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Öğe Adipose-Derived Stem Cells and Application Areas(Cukurova Univ, Fac Medicine, 2015) Kivanc, Mujde; Ozturk, Samil; Gokalp, Sevtap; Ozdemir, Ilhan; Tuglu, IbrahimThe use of stem cells derived from adipose tissue as an autologous and self-replenishing source for a variety of differentiated cell phenotypes, provides a great deal of promise for reconstructive surgery. The secret of the human body, stem cells are reserved. Stem cells are undifferentiated cells found in the human body placed in any body tissue characteristics that differentiate and win ever known to cross the tissue instead of more than 200 diseases and thus improve and, rejuvenates the tissues. So far, the cord blood of newborn babies are used as a source of stem cells, bone marrow, and twenty years after tooth stem cells in human adipose tissue, scientists studied more than other sources of stem cells in adipose tissue and discovered that. Increase in number of in vitro studies on adult stem cells, depending on many variables is that the stem cells directly to the desired soybean optimization can be performed.. We will conclude by assessing potential avenues for developing this incredibly promising field. The aim of this paper is to review the existing literature on applications of harvest, purification, characterization and cryopreservation of adipose-derived stem cells (ASCs).Öğe Alpha-synuclein levels in multiple sclerosis patients with restless leg syndrome(Cukurova Univ, Fac Medicine, 2020) Cakina, Suat; Yucel, Selma; Polat, Cemre Cagan; Ozturk, SamilPurpose: The restless legs syndrome is more frequent and critical in Multiple Sclerosis patients, and it harms their general well-being and life quality. Alpha-synuclein is a synuclein protein that can have an impact on the pathway of signaling, affecting the Dopamin 2 receptor and its receptor trafficking. Studies have shown that the decrease in dopamine 2 receptor and Restless Legs Syndrome disease are correlated. This study is aimed to ascertain the alpha-synuclein level in multiple sclerosis patients with restless legs syndrome. Materials and Methods: We took blood samples from 40 multiple sclerosis patients and 20 healthy individuals. Half of the patient group had Multiple Sclerosis with restless leg syndrome. In the study groups, the alpha-synuclein level was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-dependent immunosorbent assay (ELISA). Results: Alpha-synuclein gene expression level was found or be significantly lower in restless leg syndrome patients with multiple sclerosis than the Alpha-synuclein gene expression level in the control group. Conclusion: Alpha-synuclein may have an impact on the pathogenesis of the restless leg syndrome of multiple sclerosis disease. Further investigations are required to determine the impact of alpha-synuclein in the pathogenesis of restless leg syndrome in multiple sclerosis disease.Öğe Ameliorative Effects of Ulva rigida (C. Agardh, 1823) on Cadmium-induced Nephrotoxicity in Wistar Albino Rats(Univ Agriculture, Fac Veterinary Science, 2022) Irkin, Latife Ceyda; Ozturk, SamilMany organs and systems, especially the kidney, are damaged by the effect of high-dose cadmium. These functional problems vary depending on the distribution of cadmium in the body, the way it is taken, the dose and the duration. Antioxidant activities of algae are due to the polyphenols, polysaccharides, pigments and vitamins they contain. Antioxidants are effective in protecting the body against damage caused by reactive oxygen species. This study was carried out to determine the therapeutic effects of Ulva rigida extract on kidney tissue fibrosis, inflammatory inflammation and apoptosis in cadmium-induced rats. In the study, 1 mg/kg CdCl2 was injected subcutaneously to the subjects four times a week for one month (G2). Concurrently, 50 mg/kg (G3) and 100 mg/kg (G4) algae extract were given to the subjects by gavage. In staining with hematoxylin-eosin, mononuclear cell infiltration in the kidney tissues, dilatation in the tubules, shrinkage of the glomeruli and degeneration of epithelium occurred with the induction of Cd. Immunohistochemically, it was determined that TGF-beta, TNF-alpha and NF-kB immunoreactivity was high due to tubular cells undergoing inflammation and apoptosis. Histopathological data show that U. rigida extract has a protective role against kidney damage in Cd-induced rats. Algae extract was found to play a protective role against cadmium-induced kidney damage. It was also found to have an important role as a therapeutic agent against oxidative stress.Öğe ANTI-APOPTOTIC AND PROLIFERATIVE EFFECT OF MODERATE EXERCISE ON TESTICULAR TISSUE IN STREPTOZOTOCIN-INDUCED RATS(Parlar Scientific Publications (P S P), 2022) Ozturk, Samil; Ozdemir, Ilhan; Kamalak, Zeynep; Irkin, Latife CeydaDM causes damage in many tissues and organs including the reproductive system. Severe damage in the male reproductive system is an important complication of DM. The aim of this study was to examine the effects of moderate exercise on testicular tissue in streptozotocin-diabetic (STZ) rats and to investigate the possible positive effects of exercise on the histological findings. Thirty adult rats were assigned to three groups: (a) control, (b) diabetes (40 mg/kg STZ) and (c) diabetes moderate exercise. The moderate exercise group started the exercise program 3 days before the induction of diabetes. After four weeks, the testes tissues of the rats were resected. Histochemical staining of the collected tissue specimens and morphometric tests were performed. Our study showed a reduction in the testis weight in the diabetes groups. The testis tissue of the control group was normal. Despite the atrophic changes, primary spermatocytes and spermatids were available in the testis tubules of the diabetic group. In the moderate exercise group, the architecture of the seminiferous tubules was close to normal in most of the specimens and the microscopic findings were not significantly different from those of the control group. Immunohistochemical results revealed that PCNA and TUNEL positive cells were significantly increased in the diabetic groups compared to the control group (p<0.001). The findings of our study supported that exercise had a significantly favorable effect on infertility, which is a complication of diabetes. Further molecular studies are required on this subject.Öğe Antiapoptotic and proliferative effect of bone marrow-derived mesenchymal stem cells on experimental Asherman model(Cukurova Univ, Fac Medicine, 2019) Ozturk, Samil; Sonmez, Pinar Kilicaslan; Ozdemir, Ilhan; Topdagi, Yunus Emre; Tuglu, Mehmet IbrahimPurpose: We investigated the effects of stem cell therapy as an alternative to surgical methods and medical treatments in endometrial injuries in Asherman syndrome (AS). Materials and Methods: In this study, AS model was created chemically in rats. The bone marrow-derived mesenchymal stem cells isolated from the tibia and femoral bone of male individuals of the same species (BMDSC) were given to female rats with asherman syndrome and the changes in the endometrium were evaluated by histopathological parameters. Asherman + medium, Asherman + niche, Asherman + BMDSCs, Asherman + BMDSCs + niche were formed in four groups. Results: It was observed that increased endometrial thickness, gland count and vascularization and decreased fibrous areas and apoptotic cell death with regeneration in epithelium and lamina propria in treatment groups. No histopathologic changes were observed in the right uterine horns, which were evaluated as control group.. Conclusion: BMDSCs and Niche applications can contribute to the clinic by reducing the formation of adhesion within the mechanisms causing infertility. These positive results are promising in terms of transporting Asherman studies to the clinic.It has been shown that BMDSCs and Niche may contribute to the clinic by treatment with adhesion molecules in mechanisms that cause infertility.Öğe Boswellic Acid Enhances Gemcitabine's Inhibition of Hypoxia-Driven Angiogenesis in Human Endometrial Cancer(Mdpi, 2025) Alkan Akalin, Senem; Afsin, Yasemin; Ozdemir, Ilhan; Tuncer, Mehmet Cudi; Ozturk, SamilBackground and Objectives: Endometrial carcinoma is among the most common gynecological malignancies, with recurrence and chemoresistance remaining major clinical challenges. This study aimed to evaluate the combined effects of Boswellic acid (BA), a natural pentacyclic triterpene, and Gemcitabine (GEM), a nucleoside analog chemotherapeutic, on hypoxia, angiogenesis, and apoptosis in human endometrial cancer cells. Materials and Methods: ECC-1 cells were treated with BA, GEM, or their combination under normoxic and hypoxic conditions. Cell viability (MTT assay); nuclear morphology (NucBlue staining); cell cycle distribution (PI flow cytometry); angiogenesis (VEGF ELISA expression); apoptosis (Caspase-3/7 activity; Bax; Bcl-2 expression); inflammatory cytokines (IL-1 beta; IL-6; TNF-alpha); and gene ontology enrichment were analyzed. Results: Both BA and GEM reduced cell viability in a dose- and time-dependent manner, with the combination producing synergistic cytotoxicity and lower IC50 values. Hypoxia enhanced drug sensitivity, particularly in combination therapy. BA and GEM significantly suppressed HIF-1 alpha and VEGF expression, with maximal inhibition observed in the combination group. Apoptotic induction was confirmed by increased Bax and Caspase-3 and decreased Bcl-2 expression, together with elevated Caspase-3/7, -8, and -9 activity. Pro-inflammatory cytokine levels were markedly reduced, and gene ontology analysis revealed enrichment of apoptotic, anti-proliferative, and anti-angiogenic pathways. Conclusions: BA + GEM combination synergistically suppresses hypoxia-driven angiogenesis and promotes apoptosis in endometrial cancer cells. These findings support its potential as an adjuvant therapeutic approach, warranting further preclinical and clinical validation.Öğe Combined Hesperidin and Doxorubicin Treatment Induces Apoptosis and Modulates Inflammatory Cytokines in HeLa Cervical Cancer Cells(Mdpi, 2025) Ozdemir, Ilhan; Afsin, Yasemin; Tuncer, Mehmet Cudi; Ozturk, SamilCervical cancer is a major gynecological malignancy linked to hormonal dysregulation and genetic alterations. Chemotherapy is standard but limited by toxicity and chemoresistance, prompting interest in plant-derived adjuncts. This study examined the anticancer and immunomodulatory effects of Hesperidin (Hes), a citrus flavonoid, with Doxorubicin (DX) in HeLa cervical cancer cells. Cell viability was assessed by MTT assay, apoptotic markers (Bcl-2, Caspase-3) by RT-qPCR, and inflammatory cytokines (IL-1 beta, IL-6, TNF-alpha, IFN-gamma) by ELISA. Cytokine levels were normalized to 10(4) viable cells, and mRNA expression of all four cytokines was quantified by RT-qPCR, confirming protein-level changes and showing the strongest IL-6 suppression with Hes+DX. Chou-Talalay combination index (CI) analysis demonstrated synergistic interactions (CI < 1.0) between Hes and DX across all tested concentrations, with strong synergism (CI < 0.7) at medium and high doses, particularly at 48 and 72 h. Hes alone showed dose-dependent cytotoxicity, while the combination markedly increased Caspase-3, reduced Bcl-2, and decreased IL-1 beta, IL-6, and TNF-alpha, indicating enhanced intrinsic apoptosis and complementary immunomodulation. These results suggest that Hes augments DX's pro-apoptotic and anti-inflammatory effects, potentially allowing lower chemotherapy doses and reduced systemic toxicity in cervical cancer treatment.Öğe Combined Hesperidin and Gemcitabine Therapy Modulates Apoptosis and Angiogenesis Pathways in ISHIKAWA Human Endometrial Adenocarcinoma Cells(Mdpi, 2025) Afsin, Yasemin; Ozdemir, Ilhan; Toprak, Veysel; Tuncer, Mehmet Cudi; Ozturk, SamilBackground and Objectives: Endometrial adenocarcinoma is among the most prevalent malignancies of the female reproductive system, and therapeutic options remain limited, particularly in advanced stages. In recent years, natural agents, especially flavonoids, have gained considerable interest for their capacity to enhance the effectiveness of chemotherapeutic drugs and modulate tumor-related molecular mechanisms. Hesperidin, a citrus-derived flavonoid, is recognized for its antioxidant and anti-inflammatory effects, while Gemcitabine, a nucleoside analog, is widely used in cancer treatment. Investigating their combined effects on endometrial carcinoma cells could yield novel insights into multimodal therapeutic development. This current study aimed to assess the impact of Hesperidin (Hes) and Gemcitabine (Gem) on ISHIKAWA cells, a human endometrial adenocarcinoma model, with particular attention to pathways associated with hypoxia, angiogenesis, apoptosis, and oxidative stress. Materials and Methods: ISHIKAWA cells were treated with varying concentrations of Hes (50-200 mu M) and Gem (10-50 nM), either individually or together, for 24 and 48 h. Cell viability was determined using the MTT assay, while apoptosis was measured by Caspase-3/7 activity and NucBlue nuclear staining. Intracellular reactive oxygen species (ROS) generation was quantified via DCFH-DA fluorescence. Expression levels of HIF-1 alpha, VEGF, Bax, Bcl-2, and Caspase-3 were examined by RT-qPCR. Synergistic interactions were analyzed with the Chou-Talalay combination index. Biological enrichment was further explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Both Hes and Gem significantly decreased ISHIKAWA cell viability in a concentration- and time-dependent manner (p < 0.001). The combined treatment induced stronger apoptotic effects, as reflected by increased Caspase-3/7 activity and nuclear morphological changes. RT-qPCR demonstrated upregulation of Bax and Caspase-3, together with downregulation of Bcl-2, HIF-1 alpha, and VEGF. While Hes reduced intracellular ROS, Gem elevated it; their combination produced a balanced oxidative response. All dose combinations displayed strong synergism (CI < 1). GO and KEGG enrichment confirmed the involvement of apoptosis-, angiogenesis-, and hypoxia-related pathways. Conclusions: Co-treatment with Hes and Gem exhibits synergistic anticancer activity in endometrial cancer cells by promoting apoptosis, suppressing angiogenesis- and hypoxia-related gene expression, and modulating oxidative stress. This combined therapeutic approach highlights its potential as a promising adjuvant option, warranting further evaluation in in vivo and translational studies.Öğe Integrated Molecular Analysis of Thymoquinone-Methotrexate Synergy in Breast Cancer Cells: Apoptosis, Oxidative Stress, and Pathway Modulation(Mdpi, 2025) Akalin, Senem Alkan; Afsin, Yasemin; Ozdemir, Ilhan; Tuncer, Mehmet Cudi; Ozturk, SamilBackground/Objectives: Breast cancer remains one of the leading causes of cancer-related mortality in women worldwide, highlighting the urgent need for effective and less toxic therapeutic strategies. Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, possesses antioxidant and anticancer activities. Methotrexate (MTX), a widely used folate antagonist, is an established chemotherapeutic agent but is limited by toxicity and resistance. This study aimed to investigate the potential synergistic effects of TQ and MTX in estrogen receptor-positive MCF-7 breast cancer cells. Methods: MCF-7 cells were exposed to TQ (0-100 mu M), MTX (0-10 mu M), and their combinations for 24-72 h. Cell viability was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and drug interactions were evaluated using the Chou-Talalay method. Apoptosis was quantified by Annexin V/Propidium Iodide (PI) flow cytometry, and cell cycle distribution was analyzed by PI staining. Intracellular reactive oxygen species (ROS) generation was measured using a 2 ',7 '-Dichlorofluorescin diacetate (DCFH-DA) assay, while antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT)) activities were quantified spectrophotometrically. Gene expression of Bax, Bcl-2, NF-kappa B, MMP-2, and MMP-9 was determined by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: TQ and MTX each reduced cell viability in a dose- and time-dependent manner, while combination treatment significantly enhanced cytotoxicity compared with single agents (p < 0.01). Combination Index (CI) values < 1 confirmed a synergistic interaction, particularly at 50 mu M TQ + 5 mu M MTX and 100 mu M TQ + 10 mu M MTX. Combination therapy increased total apoptosis up to 83.6%, markedly elevated the Bax/Bcl-2 ratio, and enhanced caspase-3 activation. Cell cycle analysis revealed pronounced G2/M arrest. ROS levels increased approximately six-fold, accompanied by significant suppression of SOD and CAT activities. qRT-PCR results demonstrated upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic B-cell lymphoma 2 (Bcl-2), nuclear factor kappa B (NF-kappa B), matrix metalloproteinase (MMP)-2, and MMP-9. Conclusions: TQ potentiates the anticancer activity of MTX in MCF-7 breast cancer cells by synergistically inducing apoptosis, oxidative stress, and cell cycle arrest while suppressing metastasis-related genes. This combination may represent a promising therapeutic strategy for breast cancer, warranting further validation in in vivo and clinical studies.Öğe Oxidative stress markers in liver in streptozocin-induced diabetic rats: effects of metformin and sitagliptin(Cukurova Univ, Fac Medicine, 2020) Cakina, Suat; Ozturk, SamilPurpose: This study aims at investigating the oxidative stress effect of antidiabetic drugs of Metformin (MET) and sitagliptin (STG) in the liver tissue of diabetic rats from streptozotocin (STZ). Materials and Methods: Thirty-five female Wistar rats (3-4 months old, weighing 200 +/- 25 g) were divided into five groups (with seven rats each) and treated as follows: control (Cont), streptozotocin alone (STZ), streptozotocin + metformin (STZ+MET), streptozotocin + sitagliptin (STZ+STG), streptozotocin + metformin + sitagliptin (STZ+MET+STG). Sitagliptin, Metformin, and combined metformin sitagliptin treated subgroups for four weeks. Malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS) levels, and oxidative stress index (OSI) ratio were measured in rat liver tissue. Besides, cells undergoing apoptotic cell death were determined using the TUNEL technique through histopathological evaluation. Results: MDA, TAS, and OSI of STZ+MET+STG administered group decreased compared to STZ. TOS of STZ+MET+STG administered group decreased compared to STZ. Conclusion: In the experimental T2D model in rats, it shows protective effect when sitagliptin is used with metformin against oxidative damage in liver tissue caused by STZ.Öğe Rosmarinic acid inhibits the proliferation of ovarian carcinoma cells by activating the p53/BAX signaling pathway(F Hernandez, 2025) Ozdemir, Ilhan; Bas, Dilek Dogan; Ozturk, Samil; Karaosmanoglu, Ozge; Tuncer, Mehmet CudiObjective. While chemotherapeutic agents stop the development of cancer cells, they also kill healthy cells. This study aimed to increase anticancer effects and reduce side effects by combining a phytotherapeutic compound with a chemotherapeutic drug. Methods. This study examined the effects of nine concentrations of rosmarinic acid (RA) and doxorubicin (DOX) on human ovarian adenocarcinoma (OVCAR3) and skin keratinocyte (HaCaT) cell lines. Their cytotoxic effects were assessed based on cell viability, evaluated using the MTT assay, and apoptotic activity, evaluated using NucBlue staining and the gene and protein expression of tumor protein p53 (TP53) and BCL2 associated X, apoptosis regulator (BAX) quantified by qRT-PCR and western blots, respectively. Results. The half-maximal inhibitory concentration after 48 hours was 880.4 mu M for RA and 2.26 mu M for DOX. The cytotoxicity analysis revealed that cell viability decreased with the RA concentration. RA increased apoptosis in OVCAR3 cells by activating the p53/BAX pathway. Western blots showed that RA and DOX upregulated p53 and BAX protein levels in OVCAR3 cells. Conclusions. The RA and DOX combination inhibited cell proliferation by inducing apoptosis in OVCAR3 cells. These results suggest that RA may reduce the side effects of DOX toxicity.Öğe Synergistic Anticancer Effects of Metformin and Doxorubicin in Ovarian Cancer Cells Through Dual Apoptotic Pathway Activation and Oxidative Stress Enhancement(Mdpi, 2025) Alkan Akalin, Senem; Afsin, Yasemin; Toprak, Veysel; Ozdemir, Ilhan; Tuncer, Mehmet Cudi; Ozturk, SamilThis study aimed to evaluate the antiproliferative, apoptotic, and oxidative stress-inducing effects of the combination of metformin and doxorubicin (adriamycin) in OVCAR3 and SKOV3 ovarian cancer cell lines and to investigate the potential synergistic interactions between the two agents. Cell viability was assessed using the MTT assay. Apoptosis was quantified via Annexin V/PI staining followed by flow cytometry. Caspase-8 and caspase-9 activities were measured using colorimetric assays. Oxidative stress parameters, including reactive oxygen species (ROS) and nitric oxide (NO), were determined using DCFH-DA fluorescence and the Griess assay, respectively. The mRNA expression levels of apoptosis-related genes (Bcl-2, Survivin, Bax, and Caspase-3) were analyzed by qRT-PCR. Drug interaction and synergy were evaluated using the Chou-Talalay combination index (CI) model and the highest single agent (HSA) model. Prognostic relevance of target genes and protein interaction networks was examined through TCGA and STRING databases. The metformin-doxorubicin combination demonstrated strong synergistic antiproliferative effects in both cell lines (CI < 0.7 in OVCAR3). The combination significantly increased apoptosis compared with single-agent treatments, yielding a total apoptotic rate of 62.5 +/- 4.2% in OVCAR3. Caspase-8 and caspase-9 activities were elevated by 5.6 +/- 0.7-fold and 7.3 +/- 0.8-fold, respectively. Combination treatment also induced marked oxidative stress, increasing NO levels to 12.4 +/- 1.1 M and ROS levels to 412 +/- 25% in OVCAR3 cells. qRT-PCR analyses revealed downregulation of anti-apoptotic Bcl-2 (0.28 +/- 0.04-fold) and Survivin (0.25 +/- 0.03-fold), along with upregulation of pro-apoptotic Bax (5.8 +/- 0.6-fold) and Caspase-3 (6.5 +/- 0.7-fold). Bioinformatic analyses indicated that high Bcl-2 and Survivin expression correlated with poorer overall survival in ovarian cancer patients. Metformin enhances the anticancer efficacy of doxorubicin through synergistic activation of intrinsic and extrinsic apoptotic pathways, induction of oxidative and nitrosative stress, and transcriptional regulation of key apoptotic markers. These findings support the potential use of metformin as an adjuvant agent to strengthen doxorubicin-based chemotherapy in ovarian cancer.
