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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 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 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 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.
