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    An in vitro assessment of ionizing radiation impact on the efficacy of radiotherapy for breast cancer
    (2024) Girgin, Merve; Akat, Ayberk; Akgül, Büşra; Nalbant, Nilgül; Karaçetin, Didem; Abamor, Emrah Şefik; Uğurel, Osman Mutluhan; Turgut-Balık, Dilek
    Objectives Ionizing radiation is still one of the most effective treatment options for various cancers. It is possible to reduce the side effects of this effective treatment method and increase the chance of success by elucidating the responses it creates at the molecular level in the cell. This study aims to investigate of the molecular effects of therapeutic ionizing radiation on breast cancer, which is the most prevalent cancer type. Methods MDA-MB-231 and MCF7 cell lines were irradiated with 4 and 8 Gy ionizing radiation and monitored for up to 7 days. RNA was collected at 48 and 96 h, when cellular molecular mechanisms became most evident, and quantitative expression levels of microRNAs (miR-208a, miR-124, miR-145), for which cancer-radiation associations have been determined from existing literature and databases, were evaluated. Results Exposure to ionizing radiation resulted in a dose-dependent reduction in cell viability in both MCF7 and MDA-MB-231 breast cancer cell lines. Furthermore, microRNA expression analysis revealed notable changes at all levels. The research demonstrates that miR-208a, miR-145, and miR-124 are crucial in the biological response to ionizing radiation. Conclusions Therapeutic ionizing radiation profoundly affects cell viability and microRNA expression in breast cancer cell lines, showing dose and time-dependent effects. The observed microRNA expression patterns suggest potential biomarkers for radiation response and therapeutic targets to improve radiotherapy efficacy. Further in vivo validation and exploration of these microRNAs' roles in modulating cellular response to ionizing radiation are needed.
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    Formulating and characterizing an exosome-based dopamine carrier system
    (Journal of Visualized Experiments, 2022) Yavuz, Burçak; Darici, Hakan; Zorba Yildiz, Aslı Pınar; Abamor, Emrah Şefik; Topuzoğullari, Murat; Bağirova, Melahat; Karaoz, Erdal; Allahverdiyev, Adile
    Exosomes between 40 and 200 nm in size constitute the smallest subgroup of extracellular vesicles. These bioactive vesicles secreted by cells play an active role in intercellular cargo and communication. Exosomes are mostly found in body fluids such as plasma, cerebrospinal fluid, urine, saliva, amniotic fluid, colostrum, breast milk, joint fluid, semen, and pleural acid. Considering the size of exosomes, it is thought that they may play an important role in central nervous system diseases because they can pass through the blood-brain barrier (BBB). Hence, this study aimed to develop an exosome-based nanocarrier system by encapsulating dopamine into exosomes isolated from Wharton's jelly mesenchymal stem cells (WJ-MSCs). Exosomes that passed the characterization process were incubated with dopamine. The dopamine-loaded exosomes were recharacterized at the end of incubation. Dopamine-loaded exosomes were investigated in drug release and cytotoxicity assays. The results showed that dopamine could be successfully encapsulated within the exosomes and that the dopamine-loaded exosomes did not affect fibroblast viability.
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    Investigation of neurosphere activity of injectable 3D graphene bioink biomaterial
    (2024) Yıldız, Aslı Pınar Zorba; Yavuz, Burçak; Abamor, Emrah Şefik; Darıcı, Hakan; Allahverdiyev, Adil
    PurposeThe aim of this study includes the comparative examination of neurosphere formation by WJ-derived mesenchymal stem cells in both 2D media and 3D injectable graphene and graphene-free bioink systems in terms of both immunostaining and gene expression levels.MethodsFor this purpose, hydrogel bioinks were first created and the wj-MKH spheroidal structure was formed on 3D-B (without graphene) and 3D-G (containing graphene). Then, following the differentiation procedure, neurosphere transformations were identified by both immunostaining (b-III Tubulin and Sox2), and Tubulin 3, Sox2, and Nestin markers were examined at the gene expression level with Real-Time PCR, and the results were compared with the 2D environment.ResultsAccording to the results obtained, neurosphere formation occurred more in the 3D environment compared to the 2D environment, obtained both by immunostaining and gene expression levels. It was also observed that differentiation formed neuron-like structures, especially in the 3D-G group containing graphene.ConclusionAs a result, it has been observed that the use of graphene with a non-toxic concentration in the hydrogel injectable system provides better differentiation of stem cells, especially those that will form the cell leg of the biomaterial.Lay SummaryTherefore, the use of graphene-containing hydrogels in injectable systems in nerve damage may increase the effectiveness on nerve regeneration.
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    Preparation and characterization of graphene-based 3D biohybrid hydrogel bioink for peripheral neuroengineering
    (Jove, 2022) Zorba Yıldız, Aslı Pınar; Darıcı, Hakan; Yavuz, Burçak; Abamor, Emrah Şefik; Özdemir, Ceren; Yasin, Müge Elif; Bağırova, Melahat; Allahverdiyev, Adil; Karaöz, Erdal
    Peripheral neuropathies can occur as a result of axonal damage, and occasionally due to demyelinating diseases. Peripheral nerve damage is a global problem that occurs in 1.5%-5% of emergency patients and may lead to significant job losses. Today, tissue engineering-based approaches, consisting of scaffolds, appropriate cell lines, and biosignals, have become more applicable with the development of three-dimensional (3D) bioprinting technologies. The combination of various hydrogel biomaterials with stem cells, exosomes, or bio-signaling molecules is frequently studied to overcome the existing problems in peripheral nerve regeneration. Accordingly, the production of injectable systems, such as hydrogels, or implantable conduit structures formed by various bioprinting methods has gained importance in peripheral neuro-engineering. Under normal conditions, stem cells are the regenerative cells of the body, and their number and functions do not decrease with time to protect their populations; these are not specialized cells but can differentiate upon appropriate stimulation in response to injury. The stem cell system is under the influence of its microenvironment, called the stem cell niche. In peripheral nerve injuries, especially in neurotmesis, this microenvironment cannot be fully rescued even after surgically binding severed nerve endings together. The composite biomaterials and combined cellular therapies approach increases the functionality and applicability of materials in terms of various properties such as biodegradability, biocompatibility, and processability. Accordingly, this study aims to demonstrate the preparation and use of graphene-based biohybrid hydrogel patterning and to examine the differentiation efficiency of stem cells into nerve cells, which can be an effective solution in nerve regeneration.