Researcher:
Söyler, Gizem

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PhD Student

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Gizem

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Söyler

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Söyler, Gizem

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2020 - 20228

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    Effects of corchorus olitorius and protacatechuic acid on diabetic rat testis tissue
    (Soc Chilena Anatomia, 2020) Mercan, Nedime; Toros, Pelin; Hanoğlu, Azmi; Kükner, Aysel; Söyler, Gizem; PhD Student; Graduate School of Health Sciences; N/A
    The aim of this study is to investigate the effects of Protocatechuic acid and Corchorus olitorius on sire (STZ) induced diabetic rat testis tissue. Randomly selected Wistar Albino rats were divided into five groups as; Diabetes Mellitus, Diabetes Mellitus treated with Corchorus Olitorus (STZ+CO), Diabetes Mellitus treated with Protacatechuic acid (STZ+PCA), Corchorus olitorius (CO), Protocatechuic acid (PCA) and Control. Diabetic model was generated by intraperitoneal injection of 60 mg/kg Streptozotosin. After 48 hours of the STZ injection, blood samples were collected from tail vein in order to measure blood glycose levels. Over 250 mg/d1, accepted as diabetic subjets and fed with 250 mg/kg Corchorus olitorius or 20 mg/kg PCA by oral gavage for three weeks. At the end of the experiment, right testes were removed and fixed in 10 % neutral formaldehyde for paraffme embedding. Sections were stained by HE, Masson trichrome, PAS and TUNEL for microscopic evaluation. Control, PCA-only and Corchorus olitorius-only treated group testes tissues showed a normal tissue organization, when degeneration in seminiferous tubules, the vacuolization, seperations in spermatogenic cell series, outpouring of cell groups in the lumen, vesicular body formation, liquid accumulation in the interstitial region and edema were observed in STZ induced diabetic models and untreated groups. Besides, higher amount of TUNEL (+) stained cells were determined in STZ group. On the other hand, blood glucose level and number of TUNEL (+) stained cells were decreased as a result of PCA and Corchorus olitorius treatment. Because of the reduction of blood glucose level and apoptotic cell numbers, PCA and Corchorus olitorius decreace the complications of diabetes mellitus induced rat testis
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    Parabiosis improves endothelial dysfunction in aged female mice
    (Elsevier, 2022) Farisoglu, Ulfet; Balcioglu, Ozlem; Ozcem, Barcin; Kilic, Ali Onder; Ulker, Seher Nasircilar; Kocer, Gunnur; Söyler, Gizem; PhD Student; Graduate School of Health Sciences; N/A
    Introduction: The study aims to investigate the effect of parabiosis method on endothelial dysfunction in naturally aging mice and determine the time projections for predicted improvement in the mentioned target group. Methods: The balb/c mice were separated into six groups, these being; isochronic old, heterochronic old (HP-O), isochronic young, heterochronic young, young control, and old control. After parabiosis protocol, animals were sacrificed at the third, fifth, seventh, and ninth weeks, and their thoracic aortas were isolated. The vasodilatation and vasoconstriction responses of the vessels were detected using potassium chloride and phenylephrine, acetylcholine (ACh), and sodium nitroprusside. Results: Aging had a significant decreasing effect on maximum ACh relaxation responses (P < 0.01). However, in the HP-O group, the maximum ACh relaxation response in the third week was significantly lower (P < 0.05), but this effect disappeared in the ninth week. Maximum phenylephrine contraction responses were lower in the heterochronic parabiosis group (P < 0.05). Conclusions: ACh responses increased at the end of the ninth week in the HP-O group, therefore, the parabiosis model may have an improving effect on endothelial dysfunction seen in aging.
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    Effects of corchorus olitorius and protocatechuic acid on cadmium-induced rat testicular tissue degeneration
    (Galenos Publ House, 2022) Komili, Katriye; Toros, Pelin; Çalış, İhsan; Kükner, Ayşel; Söyler, Gizem; PhD Student; Graduate School of Health Sciences; N/A
    Background/Aims: Cadmium element, a heavy metal, has toxic effects on the reproductive system. The current study investigates the possible therapeutic effects of Corchorus olitorius (CO) and Protocatechuic acid (PCA) on the damage caused by cadmium chloride on rat testicular tissue. Materials and Methods: Control, CO, PCA, cadmium chloride, cadmium chloride + PCA and cadmium chloride + CO was formed groups. CO and PCA was administered orally 250 mg/kg and 20 mg/kg respectively. Cadmium chloride dose of 3.5 mg/kg was administered intraperitoneally. At the end of the three-week experiment period, body weight of rats was measured then testicular tissues were removed and weighed separately. Testicular tissue sections were stained with, Hematoxylene & Eosin, Periodic Acid Shiff, Masson trichrome and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). TUNEL (+) apoptotic cells were counted and evaluated statistically. Results: Testicular weights of the cadmium-given group decreased significantly compared to the control groups. In the cadmium-administered group, basal membrane structures and seminiferous tubules were disrupted, tubules without sperm were observed, connective tissue and inflammatory cell increase and oedema occurred in the interstitial space. It was determined that degeneration was continuing in the treatment groups, but inflammatory cell numbers and oedema in the interstitial tissue were reduced. Additionally, the same seminiferous tubules with sperm were also observed. It was observed that apoptotic cells increased significantly in the cadmium-administered group compared to the control groups and decreased in the treatment groups. Conclusion: PCA and CO were realized to be unable to completely prevent but reduce the toxic effects of cadmium on testicular tissue.
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    P567 re-establishment of fertilization competency of the oocyte via CRISPR/dCas9 epigenome edition technology
    (Oxford Univ Press, 2021) N/A; N/A; N/A; N/A; N/A; N/A; Şahin, Gizem Nur; Söyler, Gizem; Kayabölen, Alişan; Kocabay, Ahmet; Taşkın, Ali Cihan; Karahüseyinoğlu, Serçin; PhD Student; PhD Student; PhD Student; Other; Other; Faculty Member; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; N/A; N/A; School of Medicine; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; N/A; N/A; 291296; 110772
    Study question: Is it possible to increase the decreased levels of the sperm-oocyte binding protein, Juno, to restore the fertilization capacity of the oocyte, via the use of the CRISPR/dCas9 activation system? Summary answer: JUNO domain (in the oocyte) suppressed with melamine was opened using the CRISPR/dCas9 system and sperm-oocyte binding and fertilization capability have been restored. What is known already: Melamine is a chemical that is widely used in the manufacture of laminates, plastics, etc. Evidence reveals that long-term exposure to melamine could damage reproductive systems in mammals leading to infertility. Izumo1 is the only cell surface protein expressed on sperm that is known to be essential for sperm-egg interaction in vivo. It was in vitro shown that high-dose feeding of melamine to female mice led to a significant decrease of JUNO on the plasma membrane of eggs. CRISPR/dCas9 system can provide the gene activation or repression to activate the target gene via Sam and Tet1 based systems. Study design, size, duration: Six different gRNAs were designed for the transfection of oocytes. Six-week-old mice were fed with melamine (50mg/kg/day) for 2 weeks via gavage. Melamine gavage, water gavage, and control groups (n = 15 /each group) were created. CRISPR activation plasmids (SAM) were given by piezo microinjection into the GV oocytes (n = 100 oocytes/each group). Fertilization capacity was evaluated by sperm binding assay, qPCR, Western blotting, and IF staining. Two technical replicates were used in molecular studies. Participants/materials, setting, methods 293T cells were transfected (dCas9 SAM plasmids+gRNA) with Fugene. Mice randomly were assigned to 3 groups (n = 15), as each was given orally a dose of 50mg/kg/d of melamine, only water or no water via gavage. Microinjection of plasmids was performed. Post-injection, oocytes were incubated until MII stage. For binding and fertilization evaluation, motile sperms were incubated with oocytes, and pronuclei were checked. Juno and IZUMO1 levels were evaluated by qPCR, Western blotting, and IF staining. Main results and the role of chance: As the SAM system is more efficient compared to the Tet1 system when tested in 293t cells, the SAM system was used for mouse experiments. As a result of qPCR performed in oocytes collected at the end of gavage, it was observed that the JUNO expression levels were decreased by 40 folds in melamine fed mice (p < 0.05). The decrease in the level of JUNO protein was demonstrated by IF stainings, and a decrease in the oocyte count along with abnormal uterine shapes was also observed in this group. IZUMO1 expression in motile sperms was demonstrated by qPCR before sperm binding assay and the position of the IZUMO 1 domain before the acrosome reaction was demonstrated by IF stainings. Sperm binding assay has demonstrated a 70% reduction in fertilization competency of melamine-treated oocytes (p < 0.05). SAM plasmids and JUNO gRNA were given to oocytes by piezo injection. By sperm binding experiments conducted to evaluate fertilization capacities after microinjection, it was shown that the fertilization capacity was restored by 75% (p < 0.05). Re-gaining of Juno expression in the oocytes was supported by a 60 fold increase in qPCR results. Recovery of JUNO protein expression in the oocytes was also demonstrated by IF stainings. Limitations, reasons for caution: There is no known promoter region for the JUNO gene in the mouse. Therefore, we designed gRNAs targeting possible promoter regions. However, we have used two activation systems(SAM and Tet1) that are widely used to open a closed gene, but other activation systems (acetylation, etc.) can also be tried. Wider implications of the findings: This study is valuable since: -it presents a possible cure for unsuccessful fertilization in related cases. -it possibly reveals melamine’s unknown way of action. - it presents a new approach as a sperm-binding assay to be used in IVF clinics since Juno can also be expressed in somatic cell lines. Trial registration number: non-clinical trials
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    Effect of kefir on increased apoptosis in liver and kidney in cisplatin toxicity
    (Universidad de la Frontera, 2022) Şah, Hüseyin; Gülmez, Nurhayat; Sayıner, Serkan; Sehirli, Ahmet Özer; Kükner, Aysel; Söyler, Gizem; PhD Student; Graduate School of Health Sciences; N/A
    Cisplatin is a chemotherapeutic agent inducing liver and kidney damage. In this study, we intended to investigate the impact of kefir beverage, an essential probiotic and functional food, on liver and kidney damage induced by cisplatin. Wistar albino rats were divided into four groups: Control, Cisplatin (single dose of 7 mg/kg, intraperitoneal), Kefir (2 ml/d, 7 d, oral gavage), and Cisplatin+Kefir (CK). At the end of day 7, animals were euthanized. Blood, kidney, and liver tissue samples were collected. For both tissues, biochemically ALT, AST, Urea, Creatine; histomorphologically, hematoxylin-eosin, Masson's Trichrome, and immunohistochemical staining of caspase-3, a marker of apoptosis, were performed. Serum urea and creatinine levels of the Cisplatin group were significantly higher than the Control group (p<0.05). In the CK group, kefir consumption decreased urea and creatinin levels approached to Control and Kefir groups. Cisplatin resulted in higher ALT and AST activities, indicating hepatocellular damage, compared to the Control group (p<0.05). Kefir consumption decreased ALT activities approached to both the Control and Kefir group. Histomorphological observations were in agreement biochemical results. In liver and kidney tissues, structural damage was observed with an increase in collagen fibers in the Cisplatin group, and Caspase-3 activity was immunohistochemically higher than in the other groups. In the CK group, collagen fiber increase, structural damage, and Caspase-3 activities were less than in the Cisplatin group. Kefir consumption alleviated liver and kidney damage. However, more research is required to understand such effect of kefir better.
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    PublicationOpen Access
    Protective effect of Coriandrum sativum extract against inflammation and apoptosis in liver ischemia reperfusion injury
    (Via Medica Journals, 2020) Kükner, A.; Toros, P.; Dede, G.; Meriçli, F.; Işık, S.; Edebul, O.; Özoğul, C.; Söyler, Gizem; PhD Student; School of Medicine
    Background: the aim of this study was to investigate the anti-inflammatory and antioxidant effects of Coriandrum sativum extract on liver ischemia reperfusion injury at light microscopic and biochemical levels. Material and methods: sham, ischemia/reperfusion injury (IRI), IRI+Coriandrum sativum extract and only Coriandrum sativum extract groups were formed. Sixty minutes of ischemia and 60 minutes of reperfusion were performed. In the treatment group, 300 mg/kg/day Coriandrum sativum was given by gavage. Hepatic tissues were fixed in 4% paraformaldehyde. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) enzymes were measured. Nuclear factor- kappa beta (NF-kappa B), Tumor necrosis factor-alpha (TNF-α) and Caspase-3 (Cas-3) 2 immunohistochemistry staining was performed. Microscopic scoring was performed in terms of sinusoidal congestion, vacuolization, and necrosis. Results: sinusoidal enlargement and diffuse congestion, Kupffer cell increase, neutrophil increase in necrotic areas, and vacuolization in hepatocytes, and bile duct proliferation in the portal triad were observed in ischemia/reperfusion hepatic tissue. Very rare, necrotic areas were observed in the Coriandrum sativum treatment group, while congestion and vacuolization and bile duct proliferation were decreased compared to the ischemic group. The AST and ALT levels were increased in the IRI and IRI+Coriandrum sativum groups. When compared to the IRI group, the AST and ALT levels of the Coriandrum sativum were considerably decreased. The IRI and IRI+Coriandrum sativum groups had statistically significant differences in ALP compared to that of the Coriandrum sativum and Sham groups. There was no significant difference between the ALP levels of the IRI and IRI+Coriandrum sativum groups TNF-α, NF-kappa B and Cas-3 immune positive stained hepatocytes were numerous and widely observed in the injury group. There were positive TNF-α immunohistochemical staining Kupffer cells in the IRI group. In the group treated with Coriandrum sativum, Kupffer cells were not stained, while TNF-α, NF-kappa B and Cas-3 expressing hepatocytes were found to be decreased compared to the IRI group. When the expression values of the TNF-α, NF-kappa B and Cas-3 groups were evaluated statistically, it was seen that there was a significant decrease in the group treated with Coriandrum sativum. Conclusions: it was found that Coriandrum sativum extract decreased proinflammatory cytokine TNF-α and apoptotic cell death and liver enzymes in liver ischemia reperfusion injury.
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    PublicationOpen Access
    Protein scaffold-based multimerization of soluble ACE2 efficiently blocks SARS-CoV-2 infection in vitro and in vivo
    (Wiley, 2022) Ulbegi Polat, Hivda; Yıldırım, İsmail Selim; Kayabölen, Alişan; Akcan, Uğur; Özturan, Doğancan; Şahin, Gizem Nur; Değirmenci, Nareg Pınarbaşı; Bayraktar, Canan; Söyler, Gizem; Sarayloo, Ehsan; Nurtop, Elif; Özer, Berna; Esken, Gülen Güney; Barlas, Tayfun; Doğan, Özlem; Karahüseyinoğlu, Serçin; Lack, Nathan Alan; Kaya, Mehmet; Albayrak, Cem; Can, Füsun; Solaroğlu, İhsan; Önder, Tuğba Bağcı; PhD Student; PhD Student; Master Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; Koç University Hospital; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 170418; 110772; 120842; 10486; N/A; 103165; 102059; 184359
    Soluble ACE2 (sACE2) decoys are promising agents to inhibit SARS-CoV-2, as their efficiency is unlikely to be affected by escape mutations. However, their success is limited by their relatively poor potency. To address this challenge, multimeric sACE2 consisting of SunTag or MoonTag systems is developed. These systems are extremely effective in neutralizing SARS-CoV-2 in pseudoviral systems and in clinical isolates, perform better than the dimeric or trimeric sACE2, and exhibit greater than 100-fold neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag fused to a more potent sACE2 (v1) achieves a sub-nanomolar IC50, comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutations for variants of concern, including delta and omicron, are also neutralized efficiently with multimeric sACE2. Finally, therapeutic treatment of sACE2(v1)-MoonTag provides protection against SARS-CoV-2 infection in an in vivo mouse model. Therefore, highly potent multimeric sACE2 may offer a promising treatment approach against SARS-CoV-2 infections.
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    PublicationOpen Access
    Effects of corchorus olitorius and protacatechuic acid on diabetic rat testis tissue
    (Sociedad Chilena de Anatomia, 2020) Mercan, Nedime; Toros, Pelin; Hanoǧlu, Azmi; Kükner, Aysel Şahap; Söyler, Gizem; PhD Student; Graduate School of Health Sciences
    The aim of this study is to investigate the effects of Protocatechuic acid and Corchorus olitorius on streptozotocin (STZ) induced diabetic rat testis tissue. Randomly selected Wistar Albino rats were divided into five groups as; Diabetes Mellitus, Diabetes Mellitus treated with Corchorus Olitorus (STZ+CO), Diabetes Mellitus treated with Protacatechuic acid (STZ+PCA), Corchorus olitorius (CO), Protocatechuic acid (PCA) and Control. Diabetic model was generated by intraperitoneal injection of 60 mg/kg Streptozotosin. After 48 hours of the STZ injection, blood samples were collected from tail vein in order to measure blood glycose levels. Over 250 mg/dL accepted as diabetic subjets and fed with 250 mg/kg Corchorus olitorius or 20 mg/kg PCA by oral gavage for three weeks. At the end of the experiment, right testes were removed and fixed in 10 % neutral formaldehyde for paraffine embedding. Sections were stained by HE, Masson trichrome, PAS and TUNEL for microscopic evaluation. Control, PCA-only and Corchorus olitorius-only treated group testes tissues showed a normal tissue organization, when degeneration in seminiferous tubules, the vacuolization, seperations in spermatogenic cell series, outpouring of cell groups in the lumen, vesicular body formation, liquid accumulation in the interstitial region and edema were observed in STZ induced diabetic models and untreated groups. Besides, higher amount of TUNEL (+) stained cells were determined in STZ group. On the other hand, blood glucose level and number of TUNEL (+) stained cells were decreased as a result of PCA and Corchorus olitorius treatment. Because of the reduction of blood glucose level and apoptotic cell numbers, PCA and Corchorus olitorius decreace the complications of diabetes mellitus induced rat testis.