Objective: The circadian rhythm is one of the primary regulatory systems with near 24-hour oscillations. It has a crucial role in regulating physiological conditions in the human body, including body temperature and the secretion of hormones. Numerous disorders, such as cancer and diabetes, have been linked to disruptions of the cellular circadian rhythm. Herein, we aimed to investigate the relationship between the circadian rhythm and unfolded protein response (UPR) signaling, which is one of the important physiological mechanisms in mammalian cells and has recently been associated with drug resistance, invasion and metastasis in cancer. Material and Method: Human embryonic kidney cell line HEK293 was provided from the American Type Culture Collection and propagated in DMEM containing 10% FBS and growth ingredients. For in vitro circadian synchronization, cells were exposed to 50% and then the oscillation pattern of gene and protein expression of UPR-related target genes was analyzed by agarose gel electrophoresis and immunoblotting, respectively. The oscillation pattern was commented on through curve-fitting analysis. Result and Discussion: Our findings demonstrated that UPR components, including IRE1α, XBP-1s, eIF2α, phospho(Ser51)-eIF2α, PERK, ATF4, GADD34 and ATF6, tightly exhibit oscillation patterns under a circadian rhythm on a 48-hour time scale like the PER1 gene that is a core component of the circadian rhythm. Moreover, endoplasmic reticulum (ER) stress genes, BiP/GRP78 and CHOP, were similar to UPR components under the circadian rhythm. Additionally, we found the activation of UPR signaling harmoniously modulated with the circadian rhythm. Present data indicated that the expression level of UPR components exhibited strict oscillation under the circadian rhythm. Our findings may guide experimental studies of new-generation UPR-targeted drugs to be developed to treat various pathologies in accordance with the circadian rhythm.
{"title":"DETERMINATION OF THE CIRCADIAN OSCILLATION PATTERN OF UNFOLDED PROTEIN RESPONSE SIGNALING COMPONENTS IN HUMAN EMBRYONIC KIDNEY HEK293 CELLS","authors":"Y. Erzurumlu, Hatice Kübra Doğan, Deniz Çataklı","doi":"10.33483/jfpau.1487169","DOIUrl":"https://doi.org/10.33483/jfpau.1487169","url":null,"abstract":"Objective: The circadian rhythm is one of the primary regulatory systems with near 24-hour oscillations. It has a crucial role in regulating physiological conditions in the human body, including body temperature and the secretion of hormones. Numerous disorders, such as cancer and diabetes, have been linked to disruptions of the cellular circadian rhythm. Herein, we aimed to investigate the relationship between the circadian rhythm and unfolded protein response (UPR) signaling, which is one of the important physiological mechanisms in mammalian cells and has recently been associated with drug resistance, invasion and metastasis in cancer. \u0000Material and Method: Human embryonic kidney cell line HEK293 was provided from the American Type Culture Collection and propagated in DMEM containing 10% FBS and growth ingredients. For in vitro circadian synchronization, cells were exposed to 50% and then the oscillation pattern of gene and protein expression of UPR-related target genes was analyzed by agarose gel electrophoresis and immunoblotting, respectively. The oscillation pattern was commented on through curve-fitting analysis.\u0000Result and Discussion: Our findings demonstrated that UPR components, including IRE1α, XBP-1s, eIF2α, phospho(Ser51)-eIF2α, PERK, ATF4, GADD34 and ATF6, tightly exhibit oscillation patterns under a circadian rhythm on a 48-hour time scale like the PER1 gene that is a core component of the circadian rhythm. Moreover, endoplasmic reticulum (ER) stress genes, BiP/GRP78 and CHOP, were similar to UPR components under the circadian rhythm. Additionally, we found the activation of UPR signaling harmoniously modulated with the circadian rhythm. Present data indicated that the expression level of UPR components exhibited strict oscillation under the circadian rhythm. Our findings may guide experimental studies of new-generation UPR-targeted drugs to be developed to treat various pathologies in accordance with the circadian rhythm.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"7 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797120","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}
Ahmet Hüsamettin Baran, Ahmet Berk, AB Uyumlu, Özgen Arslan Solmaz, Göknur Yalım
Objective: This study aimed to evaluate the effects of sildenafil (SIL) on inflammation and histopathological changes in cadmium (Cd)-induced toxicity in female rats. Material and Method: Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF- α) levels were measured to assess the degree of inflammation. Histopathological changes in the liver, lungs and kidneys were also assessed. Result and Discussion: SIL significantly reduced the cellular release of TNF-α and IL-6, which have been implicated in the pathogenesis of Cd-induced tissue damage. When SIL was administered alone, it showed histopathological effects similar to the control group. However, it was found that co-administration of SIL with Cd prevented portal vein dilation and central vein enlargement in the liver, prevented necrosis in kidney tissue, but did not affect the lung. Although SIL has variable protective effects on tissues, our results are in support of the idea that the use of SIL in tissue damage management can be investigated for its efficacy in modulating oxidative stress-induced proinflammatory cytokine activation in vivo and ultimately help prevent Cd-induced tissue damage. Our study has shown that SIL can reduce Cd-induced acute toxicity in rats. SIL may be use as a protective agent against toxicity of heavy metals.
研究目的本研究旨在评估西地那非（SIL）对雌性大鼠镉（Cd）毒性诱导的炎症和组织病理学变化的影响：测量白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF- α）水平以评估炎症程度。还评估了肝、肺和肾的组织病理学变化：SIL 能明显减少细胞释放的 TNF-α 和 IL-6，这两种物质与镉诱导的组织损伤的发病机制有关。单用 SIL 时，其组织病理学效果与对照组相似。但研究发现，SIL 与镉联合给药可防止肝脏门静脉扩张和中心静脉扩大，防止肾脏组织坏死，但对肺部没有影响。虽然 SIL 对组织的保护作用不尽相同，但我们的研究结果支持这样一种观点，即可以研究 SIL 在组织损伤管理中的应用，以了解其在调节体内氧化应激诱导的促炎细胞因子活化方面的功效，并最终帮助预防镉诱导的组织损伤。我们的研究表明，SIL 可降低镉诱导的大鼠急性毒性。SIL 可用作重金属毒性的保护剂。
{"title":"SILDENAFIL DECREASED TNF-α AND IL-6 LEVELS IN CD‐INDUCED ACUTE TOXICITY","authors":"Ahmet Hüsamettin Baran, Ahmet Berk, AB Uyumlu, Özgen Arslan Solmaz, Göknur Yalım","doi":"10.33483/jfpau.1443799","DOIUrl":"https://doi.org/10.33483/jfpau.1443799","url":null,"abstract":"Objective: This study aimed to evaluate the effects of sildenafil (SIL) on inflammation and histopathological changes in cadmium (Cd)-induced toxicity in female rats.\u0000Material and Method: Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF- α) levels were measured to assess the degree of inflammation. Histopathological changes in the liver, lungs and kidneys were also assessed.\u0000Result and Discussion: SIL significantly reduced the cellular release of TNF-α and IL-6, which have been implicated in the pathogenesis of Cd-induced tissue damage. When SIL was administered alone, it showed histopathological effects similar to the control group. However, it was found that co-administration of SIL with Cd prevented portal vein dilation and central vein enlargement in the liver, prevented necrosis in kidney tissue, but did not affect the lung. Although SIL has variable protective effects on tissues, our results are in support of the idea that the use of SIL in tissue damage management can be investigated for its efficacy in modulating oxidative stress-induced proinflammatory cytokine activation in vivo and ultimately help prevent Cd-induced tissue damage. Our study has shown that SIL can reduce Cd-induced acute toxicity in rats. SIL may be use as a protective agent against toxicity of heavy metals.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797135","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}
Objective: Cholinesterase and tyrosinase inhibitory activity potential of microwave-assisted and subcritical water extracts of Raphanus sativus L. Red Meat roots were investigated. Material and Method: Total phenol, flavonoid and anthocyanin content of extracts from conventional solvent and advanced extraction systems were spectrophotometrically quantified. Acetylcholinesterase, butyrylcholinesterase and tyrosinase inhibitory activities were investigated with the calculation of the rate of absorbance change with kinetic readings. Result and Discussion: The subcritical water extract was found to provide highest acetylcholinesterase, butyrylcholinesterase and tyrosinase inhibitory activities with an IC50 of 0.71 mg/ml, 2.13 mg/ml and 1.21 mg/ml, respectively. Consistent with the anaylsis of total phenol (27.57 mg GAE/g) and flavonoid (4.80 mg QE/g) contents, subcritical water extract of red meat radish can be considered as a potential source for products aiming enzyme inhibitory activity.
{"title":"CHOLINESTERASE AND TYROSINASE INHIBITORY ACTIVITY OF SUBCRITICAL WATER AND MICROWAVE EXTRACTS OF RAPHANUS SATIVUS L. ‘RED MEAT’ RADIX","authors":"H. Koyu","doi":"10.33483/jfpau.1484457","DOIUrl":"https://doi.org/10.33483/jfpau.1484457","url":null,"abstract":"Objective: Cholinesterase and tyrosinase inhibitory activity potential of microwave-assisted and subcritical water extracts of Raphanus sativus L. Red Meat roots were investigated.\u0000Material and Method: Total phenol, flavonoid and anthocyanin content of extracts from conventional solvent and advanced extraction systems were spectrophotometrically quantified. Acetylcholinesterase, butyrylcholinesterase and tyrosinase inhibitory activities were investigated with the calculation of the rate of absorbance change with kinetic readings.\u0000Result and Discussion: The subcritical water extract was found to provide highest acetylcholinesterase, butyrylcholinesterase and tyrosinase inhibitory activities with an IC50 of 0.71 mg/ml, 2.13 mg/ml and 1.21 mg/ml, respectively. Consistent with the anaylsis of total phenol (27.57 mg GAE/g) and flavonoid (4.80 mg QE/g) contents, subcritical water extract of red meat radish can be considered as a potential source for products aiming enzyme inhibitory activity.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141802710","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}
Objective: This study investigates the interaction between melittin (PDB ID: 2MLT), a bioactive peptide from honeybee venom, and CD147 (PDB ID: 5XF0), a glycosylated transmembrane protein implicated in tumor progression. Material and Method: Employing molecular docking and bioinformatics tools, our structural analysis reveals diverse binding features, including hydrogen bonds, salt bridges, and non-bonded contacts, between the CD147 complex and melittin. Result and Discussion: Non-bonded interactions between 2MLT and specific amino acids (Gly181 and Arg201) of CD147 are highlighted, resembling aspects of the CypA/CD147 binding mechanism (Pro180-Gly181 and Arg201). The elevated anticancer potential of 2MLT was substantiated by utilizing the AntiCP 2.0 server and the ENNAACT server, employing machine learning and artificial neural network algorithms. Additionally, hydrophobicity analysis aligns with characteristics associated with anticancer peptides. Notably, thermodynamic stability variations with temperature underscore the robust binding affinity of 2MLT to the 5XF0 receptor. While our study comprehensively explores molecular interactions and predictive analyses, further in vitro and in vivo investigations are crucial to validate these findings for potential therapeutic applications.
{"title":"STRUCTURAL INSIGHTS AND ANTICANCER POTENTIAL OF MELITTIN IN CD147 INTERACTION","authors":"B. Denk","doi":"10.33483/jfpau.1405409","DOIUrl":"https://doi.org/10.33483/jfpau.1405409","url":null,"abstract":"Objective: This study investigates the interaction between melittin (PDB ID: 2MLT), a bioactive peptide from honeybee venom, and CD147 (PDB ID: 5XF0), a glycosylated transmembrane protein implicated in tumor progression.\u0000Material and Method: Employing molecular docking and bioinformatics tools, our structural analysis reveals diverse binding features, including hydrogen bonds, salt bridges, and non-bonded contacts, between the CD147 complex and melittin.\u0000Result and Discussion: Non-bonded interactions between 2MLT and specific amino acids (Gly181 and Arg201) of CD147 are highlighted, resembling aspects of the CypA/CD147 binding mechanism (Pro180-Gly181 and Arg201). The elevated anticancer potential of 2MLT was substantiated by utilizing the AntiCP 2.0 server and the ENNAACT server, employing machine learning and artificial neural network algorithms. Additionally, hydrophobicity analysis aligns with characteristics associated with anticancer peptides. Notably, thermodynamic stability variations with temperature underscore the robust binding affinity of 2MLT to the 5XF0 receptor. While our study comprehensively explores molecular interactions and predictive analyses, further in vitro and in vivo investigations are crucial to validate these findings for potential therapeutic applications.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"81 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141807853","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}
Senanur Özsoy, Özge Cemiloğlu Ülker, Aylin Üstündağ
Amaç: Bugüne kadar oral kolajen takviyeleri hakkında yapılan birçok çalışma kolajen takviyelerinin eklem ve cilt sağlığına üzerindeki etkileri üzerinedir. Kolajenlerin vücudun diğer fonksiyonları üzerine yararlı etkileri bilinmekte olup bunlar hakkında yapılan çalışmalar yetersiz kalmaktadır. Mevcut veriler birçok insan tarafından günlük diyetin önemli bir parçası haline gelen kolajen takviyelerinin herhangi bir toksik etkisi olmadığını, kullanımlarının güvenli olduğunu göstermektedir. Ancak yapılan çalışmalar sonucu birbirini destekleyen verilerin olmamasından dolayı kolajen takviyelerinin bu kadar sık kullanımlarına rağmen toksisiteleri üzerine ek çalışmalar yapılmasına ihtiyaç duyulmaktadır. Sonuç ve Tartışma: Yapılan literatür taramalarının sonuçları incelendiğinde, olası advers etkilere ait çok az veriye rastlanmıştır. Spesifik kolajenin uzun süreli oral uygulanması vücutta zararlı hücresel hasarlara sebep olabilir, kilo kaybına sebep olabilir, organları hedef alarak işleyişini aksatabilir. Değişken kolajen kaynaklarının içerikleri hakkında bilgi sahibi olmak ve kullanım sürelerine, kullanım miktarlarına dikkat edilmesi gerekir.
{"title":"ORAL KOLAJEN TAKVİYELERİ VE OLASI ADVERS ETKİLERİNİN DEĞERLENDİRİLMESİ","authors":"Senanur Özsoy, Özge Cemiloğlu Ülker, Aylin Üstündağ","doi":"10.33483/jfpau.1423707","DOIUrl":"https://doi.org/10.33483/jfpau.1423707","url":null,"abstract":"Amaç: Bugüne kadar oral kolajen takviyeleri hakkında yapılan birçok çalışma kolajen takviyelerinin eklem ve cilt sağlığına üzerindeki etkileri üzerinedir. Kolajenlerin vücudun diğer fonksiyonları üzerine yararlı etkileri bilinmekte olup bunlar hakkında yapılan çalışmalar yetersiz kalmaktadır. Mevcut veriler birçok insan tarafından günlük diyetin önemli bir parçası haline gelen kolajen takviyelerinin herhangi bir toksik etkisi olmadığını, kullanımlarının güvenli olduğunu göstermektedir. Ancak yapılan çalışmalar sonucu birbirini destekleyen verilerin olmamasından dolayı kolajen takviyelerinin bu kadar sık kullanımlarına rağmen toksisiteleri üzerine ek çalışmalar yapılmasına ihtiyaç duyulmaktadır.\u0000Sonuç ve Tartışma: Yapılan literatür taramalarının sonuçları incelendiğinde, olası advers etkilere ait çok az veriye rastlanmıştır. Spesifik kolajenin uzun süreli oral uygulanması vücutta zararlı hücresel hasarlara sebep olabilir, kilo kaybına sebep olabilir, organları hedef alarak işleyişini aksatabilir. Değişken kolajen kaynaklarının içerikleri hakkında bilgi sahibi olmak ve kullanım sürelerine, kullanım miktarlarına dikkat edilmesi gerekir.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"36 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141808134","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}
Objective: The abundance of bioactive metabolites in Verbena officinalis explains the biological benefits and folkloric use of the plant. Liver cancer is an extremely heterogeneous malignant disease compared to other defined tumors. To explore the potential therapeutic value of bioactive metabolites in Verbena officinalis, this study aimed to filter secondary metabolites, conduct ADME-Tox assessments, perform drug similarity tests, and analyze with molecular dynamic simulations. The objective was to evaluate how potential drug candidates derived from Verbena officinalis behave in biological systems and assess their potential toxicity risks. Material and Method: Ligands selected from the ADME assay were utilized in in silico molecular docking studies against Glucose-6-phosphate dehydrogenase enzyme in the oxidative part of the pentose phosphate pathway, which is crucial for liver diseases. These studies were conducted using Autodock Vina embedded in Chimera 1.16. Molecular dynamics simulations were performed with the AMBER16. Result and Discussion: When the ADME test results were evaluated, 88 secondary metabolites were identified as ligands. Among all the ligands evaluated against Glucose-6-phosphate dehydrogenase enzyme, which is the key enzyme of the pentose phosphate pathway, quercetin flavonoid was determined to be the most active ligand with a docking score of -8.1 kcal/mol and binding energy of -118.51 kcal/mol. A molecular dynamics simulation performed for 300 nanoseconds confirmed that quercetin can remain stable in its microenvironment. The activity of this metabolite is worthy of further testing in vitro and in vivo as it may highlight a therapeutic modality within the pentose phosphate pathway.
{"title":"IN SILICO TRIAL APPROACHES BETWEEN PHYTOCHEMICAL COMPOSITION OF VERBENA OFFICINALIS AND LIVER CANCER TARGETS","authors":"Hatice Akkaya, Aydın Özmaldar","doi":"10.33483/jfpau.1417289","DOIUrl":"https://doi.org/10.33483/jfpau.1417289","url":null,"abstract":"Objective: The abundance of bioactive metabolites in Verbena officinalis explains the biological benefits and folkloric use of the plant. Liver cancer is an extremely heterogeneous malignant disease compared to other defined tumors. To explore the potential therapeutic value of bioactive metabolites in Verbena officinalis, this study aimed to filter secondary metabolites, conduct ADME-Tox assessments, perform drug similarity tests, and analyze with molecular dynamic simulations. The objective was to evaluate how potential drug candidates derived from Verbena officinalis behave in biological systems and assess their potential toxicity risks. \u0000Material and Method: Ligands selected from the ADME assay were utilized in in silico molecular docking studies against Glucose-6-phosphate dehydrogenase enzyme in the oxidative part of the pentose phosphate pathway, which is crucial for liver diseases. These studies were conducted using Autodock Vina embedded in Chimera 1.16. Molecular dynamics simulations were performed with the AMBER16.\u0000Result and Discussion: When the ADME test results were evaluated, 88 secondary metabolites were identified as ligands. Among all the ligands evaluated against Glucose-6-phosphate dehydrogenase enzyme, which is the key enzyme of the pentose phosphate pathway, quercetin flavonoid was determined to be the most active ligand with a docking score of -8.1 kcal/mol and binding energy of -118.51 kcal/mol. A molecular dynamics simulation performed for 300 nanoseconds confirmed that quercetin can remain stable in its microenvironment. The activity of this metabolite is worthy of further testing in vitro and in vivo as it may highlight a therapeutic modality within the pentose phosphate pathway.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"14 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141809401","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}
Amaç: Günümüzde en çok çalışılan Fusarium mikotoksin türleri arasında fumonisin B1 (FB1) ve zearalenon (ZEA) bulunmaktadır. FB1 ve ZEA farklı moleküler mekanizmaları etkilemekte olup birçok toksik etkiye sebep olmaktadır. Bu derlemede FB1 ve ZEA’nın DNA metilasyonu, histon modifikasyonları ve mikroRNA (miRNA) seviyeleri gibi epigenetik mekanizmalar üzerine etkileri ve moleküler düzeyde gözlenen toksik etkilerinin özetlenmesi amaçlanmıştır. Sonuç ve Tartışma: FB1 ve ZEA’nın DNA metilasyonunu, histon modifikasyonunu ve miRNA seviyelerini uygulama süresi ve doza bağlı olarak değiştirdiği çeşitli çalışmalarda gösterilmiş olup bu mikotoksinlerin moleküler mekanizmalarında epigenetik çalışmaların önemi vurgulanmıştır.
目的：伏马菌素 B1（FB1）和玉米赤霉烯酮（ZEA）是研究最广泛的镰刀菌霉菌毒素种类。FB1 和 ZEA 影响不同的分子机制，并导致多种毒性效应。在这篇综述中，我们旨在总结 FB1 和 ZEA 对 DNA 甲基化、组蛋白修饰和微 RNA（miRNA）水平等表观遗传机制的影响，以及在分子水平上观察到的毒性效应。结论与讨论：多项研究表明，FB1 和 ZEA 会改变 DNA 甲基化、组蛋白修饰和 miRNA 水平，具体取决于施用时间和剂量。
{"title":"FUSARİUM TOKSİNLERİNİN EPİGENETİK MEKANİZMALAR ÜZERİNE ETKİLERİ: FUMONİSİN B1 VE ZEARALENON","authors":"E. Perçin, Ecem Fatma Karaman, Sibel Özden","doi":"10.33483/jfpau.1459437","DOIUrl":"https://doi.org/10.33483/jfpau.1459437","url":null,"abstract":"Amaç: Günümüzde en çok çalışılan Fusarium mikotoksin türleri arasında fumonisin B1 (FB1) ve zearalenon (ZEA) bulunmaktadır. FB1 ve ZEA farklı moleküler mekanizmaları etkilemekte olup birçok toksik etkiye sebep olmaktadır. Bu derlemede FB1 ve ZEA’nın DNA metilasyonu, histon modifikasyonları ve mikroRNA (miRNA) seviyeleri gibi epigenetik mekanizmalar üzerine etkileri ve moleküler düzeyde gözlenen toksik etkilerinin özetlenmesi amaçlanmıştır. \u0000Sonuç ve Tartışma: FB1 ve ZEA’nın DNA metilasyonunu, histon modifikasyonunu ve miRNA seviyelerini uygulama süresi ve doza bağlı olarak değiştirdiği çeşitli çalışmalarda gösterilmiş olup bu mikotoksinlerin moleküler mekanizmalarında epigenetik çalışmaların önemi vurgulanmıştır.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"14 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141809397","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}
Objective: This study aims to explore potential molecular mechanisms and targets of cardiovascular toxicities caused by tyrosine kinase inhibitors. Therefore, toxicogenomic data mining was conducted focusing on sunitinib, sorafenib, pazopanib, axitinib, and their associations with cardiovascular diseases. Material and Method: Common genes between tyrosine kinase inhibitors and cardiovascular diseases were uncovered via comparative toxicogenomic databases. Additionally, protein-protein and gene-gene interactions were identified using STRING and GeneMANIA, respectively. Subsequently, hub proteins associated with tyrosine kinase inhibitor-induced cardiovascular diseases were determined through Metascape. Transcription factors and microRNAs related to this toxicity were identified using ChEA3 and MIENTURNET, respectively. Finally, gene ontology enrichment analysis and the most associated molecular pathways were identified using the DAVID database and Metascape, respectively. Result and Discussion: Toxicogenomic data mining revealed six genes common between tyrosine kinase inhibitors and cardiovascular diseases, with five of these genes (FLT1, FLT4, KDR, MAPK1, and MAPK3) identified as hub genes. Physical interaction was dominant among these hub genes (77.64%). Sunitinib, sorafenib, pazopanib, and axitinib generally downregulated the activities of these proteins. SOX17 and SOX18 were prominent among transcription factors, while hsa-miR-199a-3p was the most important microRNA associated with this toxicity. Moreover, the Ras signaling pathway was mostly associated with tyrosine kinase inhibitor-induced cardiovascular toxicities. These findings make a substantial contribution to understanding the processes underlying cardiovascular diseases induced by sunitinib, sorafenib, pazopanib, and axitinib. They also reveal novel potential therapeutic targets, including genes, proteins, transcription factors, microRNAs, and pathways.
{"title":"NETWORK TOXICOLOGY FOR THE CARDIOVASCULAR TOXICITY ANALYSIS OF TYROSINE KINASE INHIBITORS","authors":"Fuat Karakuş","doi":"10.33483/jfpau.1478733","DOIUrl":"https://doi.org/10.33483/jfpau.1478733","url":null,"abstract":"Objective: This study aims to explore potential molecular mechanisms and targets of cardiovascular toxicities caused by tyrosine kinase inhibitors. Therefore, toxicogenomic data mining was conducted focusing on sunitinib, sorafenib, pazopanib, axitinib, and their associations with cardiovascular diseases.\u0000Material and Method: Common genes between tyrosine kinase inhibitors and cardiovascular diseases were uncovered via comparative toxicogenomic databases. Additionally, protein-protein and gene-gene interactions were identified using STRING and GeneMANIA, respectively. Subsequently, hub proteins associated with tyrosine kinase inhibitor-induced cardiovascular diseases were determined through Metascape. Transcription factors and microRNAs related to this toxicity were identified using ChEA3 and MIENTURNET, respectively. Finally, gene ontology enrichment analysis and the most associated molecular pathways were identified using the DAVID database and Metascape, respectively.\u0000Result and Discussion: Toxicogenomic data mining revealed six genes common between tyrosine kinase inhibitors and cardiovascular diseases, with five of these genes (FLT1, FLT4, KDR, MAPK1, and MAPK3) identified as hub genes. Physical interaction was dominant among these hub genes (77.64%). Sunitinib, sorafenib, pazopanib, and axitinib generally downregulated the activities of these proteins. SOX17 and SOX18 were prominent among transcription factors, while hsa-miR-199a-3p was the most important microRNA associated with this toxicity. Moreover, the Ras signaling pathway was mostly associated with tyrosine kinase inhibitor-induced cardiovascular toxicities. These findings make a substantial contribution to understanding the processes underlying cardiovascular diseases induced by sunitinib, sorafenib, pazopanib, and axitinib. They also reveal novel potential therapeutic targets, including genes, proteins, transcription factors, microRNAs, and pathways.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"55 19","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141807020","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}
Objective: Probiotics are an important and fast-growing functional food group. Pharmacy students, as pharmacists of the future, need to have sufficient knowledge on this subject. Therefore, this study aims to evaluate pharmacy students' knowledge, attitudes, and practices about probiotics. Material and Method: A cross-sectional survey study was conducted among students of Suleyman Demirel University Faculty of Pharmacy in Türkiye between 9 October and 30 October 2023. The paper-based questionnaires consisted of 23 questions and were administered for approximately 10-15 minutes. Result and Discussion: The questionnaires were answered by 347 (74.7%) students. The mean±SD of the knowledge score was 5.14±1.53. The majority of respondents (79%) correctly identified probiotics. Approximately half of the participants knew the type of bacteria used in probiotic production The mean±SD of the attitude score was 11.13±1.44. Most respondents (91.9%) believed that probiotic consumption was beneficial for health. The mean±SD of the practice score was 3.72±2.77. 45.2% of respondents stated that they had used probiotic supplements before and 31.1% stated that they had sought additional information about probiotics from various sources. 40.6% of the respondents stated that they recommend probiotics to their family/close relatives. This study showed that although the attitudes of pharmacy students were acceptable, they had some knowledge deficiencies and their practices were poor. To increase the knowledge and practices of pharmacy students about probiotics, this subject should be given more space in undergraduate education and relevant scientific events should be organized.
{"title":"PHARMACY STUDENTS' KNOWLEDGE, ATTITUDES AND PRACTICES ABOUT PROBIOTICS","authors":"Aslınur Albayrak, Şimal Mülazım","doi":"10.33483/jfpau.1458564","DOIUrl":"https://doi.org/10.33483/jfpau.1458564","url":null,"abstract":"Objective: Probiotics are an important and fast-growing functional food group. Pharmacy students, as pharmacists of the future, need to have sufficient knowledge on this subject. Therefore, this study aims to evaluate pharmacy students' knowledge, attitudes, and practices about probiotics.\u0000Material and Method: A cross-sectional survey study was conducted among students of Suleyman Demirel University Faculty of Pharmacy in Türkiye between 9 October and 30 October 2023. The paper-based questionnaires consisted of 23 questions and were administered for approximately 10-15 minutes.\u0000Result and Discussion: The questionnaires were answered by 347 (74.7%) students. The mean±SD of the knowledge score was 5.14±1.53. The majority of respondents (79%) correctly identified probiotics. Approximately half of the participants knew the type of bacteria used in probiotic production The mean±SD of the attitude score was 11.13±1.44. Most respondents (91.9%) believed that probiotic consumption was beneficial for health. The mean±SD of the practice score was 3.72±2.77. 45.2% of respondents stated that they had used probiotic supplements before and 31.1% stated that they had sought additional information about probiotics from various sources. 40.6% of the respondents stated that they recommend probiotics to their family/close relatives. This study showed that although the attitudes of pharmacy students were acceptable, they had some knowledge deficiencies and their practices were poor. To increase the knowledge and practices of pharmacy students about probiotics, this subject should be given more space in undergraduate education and relevant scientific events should be organized.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"15 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648149","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}
Objective: Due to the increase in the market share of pharmaceuticals and the unconscious use of medicines, unused or expired medicines are being discarded in a way that harms the environment. This study aims to examine which medicines are brought to collection points as household waste in order to reduce waste medicines from the source. Material and Method: The medicines collected in 12 spontaneously selected pharmacies operating in low and high income levels in the Ankara region were recorded at different periods during one year and the results were statistically evaluated. 4852 waste medicines were sorted and classified according to pharmaceutical dosage form and indication Result and Discussion: Unopened 521 medicines were discarded. In addition, it was seen which drug groups create waste in socio-economic terms. In addition to the damage to the environment, it has created a foresight to prevent drug waste that creates a deficit in the budget.
{"title":"INVESTIGATION OF THE PREVALENCE OF EXPIRED AND UNUSED PHARMACEUTICALS IN THE ANKARA REGION","authors":"O. M. Saka","doi":"10.33483/jfpau.1473405","DOIUrl":"https://doi.org/10.33483/jfpau.1473405","url":null,"abstract":"Objective: Due to the increase in the market share of pharmaceuticals and the unconscious use of medicines, unused or expired medicines are being discarded in a way that harms the environment. This study aims to examine which medicines are brought to collection points as household waste in order to reduce waste medicines from the source.\u0000Material and Method: The medicines collected in 12 spontaneously selected pharmacies operating in low and high income levels in the Ankara region were recorded at different periods during one year and the results were statistically evaluated. 4852 waste medicines were sorted and classified according to pharmaceutical dosage form and indication\u0000Result and Discussion: Unopened 521 medicines were discarded. In addition, it was seen which drug groups create waste in socio-economic terms. In addition to the damage to the environment, it has created a foresight to prevent drug waste that creates a deficit in the budget.","PeriodicalId":7891,"journal":{"name":"Ankara Universitesi Eczacilik Fakultesi Dergisi","volume":"57 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141649540","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：