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Öğe Assessing lipoxin-mediated inflammatory responses in the second trimester of pregnancy among women with obesity: A comprehensive analysis(Galenos Publ House, 2023) Otlu, Oender; Melekoglu, Rauf; Kiran, Tugba Raika; Inceoglu, Feyza; Erenler, Ayse SebnemObjective: This study aimed to explore the relationship between maternal plasma lipoxin A4 (LXA4) levels during the second trimester of pregnancy and certain proinflammatory molecules, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), as well as the antiangiogenic factor vascular endothelial growth factor receptor 1 (VEGFR-1), in conjunction with obesity among pregnant women. Materials and Methods: A total of 30 pregnant women with obesity were compared with 30 pregnant women of normal weight, matched for both age and gestational week. Plasma samples were collected from all participants between the 18th and 28th weeks of pregnancy. The levels of LXA4, VEGFR-1, IL-6, and TNF-alpha were quantified using enzyme-linked immunosorbent assay. Results: Plasma levels of LXA4 were notably lower in pregnant women with obesity, whereas levels of TNF-alpha and VEGFR1 were significantly higher (p=0.041, p<0.001, and p<0.001, respectively). There was no significant difference in IL-6 levels between groups (p=0.072). The binary logistic regression model revealed significant associations between obesity and the examined inflammatory mediators. Specifically, the results demonstrated that higher levels of LXA4 were linked to a reduced obesity risk, with each unit increase corresponding to a 0.926-fold decrease in the likelihood of obesity. Conversely, elevated levels of TNF-alpha and VEGFR1 were associated with an increased risk of obesity. Conclusion: The study concluded that increased body mass index during pregnancy affects the levels of plasma lipoxin, cytokines, and angiogenesis-related factors. Although the exact mechanisms remain unclear, the observed changes suggest a disruption in the metabolic systems of women with obesity, which may influence physiological changes during pregnancy and lead to obesity-related pathological conditions.Öğe Assessment of the Antifungal Effect of Biotechnological Product-A New Vegan Agent Microbial Chondroitin Sulfate Against Predominant Candida Strains(Jihad Daneshgahi, 2024) Erenler, Ayse Sebnem; Unver, Tuba; Melekoglu, RaufMicrobial Chondroitin Sulfate (CS), possesses biocompatible, antiallergic, and non-toxic properties due to its polyanionic structure hold potential as an antifungal agent. This study investigated the effectiveness of microbial CS generated from recombinant Escherichia coli C2987 by biotechnological techniques as an antifungal product for treating Candida infections. Chondroitin biosynthesis was conducted utilizing a recombinant non-pathogenic E. coli, generated through the transformation of plasmid pETM6-PACF-vgb, which carries genes (kfoA, kfoC, and kfoF) responsible for chondroitin synthesis, along with the Vitreoscilla hemoglobin gene (vgb). The broth microdilution and agar dilution assays were employed to assess the antifungal activity of microbial CS and commercial CS against predominant Candida strains comparatively. The inhibitory effect of microbial CS against Candida albicans, Candida tropicalis, Candida parapsilosis, , and Candida krusei was greater than that of commercial CS. This study demonstrates the antifungal activity of microbial CS, a pharmacological agent produced from a recombinant source (vegan-halal). Microbial CS can be a potential supportive treatment not only for vaginal candidiasis but also for other Candida infections that may cause skin and mucosal infections, with its supportive effect on connective tissues and its therapeutic-preventive effect on possible Candida infections.Öğe BIOCHEMICAL EFFECT EVALUATION OF MICROBIAL CHONDROITIN SULPHATE IN EXPERIMENTAL KNEE OSTEOARTHRITIS MODEL(Parlar Scientific Publications (P S P), 2022) Erenler, Ayse Sebnem; Karabulut, Aysun Bay; Sevimli, Resit; Geckil, Hikmet; Akpolat, Nusret; Unver, Tuba; Otlu, OnderOsteoarthritis (OA) is the most common chronic joint disease, primarily due to aging. Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) commonly used to treat osteoarthritis. CS can delay the progression of pathology or reverse morphological changes in joint structure. Traditionally CS is produced from animal sources. However, due to different reasons such as contamination, ecological risk, and the possibility of infectious diseases, the trend towards microbial sources has increased because of its advantages such as purer, more antiallergic, and lower Molecular Weight (MW) than animal sources. Biochemical analysis of Microbial CS (MCS), which is a new and significant alternative as a source of CS in the OA healing process, has not been evaluated in the literature yet. This study was designed to analyze the biochemical effects of MCS produced by our team from a microbial source, with an MW value of 269 Daltons, on the osteoarthritis healing process compared to the commercial foiut. We aim to reach data that MCS has a higher antioxidant effect than animal -sourced CS, and in this way, it is a more suitable production for the treatment of osteoarthritis. In this study, knee osteoarthritis was surgically induced in experimental rabbits; and TGF113, CAT, MPO, TOS, and OSI parameters measured in blood samples before the operation and after the healing period were analyzed comparatively. After the surgical application, the rabbits were randomly divided into three groups: control, animal -sourced CS, and E. cull sourced. MCS. The standard rabbit diet was administered daily to 10 rabbits in Group 1 (control), and. CS and MCS were applied daily to the other groups as 17 mg/kg for 12 weeks. Blood samples were taken from rabbits at the 12th week after surgery, and TGF-113, CAT, MPO, TOS, and OSI parameters were biochemically evaluated. This study has confirmed that the antioxidant properties of MCS and data on its effectiveness in controlling oxidative stress compared to animal -sourced CS. Based on these results, it can be concluded that MCS has a significant potency of nutraceutical and therapeutic agents for OA treatment.Öğe Capsular Polysaccharide Biosynthesis from Recombinant E. coli and Chondroitin Sulfate Production(C M B Assoc, 2019) Erenler, Ayse SebnemChondroitin sulfate (CS) is an important biomedical product. CS is the basic structural component of the mammalian extracellular matrix and is widely used in many applications in the fields of medicine, veterinary medicine, pharmaceuticals and cosmetics. For CS production, mainly animal sources are used. However, in today's conditions, due to various risks and artificial synthesis, there has been an increase in alternative sources of production methods for CS, instead of using animal resources. In this study as a powerful alternative microbial production of CS has been targeted. By using recombinant E. coli strains to integrate VHb/vgb(+) and kfo(+) systems, the aim was to obtain high purity CS from reliable biotechnological processes. Plasmid pUC8:15 bearing the vgb gene region, and plasmid pETM6-PACF carrying the kfoA, kfoC and kfoF genes responsible for chondroitin synthesis, were transferred to E. coli bacteria. Microbial CS was obtained by adding sulfate groups to chondroitin acquired after the treatments. The results were confirmed by HPLC and NMR analyses. The product, compared to its counterparts, was found to be an effective drug, potentially with a low molecular weight value.Öğe Cloning and Expression vgb-kfo Genes in E. coli and Microbial Chondroitin Sulfate Production(Amer Scientific Publishers, 2019) Erenler, Ayse Sebnem; Geckil, Hikmet; Karabulut, Aysun Bay; Akpolat, Nusret; Sevimli, Resit; Ulke, Esra; Aliyeva, AygunThis study focused on a new plasmid and new recombinant strain developed for the production of microbial chondroitin sulfate a new and limited area of study the strategies we applied for the production of microbial chondroitin sulfate, and the possible contributions of this study to published research literature. In this study, pETM6-PACF, which carries the genes responsible for capsular chondroitin synthesis [kfA, kfoC, kfoF] was used as the basic plasmid. The Vitreoscilla hemoglobin gene region was transformed into this basic plasmid and the common expression of both gene groups was added to research literature for the first time. This plasmid was transferred to non-pathogenic E. coil (C2987) to produce a completely new chondroitin source specific to this study. Following the transformation by chondroitin synthesis, and the subsequent microbial production of chondroitin by the application of purification protocols, microbial chondroitin sulfate was produced in sulfate form. Consequently, in comparison to published literature, a product with a low molecular weight value of 269 Daltons was developed. This product, which has significant potential drug potency, can be used in many different areas as a novel and unique biomedical product.Öğe Comparative Analysis of Antioxidant, Anticholinesterase, and Antibacterial Activity of Microbial Chondroitin Sulfate and Commercial Chondroitin Sulfate(Wiley-V C H Verlag Gmbh, 2023) Unver, Tuba; Erenler, Ayse Sebnem; Bingul, Murat; Boga, MehmetChondroitin synthesis was performed using the recombinant Escherichia coli(C2987) strain created by transforming the plasmid pETM6-PACF-vgb, which carries the genes responsible for chondroitin synthesis, kfoA, kfoC, kfoF, and the Vitreoscilla hemoglobin gene (vgb). Then, Microbial chondroitin sulfate (MCS)'s antioxidant, anticholinesterase, and antibacterial activity were compared with commercial chondroitin sulfate (CCS). The antioxidant studies revealed that the MCS and CCS samples could be potential targets for scavenging radicals and cupric ion reduction. MCS demonstrated better antioxidant properties in the ABTS assay with the IC50 value of 0.66 mg than CCS. MCS showed 2.5-fold for DPPH and almost 5-fold for ABTS *+ (with a value of 3.85 mg/mL) better activity than the CCS. However, the compounds were not active for cholinesterase enzyme inhibitions. In the antibacterial assay, the Minimum inhibitory concentration (MIC) values of MCS against S. aureus, E. aerogenes, E. coli, P. aeruginosa, and K. pneumoniae (0.12, 0.18, 0.12, 0.18, and 0.18 g/mL, respectively) were found to be greater than that of CCS (0.42, 0.48, 0.36, 0.36, and 0.36 g/mL, respectively). This study demonstrates that MCS is a potent pharmacological agent due to its physicochemical properties, and its usability as a therapeutic-preventive agent will shed light on future studies.Öğe Comparative evaluation of cytotoxic and anti-metastatic function of microbial chondroitin sulfate and animal-originated commercial chondroitin sulfate in cancer cells(C M B Assoc, 2023) Unver, Tuba; Celik-Uzuner, Selcen; Erenler, Ayse SebnemCancer has the second-highest mortality rate worldwide after cardiovascular disease. In addition, cervical and breast cancer are two of the leading causes of cancer-related deaths among women. The tumor microenvironment, which consists of cells that form blood vessels, proteins, fibroblasts, and immune cells, is a therapeutic target for cancer therapy. As part of the extracellular matrix (ECM), glycosaminoglycan Chondroitin Sulfate (CS) is related to diverse aspects of tumor growth and metastasis depending on the CS sulfate pattern. This study analyzed the roles of Microbial CS and Commercial CS in tumor growth and metastasis using HeLa cervical cancer cells, MDA-MB-231 metastatic breast cancer cells, and normal fibroblasts. In addition, the role of CS types in wound healing was also assessed comparatively. Microbial CS was more cytotoxic in MDA-MB-231 cells than HeLa compared to Commercial CS. Although both CS reduced cell viability in normal cells, the selective index of Microbial CS in MDA-MB-213 cells was higher than its commercial counterpart. In addition, the role of CS types in wound healing was also assessed comparatively. Both types of CS decreased the cell migration in MDA-MB-231 breast cancer cells, but HeLa cells were more sensitive to Microbial CS than Commercial CS to heal the wound. The wound healing of NIH3T3 cells after Microbial CS was similarly high to the healing after Commercial CS. This preliminary study shows that microbial CS produced by biotechnological methods from a recombinant source created by our team can be an effective therapeutic agent in various types of cancer.Öğe DESIGN OF HIGH-PERFORMANCE MICROBIAL FUEL CELL WITH ENTEROBACTER AEROGENES CARRYING THE VITREOSCILLA HEMOGLOBIN GENE(Parlar Scientific Publications (P S P), 2019) Erenler, Ayse Sebnem; Ulke, Esra NezafedIn this work, in order to achieve high energy efficiency, we designed a microsize microbial fuel cell (MCF) based on Enterobacter aerogenes (E. aerogenes) and vgb(-)/vgb(+) recombinants. In this design, firstly, E. aerogenes as microorganism was used to compare energy efficiency. Then E. aerogenes modified with Vitreoscilla Hemoglobin Gene to enhance its ability to produce protons. The modified E. aerogenes vgb(-)/vgb(+) recombinants were tested in the fuel cell as microorganism. In MCF, bacteria play an important role for the energy production. E. aerogenes is a bacterium that can easily adapt to MFC systems and has high energy production. The aim of the study was to generate electricity in an MFC system that was modeled by us according to current principles using E. aerogenes and vgb(-)/vgb(+) recombinants known to produce high levels of hydrogen. In our study, the voltages produced by the hosts and recombinants under certain feeding environments were measured. Bacteria grown under optimal conditions, at pH 7 and 37 degrees C showed effective performances in the novel MFC system by producing voltages of 0.508 and 0.440 V in 10 mL MCF. The results show that advanced optimization of the medium, MFC elements, and environmental conditions can make our system much more productive and offer a significant contribution to MFC studies. This is the first measurement of the performance of a vgb gene system in MFC.Öğe Effect of vgb gene on microbial chondroitin sulfate production in recombinant Escherichia coli pETM6-PACF-vgb and physicochemical characterization of produced chondroitin sulfate(Cellular and Molecular Biology Association, 2025) Erenler, Ayse Sebnem; Unver, Tuba; Ceylan, Ahmet Faruk; Ozcan, Imren; Geckil, HikmetChondroitin Sulfate (CS) is an essential component of the extracellular matrix and is a sulfated glycosaminoglycan structurally composed of a polysaccharide chain consisting of N-acetyl galactosamine and glucuronic acid. The use of CS of animal origin is common in pharmacological research. The disadvantages of traditional sources and methods used in the production of CS, which is used in various applications in the medicine, veterinary, pharmacy, and cosmetic sectors, have made microbial production a vital alternative. In this study, recombinant Escherichia coli (pETM6-PACF-vgb) strain, in which kfoA, kfoC, kfoF and vgb gene regions are co-expressed, and E. coli pETM6-PACF strain, which does not contain the vgb gene, were used in the microbial production of CS. The vgb gene is the region responsible for expressing the bacterial protein Vitreoscilla hemoglobin (VtHb). This study investigated the effect of the expression of VtHb in E. coli on increasing bacterial cell respiration and, therefore, how ATP production would affect cell growth and the acquisition of chondroitin and microbial chondroitin sulfate (MCS) from biomass. The analysis results determined a 23.07% increase in the amount of MCS produced from the vgb+ strain. The presence of vgb had positively affected culture age and reproductive kinetics. Spectrophotometric measurements, NMR, HPLC, FT-IR, TGA, DTA, and DSC analyses for the reproductive values and physicochemical characterization of the obtained MCS were applied to discuss this production process. For more detailed results on this subject, future research focused on optimization is needed. © 2025 Cellular and Molecular Biology Association. All rights reserved.Öğe Electrospun Polycaprolactone (PCL)/Microbial Chondroitin Sulfate (CS)-Based Transdermal Patches for Optimized Ribociclib Delivery(Amer Chemical Soc, 2025) Gunduz Tavlar, Nermin; Balcioglu, Sevgi; Erenler, Ayse Sebnem; Ates, BurhanBreast cancer remains the most prevalent cancer worldwide and a leading cause of mortality in women, demanding advanced drug delivery strategies. Ribociclib, a CDK4/6 inhibitor used in hormone-dependent breast cancer therapy, is effective but requires high oral doses, leading to severe systemic toxicity. To overcome this limitation, we developed electrospun PCL/CS-based transdermal patches designed to enhance drug bioavailability, prolong half-life, and minimize side effects. Extensive characterization confirmed the structural integrity and performance of the patches, demonstrating high swelling capacity (81-93%), superior thickness uniformity (95-100%), and exceptional folding endurance (1000-1540 cycles). The patches exhibited excellent weight homogeneity (92-99%) for consistent drug distribution, while adhesion strength (144-386 kPa) ensured stable skin attachment. HPLC analysis revealed sustained Ribociclib release (similar to 95% over 48 h), and ex vivo rat skin diffusion studies confirmed high permeability (68-81%), indicating effective transdermal absorption. Drug retention efficiency exceeded 95% in both the reservoir and drug release layers. Biocompatibility assessments with L-929 fibroblasts demonstrated excellent cell viability (90-95%), while MCF-7 breast cancer cells exhibited potent cytotoxicity (93-94%), comparable to standard Ribociclib treatment. Despite the therapeutic potential of transdermal drug delivery systems (TDDS), Ribociclib has been scarcely explored in this context. This study pioneers a promising alternative for controlled, sustained drug release, potentially revolutionizing breast cancer treatment by improving patient compliance, reducing systemic toxicity, and enhancing therapeutic outcomes.Öğe Evaluation of second trimester plasma lipoxin A4, VEGFR-1, IL-6, and TNF-a levels in pregnant women with gestational diabetes mellitus(De Gruyter Poland Sp Z O O, 2023) Kiran, Tugba Raika; Melekoglu, Rauf; Otlu, Onder; Inceoglu, Feyza; Karabulut, Ercan; Erenler, Ayse SebnemIn this study, our objective was to explore the association between gestational diabetes mellitus (GDM) and second trimester maternal plasma levels of lipoxin A4 (LXA4), along with proinflammatory markers such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-a), and the anti-angiogenic factor vascular endothelial growth factor receptor 1 (VEGFR-1) in pregnant women. The study included a cohort of 30 pregnant women with GDM and a control group of 30 normoglycaemic pregnant women matched for age, body mass index, and gestational age. Plasma samples were collected and analysed by enzyme-linked immunosorbent assay to assess specific biomarkers. The GDM group had significantly lower levels of LXA4 and higher levels of TNF-a and VEGFR-1 compared to the control group (p = 0.038, p = 0.025, and p = 0.002, respectively). A statistically significant decrease in the LXA4/TNF-a ratio was observed in the GDM group (p = 0.004). The results suggest that each unit decrease in the LXA4/TNF-a ratio is associated with a 1.280-fold increase in the risk of GDM. These findings suggest a potential diagnostic role for the LXA4/TNFa ratio as a marker for women with GDM. This work provides new insights into the pathogenesis of GDM and highlights the important interplay between inflammation and metabolic dysregulation.Öğe Response: The role of carbonic anhydrase I and II enzymes in the pathogenesis of gestational diabetes mellitus and their relationship with oxidative stress(Wiley, 2026) Melekoglu, Rauf; Erenler, Ayse Sebnem; Kiran, Tugba Raika; Inceoglu, Feyza; Alkan Uckun, Aysel[No abstract available]Öğe The role of carbonic anhydrase I and II enzymes in the pathogenesis of gestational diabetes mellitus and their relationship with oxidative stress(Wiley, 2026) Melekoglu, Rauf; Erenler, Ayse Sebnem; Kiran, Tugba Raika; Inceoglu, Feyza; Alkan Uckun, AyselObjective Gestational diabetes mellitus (GDM) is a hyperglycemic condition that develops during pregnancy and poses significant risks to maternal and fetal health. Oxidative stress plays a crucial role in the pathogenesis of GDM by disrupting insulin signaling pathways and contributing to beta-cell dysfunction. Carbonic anhydrase (CA) enzymes, particularly CA-I and CA-II, are involved in pH regulation and metabolic homeostasis. However, the relationship between oxidative stress and CA enzyme activity in GDM remains unclear. The aim of the present study was to evaluate CA-I and CA-II levels and their association with oxidative stress parameters in GDM patients. Methods This case-control study included 30 pregnant women with GDM and 30 healthy pregnant controls. Baseline characteristics were fully reported; differences between groups were examined using covariate-adjusted analyses. Serum levels of CA-I, CA-II, malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant capacity (TAC) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Statistical analysis was performed using SPSS 25, with significance set at P < 0.05. Results CA-I and CA-II levels were significantly higher in the GDM group compared to control (P < 0.05). MDA and TOS levels were also elevated in GDM patients, indicating increased oxidative stress, whereas TAC levels were significantly lower (P < 0.05). Receiver operating characteristic (ROC) analysis revealed that CA-I, CA-II, MDA, and TOS exhibited strong discriminatory power in differentiating GDM patients from healthy controls. In a multivariable linear regression adjusting for age, body mass index (BMI), gestational age at sampling, and parity, GDM was associated with higher CA-I (beta = 3.1, 95% confidence interval [CI]: 1.6-4.6) and CA-II (beta = 2.4, 1.1-3.7), higher MDA (beta = 0.27 per 0.1-unit) and TOS (beta = 4.1 per unit), and lower TAC (beta = -0.22 per 0.1-unit; all P <= 0.004). In logistic regression, CA-I, CA-II, MDA, and TOS independently increased the odds of GDM, while TAC was inversely associated (adjusted odds ratios [ORs] 1.28, 1.17, 1.15, 1.05, and 0.87, respectively), with excellent model performance (area under the curve [AUC] 0.86; Hosmer-Lemeshow P = 0.67). Conclusion Increased CA-I and CA-II levels in GDM patients suggest a potential role for CA enzymes in the metabolic dysregulation associated with GDM. The strong correlation between oxidative stress markers and CA enzyme activity highlights their potential as diagnostic and prognostic biomarkers for GDM. Future studies should explore the mechanistic pathways linking CA enzymes with oxidative stress and insulin resistance to identify novel therapeutic targets.Öğe Triumph or tragedy: progress in cancer(Tubitak Scientific & Technological Research Council Turkey, 2014) Erenler, Ayse Sebnem; Geckil, HikmetCancer is probably the number one research area among all human endeavors, receiving the largest portion of science funding in most countries. This is because cancer remains one of the oldest conundrums among all human maladies. Although we now have a greater understanding of the biological and molecular basis of cancer, its diagnosis and therapy still pose great challenges. In this review, our aim is not to establish a comprehensive understanding of cancer, which is essentially impossible, but to outline, in a more provocative way, why cancer research in the pursuit of a cure did not live up to its promise, as the death rate from cancer has not changed much after almost half a century. In addition, we discuss some future perspectives to give some insight into cancer research and debunk the old view that pouring money into cancer research is the only way to overcome this dreadful disease.
