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    Artificial Intelligence in Cancer: A SWOT Analysis
    (İzmir Academy Association, 31 Aralık 2024) Torkay, Gülşah; Fadlallah, Nouran; Karagöz, Ahmet; Canlı, Mesut; Saydam, Ezgi; Mete, Ayşenur; Kızılışık, Furkan; Darici, Hakan; Yeşil, Yusuf
    Cancer, a collection of maladies that has undergone extensive examination over centuries, remains a formidable challenge. Despite the array of available pharmacological and therapeutic interventions, the intricate molecular dynamics and heterogeneity of cancer continue to challenge the scientific community. Artificial Intelligence (AI) emerges as a promising avenue, offering the potential for expedited, precise diagnostics devoid of human expertise. Additionally, AI facilitates the tailoring of patient-specific therapeutic strategies targeting various facets of cancer, spanning macroscopic to microscopic levels. Nonetheless, it is imperative to scrutinize the potential benefits and limitations of AI technologies in this context. This review undertakes a comprehensive Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis of AI's application in cancer. An extensive compilation of AI applications encompasses predictive modeling, diagnostic capabilities, prognostic assessments, and personalized therapeutic modalities, spanning genomic analyses to individualized treatment regimens. The synthesis of evidence suggests that the advantages of AI outweigh its drawbacks; nevertheless, obstacles to its widespread integration persist.
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    Controlled Sr(ii) ion release from in situ crosslinking electroactive hydrogels with potential for the treatment of infections
    (Royal Soc Chemistry, 2024) Demirkan, Melike Firlak; Ozturk, Dilek; Cifcibasi, Zeynep Sude; Ertan, Fatma; Hardy, John George; Nurseval Oyunlu, Asli; Darici, Hakan
    The development of electrochemical stimuli-responsive drug delivery systems is of both academic and industrial interest due to the ease with which it is possible to trigger payload release, providing drug delivery in a controllable manner. Herein, the preparation of in situ forming hydrogels including electroactive polypyrrole nanoparticles (PPy-NPs) where Sr2+ ions are electrochemically loaded for electrically triggered release of Sr2+ ions is reported. The hydrogels were characterized by a variety of techniques including Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), X-ray diffraction (XRD), cyclic voltammetry (CV), etc. The cytocompatibility towards human mesenchymal stem cells (MSCs) and fibroblasts were also studied. The Sr2+ ion loaded PEC-ALD/CS/PPy-NPs hydrogel showed no significant cytotoxicity towards human mesenchymal stem cells (MSCs) and fibroblasts. Sr2+ ions were electrochemically loaded and released from the electroactive hydrogels, and the application of an electrical stimulus enhanced the release of Sr2+ ions from gels by ca. 2-4 fold relative to the passive release control experiment. The antibacterial activity of Sr2+ ions against E. coli and S. aureus was demonstrated in vitro. Although these prototypical examples of Sr2+ loaded electroactive gels don't release sufficient Sr2+ ions to show antibacterial activity against E. coli and S. aureus, we believe future iterations with optimised physical properties of the gels will be capable of doing so.
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    Hyperbranched polymer-based nanoparticle drug delivery platform for the nucleus-targeting in cancer therapy
    (Elsevier, 2023) Bal-Ozturk, Ayca; Tietilu, Sherif Domingo; Yuecel, Oguz; Erol, Tugba; Akguner, Zeynep Puren; Darici, Hakan; Alarcin, Emine
    Hyperbranched polymers (HPB) are drawing attention as one of the drug delivery platforms that can encapsulate drugs owing to the internal voids in their three-dimensional construct. It is feasible to develop HBP-based nano -sized drug delivery platforms and improve the efficacy of cancer treatment due to its potential properties. In particular, the contribution of targeted drug delivery systems that can target malignant tissues in the treatment processes is undeniable. For this purpose, modifying an HBP-based nanoparticle delivery system with a targeting molecule is vital. In this study, we synthesized folic acid-modified HBP-based nanoparticles and their physical (DLS, zeta potential) and chemical (FTIR, NMR) characterizations were performed, and finally 5-Fluorouracil (5-FU) was loaded as a model active agent. The release properties (UV-VIS) and release kinetic models of 5-FU-loaded folic acid-modified nanoparticles were investigated in different pHs. In vitro cellular activities (MTT, cellular uptake) and targeting properties to the folate receptor (FR) were determined by flow cytometry on HeLa (FR, +) and L929 (FR,-) cells. According to all the results, folic acid-modified HBP-based nanoparticles were efficiently transported to the cell nucleus in the targeted FR + cells, and internalization of nanoparticles in HeLa cells is similar to 2.5 times higher than L929 cells. All results suggest that folic acid modification to the nanoparticles is critical in folate receptor-positive cancer treatment.
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    Neuroprotective Effects of Wharton Jelly Stem Cell-Derived Exosomes Developed as Nano-Drug Delivery System in 6-OHDA-Induced Neurotoxicity in 2D and 3D Neuronal Cell Line
    (Springer Heidelberg, 2023) Yavuz, Burcak; Yildiz, Asli Pinar Zorba; Abamor, Emrah Sefik; Darici, Hakan; Allahverdiyev, Adil M.
    PurposeThe underlying mechanism of today's neurodegenerative diseases is disordered due to neuronal damage and very limited neuronal regeneration. Formulations that can be developed against the factors that cause damage must have a neuroprotective effect. Particularly, formulations that can be developed in nanoscales may play a key role in central nervous system diseases. This article aimed to investigate the neuroprotective activity of dopamine-loaded exosomes in which exosomes derived from Wharton jelly stem cells (WJ-MSCs) are used as carrier systems in 2D and 3D cell cultures induced in cell damage.Materials and MethodsThis study created 2D and 3D cell cultures with a bioprinter in the dopaminergic neuroblastoma cell line (SH-SY5Y). Cell lines were damaged with 6-OHDA. The neuroprotective effect of dopamine-loaded exosomes was investigated by Live&Dead analysis and immunostaining.ResultsThe findings showed that dopamine-loaded exosomes protected against 6-OHDA-induced neurotoxicity in both cultures. The increase in the number of viable cells in the 6-OHDA administered groups proved the neuroprotective effect.ConclusionWe predict that the carrier systems developed with exosomes obtained from Wharton jelly stem cells will be a light of hope in the treatment of neurodegenerative diseases, considering both their size and their contribution to regeneration.Lay SummaryEspecially in neurodegenerative diseases, it is very important to be able to protect and regenerate neurons. Wharton jelly stem cell-based exosomes are known to have many properties, including other wound healing activities. In addition, considering both the structure and size of exosomes, its development as a drug delivery system is promising.
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    The effects of lithium, metformin and everolimus substances on cell growth in 2D and 3D Ishikawa endometrial carcinoma cell culture
    (Pamukkale Üniversitesi, 5 Temmuz 2024) Tural, Emine; Çil, Nazlı; Seçme, Mücahit; Mete, Gülçin Abban; Darici, Hakan; Bilir, Ayhan; Karaoz, Erdal
    Purpose: Our aim is to study the effects of the single and combined treatments of Everolimus, Metformin, and Lithium Chloride in two-dimensional (2D, monolayer) and three-dimensional (3D, spheroid) cell cultures of Ishikawa cells, which comprise the endometrial cancer cell line. Materials and methods: As part of the study, the effects of single and combined forms of Everolimus, Metformin, and Lithium Chloride were determined on cell viability, invasion, colony formation and apoptosis, and PI3K/AKT/mTOR pathway. Cell viability was assessed using XTT assay. CASP3, CASP8, CASP9, FASL, FADD, TNF, TRADD, BAX, P53, PI3KCA, PI3KCB, PTEN, MTOR, AKT1 genes were evaluated with RT-PCR, apoptosis was evaluated by flow cytometry and 3D spheroid results were evaluated with invert microscope analysis. Results: Everolimus, metformin, and lithium's IC50 levels were found at 48 hours to be 37.46 nM, 48.59 mM, and 100 μM, respectively. It was determined that the invasive capacities of Ishikawa cells in treatment groups, as well as cell colony formation were significantly reduced. In addition, Ishikawa spheroid cells were significantly suppressed compared with the control groups. RT-PCR results revealed that substances and their combinations affect genes associated with PI3K/AKT/mTOR pathway and apoptosis. Flow cytometry results showed notably increased apoptosis by single and combined treatments. Conclusion: As a result, the single and combination forms of everolimus, metformin, and lithium have reduced cell proliferation, induced apoptosis, and decreased mTOR activation through various mechanisms in Ishikawa cells. However, our study has shown that Eve alone and triple combination therapy (Eve+Met+Lit) are more effective than other therapies in the treatment of endometrial cancer.