Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 5Citation - Scopus: 5Multiorgan-On for Cancer Drug Pharmacokinetics-Pharmacodynamics (pk-Pd) Modeling and Simulations(Springer/plenum Publishers, 2025) Mohammed, Abdurehman Eshete; Kurucaovali, Filiz; Okvur, Devrim PesenCancer is one of the most common and fatal diseases worldwide and kills millions of people every year. Cancer drug resistance, lack of efficacy, and safety are significant problems in cancer patients. A multiorgan-on-a-chip (MOC) device consisting of breast and liver compartments was designed with AutoCAD software. The MOC molds were printed by a Formlabs Form 2 3D printer. MDA-MB-231, HepG2, and MCF-10 A cells were used for the MOC experiments. The cell lines were cultured at 37 degrees C with 5% CO2, and cell viability was assessed via Alamar blue dye to generate pharmacodynamics (PD) data. Drug concentrations from the cell culture media were analyzed via Agilent 1260 Infinity II HPLC with a Waters Symmetry C18 column and used to generate pharmacokinetics (PK) data. The PK and PD data were modeled and simulated by Monolix and Simulix software, respectively. The safety and efficacy of drug dosing regimens were compared, and the best dosing regimens were selected. This research designed and fabricated a unique MOC consisting of liver and breast compartments that overcomes the need for sealing or assembling. It was used for PK-PD modeling and simulations, and its functionality was proven experimentally. The new MOC will be helpful in preclinical trials to evaluate the efficacy and safety of drugs.Correction Diaph1-Deficiency Is Associated With Major T, Nk and Ilc Defects in Humans (vol 44, 175, 2024)(Springer/plenum Publishers, 2025) Azizoglu, Zehra Busra; Babayeva, Royala; Haskologlu, Zehra Sule; Acar, Mustafa Burak; Ayaz-Guner, Serife; Okus, Fatma Zehra; Eken, Ahmet[No Abstract Available]Article Citation - WoS: 6Citation - Scopus: 7Diaph1-Deficiency Is Associated With Major T, Nk and Ilc Defects in Humans(Springer/plenum Publishers, 2024) Azizoglu, Zehra Busra; Babayeva, Royala; Haskologlu, Zehra Sule; Acar, Mustafa Burak; Ayaz-Guner, Serife; Okus, Fatma Zehra; Eken, AhmetLoss of function mutations in Diaphanous related formin 1 (DIAPH1) are associated with seizures, cortical blindness, and microcephaly syndrome (SCBMS) and are recently linked to combined immunodeficiency. However, the extent of defects in T and innate lymphoid cells (ILCs) remain unexplored. Herein, we characterized the primary T, natural killer (NK) and helper ILCs of six patients carrying two novel loss of function mutation in DIAPH1 and Jurkat cells after DIAPH1 knockdown. Mutations were identified by whole exome sequencing. T-cell immunophenotyping, proliferation, migration, cytokine signaling, survival, and NK cell cytotoxicity were studied via flow cytometry-based assays, confocal microscopy, and real-time qPCR. CD4+ T cell proteome was analyzed by mass spectrometry. p.R351* and p.R322*variants led to a significant reduction in the DIAPH1 mRNA and protein levels. DIAPH1-deficient T cells showed proliferation, activation, as well as TCR-mediated signaling defects. DIAPH1-deficient PBMCs also displayed impaired transwell migration, defective STAT5 phosphorylation in response to IL-2, IL-7 and IL-15. In vitro generation/expansion of Treg cells from na & iuml;ve T cells was significantly reduced. shRNA-mediated silencing of DIAPH1 in Jurkat cells reduced DIAPH1 protein level and inhibited T cell proliferation and IL-2/STAT5 axis. Additionally, NK cells from patients had diminished cytotoxic activity, function and IL-2/STAT5 axis. Lastly, DIAPH1-deficient patients' peripheral blood contained dramatically reduced numbers of all helper ILC subsets. DIAPH1 deficiency results in major functional defects in T, NK cells and helper ILCs underlining the critical role of formin DIAPH1 in the biology of those cell subsets.Graphical AbstractThe summary of findings are presented as a graphical abstract. DIAPH1 deficiency results in multiple defects in CD4+ T, Treg, NK cells and ILCs.