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Öğe Adrenergic receptor behaviors of mesenchymal stem cells obtained from different tissue sources and the effect of the receptor blockade on differentiation(Taylor & Francis Ltd, 2022) Maytalman, Erkan; Alizadeh Yegani, Arash; Kozanoglu, Ilknur; Aksu, FaziletIn this study, it was aimed to analyze behavioral changes of adrenergic receptors (ARs) in first three passages and osteogenic/adipogenic differentiation of mesenchymal stem cells (MSCs) derived from placenta fetal membrane (FM) and bone marrow (BM). It was also aimed to evaluate effects of receptor blockade on differentiation. We obtained first three passages of MSCs from placenta and BM samples. For cell identification, the cells were analyzed by flow cytometry using CD34, CD45 and CD3, CD105 antibodies in each passage. The effects of propranolol and phenoxybenzamine at incremental doses were analyzed by MTT. In addition, cell cultures were separately maintained with the blockers or without after second passage. After each passage and differentiation, alpha 1A, alpha 1B, alpha 2A, alpha 2B, beta 1, beta 2, beta 3 AR-mRNA expressions analyzed by RT-qPCR technique. BMP6 and PPARG mRNA expressions only after differentiation and passage 3 were analyzed. A microscopic examination was also performed. Our results showed that AR expression behaviors were different in MSCs obtained from different tissue sources. In particular, alpha(1A)-AR and alpha(2A)-AR were expressed with considerably high coefficients in differentiation under blocker effect in BM-derived MSCs. No such coefficients were observed in any group of placental MSCs. In addition, it was found that the blockers stimulated adipogenesis in BM-derived MSCs during osteogenic differentiation. MSCs exhibit protein expressions that vary according to source of tissue and differentiation. Given that MSCs from different sources are used for repair and modulation, our study makes implications of this variable expression intriguing in the clinical practice.Öğe An in vitro pilot study investigating placenta-derived mesenchymal stem cell coating on polypropylene mesh materials(Springer London Ltd, 2024) Aslan, Erdogan; Maytalman, Erkan; Samur, Dilara Nemutlu; Kole, Emre; Gunizi, Ozlem CerenIntroduction and hypothesis: Polypropylene meshes (PM) used in pelvic organ prolapse surgery are being withdrawn from the market. Although concerns about the usage of PMs in stress incontinence surgery have been raised, it is still one of the best methods of curing stress urinary incontinence. With advancements in stem cell-based therapies, especially mesenchymal stem cells (MSCs), it is believed that coating the synthetic meshes with MSCs may minimize excessive tissue reactions ultimately leading to clinical problems such as pain, erosion or extrusion of the implanted material. In our study we tried to show the possibility of coating the PM with placenta-derived MSCs.Methods: Mesenchymal stem cells obtained from six placentas were isolated, cultured, and identified. MSCs were then soaked in either fibronectin or collagen prior to co-culturing with strips of PMs. One group is used as a control, and hence was not pretreated before co-culturing. Specimens were fixed and stained with both Gram and hematoxylin and eosin and marked with Vybran Dil and DAPI. All preparations were examined under a light microscope. The IMAGEJ program was utilized to determine the surface area of meshes coated with MSCs.Results: We clearly showed that PMs can be coated successfully with placenta-derived MSCs. The percentage of the coated area is significantly increased when meshes were pretreated with fibronectin or collagen (p<0.0001).Conclusions: Placenta-derived MSCs can successfully coat PMs. The immunomodulatory properties of MSCs, which may be of great advantage in preventing the side effects of meshes, should be tested by in vivo and hopefully human studies before clinical applications.Öğe Analgesic use may not decrease in the first postoperative year in patients underwent total knee arthroplasty due to advanced osteoarthritis(Elsevier B.V., 2024) Aslan, Ahmet; Maytalman, Erkan; Gulcu, AnilBackground: Total knee arthroplasty (TKA) is expected to relieve pain and reduce the use of analgesics in patients with advanced knee osteoarthritis. However, in some cases, there is no relief in the pain of the patients and the use of analgesics continues. The aim of this study was to compare analgesic consumption one year before and after TKA in the same patient group and to evaluate whether there is a decrease in analgesic consumption after TKA. Method: The cumulative amounts of analgesia used by the patients in the one-year periods before and after the operation were checked from the automated patient records system and the national systems showing drug prescriptions. The dosages of all the analgesics used in the one-year periods before and after the operation were calculated and converted to oral morphine equivalents (OME). The demographic data of the patients, cumulative OME and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used in the assessment. Results: It was observed that there was a statistically significant improvement in Womac scores after the treatment compared to the pre-treatment. Although the mean amount of analgesics decreased compared to pre-treatment, it was not statistically significant. Also, age and preoperative analgesic use were found to be the two most important factors in relation to total postoperative analgesic consumption. Conclusion: The results of this study indicate that there may not be a substantial reduction in the use of analgesic by patients within the first year after TKA. Furthermore, the age and preoperative analgesic use were identified as the two primary factors influencing postoperative analgesic consumption. Level of evidence: Retrospective Cohort Study. © 2024 Delhi Orthopedic AssociationÖğe Biological behaviors of muscarinic receptors in mesenchymal stem cells derived from human placenta and bone marrow(Mashhad Univ Med Sciences, 2020) Yegani, Arash Alizadeh; Maytalman, Erkan; Kozanoğlu, İlknur; Terzi, Menderes Yusuf; Aksu, FaziletObjective(s): Cells perform their functional activities by communicating with each other through endogenous substances and receptors. Post-translation, stem cells function properly in new host tissue by carrying specific cell surface receptors. We aimed to characterize muscarinic receptor subtypes in mesenchymal stem cells (MSCs) together with osteogenic and adipogenic differentiation markers. Materials and Methods: mRNA levels of 5 muscarinic receptor subtypes (CHRM1 to 5), BMP-6, and PPAR gamma during osteogenic and adipogenic differentiation, under the effect of atropine blockade, were measured in MSCs obtained from human fetal membrane (FM) and bone marrow (BM). Additionally, the effect of atropine on differentiation in the 1st, 2nd, and 3rd passages of MSCs, obtained from human FM and BM, were analyzed by RT-qPCR. Results: CHRM1 mRNA levels increased in the FM group, while decreasing in the BM group. We found significant decreases in CHRM3 and CHRM5 mRNA levels in FM and BM groups, respectively. Atropine had variable effects based on cell source and receptor type. BMP-6 mRNA levels in differentiated osteogenic cells increased significantly compared to undifferentiated cells in both FM and BM groups. In MSCs derived from both sources, PPAR gamma mRNA levels in differentiated adipogenic cells increased significantly. Atropine showed no effect on MSCs differentiation. Conclusion: These results indicate that expressions of muscarinic receptors in MSCs derived from BM and FM can vary and these cells keep the potential of osteogenic and adipogenic differentiation in vitro. Besides, atropine had no effect on adipogenic and osteogenic differentiation of MSCs.Öğe Covid-19 Pandemisi ile Gündeme Gelen İlaçlar ve Potansiyel Etkin Olabilecek Auranofin’in Değerlendirilmesi(2023) Candan, Ibrahım Aydın; Maytalman, Erkan; Gülpak, Malik EjderSars-Cov 2 virüsünün neden olduğu ve Çin’den yayılarak dünyanın tamamını etkileyen Covid-19 salgınında, enfekte bireylerin tedavisini sağlamak amacıyla birçok ilaç denenmekte ve kullanılmaktadır. Bununla birlikte profilaksi için dünyanın dört bir yanındaki araştırma laboratuvarlarında yeni tip korona virüs için aşılar geliştirilmiş ve uygulamaya başlanmıştır. Bu gelişmelere rağmen aşının profilaktik etkinliği ve kullanılan ilaçların tedavideki etkinliği konusunda tartışmalar mevcuttur. Bu durumlar özellikle hastalığın tedavisinde alternatif acil yeni arayışlara yönlendirmektedir. Altın partikülleri içeren bir ilaç olan Auranofin’in (AF) antiviral, anti-inflamatuar ve immün sistemi baskılama özelliklerinden dolayı Covid-19 enfeksiyonunun neden olduğu sitokin fırtınası ve aşırı immün reaksiyonları yönetebileceği öngörülmektedir. Bu derlemedeki amacımız, covid-19 üzerine AF’nin terapötik potansiyele sahip olup olmayacağını etki mekanizmaları ve yapılan çalışmalar üzerinden değerlendirmektir.Öğe Effect of milk and whey on proliferation and differentiation of placental stromal cells(Springer, 2023) Boga, Bircan; Akbulut, Merve; Maytalman, Erkan; Kozanoglu, IlknurFetal bovine serum (FBS), which is widely used in cell culture media, has the potential to cause medical and ethical problems. Here, an experimental study using milk or whey proteins containing essential nutrients and growth factors is presented to limit the use of FBS in cell culture media produced for cell and tissue regeneration. Study groups were formed by culturing human placenta mesenchymal stem cells, known to have high proliferation and differentiation capacity, with milk or whey solution at increasing concentrations, alone or in combination with FBS. Osteogenic and adipogenic differentiation capacities of proliferating cells were observed in FBS, milk or whey groups. Milk, whey or FBS groups obtained in P3 and after differentiation were separately analyzed for protein mRNA expression by reverse transcriptase-polymerase chain reaction (RT-qPCR). Fibroblast Growth Factor 2 (FGF2), Octamer-binding Transcription Factor 4 (OCT4), Bone Morphogenetic Protein 6 (BMP6), and adipogenic differentiation marker Peroxisome Proliferator-Activated Receptor Gamma (PPARG) were analysed by RT-qPCR. Proliferation was more pronounced in FBS alone and in its combinations with milk-whey compared to the groups in which only milk and whey were used. OCT4 mRNA and FGF2 mRNA expression decreased in differentiated cells. BMP6 mRNA expression increased with osteogenic and adipogenic stimuli. As expected, PPRG expression also increased with adipogenic stimulation. With this experimental study, evidence has been obtained that milk or whey can provide nutritional support to the culture media of repair cells and preserve the functional capacity of the cells, with a slightly more limited capacity than FBS. [GRAPHICS] .Öğe Elevated Blood Levels of VEGF Exhibiting Positive Correlation with HIF-1? in Obesity: A Single Center Study(2025) Uluergüven, Nazmiye; Eksi, Durkadin Demir; Maytalman, Erkan; Gunesacar, RamazanAim: The objective of this study was to investigate the relevance of plasma hypoxia-inducible factor-1 alpha (HIF-1?) and vascular endothelial growth factor (VEGF) levels in obesity and their associations with body mass index (BMI), body fat percentage, and waist to-hip ratio. Material and Methods: The study included 45 obese subjects and 28 healthy controls recruited from a private clinic in Manavgat, Antalya. The measurement of BMI, percentage of body fat, and waist-to-hip ratio was conducted in all subjects using a bioelectrical impedance analysis device. The plasma levels of HIF-1? and VEGF were measured using the micro-ELISA method. Results: In the Mann-Whitney U test, HIF-1? levels were similar in obese subjects (median=1.439 ng/L [Interquartile range (IQR)=11.62, min-max=0.904-12.53] and control group (median=1.377 ng/L [1.323, 0.852-2.175], p=0.0821). VEGF levels were found to be significantly higher in obese subjects compared to the controls (medians; 729.8 ng/L [5515, 485.3-6000] vs. 589.5 ng/L, [416.8, 396.4-813.2], respectively, pÖğe INHIBITORY EFFECT OF CELL PHONES AGAINST HUMAN BREAST CANCER AND MYELOID LEUKEMIA CELLS GROWTH IN CULTURE MEDIA(2023) Boğa, Bircan; Akbulut, Merve; Maytalman, Erkan; Kozanoglu, IlknurObjective: There is current news that emerges regarding the relationship between the magnetic effects of cell phones and some types of cancer. In spite of the studies carried out, the level of evidence of this news is low, and also the relationship between the magnetic effects of cell phones and other types of cancer is not certain except for brain cancer. In this study, it is aimed to examinethe effects of magnetic field of cell phones on the samples of breast cancer human myeloid leukemia cell growth. Methods: In the study, breast cancer MCF-7 and leukemia K562 cell lines were used as the source of cancer cells. During the six-day cell culture, cancer cells were subjected to the effects of cell phone by using a telephone call program (Automated outbound call software). The system made 6 calls for 1 minute for each call once in 144 minutes from a fixed line. The number of cultured cells and proliferation capacities of the two types of tumor cells in the control and experimental groups were assessed. Results: The number of cancer cells, which were subjected to the effects of cell phone as a result of the culture of tumor cells, was found lower when compared with control group (7500000 ± 100000 vs 6625000 ± 225000 for MCF-7; 15412500 ± 112500 vs 13700000 ± 250000 for K562; P < 0.05 for both). In MTT test, it was found out that two types of cell proliferation were inclined to slow down with the effect of cell phone. Conclusion: The results can be translated that cell phone may inhibit neoplastic transformation, and this observation may promote to initiate new clinical studies both for healthy people and for patients with cancer.Öğe Metamizole limits proliferation in chronic myeloid leukemia cells and triggers apoptosis via the bax/bcl-2/caspase-3 cascade(Humana Press Inc, 2025) Maytalman, Erkan; Samur, Dilara NemutluMetamizole is a controversial non-steroidal anti-inflammatory drug because it may cause agranulocytosis usually in long-term use. It may reduce proliferation while increasing apoptosis in some cancer cells. In our study, the effects of increasing concentrations of metamizole on chronic myeloid leukemia (CML) cell line K562 were evaluated in terms of proliferation and apoptosis. K562 cells were cultured with 1,10,50,100 mu M concentrations of metamizole in addition to the control group. The effect on cell proliferation was determined by MTT and analysis of mitotic cell counts. The apoptotic effects were analyzed by flow cytometry using Annexin V/Propidium iodide, ELISA for caspase-3 concentrations, and RT-qPCR for Bax-Bcl-2 mRNA expression levels. Evaluations were performed for 24 and 48 h of exposure. MTT assay revealed that metamizole limited the proliferation of cells at 10 mu M concentration. Caspase-3 concentrations increased in cells exposed to concentrations of 50 mu M and above. Flow cytometry results obtained using Annexin V/PI showed that especially 50 and 100 mu M concentrations promoted apoptosis compared to the control. Bcl-2 mRNA expression was also significantly decreased at concentrations of 50 and 100 mu M, while Bax mRNA expression was significantly increased only for 100 mu M. Mitotic cell numbers also decreased with increasing concentrations. The known adverse effect of metamizole, agranulocytosis, suggests it may negatively affect cell proliferation. In this study, metamizole had both antiproliferative and pro-apoptotic effects on K562. The results of our study indicate that the synergistic effects of metamizole in the treatment of CML, especially in cases resistant to tyrosine kinase inhibitors, should be evaluated with further studies under in vitro and in vivo conditions.Öğe Metamizole modulates the concentrations of cytokines and hematopoietic growth factors in an experimental model of depression(2025) Maytalman, Erkan; Kıroğlu, Olcay; Berktaş, Fatih; Samur, Dilara Nemutlu; Aksu, FazıletObjective: In recent years, evidence of antidepressant-like activity of non-steroidal anti-inflammatory drugs has been presented. Furthermore, associations between cytokines, which are important components of the immune system, as well as hematopoietic growth factors and depression have also been demonstrated. In this study, it was aimed to analyze the effect of metamizole on the expression of cytokines and hematopoietic growth factors in mice exposed to unpredictable stress models. Method: In order to develop chronic depression behaviors, an unpredictable chronic mild stress model was applied to mice. The depression group was not given any drug and other groups were given 100 and 200 mg/kg metamizole. Forced swimming test was performed to evaluate the effect of metamizole against depression. Relative concentrations of interleukin-1 alpha (IL-1?), IL-1 beta (IL-1-ß), IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, Interferon gamma (IFN-?)-, tumor necrosis factor-alpha (TNF-?), Granulocyte-colony-stimulating factor (G-CSF), and Granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in serum samples of animals with semi-quantitative ELISA. Results: In the forced swimming test, the immobility time of the depression group significantly increased compared to the control group. The immobility time of groups treated with metamizole significantly decreased compared to the depression group and approached the control. Significant decreases were observed in the relative concentration levels of cytokines and hematopoietic growth factors in the groups treated with 100 and/or 200 mg/kg metamizole compared to the depression group except for IL-1?, IL-4, and IL-10. Conclusion: Evidence showing the contribution of COX enzymes to the pathophysiology of depression is increasing. In this context, the results indicate that metamizole, which can inhibit both isoforms of COX, may cause changes in cytokine levels and hematopoietic growth factors in a depression model. However, more controlled clinical studies are needed.Öğe Metamizole Reduces The Expression of OCT4, SOX2, SOX4 in Hematopoietic Stem/Progenitor Cells Directed to Differentiation in In Vitro Hematopoiesis Simulation(2025) Maytalman, Erkan; Samur, Dilara NemutluAim: Metamizole is a non-steroidal anti-inflammatory drug used for its analgesic and antipyretic effects. Metamizole-associated agranulocytosis is a significant adverse effect limiting its use in some countries, but it has also been shown to promote apoptosis in cancer cells with possible mechanisms underlying this adverse effect. The mechanisms underlying these effects have not been sufficiently elucidated. Methods: The cells obtained from stem cell product samples collected from healthy allogeneic stem cell donors were used in the study. MTT assay was used to analyse the proliferative-cytotoxic effects of metamizole on cells. CFU-Mix culture was also performed for cell differentiation to granulocyte and analysis of expression of OCT4, SOX2, SOX4. The expression fold change of transcription factors was determined by RT-qPCR. Results: Metamizole limited the proliferation of cells at increasing concentrations starting at 10 µM. The IC50 values of metamizole were significantly different between the samples. The lowest value for IC50 was 50.96±7.60 µM and the highest value was 165.5±18.21 µM. Granulocyte-macrophage colony counts and OCT4, SOX4 mRNA expressions decreased at metamizole concentrations of 10 and 100 µM. For SOX2, the decrease occurred at a concentration of 100 µM. Conclusion: Our results indicated that metamizole may limit the proliferation and differentiation of hematopoietic stem/progenitor cells via transcription factors and this effect may be responsible for possible agranulocytosis cases. NSAIDs have also been shown to have apoptotic effects on cancer cells. The ability to limit the expression of transcription factors that play important roles in cell development and differentiation may pave the way for the synergistic use of this drug with antineoplastic drugs.Öğe Neuroendocrine modulation by metamizole and indomethacin: investigating the impact on neuronal markers and GnRH release(Springer, 2024) Maytalman, Erkan; Samur, Dilara NemutluPurposeSome evidence that non-steroidal anti-inflammatory drugs have neuroprotective effects indicates their potential for use in a new field. However, their effects on hormone secretion have yet to be adequately discovered. Therefore, we aimed to evaluate the effects of metamizole and indomethacin on neuronal markers as well as the GnRH expression in the GT1-7 cell line.MethodsThe effects of these drugs on proliferation were evaluated by MTT analysis. The effect of 10-50-250 mu M concentrations of the drugs also on the expression of neuronal factors and markers, including NGF, nestin and beta III Tubulin, and additionally GnRH, was determined by the RT-qPCR method.ResultsNGF and nestin mRNA expressions were increased in all concentrations of both metamizole and indomethacin. No changes were detected in beta III Tubulin. While metamizole showed an increase in GnRH mRNA expression, there was no change at 10 and 50 mu M concentrations of indomethacin, but a remarkable decrease was observed at 250 mu M concentrations.ConclusionsThe results of our study showing an increase in the expression of neuronal factors reveal that metamizole and indomethacin may have possible neuroprotective effects. Moreover, the effects on the GnRH expression appear to be different. Animal models are required to confirm these effects of NSAIDs on neurons.Öğe Sıçan Kökenli Enteroglial Hücrelerde Rotenon ile İndüklenen İnflamatuvar Değişiklikler Üzerine Vortioksetinin Etkileri: TLR4/NF?B Sinyal Yolağının Rolü(Eskişehir Osmangazi Üniversitesi, 2025) Samur, Dilara Nemutlu; Maytalman, Erkan; Zorlu, ÖyküParkinson hastalığı (PH) progresif bir nörodejeneratif hastalık olup günümüzde hastalığı durdurmaya yönelik kesin bir tedavi seçeneği bulunmamaktadır. Gastrointestinal inflamasyon, PH ile ilişkili motor-olmayan bulgulardan biridir. Son yıllarda antidepresanların potansiyel antiinflamatuvar etkileri nedeniyle nörodejeneratif hastalıkların tedavisinde kullanılabileceğine dair ilgi artmıştır. Bu çalışmada, vortioksetinin enterik glia hücrelerinde rotenon ile indüklenen inflamatuvar yanıtlar üzerindeki etkisi ve bu etkisinde TLR4/NF-?B sinyal yolağının rolü araştırılmıştır. Rotenon (10 ?M) ve vortioksetin (1 ve 5 ?M) ile muamele edilmiş hücre örneklerinde TLR4 ve NF-?B mRNA ekspresyonları RT-qPCR ile, TNF-?, IL-1? ve IL-6 düzeyleri ise ELISA yöntemiyle değerlendirilmiştir. Bulgular, rotenonun glial hücrelerin immün yanıtlarını bozarak TLR4 ve NF-?B ekspresyonunu belirgin şekilde baskıladığını ve bu etkinin 5 ?M vortioksetin uygulamasıyla daha da arttığını göstermiştir. Ayrıca rotenon gruplarında TNF-? ve IL-1? düzeylerinde gözlenen düşüş, vortioksetin uygulaması ile tersine dönmüştür. Sonuçlar, vortioksetinin enterik glia hücrelerinde TLR4/NF-?B yolakları üzerinden inflamatuvar yanıtı düzenleyebileceğini ve PH’nin bağırsak-beyin eksenine dayalı inflamasyon modelinde potansiyel bir terapötik madde olarak çalışılabileceğini göstermektedir.Öğe The effect of thymoquinone and propranolol combination on epidermoid laryngeal carcinoma cell(Springer, 2023) Sahin, Caner; Maytalman, Erkan; Samur, Dilara Nemutlu; Dogan, BoraPurpose We aimed to evaluate the effects of thymoquinone and propranolol on Hep-2 cells representing laryngeal Ca cell type in comparison with cisplatin. We also evaluated their combined effects. Methods Apoptotic effects were directly analyzed via mitochondrial membrane potential and caspase-3 assays. In addition, effects on apoptosis and cell cycle via Bcl-2, Bax, P53, and Cyclin D1 mRNA expressions and effects on angiogenesis via VEGFA mRNA expression were evaluated by RT-qPCR. Results According to our results, it was determined that the anticancer effects of thymoquinone on Hep-2 cells were higher than propranolol. Our JC-1 and caspase-3 results showed an effect close to cisplatin, especially for 50 mu M thymoquinone. Significant differences were also obtained in Bcl-2, Bax, P53, and cyclin D1 results for similar concentrations compared to the control. No effect of thymoquinone was seen for VEGFA. Propranolol alone had no significant effect on JC-1 and Caspase-3. Propranolol had an effect on Bcl-2, Bax mRNA expressions compared to the control, only at 250 mu M concentration. Propranolol and its combinations increased VEGFA mRNA expression-like cisplatin. Conclusion Thymoquinone induced apoptosis and blocked the cell cycle in Hep-2 cells. The effects of propranolol, which was reported to have an antiangiogenesis effect in some studies, on apoptosis and cell cycle were limited except at high concentrations. For this cell line, why propranolol causes an increase in VEGFA expression should be evaluated extensively. Thymoquinone shows promise for cancer therapy, but studies need to be designed in vivo to evaluate the effects more reliably.Öğe The effects of mesenchymal stem cells applied during the subacute period in peripheral neuropathy(2024) Kıroğlu, Olcay; Maytalman, Erkan; Alizade, Ares; Emre, Mustafa; Zorludemir, Suzan; Aksu, FazıletPurpose: The study aims to investigate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) administered subacute period to neuropathic mice on allodynia and nerve-muscle tissue functions during 24 weeks. Materials and Methods: Peripheral neuropathy was induced by partial sciatic nerve ligation. Experiments were conducted in Control, Sham, Neuropathic, BM-MSC, and Neuropathic+BM-MSC groups. Allodynia was measured by cold plate test at the 2nd, 6th, and 24th weeks. Electrophysiological and histopathological examinations were performed on isolated nerve-muscle tissues at the end of the 24th week. Results: Allodynia threshold increased in the Neuropathic+BM-MSC group (7.76±0.33 sec) from the 6th week and continued to increase along 24 weeks compared to the Neuropathic group (4.36±0.21 sec). Action potential (137.9±7.85 mV) and depolarization (0.74±0.01 msec) values of the Neuropathic+BM-MSC group exhibited partial improvement compared to the Neuropathic group (121.5±3.03 mV and 0.81±0.02 msec, respectively) at the 24th week. Muscle tissue's resting membrane potential values increased in the Neuropathic+BM-MSC group compared to the Neuropathic group (-73.4±0.2 and -87.7±0.2 mV, respectively). Histopathological examination of nerve tissue revealed loss of myelinated axons and significant fibrosis in the endoneurium in the Neuropathic group while Schwann cell proliferation and preservation of myelinated axons were observed in the Neuropathic+BM-MSC group. Muscle fiber atrophy, compensatory hypertrophic fibers, and increased central nuclei were seen in the Neuropathic group, while small atrophic muscle fiber groups were identified in the Neuropathic+BM-MSC group. Conclusion: BM-MSC application in the subacute period is found to reduce allodynia and provide functional recovery in nerve-muscle tissue in experimental peripheral neuropathy.Öğe The effects of mesenchymal stem cells applied during the subacute period in peripheral neuropathy(Cukurova Univ, Fac Medicine, 2024) Kiroglu, Olcay; Maytalman, Erkan; Alizade, Ares; Emre, Mustafa; Zorludemir, Suzan; Aksu, FaziletPurpose: The study aims to investigate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) administered subacute period to neuropathic mice on allodynia and nerve-muscle tissue functions during 24 weeks. Materials and Methods: Peripheral neuropathy was induced by partial sciatic nerve ligation. Experiments were conducted in Control, Sham, Neuropathic, BM-MSC, and Neuropathic+BM-MSC groups. Allodynia was measured by cold plate test at the 2nd, nd , 6th, th , and 24th th weeks. Electrophysiological and histopathological examinations were performed on isolated nerve-muscle tissues at the end of the 24th th week. Results: Allodynia threshold increased in the Neuropathic+BM-MSC group (7.76 +/- 0.33 sec) from the 6 th week and continued to increase along 24 weeks compared to the Neuropathic group (4.36 +/- 0.21 sec). Action potential (137.9 +/- 7.85 mV) and depolarization (0.74 +/- 0.01 msec) values of the Neuropathic+BM-MSC group exhibited partial improvement compared to the Neuropathic group (121.5 +/- 3.03 mV and 0.81 +/- 0.02 msec, respectively) at the 24th th week. Muscle tissue's resting membrane potential values increased in the Neuropathic+BM-MSC group compared to the Neuropathic group (-73.4 +/- 0.2 and-87.7 +/- 0.2 mV, respectively). Histopathological examination of nerve tissue revealed loss of myelinated axons and significant fibrosis in the endoneurium in the Neuropathic group while Schwann cell proliferation and preservation of myelinated axons were observed in the Neuropathic+BMMSC group. Muscle fiber atrophy, compensatory hypertrophic fibers, and increased central nuclei were seen in the Neuropathic group, while small atrophic muscle fiber groups were identified in the Neuropathic+BM-MSC group. Conclusion: BM-MSC application in the subacute period is found to reduce allodynia and provide functional recovery in nerve-muscle tissue in experimental peripheral neuropathy.Öğe The effects of metamizole on hematopoietic progenitor cells: Suppression of hematopoiesis stimulation in vitro(2023) Maytalman, Erkan; Samur, Dilara Nemutlu; Günizi, Özlem Ceren; Kozanoğlu, lknurBACKGRAUND: There is evidence that the adverse effects of metamizole occur due to the effect of the drug on the hematopoietic stem/progenitor cells, and therefore, the disruption of hematopoiesis. Therefore, our study aimed to evaluate the effects of metamizole on hematopoietic stem/progenitor cells using cell culture techniques. MATERIAL AND METHODS: In our study, samples were taken from stem cell products of healthy allogeneic stem cell transplant donors. The colony-forming unit (CFU) assay was used for the cells obtained from these samples. In addition, the drug effects on cell proliferation were evaluated with the MTT. Furthermore, the cell colonies were labelled with immunofl uorescent antibodies and the effects of metamizole on cell types formed in culture were evaluated. RESULTS: We determined that metamizole negatively affects the proliferation of cells, especially starting from 10 ?M. As a result of the evaluation of colonization, we saw that the number of colonies decreased with increasing concentrations. Granulocyte-macrophage colonies were more affected at increasing concentrations than other colonies. As a result of the evaluations of our in vitro study, it was also shown as an important fi nding that the individual effects of the drug were highly variable. CONCLUSION: CFU method can be used as a suitable method to investigate the effects of drugs and toxic substances on hematopoiesis. We also think it may be suitable for pre-analysing hematopoietic side effects in new drug research. In addition, using stem cell samples in studies may contribute more easily to the in vitro simulation of hematopoietic differentiations (Fig. 7, Ref. 29)Öğe Vortioksetinin, Enterik Sinir Sisteminde Rotenon Maruziyeti Ile Indüklenen Patofizyolojik Değişiklikler Üzerine Etkilerinde Tlr2/S100b Sinyal Yolağının Rolü(2023) Samur, Dilara Nemutlu; Özbey, Gül; Maytalman, Erkan; Tanriover, Gamze; Kalay, Merzuka; Yikit, MuratAmaç: Enterik sinir sistemi patolojisi, Parkinson hastalığında en erken görülen bulgular arasındadır. Hatta, hastalığın enterik sistemden başlayarak beyin bölgelerine yayıldığı düşünülmektedir. Enteroglial hücreler (EGC?ler), beyindeki astrositlerin eşdeğerini temsil eder. Bu hücreler inflamasyon varlığında aktive olur, S100B ve Toll-benzeri reseptör (TLR)?ler aracılığıyla proinflamatuvar sitokin salımına neden olur. Gastrointestinal semptomlar ile duygudurum bozuklukları arasındaki çift yönlü ilişki de göz önünde bulundurularak, bu çalışmada, serotonerjik bir antidepresan olan vortioksetinin ESS?de rotenon tarafından indüklenen patofizyolojik değişiklikler üzerine olan etkilerinin ve olası etki mekanizmalarının aydınlatılması amaçlandı. Yöntem: 28 gu?n boyunca rotenon (2 mg/kg/gu?n, s.c.) ve/veya vortioksetin (10 mg/kg/gu?n, s.c.) uygulanan sıçanlardan elde edilen duodenum dokularında tirozin hidroksilaz (TH), ?-sinu?klein, serin-129 bölgesinde fosforile olmuş ?-sinu?klein, TLR2 ve S100B ekspresyonlarını belirlendi. Etki mekanizması çalışmaları için, sıçanlardan dönüştürülmüş EGC?ler, rotenon (10 uM) ve/veya vortioksetin (5 uM veya 1 uM) ile muamele edildi. Kontrol, rotenon, yüksek doz vortioksetin (5 ?M, V1), düşük doz vortioksetin (1 ?M, V2), ROT+V1 ve ROT+V2 grupları oluşturuldu. Vortioksetinin etkileri, TLR2 antagonisti C29 ve S100B inhibitörü pentamidin varlığında da değerlendirildi. S100B, TLR2 ve NF?B mRNA seviyeleri RT-qPCR, proinflamatuvar sitokin seviyeleri ise ELISA yöntemi ile tayin edildi. Bulgular: İn vivo çalışmalarda, rotenon uygulaması ile duodenum dokusunda artış gösteren inflamatuvar belirteçlerin ekspresyonları vortioksetin uygulaması ile azaldı. İn vitro çalışmalarda, rotenonun toksik etkiler aracılığıyla glial hücre yanıtlarını bozarak S100B ve NF?B gibi belirteçlerin azalmasına yol açtığı, vortioksetinin ise hücresel yanıtları iyileştirerek EGC?lerin inflamatuvar molekülleri yeniden sentezleyebilmesini sağladığı gösterildi. C29 ve pentamidin uygulamalarıyla hem S100B ve NF?B mRNA ekspresyon düzeyleri hem de TNF-?, IL-1ß ve IL-6 seviyelerinde anlamlı değişiklikler meydana geldi. Sonuç: Bu çalışma, vortioksetinin duodenum dokusunda ve EGC?lerde rotenon ile indüklenen patolojik değişiklikler üzerinde yararlı etkileri olduğunu gösteren ilk çalışmadır. Vortioksetinin göstermiş olduğu bu etkilerinin bir kısmına S100B/TLR2/NF?B yolağının aracılık ettiği düşünülmektedir.Öğe Vortioxetine attenuates rotenone-induced enteric neuroinflammation via modulation of the TLR2/S100B/RAGE signaling pathway in a rat model of Parkinson's disease(Pergamon-Elsevier Science Ltd, 2025) Samur, Dilara Nemutlu; Yildirim, Sendegul; Maytalman, Erkan; Kalay, Merzuka; Tanriover, Gamze; Ozbey, GulEmerging evidence suggests that gastrointestinal dysfunction and enteric nervous system pathology play a critical role in the early stages of Parkinson's disease. Considering the bidirectional relationship between gastrointestinal symptoms and mood disorders, this study aimed to elucidate the effects and possible mechanisms of action of vortioxetine, a serotonergic antidepressant, on the pathophysiological changes induced by rotenone in the enteroglial cells. alpha-synuclein, phosphorylated alpha-synuclein, TLR2, S100B and RAGE expression were detected in duodenal tissues of rats administered rotenone (2 mg/kg/day, s.c.) and/or vortioxetine (10 mg/kg/ day, s.c.) for 28 days. For the mechanism of action studies, rat-derived enteroglial cells were treated with rotenone (10 mu M) and/or vortioxetine (5 mu M or 1 mu M) for 24 h. The effects of vortioxetine were evaluated in the presence of the TLR2 antagonist C29, RAGE antagonist FPS-ZM1 and the S100B inhibitor pentamidine. TLR2, S100B, RAGE, and NF kappa B mRNA levels and proinflammatory cytokines via RT-qPCR and ELISA. Our results demonstrate that rotenone treatment significantly increased alpha-synuclein, pS129-alpha-synuclein, TLR2, and S100B expression while reducing RAGE levels, indicating marked enteric pathology. Vortioxetine administration attenuated these effects, reducing alpha-synuclein accumulation and proinflammatory markers. In vitro, rotenone impaired glial responses, decreasing S100B, RAGE, and NF kappa B markers, while vortioxetine improved these responses, promoting resynthesis of inflammatory molecules. Notably, S100B, NF kappa B, and cytokine levels (TNF-alpha, IL-1 beta, IL-6) were affected by C29, FPS-ZM1, and pentamidine pretreatments. Thus, vortioxetine is thought to have beneficial effects on rotenone-induced pathological changes in EGCs, and some of these effects are thought to be mediated by the TLR2/S100B/RAGE pathway.
