Fakülteler / Faculties
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Item Role of autophagy and evaluation the effects of microRNAs 214, 132, 34c and prorenin receptor in a rat model of focal segmental glomerulosclerosis(2021) Yildirim, Derya; Bender, Onur; Karagoz, Zehra Firat; Helvacioglu, Fatma; Bilgic, Mukadder Ayse; Akcay, Ali; Ruzgaresen, Nuket Bavbek; 0000-0002-6026-0045; 34087284Aims: Focal segmental glomerulosclerosis (FSGS) is the common cause of chronic renal disease worldwide. Although there are many etiologic factors which have common theme of podocyte injury conclusive etiology is not clearly understood. In this study, we aimed to explore the role of autophagy in the pathogenesis of podocyte injury, which is the key point in disease progression, and the roles of intrarenal microRNAs and the prorenin receptor (PRR) in the 5/6 nephrectomy and adriamycin nephropathy models of FSGS. Main methods: For experimental FSGS model, 5/6 nephrectomy and adriamycin nephropathy models were created and characterized in adult Sprague Dawley rats. Microarray analysis was performed on FSGS and control groups that was confirmed by q-RT-PCR. Beclin1, LC3B, PRR, ATG7 and ATG5 expression were evaluated by western blotting and immunohistochemistry. Also, Beclin1 and PRR expression were measured by ELISA. Glomerular podocyte isolation was performed and autophagic activity was evaluated in podocytes before and after transfection with miRNA mimic and antagonists. Key findings: Glomerular expression of Beclin1, LC3B, PRR, ATG7 and ATG5 were significantly lower in the 5/6 nephrectomy than adriamycin nephropathy group and in both groups lower when compared to control groups. Western blot results were consistent with immunohistochemical data. Electron microscopy revealed signs of impaired autophagy in FSGS. Autophagic activity decreased significantly after miR-214, miR-132 and miR-34c mimics and increased after transfection with antagonists. Significance: These results showed that the role of autophagic activity and decreased expression of PRR in FSGS pathogenesis and miR-34c, miR-132 and miR-214 could be a potential treatment strategy by regulating autophagy.Item Effect of intravitreal and intraperitoneal cyanidin-3-glucoside injection in oxygen-induced retinopathy mouse model(2019) Ercan, Zeynep E.; Haberal, Nihan; Helvacioglu, Fatma; Dagdeviren, Atilla; Yİlmaz, Gursel; 0000-0002-9915-3781; 31124490; AAQ-3136-2020Purpose: To evaluate the effect of cyanidin-3-glucoside (C3G) in oxygen-induced retinopathy (OIR) mouse model. Methods: In this experimental study, 10 C57BL / 6J type mice exposed to room air comprised two control groups (n = 5 each; a negative control and a group receiving intravitreal sterile dimethyl sulfoxide [IVS DMSO]). Thirty C57BL / 6J type mice exposed to 75% +/- 2% oxygen from postnatal day 7 to postnatal day 12 comprised the OIR groups. On postnatal day 12, these mice were randomized into six groups (n = 5 each): two OIR control groups (negative control and IVS DMSO), two intravitreal C3G groups (300 and 600 ng/mu L), and two intraperitoneal C3G groups (0.05 and 0.1 mg/kg). We quantified neovascularization by counting endothelial cell proliferation on the vitreal side of the inner limiting membrane of the retina and examined histological and ultrastructural changes via light and electron microscopy and apoptosis by terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling. Results: The intravitreal C3G groups yielded lower endothelial cell counts compared with the intravitreal DMSO group. The intraperitoneal high-dose group had lower cell counts compared with the OIR control groups. Electron microscopy revealed significantly less mitochondrial dysmorphology in intravitreal groups and the high-dose intraperitoneal mice. We noted no difference in apoptotic cell count between the controls, low-dose intravitreal, and both intraperitoneal groups. However, apoptotic cell count was significantly higher in the high-dose intravitreal group. Conclusion: C3G suppresses endothelial cell proliferation in an OIR mouse model, leads to a reduced hyperoxia-induced mitochondrial dysmorphology, but increases apoptotic cell death in high concentrations.Item Intussusceptive Growth of Vascular Bed in Human Placenta(2019) Fidan, Pinar Ayran; Helvacioglu, Fatma; Dagdeviren, Atilla; 0000-0003-3047-0305; ABG-5365-2020Objective: Normal embryonic and fetal development is strictly bound to maternal health and functioning placenta. Besides the invasion and differentiation of trophoblastic cell lineage; development of effective vasculature is crucial for the function of placenta. Placental vessels first arise by vasculogenesis in early development of villi and then succeeded by angiogenesis during fetal life. In the recent decades a new form of angiogenesis, "intussusceptive angiogenesis", besides classical sprouting angiogenesis is well documented. The presence of intussusception was shown at multiple organs but in placenta, in recent literature. We aimed to determine whether intussusceptive angiogenesis is present in human placenta to obtain further evidence on the development of vascular bed. Methods: The term placenta samples were obtained from 10 healthy pregnancies following caesarean sections. Tissues were processed using routine plastic embedding technique; thin sections were contrasted with uranyl acetate & lead citrate; observed and photographed by transmission electron microscope. Results: Our examinations revealed that both sprouting and intussusceptive angiogenesis is present in floating villi of term placenta. Phases of intussusception were documented in various samples. Conclusion: The presence of intussusceptive angiogenesis will help our understanding of microvascular bed remodeling during pregnancy. We believe that this new finding will help us to determine the relation of microvascular bed development in normal and abnormal placentas.Item Prostaglandin F receptor expression in intrauterine tissues of pregnant rats(2014) Anadol, Elvan; Kanca, Halit; Yar, Atiye Seda; Helvacioglu, Fatma; Menevse, Sevda; Calguner, Engin; Erdogan, DenizIn this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term.Item Histomorphometric and Ultrastructural Evaluation of Long-Term Alpha Lipoic Acid and Vitamin B12 Use After Experimental Sciatic Nerve Injury in Rats(2016) Arikan, Murat; Togral, Guray; Hasturk, Askin Esen; Horasanli, Bahriye; Helvacioglu, Fatma; Dagdeviren, Atilla; Tekindal, Mustafa Agah; Parpucu, Murat; 0000-0002-6026-0045; 0000-0002-4060-7048; 0000-0003-0376-5589; 0000-0003-3142-1011; 27476916; AAH-8887-2021; AAE-5065-2019; U-9270-2018; S-4175-2018AIM: To analyze the therapeutic effects of long-term alpha lipoic acid (A-LA) and vitamin B12 use via histomorphometric methods and electron microscopy in the transected sciatic nerves of rats. MATERIAL and METHODS: Forty rats were randomized into five groups (n=8/group). In group I, 1 cm segment of sciatic nerve was resected without any other intervention. In group II (sham), following right sciatic nerve transection, primary epineurial anastomosis was performed by placing the edges of the nerve end-to-end. In group III (saline), after right sciatic nerve transection, the ends of the nerves were brought together and closed after application of intraperitoneal physiologic saline. In group IV, 2 mg/kg of alpha lipoic acid and in group V, 2 mg/kg of vitamin B12 was administered intraperitoneally before surgical intervention. RESULTS: Histomorphometric and electron microscopic analyses revealed that vitamin 312 did not prevent structural changes, abnormal myelination and g-ratio deviations regarding the functional aspects of the sciatic nerve. Alpha lipoic acid was more effective in restructuring the histomorphometric and structural aspects of the nerve with more myelinated fibers with optimal values (0.55-0.68) than vitamin B12 groups, in which the number of myelinated nerve fibers significantly decreased at optimal intervals (0.55-0.68). CONCLUSION: A-LA administration following peripheral nerve transection injury is more effective in promoting nerve healing regarding the structural aspects of the sciatic nerve compared to vitamin B12 and also myelination of nerve fibers by increasing g-values.Item Effect of Creatine on Rat Sciatic Nerve Injury: A Comparative Ultrastructural Study(2018) Helvacioglu, Fatma; Kandemir, Ersin; Karabacak, Busra; Karatas, Idil; Pecen, Ahmet; Ercan, Ipek; Sencelikel, Tugce; Dagdeviren, Attila; 0000-0002-6048-3951; 0000-0002-6026-0045; 0000-0001-8990-8282; 27858383; AAI-6791-2021; AAH-8887-2021; P-2877-2014AIM: Creatine is an endogenous molecule synthesized in the liver, kidney and pancreas from glycine and arginine and is important for mitochondrial metabolism. It is widely used as a supplement for improving muscle mass and function for many years. As it is expected to prevent apoptosis and diminish oxidative stress, it is also studied in a number of neurodegenerative diseases for its beneficial effect in recent years. We studied the effect of creatine on the peripheral nerve injury in an experimental rat crush injury model to obtain ultrastructural evidence. MATERIAL and METHODS: Animals were randomly divided into 3 groups having 5 animals in each group. Group 1 was the control group, Group 2 the trauma group and Group 3 the trauma+ creatine group. The first group served as sham control. In group 2 and group 3, sciatic nerves of the rats received crush injury using aneurysm clips. In group 3, daily 2 g/kg creatine monohydrate was administered via gavage after the trauma. Nerve samples were obtained at the 28th day after trauma for light and electron microscopic evaluation. RESULTS: Our comparative analysis results suggest a possible positive effect of creatine supplement on peripheral nerve regeneration as statistical analysis revealed significant differences between group 2 and group 3. Though our finding does not represent a miracle of regenerative support, beneficial usage of creatine is documented in the present study. CONCLUSION: Creatine supplement helps to diminish the harmful effects of peripheral nerve crush injury which is also supported by electron microscopy findings.