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indexedOpen AccessTRBCL-2 inhibitörü navitoclax ve HSP27 inhibitörü J2 moleküllerinin akciğer adenokarsinom kanseri üzerinde in vitro sinerjistik antikanser etkilerinin incelenmesi
Küçük hücreli dışı akciğer kanseri (NSCLC), akciğer kanserlerinin en yaygın alt tiplerinden biri olup tedavi direnci ve apoptotik mekanizmaların baskılanması ile karakterize edilen, agresif öneme sahip bir malignitedir. Bu çalışmada, Bcl-2 inhibitörü Navitoclax ve HSP27 inhibitörü J2 moleküllerinin küçük hücreli dışı akciğer kanserinde in vitro sinerjik antikanser etkilerini araştırmak amacıyla A549 hücre hattı model sistem olarak kullanılmıştır. Hücre canlılığı MTT yöntemiyle, ilaç etkileşimleri CompuSyn ve Bliss bağımsızlık modeli ile, doz-yanıt ilişkileri ise Yanıt Yüzey Yöntemi (YYY) ile değerlendirilmiştir. Ayrıca BCL2, BAX, APAF-1, CTNNB1 ve CASP9 gen ekspresyon düzeyleri RT-qPCR ile, Bax, Bcl-2 ve Casp-3 protein düzeyleri ise ELISA yöntemiyle analiz edilmiştir. Bliss analizine göre ters orantılı kombinasyonda en belirgin sinerjik etki 0,625 µM Navitoclax + 10 µM J2 dozunda saptanmış; doğru orantılı kombinasyonda ise 0,625 µM Navitoclax + 0,156 µM J2 dozunda saptanmıştır. Bulgular, kombinasyonun A549 hücrelerinde daha seçici antiproliferatif etki gösterebileceğini desteklemektedir.
Östrojen hormonunun sıçan kemik iliğinden alınmış mezenkimal kök hücrelerinin muhafazasında ve hasarlı dokuya ulaşmasındaki rolü
Mesenchymal Stem Cells (MSCs) can self renew and differentiate into different cell types like, adipocytes, osteoblasts, chondrocytes, neurons, hepatocytes and endothelial cells. Their ability to differentiate into wide variety of cell types, non-immunogenic characteristics, along with homing capacity to injured tissue and the absence of any ethical issue related to their uses, make MSCs important in regenerative medicine and tissue engineering. Their ability to migrate to the site of injury raises the opportunity of these stem cells to be considered also as in vivo delivery agents. However, one major obstacle in using MSCs in cell based therapies is their limited numbers. Estrogen is known to have role in growth, proliferation and apoptosis. Therefore our aim was to study the possible role and mechanism of estrogen in their maintenance and their homing capacity. We used MSCs derived from female and ovariectomized female rat bone marrow in our research. Our results revealed that estrogen treatment increased the number of colonies and the number of cells constituting a colony. Estrogen decreased the differentiation capacity of MSCs to the adipogenic lineages as shown by reduced of Oil Red O staining Estrogen also affected MSCs? homing capacity. Estrogen treatment resulted in the migration of increased number of DiI labeled MSCs to the site of injury after partial hepatectomy (PH) compared to that of untreated MSCs. Furthermore, estrogen treatment decreased the rate of apoptosis. Our data showed that estrogen regulates apoptosis through Bcl-2 family of genes in MSCs. This regulation was at the protein level but not at the transcript level. Estrogen addition increased the expression of anti-apoptotic members of the Bcl-2 family of proteins, Bcl-2 and Bcl-xL. The decrease in the apoptosis was not observed when Bcl-xL and Bcl-2 genes were knocked down. The silencing histone code H3K27me3 was also decreased in estrogen treated MSCs, suggesting an epigenetic regulation of MSCs upon estrogen treatment. Altogether our results show that estrogen increased the number of functional MSCs, decreased spontaneous apoptosis in these cells, and improved the homing capacity of rat bone marrow derived MSCs. Therefore, estrogen treatment of MSCs may offer new opportunities for the therapeutic actions of these cells.
Farklı dozlarda kapari (Capparis ovata desf.) uygulamasının sazan (Cyprinus carpio L.,1758) balıklarında hipotalamo-hipofiz-interrenal aks aktivitesi üzerine etkisi
Bu tez çalışmasında, etanol ile muamele edilmiş kapari (Capparis ovata, Desf.) bitkisi meyve özütlerinin, sazan balıklarında (Cyprinus carpio L., 1758) serum Adrenokortikotropik (ACTH), Kortizol ve Glikoz (Glu) düzeyleri üzerine etkisi araştırılmıştır. Araştırmada sazan balıklarına akut ve sub-kronik (4 ve 30 gün) fazlarda ve farklı dozlarda (0, 5, 10 ve 20) kapari özütüne maruz bırakılmıştır. Deney sonrası kan serumu hormonal ve biyokimyasal analizler sonucunda kontrol grubuna göre, ACTH seviyeleri her iki fazda ve 10 ve 20ppm doz gruplarında anlamlı bir artma tespit edilmiştir. (p<0,05). Serum kortizol ve glikoz düzeylerinde akut fazda 10 ve 20 ppm doz gruplarında azalma, sub-kronik fazda ise artma anlamlı bulunmuştur (p<0,05). Söz konusu doz grupların akut fazda sazan balıklarında sedatif bir etkiye neden olduğu, sub-kronik fazda ise immünolojik düzenlemeler sonucu salınan mediatörlerin etkisi (sitokin salınımı) ile yeniden fizyolojik düzenleme (hormonal homeostasis) şeklinde olabileceği ve bu nedenlede strese karşı olabileceğini düşündürmüştür.
Ustilago maydis (DC.) Corda'dan kitin izolasyonu ve karakterizasyonu
Arthropoda (Eklem bacaklılar) şubesinde vücudun dış yüzeyini örten, mantarların hücre duvarında yer alan, mercan, nematod ve diatom gibi canlıların vücut yapısına katılan kitin doğada selülozdan sonra en çok bulunan biyopolimerdir. Farklı kaynaklardan izole edilen kitin ve türevleri tıp, tarım, kozmetik, su arıtımı gibi oldukça fazla alanda kullanılmaktadır. Bu çalışmada mısır bitkisinde mısır rastığı hastalığına neden olan Ustilago maydis (DC.) Corda mantarından kitin izole edilmiştir. İzolasyon işleminde asitleri uzaklaştırmak için 4 M HCl ve proteinleri uzaklaştırmak amacıyla 2 M NaOH çözeltileri kullanılmıştır. U. maydis'in kuru ağırlık üzerinden %11 kitin içeriğine sahip olduğu belirlenmiştir. İzole edilen kitin, FTIR, XRD, TGA ve SEM teknikleri ile karakterize edilmiştir. FTIR analizinde 1656 cm-1, 1621 cm-1 ve 1557 cm-1'de gözlenen üç pik izole edilen kitinin alfa kitin karakterinde olduğunu göstermiştir. TGA analizinde 0-150°C aralığında %5.86 ve 331.7°C de %50.64 oranında iki kütle kaybının olduğu gözlenmiştir. Alfa kitinin XRD analizi sonucunda kristal indeksi %74 olarak hesaplanmıştır. SEM çekimleri ise kitinin düz bir yüzeye sahip olup, fiber ve por yapılarının bulunmadığını göstermektedir. Sonuç olarak mısır üzerinde parazit olarak yaşayan ve ekonomik açıdan oldukça zararlı olan bu canlının çok amaçlı kullanılan teknolojik bir ürüne dönüşümü sağlanmıştır. Bu çalışma ile bu parazit mantarın kitin ve türevleri için alternatif bir kaynak olarak kullanılabileceği ortaya konmuştur.
Türkiye Quercus L. (Fagaceae) türlerinin Ilex seksiyonu üzerine karşılaştırmalı biyosistematik çalışma
Evergreen Quercus taxa are placed in Ilex section. This section contains Q. ilex, Q. coccifera and Q. aucheri which is distributed only in Turkey, and in some East Aegean islands of Greece. However, Q. coccifera and Q. aucheri usually confused with each other. For this reason, species boundary of Q. aucheri and its biosystematic features are not known well. On the other hand, Q. coccifera and Q. calliprinos are accepted as different species by some researchers or sometimes they can be referred as the same species but two subspecies. Thus, the real phenetics and phylogenetics relations among these species have not still been fully explained.Due to having hybrids among the taxa which belong to Ilex section and complex vegetative variations cause problems and make difficult to determine the borders of taxa. In order to solve this problem, variations within and between populations of taxa were pointed out by using some statistical analyses. According to the results of statistical analyses, it was attempted to draw the most possible borders of taxa. Furthermore, those vegetative characters which show high correlation with each other were selected and involved in morphometric analyses. As a result, a phenetic classification, which based on vegetative characters, was carried out. Likewise, a molecular but phenetic classification was produced based on the DNA bands obtained from RAPD analyses too. Finally; comparison within and among species was made with cytogenetic study. Congruence between morphology, molecular, and cytogenetic results was compared to make a better phenetic classification.Key words: Quercus, Section Ilex, Biosystematics, Cytogenetic, RAPD.
Karakter seçimi metodunun moleküler ve morfolojik data kullanılarak filogenetik ağaç oluşturulmasında uygulanması
This thesis analyzes biological datasets in the form of (morphological data and molecular sequences data) by utilization of Genetic Algorithms as the Feature Selection method. Information contents of the datasets were investigated and discussed. The thesis also traced the congruencies and incongruences within the dataset and seek to answer questions such as what is the minimum number of characters required to reconstruct a desired tree, or which part of the dataset carries what type of information especially for taxonomic applications.This study is composed of two parts; analysis of morphological data and molecular sequence data. In the analysis of morphological data, I have analyzed a classical dataset based on Hoplitis taxa which can be accepted as a benchmark numerical taxonomy dataset and acorn dataset. The proposed method successfully optimized the Hoplitis dataset to a set of 67 characters which was very close to predictions of the authors of the dataset. Optimization of the acorn dataset was also quiet successful by returning reasonable characters.Shorter molecular sequences up to 1000 nt were also analyzed by the optimization algorithm. Heme Cupper Oxidase dataset were resulted with positions that are found within the solution subsets frequently. Some of those positions were highly accurate with the current literature. For the longer sequences, a similar algorithm has been designed by the use of Longest Common Substring method. In this method, only the difference is that analyses were performed on small subsets separated by common blocks rather than characters or residues. In this part, we have used a well-known mammalian mitochondrial genome dataset. The algorithm has returned a relatively small subset of data to construct the same phylogeny.
Rhodobacter capsulatus ın CBB3-tipi sitokrom oksidaz enzimininde kısmi olarak korunmuş üç aminoasit mutasyonunun karakterizasyonu
Heme-Copper Oxygen reductases are responsible for catalyzing the reduction of oxygen to water and generate an electrochemical gradient, which is used for ATP synthesis. cbb3-type oxidases are the most distinct members of the HCOs which are characterized by high catalytic activity at low oxygen concentrations and reduced proton pumping. Analyses on genomic sequences for C-type oxygen reductase family and mutagenesis studies on conserved residues showed that each of these conserved residues has a critical role in structure and/or function of the enzyme. In this study, three partially conserved residues Aspargine 265, Tyrosine 420 and Phenylalanine 480, which are unique to C-type oxygen reductase family, were substituted to Valine, Phenylalanine and Alanine respectively by site directed mutagenesisfor the investigation ofthe diversity, mechanism and structure of this highly diverse family. Characterization of the mutants from Rhodobacter capsulatuswas done with respect to their effects on activity, assembly and proton pumping stoichiometry.Mutations at the position of N265 and Y420 showed that, they have critical role on the enzyme activity and assembly while F480 has role in function,proton translocation.Findings support the assumption that partially conserved residues may also have important role in the structure and/or function of thecbb3-type oxidases.
Sıçan kalp dokusunda ökse otu nun (Viscum album L.) etkileri
Viscum album L. (European mistletoe) comprises a semi parasitic plant which grows on various host trees in Turkey and Europe. It has been widely used as a herbal treatment since ancient times for hypertension and other cardiovascular disorders. Its cardioprotective action has been attributed to the vasodilatation increased by nitric oxide synthase activity and antioxidant activity. However, little is known about its effects on atrial tissue and myocardial ischaemia-reperfusion injury. We hypothesized that V. album is able to limit infarct size under ischeamia-reperfusion injury. This study was designed to evaluate the cardiac & cardioprotective effects of V. album crude extracts on isolated heart preparation, using the Langendorff technique in an ischaemia-reperfusion infarct model and isolated rat atrial muscle. Both administration of aqueous V. album (AVa) and methanolic V. album (MVa) extracts during ischaemia - reperfusion significantly limited infarct size compared to controls. Inhibition of nitric oxide synthesis completely abrogated this protection in both extracts. KATP channel blockage by glibenclamide also abrogated the protection afforded by MVa but perfusion of glibenclamide along with AVa showed a synergistic action. Nevertheless, aqueous V. album extract induced negative inotropic and chronotropic effects in the rat atrial muscles, in vitro. None of the pharmacological agents used in this study abrogated the negative inotropic effects of V. album extract. These data suggest that V. album extracts can afford cardioprotection by limiting infarct size during ischaemia reperfusion. Furthermore, our study is of great significance in terms of being the first research in the experimental field of infarct model with V. album. Further studies need to be performed to investigate the interaction of V. album extracts and more specific agents. These need to be focused on the isolation, purification, structural dilucidation, pharmacological reevaluation in order to find the chemical compound responsible for such a pharmacological effect. Keywords: Viscum album L., cardioprotective, ischaemia - reperfusion injury, nitric oxide, vasodilation, Langendorff, infarct, KATP channel, inotropy, antioxidant.
Gölköy ve Yumrukaya'nın sucul bitki çeşitliliği(Bolu,Türkiye)
In this thesis vascular aquatic macrophyte flora of Lake Gölköy and Yumrukaya wetland (Bolu, Turkey) were studied. Field studies were done between July and November for 2011, between April and October for 2012. After identification of the collected specimens 80 taxa belonging to 30 families and 50 genera were found. 8 taxa are new records for the Bolu province. The largest 5 families according to their species number in the two study areas are: Cyperaceae (11 sp.), Lamiaceae (8 sp.), Potamogetonaceae (6 sp.), Asteraceae (5 sp.) and Ranunculaceae (5 sp.). The largest 5 genera according to their species number in the two study areas are: Carex (5 sp.), Potamogeton (5 sp.), Salix (5 sp.), Juncus (4 sp.) and Polygonum (4 sp.). Identified aquatic plants were also classified according to their life forms, as being submerged, free floating, attached floating or as emergent. The study sites were compared with 5 other wetland of Bolu according to their species compositions. TWINSPAN two-way indicator species analyze resulted in four groups. Non-metric multidimensional scaling (NMDS) analysis separated Gölcük, Sülüklügöl and Lake Sünnet from the cluster formed by Lake Gölköy, Yumrukaya, Abant and Yeniçağa. Keywords: Bolu, Gölköy, Macrophyte, NMDS, TWINSPAN, Yumrukaya.
Ultrasonikasyon ve hardal tohumu kombinasyonuyla çeşitli meyve sularında bazı gıda kaynaklı patojenlerin yok edilmesi
Foodborne infections are reported to cause important problems in human beings worldwide. Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp., mostly known as pathogenic strains are responsible to cause foodborne infections due to the consumption of viable pathogen containing fruit juices and other food materials. Nowadays, in order to combat these infections effectively, hurdle technologies have gained great importance in food industry. Non-thermal methods, in combination with natural substances is an alternative way for these technologies. In this study, sole mustard seed, sole ultrasonication and a combination of mustard seed and ultrasonication were used to inactivate these pathogenic species in apple, alpine strawberry and blackberry juices. It was found that in alpine strawberry and blackberry juices, the combination of ultrasound at a frequency of 24 kHz at the amplitude of 90% and 0.6 g/L mustard seed resulted an effective inhibition to these important foodborne pathogens mentioned, with respect to the control, without disrupting chemical and physical properties of the fruit juices.