TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article Upregulated Acute Systemic Inflammation-Related Genes Based on Endotoxin Exposure Provide ‘Survival Benefit’ or Create ‘High Risk of Death’ in Leukaemia and Colon Cancer(Istanbul University, 2024-07-10) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem Ayna; Ayna Duran, GizemObjective: Although endotoxin exposure has been shown to trigger innate immune responses and promote cancer, it has also been shown to prevent cancer formation. In our study, survival analysis was performed to determine whether the upregulated genes triggered by endotoxins have hazardous effects on cancers or provide a survival benefit. Materials and Methods: Gene intensity values of control and bacterial endotoxin-administered individuals were obtained from the Gene Expression Omnibus database. Using the R "Linear Models for Microarray Data" package, differentially expressed gene analyses were conducted to determine genes that differ between healthy and bacterial endotoxin-administered samples. "ShinyGo 0.80" web-based tool was used to determine the disease types indicated by these genes. The "Kaplan-Meier Plotter" web-based tool was used to conduct survival analysis. Results: Genes that create an innate immune response to bacterial endotoxin exposure and are upregulated differently than in individuals without exposure were identified. According to gene enrichment analyses, the two main types of cancer identified were leukaemia/lymoma and colon cancer. We detected that MLF1, STAT5B, and BCL3 genes led to poor survival; however, the ARHGAP26 gene was protective for acute myeloid leukaemia patients. In the case of colon cancer, SMAD7 and TLR2 genes were determined as leading to "high risk of death". Conclusion: Once the systemic inflammation-related genes identified in our study are confirmed through laboratory experiments in samples taken from solid tissue in the case of colon cancer and at the level of genes obtained from blood samples in leukemias, genetically targeted treatments will also be possible.Article Citation - WoS: 6Prospective, Multicenter, Turkish Out of Hospital Cardiac Arrest Study: Trohca(Wolters Kluwer Medknow Publications, 2024-07) Günaydın, Gül Pamukçu; Genç, Sınan; Utlu, Sibel Güçlü; Sabak, Mustafa; Ozhasenekler, Ayhan; Şener, Alp; Demirbağ, Mehmet; Aksay, Ersin; Aksel, Gokhan; Pekdemir, Murat; Islam, Mehmet Muzaffer; Karahan, Sevilay; Bozkurt, MustafaOBJECTIVES: There is no sufficient data to provide a clear picture of out of hospital cardiac arrest (OHCA) across Türkiye. This study is the first to present the prognostic outcomes of OHCA cases and the factors associated with these outcomes. MATERIALS AND METHODS:The study was conducted in a prospective, observational, multicenter design under the leadership of the Emergency Medicine Association of Turkey Resuscitation Study Group. OHCA cases aged 18 years and over who were admitted to 28 centers from Türkiye were included in the study. Survived event, return of spontaneous circulation (ROSC), survival to hospital discharge, and neurological outcome at discharge were investigated as primary outcomes. RESULTS: One thousand and three patients were included in the final analysis. 61.1% of the patients were male, and the average age was 67.0 ± 15.2. Cardiopulmonary resuscitation (CPR) was performed on 86.5% of the patients in the prehospital period by emergency medical service, and bystander CPR was performed on only 2.9% by nonhealth care providers. As a result, the survived event rate was found to be 6.9%. The survival rate upon hospital discharge was 4.4%, with 2.7% of patients achieving a good neurological outcome upon discharge. In addition, the overall ROSC and sustained ROSC rates were 45.2% and 33.4%, respectively. In the multiple logistic regression analysis, male gender, initial shockable rhythm, a shorter prehospital duration of CPR, and the lack of CPR requirement in the emergency department were determined to be independent predictors for the survival to hospital discharge. CONCLUSION: Compared to global data, survival to hospital discharge and good neurological outcome rates appear to be lower in our study. We conclude that this result is related to low bystander CPR rates. Although not the focus of this study, inadequate postresuscitative care and intensive care support should also be discussed in this regard. It is obvious that this issue should be carefully addressed through political moves in the health and social fields.Article Exploring Pi3k Pathway Inhibitors for Acute Myeloid Leukemia: a Drug-Repurposing Approach(Istanbul University Press, 2023-12-28) Ergun, Cansu; Kiremitci, Buse Zeren; Arslantas, Gizem; Bozkurt, Busenur; Duran, Gizem Ayna; Kiraz, YağmurObjective: Acute myeloid leukemia (AML) is a malignant disease characterized by the uncontrolled growth, differentiation, and proliferation of immature hematopoietic cells. Patients with AML often have poor survival rates, which are associated with specific gene mutations in FLT3, CEBPA, and NPM1. The phosphatidylinositol 3-kinase (PI3K) pathway, a lipase pathway, is activated in many malignancies, including AML. Given the low survival rates in AML, this study identified candidate drugs that could inhibit the PI3K pathway, thereby offering a potential treatment for AML, by using a drug-repurposing approach. Materials and Methods: Online bioinformatics tools were utilized to identify pathway-related genes and FDA-approved drugs. Subsequently, molecular docking was performed to determine the binding affinity values. Important genes were identified by evaluating their impact on survival and their aberrant expression in the tumor. In this study, genes such as VAV1, GSK3B, MTOR, PDPK1, PRR5, TSC2, AKT3, and CREB1 were determined and docked with their potential inhibitors. Particular attention was paid to VAV1 because there were no known potential VAV1 inhibitors used in AML. Results: The docking results were ranked, and the proposed gene–drug pairs were identified as tideglusib and fostamatinib for the inhibition of GSK3B, pimecrolimus and fostamatinib for the inhibition of MTOR, and fostamatinib for the inhibition of PDPK1. Furthermore, nebivolol, darifenacin, dihydroergotamine, libanserin and entereg were identified as potential inhibitors of VAV1 in AML. Conclusion: To sum up, most effective gene–drug pairs according to binding affinities were proposed as candidate inhibitor drugs for AML.