrect responses.

Background: Metabolic syndrome is associated with some medical disorders such as central obesity, being overweight, insulin resistance and hypertension. This study was designed to determine the effect of pioglitazone on oxidative stress in the insulin resistance rat model.Methods: In this study, the model was induced by high sucrose (935 mm) diet for 20 weeks. Three groups were used in the experiment. Control group received standard laboratory diet and drinking water. Metabolic syndrome induced group received 32% sucrose containing drinking water for 20 weeks. Pioglitazone-treated metabolic syndrome group has received pioglitazone treatment (30 mg/kg/day, via oral gavage) for two weeks at the end of the 18th week of metabolic syndrome group. After experimental period, skeletal muscle tissues were homogenized to measure important enzymes such as aspartate aminotransferase, lactate dehydrogenase and as the marker of oxidative stress; total-antioxidant-status, total-oxidant-status and malondialdehyde. Western blot technique was used to determine protein level of thioredoxin1.Results: Aspartate aminotransferase and lactate dehydrogenase levels increased in metabolic syndrome group but pioglitazone treatment decreased these levels. In metabolic syndrome group the oxidative stress status increased but the treatment of pioglitazone decreased the level of oxidative stress in the skeletal muscle. In addition, thioredoxin1 decreased in metabolic syndrome group but administration of pioglitazone increased this level.Conclusions: There was an elevated effect of oxidative stress in high sucrose fed rats but the treatment of pioglitazone improved glucose tolerance and insulin sensitivity.

Cholera is a disease that is developed by parasitizing the bacteria called vibrio cholera in the small intestine of people and it causes severe watery diarrhea, if it is left untreated, it can result in death. The bacteria is transmitted to the people through the digestive tract with water and nutrients, starting with vomiting and going on with severe diarrhea. A potent enterotoxin, Cholera Toxin (CT) which is secreted by vibrio cholera is largely responsible for the disease. It first emerged in India and began to spread to the world between 1827-1975. The cause of the disease, Vibrio cholerae bacteria, which has been known since ancient times with high outbreaks and high mortality rates, has less resistance to external influences and dies in 10-15 minutes at 55°C and in 1-2 minutes at boiling temperature. They are not able to resist dryness, sunlight and acids. Gastric acidity inactivates the vibrations in a short time, which protects many people from being caught in cholera. ADP-Ribosylating Toxins (ADPRT), also including cholera toxin synthesized by this bacteria, are a large and potentially fatal toxin family. They are secreted by pathogenic bacteria and inhibit the functions of human target proteins. Based on structure-based multiple sequence alignments, the ADPRT family is classified into two groups according to the Nicotinamide Adenine Dinucleotide (NAD) that binds Diphtheria Toxin (DT) and CT. DT group toxins change eukaryotic elongation factor 2 and disrupt protein synthesis in eukaryotic cells. DT, exotoxin A (ETA) and cholix toxin are among the members of this group. CT group toxins target various essential proteins in host organisms. For example, CT and temperature-varying enterotoxin target Arg on Gs-R on G protein. This leads to uncontrolled adenylate cyclase activity. Although ADPRT enzymes exhibit a variety of functions and low sequence identities, they share common structural and functional characteristics. This toxin family has the ability to catalyze NAD by using the same pathway with poly ADP-ribose polymerases. We think that being clarified as a matter of the cholera toxin structure, which is the member of this family, will play an important role in the development of many drug design studies such as being able to interfere in significant proteins structure for cancer cells and the development of various catalysis mechanisms. In this study, we investigated the three-dimensional structure of cholera toxin, which is an important member of the ADPRT family, and the interface which will interact with the other amino acids whose binding energies are higher than other amino acids which are situated in the structure (hot spot) by using theoretical and experimental methods. As a result of our theoretical and experimental studies we think that the 12 amino acid sequence of Cholera toxin, constituting the common structural region that binds to NAD in the ADP-ribosylating toxins family is the sequence of 61- STSISLRSAHLV-72.

Kidney stone, also known as calcium oxalate nephrolithiasis, is one of the most common diseases worldwide. Calculi usually forms when urine becomes supersaturated with particular calcium salts such as calcium oxalate. In the present study, we investigated the ameliorative potential of the root extract of the Common golden thistle, Scolymus hispanicus L. (SH) on rats with ethylene glycol (EG) induced kidney stone disease. Sprague-Dawley rats, each weighing 250-300 g, were divided into three groups (n=6 per group): (i) Control (C); (ii) EG; and (iii) EG+SH. To induce nephrolithiasis, the rats received 1% of EG with drinking water, while the C group received normal drinking water during the study. SH extract 2 g/kg was added to the treatment from the 4th week onwards in EG+SH group. At the end of each experiment, rats were decapacitated and serum levels of calcium, magnesium, phosphorus, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were assessed in all groups at 0, 4, and 8 weeks. Oxalic acid and creatininelevels were measured in urine samples collected at 24 h in metabolic cages. Renal tissues were evaluated histopathologically at the end of the experiment. After 8 weeks, serum creatinine levels were found decreased in the SH group while increased in the EG group. Serum magnesium and AST levels were also found decreased in the EG group, however, SH treatment reversed these values. The SH treatment also increased urinary oxalic acid levels. When the kidney tissue of EG group was examined, there was a high level of crystal/stone, especially in the renal cortex. In kidney tissues of the SH group, only small amounts of crystal/stone were observed. Our experimental findings have demonstrated the ameliorative potential of the aqueous extracts of S. hispanicus roots and shells on EG-induced in the kidney stones in rats. Isolation of active compounds of SH would be desirable to understand the biochemical mechanism behind the process better.

Birçok kanserin tedavisinde yaygın olarak kullanılan kemoterapötik bir ajan olan doksorubisin (DOX), hedef dışı organlarda ciddi toksik etkilere sebep olmaktadır. Bu çalışmanın amacı, DOX'un sıçan karaciğer ve kan dokularında meydana getirdiği zararlı etkileri ve bu hasar üzerinde güçlü antioksidan maddeler içeren bir arı ürünü olan propolis (PRPLS)'in olası koruyucu etkisini Azaltılmış Toplam Yansıma-Fourier Dönüşüm Kızılötesi (ATR-FTIR) spektroskopisi ve biyokimyasal testler ile moleküler düzeyde ortaya çıkarmaktır. Bu amaç doğrultusunda, erkek Sprague dawley sıçanlar 4 farklı gruba ayrılmıştır; kontrol (n=7), DOX (2,5 mg/kg'lık 6 enjeksiyon, kümülatif doz: 15 mg/kg; n=7), PRPLS (200 mg/kg, günlük; n=6) ve DOX + PRPLS (15 mg/kg, kümülatif; 200 mg/kg, günlük, sırasıyla; n=7). Sıçanlara 20 gün boyunca her gün 200 mg/kg PRPLS oral gavaj yöntemi ile 2,5 mg/kg DOX 10., 12., 14., 16., 18. ve 20. günlerde intraperitonel olarak verilmiştir. Deneyin 21. günü hayvanlardan karaciğer ve kan örnekleri alınmış, karaciğer dokuları ATR-FTIR spektroskopisi ile incelenmiş, kan plazma örneklerinde total antioksidan seviyesi (TAS) ve total oksidan seviyesi (TOS) ölçülmüş ve oksidatif stres indeksi (OSI) hesaplanmıştır. Sonuçlar DOX'un karaciğerde glikojen ve nükleik asit miktarında azalmaya, lipid ve protein miktarında artışa ve bu moleküllerin metabolizmasında, yapısında ve konformasyonunda bazı önemli değişikliklere sebep olduğunu göstermiştir. DOX ayrıca lipid peroksidasyonuna, membran akışkanlığında bir artışa, membran düzeninde bir azalmaya ve protein denatürasyonuna neden olmuştur. TAS ve TOS deney sonuçları, DOX'un kan dokusunda oksidatif stres yarattığını göstermiştir. PRPLS tek başına verildiğinde karaciğerde herhangi bir toksik etkiye sebep olmamış ancak kanın TAS miktarını artırarak organizmaya fayda sağlamıştır. DOX'tan önce verilen PRPLS DOX'un kanda yarattığı oksidatif stresi önlemiş ancak karaciğer dokusundaki biyomoleküllerde yarattığı zararlı etkilere karşı yeterli koruyucu etki gösterememiştir. Bu çalışma, DOX'un karaciğer ve kan dokularında önemli derecede hasar oluşturduğunu ve PRPLS'nin burada uygulanan doz ve zamanda kandaki oksidatif stresi önlediğini fakat karaciğer dokusunda bu hasarı önlemede yetersiz olduğunu göstermiştir. Doxorubicin (DOX), a chemotherapeutic agent widely used in the treatment of many cancers, causes serious toxic effects in non-target organs. The aim of this study is to examine the harmful effects of DOX on the rat liver and blood tissues and the possible protective effect of propolis (PRPLS), a bee product containing strong antioxidant substances, on these damage at the molecular level with Attenuated Total Reflection-Fourier Transformation Infrared (ATR-FTIR) spectroscopy and biochemical tests. For this purpose, male Sprague Dawley rats were divided into 4 groups; control (n=7), DOX (2.5 mg/kg in six injections; cumulative dose: 15 mg/kg; n=7), PRPLS (200 mg/kg, daily; n=6) and DOX + PRPLS (15 mg/kg, cumulatively; 200 mg/kg, daily; respectively; n=7). The rats were given 200 mg/kg PRPLS by oral gavage every day for 20 consecutive days and 2.5 mg/kg DOX intraperitoneally on the 10th, 12th,14th,16th, 18th and 20th day of the experiment. On the 21st day of the experiment liver and blood samples were collected, the liver tissues were examined by ATR-FTIR spectroscopy, total antioxidant level (TAS) and total oxidant level (TOS) were measured in blood plasma samples obtained from animals and oxidative stress index (OSI) was calculated. The results showed that DOX caused a decrease in the amount of glycogen and nucleic acid, an increase in the amount of lipid and protein and some important changes in the metabolism, structure and conformation of these molecules in the liver. It also induced lipid peroxidation, a decrease in membrane order and an increase in membrane dynamics. DOX also induced lipid peroxidation, an increase in membrane fluidity, a decrease in membrane alignment, and protein denaturation. The results of TAS and TOS experiments showed that DOX induces oxidative stress in the blood tissue. When PRPLS was given alone, it did not cause any toxic effects in the liver but it benefited the organism by increasing the amount of TAS in the blood. PRPLS administered before DOX, prevented the oxidative stress induced by DOX in the blood however, it was not able toshow a protective effect against the harmful effects of DOX on biomolecules in the liver. This study revealed that DOX causes significant damage to liver and blood tissues, and PRPLS at the dose and time administered here prevents oxidative stress in the blood but is insufficient to prevent this damage in liver tissue.

BK (large conductance Ca2+-activated potassium) channels are expressed in myocytes though changes in their molecular levels in the presence of oxidative stress is not clear, yet. Excessive production of reactive oxygen species leads to many diseases including periodic paralysis. Therefore, determination the molecular effects of various oxidative stress conditions may reveal the possible mechanism and potential therapeutic effects. In the present study, isolated rat soleus muscle where KCNMA1 genes encoding BK channel protein expressed widely in skeletal muscle, were exposed to cyclopiazonic acid (CPA) and also hydrogen peroxide (H2O2) as oxidative stress inducers. Streptozotocin-induced diabetes mellitus model was also used to demonstrate the effects of the endogenous source of oxidative stress. Moreover, NS1619, a BK channel opener was used whether the activation of the channel re-regulate the channel expression back. After the incubation periods, KCNMA1 gene expression levels of each groups were determined by real-time PCR experiments. While CPA and H2O2 decreased the KCNMA1 expression significantly, its expression did not change in systemic diabetes mellitus condition. However, the transcriptional level significantly decreased in diabetes in the presence of H2O2. On the other hand, KCNMA1 expression was re-regulated back to the control’s level by addition of NS1619 in solely hydrogen peroxide groups. The results demonstrated for the first time that acute oxidative stress, rather than systemic conditions, effects the KCNMA1 gene expression level in skeletal muscle. The study was also showed the effects of NS1619 on the regulation of transcriptional levels of BK channel protein in hydrogen peroxide conditions.

Prostat kanseri, Dünya çapında erkekler arasında kansere bağlı ölümlerin ikinci önde gelen nedenidir. Prostat kanseri, prostat bezindeki hücrelerin sinyalizasyonunun bozulması sonucunda hücrelerin kontrolsüz çoğalmasıyla meydana gelmektedir. Primer prostat kanser hücreleri çoğunlukla androjen yoksunluğu tedavisine duyarlıdır. Ancak, prostat kanserinin ileri evrelerinde hastaların çoğunda metastaz gelişmektedir. Mevcut tedavi seçenekleri arasında yer alan cerrahi müdahale, radyoterapi, kemoterapi ve hormon tedavisi prostat kanserinde sınırlı etkiye sahiptir. Bu nedenle, metastatik prostat kanseri tedavisi için alternatif tedavi seçeneklerine ihtiyaç duyulmaktadır. Fotodinamik tedavi (FDT) halihazırda malign kanser türlerinde alternatif tedavi seçeneklerinden biri olarak dikkat çekmektedir. FDT'de, dokuda akümüle olabilen fotosensitizer (FS) adı verilen ışığa duyarlı ajana, FS'ı uyarabilecek belirli dalga boyunda ışık kaynağına ve ortamda oksijen varlığına ihtiyaç duyulmaktadır. Bu üç komponentden her birinin tek başına zararı bulunmazken uygun kombinasyonlarla ve koşullarda bir araya geldiklerinde reaktif oksijen türleri (ROS) oluşturarak kanser hücrelerinde hücre ölümüne yol açmaktadır. Bu çalışmada PC-3 metastatik prostat kanseri hücrelerinde, ışığa duyarlı ajan olarak kullanılan 5-Aminolevulinik asid (5-ALA) temelli FDT'nin anti-kanser etkisinin belirlenmesi amaçlanmıştır. 5-ALA'nın dozu, lazer enerji yoğunluğu, hedef dokuda birikme süresi parametreleri araştırılarak, PC-3 hücrelerinde en etkin FDT protokolü belirlenmiştir. Bu kapsamda, 5-ALA/FDT'nin sitotoksik etkisi WST-1 analizi ile belirlenmiş olup, Annexin V ve akridin oranj / etidyum bromür boyaması hücrelerde neden olduğu apoptotik etki analiz edilmiştir. Yapılan optimizasyon çalışmaları sonucunda 1 mM 5-ALA'nın 4 saat boyunca inkübe edilmesi ve 60 J/cm2 lazer enerji yoğunluğunda gerçekleştirilen FDT sonrasında en iyi sonucu veren parametreler olarak belirlenmiştir. Bu parametreler ile ana çalışmaya geçilmiş ve yapılan analizler sonucunda 60 J/cm2 enerji ile uyarılmış FDT grubundaki hücrelerin %32,20'i erken apoptotik ve %3,50'i geç apoptotik olarak belirlenmiştir. Sonuç olarak, 5-ALA temelli FDT'nin PC-3 hücrelerinde %32 oranında apoptoza neden olduğu in vitro bir çalışma ile belirlenmiştir. Anahtar Kelimeler: Prostat Kanseri, Fotodinamik Tedavi, 5-ALA, Lazer Işık Prostate cancer is the second leading cause of cancer-related death among males globally. Prostate cancer is characterized by excessive cell growth induced by a breakdown in cell signaling in the prostate gland. Primary prostate cancer cells are mostly sensitive to androgen deprivation therapy. However, in the advanced stages of prostate cancer, most patients develop metastases. Surgical intervention, radiotherapy, chemotherapy and hormone therapy, which are among the current treatment options, have limited effects in prostate cancer. As a result, there is a need for innovative therapeutic options for metastatic prostate cancer. Photodynamic therapy (PDT) is currently attracting attention as one of the alternative treatment options in malignant cancer types. In PDT, a photosensitive agent called photosensitizer (FS) that can accumulate in the tissue, a light source of a certain wavelength that can stimulate FS, and the presence of oxygen in the environment are needed. While each of these three components is harmless on its own, when combined with appropriate combinations, it creates reactive oxygen species (ROS) and causes cell death in cancer cells. The goal of this study was to see if 5-Aminolevulinic acid (5-ALA)-based PDT, which is utilized as a photosensitive agent in PC-3 metastatic prostate cancer cells, had an anti-cancer impact. The most effective PDT protocol in PC-3 cells was determined by investigating the parameters of 5-ALA dose, laser energy density, and accumulation time in the target tissue. In this context, WST-1 analysis was conducted to analyze the cytotoxic effect of 5-ALA/FDT, and Annexin V and acridine orange / ethidium bromide staining procedures were used to determine its apoptotic effect on cells. Following the optimization tests, the parameters that gave the best outcomes after PDT were identified to be 1 mM 5-ALA incubation for 4 hours and 60 J/cm2 laser energy density. The main investigation was started with these parameters, and the analysis revealed that 32.20% of the cells in the FDT group stimulated with 60 J/cm2 energy were determined as early apoptotic and 3.50% as late apoptotic. In conclusion, in the current thesis study, it was determined by an in vitro study that 5-ALA-based FDT caused apoptosis at a rate of 32% in PC-3 cells. Keywords: Prostate Cancer, Photodynamic Therapy, 5-ALA, Laser Light

The high energy photons produced by the Linear accelerator (Linac) induce some nuclear reactions in the materials in the Linac room and Linac head. Neutrons formed as a result of the interaction of photons with materials are called photoneutrons. The aim of the study is to examine the neutron doses formed in the environment for 6 different photon energies. In the study, the components in the Linac head and the Linac chamber are modeled with the help of the Monte Carlo N-Particle (MCNP) program. Then, the flux and dose of photoneutrons formed at 8 different points as a result of 6 different photon energies obtained from the Linac head were measured. as can be seen from the results, as the photon energy used in the Linac increases, the resulting dose and flux of photoneutron increase. It can be understood from results that the amount of neutron dose to be received by the organs in the treatment field may be higher than the other organs. Especially in the treatments where the patient is lying in the prone position, there may be a possibility of neutrons reaching the patient spinal cord. Since photoneutrons with high radiobiological ability may pose a risk of secondary cancer for patients, the photon energy chosen for patient treatments should be chosen appropriately and the use of unnecessary high photon energy should be avoided.

Aim: The aim of our study was to investigate the effect of electromagnetic fields originating from high voltage lines on serum malondialdehyde level of male rats wistar albino. Materials and Methods: A total of 32 rats were randomly assigned to study in 4 groups. Groups were; Group 1: high voltage, Group 2: high voltage + ganoderma l., Group 3: high voltage + melatonin, Group 4: control. Experimental groups were exposed to high voltage for 8 hours daily for 52 days. The electric field and the magnetic field were measured. Ganoderma was administered 20 mg/kg/day as a gavage and melatonin intraperitoneally as 10 mg/kg/day. Results: In the study, the malondialdehyde (MDA) levels of the experimental and control groups were compared. There was no significant difference between the groups. According to the control group, it was found that the MDA level of the high voltage group increased, while the Ganoderma and Melatonin groups had a small decrease at the MDA level. Conclusion: These results show that electromagnetic fields originating from high tension increase the MDA serum level, which is found to decrease in the presence of ganoderma and melatonin.

Neurological disorders are an important cause of mortality and constitute 11.84% of total deaths globally according to WHO data 2015. It is estimated to increase up to 12.22% in year 2030. Most common NDs can be account for four main groups such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease (HD) and Parkinson’s disease (PD). Among these diseases, only AD is the seventh common death cause worldwide and until recently the therapeutic approaches are still lack to decrease of prevalence. Hence, developing new strategies to understand molecular targets or break down to cascade of cellular degenerative process in the neurodegeneration should be investigated by future studies. In cell culture studies, many types of tissues and cells can be cultivated to be a minimized model to normal or pathophysiological status of disorders. There are lots of methodology or technique to compose efficient and respective neurodegenerative disease models in cell lines such as COS-7, HC2S2, HEK-293, HeLa, Neuro-2a, NSC-34, PC-12, and SH-SY5Y. We indicated best medium formula to growth of neuronal cells as well as differentiation chemicals and time/dosages. In the review it was aimed to summarize not only give information about cell lines, methodological procedures and molecular mechanisms of the diseases but also represent future perspective and offers to this field of neuroscience research.

The aim of this study was to assess vitamin D serum levels in autoimmune thyroid disease, Hashimato thyroiditis in the Turkish population. the subjects with Hashimato thyroiditis (HT, n=67, mean age 45.1±10.9,F/M-61/6), control subjects (mean age 42.1±15.7, n=29, F/M-26/3) were recruited for the study. Thyroid function tests, thyroid antibodies (AntiTg, AntiTPO, TSHRAb), ultrasound features, demographic and antropometric variables were recorded. Vitamin D level was not different between the HT and the control groups (53.1±24.7 nmol/L and 54.1±19.8 nmol/L, as mean, respectively, p = 0.482) in the HT group, 35.8% of subjects had vitamin D insufficiency, only 16.4% of subjects with HT were vitamin D sufficient. There was no significant difference between the HT and the control groups according to the vitamin D classification status (p = 0.666). Vitamin D levels were significantly higher in the subjects who were taking replacement compared to subjects who were not (58.7 ± 26.0 vs. 46.0 ± 23.3, as mean, respectively, p = 0.033). There was no significant correlation between vitamin D levels and TgAb and TPOAb levels in HT group (p = 0.754 r = -0.039, p = 0.134 r = -0.290, respectively). in both HT and control groups, vitamin D levels were significantly correlated only with the fT4 levels (p

The achievement of euthyroid state has been suggested in patients with thyrotoxicosis undergoing surgery to reduce the risk of thyroid storm. However, euthyroid state could not always be achieved by antithyroid drugs. Therefore, therapeutic plasma exchange (TPE) is an option in this condition. A 58-year-old male patient with a history of type-2 diabetes using 200 mg amiodarone per day, admitted for diabetic ketoacidosis (DKA), induced by thyrotoxicosis. with palpitation, sweating, polyuria, and polydipsia. Euthyroid state could not be achieved, despite all apropriate treatments for thyrotoxicosis. Therefore, preparation with TPE followed by total thyroidectomy was planned. A 35% decrease in fT3 (free T3) and fT4 (free T4) levels were achieved, after two sessions of TPE. A 74-year-old male patient, admitted for acute anterior myocardial infarction (AMI) induced by thyrotoxicosis due to Graves disease. Multiple vessel disease was detected on primer percutanous coronary angiography, and an emergency coronary artery bypass grafting (CABG) was planned. Therefore, preperation with TPE was planned before surgery. A substential decrease in fT4 and fT3 levels (45% and 72%, respectively) levels were achieved, after one session of TPE. Most of the studies evaluating the efficacy of TPE in patients with thyrotoxicosis are including patients with Graves disease and toxic multinodular goiter, and TPE was indicated as an effective option for preparation of these patients for surgery. However, as presented in case 1, TPE may not be effective in amiodarone induced thyrotoxicosis (AIT) as in cases with thyrotoxicosis due to Graves disease. [Med-Science 2019; 8(1.000): 233-6]

Theobromine exists in cocoa, which has an antioxidant ingredient. It is also affect our nervous system. For this reason, it’s very important to know the properties of the theobromine. Theobromine is an experimentally studied molecule in the health and pharmaceutical fields. However, there are not many studies on theobromine properties in the theoretical field. Here, we show how theobromine electronic and antioxidant properties change with temperature theoretically. The calculations, were done by using Density Functional Theory (DFT), at B3LYP/6-31G(d,p) level. Six different temperature values (263.15 K, 273.15 K, 288.15 K, 298.15 K, 318.15 K, 328.15 K) were taken into account. Our results presented that the electronic structure of the theobromine didn’t change while the antioxidant properties were changed. Theobromine indicated the most antioxidant property at 263.15 K. Therefore, this situation should be taken into consideration in order to benefit more from the antioxidant properties of theobromine in the field of health and pharmaceuticals.

Gastric cancer comprises 10% of all cancers in the world and is rarely seen before the age of 30. Different genetic interactions or molecular changes like e-cadherin, P16, APC, c-erb B2, c-met, ras, or c-myc have been described in the pathogenesis of the disease. MiRNAs play critical roles in various biological processes such as cell proliferation, cell differentiation, apoptosis, repairing of DNA damage, angiogenesis, stress response, and stem cell division. The aim of this study is to investigate the relationship between miRNA gene expressions and gastric cancer. Method: Sixty-four patients with gastric cancer diagnosed consecutively in our pathology laboratory and 30 consecutive participants with normal gastric tissue, as a control group, were included in our study between 2011 and 2013. Total miRNAs were obtained by using genomic miRNA extraction kit (QIAGEN Sample & Assay Technologies, Hilden, Germany) after the samples had been deparaffinized. MiR-21, 107, 141, 150, 192, 202, 218, 331 gene expressions were evaluated by using real time-PCR (RT-PCR) from the whole miRNA. Results: MiR-331 was downregulated in the stage 2 patients and the rest of the miRNAs were significantly upregulated (p < 0.001). All miRNAs were significantly upregulated in the stage 3a patients (p < 0.001). In the antrum localized tumors, miR-107, -150, -202, -218, and -331 were significantly upregulated, whereas miR-21, -192 were statistically downregulated (p < 0.05). In the cardia localized tumors, miR-21 (p > 0.05) was downregulated and miR-107, -150, -202, -218, and -331 were upregulated (p < 0.05) Different gene expressions of miRNAs according to the different localizations of gastric cancer and different stages suggest that it can be tumor marker to predict the stage and localization of gastric cancer. [Med-Science 2019; 8(1.000): 255-9]

Chest pain (CP) is the major presenting symptom of coronary artery disease (CAD) wherein history remains to be a fundamental and challenging diagnostic step. Despite the clarity of typical CP characteristics in guidelines; interpretation and description of CP by patients are open to wide variations. The aim of this study was to define the components of CP that most closely associate to presence of obstructive CAD and determine the influence of gender on CP features. Herein, consecutive patients with suspected stable CAD who were scheduled for a coronary angiography(CAG) were prospectively enrolled. The data on demographic and pain characteristics were collected by a questionnaire. Patients were categorized into CAD and Normal groups with respect to presence of obstructive CAD in CAG. Among 402 patients, 86 had chest discomfort or equivalent symptoms but denied CP. Patients with CAD were more commonly male; with older age, lower BMI, more frequent prior revascularization, clopidogrel use, higher creatinine and lower HDL levels. When classical features of CP such as quality; location, duration, relationship to exertion were compared; stabbing/sharp pain, CP related to cold or emotional stress and CP that radiates to back were significant factors against CAD; while absence of precipitating factors was related to CAD. Yet, none of the features of typical angina pectoris were significantly related to presence of CAD. Determinants of CAD were; prior revascularization (OR= 22.7, p=0.021), body mass index (OR=1.4, p=0.007), clopidogrel use(OR=55.5, p=0.018) and blood glucose (OR=1.02, p=0.046) in women; and age (OR=1.2, p=0.029) was the single predictor of CAD in men. This study demonstrated no association between classical features of typical CP and presence of CAD in patients with stable angina pectoris. Clinical factors that influenced presence of CAD in different genders were also different. [Med-Science 2019; 8(1.000): 88-92]

HHV-8 is associated with Kaposi sarcoma, multicentric Castleman disease and primary effusion lymphoma mostly in immunocompromised patients. in this report, we describe a female patient without any immunosuppressive state, encountering those three malignancies throughout her lifetime. A-69-year-old female patient was diagnosed with Kaposi sarcoma in 2009 and multicentric Castleman disease in 2011. She received several chemotherapy regimens during 4 years and stayed in remission during following 5 years. Then, she was diagnosed with primary effusion lymphoma, extracavitary/solitary variant on excisional biopsy of her cervical lymphadenopathy. Despite having 5 different lines of chemotherapy protocols, including autologous stem cell transplantation, and systemic cidofovir treatment, she died because of progressive disease. HHV-8 associated malignancies are not prevalent in immunocompetent patients. Our patient, who has suffered from all three malignancies related to HHV-8, is the only HIV negative patient in the literature with primary effusion lymphoma, extracavitary/solitary variant.

Amaç: Bu çalışmada, MCF-7 meme kanseri ve MCF-10A meme epiteli hücrelerine uygulanan flurbiprofen türevi SGK597 bileşiğinin sitotoksik ve apoptotik etkilerinin in vitro olarak belirlenmesi amaçlandı. Gereç ve yöntem: MCF-7 ve MCF-10A hücrelerinde SGK597’n

Amaç: Bu çalışmada metastatik meme kanseri olan ve CDK4/6 inhibitörlerini kullanan 50 yaş altı ve 50 yaş üstü gönüllü meme kanseri hastalarında yaşam kalitesindeki değişikliklerin ve yan etkilerin değerlendirmesi hedeflenmektedir. Gereç ve Yöntem: Çalışm

1. ÖZETNaproksen Türevi Bileşiklerin Meme Epiteli Ve Farklı Meme Kanseri Hücre Hatlarında Antikanser Etkisinin İncelenmesiÖğrenci Adı: Ozan ÇuhadarDanışman Adı: Doç. Dr. Pınar Mega TiberAnabilim Dalı : Biyofizik Anabilim Dalı Amaç: Çalışmamızda, Marmara Üniversitesi Eczacılık Fakültesi Farmasötik Kimya Anabilim Dalı laboratuvarlarında sentezlenen S-naproksen türevi triazol-tiyoeter hibrit moleküllerinden biri olan SGK669 nolu bileşiğin, meme epiteli MCF10A ve iki farklı meme kanseri hücre hattında kullanılması (T47D, MDA-MB-453) ve yarattığı biyolojik ve antikanser etkilerinin belirlenmesi amaçlandı.Gereç ve yöntem: Hücre hatlarının SGK669 nolu bileşiğin farklı konsantrasyonları (10,25,50,75,100 µM) ile 24 ve 48 saatlik inkübasyonu sonrasında maddelerin hücre canlılığı ve sitotoksitesi MTT testi ile belirlendi. Apoptotik etkiler JC-1 floresan probu kullanılarak mitokondrial membran potansiyelleri değişimi ve Annexin V ve PI floresan boyama ile Tali görüntü tabanlı sitometrede belirlenmiştir. Bulgular: SGK669 bileşiğinin %50 inhibisyon konsantrasyonları 24 ve 48 saat için sırasıyla, MCF10A; 27 µM ve 30 µM, T47D; 6 µM ve 15 µM, MDA-MB-453; 13 µM ve 15 µM olarak belirlenmiştir. Belirlenen IC50 dozlarında mitokondriyal membran potansiyelinde 24 ve 48 saat için sırasıyla, T47D’de %48 ve %56, MDA-MB-453’de %12 ve %23 azalma ve Annexin V/PI boyama testi ile T47D’da %16 ve %16, MDA-MB-453’da %15 ve %15 oranlarında apoptoz gözlenmiştir.Sonuç: Araştırmamızda, SGK669 nolu bileşiğin, T47D, MDA-MB-453 hücre hatlarında doza bağlı olarak apoptotik etkiyi arttırıcı ve çoğalmayı önleyici etkisi olduğu, bu nedenle terapötik bir potansiyele sahip olduğu belirlenmiştir.--------------------2. SUMMARYInvestigation of Anticancer Effect of Naproxen Derivative Compounds On Breast Epithelium And Different Breast Cancer Cell LinesStudent Name: Ozan ÇuhadarName of Supervisor: Doç. Dr. Pınar Mega TiberDepartment: Department Of BiophysicsObjective: In this study, we aimed to determine the anticancer and biological effects of triazole-thioether hybrid molecule derived from S-Naproxen, SGK669, which was synthesized in Marmara University Faculty of Pharmacy Department of Pharmaceutical Chemistry, on breast epithelial cell line MCF10A and two different breast cancer cell lines (T47D, MDA-MB-453).Material and methods: Using the MTT colorimetric method, SGK669 was evaluated in vitro against the cell lines, for cell viability and cytotoxicity at different doses (10, 25, 50, 75, 100 µM) following 24 and 48 hours incubation. Apoptosis was evaluated by mitochondrial membrane potential changes using JC-1 probe and Annexin-V/PI staining by using the Tali image-based cytometer. Results: The 50% inhibition concentrations of compound SGK669 for 24 and 48 hours respectively were 27 µM and 30 µM for MCF10A cell line; 6 µM and 15 µM for T47D cell line; 13 µM and 15 for MDA-MB-453 cell line. IC50 values were further used to determine changes in mitochondrial membrane potential for 24and 48 hours respectively a decrease of 48 ve 56% for T47D; 12 and 23% for MDA-MB-453 were noted in MMP tests and Annexin V/PI staining displayed 16 and 16% apoptotsis for T47D; and 15 and 15% for MDA-MB-453.Conclusion: As a result of this research, the compound SGK669 was found to induce apoptosis and inhibited cell proliferation in cell lines T47D and MDA-MB-453 in a dose-dependent manner, suggesting a theurapeutic potential.

Tüm yaşam süreçlerinde kritik rol oynayan proteinlerin nasıl kompleks yapı oluşturdukları henüz tam olarak açıklanamamıştır. Bu çalışmada tekil proteinler ve protein komplekslerinin yapılarından elde edilmiş olan tetrahedronlar ve bu tetrahedronlara ait hacim değerleri ve küresellik değerleri incelenerek protein komplekslerinin yüzey ve arayüzlerinin karakterize edilmesi amaçlanmıştır. Bu çalışmada kullanılan proteinler ComSin veri tabanından seçilmiş ve her bir proteinin Protein Data Bankasındaki (PDB) elde edilmiş atom koordinatlarından yararlanılarak Delaunay teselasyonu ile tetrahedronlar belirlenmiştir. Bu tetrahedronlar kullanılarak tetrahedronların hacim ve ku?resellik değerleri hesaplanmıştır. Çalışma sonucunda protein yüzeyini oluşturan tetrahedronların, toplam tetrahedronların ~%10'unu oluşturduğu görülmüştür. Yüzey tetrahedronlarının ~%95'nin oluşturduğu homo-dimer protein arayüzlerine ait tetrahedronlarının hacmi, yüzeydekilerin hacimlerine göre büyük bulunmuşken küresellik değerleri küçük bulunmuştur. Yüzey tetrahedronları belirlenirken az sayıda tetrahedronun protein yüzeyinde iki üçgene sahip oldukları fark edilmiş ve bunlara "keskin tetrahedronlar" denilmiştir. Keskin tetrahedronların protein arayüzüne geçme oranlarının daha yüksek olduğu gözlemlenmiştir. Retroviral proteaz ailesine ait proteinlerde tespit edilen keskin tetrahedronlara ait olan rezidülerin arasında deneysel olarak önemli oldukları belirlenen rezidülerin de olduğu gösterilmiştir. Bu sonuç keskin tetrahedronların proteinlerin kompleks yapılarında önemli bölgeleri temsil ettiklerine işaret etmektedir. Protein komplekslerindeki protein yüzeyinin ve arayüzünün belirlenmesi, kanser ve Alzheimer hastalığı gibi yaşamı tehdit eden durumlar için yeni tedavilerin ve yeni ilaçların geliştirilmesine olanak sağlayacaktır. It has not been fully explained how proteins, which play a critical role in all life processes, form complex structures. In this study, it is aimed to characterize the surfaces and interfaces of protein complexes by examining the tetrahedra obtained from the structures of individual proteins and protein complexes, and the volume and sphericity values of these tetrahedra. The proteins used in this study were selected from the ComSin database and tetrahedra were determined by Delaunay tessellation of the atomic coordinates of each protein obtained from the Protein Data Bank (PDB). Using these tetrahedra, the volume and sphericity values of the tetrahedra were calculated. As a result of the study, it was found that the tetrahedra forming the protein surface constitute ~10% of the total tetrahedra. While the volume of the tetrahedra belonging to the homo-dimer protein interfaces formed by ~95% of the surface tetrahedra was found to be large compared to the volumes of the surface tetrahedra, the sphericity values were found to be small. When the surface tetrahedra was examined, it was noticed that a few tetrahedra had two triangles on the protein surface and these were called "sharp tetrahedra" in this study. It was observed that sharp tetrahedra had a higher rate of transition to the protein interface. It has been shown that residues belonging to sharp tetrahedra detected in proteins belonging to the Retroviral Protease family consisted the residues studied experimentally and determined to be important. This result indicates that sharp tetrahedra represent important regions in the complex structures of proteins. Determining the protein surface and interface in protein complexes will enable the development of new treatments and new drugs for life-threatening conditions such as cancer and Alzheimer's disease.

Amaç: Acinetobacter baumannii suşları çoklu ilaç direnci gösteren (ÇİD) nozokomiyal kökenli enfeksiyonlardan sorumlu patojenlerdir. Kolistin ÇİD gösteren A. baumannii enfeksiyonlarına son çare olarak kabul edilmektedir. Ancak kolistin direncinin gelişmesi

Amaç: Metavinkülinin ek bölgesinde meydana gelen mutasyonlar kardiyomiyopatiye neden olur. Bu tez çalışmasının amacı metavinkülin kardiyomiyopati mutantlarını rekombinant olarak üretmek, kromatografik yöntemlerle saflaştırmak ve biyofiziksel karakterizasy

Kanser Hücre Hatlarında Etodolak ve Türevlerinin Siklooksijenaz (COX-2)Sentezi Üzerine Etkilerinin AraştırılmasıÖğrencinin Adı: Sevgi KOÇYİĞİT SEVİNÇDanışmanı: Prof. Dr. Oya ORUNAnabilim Dalı: Biyofizik Anabilim DalıAmaç: Çalışmamızda, Marmara Üniversitesi Ecz. Fakültesi Farmasötik Kimya AbDlaboratuvarında sentezlenen etodolak hidrazon, tiyazolidinon ve triazol türevlerinin (SGK 206, SGK 217 ve SGK 242) anti-kanser etkilerinin belirlenmesi amaçlandı.Gereç ve Yöntem: Etodolak ve türevlerinin hücreler üzerindeki anti-kanserojen etkisi, hücre canlılığı ve apoptoz deneyleri ile belirlenmiştir. PGE2 seviyeleri ise enzimatik kitlerle tespit edilmiştir.Bulgular ve Sonuç: Etodolak'ın anti-proliferatif etkilerinin, MCF-7 ve MDA-MB231 meme kanseri hücreleri ile L-929 kontrol fibroblast hücrelerinde 0-100 μM arasında çok düşük olduğu ancak 0,5 mM'den sonra etki gösterdiği tespit edilmiştir. SGK 206 ve SGK 217 ise çok daha düşük derişimlerde etkili olup, L-929 hücrelerinde herhangi bir toksik etki göstermezken, her iki meme kanseri hücresinde sitotoksik etki göstermiştir. SGK 242 ise tüm hücrelerde toksik etki göstermiştir. Çoğalmaya benzer şekilde, SGK 206 ve SGK 217 meme kanseri hücrelerinde düşük derişimlerde önemli bir apoptotik etki göstermiştir. 50 µM derişimde uygulanan SGK 206 ve SGK 217, kanser hücrelerinde COX-2 protein ekspresyonunu önemli ölçüde inhibe etmiştir. Ayrıca SGK 206’nın, kanser hücrelerinde PGE2 salınımını etodolak ilacından daha fazla inhibe ettiği belirlenmiştir. Bu bulgulara dayanarak hidrazon türevi SGK 206 ile tiyazolidinon türevi SGK 217’nin etodolak temelli tedavileri hedefleyen gelecekteki çalışmalar için destekleyici olacağına inanıyoruz.Investigation of the Effects of Etodolac and Its Derivatives on Cyclooxygenase (COX-2) Synthesis in Cancer Cell LinesStudent Name: Sevgi KOÇYİĞİT SEVİNÇName of Supervisor: Prof. Dr. Oya ORUNDepartment: Department Of BiophysicsObjective: In our study, it was aimed to determine the anti-cancer effects of etodolac hydrazone, thiazolidinone and triazole derivatives (SGK 206, SGK 217 and SGK 242) which were synthesized in Marmara University Faculty of Pharmacy, Department of Pharmaceutical Chemistry.Material and methods: Anti-carcinogenic effect of etodolac and its derivatives was determined with cell viability and apoptosis experiments. PGE2 levels were determined with enzymatic kits.Results and Conclusion: Anti-proliferative effects of etodolac were very low between 0-100 μM on MCF-7 and MDA-MB-231 breast cancer cells and L-929 control fibroblast cells but it was effective after 0,5 mM. SGK 206 and SGK 217didn’t show any toxic effect on fibroblast cells while they had cytotoxic effect on breast cancer cells at much lower concentrations. SGK 242 showed toxic effect in all cells. Similar to proliferation, SGK 206 and SGK 217 had a significant apoptotic effect in breast cancer cells at low concentrations. SGK 206 and SGK 217 significantly inhibited COX-2 protein expression of cancer cells at 50 µM. In addition, SGK 206 inhibited PGE2 release more than etodolac in cancer cells. Based on these findings, we believe that the hydrazone derivative (SGK 206) and the thiazolidinone derivative (SGK 217) would be supportive for future studies targeting etodolac-based therapies.

Şizofreni (SZ) ve Bipolar duygu durum bozukluğu (BP), dünyada yaklaşık olarak nüfusun %2'sini etkileyen nöropsikiyatrik sendromları olan ve bu sendromların çok çeşitlilik gösterdiği ve dolayısıyla tanılanmaları oldukça zor olan hastalıklardır. Bipolar bozukluk; manik epizod BP(M), depresif episod ve ötimik olmak üzere 3 fazda gözlenmektedir. Bipolar bozukluğun manik fazının Şizofreni ile benzer semptomlar göstermesi bu iki bozukluğun ayrıştırılmasını zorlaştırmakta ve tanılarında güçlükler yaşanmasına neden olmaktadır. Şizofren ve Bipolar hastalıkların tanısında, hastalar ile birebir yapılan görüşmelerde ortaya çıkan bazı sübjektif verilere dayanılarak, sonuca gidilmeye çalışılmaktadır. Hâlihazırda bu hastalıkların tanısı için geliştirilmiş, klinik tanı yöntemlerini destekleyecek nitelikte moleküler tabanlı herhangi bir tanı yöntemi bulunmamaktadır. Bu tez çalışması çerçevesinde SZ ve BP(M) hastalarını birbirinden ve sağlıklı bireylerden ayırabilen, hastaların kan serumunun Raman spektrumları analizine dayanan, SZ ve BP(M)'nin yardımcı ayırıcı tanısı için analitik bir model geliştirildi. Bu model, Raman spektrumlarının X-bağımsız değişkenlerinin olduğu iki sınıflı, iki PLS-DA adımının hiyerarşik bir dizimine dayanmaktadır. Analizler sonucunda 400-3100 cm-1 Raman spektroskopik aralığının bu bozukluklar için hassas bir spektroskopik biyobelirteç olarak çalıştığı sonucuna varıldı. Önerilen metodoloji güvenilir, hızlı, ucuz, portatif ve klinik ortamda kolayca uygulanabilir niteliktedir. Schizophrenia (SZ) and Bipolar mood disorder (BP) are neurological diseases that have neuropsychiatric syndromes and together affecting approximately 2% of the world population. Due to the diversity of their syndromes, they are difficult to be diagnosed. BP exhibits three distinct phases: manic and depressive episodes and the euthymic phase. The manic phase of bipolar disorder showing similar symptoms with schizophrenia which makes it difficult to differentiate these two disorders and causes difficulties in their diagnosis. Diagnostic approaches are based on constructed interviews and subjective evaluations of clinical symptoms of these disorders. Currently, there is no molecular-based diagnostic method developed for the diagnosis of these diseases that supports clinical diagnostic methods. Within the framework of this thesis study, an analytical model was developed for the auxiliary differential diagnosis of SZ and BP(M), based on the analysis of patients' blood serum Raman spectra, which can distinguish SZ and BP(M) patients from each other and from healthy individuals. This model is based on a hierarchical sequence of two PLS-DA steps of two classes, where spectra are X-predictor variables. As a result of the analysis, it was concluded that the 400-3100 cm-1 Raman spectroscopic range works as a sensitive spectroscopic biomarker for these disorders. The propounded methodology is reliable, fast, inexpensive, portable, and easily applicable in a clinical environment.

Nanotüp tünelleme hücreler arası iletişimde rol almaktadır. Ökaryotik hücrelerin yenilenmek, hayatta kalmak ya da strese direnmek üzere nanotüp tüneller oluşturduğu düşünülmektedir. Homotipik ya da heterotipik hücreler arasında köprüler oluşturan nanotüp tünellerin kalsiyum iyon akışı gibi sinyal moleküllerini ilettiği, organel, patojen ya da onkojenik molekülleri aktardığı gösterilmiştir. Nanotüp tünellerin temel yapısı mikrofilamentlerdir. Stres oluşturan çevresel etkenler altında aktin iskeletinin nanotüp tünellerin oluşmasını tetiklediği ve birbirinden uzak iki hücre arasında köprü oluşturduğu belirlenmiştir. Uzun-süreli hücre kültürü ortamı endotel hücrelerinde strese neden olmakta ve hücresel yaşlanma oluşmaktadır. Bu çalışmada standart hücre kültürü ortamında tekrarlayan pasajlar (P) ile çoğaltılan insan göbek kordonu damar endotel hücreleri (HUVEC) arasında nanotüp tünellemenin görüntülenmesi amaçlandı. Floresan mikroskop incelemesi için aktin iskeleti ve endozomlar sırası ile falloidin ve anti-EEA1 antikoru ile işaretlendi. Kontrol grubu (P3-4) ve deney grubu (P8-10) HUVEC’ler ile hazırlanan preparatlarda nanotüp tünel uzunlukları ölçüldü. P8-10 için ortalama uzunluk 30 μm olarak belirlendi. Endozomların nanotüp tünel yapısındaki aktin iskeleti ile birlikte konumlandığı gösterildi. Bu bulgular, hücre içinde kargo taşıyan endozomların, nanotüp tünelleme ile HUVEC’ler arasında da madde aktarımı yapabileceğini göstermektedir. Sonuçta tekrarlayan pasajlar ile çoğaltılan HUVEC’ler arasındaki nanotüp tünellerin mikrofilamentlerin dinamiğine bağlı olarak işlevsel olduğu belirlenmiştir. Hücreler arasında yeni bir iletişim yolu olarak kabul gören nanotüp tünelleme, stres cevabının irdelendiği çalışmalarda morfolojik bir parametre olarak değerlendirilebilir., The tunneling nanotube plays a role in intercellular communication. Nanotube tunnels are thought to be formed to regenerate, to survive or to resist stress by eukaryotic cells. Nanotube tunnels, forming bridges between homotypic and heterotypic cells, have shown to transmit signaling molecules such as calcium ion flux, and to transport organelles, pathogens or oncogenic molecules. The basic structure of nanotube tunnels is microfilaments. The actin skeleton triggers the formation of a nanotube tunnel and a bridge between two distant cells under stressing conditions. Cellular aging occurs in endothelial cells in a long-term cell culture. In this study, it is aimed to visualize nanotube tunneling between endothelial cells under cellular aging. Human umbilical cord vascular endothelial cells (HUVECs) were grown in the standard cell culture conditions with repeated passages (P). The actin cytoskeleton and endosomes were labeled with phalloidin and anti-EEA1 antibody respectively, for fluorescence microscopy. Nanotube tunnel lengths were measured in control (P3-4) and experimental (P8-10) HUVECs preparations. The average length for P8-10 was determined to be 30 μm. The endosomes were located together with the actin cytoskeleton in the nanotube tunnel. These findings show that endosomes, cargo-carrier inside the cell, can also transfer substances between HUVECs by nanotube tunneling. As a result, nanotube tunnels, formed between HUVECs of high passages depending on the dynamics of the microfilaments, were found to be functional. Nanotube tunneling, accepted as a new way of communication between cells, can be evaluated as a morphological parameter in studies of stress responses.

In the postmenopausal period, women undergo physical and morphological changes that may result in insufficiency and deterioration in physiological functions. It is accepted that oxidative stress is involved in the etiology of postmenopausal changes. It is known that the decrease in ovarian hormones, especially 17β-estradiol (17-β) after menopause induces apoptosis and oxidative stress in many tissues. It is well known that 17-β has an antioxidant role in non-menopausal women. Recently, we observed that the treatments of 17-β, raloxifene (RAL), and tamoxifen (TAM) diminished apoptotic factors, oxidative stress, and mitochondrial membrane depolarization in the brain and dorsal root ganglia of ovariectomized rats. There is no enough information about the effects of triple therapy [17-β, and selective estrogen receptor modulators (TAM and RAL)] effects on liver and kidney tissues. We aimed to investigate the effects of 17-β, TAM, and RAL on apoptosis, cell viability (MTT), and oxidative stress in the kidney and OV+TAM, and OV+RAL. 17-β, TAM, and RAL were subcutaneously given to three groups (OV+17-β, OV+TAM, and OV+RAL) for 14 days after ovariectomy. While kidney and liver cells lipid peroxidation levels were high in the OV group, they were low in the OV+17-β, OV+TAM, and OV+RAL groups. The treatments of 17-β, TAM, and RAL in the groups of OV+17-β, OV+TAM, and OV+RAL increased the glutathione peroxidase (GSH Px) activity and glutathione (GSH) levels in the cells of kidney and liver. In addition, the MTT level of kidney and liver cells was low in the OV group and higher in the OV+17-β, OV+TAM, and OV+RAL groups. The treatments of OV+17-β, OV+TAM, and OV+RAL decreased the apoptosis and ROS levels in kidney and liver cells. In conclusion, we observed that 17-β, TAM, and RAL administrations were beneficial on cell viability (MTT), apoptosis, and ROS levels in the kidney and liver cells of OV rats by modulating antioxidant systems. liver of bilateral ovariectomized (OV) rats. Forty female rats used in the experiment, and they were divided into five groups as control, OV, OV+17-β

Despite the clear effects and harm of the Bisphenol-A (BPH-A) chemical, it is one of the highest produced chemicals worldwide. The main areas of use include building materials, from automotive to food materials. It is important to find therapeutic agents against the damage caused by the BPH-A. Bisphenol A exposure is the major cause of increased oxidative stress (OS) and mitochondrial dysfunction, especially in cells. Thus, our study aimed to research the protective effect of selenium in BPH-A-induced SH-SY5Y neuroblastoma cells. The SH-SY5Y cells were divided into 4 groups as 1- Control group: No drug was applied to these cells. 2- BPH-A group: Bisphenol A was incubated with 100 µM for 24 hours. 3- BPH-A+Na-Se group: This group was incubated with BPH-A for 24 hours. Na-Se (1 µM) was added in the last 2 hours of the 24 hours. 4- Na-Se group: Na-Se was incubated with 1 µM for 2 hours. In the cells, intracellular ROS and JC-1 levels were highest in the BPH-A group, although there was a significant reduction in the selenium-treated group (BPH-A+Na-Se). In addition to these, when the Caspase-3 and Caspase-9 enzyme activities were examined between the groups, it was seen that Selenium reduces the increased caspase activity caused by BPH-A. Finally, when the apoptosis and MTT analysis results between the groups were examined, it was observed that apoptosis and MTT levels were highest in the BPH-A group, while it was significantly lower in the Na-Se group compared to the BPH-A group. In conclusion, this study revealed that Selenium, with its antioxidant properties, can be used as a neuroprotective agent by reducing BPH-A-induced oxidative stress.

Hücre biyolojisi, hücre sayımı ve hücre tespiti gibi alanlarda meydana gelen gelişmeler; hastalık teşhisi, biyoteknoloji, ilaç endüstrisi ve malzeme biliminde kullanılacak yeni parçacık karakterizasyon yöntem ve araçlarının geliştirilmesini gerekli kılmaktadır. Akış sitometri teknolojisi bu alandaki ihtiyacı neredeyse bir asırdır karşılayan öncü teknolojidir. Günümüzde hızlı, hassas, doğru ve düşük maliyetli hasta-başı teşhis cihazlarına ve hücre sayma teknolojilerine olan yoğun bir talep artışı söz konusudur. En gelişmiş ticari akış sitometri cihazları dahi teknolojik açıdan bu talebe cevap vermekte yetersiz kalabilmektedir. Bu talep, yenilikçi ve hassas parçacık hizalama teknikleri, çoklu algılama yöntemleri ve birbirine entegre akışkan, optik ve elektronik üniteler kullanılarak geliştirilen yenilikçi sitometri teknolojileri ile karşılanabilir. Bu tip özellikler konusunda tartışmasız derecede avantajlara sahip olan mikroakışkan akış sitometri platformları, yeni nesil akış sitometri teknolojilerinin geleceği adına ilgi çekici ve umut vericidir.Bu tez çalışmasında, optik, empedans ve görüntü tabanlı mikroakışkan sitometri ölçüm yöntemleriyle uyumlu olan viskoelastik parçacık hizalama tekniği geliştirildi. Viskoelastik akışkanların elastik doğası, süspansiyon haldeki parçacıkların kanal akış eksenine dik düzlemde pozisyon değiştirerek, tek bir akış çizgisi boyunca hizalanmasını sağlar. Bu sayede akış sitometri cihazlarındaki ölçüm hassasiyetini artırmak için gerekli olan merkezi parçacık hizalanma sağlanmış olur. Viskoelastik parçacık hizalama tekniği pasif bir yöntemdir ve kılıf akışına veya herhangi bir aktif parçacık hizalama mekanizmasına olan ihtiyacı ortadan kaldırır. İlk olarak, avuç içi büyüklüğünde bir cam mikrokılcal cihazda optik mikroakışkan akış sitometrisi için viskoelastik odaklama tekniği geliştirildi. Optik ölçüm ve algılama işlemleri fiber kuplajlı lazer kaynağı ve fotodedektör yardımıyla yapıldı. Polietilen oksit (PEO), Hyalüronik asit (HA) ve Polivinilpirolidon (PVP) tabanlı üç farklı viskoelastik solüsyonda süspansiyon halindeki polistren sitometri kalibrasyon parçacıklarının tespiti gösterildi. İkinci olarak, empedans tabanlı mikroakışkan akış sitometrilerinde kullanımlarını göstermek için PEO tabanlı viskoelastik solüsyonların farklı iyonik konsantrasyonlardaki viskoelastik parçacık hizalama etkinliği araştırıldı. Ardından, polistren ve kırmızı kan hücreleri kullanarak empedans sitometri ölçümleri gerçekleştirildi. Yüksek verimli akış sitometri uygulamaları için ataletsel ve viskoelastik etkilerin kombinasyonu kullanılarak küresel polistren parçacıklarının yüksek akış hızlarında merkezi hizalanmasının mümkün olduğu gösterildi. Buna ek olarak küresel olmayan kırmızı kan hücrelerinin tamamının kanal merkez çizgisi boyunca paraşüt şeklinde hizalanması ve bu sayede empedans sitometri cihazlarında gözlenen küresel olmayan parçacık kaynaklı ölçüm varyasyonlarının azaltılarak tutarlı empedans sinyalleri elde edilmesi sağlandı. Elde edilen sonuçlar, önerilen akış sitometri cihazlarının, verimlilik ve ölçüm hassasiyeti açısından en gelişmiş sitometri cihazlarıyla kıyaslanabilir performans değerleri elde ettiğini gösterdi. Optik ve empedans tabanlı akış sitometri uygulamaları, yalnızca basınçlı hidrodinamik akış kullanılarak geliştirildi. Basınçlı hidrodinamik akış ve elektrik alan kaynaklı elektroforez eşzamanlı olarak uygulandığında, mikroakışkan kanalların içindeki süspanse parçacıklar karmaşık hizalanma davranışları ve birbirinden farklı nihai denge konumları sergilediği bilinmektedir. Mevcut deneysel ve analitik çalışmalar parçacıkların nihai denge konumlarının neden farklı olduğuna dair ayrıntılı bir açıklama sunmakta yetersiz kalmaktadır. Ayrıca, şimdiye kadar yapılan çalışmalar yalnızca Newtonsal ve yüksüz viskoelastik sıvılarla sınırlıdır. Bu tez çalışmasında üçüncü olarak, elektroforez, akış ve viskoelastik sıvı kaynaklı kaldırma kuvvetlerinin birbiri ile etkileşimini ayrıntılı olarak açıklamak için bütüncül bir yaklaşım benimsenmiştir. Parçacık hizalanmasının kapsamlı bir şekilde anlaşılmasını sağlamak için Newton, yüksüz viskoelastik ve polielektrolit viskoelastik ortamlarda sıvı akış yönüne dik parçacık hareketleri deneysel olarak incelendi. Viskoelastik ortam ile yapılan deneyler neticesinde, şimdiye kadar yapılmış olan mevcut çalışmalardan daha farklı sonuçlar elde edildi. Sonrasında hem Newton hem de yüklü ve yüksüz viskoelastik sıvılarda gözlemlenen farklı parçacık hizalanma davranışlarına bütüncül bir yaklaşım ile açıklık getiren Elektro-Viskoelastik Hizalanma (EVH) teorisi geliştirildi. Buna ek olarak, EVH tekniğinde gözlenen farklı parçacık hizalanma davranışlarının altında yatan sebepleri keşfetmek için floresan etiketli viskoelastik polimer çözeltisi oldukça şaşırtıcı olarak sıvı akışına dik kanal kesitinde homojen olmayan viskoelastik çözelti oluşumu gözlemlendi. EVH tekniği ile elde edilen bu bulguların mikroakışkan camiasında şimdiye kadar keşfedilmemiş homojen olmayan viskoelastik akış gibi eşsiz uygulamalara kapı açacağı düşünülmektedir.Özet olarak, sunulan sistemler tek bir düz mikrokılcal ya da mikrokanal üzerinde basit fabrikasyon teknikleri kullanılarak geliştirilmiştir. Akışkan düzeneği, optik, ve empedans tabanlı algılama üniteleri aynı akış sistemi üzerinde birbirine kolayca entegre edilebilir ve viskoelastik hizalama tekniği kullanılarak başarılı sitometri uygulamaları gerçekleştirilebilir. Mikroakışkan akış sitometri uygulamalarındaki yenilikçi yaklaşımımız viskoelastik sıvıların, gelişmekte olan ülkeler ve düşük gelir kaynaklı ortamlar için entegre, taşınabilir ve düşük maliyetli yeni nesil sitometri platformlarının geliştirilebilmesi adına iyi bir aday olduğunu göstermektedir. Buna ek olarak, EVH tekniği, jel elektroforez veya kromatografi uygulamalarının yerine geçebilecek seviyede, polyelektrolitlerin DNA fraksiyonlarının ve proteinlerin elektriksel yüklerine ve boyutlarına göre bir mikrokanal boyunca hassas bir şekilde hizalanmasını ve ayrıştırılmasını sağlayabilecek güçlü bir potansiyele sahiptir.tileri hazırlanarak konfokal mikroskop altında floresan boyalı polimerlerin hareketi incelendi Advances in cell biology, quantification, and identification procedures are essential to develop novel particle characterization tools on the diagnostics, biotechnology, pharmaceutical industry, and material science. Flow cytometry is a pivotal technology and meets the need for almost a century. An increase in today's demand for fast, precise, accurate, and low-cost point-of-care diagnostic tools and cellcounting technologies necessitate further improvements for state-of-the-art flow cytometry platforms. These improvements are achievable using novel and precise particle focusing techniques, multiple detection methods, integrated fluidic, optical, and electronic units in the same workflow. Thanks to its indisputable advantages in such integrities, microfluidic flow cytometry platforms are attractive and promising tool for the future of next-generation flow cytometry technologies. In this thesis, we developed viscoelastic focusing technique compatible with optical, impedimetric, and imaging-based microfluidic flow cytometry methods. Elastic nature of the viscoelastic fluids induces lateral migration for suspended particles into a single streamline and meets the requirement for central particle focusing on flow cytometry devices. Viscoelastic focusing is a passive particle manipulation technique and eliminates the need for sheath flow or any other active actuation mechanism. Firstly, we developed viscoelastic focusing technique for optical microfluidic flow cytometry in a palm-sized glass capillary device. Optical detection was performed by fiber-coupled laser source and photodetectors. We demonstrated the detection of polystyrene (PS) cytometry calibration beads suspended in three viscoelastic solutions: Polyethylene oxide (PEO), Hyaluronic acid (HA), and Polyvinylpyrrolidone (PVP). Secondly, we investigated the viscoelastic focusing efficiency of PEO-based viscoelastic solutions at varying ionic concentrations to demonstrate their use in impedance-based microfluidic flow cytometry. We performed cytometry measurements using PS beads and human red blood cells (RBCs). We showed that elasto-inertial focusing of PS beads is possible with the combination of inertial and viscoelastic effects for high-throughput flow cytometry applications. Additionally, non-spherical shape RBCs were aligned along the channel centerline in parachute shape, which yielded to decrease the non-spherical shape-based signal variations in impedance cytometry devices consistent impedimetric signals. Our results showed that proposed flow cytometry devices give similar performance to state-of-the-art systems in terms of throughput and measurement accuracy. Optical- and impedance-based flow cytometry applications were demonstrated using only pressure-driven flow. Under the simultaneous use of pressure-driven flow and DC electric field, particles inside microfluidic channels exhibit intricatemigration behavior at different particle equilibrium positions. Available experimental and analytical studies fall short in giving a thorough explanation to particle equilibrium states. Also, the understanding is so far limited to the results based on Newtonian and neutral viscoelastic fluids. Thirdly in this thesis study, a holistic approach is taken to elaborate the interplay of governing electrophoretic and slip-induced/elastic/shear gradient lift forces. Experimental studies were carried on particle migration in Newtonian, neutral viscoelastic, and polyelectrolyte viscoelastic media to provide a comprehensive understanding of particle migration. Our experiments with the viscoelastic media led to contradictory results with the existing explanations. Then, we introduced the Electro-Viscoelastic Migration (EVM) theory to provide a unifying explanation for particle migrationin Newtonian and viscoelastic solutions. Additionally, we performed confocal imaging experiments with fluorescent-labeled polymer solutions to explore the underlying migration behavior in the EVM technique. We observed the formation of cross-sectionally non-uniform viscoelastic solution would pave the way for undiscovered unique applications in the microfluidic community.In summary, presented devices were demonstrated with straightforward fabrication techniques on a single straight microcapillary or microchannel. It is possible to couple fluidics, optical, and impedimetric detection units into the same workflow. Our approach in microfluidic flow cytometry applications proved that viscoelastic fluids are good candidates for the development of integrated, portable,and cost-efficient next-generation cytometry platforms and low resource settings. Additionally, the unifying EVM technique has a strong potential to precisely focusing and separating cells, polyelectrolytes, DNA fractions, and proteins according to their charge and size with a comparable resolution and measurement time as a replacement for gel electrophoresis or chromatography applications. 150

Aim: Osteoarthritis (OA) is a common joint disease that is caused by mechanical, genetic, and biochemical factors, and knee OA is one of the reasons of mobility limitation and disability. The receptor activator of NF-κB ligand (RANKL) is directly involved in the differentiation of osteoclasts through its receptor RANK. In this study, we aimed to study circulating serum levels of RANKL, and assess knee bioelectric impedance in control and patients with knee OA. Methods: In this case-control study, OA severity was evaluated by the Kellgren–Lawrence grading scale, based on which we categorized patient groups. There were 22 control individuals (Grades 0 and 1), 11 early (Grade 2) and 30 late OA patients (Grades 3 and 4). We evaluated the performance of the bioimpedance phase angle values at 50 kHz. The RANKL protein levels in the serum were quantified using Enzyme-Linked Immunosorbent Assay (ELISA).Results: It was observed that the control group could not be differentiated from the study group by using phase angle values (P=0.925). Concerning the RANKL levels, although it shows a relative increase in the study group, it did not reach a significant level (P=0.116). Conclusion: The phase angle values at 50 kHz and RANKL levels may not be used in predictive detection of knee OA. Additional studies with larger sample sizes are needed to interpret if these changes are consistent and clinically related., Amaç: Osteoartrit (OA), mekanik, genetik ve biyokimyasal faktörlerin etkilerinden kaynaklanan yaygın bir eklem hastalığıdır ve diz OA’i, hareket kısıtlaması ve engel nedenlerinden biridir. Bu çalışmada NF-κB ligandının (RANKL) reseptör aktivatörünün dolaşımdaki serum seviyelerini incelemeyi ve kontrolde ve diz OA'i olan hastalarda biyoelektrik empedansını değerlendirmeyi amaçladık.Yöntemler: Çalışmamız bir vaka-kontrol çalışması olarak tasarlanmıştır. OA şiddeti Kellgren-Lawrence derecelendirme skalası ile değerlendirildi, gruplar 22 sağlıklı kontrol (derece 0 ve 1), ve çalışma grubu 11 erken (derece 2) ve 30 geç OA (derece 3 ve 4) olarak tanımlandı. 50kHz’te biyoimpedans faz açısı değerlendirildi. Serumdaki RANKL protein seviyeleri Enzyme Linked Immunosorbent Assay (ELISA) metodu ile ölçüldü. Bulgular: Kontrol grubunun faz açısı değerleri kullanılarak diz OA grubundan ayırt edilemediği gözlendi (P=0,925). RANKL düzeyleri ile ilgili olarak, çalışma grubunda göreceli bir artış tespit edilse de, anlamlı bir seviyeye ulaşmadı (P=0,116).Sonuç: 50 kHz faz açısı değerleri ve RANKL seviyeleri, diz OA'sının tespitinin öngörülmesinde kullanılamayabileceği belirlenmiştir. Bu değişikliklerin tutarlı ve klinik olarak ilişkili olup olmadığını yorumlamak için daha büyük örnek büyüklüklerine sahip ek araştırmalara ihtiyaç vardır.