Araştırma Makalesi
Mikroçoğaltılan Alternanthera reineckii Briq.'nin İnsan Keratinosit Hücrelerinde Çinko Oksit Nanopartiküllerine Karşı Detoksifikasyon Etkinliği
Öz
Nanoteknolojideki hızlı gelişmeler göz önüne alındığında, nanoteknolojinin insan sağlığı üzerindeki tehlikelerinin önüne geçebilmek için nanotoksikoloji alanında bilimsel araştırmalara ihtiyaç duyulmaktadır. Bu amaçla birçok kozmetik üründe yer alan ZnO nanopartikülünün (NP) insan keratinosit hücreleri (HaCaT) üzerindeki sitotoksik etkisini test ettik. Ek olarak, doku kültür yöntemi ile üretilen bir su bitkisi olan Alternanthera reineckii Briq. ile bu sitotoksik etkiyi inhibe etme potansiyelini değerlendirdik. A. reineckii'nin nodal eksplantları, 0,25-1,25 mg/L Thidiazuron (TDZ) ve 0,25 mg/L indol-3-bütirik asit (IBA) kombinasyonlarını içeren Murashige & Skoog bazal ortamında (MS) kültüre edildi. Eksplant başına maksimum sürgün sayısı (22,50 sürgün/eksplant) 0,75 mg/L TDZ+0,25 mg/L IBA içeren kültür ortamında elde edilmiştir. En yüksek sürgün uzunluğu (1,77 cm) 0,25 mg/L TDZ+0,25 mg/L IBA içeren MS ortamında belirlenmiştir. A. reineckii'den Soxhlet ekstraksiyonu yoluyla aseton ve su özütleri elde edilmiştir. Tek başına ZnO'nun HaCaT üzerindeki sitotoksik etkisi, aseton ve su özütleri ile inhibe edilmiştir. ZnO'nun etkisiyle %26,04'e düşen hücre canlılığı, aseton özütü uygulamasıyla %67,83'e kadar yükselmiştir. Genel olarak, sonuçlarımız bu bitkinin ZnO tarafından indüklenen nanotoksisiteye karşı koruyucu potansiyelini ortaya koymuş ve gelecekteki çalışmalara ışık tutmuştur.
Anahtar Kelimeler
Kaynakça
- Abdullah, A.H.D., Putri, O.D., Fikriyyah, A.K., Nissa, R.C., Hidayat, S., Septiyanto, R.F., Karina, M., & Satoto, R. (2020). Harnessing the Excellent Mechanical, Barrier and Antimicrobial Properties of Zinc Oxide (ZnO) to Improve the Performance of Starch-Based Bioplastic. Polymer-Plastics Technology and Materials 59(12), 1259–1267.
- Agustina, T.E., Melwita, E., Bahrin, D., Gayatri, R., & Purwaningtyas, I.F. (2020). Synthesis of Nano-Photocatalyst ZnO-Natural Zeolite to Degrade Procion Red. International Journal of Technology 11(3), 472–481.
- Akbaba, G.B., & Türkez, H. (2018). Investigation of the Genotoxicity of Aluminum Oxide, β-Tricalcium Phosphate, and Zinc Oxide Nanoparticles In Vitro. International Journal of Toxicology 37(3), 216–222.
- Anderson, L.W.J., Fried, G., Gunasekera, L., Hussner, A., Newman, J., Starfinger, U., Stiers, I., van Valkenburg, J., & Tanner, R. (2015). Pest risk analysis for Alternanthera philoxeroides. EPPO, Paris.
- Braakhuis, H.M., Kloet, S.K., Kezic, S., Kuper, F., Park, M.V.D.Z., Bellmann, S., van der Zande, M., Le Gac, S., Krystek, P., Peters, R.J.B., Rietjens, I.M.C.M., & Bouwmeester, H. (2015). Progress and Future of In Vitro Models to Study Translocation of Nanoparticles. Archives of Toxicology 89(9), 1469–1495.
- Braakhuis, H.M., Park, M.V.D.Z., Gosens, I., De Jong, W.H., & Cassee, F.R. (2014). Physicochemical Characteristics of Nanomaterials That Affect Pulmonary Inflammation. Particle and Fibre Toxicology 11(1), 18.
- Celik, M., Keskin, N., & Ozdemir, F.A. (2020). The Effects of UV Irradiation and Incubation Time on In Vitro Phenolic Compound Production in ‘Karaerik’ Grape Cultivar. KSÜ Tarım ve Doğa Dergisi 23(6), 1428–1434.
- Das, A., Kamle, M., Bharti, A., & Kumar, P. (2019). Nanotechnology and It’s Applications in Environmental Remediation: An Overview. Vegetos 32(3), 227–237.
- Dewir, Y.H., Nurmansyah, N., Naidoo, Y., & Teixeira da Silva, J.A. (2018). Thidiazuron-Induced Abnormalities in Plant Tissue Cultures. Plant Cell Reports 37(11), 1451–1470.
- Dhavala, A., & Rathore, T.S. (2010). Micropropagation of Embelia Ribes Burm f. through Proliferation of Adult Plant Axillary Shoots. In Vitro Cellular and Developmental Biology - Plant 46(2), 180–191.
- Dilkalal, A., Annapurna, A.S., & Umesh, T.G. (2021). In Vitro Regeneration, Antioxidant Potential, and Genetic Fidelity Analysis of Asystasia gangetica (L.) T. Anderson. In Vitro Cellular and Developmental Biology - Plant 57(3), 447–459.
- El-Sherif, N.A. (2019). Impact of Plant Tissue Culture on Agricultural Sustainability. Handbook of Environmental Chemistry 77, 93–107.
- Emsen, B., Aslan, A., Turkez, H., Taghizadehghalehjoughi, A., & Kaya, A. (2018). The Anti‑cancer Efficacies of Diffractaic, Lobaric, and Usnic Acid: In Vitro Inhibition of Glioma. Journal of Cancer Research and Therapeutics 14(5), 941–951.
- Emsen, B., & Dogan, M. (2018). Evaluation of Antioxidant Activity of In Vitro Propagated Medicinal Ceratophyllum demersum L. Extracts. Acta Scientiarum Polonorum-Hortorum Cultus 17(1), 23–33.
- Emsen, B., & Turkez, H. (2017). The Protective Role of Resveratrol against Zinc Oxide Induced Nanotoxicity. Anatolian Journal of Botany 1(2), 21–25.
- Giannenas, I., Sidiropoulou, E., Bonos, E., Christaki, E., & Florou-Paneri, P. (2019). The History of Herbs, Medicinal and Aromatic Plants, and Their Extracts: Past, Current Situation and Future Perspectives. In: Feed Additives: Aromatic Plants and Herbs in Animal Nutrition and Health. pp 1–18.
- Giordo, R., Nasrallah, G.K., Al-Jamal, O., Paliogiannis, P., & Pintus, G. (2020). Resveratrol Inhibits Oxidative Stress and Prevents Mitochondrial Damage Induced by Zinc Oxide Nanoparticles in Zebrafish (Danio Rerio). International Journal of Molecular Sciences 21(11), 3838.
- Gollavilli, H., Hegde, A.R., Managuli, R.S., Bhaskar, K.V., Dengale, S.J., Reddy, M.S., Kalthur, G., & Mutalik, S. (2020). Naringin Nano-Ethosomal Novel Sunscreen Creams: Development and Performance Evaluation. Colloids and Surfaces B: Biointerfaces 193, 111122.
- Hosseini Tafreshi, S.A., Aghaie, P., Momayez, H.R., & Hejaziyan, S.A. (2021). Response of In Vitro-Regenerated Myrtus communis L. Shoots to PEG-Induced Water Stress. Biocatalysis and Agricultural Biotechnology 34, 102033.
- Jahan, I., & Isildak, I. (2021). Lemon Peel Extract for Synthesizing Non-Toxic Silver Nanoparticles through One-Step Microwave-Accelerated Scheme. KSÜ Tarım ve Doğa Dergisi 24(1), 1–10.
- Jeong, S.H., Kim, H.J., Ryu, H.J., Ryu, W.I., Park, Y.H., Bae, H.C., Jang, Y.S., & Son, S.W. (2013). ZnO Nanoparticles Induce TNF-α Expression via ROS-ERK-Egr-1 Pathway in Human Keratinocytes. Journal of Dermatological Science 72(3), 263–273.
- Jirakiattikul, Y., Rithichai, P., Songsoem, K., & Itharat, A. (2021). Elicitation of Salicylic Acid on Secondary Metabolite Production and Antioxidant Activity of In Vitro Musa acuminata L. Cv. ‘Gros Michel’ Shoots. Current Applied Science and Technology 21(3), 569–578.
- Kavitha, P., Shanthi, C., & Kannan, R. (2022). A Facile Green Synthesis of Nanostructured Gold–Silver@Carbon (Au–Ag@C) Nano Catalyst and Its Applications. Kuwait Journal of Science 49(2), 1–12.
- Lee, C.-C., Lin, Y.-H., Hou, W.-C., Li, M.-H., & Chang, J.-W. (2020). Exposure to ZnO/TiO2 Nanoparticles Affects Health Outcomes in Cosmetics Salesclerks. International Journal of Environmental Research and Public Health 17(17), 1–12.
- Lee, S.H., Pie, J.E., Kim, Y.R., Lee, H.R., Son, S.W., & Kim, M.K. (2012). Effects of Zinc Oxide Nanoparticles on Gene Expression Profile in Human Keratinocytes. Molecular and Cellular Toxicology 8(2), 113–118.
- Lee, W.-M., & An, Y.-J. (2013). Effects of Zinc Oxide and Titanium Dioxide Nanoparticles on Green Algae under Visible, UVA, and UVB Irradiations: No Evidence of Enhanced Algal Toxicity under UV Pre-Irradiation. Chemosphere 91(4), 536–544.
- Máthé, Á., Hassan, F., & Abdul Kader, A. (2015). In Vitro Micropropagation of Medicinal and Aromatic Plants. In: Medicinal and Aromatic Plants of the World. Springer, Dordrecht, pp 305–336.
- Mohajerani, A., Burnett, L., Smith, J.V., Kurmus, H., Milas, J., Arulrajah, A., Horpibulsuk, S., & Kadir, A.A. (2019). Nanoparticles in Construction Materials and Other Applications, and Implications of Nanoparticle Use. Materials 12(19), 3052.
- Monsé, C., Raulf, M., Hagemeyer, O., Van Kampen, V., Kendzia, B., Gering, V., Marek, E.-M., Jettkant, B., Bünger, J., Merget, R., Merget, R., & Brüning, T. (2019). Airway Inflammation after Inhalation of Nano-Sized Zinc Oxide Particles in Human Volunteers. BMC Pulmonary Medicine 19(1), 266.
- Novikova, T.I., Asbaganov, S.V., Ambros, E.V., & Zaytseva, Y.G. (2020). TDZ-Induced Axillary Shoot Proliferation of Rhododendron mucronulatum Turcz and Assessment of Clonal Fidelity Using DNA-Based Markers and Flow Cytometry. In Vitro Cellular and Developmental Biology - Plant 56(3), 307–317.
- Novikova, T.I., & Zaytseva, Y.G. (2018). TDZ-Induced Morphogenesis Pathways in Woody Plant Culture. In: Ahmad N, Faisal M (eds) Thidiazuron: From Urea Derivative to Plant Growth Regulator. pp 61–94
- Ozelci, D., & Yigit, E. (2022). Micropropagation of the Morus nigra L. (Black Mulberry) cv. ‘Eksi Kara’. KSÜ Tarım ve Doğa Dergisi 25(1), 49–56.
- Rani, A., & Kumar, S. (2017). Tissue Culture as a Plant Production Technique for Medicinal Plants: A Review. International Conference on Innovative Research in Science, Technology and Management 6(1), 784–795.
- Sagadevan, S., Raj, K.P., Aziz, F.A., Chowdhury, Z.Z., Johan, M.R.B., & Podder, J. (2018). Structure, Properties, Photocatalytic and Antibacterial Activity and Applications of Zinc Oxide Nanoparticles-an Overview. Journal of Bionanoscience 12(4), 457–468.
- Sujatha, K., Panda, B.M., & Hazra, S. (2008). De Novo Organogenesis and Plant Regeneration in Pongamia pinnata, Oil Producing Tree Legume. Trees - Structure and Function 22(5), 711–716.
- Uma, H.B., Ananda, S., & Nandaprakash, M.B. (2019). High Efficient Photocatalytic Treatment of Textile Dye and Antibacterial Activity via Electrochemically Synthesized Ni-Doped ZnO Nano Photocatalysts. Chemical Data Collections 24, 100301.
Detoxification Efficiency of Micropropagated Alternanthera reineckii Briq. against Zinc Oxide Nanoparticles in Human Keratinocyte Cells
Öz
Considering the rapid developments in nanotechnology, scientific research in the field of nanotoxicology is required in order to prevent the dangers of nanotechnology on human health. For this purpose, we tested the cytotoxic effect of ZnO nanoparticle (NP), which is included in many cosmetic products, on human keratinocyte cells (HaCaT). In addition, we evaluated to potentially inhibit this cytotoxic effect with an aquatic plant, Alternanthera reineckii Briq. produced by tissue culture method. The nodal explants of A. reineckii were cultured in Murashige & Skoog basal medium (MS) including the combinations of 0.25-1.25 mg/L Thidiazuron (TDZ) and 0.25 mg/L indole-3-butyric acid (IBA). Maximum number of shoots per explant (22.50 shoots/explant) was obtained in the culture medium with 0.75 mg/L TDZ+0.25 mg/L IBA. The highest shoot length (1.77 cm) was determined in MS medium with 0.25 mg/L TDZ+0.25 mg/L IBA. Acetone and water extracts were obtained from A. reineckii through Soxhlet extraction. The cytotoxic effect of ZnO alone on HaCaT was inhibited by acetone and water extracts. The cell viability, which decreased to 26.04% with the effect of ZnO, increased up to 67.83% with the application of acetone extract. Overall, our results revealed the protective potential of this plant against nanotoxicity induced by ZnO and shed light on future studies
Anahtar Kelimeler
Kaynakça
- Abdullah, A.H.D., Putri, O.D., Fikriyyah, A.K., Nissa, R.C., Hidayat, S., Septiyanto, R.F., Karina, M., & Satoto, R. (2020). Harnessing the Excellent Mechanical, Barrier and Antimicrobial Properties of Zinc Oxide (ZnO) to Improve the Performance of Starch-Based Bioplastic. Polymer-Plastics Technology and Materials 59(12), 1259–1267.
- Agustina, T.E., Melwita, E., Bahrin, D., Gayatri, R., & Purwaningtyas, I.F. (2020). Synthesis of Nano-Photocatalyst ZnO-Natural Zeolite to Degrade Procion Red. International Journal of Technology 11(3), 472–481.
- Akbaba, G.B., & Türkez, H. (2018). Investigation of the Genotoxicity of Aluminum Oxide, β-Tricalcium Phosphate, and Zinc Oxide Nanoparticles In Vitro. International Journal of Toxicology 37(3), 216–222.
- Anderson, L.W.J., Fried, G., Gunasekera, L., Hussner, A., Newman, J., Starfinger, U., Stiers, I., van Valkenburg, J., & Tanner, R. (2015). Pest risk analysis for Alternanthera philoxeroides. EPPO, Paris.
- Braakhuis, H.M., Kloet, S.K., Kezic, S., Kuper, F., Park, M.V.D.Z., Bellmann, S., van der Zande, M., Le Gac, S., Krystek, P., Peters, R.J.B., Rietjens, I.M.C.M., & Bouwmeester, H. (2015). Progress and Future of In Vitro Models to Study Translocation of Nanoparticles. Archives of Toxicology 89(9), 1469–1495.
- Braakhuis, H.M., Park, M.V.D.Z., Gosens, I., De Jong, W.H., & Cassee, F.R. (2014). Physicochemical Characteristics of Nanomaterials That Affect Pulmonary Inflammation. Particle and Fibre Toxicology 11(1), 18.
- Celik, M., Keskin, N., & Ozdemir, F.A. (2020). The Effects of UV Irradiation and Incubation Time on In Vitro Phenolic Compound Production in ‘Karaerik’ Grape Cultivar. KSÜ Tarım ve Doğa Dergisi 23(6), 1428–1434.
- Das, A., Kamle, M., Bharti, A., & Kumar, P. (2019). Nanotechnology and It’s Applications in Environmental Remediation: An Overview. Vegetos 32(3), 227–237.
- Dewir, Y.H., Nurmansyah, N., Naidoo, Y., & Teixeira da Silva, J.A. (2018). Thidiazuron-Induced Abnormalities in Plant Tissue Cultures. Plant Cell Reports 37(11), 1451–1470.
- Dhavala, A., & Rathore, T.S. (2010). Micropropagation of Embelia Ribes Burm f. through Proliferation of Adult Plant Axillary Shoots. In Vitro Cellular and Developmental Biology - Plant 46(2), 180–191.
- Dilkalal, A., Annapurna, A.S., & Umesh, T.G. (2021). In Vitro Regeneration, Antioxidant Potential, and Genetic Fidelity Analysis of Asystasia gangetica (L.) T. Anderson. In Vitro Cellular and Developmental Biology - Plant 57(3), 447–459.
- El-Sherif, N.A. (2019). Impact of Plant Tissue Culture on Agricultural Sustainability. Handbook of Environmental Chemistry 77, 93–107.
- Emsen, B., Aslan, A., Turkez, H., Taghizadehghalehjoughi, A., & Kaya, A. (2018). The Anti‑cancer Efficacies of Diffractaic, Lobaric, and Usnic Acid: In Vitro Inhibition of Glioma. Journal of Cancer Research and Therapeutics 14(5), 941–951.
- Emsen, B., & Dogan, M. (2018). Evaluation of Antioxidant Activity of In Vitro Propagated Medicinal Ceratophyllum demersum L. Extracts. Acta Scientiarum Polonorum-Hortorum Cultus 17(1), 23–33.
- Emsen, B., & Turkez, H. (2017). The Protective Role of Resveratrol against Zinc Oxide Induced Nanotoxicity. Anatolian Journal of Botany 1(2), 21–25.
- Giannenas, I., Sidiropoulou, E., Bonos, E., Christaki, E., & Florou-Paneri, P. (2019). The History of Herbs, Medicinal and Aromatic Plants, and Their Extracts: Past, Current Situation and Future Perspectives. In: Feed Additives: Aromatic Plants and Herbs in Animal Nutrition and Health. pp 1–18.
- Giordo, R., Nasrallah, G.K., Al-Jamal, O., Paliogiannis, P., & Pintus, G. (2020). Resveratrol Inhibits Oxidative Stress and Prevents Mitochondrial Damage Induced by Zinc Oxide Nanoparticles in Zebrafish (Danio Rerio). International Journal of Molecular Sciences 21(11), 3838.
- Gollavilli, H., Hegde, A.R., Managuli, R.S., Bhaskar, K.V., Dengale, S.J., Reddy, M.S., Kalthur, G., & Mutalik, S. (2020). Naringin Nano-Ethosomal Novel Sunscreen Creams: Development and Performance Evaluation. Colloids and Surfaces B: Biointerfaces 193, 111122.
- Hosseini Tafreshi, S.A., Aghaie, P., Momayez, H.R., & Hejaziyan, S.A. (2021). Response of In Vitro-Regenerated Myrtus communis L. Shoots to PEG-Induced Water Stress. Biocatalysis and Agricultural Biotechnology 34, 102033.
- Jahan, I., & Isildak, I. (2021). Lemon Peel Extract for Synthesizing Non-Toxic Silver Nanoparticles through One-Step Microwave-Accelerated Scheme. KSÜ Tarım ve Doğa Dergisi 24(1), 1–10.
- Jeong, S.H., Kim, H.J., Ryu, H.J., Ryu, W.I., Park, Y.H., Bae, H.C., Jang, Y.S., & Son, S.W. (2013). ZnO Nanoparticles Induce TNF-α Expression via ROS-ERK-Egr-1 Pathway in Human Keratinocytes. Journal of Dermatological Science 72(3), 263–273.
- Jirakiattikul, Y., Rithichai, P., Songsoem, K., & Itharat, A. (2021). Elicitation of Salicylic Acid on Secondary Metabolite Production and Antioxidant Activity of In Vitro Musa acuminata L. Cv. ‘Gros Michel’ Shoots. Current Applied Science and Technology 21(3), 569–578.
- Kavitha, P., Shanthi, C., & Kannan, R. (2022). A Facile Green Synthesis of Nanostructured Gold–Silver@Carbon (Au–Ag@C) Nano Catalyst and Its Applications. Kuwait Journal of Science 49(2), 1–12.
- Lee, C.-C., Lin, Y.-H., Hou, W.-C., Li, M.-H., & Chang, J.-W. (2020). Exposure to ZnO/TiO2 Nanoparticles Affects Health Outcomes in Cosmetics Salesclerks. International Journal of Environmental Research and Public Health 17(17), 1–12.
- Lee, S.H., Pie, J.E., Kim, Y.R., Lee, H.R., Son, S.W., & Kim, M.K. (2012). Effects of Zinc Oxide Nanoparticles on Gene Expression Profile in Human Keratinocytes. Molecular and Cellular Toxicology 8(2), 113–118.
- Lee, W.-M., & An, Y.-J. (2013). Effects of Zinc Oxide and Titanium Dioxide Nanoparticles on Green Algae under Visible, UVA, and UVB Irradiations: No Evidence of Enhanced Algal Toxicity under UV Pre-Irradiation. Chemosphere 91(4), 536–544.
- Máthé, Á., Hassan, F., & Abdul Kader, A. (2015). In Vitro Micropropagation of Medicinal and Aromatic Plants. In: Medicinal and Aromatic Plants of the World. Springer, Dordrecht, pp 305–336.
- Mohajerani, A., Burnett, L., Smith, J.V., Kurmus, H., Milas, J., Arulrajah, A., Horpibulsuk, S., & Kadir, A.A. (2019). Nanoparticles in Construction Materials and Other Applications, and Implications of Nanoparticle Use. Materials 12(19), 3052.
- Monsé, C., Raulf, M., Hagemeyer, O., Van Kampen, V., Kendzia, B., Gering, V., Marek, E.-M., Jettkant, B., Bünger, J., Merget, R., Merget, R., & Brüning, T. (2019). Airway Inflammation after Inhalation of Nano-Sized Zinc Oxide Particles in Human Volunteers. BMC Pulmonary Medicine 19(1), 266.
- Novikova, T.I., Asbaganov, S.V., Ambros, E.V., & Zaytseva, Y.G. (2020). TDZ-Induced Axillary Shoot Proliferation of Rhododendron mucronulatum Turcz and Assessment of Clonal Fidelity Using DNA-Based Markers and Flow Cytometry. In Vitro Cellular and Developmental Biology - Plant 56(3), 307–317.
- Novikova, T.I., & Zaytseva, Y.G. (2018). TDZ-Induced Morphogenesis Pathways in Woody Plant Culture. In: Ahmad N, Faisal M (eds) Thidiazuron: From Urea Derivative to Plant Growth Regulator. pp 61–94
- Ozelci, D., & Yigit, E. (2022). Micropropagation of the Morus nigra L. (Black Mulberry) cv. ‘Eksi Kara’. KSÜ Tarım ve Doğa Dergisi 25(1), 49–56.
- Rani, A., & Kumar, S. (2017). Tissue Culture as a Plant Production Technique for Medicinal Plants: A Review. International Conference on Innovative Research in Science, Technology and Management 6(1), 784–795.
- Sagadevan, S., Raj, K.P., Aziz, F.A., Chowdhury, Z.Z., Johan, M.R.B., & Podder, J. (2018). Structure, Properties, Photocatalytic and Antibacterial Activity and Applications of Zinc Oxide Nanoparticles-an Overview. Journal of Bionanoscience 12(4), 457–468.
- Sujatha, K., Panda, B.M., & Hazra, S. (2008). De Novo Organogenesis and Plant Regeneration in Pongamia pinnata, Oil Producing Tree Legume. Trees - Structure and Function 22(5), 711–716.
- Uma, H.B., Ananda, S., & Nandaprakash, M.B. (2019). High Efficient Photocatalytic Treatment of Textile Dye and Antibacterial Activity via Electrochemically Synthesized Ni-Doped ZnO Nano Photocatalysts. Chemical Data Collections 24, 100301.
Toplam 36 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Yapısal Biyoloji |
| Bölüm | ARAŞTIRMA MAKALESİ (Research Article) |
| Yazarlar | |
| Erken Görünüm Tarihi | 27 Mayıs 2023 |
| Yayımlanma Tarihi | 31 Ekim 2023 |
| Gönderilme Tarihi | 24 Ocak 2023 |
| Kabul Tarihi | 14 Mart 2023 |
| Yayımlandığı Sayı | Yıl 2023Cilt: 26 Sayı: 5 |
Kaynak Göster
2022-JIF = 0.500
2022-JCI = 0.170
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