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    Investigation of the Effect of Farnesol on Biofilm Formation by Candida albicans and Candida parapsilosis Complex Isolates
    (Ankara Microbiology Soc, 2024) Erdal, Berna; Baylan, Bensu; Batar, Bahadir; Ozturk, Ali; Topcu, Birol
    The incidence of infections caused by Candida species has significantly increased over the past three decades. Candida albicans is commonly recognized as the primary causative agent in cases of candidiasis; however, non-albicans Candida species, including Candida parapsilosis, are also frequently defined as pathogens. Treatment -resistant infections arise as a result of biofilm formation, which is one of the effective mechanisms in the pathogenesis of Candida infections. However, the mechanisms of action of farnesol, a quorum sensing (QS) system molecule, on biofilm formation by Candida species remain unclear. This study aimed to demonstrate the changes in the biofilm biomass of C.albicans and C.parapsilosis complex isolates in the presence of farnesol and reveal the expression of the EFG1 and BCR1 genes, which are believed to play a role in the production of QS molecules, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis. C.albicans (n= 91) and C.parapsilosis complex (n= 29) isolates obtained from different clinical samples were included in the study. The minimum inhibitory concentration (MIC) values of farnesol were determined using the broth microdilution method according to the M27 -A3 protocol of the Clinical and Laboratory Standards Institute (CLSI). The biofilm biomass of the isolates was examined without farnesol and at the MIC-0 and MIC-2 concentrations of farnesol. Changes in the expression of the biofilm-associated EFG1 and BCR1 genes were investigated using qRT-PCR. According to the results of the study, the MIC values of farnesol were detected in the range of 1-2 mM in 82.4% (n= 75) of the C.albicans isolates and in the range of 0.5-1 mM in 72.4% (n= 21) of the C.parapsilosis complex isolates. Of the C.albicans isolates, 27 (29.7%) exhibited a strong biofilm formation and 58 (63.7%) demonstrated a weaker biofilm formation, while these rates were 34.4% (n= 10) and 62.1% (n= 18), respectively, for the C.parapsilosis complex isolates. At the MIC-0 and MIC-2 concentrations, farnesol was observed to reduce biofilm biomass among C.albicans (n= 24, 88.9%) and C.parapsilosis complex (n= 8, 80.0%) isolates that formed strong biofilms and observed to increase biofilm biomass among those that formed weak biofilms [60.3% (n= 35) and 55.6% (n= 10), respectively]. On completion of the qRT-PCR analysis supporting the results of the biofilm experiment, it was determined that the expressions of the EFG1 and BCR1 genes decreased at the MIC-0 and MIC-2 concentrations of farnesol among the strong biofilm-forming C.albi- cans and C.parapsilosis complex isolates, but there was an increase in gene expressions among the weak biofilm-forming isolates. In addition to the antifungal effect of farnesol on Candida species, this study provided data on the efficacy of the MIC-0 and MIC-2 concentrations of farnesol against Candida biofilm biomass. Although our results suggest that farnesol can be used as an alternative agent to reduce biofilm formation in Candida infections, they need to be supported by further studies. Moreover, this research has significance as it represents the first study to determine the EFG1 and BCR1 gene expressions among C.parapsilosis complex isolates in the presence of farnesol.
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    MicroRNAs in cancer management
    (Nova Science Publishers, Inc., 2018) Batar, Bahadir; Ozoran, Emre; Guven, Mehmet
    MicroRNAs (miRNAs) are small non-coding single-stranded RNA molecules of 19- 25 nucleotides in length. miRNAs' main function is the post-transcriptional regulation of gene expression through messenger RNA (mRNA) repression or degradation by binding to 3' untranslated region (3'UTR) of target mRNAs. More than 60% of human proteincoding genes contain miRNA-binding regions within their 3' UTRs. miRNA-mRNA interactions are mediated by a 6 to 8 nucleotide long seed sequence in the miRNA 5' end. miRNAs can target different mRNAs. miRNAs have been linked to the etiology, initiation, progression, and prognosis of all kinds of human cancers. Experimental evidence showed that dysregulated miRNAs affect the hallmarks of malignant cells including, self-sufficiency in growth signals, evading apoptosis, sustaining proliferative signals, inducing angiogenesis, activating invasion, and metastases. miRNAs can have oncogenic or tumor suppressive function in the majority of cancers. Tumor suppressor miRNAs target cellular oncogenes and are downregulated in cancer. Oncogenic miRNAs regulate tumor suppressor genes and are overexpressed in cancer. Numerous human miRNA genes are located at fragile sites or in genomic regions that are deleted, amplified or translocated in cancer. miRNA expression is dysregulated in human malignancies through various mechanisms, containing miRNA gene amplification or deletion, aberrant transcriptional control of miRNAs, epigenetic alterations and defects in the miRNA biogenesis machinery. In addition to genomic alterations, dysregulated miRNA expression could be due to alterations in tumor suppressor or oncogenic transcription factors that function as transcriptional activators or repressors to control pri-miRNA transcription, such as c-myc and p53. Genome-wide profiling studies revealed that miRNA expression signatures are related with tumor type, tumor grade and clinical outcomes, so miRNAs could be potential candidates for diagnostic and prognostic biomarkers and development of therapeutic strategies. © 2018 Nova Science Publishers, Inc. All rights reserved.
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    Myxoma Virus Combination Therapy Enhances Lenalidomide and Bortezomib Treatments for Multiple Myeloma
    (Mdpi, 2024) Yesilaltay, Alpay; Muz, Dilek; Erdal, Berna; Bilgen, Turker; Batar, Bahadir; Turgut, Burhan; Topcu, Birol
    This study aimed to explore the effectiveness and safety of Myxoma virus (MYXV) in MM cell lines and primary myeloma cells obtained from patients with multiple myeloma. Myeloma cells were isolated from MM patients and cultured. MYXV, lenalidomide, and bortezomib were used in MM cells. The cytotoxicity assay was investigated using WST-1. Apoptosis was assessed through flow cytometry with Annexin V/PI staining and caspase-9 concentrations using ELISA. To explore MYXV entry into MM cells, monoclonal antibodies were used. Moreover, to explore the mechanisms of MYXV entry into MM cells, we examined the level of GFP-labeled MYXV within the cells after blocking with monoclonal antibodies targeting BCMA, CD20, CD28, CD33, CD38, CD56, CD86, CD117, CD138, CD200, and CD307 in MM cells. The study demonstrated the effects of treating Myxoma virus with lenalidomide and bortezomib. The treatment resulted in reduced cell viability and increased caspase-9 expression. Only low-dose CD86 blockade showed a significant difference in MYXV entry into MM cells. The virus caused an increase in the rate of apoptosis in the cells, regardless of whether it was administered alone or in combination with drugs. The groups with the presence of the virus showed higher rates of early apoptosis. The Virus, Virus + Bortezomib, and Virus + Lenalidomide groups had significantly higher rates of early apoptosis (p < 0.001). However, the measurements of late apoptosis and necrosis showed variability. The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.
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    The Long-Term Impact of Ionizing Radiation on DNA Damage in Patients Undergoing Multiple Cardiac Catheterizations
    (Humana Press Inc, 2023) Cimci, Murat; Batar, Bahadir; Bostanci, Merve; Durmaz, Eser; Karayel, Bahadir; Raimoglou, Damla; Guven, Mehmet
    Ionizing radiation (IR) exposures have increased exponentially in recent years due to the rise in diagnostic and therapeutic interventions. A number of small-scale studies investigated the long-term effect of IR on health workers or immediate effects of IR on patients undergoing catheterization procedures; however, the long-term impact of multiple cardiac catheterizations on DNA damage on a patient population is not known. In this study, the effects of IR on DNA damage, based on micronuclei (MN) frequency and 8-hydroxy-2 & PRIME;-deoxyguanosine (8-OHdG) as markers in peripheral lymphocytes, were evaluated in patients who previously underwent multiple cardiac catheterization procedures. Moreover, genetic polymorphisms in genes PARP1 Val762Ala, OGG1 Ser326Cys, and APE1 Asn148Glu as a measure of sensitivity to radiation exposure were also investigated in the same patient population. The patients who underwent & GE; 3 cardiac catheterization procedures revealed higher DNA injury in comparison to the patients who underwent & LE; 2 procedures, documented with the presence of higher level of MN frequency (6.4 & PLUSMN; 4.8 vs. 9.1 & PLUSMN; 4.3, p = 0.002) and elevated serum 8-OHdG levels (33.7 & PLUSMN; 3.8 ng/mL vs. 17.4 & PLUSMN; 1.9 ng/mL, p = 0.001). Besides, OGG1 Ser326Cys and APE1 Asn148Glu heterozygous and homozygous polymorphic types, which are related with DNA repair mechanisms, were significantly associated with MN frequency levels (p = 0.006 for heterozygous and p = 0.001 for homozygous with respect to OGG1 Ser326Cys, p = 0.007 for heterozygous and p = 0.001 for homozygous with respect to APE1 Asn148Glu). There was no significant difference in terms of PARP1 Val762Ala gene polymorphism between two groups.