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Öğe Antioxidant activities of inula viscosa extract and curcumin on U87 cells induced by beta-amyloid(Cukurova Univ, Fac Medicine, 2021) Alizade, Ares; Ozbolat, GuluzarPurpose: The aim of this study was to investigate the effects of Inula viscosa extract and Curcumin on the U87 (human astrocytoma cell line) treated with amyloid-beta (A beta), which is the Alzheimer's disease (AD) model cell line. Materials and Methods: Firstly, the cytotoxic potential of inula and curcumin was investigated in the U87 cells by the colorimetric MF1 (3-4,5-dimethyl-thiazolyl-2,5-diphenyltetrazolium bromide) assay. Then, the amount of Total Glutathione, Malondialdehyde (MDA), Glutathione reductase (GR) activities were investigated. ELISA test was used to examine the expression and activity of cleaved Bax and Bcl-2 proteins in the Inula viscosa and Curcumin treated U87 cell lines. Results: Inula viscosa and Curcumin treatment reduced cell death caused by amyloid-B in cells. It also reduced oxidative stress caused by amyloid-B, while reducing the activation of the proapoptotic protein Bax, and Bcl-2. Conclusion: Our results suggest that inula viscosa may represent a new approach in the treatment of Alzheimer's.Öğe Artificial intelligence-driven epigenetic CRISPR therapeutics: a structured multi-domain meta-analysis of therapeutic efficacy, off-target prediction, and gRNA optimization(Springer Heidelberg, 2025) Basarali, Mustafa Kemal; Daemi, Amin; Tahiraga, Ruhiyya Guliyeva; Ozbolat, Guluzar; Hooshiar, Mohammad Hosseini; Shirazi, Malihe Sagheb Ray; Dogus, YusufCRISPR-based epigenetic editing enables reversible regulation of gene expression without permanent DNA modification. The integration of artificial intelligence (AI) enhances guide RNA (gRNA) design, off-target prediction, and delivery optimization. We conducted a systematic review and meta-analysis (2015-2025) in accordance with PRISMA 2020 guidelines to evaluate the impact of AI on the precision, safety, and therapeutic efficacy of epigenetic CRISPR tools. From 540 screened records, 58 studies met inclusion criteria, of which 41 provided extractable quantitative data for meta-analysis and 17 contributed to qualitative synthesis. Random-effects models, subgroup analyses, and bias assessments were applied. Pooled analyses demonstrated strong positive effects across three domains: therapeutic efficacy (SMD = 1.67), gRNA optimization (SMD = 1.44), and off-target prediction (AUC = 0.79). Publication bias was minimal, and subgroup analyses indicated the strongest impact in therapeutic applications. Deep learning models were consistently associated with higher effect sizes. Qualitative synthesis revealed trends in interpretable AI, omics integration, and delivery innovations, underscoring AI's role in safer and more precise CRISPR editing. Overall, AI significantly improves the precision and therapeutic performance of CRISPR-based epigenetic tools, with the strongest effects observed in therapeutic efficacy, supporting their potential for personalized gene editing.Öğe Effects of Curcumin on Iron Overload in Rats(Knowledge E, 2021) Ozbolat, Guluzar; Yegani, Arash AlizadehBackground: Iron overload, common in patients with hematological disorders, is a key target in drug development. This study investigated the effects of curcumin on iron overload in rats. Methods: Forty male Wistar rats weighing 139.78 +/- 11.95 gm (Mean +/- SD) were divided into three equal groups: (i) controls; (ii) iron overload group that received six doses of iron dextran 1000 mg/kg(--1) by intraperitoneal injections (i.p.); and (iii) iron overload curcumin group that received six doses of curcumin (1000 mg/kg BW by i.p.). In addition to six doses of iron dextran 1000 mg/kg(--1) by i.p., we studied the effects of curcumin on liver function enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]); antioxidant enzymes (malondialdehyde [MDA], total oxidant status [TOS], total antioxidant status [TAS]); hematological parameters (hemoglobin [Hb], hematocrit [Hct], red blood cells [RBC], white blood cells [WBC], mean corpus volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC]); and iron parameters (serum iron profile, transferrin, total iron-binding capacity [TIBC], ferritin, and transferrin saturation [TS%]). Results: Curcumin caused a significant decrease in the Hct and Hb concentrations in Group III (P < 0.05). It also significantly reduced the serum levels of ALT (52.45 +/- 4.51 vs 89.58 +/- 4.65 U/L) and AST (148.03 +/- 6.47 vs 265.27 +/- 13.02 U/L) at the end of the study (P < 0.05). The TIBC, transferrin levels, and TS significantly decreased when the rats were administered curcumin serum iron (P < 0.05). The TAS level significantly increased in Group III in comparison to Group I (the control group) (P < 0.05). At the end of the study, curcumin significantly reduced the serum levels of TOS (12.03 +/- 2.8 vs 16.95 +/- 5.05 mmol H2O2/L) while the TAS (1.98 +/- 0.42 vs 1.06 +/- 0.33 mmol Trolox equiv./L) was increased. Conclusion: The findings of the present study suggest the therapeutic potential of curcumin against iron overload.Öğe IN VITRO EFFECTS OF ANTIOXIDANT AND PROAPOPTOTIC ACTIVITIES OF THYMOQUINONE IRON COMPLEX(Dokuz Eylul Univ Inst Health Sciences, 2022) Ozbolat, Guluzar; Alizade, AresIntroduction: This study aimed to investigate the proapoptotic and antioxidant effects of the Thymoquinone (TQ) iron complex on the SW480 cell line. This study investigates the proapoptotic and antioxi-dant effects of the TQ iron complex on the SW480 cell line. Material and Methods: The SW480 cells were routinely cultured in a medium for 48 h. and incubated at 37 degrees C in a 5% CO2 in the air. After the incubation period, the cells were washed with buffer, and 100 ml of the denaturing lysis buffer per 0.5 was added to 2x10(7) cells for 15 min, and supernatants were tak-en. ELISA test was used to examine the expression and activity of GADD153, Wee1, cleaved Caspase-3, Bax, GRP78, and Bcl-2 proteins in SW480 cells. In this study, to measure activities of total antioxidant capacity (TAS), catalase (CAT), total oxidant capacity (TOS), and superox-ide dismutase (SOD) activities were investigated by the ELISA method in cell lines SW480 treated with the TQ iron complex. Results: ELISA test results indicated that the activities of apoptotic proteins Bax, Wee1 Caspase-3, GADD153, GRP78, and Bcl-2 in human SW480 cell lines were significantly increased in the 48-hour treatment. Conclusion: Our results of this study demonstrated that in untreated cultures, high TAS, SOD and CAT ac-tivities were found in SW480 cell lines than in control cell lines.Öğe In vitro effects of iron chelation of curcumin Fe (III) complex(Cukurova Univ, Fac Medicine, 2019) Ozbolat, Guluzar; Yegani, Arash AlizadehPurpose: The aim of this study was to investigate the cytotoxicity effect, iron chelator and antioxidant activities of iron (III) ions with curcumin ligand that may be used in the treatment of iron overload. Materials and Methods: The cytotoxic activities of the ligand and the complex were evaluated by the MTT assay. The SOD activity of the complex of curcumin was determined by using its ability to inhibit the reduction of NBT. The catalytic activity studies of Fe(III) complex in DMSO towards the disproportionation of hydrogen peroxide were also performed. Results: The IC50 values are found in 6.8 mu M catalase activity was measured. Where at a concentration of 2.0 mM, the activity was equivalent to 183.30 U/L. The complex shows a catalase activity. The complex showed minimal toxicity. IC50 values found 5.3 mg/ml. The observed cytotoxicity could be pursued to obtain a potential drug. The iron chelator effects were determined by Ferrozine reagent. Curcumin, the most active extract interfered with the formation of ferrous and ferrozine complex. It demonstrated strong chelating activities. The result showed that the complexes possess considerable SOD activity. This finding indicates that the iron complex is capable of removing free radicals. Conclusion: The study results revealed that the iron(III) complex of curcumin with an appropriate potential drug may act as a protector against oxidative stress. Therefore, all results suggest that curcumin may represent a new approach in the treatment of iron overload.Öğe IN VITRO STUDIES ON THE PROTECTIVE EFFECT OF TANNIC ACID OF U87 CELLS INDUCED BY BETA-AMYLOID(Dokuz Eylul Univ Inst Health Sciences, 2021) Ozbolat, Guluzar; Alizade, AresBackground: While the prevalence of Alzheimer's disease continues to increase throughout the twentieth century, the cause and pathology of the disease are not well understood and scientists are seeking treatments for the disease. Tannic acid can be used effectively to treat Alzheimer's disease and seems to be one of the alternative therapeutic strategies in medicine. In this study, we aimed to investigate the effects of tannic acid on the U87 (human astrocytoma cell line) treated with amyloid-beta (A beta), which is the Alzheimer's disease (AD) model cell line. Materials and Methods: In the study; three groups were formed as the control group, the A beta group, and the A beta + tannic acid group obtained by adding tannic acid to the A beta group. Firstly, the cytotoxic potential of TA in U87 cells was investigated by the colorimetric MTT (3-4,5-dimethyl-thiazolyl-2,5 diphenyltetrazolium bromide) test. To determine the antioxidant status in the cell line treated with tannic acid, to examine the effects of total oxidant status (TOS), superoxide dismutase (SOD), total antioxidant status (TAS) and catalase (CAT) activities, were measured by the ELISA method. Results: In our study, the viability and proliferation of the cell decreased in U87 cells treated with amyloidB compared to the control group, but tannic acid increased cell viability and proliferation when compared with the group treated with amyloid-B. When compared to the control group, the TAS, SOD, and CAT levels were significantly decreased in the U87 cell line exposed to A beta; TOS levels were found to increase significantly. Conclusions: In in vitro experiments, we determined that tannic acid has a protective effect by increasing antioxidant parameters in the amyloid beta-induced cell line.Öğe Investigating monoclonal antibody against cytokeratin 19 tumor marker(Bmc, 2025) Momeni-Moghaddam, Mohammad Amin; Mohammadnejad, Javad; Ghahremani, Hossein; Khaghani, Shahnaz; Moradi, Nariman; Daemi, Amin; Ozbolat, GuluzarCytokeratin 19 (CK 19) is a member of the intermediate filaments that are widely expressed in thyroid, breast, colon, small and non-small cell lung, and prostate cancer cells. This paper aims to produce the monoclonal antibody against CK 19. Recombinant CK 19 was used to immunize of two 6-8 weeks old female Balb/c mice. For the first injection, recombinant antigen was mixed with the complete Freund ' s Adjuvant, and for the second and third injections, mixed with the Incomplete Freund ' s Adjuvant. Injections were performed at intervals of 15 days. Four days after the third injection, titration of mice serum was determined using indirect ELISA and better-immunized mice selected for fusion. Intravenous (IV) injection was performed 4 days before the fusion. The spleen cells of the mice were fused with sp2/0 cells using 50% v/v polyethylene glycol (PEG) and cells were suspended in HAT (Hypoxanthine-Aminopterin-Thymidine) medium. Supernatants of hybridoma cells were screened for antibody secretion by indirect ELISA. Two stable hybridomas were obtained among 78 hybridoma clones that reacted with the recombinant CK 19 by indirect ELISA. These hybridoma cells were monoclonal twice by limiting dilution. Besides, immunization by recombinant CK 19 led to the obtaining of two stable monoclonal antibodies against this antigen. Western blotting with HT-29 cell line demonstrated a band of upper than 43 kDa. Result of HepG2 indicated a band of lower than 45 kDa while MCF7 bands of 45 kDa and higher were observed for MCF7. A431 cell line was epidermoid carcinoma, as CK 19 did not exist in the epidermis, therefore no band was observed in A431 cell line.Öğe Investigating the Effects of Curcumin on Lipid Metabolism and Cell Viability in HepG2 Cells: Potential Therapeutic Implications for Nonalcoholic Fatty Liver Disease(Wiley, 2025) Qaleban, Faeze; Mohammadnejad, Javad; Daemi, Amin; Ozbolat, Guluzar; Dogus, YusufMetabolic dysfunction-associated steatotic liver disease (MASLD), poses a significant global health challenge, necessitating novel therapeutic strategies. This study investigates examines the efficacy of curcumin (Cur), a natural bioactive compound, in suppressing inhibiting the proliferation of hepatocellular carcinoma proliferation and reducing lipid accumulation in vitro. HepG2 cells were treated with Cur (1.25-10 mu g/mL) for 24-72 h, revealing a dose- and time-dependent reduction in viability, with an IC50 of 10 mu g/mL at 72 h. Oil Red O staining demonstrated Cur's lipid-lowering effects, reducing lipid content by 57% at 5 mu g/mL and 78% at 10 mu g/mL, suggesting enhanced efficacy at higher concentrations. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis revealed that Cur downregulated key lipogenic regulators Peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer-binding protein alpha (C/EBP-alpha) by 2.3- and 1.8-fold, respectively, while modulating 14-3-3 gamma/beta expression, implicating these pathways in its mechanism. These findings highlight Cur's potential to attenuate hepatic lipid accumulation and cancer cell growth in vitro, warranting further validation in primary hepatocytes and preclinical models to advance its therapeutic prospects for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Öğe Investigation of apoptotic effects of D-pantothenic acid on PC-3 prostate cancer cells(Cukurova Univ, Fac Medicine, 2020) Alizade, Ares; Ozbolat, GuluzarPurpose: The anti-inflammatory and antioxidant properties of D-pantothenic acid have been demonstrated and the effects of dexpentanol on inflammatory pathways and apopototic pathways that trigger cell death are of interest. Apoptotic pathways are important in resistance to chemotherapeutics in cancer diseases and in cancer development. Therefore, we planned how treatment of PC-3 human prostate cancer cells with dexpanthenol will affect the levels and activities of apoptotic and inflammation mediators. For this purpose, human prostate cancer cell culture was performed. Materials and Methods: The human prostate cancer cells were treated with dexpentanaol then protein levels and activities of inflammatory and apoptotic pathway mediators such as gadd153, AIF, grp78, bax and bcl-2 in the cells were analyzed by ELISA. Results: The results of our study showed that, Dpantothenic acid did not statisticaly decreased the leves of bax, bcl-2 and grp78 protein expression in PC-3 prostate cancer cells. The effect of D-pantothenic acid on gadd153 and AIF proteins in PC-3 cells was increased but this increased level did not statisticaly significant. Conclusion: Recent studies have demonstrated the potential benefits of anti-inflammatory drugs. Our study showed that D-pantothenic acid had no significant effect on the growth of PC-3 cells and has no significant effect on intracellular apoptotic pathways.Öğe Optimizing Attenuation Correction in 68Ga-PSMA PET Imaging Using Deep Learning and Artifact-Free Dataset Refinement(Mdpi, 2025) Giv, Masoumeh Dorri; Ozbolat, Guluzar; Arabi, Hossein; Malmir, Somayeh; Naseri, Shahrokh; Ravan, Vahid Roshan; Akbari-Lalimi, HosseinBackground/Objectives: Attenuation correction (AC) is essential for achieving quantitatively accurate PET imaging. In 68Ga-PSMA PET, however, artifacts such as respiratory motion, halo effects, and truncation errors in CT-based AC (CT-AC) images compromise image quality and impair model training for deep learning-based AC. This study proposes a novel artifact-refinement framework that filters out corrupted PET-CT images to create a clean dataset for training an image-domain AC model, eliminating the need for anatomical reference scans. Methods: A residual neural network (ResNet) was trained using paired PET non-AC and PET CT-AC images from a dataset of 828 whole-body 68Ga-PSMA PET-CT scans. An initial model was trained using all data and employed to identify artifact-affected samples via voxel-level error metrics. These outliers were excluded, and the refined dataset was used to retrain the model with an L2 loss function. Performance was evaluated using metrics including mean error (ME), mean absolute error (MAE), relative error (RE%), RMSE, and SSIM on both internal and external test datasets. Results: The model trained with the artifact-free dataset demonstrated significantly improved performance: ME = -0.009 +/- 0.43 SUV, MAE = 0.09 +/- 0.41 SUV, and SSIM = 0.96 +/- 0.03. Compared to the model trained on unfiltered data, the purified data model showed enhanced quantitative accuracy and robustness in external validation. Conclusions: The proposed data purification framework significantly enhances the performance of deep learning-based AC for 68Ga-PSMA PET by mitigating artifact-induced errors. This approach facilitates reliable PET imaging in the absence of anatomical references, advancing clinical applicability and image fidelity.Öğe Regulation of Nrf2 and Nrf2-related proteins by ganoderma lucidum in hepatocellular carcinoma(Springer, 2022) Aslaminabad, Ramin; Rahimianshahreza, Negin; Hosseini, Seyed Amirhossein; Armagan, Guliz; Khan, Ahmad Kashif; Ozbolat, Guluzar; Ahmed, Omar SaadBackground HCC is among the most common cancer. Ganoderma lucidum (G.lucidum) has been essential in preventing and treating cancer. The Nrf2 signaling cascade is a cell protective mechanism against further damage, such as cancer development. This signaling pathway upregulates the cytoprotective genes and is vital in eliminating xenobiotics and reactive oxygen. This study aimed to show the potential cytotoxic activity of G. lucidum aqueous extract in HCC. Methods and results MTT assay was used to detect cell viability. Nrf2-related proteins were measured by western blotting, and the flow cytometry method assayed cell population in different cycle phases. Cell viability was 49% and 47% following G. lucidum extract at 100 mu g/ml at 24 and 48 h treatments, respectively. G. lucidum extract (aqueous, 100 or 50 mu g/ml) treatments for 24, 48, or 72 h were able to significantly change the cytoplasmic/nuclear amount of Nrf2 and HO-1, NQO1 protein levels. Moreover, at both concentrations, arrest of the G0/G1 cell cycle was stimulated in HCC. Conclusions The activation of the Nrf2 signaling pathways seems to be among the mechanisms underlining the protective and therapeutic action of G. lucidum against HCC.Öğe Revolutionizing personalized medicine using artificial intelligence: a meta-analysis of predictive diagnostics and their impacts on drug development(Springer-Verlag Italia Srl, 2025) Daemi, Amin; Kalami, Sahar; Tahiraga, Ruhiyya Guliyeva; Ghanbarpour, Omid; Barghani, Mohammad Reza Rahimi; Hooshiar, Mohammad Hosseini; Ozbolat, GuluzarArtificial intelligence (AI) is transforming the landscape of laboratory medicine by enhancing diagnostic accuracy and enabling more personalized care. Given its growing use in clinical settings, evaluating the performance of AI models in diagnostic tasks is essential to inform evidence-based implementation strategies. This meta-analysis systematically assessed the diagnostic effectiveness of AI-based models. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and IEEE Xplore using predefined keywords related to AI and diagnostic accuracy. From 430 retrieved studies, 17 met the inclusion criteria. Data extracted included study design, AI model type, input modality, and performance metrics such as sensitivity, specificity, and area under the curve (AUC). Random-effects meta-analysis and subgroup analyses were performed to investigate heterogeneity and model-specific trends. The pooled analysis yielded a high combined AUC of 0.9025, indicating strong diagnostic capability of AI models. However, substantial heterogeneity was detected (I2 = 91.01%), attributed to differences in model architecture, diagnostic domains, and data quality. Subgroup analyses showed that convolutional neural networks and random forest models achieved higher AUC values, while domains like endocrinology demonstrated greater performance variability. Funnel plot inspection and sensitivity analysis indicated the presence of publication bias. AI shows strong potential to enhance diagnostic accuracy in personalized laboratory medicine. Nonetheless, methodological heterogeneity and publication bias remain significant challenges. Future research should prioritize standardized evaluation frameworks, transparency, and the development of explainable AI systems to ensure responsible clinical integration.Öğe Sodium butyrate entrapped chitosan-PAMAM for suppression of colorectal cancer cells(Bmc, 2025) Al-Zihaymee, Ruaa Mahdi Mayih; Mohammadnejad, Javad; Narmani, Asghar; Jafar, Hanieh; Ozbolat, Guluzar; Daemi, Amin; Dogus, YusufObjective Cancer treatment is a major concern of health worldwide. Nowadays, colorectal cancer is one of the most prevalent diseases throughout the globe. Therefore, novel cancer treatment modalities are required to stop cancer. Thus, this paper aims to develop a novel drug delivery system (DDS) based on Chitosan (CS), polyamidoamine (PAMAM G4), and Nanoparticles (NP) for efficient delivery of sodium butyrate (NB) and Fe2O3 to SW480 colorectal cancer cells. Methods To do so, after characterizing the nanocarrier with FT-IR, DLS, TEM, and TGA, nanometric size (40-65 nm), high drug content (23% Fe2O3 and 3% NB), controlled NB release (4% within 2 h), and pH-sensitive NB release (35% within 2 h) were measured for CS-PAMAM-Fe2O3-NB. Result In biomedical tests, MTT assay indicated 10% (after 24 h), 8% (after 48 h), and 7% (after 72 h) cell viabilities for 200 nM concentration of CS-PAMAM-Fe2O3-NB nanocarrier on SW480 cells while pure NB did not have potential toxicity on cancer cells. IC50 determined for 25 nM after 24 h. qRT-PCR test indicated a 7-fold and 10-fold increase for Caspase9 and Bax apoptotic genes whereas 0.3-fold expression quantified for Bcl2 anti-apoptotic gene. Conclusion According to the obtained results, it can be concluded that the fabricated nanocarrier would be a potential DDS against colorectal cancer cells. The results of these biomedical tests have approved potential the ability of the synthesized DDS in the inhibition of colorectal cancer cells. High biocompatibility was shown in MSC normal cells which further verified the efficiency of CS-PAMAM-Fe2O3-NB.Öğe Synthesis, characterization, biological activity and electrochemistry studies of iron(III) complex with curcumin-oxime ligand(Wiley, 2020) Ozbolat, Guluzar; Yegani, Arash AlizadehIron overload is a key target in drug development. This study aimed to investigate the coordination of Fe(III) ions with a curcumin-oxime ligand that may be used in the treatment of iron overload. The synthesis of the curcumin-oxime ligand and curcumin-oxime-Fe(III) complex was successfully made and characterized in its solid-state and solution-state using FT-IR, UV-Vis, elemental analysis, and H-1-NMR. However, in this study, we investigated the apoptotic effects of the curcumin-oxime Fe (III) complex on SW480. SW480 cells were exposed to 99.2% medium for 48 hours. After 48 hours, the incubation period, cells were harvested by centrifugation and washed in phosphate-buffered saline (PBS) and lysed in radio-immunoprecipitation assay (RIPA) buffer for 20 minutes and supernatants were taken and pellets were discarded. ELISA test was used to examine the expression, and activity of cleaved caspase-3, Bax, and Bcl-2 proteins in SW480 cells. ELISA test results indicated that the activities of apoptotic proteins Bax, caspase 3 and Bcl-2 in human SW480 cell lines significantly increased in 48 hours treatment. Also, the activity of Bcl-2 was observed to decrease significantly. Catalase activities of the complex were investigated. The findings showed that the complex has a catalase activity. The findings suggest that this type of complex may constitute a new and interesting basis for the future search of new and more potent drugs. The SOD activity of the result showed that the complexes possessed a considerable SOD activity with an IC50 value of 7.685 mu M. Also, when compared with the control, a complex increased the SOD levels (P < .05). Electrochemistry studies in the literature have shown that the Fe3+/Fe(2+)couple redox process occurs in low potential. This value is within the range of compounds that are expected to show superoxide dismutase activity. The I-pc/I(pa)shows that one electron transport takes place in the complex. Our results suggest that curcumin-oxime may represent a new approach in the treatment of iron overload.
