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Öğe AuNPs with Cynara scolymus leaf extracts rescue arsenic-induced neurobehavioral deficits and hippocampal tissue toxicity in Balb/c mice through D1R and D2R activation(Elsevier, 2024) Cicek, Betul; Hacimuftuoglu, Ahmet; Yeni, Yesim; Kuzucu, Mehmet; Genc, Sidika; Cetin, Ahmet; Taghizadehghalehjoughi, AliThe present study was designed to evaluate whether AuNPs (gold nanoparticles) synthesized with the Cynara scolymus (CS) leaf exert protective and/or alleviative effects on arsenic (As)-induced hippocampal neurotoxicity in mice. Neurotoxicity in mice was developed by orally treating 10 mg/kg/day sodium arsenite (NaAsO2) for 21 days. 10 mu g/g AuNPs, 1.6 g/kg CS, and 10 mu g/g CS-AuNPs were administered orally simultaneously with 10 mg/ kg As. CS and CS-AuNPs treatments showed down-regulation of TNF-alpha and IL-1 beta levels. CS and CS-AuNPs also ameliorated apoptosis and reduced the alterations in the expression levels of D1 and D2 dopamine receptors induced by As. Simultaneous treatment with CS and CS-AuNPs improved As-induced learning, memory deficits, and motor coordination in mice assessed by water maze and locomotor tests, respectively. The results of this study provide evidence that CS-AuNPs demonstrated neuroprotective roles with antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as improving D1 and D2 signaling, and eventually reversed neurobehavioral impairments.Öğe Effects of quercetin-immobilized albumin cerium oxide nanoparticles on glutamate toxicity: in vitro study(Springer, 2025) Yeni, Yesim; Genc, Sidika; Nadaroglu, Hayrunnisa; Hacimuftuoglu, AhmetOne aspect of glutamate (Glut) toxicity may be the opening of the blood-brain barrier to albumin (Al), which in itself can cause nerve cell death. Quercetin (Q) is a polyphenolic substance and has a neuroprotective effect. Cerium oxide nanoparticles (Ce(2)O(3)NPs) are highly interested in biological applications due to their antioxidant properties. The current study aimed to investigate the impact of Q-immobilized Al+Ce(2)O(3)NPs in Glut-induced neurotoxicity, mainly focusing on cell viability and neurobiochemical changes. Hydrothermal synthesis and characterization of Q-immobilized Al+Ce(2)O(3)NPs were performed. After preparing the primary neuron culture, it was exposed to Glut to induce neurotoxicity. Then, various doses of Ce2O3NP, Al+Ce2O3NP, and Q+Al+Ce(2)O(3)NPs (1, 5, 10, and 25 mu g/ml) were applied to the wells and incubated for 24 h. Then, cell viability was determined by MTT analysis. Additionally, oxidative stress parameters were measured. When the obtained data were examined, it was shown that cell viability decreased with Glut concentration but significantly increased with Q+Al+Ce(2)O(3)NPs treatment. When oxidative stress markers were considered, Glut treatment increased LDH, AChE, and TOS levels, while TAC and GSH levels decreased. However, the trend changed after Q+Al+Ce(2)O(3)NPs treatment, suggesting that damaged neurons were protected against oxidative stress. The results of this study indicate that Q+Al+Ce2O3NP can ameliorate Glut-induced neurotoxicity, especially when used at a dose of 25 mu g/ml.Öğe Exploring the anti-inflammatory activity of boron compounds through the miR-21/PTEN/AKT pathway in cecal ligation and puncture-induced sepsis(Spandidos Publ Ltd, 2025) Sevim, Cigdem; Ozkaraca, Mustafa; Kara, Mehtap; Taghizadehghalehjoughi, Ali; Genc, Sidika; Yeni, Yesim; Mendil, Ali SefaThe present study investigated the impact of boric acid (BA) and borax (BX) on markers of inflammation and modifications in miR-21/PTEN/AKT pathway genes in the liver and kidney tissues of Sprague Dawley male rats with sepsis induced by cecal ligation and puncture (CLP). A total of 60 male Sprague Dawley rats were randomly divided into 6 groups, each containing 10 animals as follows: Control, CLP (where the model was created), 20 mg/kg BX (CLP + BX1), 40 mg/kg BX (CLP + BX2), 20 mg/kg BA (CLP + BA1) and 40 mg/kg BA (CLP + BA2). Liver and kidney tissues were analyzed for histopathological changes, immunopositivity for tumor necrosis factor-alpha, interleukin (IL)-6 and IL-10, and gene expression of microRNA-21 (miR-21), phosphatase and tensin homolog (PTEN) and AKT. Gene expression analysis in the liver tissues revealed a significant decrease in miR-21, and a marked but not significant decrease in PTEN levels in the CLP group, while AKT expression was significantly increased in the CLP group, and was significantly decreased in CLP + BA1 group compared with in the CLP group. In the kidney tissues, miR-21 levels were significantly decreased in the CLP group, but the CLP + BA2 group showed a significant increase compared with in the CLP group. These results suggest the potential therapeutic benefits of low-dose BA and BX in ameliorating sepsis-induced tissue damage, emphasizing the need for further exploration of their mechanisms of action.Öğe Glioblastoma cell-derived exosomes induce cell death and oxidative stress in primary cultures of olfactory neurons. Role of redox stress(Springer, 2023) Yeni, Yesim; Taghizadehghalehjoughi, Ali; Genc, Sidika; Hacimuftuoglu, Ahmet; Yildirim, Serkan; Bolat, IsmailBackgroundGlioblastoma multiforme, described as glioblastoma, is a malignancy originating from glial progenitors in the central nervous system and is the most malignant subtype of brain tumors which attracted researcher's attention due to their high recurrence and mortality despite optimal treatments. In the study, we aimed to research whether glioblastoma-originated exosomes play a role in olfactory nerve cell toxicity.Methods and resultsFor this aim, exosomes obtained from U373 and T98G cells were applied to olfactory nerve cell culture at distinct doses. Then, glutathione (GSH), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT), total oxidant status (TOS) and Immunofluorescence analyzes were performed. We found that both glioblastoma-derived exosomes decreased cell viability in olfactory neurons with increasing doses. According to the obtained data, the olfactory neuron vitality rate was 71% in T98G-exosome, but the decrease in U373-exosome was more obvious (48%). In particular, the 100 mu g/ml dose exacerbated oxidative stress by increasing TOS. It also increased cellular apoptosis compared to the control group due to LDH leakage. However, the results of GSH and TAS showed that antioxidant levels were significantly reduced.ConclusionIn the microenvironment of olfactory neurons, GBM-derived exosomes increased oxidative stress-induced toxicity by reducing TAC and GSH levels. Therefore, glioblastoma cells by induction of exosome-based stress support malignant growth.Öğe Morinda citrifolia protective effects on paclitaxel-induced testis parenchyma toxicity: An experimental study(Pergamon-Elsevier Science Ltd, 2024) Genc, Sidika; Cicek, Betul; Yeni, Yesim; Kuzucu, Mehmet; Hacimuftuoglu, Ahmet; Bolat, Ismail; Taghizadehghalehjoughi, AliThe current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/ kg were noteworthy. The increased levels of IL1-beta (Interleukin 1 beta) and TNF alpha (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.Öğe Neuroprotective effects of L-Dopa-modified zinc oxide nanoparticles on the rat model of 6-OHDA-ınduced Parkinson's disease(Nature Portfolio, 2024) Yeni, Yesim; Genc, Sidika; Ertugrul, Muhammed Sait; Nadaroglu, Hayrunnisa; Gezer, Arzu; Mendil, Ali Sefa; Hacimuftuoglu, AhmetParkinson's disease (PD) is a chronic neurodegenerative case. As the disease progresses, the response time to doses of levodopa (L-Dopa) becomes shorter and the effects of the drug are severely limited by some undesirable side effects such as the 'on-off' phenomenon. In several diseases, including Parkinson's, nanoparticles can deliver antioxidant compounds that reduce oxidative stress. This study evaluates and compares the neuroprotective effects of L-Dopa-modified zinc nanoparticles (ZnNPs) in the 6-hydroxydopamine (6-OHDA)-induced PD rat model. For this purpose, the synthesis of NPs was carried out. Scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectrophotometer were used for characterization. The rats were randomized into 9 experimental groups: control, lesion group (6-OHDA), 6-OHDA + 5 mg/kg L-Dopa, 6-OHDA + 10 mg/kg L-Dopa, 6-OHDA + 20 mg/kg L-Dopa, 6-OHDA + 20 mg/kg ZnNPs, 6-OHDA + 40 mg/kg ZnNPs, 6-OHDA + 30 mg/kg ZnNPs + L-Dopa, and 6-OHDA + 60 mg/kg ZnNPs + L-Dopa. Behavioral tests were performed on all groups 14 days after treatment. Phosphatase and tensin homolog, Excitatory amino acid transporter 1/2, and Glutamine synthetase gene analyses were performed on brain samples taken immediately after the tests. In addition, histological and immunohistochemical methods were used to determine the general structure and properties of the tissues. We obtained important findings that L-Dopa-modified ZnNPs increased the activity of glutamate transporters. Our experiment showed that glutamate increases neuronal cell vitality and improves behavioral performance. Therefore, L-Dopa-modified ZnNPs can be used to prevent neurotoxicity. According to what we found, results show that L-Dopa-modified ZnNPs will lend to the effective avoidance and therapy of PD.Öğe Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries(Mdpi, 2023) Cicek, Betul; Hacimuftuoglu, Ahmet; Kuzucu, Mehmet; Cetin, Ahmet; Yeni, Yesim; Genc, Sidika; Taghizadehghalehjoughi, AliAccording to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-alpha and IL-1 beta levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.Öğe The Impact of Different Part Extracts of Peganum harmala L. on Human Colorectal Adenocarcinoma Cell Line (Caco-2)(Wiley, 2024) Tasci, Seymanur Yilmaz; Genc, Sidika; Yeni, Yesim; Karakaya, Songul[Abstract Not Available]Öğe The Impact of Various Extracts of Angelica purpurascens (Ave-Lall.) Gilli on Caco-2 Cell Line(Wiley, 2024) Tasci, Seymanur Yilmaz; Genc, Sidika; Yeni, Yesim; Karakaya, Songul[Abstract Not Available]
