Selim Gökdemir, Zeynep Gizem Todurga Seven, A. Shahzadi, Neşet Neşetoğlu, Durişehvar Ünal, Gökhan Akkan, Sibel Özyazgan
Abstract Objectives Hyperhomocysteinemia (HHcy) a significant risk factor for vascular disease, often emerges in epilepsy with the use of antiepileptic drugs. In this relationship, our study investigates the combined effects of HHcy and antiepileptics on vascular function using a rat model. Methods Fourty two rats were included and divided into six groups as, 1-Control, 2-L-Met, 3-LEV injected, 4-LEV-injected + L-Met, 5-VAL-injected, 6-VAL injected + L-Met. L-Methionine (L-Met) was added to drinking water of rats for 1 month to develop HHcy. Simultaneously, intraperitoneal (ip) injections of sodium valproate (VAL) and levetiracetam (LEV) were administered. Effects were comparatively investigated, and noradrenaline (NA), followed by acetylcholine (ACh) and glyceryl trinitrate (GTN) were applied in organ bath system. Agonist doses were expressed as ten base logarithm (M) through 10−9, 10−8, 10−7, 10−6, 10−5, 10−4 mol/L in dose-response graph. Results NA contractions between LEV and LEV + L-Met groups showed statistical significance (LEV Emax=288.50 ± 46.54, LEV + L-Met Emax=480.40 ± 78.83) (p<0.05) however, no significance was observed among the other groups. ACh relaxations between Control-L-Met (Control Inhmax=12.65 ± 2.09, L-Met Inhmax=50.05 ± 7.43) (p<0.05), and Control-Val + L-Met (Control Emax=328.20 ± 52.83, VAL + L-Met Emax=452.60 ± 71.53) (p<0.01), groups showed statistical significance. Between other groups, no significance was observed. In GTN relaxations, no statistical significance was observed. Conclusions This study highlights the adverse impact of HHcy on aortic relaxation. Further impairment was observed with VAL compared to other treatment and control groups. These findings underscore the importance of considering vascular side effects when selecting antiepileptic drugs. Ultimately, our study contributes valuable insights that may aid the choice of appropriate treatment strategies to mitigate potential vascular complications of HHcy.
{"title":"Comparative vascular effects of levetiracetam and valproate with hyperhomocysteinemia in rat models","authors":"Selim Gökdemir, Zeynep Gizem Todurga Seven, A. Shahzadi, Neşet Neşetoğlu, Durişehvar Ünal, Gökhan Akkan, Sibel Özyazgan","doi":"10.1515/tjb-2023-0061","DOIUrl":"https://doi.org/10.1515/tjb-2023-0061","url":null,"abstract":"Abstract Objectives Hyperhomocysteinemia (HHcy) a significant risk factor for vascular disease, often emerges in epilepsy with the use of antiepileptic drugs. In this relationship, our study investigates the combined effects of HHcy and antiepileptics on vascular function using a rat model. Methods Fourty two rats were included and divided into six groups as, 1-Control, 2-L-Met, 3-LEV injected, 4-LEV-injected + L-Met, 5-VAL-injected, 6-VAL injected + L-Met. L-Methionine (L-Met) was added to drinking water of rats for 1 month to develop HHcy. Simultaneously, intraperitoneal (ip) injections of sodium valproate (VAL) and levetiracetam (LEV) were administered. Effects were comparatively investigated, and noradrenaline (NA), followed by acetylcholine (ACh) and glyceryl trinitrate (GTN) were applied in organ bath system. Agonist doses were expressed as ten base logarithm (M) through 10−9, 10−8, 10−7, 10−6, 10−5, 10−4 mol/L in dose-response graph. Results NA contractions between LEV and LEV + L-Met groups showed statistical significance (LEV Emax=288.50 ± 46.54, LEV + L-Met Emax=480.40 ± 78.83) (p<0.05) however, no significance was observed among the other groups. ACh relaxations between Control-L-Met (Control Inhmax=12.65 ± 2.09, L-Met Inhmax=50.05 ± 7.43) (p<0.05), and Control-Val + L-Met (Control Emax=328.20 ± 52.83, VAL + L-Met Emax=452.60 ± 71.53) (p<0.01), groups showed statistical significance. Between other groups, no significance was observed. In GTN relaxations, no statistical significance was observed. Conclusions This study highlights the adverse impact of HHcy on aortic relaxation. Further impairment was observed with VAL compared to other treatment and control groups. These findings underscore the importance of considering vascular side effects when selecting antiepileptic drugs. Ultimately, our study contributes valuable insights that may aid the choice of appropriate treatment strategies to mitigate potential vascular complications of HHcy.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"144 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139153073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Becer, Servet Madencioğlu, H. Kabadayı, H. Vatansever
Abstract Objectives Resveratrol (RSV) is a stilbenoid compound that shows anticancer activity in many cancer cells. Exosomes might affect carcinogenesis and the development of colorectal cancer by affecting communication between tumor cells in the tumor microenvironment via their cargo content miRNA. The aim of this study is to determine the effect of RSV on the expression of Dicer, Ago2, eIf2α, CD-9, CD-63, and exosomal miRNA levels in COLO320 and COLO741 colon cancer cell lines. Methods The MTT method was used for cell growth and cytotoxicity in both COLO320 and COLO741 cell lines. Dicer, Ago2, eIF2α, CD-9, and CD-63 antibodies were used for the immunocytochemical evaluation. Total miRNA analysis was performed using a miRCURY Exosome Isolation Kit. Results As a result of immunocytochemical staining, increased CD-63 immunoreactivity was observed in RSV-treated COLO320 cells vs. RSV-treated COLO-741 cells. Dicer immunoreactivity increased after the RSV treatment in COLO320 cells. Higher eIF2α immunoreactivity was observed in RSV-treated COLO741 cells compared to both COLO741 control cells and RSV-treated COLO320 cells. Non-significant decreases were observed in miRNA concentration in RSV-treated COLO320 and COLO741 cells compared to control group cells. Conclusions RSV could increase miRNA biogenesis in COLO320 cancer cells and decrease it in COLO741 cancer cells.
{"title":"Resveratrol modulates miRNA machinery proteins in different types of colon cancer cells","authors":"E. Becer, Servet Madencioğlu, H. Kabadayı, H. Vatansever","doi":"10.1515/tjb-2023-0076","DOIUrl":"https://doi.org/10.1515/tjb-2023-0076","url":null,"abstract":"Abstract Objectives Resveratrol (RSV) is a stilbenoid compound that shows anticancer activity in many cancer cells. Exosomes might affect carcinogenesis and the development of colorectal cancer by affecting communication between tumor cells in the tumor microenvironment via their cargo content miRNA. The aim of this study is to determine the effect of RSV on the expression of Dicer, Ago2, eIf2α, CD-9, CD-63, and exosomal miRNA levels in COLO320 and COLO741 colon cancer cell lines. Methods The MTT method was used for cell growth and cytotoxicity in both COLO320 and COLO741 cell lines. Dicer, Ago2, eIF2α, CD-9, and CD-63 antibodies were used for the immunocytochemical evaluation. Total miRNA analysis was performed using a miRCURY Exosome Isolation Kit. Results As a result of immunocytochemical staining, increased CD-63 immunoreactivity was observed in RSV-treated COLO320 cells vs. RSV-treated COLO-741 cells. Dicer immunoreactivity increased after the RSV treatment in COLO320 cells. Higher eIF2α immunoreactivity was observed in RSV-treated COLO741 cells compared to both COLO741 control cells and RSV-treated COLO320 cells. Non-significant decreases were observed in miRNA concentration in RSV-treated COLO320 and COLO741 cells compared to control group cells. Conclusions RSV could increase miRNA biogenesis in COLO320 cancer cells and decrease it in COLO741 cancer cells.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"41 167","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139154513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Vlădăreanu, M. Onisâi, Iuliana Iordan, Eugen Radu, Adrian Roşca, O. Munteanu, D. Soare, Cristina Mambet, S. Voiculescu, H. Bumbea, I. Voican, A. Nicolescu, Alina Mititelu, R. Nistor, D. Secară, A. Băicuș, M. Cirstoiu
Abstract Objectives To assess the frequency of multiple thrombophilia-associated mutations and polymorphisms in a selected population of high-risk pregnancies. Methods Thrombophilia screening was performed for 1,500 pregnant women with prior pregnancy complications or thrombotic events. Nine thrombophilia-associated mutations or polymorphisms were screened: factor V Leiden, factor V H1299R, prothrombin G20210A, MTHFR C677T, MTHFR A1298C, factor XIII V34L, PAI-1 4G/5G polymorphisms, EPCR G4600A, EPCR C4678G. Results Out of the 1,500 patients, 1,291 fulfilled the criteria for data interpretation. All patients had low-risk thrombophilia-associated genetic variants. Only 1.24 % of cases presented high-risk abnormalities (homozygous factor V Leiden/prothrombin G20210A, or both mutations in heterozygous form). Heterozygous factor V Leiden occurred in 10.38 % of cases, while only 5.81 % carried heterozygous prothrombin G20210A mutation. The frequency of prothrombin G20210A mutation was higher (10.37 %) in the subgroup associating factor V Leiden, than in the subgroup lacking it (5.36 %). Low-risk genetic variants occurred with a higher frequency: 23.78 % factor V H1299R, 57.32 % MTHFR C677T, 55.54 % MTHFR A1298C, 44.07 % factor XIII V34L, 73.20 % PAI-1 4G/5G polymorphisms, 69.64 % EPCR G4600A, and 69.63 % EPCR C4678G. Conclusions All patients had at least one prothrombotic genetic mutation or variant. Our data highlight the need for thrombophilia screening, including low-risk genetic variants, in a high-risk population of pregnant women with a history of pregnancy complications or thrombotic events.
摘要 目的 评估选定的高危妊娠人群中多种血栓性疾病相关突变和多态性的频率。方法 对 1,500 名曾有妊娠并发症或血栓事件的孕妇进行血栓性疾病筛查。筛查了九种血栓性疾病相关突变或多态性:因子 V Leiden、因子 V H1299R、凝血酶原 G20210A、MTHFR C677T、MTHFR A1298C、因子 XIII V34L、PAI-1 4G/5G 多态性、EPCR G4600A、EPCR C4678G。结果 在 1,500 名患者中,1,291 人符合数据解读标准。所有患者都有低风险的血栓性疾病相关基因变异。只有 1.24% 的病例存在高风险异常(同基因 V Leiden 因子/凝血酶原 G20210A,或两种变异均为杂合型)。10.38% 的病例出现杂合因子 V Leiden,而只有 5.81% 的病例携带杂合凝血酶原 G20210A 突变。凝血酶原 G20210A 突变在与 V Leiden 因子相关的亚组中的发生率(10.37%)高于缺乏 V Leiden 因子的亚组(5.36%)。低风险基因变异出现的频率较高:23.78% 的因子 V H1299R、57.32% 的 MTHFR C677T、55.54% 的 MTHFR A1298C、44.07% 的因子 XIII V34L、73.20% 的 PAI-1 4G/5G 多态性、69.64% 的 EPCR G4600A 和 69.63% 的 EPCR C4678G。结论 所有患者都有至少一种促血栓形成基因突变或变异。我们的数据强调了在有妊娠并发症或血栓事件史的高危孕妇群体中进行血栓性疾病筛查(包括低风险基因变异)的必要性。
{"title":"Frequency of thrombophilia-associated mutations and polymorphisms in pregnant women with a history of thrombosis or pregnancy complications","authors":"A. Vlădăreanu, M. Onisâi, Iuliana Iordan, Eugen Radu, Adrian Roşca, O. Munteanu, D. Soare, Cristina Mambet, S. Voiculescu, H. Bumbea, I. Voican, A. Nicolescu, Alina Mititelu, R. Nistor, D. Secară, A. Băicuș, M. Cirstoiu","doi":"10.1515/tjb-2022-0273","DOIUrl":"https://doi.org/10.1515/tjb-2022-0273","url":null,"abstract":"Abstract Objectives To assess the frequency of multiple thrombophilia-associated mutations and polymorphisms in a selected population of high-risk pregnancies. Methods Thrombophilia screening was performed for 1,500 pregnant women with prior pregnancy complications or thrombotic events. Nine thrombophilia-associated mutations or polymorphisms were screened: factor V Leiden, factor V H1299R, prothrombin G20210A, MTHFR C677T, MTHFR A1298C, factor XIII V34L, PAI-1 4G/5G polymorphisms, EPCR G4600A, EPCR C4678G. Results Out of the 1,500 patients, 1,291 fulfilled the criteria for data interpretation. All patients had low-risk thrombophilia-associated genetic variants. Only 1.24 % of cases presented high-risk abnormalities (homozygous factor V Leiden/prothrombin G20210A, or both mutations in heterozygous form). Heterozygous factor V Leiden occurred in 10.38 % of cases, while only 5.81 % carried heterozygous prothrombin G20210A mutation. The frequency of prothrombin G20210A mutation was higher (10.37 %) in the subgroup associating factor V Leiden, than in the subgroup lacking it (5.36 %). Low-risk genetic variants occurred with a higher frequency: 23.78 % factor V H1299R, 57.32 % MTHFR C677T, 55.54 % MTHFR A1298C, 44.07 % factor XIII V34L, 73.20 % PAI-1 4G/5G polymorphisms, 69.64 % EPCR G4600A, and 69.63 % EPCR C4678G. Conclusions All patients had at least one prothrombotic genetic mutation or variant. Our data highlight the need for thrombophilia screening, including low-risk genetic variants, in a high-risk population of pregnant women with a history of pregnancy complications or thrombotic events.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"73 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139153545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ergül Mutlu Altundağ, A. T. Jannuzzi, Cahit Özbilenler, Selma Ustürk, Gülcem Altınoğlu
Abstract Objectives Glioblastoma is a fast-growing and aggressive brain tumor. Despite the current treatment methods, such as chemical and surgical operations, the prognosis is still poor. Therefore, combined therapeutic strategies are proposed to maximize therapeutic efficacy and reduce toxicity. Thymoquinone has been shown to have neuroprotective effects in addition to its anti-cancer effects on different types of cancer. 5-Fluorouracil, on the other hand, is a cytotoxic chemotherapy agent used to treat cancer. As a synergistic combinational approach, this study aimed to examine the antiproliferative effects and production of reactive oxygen species in a glioblastoma cell line. Methods We have tested thymoquinone and 5-fluorouracil alone and in their combination to observe cellular growth with MTT assay. The combinational effects of the agents were determined by the CompuSYN software program. Cell proliferation was assayed with crystal violet assay. Reactive oxygen species production was analyzed by 2′,7′-dichlorodihydrofluorescein diacetate in glioblastoma cells. Results Thymoquinone and 5-fluorouracil inhibited cell growth of glioblastoma cells with half maximal inhibitory concentrations (IC50) of 45.93 and 14.02 µM for 48 h, respectively. At synergistic combinational concentrations, the crystal violet assay demonstrated that there is a positive correlation between combination index values and cell proliferation. Also, an increment in the production of reactive oxygen species was observed upon combinational treatments. Conclusions Our results indicate that the combinational strategy of these two agents reduced cell viability and proliferation in glioblastoma cells and showed strong synergistic anticancer efficiency.
{"title":"Synergistic role of thymoquinone and 5-fluorouracil in U-251MG glioblastoma cell line","authors":"Ergül Mutlu Altundağ, A. T. Jannuzzi, Cahit Özbilenler, Selma Ustürk, Gülcem Altınoğlu","doi":"10.1515/tjb-2023-0150","DOIUrl":"https://doi.org/10.1515/tjb-2023-0150","url":null,"abstract":"Abstract Objectives Glioblastoma is a fast-growing and aggressive brain tumor. Despite the current treatment methods, such as chemical and surgical operations, the prognosis is still poor. Therefore, combined therapeutic strategies are proposed to maximize therapeutic efficacy and reduce toxicity. Thymoquinone has been shown to have neuroprotective effects in addition to its anti-cancer effects on different types of cancer. 5-Fluorouracil, on the other hand, is a cytotoxic chemotherapy agent used to treat cancer. As a synergistic combinational approach, this study aimed to examine the antiproliferative effects and production of reactive oxygen species in a glioblastoma cell line. Methods We have tested thymoquinone and 5-fluorouracil alone and in their combination to observe cellular growth with MTT assay. The combinational effects of the agents were determined by the CompuSYN software program. Cell proliferation was assayed with crystal violet assay. Reactive oxygen species production was analyzed by 2′,7′-dichlorodihydrofluorescein diacetate in glioblastoma cells. Results Thymoquinone and 5-fluorouracil inhibited cell growth of glioblastoma cells with half maximal inhibitory concentrations (IC50) of 45.93 and 14.02 µM for 48 h, respectively. At synergistic combinational concentrations, the crystal violet assay demonstrated that there is a positive correlation between combination index values and cell proliferation. Also, an increment in the production of reactive oxygen species was observed upon combinational treatments. Conclusions Our results indicate that the combinational strategy of these two agents reduced cell viability and proliferation in glioblastoma cells and showed strong synergistic anticancer efficiency.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"3 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139156945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives Cholangiocarcinoma (CCA) is usually diagnosed at a late stage due to resistance to chemotherapeutic drugs. Epithelial mesenchymal transition (EMT) is a biological process in cancer that allows multiple biochemical changes that enable epithelial cells to acquire a mesenchymal phenotype. In the present study, we focused on the EMT process which is an important in carcinogenesis and metastatic progression, and also investigate the effect of silibinin on cell proliferation, colony formation, migration, apoptosis, cell cycle and EMT. Methods Cell viability, apoptosis and cell cycle were measured by Muse Cell Analyzer. All the protein levels were determined by ELISA method. Results We found that silibinin significantly reduced cell proliferation in a dose-dependent manner and the IC50 value was 200 μM. Silibinin, significantly inhibited colony formation, inhibited cell migration of cancer cells induced total apoptosis due to the induction of early and late apoptosis, arrest cancer cells in the G0/G1 phase of the cell cycle compared to the control group. We found that E-cadherin, N-cadherin, Vimentin and α-SMA protein levels were significantly decreased in the silibinin group compared to the control group. Conclusions Our results showed that silibinin could significantly prevent tumor proliferation, reduce colony formation, prevent migration, increase the arrest of the G0/G1 phase and induce apoptosis progress in human extracellular cholangiocarcinoma cell line. Another important data is that silibinin inhibits EMT in the cholangiocarcinoma cell line (TFK-1). Our study shows significant effects of silibinin in the TFK-1 cell line, which may be exciting to explore its implications in future animal studies.
{"title":"Silibinin reduces cell proliferation and migration via EMT pathway in TFK-1 cell line","authors":"Merve Özel Yetkin, G. Baskol","doi":"10.1515/tjb-2022-0270","DOIUrl":"https://doi.org/10.1515/tjb-2022-0270","url":null,"abstract":"Abstract Objectives Cholangiocarcinoma (CCA) is usually diagnosed at a late stage due to resistance to chemotherapeutic drugs. Epithelial mesenchymal transition (EMT) is a biological process in cancer that allows multiple biochemical changes that enable epithelial cells to acquire a mesenchymal phenotype. In the present study, we focused on the EMT process which is an important in carcinogenesis and metastatic progression, and also investigate the effect of silibinin on cell proliferation, colony formation, migration, apoptosis, cell cycle and EMT. Methods Cell viability, apoptosis and cell cycle were measured by Muse Cell Analyzer. All the protein levels were determined by ELISA method. Results We found that silibinin significantly reduced cell proliferation in a dose-dependent manner and the IC50 value was 200 μM. Silibinin, significantly inhibited colony formation, inhibited cell migration of cancer cells induced total apoptosis due to the induction of early and late apoptosis, arrest cancer cells in the G0/G1 phase of the cell cycle compared to the control group. We found that E-cadherin, N-cadherin, Vimentin and α-SMA protein levels were significantly decreased in the silibinin group compared to the control group. Conclusions Our results showed that silibinin could significantly prevent tumor proliferation, reduce colony formation, prevent migration, increase the arrest of the G0/G1 phase and induce apoptosis progress in human extracellular cholangiocarcinoma cell line. Another important data is that silibinin inhibits EMT in the cholangiocarcinoma cell line (TFK-1). Our study shows significant effects of silibinin in the TFK-1 cell line, which may be exciting to explore its implications in future animal studies.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"38 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138943745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Nanobiotechnology is a specific field of biotechnology that utilizes nanoscale methods and materials to investigate biological systems and create innovative medical technologies. This review discusses the diverse use of nanobiotechnology in health, focusing on both its superior properties and challenges. The main aims of this report are to present and elaborate on the global market share of this growing field as well as the scientific output, regarding publications and patents in the last decade. Quantitative data is derived from the Statnano database, which includes information related to the articles from the Web of Science (WoS) and approved patents from the European Patent Office and the United States Patent and Trademark Office. The final aim of this review is to provide some suggestions based on these data. Government support is the most important driving force in building up research and publications. Support for advancement in nanotechnology to fabricate products for commercial and public benefit is the top priority of developed nations. Thus, entrepreneurial training of young researchers, and collaborations between scientists, policymakers, investors, and citizens, should be encouraged. To work together globally and set international standards for the creation of consistent methods in characterizing nanoscale products with biological systems is imperative.
{"title":"Critical evaluation of publications and patents in nanobiotechnology-based research in the last decade","authors":"Fulden Ulucan-Karnak, C. I. Kuru, F. Sağın","doi":"10.1515/tjb-2023-0144","DOIUrl":"https://doi.org/10.1515/tjb-2023-0144","url":null,"abstract":"Abstract Nanobiotechnology is a specific field of biotechnology that utilizes nanoscale methods and materials to investigate biological systems and create innovative medical technologies. This review discusses the diverse use of nanobiotechnology in health, focusing on both its superior properties and challenges. The main aims of this report are to present and elaborate on the global market share of this growing field as well as the scientific output, regarding publications and patents in the last decade. Quantitative data is derived from the Statnano database, which includes information related to the articles from the Web of Science (WoS) and approved patents from the European Patent Office and the United States Patent and Trademark Office. The final aim of this review is to provide some suggestions based on these data. Government support is the most important driving force in building up research and publications. Support for advancement in nanotechnology to fabricate products for commercial and public benefit is the top priority of developed nations. Thus, entrepreneurial training of young researchers, and collaborations between scientists, policymakers, investors, and citizens, should be encouraged. To work together globally and set international standards for the creation of consistent methods in characterizing nanoscale products with biological systems is imperative.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"34 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138943558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hazal B. Catalak Yilmaz, Mahnoor Sulaiman, Ozlem Aybuke Isik, Onur Çizmecioğlu
Abstract Objectives The catalytic subunits of Class IA PI3K, p110α, p110β, and p110δ, phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) into phosphatidylinositol 3,4,5-trisphosphate (PIP3) on the plasma membrane. In cancer, these catalytic subunits are usually found to be altered or amplified. Because pan-PI3K inhibition results in systemic toxicities, finding specific targets for the ubiquitous PI3K isoforms offers considerable potential for enhancing the effectiveness of PI3K-targeted therapy. Methods We aim to delineate the isoform-specific druggable targets of the PI3K by deleting PIK3CA (encoding p110α) and PIK3CB (encoding p110β) by Cre mediated excision and ectopically expressing p110α, p110β, or p110δ with or without myristoylation (Myr) tag in mouse embryonic fibroblasts (MEFs). Myr is a lipidation signal that translocates proteins to plasma membrane permanently. This translocation renders p110s constitutively activated as they remain in close proximity to PIP2 on the membrane. Results Unique and redundant Akt targets are identified downstream of different PI3K isoforms. mTORC1, one of the targets of fully-activated Akt, has been observed to be differentially regulated in MEFs upon expression of p110α or p110β. The varying dependencies on mTORC1 and Rac1 led us to analyse a potential scaffolding function of p110β with Rac1 to mediate phosphorylation and activation of mTOR using platforms for the modeling of biomolecular complexes. We also documented that p110α and p110β support cell cycle kinetics differentially. Conclusions This study suggests differential regulation of protein translation, metabolism, cell cycle, and survival signaling downstream of unique p110 targets, underlying the importance of cancer treatment according to the deregulated p110 isoform.
{"title":"Class IA PI3K isoforms lead to differential signalling downstream of PKB/Akt","authors":"Hazal B. Catalak Yilmaz, Mahnoor Sulaiman, Ozlem Aybuke Isik, Onur Çizmecioğlu","doi":"10.1515/tjb-2023-0146","DOIUrl":"https://doi.org/10.1515/tjb-2023-0146","url":null,"abstract":"Abstract Objectives The catalytic subunits of Class IA PI3K, p110α, p110β, and p110δ, phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) into phosphatidylinositol 3,4,5-trisphosphate (PIP3) on the plasma membrane. In cancer, these catalytic subunits are usually found to be altered or amplified. Because pan-PI3K inhibition results in systemic toxicities, finding specific targets for the ubiquitous PI3K isoforms offers considerable potential for enhancing the effectiveness of PI3K-targeted therapy. Methods We aim to delineate the isoform-specific druggable targets of the PI3K by deleting PIK3CA (encoding p110α) and PIK3CB (encoding p110β) by Cre mediated excision and ectopically expressing p110α, p110β, or p110δ with or without myristoylation (Myr) tag in mouse embryonic fibroblasts (MEFs). Myr is a lipidation signal that translocates proteins to plasma membrane permanently. This translocation renders p110s constitutively activated as they remain in close proximity to PIP2 on the membrane. Results Unique and redundant Akt targets are identified downstream of different PI3K isoforms. mTORC1, one of the targets of fully-activated Akt, has been observed to be differentially regulated in MEFs upon expression of p110α or p110β. The varying dependencies on mTORC1 and Rac1 led us to analyse a potential scaffolding function of p110β with Rac1 to mediate phosphorylation and activation of mTOR using platforms for the modeling of biomolecular complexes. We also documented that p110α and p110β support cell cycle kinetics differentially. Conclusions This study suggests differential regulation of protein translation, metabolism, cell cycle, and survival signaling downstream of unique p110 targets, underlying the importance of cancer treatment according to the deregulated p110 isoform.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"64 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138954576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasemin ARDICOGLU AKISIN, Nejat Akar, Mert Burkay COTELİ
Abstract Objectives Epstein–Barr virus (EBV) is a member of the herpes virus that causes infectious mononucleosis (IM). Downey cell is the atypical lymphocyte of IM and can be seen in various conditions. Peripheral blood smear (PBS) microscopic evaluation is used to identify Downey cells. A lack of experienced professionals or professional errors may obstruct early and accurate diagnostics for the microscopic evaluation. The main objective of this study is to create a decision support system by digitizing the PBS samples. A general tool providing an inexpensive and measurable solution is envisioned to analyze the PBS samples in detail to give alerting flags to prevent missing Downey cells in manual analysis. Methods The PBS dataset collected was split into Downey positives and negatives. The negative set consisted of 5 leucocyte subtypes. Mantiscope, a cloud-based slide scanner system, was used to collect images from the physical PBS samples. Clinically and laboratory-confirmed 35 IM patients and 124 healthy PBS slides were selected for this procedure. A number of cell counts were obtained after the application of annotation and augmentation methods, and a partially balanced dataset was created for the artificial intelligence (AI) network training. The verification steps included the calculation of sensitivity, specificity, and Cohen’s kappa metrics from the partitioned testing set that was not used during training. A validation process was also performed over the manually identified PBS samples to measure whether the algorithm noticed the samples or not. Results After testing this setup, we have observed 98 % sensitivity and 99 % specificity for Downey cells. According to the validation procedure of Downey positive and negative samples that were carried out by the physicians, a sensitivity of 57 %, specificity of 100 %, and Cohen’s kappa value of 0.5 were observed. Besides, the accuracy was found to be 66 % according to the physicians’ evaluations employing the digital images which were identified by Mantiscope, Conclusions Decision support systems can alert the physician for Downey cells and increase the rate of true diagnosis in PBS evaluation. A higher sensitivity and specificity for the detection of Downey cells would be achieved. However, the variance over the dataset is a constraint for effective diagnosis. As the annotation and AI development process continues to collect more data from patients, the model can be updated for future releases.
{"title":"Decision support system for the classification of Downey cells as a pre-diagnostic tool","authors":"Yasemin ARDICOGLU AKISIN, Nejat Akar, Mert Burkay COTELİ","doi":"10.1515/tjb-2023-0035","DOIUrl":"https://doi.org/10.1515/tjb-2023-0035","url":null,"abstract":"Abstract Objectives Epstein–Barr virus (EBV) is a member of the herpes virus that causes infectious mononucleosis (IM). Downey cell is the atypical lymphocyte of IM and can be seen in various conditions. Peripheral blood smear (PBS) microscopic evaluation is used to identify Downey cells. A lack of experienced professionals or professional errors may obstruct early and accurate diagnostics for the microscopic evaluation. The main objective of this study is to create a decision support system by digitizing the PBS samples. A general tool providing an inexpensive and measurable solution is envisioned to analyze the PBS samples in detail to give alerting flags to prevent missing Downey cells in manual analysis. Methods The PBS dataset collected was split into Downey positives and negatives. The negative set consisted of 5 leucocyte subtypes. Mantiscope, a cloud-based slide scanner system, was used to collect images from the physical PBS samples. Clinically and laboratory-confirmed 35 IM patients and 124 healthy PBS slides were selected for this procedure. A number of cell counts were obtained after the application of annotation and augmentation methods, and a partially balanced dataset was created for the artificial intelligence (AI) network training. The verification steps included the calculation of sensitivity, specificity, and Cohen’s kappa metrics from the partitioned testing set that was not used during training. A validation process was also performed over the manually identified PBS samples to measure whether the algorithm noticed the samples or not. Results After testing this setup, we have observed 98 % sensitivity and 99 % specificity for Downey cells. According to the validation procedure of Downey positive and negative samples that were carried out by the physicians, a sensitivity of 57 %, specificity of 100 %, and Cohen’s kappa value of 0.5 were observed. Besides, the accuracy was found to be 66 % according to the physicians’ evaluations employing the digital images which were identified by Mantiscope, Conclusions Decision support systems can alert the physician for Downey cells and increase the rate of true diagnosis in PBS evaluation. A higher sensitivity and specificity for the detection of Downey cells would be achieved. However, the variance over the dataset is a constraint for effective diagnosis. As the annotation and AI development process continues to collect more data from patients, the model can be updated for future releases.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"124 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138959373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Societal habits’ continuation is expected to result in severe consequences for climate change, causing significant environmental damage and humanitarian crises. Sustainability, defined as meeting present needs without compromising future generations, balances environment, equity, and economy. Türkiye, a middle-income developing country, has committed to achieving net-zero emissions by 2053 under the United Nations’ framework. The construction sector is increasingly adopting eco-friendly practices, emphasizing green buildings and structures. Several green hospital certification systems, including BREEAM, LEED, and Australian Green Star, are now in use, with around 20 certified “green hospitals” in Türkiye. The “Zero Waste Project” initiated in Türkiye aims to reduce waste generation and resource usage efficiently. Recent efforts have focused on sustainability in high-carbon footprint medical laboratories, however, an international standard has not been established yet. Clinical chemistry and laboratory medicine federations have established working groups on the subject. Universities and nonprofits worldwide offer green laboratory certificate programs covering energy conservation, green chemistry, waste management, and water conservation. Laboratories’ sustainability efforts encompass inventory management, green purchasing, test request reduction, greenhouse gas management, efficient building design, transportation choices, carbon footprint calculations, and education. The guides published in Türkiye are “Health Institutions Wastewater/Liquid Waste Management Handbook” and “Guide for Laboratory and Dialysis Wastes”. Türkiye’s Ministry of Health introduced the “Rational Test Request Procedure” to enhance diagnostic accuracy and cost-effectiveness by reducing unnecessary tests. Collective efforts are essential to raise awareness and implement precautions, particularly in high-carbon footprint medical laboratories, addressing climate change and sustainability challenges in the healthcare sector.
{"title":"Green transformation in the health sector and medical laboratories, adaptation to climate change in Türkiye","authors":"G. Aykal","doi":"10.1515/tjb-2023-0207","DOIUrl":"https://doi.org/10.1515/tjb-2023-0207","url":null,"abstract":"Abstract Societal habits’ continuation is expected to result in severe consequences for climate change, causing significant environmental damage and humanitarian crises. Sustainability, defined as meeting present needs without compromising future generations, balances environment, equity, and economy. Türkiye, a middle-income developing country, has committed to achieving net-zero emissions by 2053 under the United Nations’ framework. The construction sector is increasingly adopting eco-friendly practices, emphasizing green buildings and structures. Several green hospital certification systems, including BREEAM, LEED, and Australian Green Star, are now in use, with around 20 certified “green hospitals” in Türkiye. The “Zero Waste Project” initiated in Türkiye aims to reduce waste generation and resource usage efficiently. Recent efforts have focused on sustainability in high-carbon footprint medical laboratories, however, an international standard has not been established yet. Clinical chemistry and laboratory medicine federations have established working groups on the subject. Universities and nonprofits worldwide offer green laboratory certificate programs covering energy conservation, green chemistry, waste management, and water conservation. Laboratories’ sustainability efforts encompass inventory management, green purchasing, test request reduction, greenhouse gas management, efficient building design, transportation choices, carbon footprint calculations, and education. The guides published in Türkiye are “Health Institutions Wastewater/Liquid Waste Management Handbook” and “Guide for Laboratory and Dialysis Wastes”. Türkiye’s Ministry of Health introduced the “Rational Test Request Procedure” to enhance diagnostic accuracy and cost-effectiveness by reducing unnecessary tests. Collective efforts are essential to raise awareness and implement precautions, particularly in high-carbon footprint medical laboratories, addressing climate change and sustainability challenges in the healthcare sector.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"607 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138973918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anjing Zhang, Z. Zhong, Dengke Pan, Peidong Yang, Shuqi Yang, Jideng Ma, Tingting Luo, Li Chen, Jinwei Zhang, Jing Sun, Jiaxiang Du, K. Long, Mingzhou Li, Lu Lu
Abstract Objectives The final step in the production of the human Sd(a) antigen is catalyzed by beta-1,4-N-acetyl-galactosamine transferase 2 (B4GALNT2). This is done by adding a N-acetylgalactosamine residue via a beta-1,4 linkage to a subterminal galactose residue that has been substituted with an alpha-2,3-linked sialic acid. The final stage of the production of the Cad antigen is also catalyzed by B4GALNT2. Knocking out pig B4GALNT2 gene decreased human serum antibodies binding to pig cells, which greatly reduces the immunological rejection in clinical xenotransplantation trials. Interestingly, gene region LOC110255214 (hereafter named B4GALNT2-like) showed high similarity with the B4GALNT2 gene in the pig genome in our previous work, but whether B4GALNT2-like shares similar biological properties like B4GALNT2 remains to be elucidated, whether B4GALNT2-like is a potential immune gene in xenotransplantation remains to be determined. Methods In this study, we compared the tissue expression pattern of B4GALNT2-like and B4GALNT2 in Bama pigs. Results We found the expression of B4GALNT2-like was significantly higher in the duodenum, but lower in the heart, spleen, lung, kidney, comparing to B4GALNT2. Applied the Escherichia coli recombinant expression, we obtained 768 and 1,300 μg protein for B4GALNT2 and B4GALNT2-like from 1 L culture, respectively. Using the expressed recombinant proteins, the enzymatic activity of the two proteins was determined and compared. Conclusions The enzymatic assay showed that B4GALNT2-like has comparable catalytic activity with B4GALNT2 (58.7 % of B4GALNT2), addressing an important question whether B4GALNT2-like is a new immunological rejection gene.
目的制备人Sd(a)抗原的最后一步是由β -1,4- n -乙酰半乳糖胺转移酶2 (B4GALNT2)催化。这是通过-1,4链将n -乙酰半乳糖胺残基添加到亚末端半乳糖残基上,该半乳糖残基已被-2,3链唾液酸取代。Cad抗原产生的最后阶段也由B4GALNT2催化。敲除猪B4GALNT2基因可降低人血清抗体与猪细胞的结合,从而大大降低临床异种移植试验中的免疫排斥反应。有趣的是,LOC110255214基因区域(以下简称B4GALNT2-like)在我们之前的工作中显示出与猪基因组中的B4GALNT2基因高度相似,但B4GALNT2-like是否与B4GALNT2具有相似的生物学特性仍有待阐明,B4GALNT2-like是否在异种移植中具有潜在的免疫基因仍有待确定。方法比较B4GALNT2样蛋白和B4GALNT2在巴马猪组织中的表达模式。结果B4GALNT2-like在十二指肠的表达明显高于B4GALNT2,而在心脏、脾脏、肺、肾脏的表达明显低于B4GALNT2。应用大肠杆菌重组表达,从1个 L培养中分别获得B4GALNT2和B4GALNT2样蛋白768和1,300 μg。利用表达的重组蛋白对两种蛋白的酶活性进行测定和比较。结论酶促实验显示B4GALNT2-like与B4GALNT2具有相当的催化活性(58.7 % B4GALNT2),解决了B4GALNT2-like是否为一种新的免疫排斥基因的重要问题。
{"title":"Enzymatic comparison and expression pattern of pig B4GALNT2 and B4GALNT2-like proteins","authors":"Anjing Zhang, Z. Zhong, Dengke Pan, Peidong Yang, Shuqi Yang, Jideng Ma, Tingting Luo, Li Chen, Jinwei Zhang, Jing Sun, Jiaxiang Du, K. Long, Mingzhou Li, Lu Lu","doi":"10.1515/tjb-2023-0148","DOIUrl":"https://doi.org/10.1515/tjb-2023-0148","url":null,"abstract":"Abstract Objectives The final step in the production of the human Sd(a) antigen is catalyzed by beta-1,4-N-acetyl-galactosamine transferase 2 (B4GALNT2). This is done by adding a N-acetylgalactosamine residue via a beta-1,4 linkage to a subterminal galactose residue that has been substituted with an alpha-2,3-linked sialic acid. The final stage of the production of the Cad antigen is also catalyzed by B4GALNT2. Knocking out pig B4GALNT2 gene decreased human serum antibodies binding to pig cells, which greatly reduces the immunological rejection in clinical xenotransplantation trials. Interestingly, gene region LOC110255214 (hereafter named B4GALNT2-like) showed high similarity with the B4GALNT2 gene in the pig genome in our previous work, but whether B4GALNT2-like shares similar biological properties like B4GALNT2 remains to be elucidated, whether B4GALNT2-like is a potential immune gene in xenotransplantation remains to be determined. Methods In this study, we compared the tissue expression pattern of B4GALNT2-like and B4GALNT2 in Bama pigs. Results We found the expression of B4GALNT2-like was significantly higher in the duodenum, but lower in the heart, spleen, lung, kidney, comparing to B4GALNT2. Applied the Escherichia coli recombinant expression, we obtained 768 and 1,300 μg protein for B4GALNT2 and B4GALNT2-like from 1 L culture, respectively. Using the expressed recombinant proteins, the enzymatic activity of the two proteins was determined and compared. Conclusions The enzymatic assay showed that B4GALNT2-like has comparable catalytic activity with B4GALNT2 (58.7 % of B4GALNT2), addressing an important question whether B4GALNT2-like is a new immunological rejection gene.","PeriodicalId":23344,"journal":{"name":"Turkish Journal of Biochemistry","volume":"47 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138633053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}