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Öğe A different view on the pathophysiology of Parkinson's disease: a descendent neurochemical hypothesis?(Wolters Kluwer Medknow Publications, 2019) Yuluğ, Burak; Ozansoy, Mehmet; Çankaya, Şeyda[No abstract available]Öğe A different view on the platelet aggregation inhibitor clopidogrel - a well-suitable anti-oedema agent in a preclinical model of brain injury?(Czech Medical Soc, 2019) Günal, Mehmet Yalçın; Yuluğ, Burak; Çağlayan, Berrak; Ozansoy, Mehmet; Kılıç, Ülkan; Keskin, İlknur; Kılıç, ErtuğrulAim: The neuroprotective effects of clopidogrel have already been shown in various experimental models. Taking into account the fact that clopidogrel is well tolerated and approved for use in various clinical settings, it can be an attractive candidate for further clinical investigations, especially when the anti-oedema effect appears to be a reasonable adjuvant strategy, such as in brain injury (BI). Here we aimed to examine the neuroprotective role of clopidogrel in BI. Methods: To investigate the effects of clopidogrel, we induced BI in mice using a cold trauma model and evaluated the underlying cell survival/death mechanisms via cresyl violet, TUNEL staining and western blot analysis. Results: Clopidogrel at a dose of 3 mg/kg led to a significant reduction in brain swelling. Similar decreases were observed with 10 mg/kg and 30 mg/kg of clopidogrel. We also have shown that clopidogrel blocks the prominent inflammatory injury pathways and exerts a significant anti-apoptotic effect (3 and 30 mg/kg), which has boon associated with increased neuronal cell survival pathways. Clopidogrel (3, 10 and 30 mg/kg) dose-dependently altered the JNK, p-38, AKT, ERK and p53 levels. Conclusion: Our findings demonstrate that clopidogrel can be a novel candidate for the reduction of post-traumatic BI and oedema. We propose that it can be applied mainly in the acute phases of cerebral ischaemia, which is characterized by haemorrhagic transformation and brain oedema.Öğe Combined therapy with probiotic VSL#3 and Omega-3 fatty acids attenuates colonic injury and inflammation in chronic DNBS-induced colitis in mice(2022) Yoldaş İlktaç, Havvanur; Kızıltan, Gül; Lanpir, Aslı Devrim; Ozansoy, Mehmet; Günal, Mehmet Yalçın; Özmen Togay, Sine; Keskin, İlknur; Özdemir, Ekrem M.; Kılıç, UlkanWe published the abovementioned article about probiotic mixture VSL#3 on October 6, 2021. Since the product was named VSL#3 in our purchasing process in early 2016, it is referred to as VSL#3 in our article. In addition, the product currently known as VSL#3 is not the same as De Simone Formulation. De Simone Formulation is now available as Visbiome® in the United States and Vivomixx® in Europe. The authors would like to apologise for any inconvenience causedÖğe Melatonin affects the release of exosomes and tau-content in in vitro amyloid-beta toxicity model(Churchill Livingstone, 2020) Ozansoy, Mehmet; Ozansoy, Muzaffer Beyza; Yuluğ, Burak; Çankaya,Şeyda; Kılıç, Ertuğrul; Göktekin, Şule; Kılıç, ÜlkanBackground: Recent studies have been revealed that oxidative damage is the main cause of aging and age-related neurodegenerative diseases like Alzheimer's disease (AD). Melatonin is secreted from the pineal gland and its secretion has been found to be altered in AD. In the last decade the role of exosomes in spreading toxic proteins and inducing the propagation of diseases like AD has been discussed. However, it is not known how melatonin affects the amount of exosomes released from the cells and the content of the exosomes. Objective: Herein, we investigated the possible role of melatonin treatment in the releasing of exosomes and exosomal tau content in an in vitro A? toxicity model. Method: SH-SY5Y cell line was used. The optimum concentration of A? was determined by cell viability and cell proliferation tests. Melatonin (100 µM) was applied before and after A? application. Total exosomes isolated from cell culture media were immunoprecipitated. The amount of released exosomes and their tau content were analyzed by Western blots. Results: Our data demonstrated for the first time that melatonin treatment clearly affected the amount of released exosomes. It would decrease the amyloid beta load and toxicity by inhibiting exosome release. We also demonstated that melatonin also affected the level of tau carried by exosomes depending on whether melatonin was applied before or after A? application. Conclusion: It is considered that the effect of melatonin in the release of exosomes and exosomal tau content would contribute the development of therapeutic strategies in AD and related disorders. © 2019 Elsevier LtdÖğe Minocycline increases in-vitro cortical neuronal cell survival after laser induced axotomy(Bentham Science Publ Ltd, 2020) Yuluğ, Burak; Ozansoy, Mehmet; Alökten, Merve; Ozansoy, Muzaffer; Çankaya, Şeyda; Hanoğlu, Lütfü; Kılıç, ErtuğrulBackground: Antibiotic therapies targeting multiple regenerative mechanisms have the potential for neuroprotective effects, but the diversity of experimental strategies and analyses of non-standardised therapeutic trials are challenging. In this respect, there are no cases of successful clinical application of such candidate molecules when it comes to human patients. Methods: After 24 hours of culturing, three different minocycline (Sigma-Aldrich, M9511, Germany) concentrations (1 mu M, 10 mu M and 100 mu M) were added to the primary cortical neurons 15 minutes before laser axotomy procedure in order to observe protective effect of minocycline in these dosages. Results: Here, we have shown that minocycline exerted a significant neuroprotective effect at 1 and 100 mu M doses. Beyond confirming the neuroprotective effect of minocycline in a more standardised and advanced in-vitro trauma model, our findings could have important implications for future studies that concentrate on the translational block between animal and human studies. Conclusion: Such sophisticated approaches might also help to conquer the influence of humanmade variabilities in critical experimental injury models. To the best of our knowledge, this is the first study showing that minocycline increases in-vitro neuronal cell survival after laser-axotomy.Öğe Role of erythropoietin and its receptor in the development of endometriosis in rats(2019) Günal, Mehmet Yalçın; Ozansoy, Mehmet; Kılıç, Ülkan; Keskin, İlknur; Özdemir, Ekrem Musa; Aslan, İsmail; Kılıç, ErtuğrulObjective: Besides its hematopoietic function, erythropoietin (EPO) may protect tissues from degenerative disorders. As such, EPO and its receptors were revealed in nonhematopoietic cells, including stromal and endometrial epithelial cells. However, the role of EPO in endometrial disorders is still unknown. Here, we aimed to examine the role of EPO and its receptor activation in the development of endometriosis in rats. Material and Methods: Animals were treated with EPO, darbepoietin (the synthetic form of EPO) or EPO’s receptor activator, methoxy polyethylene glycol-epoetin beta (MIRCERA), after development of endometriosis. Endometriosis was induced by estrogen-administration following surgical attachment of endometrial surface on the inner abdominal wall. Treatments were started 3 weeks after induction of endometriosis and continued for the following 3 weeks. For the analysis of recurrence of endometriosis, additional analyses were conducted 3 weeks after cessation of treatments. Results: As compared with vehicle-treated animals, lesion size was reduced significantly and recurrence of endometriosis was not observed in all treatment groups. Histopathologic examination revealed that EPO and darbepoietin were more effective than MIRCERA- and vehicle-treated animals. Conclusion: Here we provide evidence that EPO is a promising candidate for the treatment of endometriosis. Our histopathologic results in particular indicate that EPO is more effective than its receptor activator MIRCERA in the development endometriosis. (J Turk Ger Gynecol Assoc 2019; 20: 41-6)Öğe Squalene attenuates the oxidative stress and activates AKT/mTOR pathway against cisplatin-induced kidney damage in mice(2019) Sakul, Arzu; Ozansoy, Mehmet; Elibol, Birsen; Ayla, Şule; Günal, Mehmet Yalçın; Yozgat, Yasemin; Kılıç, ÜlkanThe clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneys that lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to cope with nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squalene against cisplatin-induced oxidative stress and kidney damage in mice. Single dose of cisplatin (7 mg/kg) was given to male Balb/c mice. Squalene (100 mg/kg/day) was administered orogastrically to mice for 10 days. Following sacrification, molecular alterations were investigated as analysis of the levels of oxidative stress index (OSI), inflammatory cytokines and cell survival-related proteins in addition to histopathological examinations in mice kidney tissue. The level OSI and Interferon-gamma (IFN-?) decreased in the cisplatin and squalene cotreated mice compared to cisplatin-treated mice. Squalene treatment also increased the activation of protein kinase B (AKT). Furthermore, cisplatin-induced inactivation of mammalian target of rapamycin (mTOR) and histopathological damages were reversed by squalene. It may be suggested that squalene ameliorated the cisplatin-induced histopathological damages in the kidneyÖğe The association between Hba1c levels, olfactory memory and cognition in normal, pre-diabetic and diabetic persons(Bentham Science Publishers, 2020) Yuluğ, Burak; Saatçi, Özlem; Işıklar, Aysun; Hanoğlu, Lütfü; Kılıç, Ulkan; Ozansoy, Mehmet; Kılıç, ErtuğrulBackground and Aim: Recent data have shown that olfactory dysfunction is strongly related to Alzheimer’s Disease (AD) that is often preceded by olfactory deficits suggesting that olfactory dysfunction might represent an early indicator of future cognitive in prediabetes. Methods: We have applied to a group of normal (n=15), prediabetic (n=16) and type 2 diabetic outpatients (n=15) olfactory testing, 1.5-T MRI scanner and detailed cognitive evaluation including the standard Mini-Mental State Examination (MMSE) form, Short Blessed Test (SBT), Letter Fluency Test (LFT) and the category fluency test with animal, Fruit and Vegetable Naming (CFT). Results: We have shown that Odour Threshold (OT), Discrimination (OD), and Identification (OI) scores and most cognitive test results were significantly different in the prediabetes and diabetes group compared to those in the control group. OD and OT were significantly different between the prediabetes and diabetes group, although the cognitive test results were only significantly different in the prediabetes and diabetes group compared to those in the control group. In evaluating the association between OI, OT, OD scores and specific cognitive tests, we have found, that impaired olfactory identification was the only parameter that correlated significantly with the SBT both in the pre-diabetes and diabetes group. Although spot glucose values were only correlated with OT, HbA1c levels were correlated with OT, OD, and OI, as well as results of the letter fluency test suggesting that HbA1c levels rather than the spot glucose values play a critical role in specific cognitive dysfunction. Conclusion: To the best of our knowledge, this is the first prospective study to demonstrate a strong association between olfactory dysfunction and specific memory impairment in a population with prediabetes and diabetes suggesting that impaired olfactory identification might play an important role as a specific predictor of memory decline. © 2020 Bentham Science Publishers.Öğe The effect of probiotic and omega-3 supplements on total oxidant and total antioxidant levels in experimental colitis(2021) İlktaç, Havvanur Yoldaş; Kızıltan, Gül; Ozansoy, Mehmet; Kılıç, Ülkan; Togay, Sine Özmen; Keskin, İlknur; Özdemir, Ekrem Musa; Günal, Mehmet YalçınObjective: Treatment of inflammatory bowel disease (IBD) usually involves medical therapy. For this reason, it is recommended to seek alternative treatment methods such as nutritional therapy. The aim of the study is to evaluate the effects of probiotics and omega-3 fatty acids on total oxidant and total antioxidant levels in an experimental colitis model. Methods: Mice were randomly divided into five groups (n= 10/group) as healthy group, colitis group, group treated with probiotics (VSL#3), group treated with omega-3 (w-3), and group treated with both probiotics and omega-3. To induce experimental colitis, 200 mg/kg dinitrobenzene sulfonic acid (DNBS) + 30% ethanol combination was rectally administered to anesthetized mice. Total oxidant (TOS) and total antioxidant (TAS) levels were measured at the tissue level. Results: Lower concentrations of TOS were observed in the probiotics groups (2.11 +/- 0.23 mmol H2O2 Eq/L), probiotics+omega-3 (2.56 +/- 1.18 mmol H2O2 Eq/L), and omega-3 (3.02 +/- 1.88 mmol H2O2 Eq/L) groups compared to the colitis group (3.11 +/- 0.91 mmol H2O2 Eq/L) (p>0.05). Higher TOS and TAS level were observed in the control colitis group compared to other groups; however, the differences were not statistically significant. Conclusion: Our findings showed that TAS and TOS levels were positively affected by the use of probiotic supplements in IBD. It was determined that using w-3 alone was ineffective in decreasing TOS levels. Studies with higher dosages and longer treatment periods are needed to better observe the effects of nutritional supplements on TOS and TAS parameters in inflammatory bowel diseases.Öğe The effect of rifampicin on the neuronal cell survival in primary cortical neuron culture after laser axotomy(Alanya Alaaddin Keykubat Üniversitesi, 2019) Ozansoy, Mehmet; Coşkun, Ebru; Ozansoy, Muzaffer Beyza; Çankaya, Şeyda; Günal, Mehmet Yalçın; Bayraktaroğlu, Zübeyir; Hanoğlu, LütfüAim: Neurodegeneration caused by the axonal injury is a widely seen phenomenon in spinal cord and traumatic brain injuries. Due to the disintegration of the synaptic connection neurotrophic factors could not be transported retrogradely towards the cell body and the deprivation of the trophic factors lead to the degeneration and death of the injured neuron. Rifampicin is an antibiotic exhibiting several neuroprotective functions in various neurodegenerative conditions. Here we aim to investigate the acute neuroprotective effect of rifampicin in primary cortical neuron culture in which neurons are axotomized by laser axotomy. Methods: Neonatal male mice were used in order to isolate cortical neurons. Isolated primary cortical neurons were cultured. After 24 hours three different rifampicin concentrations (1 µM, 10 µM and 100 µM) were applied to the neurons and after 15 minutes of rifampicin addition, neurons were laser axotomized. Viability of the cells was evaluated by propidium iodide staining after 24 hours of axotomy. Results: Laser axotomy decreases the cortical neuron viability significantly by 80.45%, while rifampicin pre-treatment increases their viability in all three dosages in a statistically significant manner. Conclusion: Rifampicin has an acute neuroprotective effect on the viability of the laser axotomized cortical neurons.
