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    Evaluating the Neuroprotective and Acetylcholinesterase Inhibitory Properties of Four Calcineurin Inhibitor Drugs: Tacrolimus, Pimecrolimus, Cyclosporin A, and Voclosporin
    (Springer, 2025) Kocanci, Fatma Gonca; Sarban, Hamiyet Eciroglu; Yildiz, Fatma
    Neurodegenerative diseases (ND), marked by progressive neuronal degeneration, often involve dysregulation of acetylcholinesterase (AChE), a key enzyme in cholinergic neurotransmission. AChE inhibition is a well-established therapeutic strategy for Alzheimer's disease (AD), the most prevalent ND, as it aims to restore impaired cholinergic function. However, the effects of calcineurin inhibitors (CNIs), primarily used as immunosuppressants, on AChE activity remain largely unexplored. Recent evidence suggests CNIs possess neuroprotective properties, highlighting their potential for ND treatment. This study evaluated the binding affinities of FDA-approved CNIs-Tacrolimus (Tac), Pimecrolimus (Pim), Cyclosporine A (Csa), and Voclosporin (Voc)-to AChE via molecular docking and molecular dynamic simulation. AChE inhibition was assessed in vitro using the Ellman method and in H2O2-induced degenerative neuron-like SH-SY5Y cells via ELISA and qRT-PCR. Neuroprotection was examined through MTT assays and neurite analysis. Additionally, the antiapoptotic effect was examined by ELISA analysis measuring caspase-3. Docking studies confirmed strong AChE binding for all CNIs, with Voc exhibiting the highest affinity. Voc demonstrated superior in vitro AChE inhibition, surpassing galantamine at low concentrations. Cellular assays showed that CNIs, particularly Voc, significantly inhibited AChE expression at the gene level. Moreover, Voc markedly restored cell viability and reduced neuronal degeneration in H2O2-treated cells. These findings suggest CNIs, especially Voc, as promising candidates for ND treatment, targeting AChE overactivity and oxidative stress.Graphical AbstractCreated in BioRender. Hamiyet Eciroglu Sarban, (2025) https://BioRender.com/q77r137
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    Expression and diagnostic potential of circulating miR-107, miR-134-5p, miR-149-5p, miR-370-3p, and miR-221 in prostate cancer and benign prostatic hyperplasia: A preliminary study
    (Page Press Publications, 2025) Akkoç, Ali; Sarban, Hamiyet Eciroglu; Yildiz, Fatma; Günizi, Ozlem Ceren; Uçar, Murat
    Background: MicroRNAs (miRNAs) have shown promise as diagnostic biomarkers for prostate cancer (PCa). This study aimed to evaluate the expression of miR-107, miR-134-5p, miR-149-5p, miR-370-3p, and miR-221 in whole blood to distinguish PCa from benign prostatic hyperplasia (BPH) and potentially reduce unnecessary biopsies. Methods: Whole blood samples were collected from 20 PCa patients, 17 histologically-confirmed BPH patients (all with PSA > 4 ng/mL), and 20 healthy controls over 60 years without symptoms suggesting prostatic disease and PSA < 4 ng/mL. miRNA levels were quantified using qRT-PCR. Diagnostic potential was assessed via correlation analyses with clinical parameters and ROC curve evaluation. Statistical significance was set at p < 0.05. Results: miR-107, miR-134-5p, miR-149-5p, and miR-370-3p were significantly overexpressed in PCa patients compared to BPH (p < 0.0001). ROC analysis identified miR-134-5p (AUC: 0.94) and miR-149-5p (AUC: 0.93) as strong predictors of PCa. Additionally, miR-149-5p showed a positive correlation with PSA levels (r = 0.2627, p < 0.05). Conclusions: This preliminary study demonstrated that miR-107, miR-134-5p, miR-149-5p, and miR-370-3p were significantly overexpressed in PCa patients compared to the BPH group. ROC analysis highlighted their diagnostic potential in distinguishing BPH from PCa. Despite the limited sample size, these findings provide early evidence to guide future research on the diagnostic value of miRNAs in prostate cancer. © 2025, Page Press Publications. All rights reserved.
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    Phytochemical examination of Cistus laurifolius extract and its impact on cytotoxicity, apoptosis and oxidative stress in colorectal and breast cancer cell lines
    (Elsevier Gmbh, 2024) Yildiz, Fatma; Sarban, Hamiyet Eciroglu; Kocanci, Fatma Gonca; Gungor, Meltem; Yucel, Ersin; Yucel, Dilge
    Introduction: Colon and breast cancer are the most common types of cancer worldwide. This study investigatesd the anticancer properties of Cistus laurifolius L. leaf extract on breast cancer (MCF-7) and human colon cancer (Caco-2) cell lines. Methods: The research involved meticulous collection, drying and processing of C. laurifolius leaves to extract bioactive compounds, subsequently analyzed for phenolic content using advanced LC-MS/MS technology. Cell viability of the extract on MCF-7 and Caco-2 cells was demonstrated by MTT test. Levels of critical apoptotic markers (Bad, Bax/Bcl-2, Bax/Bcl-xl, Caspase-9) and Total Antioxidant Capacity (TAC) and Total Oxidant Capacity (TOC), which affect the antioxidant system, were evaluated by the ELISA method. Identification of phenolic compounds, including quercetin and rutin, through target prediction analysis enriches our understanding of bioactive molecules. Results: The results of the study showed that C. laurifolius extract inhibited cell proliferation time and dose-dependent on Caco-2 and MCF-7 cells (P<0.05). TAC, Bax/Bcl-2 and Bax/Bcl-xl ratios in MCF-7 and Caco-2 cells increased in a dose-dependent manner compared to the control group. In MCF-7 cells, TAC (p<0.05; p<0.01), Bax/Bcl-2 (p<0.001; p<0.0001) and Bax-Bcl-xl (p<0.01) ratios increased at 24 h compared to the control group. In Caco-2 cells, TAC (p<0.001), Bax/Bcl-2 ratios increased at 48 h (p<0.05), while Bax-Bcl-xl ratios decreased (p<0.01; p<0.001) compared to the control group. Conclusion: C. laurifolius leaf extracts emerge as a promising anticancer candidate, hindering cell proliferation and inducing apoptosis in colon and breast cancer cells. The classification of bioactive molecules may facilitate further clinical therapeutic interventions targeting colon and breast cancer.