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Identification of common genes associated with development of resistance against tamoxifen and doxorubicin in MCF7 cells
(Springer Nature, 2025) Karabay, Arzu Zeynep; Koç, Aslı; Hekmatshoar, Yalda
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Investigation of the effects of dietary supplement Methylsulfonylmethane on apoptosis signals in acute myeloid leukemia cell lines
(Springer Nature, 2024) Hekmatshoar, Yalda; Karabay, Arzu Zeynep; Koç, Aslı; Özkan, Tülin; Sunguroğlu, Asuman
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Multifaceted Therapeutic Potential of Plant-Derived Exosomes: Immunomodulation, Anticancer, Anti-Aging, Anti-Melanogenesis, Detoxification, and Drug Delivery
(2025) Karabay, Arzu Zeynep; Bara, Jaleh; Hekmatshoar, Yalda; Saadat, Yalda Rahbar
Most eukaryotic and prokaryotic cells have the potential to secrete a group of structures/membrane-bound organelles, collectively referred to as extracellular vesicles (EVs), which offer several advantages to producer/receiver cells. This review provides an overview of EVs from plant sources with emphasis on their health-promoting potential and possible use as therapeutic agents. This review highlights the essential biological effects of plant-derived extracellular vesicles, including immune modulation, anticancer activities, protection against chemical toxicity and pathogens, as well as anti-aging, anti-melanogenesis, and anti-arthritic effects, along with ongoing clinical studies. Evidence revealed that plant-derived EVs' contents exert their beneficial properties through regulating important signaling pathways by transferring miRNAs and other components. Taken all together, the data proposed that plant-derived EVs can be utilized as nutritional compounds and therapeutic agents, such as drug carriers. However, this emerging research area requires further in vitro/in vivo studies and clinical trials to determine the exact underlying mechanisms of EVs' positive health effects in treating various diseases.
Combating chronic kidney disease-associated cachexia: A literature review of recent therapeutic approaches
(2025) Saadat, Yalda Rahbar; Abbasi, Amin; Hejazian, Seyyed Sina; Hekmatshoar, Yalda; Ardalan, Mohammadreza; Farnood, Farahnoosh; Zahed, Sepideh Zununi
In 2008, the Society on Sarcopenia, Cachexia, and Wasting Disorders introduced a generic definition for all types of cachexia: "a complex metabolic syndrome associated with the underlying illness characterized by a loss of muscle, with or without fat loss". It is well-known that the presence of inflammatory burden in end-stage renal disease (ESRD) patients may lead to the evolution of cachexia. Since the etiology of cachexia in chronic kidney disease (CKD) is multifactorial, thus the successful treatment must involve several concomitant measures (nutritional interventions, appetite stimulants, and anti-inflammatory pharmacologic agents) to provide integrated effective therapeutic modalities to combat causative factors and alleviate the outcomes of patients. Given the high mortality rate associated with cachexia, developing new therapeutic modalities are prerequisite for ameliorating patients with CKD worldwide. The present review aims to discuss some therapeutic strategies and provide an update on advances in nutritional approaches to counteract cachexia.
Activation of Proteolysis During Oocyte In Vitro Maturation
(2025) Tepeköy, Filiz; Bulut, Berk; Karaöz, Erdal
In vitro maturation (IVM) is a form of assisted reproductive technology (ART) applied to obtain mature oocytes in culture. Decline in IVM success rates by age has led consideration of novel approaches based on cellular dynamics. Our aim was to achieve proteostasis in old bovine oocytes from 13 to 16-year-old bovine with a lower potential for fertilization. Lysosomal activation was achieved through increasing concentrations of proton pump activators PIP2 (0.1, 0.5, 1, and 5 μM), PMA (0.1, 1, 10, and 50 μM), and DOG (0.1, 1, 10, and 50 μM) at 6, 12, 18, and 24 h of IVM in old bovine oocytes. Morphological analysis was performed and IVM rates were determined. DQ-Red BSA was applied to live oocytes to determine proteolytic activation while lysosome density was determined by Lysotracker probe. Protein carbonylation was detected through oxyblot analysis. Polar body extrusion (PBE), through which a haploid nonfunctional polar body is released in the perivitelline space after completion of the first meiotic division, was observed in PIP2-0.1 μM, -0.5μM-6h; PIP2-5μM-12h; PMA-0.1μM-18h; PIP2-0.1μM, -0.5μM-24h groups. Oocyte diameter was the highest in DOG-1μM-6h, PMA-0.1μM-12h, PIP2-1μM-18h, and PIP2-0.5μM-24h groups. Morphological scores of oocytes were higher in young and old control groups. PIP2, PMA, and DOG affected oocyte quality positively after 6 h of IVM yielding in oocyte scores similar to the control group oocytes. However, they had a negative impact on the oocyte scores in longer periods of IVM, except for lower doses PMA (0.1 and 1 μM) at 12 h and PIP2 (0.5 μM) and PMA (0.1 μM) at 18 h, which were able to maintain the scores relatively closer to the control oocytes. Proteolytic activation was achieved in all groups at 6 h of culture. At all other time points PIP2 and PMA groups showed a better response to proteolytic activation. Lysosome density was increased in PIP2-5μM-6h; PIP2-0.1μM, -1μM-12h; PIP2-1μM, -5μM-18h as well as PMA-0.1μM-6h; PMA-1μM, -10μM-12h; PMA-1μM-18h; DOG-50μM-6h and DOG-0.1μM-12h. Protein carbonylation was the lowest in PIP2-0.1 μM groups at 12, 18, and 24 h. This study suggests that proton pump activators PIP2 and PMA was found to have a positive impact on IVM in terms of both morphological scores and proteolytic activation in a time and dose dependant manner.
Antimicrobial peptides: Could cecropin A and nisin be new promising agents for the treatment of anaerobic infections
(2024) Kurt, Zeynep; Demirci, Mehmet; Arı, Şule; Tokuç, Edip; Kılınçaslan, Ayşe Ceylan; Ziyad, Muhuyedin Abdirahman; Kocazeybek, Bekir Sami; Toman, Hrisi Bahar
Antimicrobial peptides (AMPs) may mitigate the danger of increasing antimicrobial resistance. We aimed to determine the activities of catestatin, temporin A, nisin and cecropin A against Bacteroides fragilis ATCC 25285, Prevotella melaninogenica ATCC 25845, Cutibacterium acnes ATCC 6919, Peptostreptococcus anaerobius ATCC 27337 and Peptostreptococcus stomatis DSM 17678. strains. The susceptibility of all anaerobic bacteria was determined by Kirby-Bauer disc diffusion method, agar dilution and broth microdilution method, recommended by CLSI. By broth microdilution the MIC of temporin A for P. anaerobius was 500µg/mL, and MBC >500µg/mL. The MIC of nisin for P. melaninogenica was 200µg/mL, with a MBC of 400µg/mL, for C. acnes, P. anaerobius, and P. stomatis, MIC were 40mg/mL. The MIC of cecropin A for B. fragilis was 50µg/mL, MBC was 500µg/mL. For C. acnes, the MIC was 4µg/mL, MBC was 8µg/mL. The MIC for P. melaninogenica, P. anaerobius and P. stomatis were 8µg/mL, with corresponding MBC values of 16, 32 and 50µg/mL, respectively. Conversely, catestatin proved ineffective against all strains. In conclusion, our study, demonstrated that cecropin A and nisin showed promising results against anaerobic standard strains. We believe thatfurther research conducted to explore those AMPs could hold promise as a treatment option for anaerobic bacterial infections.
Hyperbolic and trigonometric generators of archimedean copulas: characteristics and performance
(University of Maragheh, 2025) Kazemirad, Amirmasoud; Golshani, Leila; Najjari, Vadood; Kokabinezhad, Mohsen
In this paper, hyperbolic and trigonometric functions, based on cosecant and cotangent as generator function for the family of Archimedean copula, are proposed. For these families, the dependence characteristics are compared. Also, to show the performance of these copulas, we investigate the stochastic frontier model based on them. Then we conclude that the copulas based on hyperbolic and trigonometric cosecant and cotangent are more suitable for modeling dependence structure.
Optimization of Morris Water Maze protocols : effects of water temperature and hypothermia on spatial learning and memory in aged female rats
(Turkish Geriatrics Society, 2024) Oran, Duygu Sultan; Temel, Zeynep; Başer, İbrahim Gökşin; Temizyürek, Arzu; Selcan, Ayşin
Introduction: Aging is a highly complex process driven by a multitude of factors. The use of humans in aging research is complicated by many factors (ethical issues; environmental and social factors; long natural life span). Therefore, rats are common models for the study of aging and age-related diseases. The Morris water maze test is one of the most common cognitive tests in studies investigating age-related learning and memory. However, standardized protocols are lacking, which could influence results. This study investigated the effects of water temperature and inter-trial interval on physiological parameters, hippocampus-dependent learning, and memory in aged female rats performing the Morris Water Maze. Materials and Methods: Thirty-two female Wistar Hannover rats, aged over 18 months, were divided into four groups based on water temperature (20 °C or 24 °C) and inter-trial interval (30 seconds or 13 minutes). Results: Rats exposed to 24 °C demonstrated better spatial learning and memory retention than those at 20 °C. The interaction between inter-trial interval and water temperature significantly affected memory, with higher temperatures improving memory, especially with shorter intervals. Inter-trial interval alone did not significantly affect learning, but longer durations were associated with more stable body temperatures. Neither water temperature nor inter-trial interval significantly influenced body weight. Conclusion: These findings emphasize the need to standardize environmental conditions in Morris water maze protocols to enhance research validity and reliability. Optimizing these protocols is crucial to upholding ethical standards and ensuring animal welfare, advancing more effective and scientifically sound practices in gerontological research, and fostering a better understanding of aging processes.
Changes in secondary structure of protein in skeletal muscle due to high-carbohydrate of high-fat diets
(2024) Özer, Nazlı Ezer; Mollaoğlu, Ayça Doğan
Objective: Obesity, which arises from changes in lifestyle and feeding habits, poses a threat to human health. One essential contributor to the increase in obesity rates is the popularity of high-calorie diets. This study aims to investigate high-fat (HFD) and high-carbohydrate (HCD) diet-induced molecular changes in protein secondary structure in longissimus dorsi skeletal muscle tissues of female inbred C57BL/6J mice by utilizing Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy. Materials and Methods: Mice were fed a control diet, HCD, or HFD for 24 weeks. Their skeletal muscle tissues were collected, and their spectra were recorded using a Bruker Invenio S ATR-FTIR spectrometer in the 4000-400 cm-1 region. Results: The protein secondary structure profiles of the HCD group demonstrated a significant rise in antiparallel beta-sheet and beta-turn and a decline in parallel beta-sheets, together with the insignificant increase in aggregated beta-sheets and a decrease in alpha-helix. The impact of an HFD on protein conformation is less pronounced than HCD. The HFD diet led to an increase in antiparallel beta-sheets and a decrease in parallel beta sheets. Although insignificant, an increase was observed in beta-turn and alpha-helix. Conclusion: These results propose the appearance of protein aggregation and/or formation of protein- protein intermolecular interaction in skeletal muscle tissues of female inbred C57BL/6J mice. Collectively, these data suggest that both high-calorie diets impair secondary structures of protein in skeletal muscle that may affect its metabolic function.
Mitochondria-specific targeting to overcome imatinib resistance in chronic myeloid leukemia cells
(Elsevier, 2024) Hekmatshoar, Yalda; Özkan, Tülin; Karabay, Arzu Zeynep; Koç, Aslı; Gürel, A. Karadağ; Vignais, Marie-Luce; Sunguroğlu, A.
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Comparison of human breast milk vs commercial formula-induced early trophic enteral nutrition during postoperative prolonged starvation in an animal model
(2024) Doğan, Ayça; Severcan, Feride; Tuzlacı, Ayşe; Güvenç, B. Haluk
The present study aimed to characterize the changes in macromolecular composition and structure in ileal tissue induced by postoperative prolonged starvation (PS), human breast milk feeding (HM) and commercial formula feeding (CF) for 48 and 72 h (h). Forty-two Wistar albino rats underwent an ileal transection and primary anastomosis and were then divided into six subgroups. Two groups of seven rats were food-deprived for 48 and 72 h with free access to water only in metabolic cages (48 h PS, 72 h PS). Then, two groups of seven rats received early enteral trophic nutrition (EEN) either using HM, and CF at 48 h post-operation (48 h HM, 48 h CF). The other two groups of seven rats received the same trophic enteral nutrition at 72 h post-operation (72 h HM, 72 h CF). An additional seven rats were fed normal rat chow (control), after which the ileal tissues were harvested and freeze-dried overnight. Then sample spectra were recorded by Fourier transform infrared (FTIR) spectroscopy. PS at 48 and 72 h resulted in an increase in the concentration of lipids and a decrease in the concentration of proteins. CF and HM trophic feeding induced a decrease in membrane fluidity and an increase in lipid order. Ileal tissues showed similar compositional and structural changes in lipids and proteins in the PS and CF groups after 48 and 72 h. A marked decrease in nucleic acid concentration was seen in CF at 48 h compared to HM. The human milk feeding groups did not induce any significant alterations and showed compositional and structural data similar to the controls. In conclusion, EEN application seems to be safer when introduced at 48 h rather than 72 h and time of this nutrition is crucial to maintain ileum structure and therefore immunity and well-being. HM-induced trophic nutrition is seen to protect the ileal tissue from significant alterations within lipid and protein compositions, whereas CF caused notable changes. HM is absolutely the best nutritional source for gut health in this animal model.
Web Server-based structure prediction as a supplementary tool for basic and acidic FGF secondary structure analysis using FTIR spectroscopy and a case study comparing curve-fit with the model-based structure inspection of the FTIR data
(DergiPark, 2023) Korkmaz, Filiz; Mollaoğlu, Ayça; Adıgüzel, Yekbun
Fourier Transform Infrared (FTIR) spectroscopy can provide relative proportion of secondary structure elements in a protein. However, extracting this information from the Amide I band area of an FTIR spectrum is difficult. In addition to experimental methods, several protein secondary structure prediction algorithms serving on the Web can be used as supplementary tools requiring only protein amino acid sequences as inputs. In addition, web-server based docking tools can provide structure information when proteins are mixed and potentially interacting. Accordingly, we aimed to utilize web-server based structure predictors in fibroblast growth factor (FGF) protein structure determination through the FTIR data. Seven such predictors were selected and tested on basic FGF (bFGF) protein, to predict FGF secondary structure. Results were compared to available structure-files deposited in the Protein Data Bank (PDB). Then, FTIR spectra of bFGF and the acidic form of the protein with 50 folds more bovine serum albumin as carrier protein (1FGFA/50BSA) were collected. Optimized Amide I curve-fit parameters of bFGF with low (<5) root mean square deviation (RMSD) in the PDB data and the predictions were obtained. Those parameters were applied in curve-fitting of 1FGFA/50BSA data. Secondary structure was inspected also through applying models derived from the previously established methods. Results of model-based secondary structure estimation from FTIR data were compared with secondary structure calculated as 1 part contribution from 1FGFA/1BSA complex and 49 parts contribution from BSA. Complex structure was obtained through docking. RMSD in the PDB data and the predictions were respectively 3.05 and 2.39 with the optimized parameters. Those parameters did not work well for the 1FGFA/50BSA data. Models are better in this case, wherein one model (Model-1’) with the lowest average RMSD has 8.38 RMSD in the bFGF and 4.78 RMSD in the 1FGFA/50BSA structures. Model-based secondary structure predictions are better for determining bFGF and 1FGFA/50BSA secondary structures through the curve-fit approach that we followed, under non-optimal conditions like protein/BSA mixtures. Web servers can assist experimental studies investigating structures with unknown structures. Any web-based structure prediction supporting the experimental results would be enforcing the findings, but the unsupported results would not necessarily falsify the experimental data.
Gene expression profile as a precursor of inflammation in mouse models: BFMI860 and C57BL/6NCrl
(Istanbul University Press, 2024) Doğan, Ayça; Brockmann, Gudrun A.
Objective: We aimed to investigate the differences in the immune response to body fat content between the genetically mutant obese BFMI860 (BFMI) mouse strain and the lean C57BL/6Ncrl (B6) mouse strain as a control and the effects of obesity on gene expression on inflammation-related pathways in epididymal adipose tissue. Materials and Methods: Six males from each strain were maintained on a standard maintenance diet (SMD) or a high-fat diet (HFD). At the age of 10 weeks, serum and epididymal adipose tissue samples were collected for cytokine and gene expression analyses. RNA samples from epididymal adipose tissue were hybridized using the microarray technique to study the quantitative transcript amounts of genes. Results: Pathway analysis of gene expression data revealed no considerable development of inflammatory state in BFMI and B6 on SMD. Both strains responded to HFD distinctly; the inflammatory state was more prominent in the obese BFMI group than in the lean B6 group. Several genes, such as Adipoq, NFkbia, Plaur, F2r, C3ar1, and Nfatc4 in pathways involved in the immune system have been found to be differentially regulated in BFMI mice. Under the condition of obesity in BFMI mice, the induction of inflammation-related pathways indicates an increased risk of insulin resistance, atherosclerosis, and cardiovascular disease. Conclusion: This study identified distinct expression patterns of genes involved in inflammatory pathways, particularly those associated with the adipocytokine signaling pathway and complement and coagulation cascades, in the epididymal adipose tissue of BFMI and B6 mice. The BFMI strain is a valuable and promising model for clarifying the mechanisms underlying obesity and the activation of inflammation in adipose tissue.
Decoding myasthenia gravis: advanced diagnosis with infrared spectroscopy and machine learning
(2024) Severcan, Feride; Özyurt, İpek; Doğan, Ayça; Severcan, Mete; Gurbanov, Rafig; Küçükcankurt, Fulya; Elibol, Birsen; Tiftikçioğlu, İrem; Gürsoy, Esra; Yangın, Melike Nur; Zorlu, Yaşar
Myasthenia Gravis (MG) is a rare neurological disease. Although there are intensive efforts, the underlying mechanism of MG still has not been fully elucidated, and early diagnosis is still a question mark. Diagnostic paraclinical tests are also time-consuming, burden patients financially, and sometimes all test results can be negative. Therefore, rapid, cost-effective novel methods are essential for the early accurate diagnosis of MG. Here, we aimed to determine MG-induced spectral biomarkers from blood serum using infrared spectroscopy. Furthermore, infrared spectroscopy coupled with multivariate analysis methods e.g., principal component analysis (PCA), support vector machine (SVM), discriminant analysis and Neural Network Classifier were used for rapid MG diagnosis. The detailed spectral characterization studies revealed significant increases in lipid peroxidation; saturated lipid, protein, and DNA concentrations; protein phosphorylation; PO2-asym + sym /protein and PO2-sym/lipid ratios; as well as structural changes in protein with a significant decrease in lipid dynamics. All these spectral parameters can be used as biomarkers for MG diagnosis and also in MG therapy. Furthermore, MG was diagnosed with 100% accuracy, sensitivity and specificity values by infrared spectroscopy coupled with multivariate analysis methods. In conclusion, FTIR spectroscopy coupled with machine learning technology is advancing towards clinical translation as a rapid, low-cost, sensitive novel approach for MG diagnosis.
Methylsulfonylmethane induces caspase-dependent apoptosis in acute myeloid leukemia cell lines
(2024) Hekmatshoar, Yalda; Karabay, Arzu Zeynep; Özkan, Tülin; Koç, Aslı; Sunguroğlu, Asuman
Background: Acute myeloid leukemia (AML) is a heterogeneous ailment in both biological and clinical concepts. Numerous efforts have been devoted to discover natural compounds for combating cancer, which showed great potential in cancer management. Methylsulfonylmethane (MSM), an organosulfur dietary supplement, is utilized for improving various clinical conditions, particularly osteoarthritis. MSM can exert antitumor activity in a wide range of cancers. Objectives: The molecular mechanisms of action underlying antileukemic activity of MSM remain unclear. In this regard, we aimed to investigate the anticancer properties of MSM on human AML cell lines (U937 and HL60) with focus on underlying cell death mechanism. Methods: Anticancer activity of the MSM was examined employing MTT assay, Annexin V-PE/7AAD staining, caspase3/7 activity test, and real-time qPCR. Both cell lines were treated with different concentrations (50-400 mM) of MSM for 24 h. Pretreatment of the cells with a caspase inhibitor (i.e., Z-VAD-fmk) was performed for the assessment of apoptosis induction. Results: The results of MTT assay revealed that in both cell lines, the MSM markedly reduced cell viability in comparison to the control cells. Additionally, findings of Annexin V-7AAD staining revealed that MSM induced apoptosis and activated caspase 3/7 in both cell lines markedly. Real-time quantitative PCR results also supported the induction of apoptosis in AML cells. MSM altered the expression levels of various apoptotic genes (BAX, BAD, and BIM). Conclusion: Overall, our results indicated that MSM could induce apoptosis in AML cell lines in a dose-dependent manner, which therefore could be utilized as an antileukemic agent.
Insights from CD71 presentation and serum lipid peroxidation in myasthenia gravis - A small cohort study
(2024) Çağlayan, Sinem Tuncer; Elibol, Birsen; Severcan, Feride; Gürsoy, Esra Başar; Tiftikçioğlu, Bedile İrem; Güngördü Dalar, Zeynep; Çelik, Ceren; Dai, Ayşe Suna; Karaçam, Sevinç
Myasthenia gravis (MG) is a multifaceted autoimmune disorder affecting the postsynaptic neuromuscular junction. In this study, we examined CD4+ and CD8+ T lymphocyte levels and ratios within peripheral blood mononuclear cells (PBMCs) in MG patients. Additionally, we assessed lymphocytes for the expression of CD71, which functions as a transferrin receptor mediating the uptake of iron into the cells. Building on recent discussions regarding CD20 depletion treatments in MG, we also scrutinized lymphocytes for CD20 expression. Comparative analyses were conducted among healthy controls, newly diagnosed MG patients, those undergoing pyridostigmine treatment alone, and MG patients receiving combination therapies. In the patients, the ratio of CD3+CD4+ T lymphocytes to CD3+ T lymphocytes was found to be decreased compared to the healthy controls, while the ratio of CD3+CD8+ cells to CD3+CD4+ cells increased. An increase in the percentage of CD71-expressing lymphocytes was observed in MG patients compared to the healthy control group, while CD20+ lymphocytes exhibited no statistical changes. Moreover, heightened serum lipid peroxidation levels were found in MG patients. These results suggest a possible relationship between iron metabolism, levels of CD71-expressing cells, and lipid peroxidation in MG. Conversely, pyridostigmine treatment reduced the levels of CD71-expressing cells and lipid peroxidation, suggesting potential immunomodulatory and antioxidant impacts of pyridostigmine in MG, either directly or indirectly.
Therapeutic and prophylactic effects of fulvic acid on a breast cancer model established by MCF-7 cell line in SCID mice
(2024) Gülçiçek, Osman Bilgin; Oran, Duygu Sultan; Temizyürek, Arzu; Yavuz, Erkan; Yiğitbaş, Hakan; Erçetin, Candaş; Solmaz, Ali; Yıldırım, Funda; Sönmez, Kıvılcım; Çelik, Atilla
Introduction. There is still minimal scientific understanding of effects of fulvic acid (FA) on breast cancer. We investigated the prophylactic, therapeutic, and combined effects of FA in a breast cancer model created using MCF-7 cell line in severe combined immunodeficiency disease (SCID) mice. Results. Four experimental groups were established as the control group (Group C), prophylaxis group (Group P), therapeutic group (Group T), and prophylaxis + therapeutic group (Group P + T). Tumor growth was observed by the in vivo imaging system and macroscopically in mammary glands of all mice (100%) of Group C, microscopically in only one mouse of Group P (12.5%), in four mice in Group T (50%), but only one animal (12.5%) in Group P + T. Immunohistochemistry (IHC) showed that p53 staining was significantly higher in tissues of Group C compared to other groups (P < 0.05). No difference was found in IHC scores for p53 between Group P and P + T (P > 0.05). Bcl-2 staining was significantly higher in Group C compared to Group P + T (P = 0.015) and higher in Group P + T compared to Group T (P = 0.021) but no significant difference was found between Group P and others (P > 0.05). Bax staining was significantly higher in Group C compared to others (P < 0.05) but no significant difference was found between FA groups (P > 0.05). Conclusion. Prophylactic FA treatment can prevent tumor formation by inducing variations in the expression of p53, BcL-2, and Bax proteins in mammary glands of SCID mice before tumor formation. This suggests that FA may be a powerful inhibitory candidate for the prevention of tumorigenesis in breast cancer.
Identification of exosomal microRNAs and related hub genes associated with imatinib resistance in chronic myeloid leukemia
(2024) Karabay, Arzu Zeynep; Özkan, Tülin; Gürel, Aynur Karadağ; Koç, Aslı; Hekmatshoar, Yalda; Sunguroğlu, Asuman; Aktan, Fügen; Büyükbingöl, Zeliha
Chemotherapy resistance is a major obstacle in cancer therapy, and identifying novel druggable targets to reverse this phenomenon is essential. The exosome-mediated transmittance of drug resistance has been shown in various cancer models including ovarian and prostate cancer models. In this study, we aimed to investigate the role of exosomal miRNA transfer in chronic myeloid leukemia drug resistance. For this purpose, firstly exosomes were isolated from imatinib sensitive (K562S) and resistant (K562R) chronic myeloid leukemia (CML) cells and named as Sexo and Rexo, respectively. Then, miRNA microarray was used to compare miRNA profiles of K562S, K562R, Sexo, Rexo, and Rexo-treated K562S cells. According to our results, miR-125b-5p and miR-99a-5p exhibited increased expression in resistant cells, their exosomes, and Rexo-treated sensitive cells compared to their sensitive counterparts. On the other hand, miR-210-3p and miR-193b-3p were determined to be the two miRNAs which exhibited decreased expression profile in resistant cells and their exosomes compared to their sensitive counterparts. Gene targets, signaling pathways, and enrichment analysis were performed for these miRNAs by TargetScan, KEGG, and DAVID. Potential interactions between gene candidates at the protein level were analyzed via STRING and Cytoscape software. Our findings revealed CCR5, GRK2, EDN1, ARRB1, P2RY2, LAMC2, PAK3, PAK4, and GIT2 as novel gene targets that may play roles in exosomal imatinib resistance transfer as well as mTOR, STAT3, MCL1, LAMC1, and KRAS which are already linked to imatinib resistance. MDR1 mRNA exhibited higher expression in Rexo compared to Sexo as well as in K562S cells treated with Rexo compared to K562S cells which may suggest exosomal transfer of MDR1 mRNA.
Exploring free amino acid profiles in CCHF patients: Implications for disease progression
(2024) Büyüktuna, Seyit Ali; Yerlitaş, Serra İlayda; Zararsız, Gözde Ertük; Doğan, Kübra; Kablan, Demet; Bağcı, Gökhan; Özer, Selda; Baysal, Cihad; Çakır, Yasemin; Cephe, Ahu; Koçhan, Necla; Zararsız, Gökmen; Doğan, Halef Okan
This study investigated the intricate interplay between Crimean-Congo hemorrhagic fever virus (CCHFV) infection and alterations in amino acid metabolism. Our primary aim is to elucidate the impact of Crimean-Congo hemorrhagic fever (CCHF) on specific amino acid concentrations and identify potential metabolic markers associated with viral infection. One hundred ninety individuals participated in this study, comprising 115 CCHF patients, 30 CCHF negative patients, and 45 healthy controls. Liquid chromatography-tandem mass spectrometry techniques were employed to quantify amino acid concentrations. The amino acid metabolic profiles in CCHF patients exhibit substantial distinctions from those in the control group. Patients highlight distinct metabolic reprogramming, notably characterized by arginine, histidine, taurine, glutamic acid, and glutamine metabolism shifts. These changes have been associated with the underlying molecular mechanisms of the disease. Exploring novel therapeutic and diagnostic strategies addressing specific amino acids may offer potential means to mitigate the severity of the disease.
Evaluation of the first Candida auris isolates reported from Türkiye in terms of identification by various methods and susceptibility to antifungal drugs
(2024) Erköse Genç, Gonca; Küçükkaya, Ilvana Caklovica; Komec, Selda; Önder, İlke Toker; Toptaş, Öykü; Teke, Leyla; Turan, Deniz; Aygün, Gökhan; Gülmez, Dolunay; Arıkan Akdağlı, Sevtap; Erturan, Zayre
Purpose: Candida auris is increasingly being isolated from patients all over the world. It has five clades. In this study, it was aimed to compare the results of biochemical tests obtained using different methods and the antifungal susceptibility profiles of C. auris strains isolated from the first seven cases reported in Türkiye, and evaluate whether this information could be useful as preliminary data in determining the clade of strains in centers that lack the opportunity to apply molecular methods. Methods: Identification test results obtained using API ID 32 C, API 20 C AUX, VITEK-2 YST, and MALDI-TOF MS; colony color and morphology on Chromagar Candida, CHROMagar Candida Plus media, and cornmeal-Tween 80 agar; susceptibility to antifungals were tested and compared. Antifungal susceptibility test was studied using microdilution method according to the recommendations of EUCAST. Additionally, a pilot study was conducted to investigate the value of CHROMagar Candida Plus. Results: All seven strains were identified as Lachancea kluyveri with API ID 32 C, Rhodotorula glutinis; Cryptococcus neoformans with API 20 C AUX, and C. auris with both VITEK-2 YST and MALDI-TOF MS. MIC values for fluconazole were very high (≥64 mg/L) for all seven strains. It was observed that 11 (37.9%) of 29 Candida parapsilosis strains formed colonies with morphology similar to C. auris on CHROMagar Candida Plus medium, leading to false positivity. Conclusions: Although there have been many isolations of C. auris in our country in recent years, clade distribution of only a small number of strains is known yet. In this study, when the biochemical properties and antifungal susceptibility profiles of the seven strains were evaluated, it was concluded that they exhibited some characteristics compatible with clade I. It was also observed that strains 1 and 2 may belong to a different clade.

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