Biyomühendislik / Bioengineering

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/208

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Discovery of a C-S lyase inhibitor for the prevention of human body malodor formation: tannic acid inhibits the thioalcohol production in Staphylococcus hominis
(SPRINGER NATURE LINK, 2025) Fidan, Ozkan; Karipcin, Ayse Doga; Kose, Ayse Hamide; Anaz, Ayse; Demirsoy, Beyza Nur; Arslansoy, Nuriye; Sun, Lei; Mujwar, Somdutt; 0000-0001-5312-4742; 0009-0005-7132-842X; 0009-0008-5514-8711; 0000-0003-4037-5475; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan; Karipcin, Ayse Doga; Kose, Ayse Hamide; Anaz, Ayse; Demirsoy, Beyza Nur; Arslansoy, Nuriye
Human body odor is a result of the bacterial biotransformation of odorless precursor molecules secreted by the underarm sweat glands. In the human axilla, Staphylococcus hominis is the predominant bacterial species responsible for the biotransformation process of the odorless precursor molecule into the malodorous 3M3SH by two enzymes, a dipeptidase and a specific C-S lyase. The current solutions for malodor, such as deodorants and antiperspirants are known to block the apocrine glands or disrupt the skin microbiota. Additionally, these chemicals endanger both the environment and human health, and their long-term use can influence the function of sweat glands. Therefore, there is a need for the development of alternative, environmentally friendly, and natural solutions for the prevention of human body malodor. In this study, a library of secondary metabolites from various plants was screened to inhibit the C-S lyase, which metabolizes the odorless precursor sweat molecules, through molecular docking and molecular dynamics (MD) simulation. In silico studies revealed that tannic acid had the strongest affinity towards C-S lyase and was stably maintained in the binding pocket of the enzyme during 100-ns MD simulation. We found in the in vitro biotransformation assays that 1 mM tannic acid not only exhibited a significant reduction in malodor formation but also had quite low growth inhibition in S. hominis, indicating the minimum inhibitory effect of tannic acid on the skin microflora. This study paved the way for the development of a promising natural C-S lyase inhibitor to eliminate human body odor and can be used as a natural deodorizing molecule after further in vivo analysis.
Bovine serum albumin (BSA)-Loaded polyvinyl alcohol (PVA) / chitosan (CH) / hydroxyapatite (HA) electrospun nanofibers for bone tissue regeneration
(ELSEVIER, 2025) Bozdag, Mehmet; Urek, Ferhat; Cesur, Sumeyye; Sahin, Ali; Gunduz, Oguzhan; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Urek, Ferhat
The natural bone structure consists of three different nanocomposite layers; a porous polymer ceramic part, a lamellar, and a fiber-matrix composition gives the bone its unique physical and biological properties. During bone tissue regeneration bioactivity, and osteoinductivity are especially important with other parameters such as porosity, degradation rate, and cell adhesion. In this study, hydroxyapatite (HA) and bovine serum albumin (BSA) protein-loaded, polyvinyl alcohol (PVA) and chitosan (CH) nanofibers were fabricated via the electrospinning method. The mean diameters of PVA/CH/HA/BSA-5, PVA/CH/HA/BSA-10, and PVA/CH/HA/BSA-15 nanofibers were measured as 325.39 +/- 77.512 nm, 332.45 +/- 82.251 nm, 447.03 +/- 101.382 nm respectively, required porosity and properties for bone tissue engineering were considered achieved. BSA release profiles of BSA-5, BSA-10, and BSA-15 nanofibers were similar in terms of burst release which continued until the 12th hour, 58 %, 78 %, and 73 % of the BSA were released, respectively. After 72 h 100 % of BSA were released from all nanofibers. Cell viability tests showed that PVA/CH/HA/BSA nanofibers exceeded the control group in terms of cell viability by 119.9 %. In future bone injury treatment, PVA/CH/HA/BSA nanofibers can assist the healing process of cracks and fractures, and decrease the recovery time of bone as an alternative bone healing nanofiber.
Revolutionizing dermatology: harnessing mesenchymal stem/stromal cells and exosomes in 3D platform for skin regeneration
(Springer Nature Link, 2024) Bicer,Mesude; 0000-0001-7089-5661; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Bicer, Mesude
Contemporary trends reveal an escalating interest in regenerative medicine-based interventions for addressing refractory skin defects. Conventional wound healing treatments, characterized by high costs and limited efficacy, necessitate a more efficient therapeutic paradigm to alleviate the economic and psychological burdens associated with chronic wounds. Mesenchymal stem/stromal cells (MSCs) constitute cell-based therapies, whereas cell-free approaches predominantly involve the utilization of MSC-derived extracellular vesicles or exosomes, both purportedly safe and effective. Exploiting the impact of MSCs by paracrine signaling, exosomes have emerged as a novel avenue capable of positively impacting wound healing and skin regeneration. MSC-exosomes confer several advantages, including the facilitation of angiogenesis, augmentation of cell proliferation, elevation of collagen production, and enhancement of tissue regenerative capacity. Despite these merits, challenges persist in clinical applications due to issues such as poor targeting and facile removal of MSC-derived exosomes from skin wounds. Addressing these concerns, a three-dimensional (3D) platform has been implemented to emend exosomes, allowing for elevated levels, and constructing more stable granules possessing distinct therapeutic capabilities. Incorporating biomaterials to encapsulate MSC-exosomes emerges as a favorable approach, concentrating doses, achieving intended therapeutic effectiveness, and ensuring continual release. While the therapeutic potential of MSC-exosomes in skin repair is broadly recognized, their application with 3D biomaterial scenarios remains underexplored. This review synthesizes the therapeutic purposes of MSCs and exosomes in 3D for the skin restoration, underscoring their promising role in diverse dermatological conditions. Further research may establish MSCs and their exosomes in 3D as a viable therapeutic option for various skin conditions.
Revolutionizing dermatology: harnessing mesenchymal stem/stromal cells and exosomes in 3D platform for skin regeneration
(SPRINGER NATURE LINK, 2024) Bicer, Mesude; 0000-0001-7089-5661; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Bicer, Mesude
Contemporary trends reveal an escalating interest in regenerative medicine-based interventions for addressing refractory skin defects. Conventional wound healing treatments, characterized by high costs and limited efficacy, necessitate a more efficient therapeutic paradigm to alleviate the economic and psychological burdens associated with chronic wounds. Mesenchymal stem/stromal cells (MSCs) constitute cell-based therapies, whereas cell-free approaches predominantly involve the utilization of MSC-derived extracellular vesicles or exosomes, both purportedly safe and effective. Exploiting the impact of MSCs by paracrine signaling, exosomes have emerged as a novel avenue capable of positively impacting wound healing and skin regeneration. MSC-exosomes confer several advantages, including the facilitation of angiogenesis, augmentation of cell proliferation, elevation of collagen production, and enhancement of tissue regenerative capacity. Despite these merits, challenges persist in clinical applications due to issues such as poor targeting and facile removal of MSC-derived exosomes from skin wounds. Addressing these concerns, a three-dimensional (3D) platform has been implemented to emend exosomes, allowing for elevated levels, and constructing more stable granules possessing distinct therapeutic capabilities. Incorporating biomaterials to encapsulate MSC-exosomes emerges as a favorable approach, concentrating doses, achieving intended therapeutic effectiveness, and ensuring continual release. While the therapeutic potential of MSC-exosomes in skin repair is broadly recognized, their application with 3D biomaterial scenarios remains underexplored. This review synthesizes the therapeutic purposes of MSCs and exosomes in 3D for the skin restoration, underscoring their promising role in diverse dermatological conditions. Further research may establish MSCs and their exosomes in 3D as a viable therapeutic option for various skin conditions.
Rapamycin and Niacin combination induces apoptosis and cell cycle arrest through autophagy activation on acute myeloid leukemia cells
(SPRINGER NATURE LINK, 2025) Subay, Lale Beril; Akcok, Emel Basak Gencer; Akcok, Ismail; 0000-0002-5444-3929; 0000-0002-6559-9144; 0009-0003-3594-4781; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Subay, Lale Beril; Akcok, Emel Basak Gencer; Akcok, Ismail
BackgroundAcute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by disorders in stem cell differentiation and excessive proliferation resulting in clonal expansion of dysfunctional cells called myeloid blasts. The combination of chemotherapeutic agents with natural product-based molecules is promising in the treatment of AML. In this study, we aim to investigate the anti-cancer effect of Rapamycin and Niacin combination on THP-1 and NB4 AML cell lines.Methods and ResultsThe anti-proliferative effects of Rapamycin and Niacin were determined by MTT cell viability assay in a dose- and time-dependent manner. The combination indexes were calculated by isobologram analysis. Furthermore, apoptosis was investigated by Annexin-V/Propidium Iodide(PI) double staining and cell cycle distribution was measured by PI staining. The expression levels of autophagy-related proteins were detected by western blotting. The combination of Rapamycin and Niacin synergistically decreased cell viability of AML cell lines. The combination treatment induced the apoptotic cell population of THP-1 and NB4 by 4.9-fold and 7.3-fold, respectively. In THP-1 cells, the cell cycle was arrested at the G2/M phase by 10% whereas the NB4 cells were accumulated at the G0/G1 phase. The combination treatment decreased Akt and p-Akt expression. Besides, the ATG7 expression was reduced by combination treatment on THP-1 cells. Similarly, the ATG5 level was downregulated in NB4 cells. The level of LC3B-II/LC3B-I, which is an indicator of autophagy flux, was upregulated in THP-1 and NB4 cells.ConclusionAlthough further studies are required, the combination of Rapamycin and Niacin combats cell proliferation by inducing cellular apoptosis, cell cycle arrest and autophagy activation.
Preparation of antibacterial electrospun poly(D, L-lactide-co-glycolide)/gelatin blend membranes containing Hypericum capitatum var. capitatum
(TAYLOR & FRANCIS AS, 2021) Akşit, Nazende Nur; Gürdap, Seda; Dinçer İşoğlu, Sevil; İşoğlu, İsmail Alper; 0000-0002-8697-1654; 0000-0002-6887-6549; 0000-0001-6428-4207; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Akşit, Nazende Nur; Gürdap, Seda; Dinçer İşoğlu, Sevil; İşoğlu, İsmail Alper
In this study, we fabricated poly(D, L-lactide-co-glycolide)/gelatin (PLGA/gelatin) membranes containing different amounts of Hypericum capitatum var. capitatum (HCC) extract (1, 5, 7.5, 10 wt%) by electrospinning technique. We investigated chemical, morphological, physical, and mechanical properties as well as in vitro degradation behavior of the electrospun membranes. We also evaluated the antibacterial activity of the electrospun membranes against Escherichia coli and Staphylococcus aureus. Viability, adhesion, and attachment of human fibroblast cells on the electrospun membranes on pre-set days were evaluated by the colorimetric CellTiter 96(R) AQueous One Solution Cell Proliferation Assay (MTS assay), scanning electron microscopy (SEM), and 4',6-Diamidino-2-Phenylindole (DAPI) staining.
ARL13B regulates juxtaposed cilia-cilia elongation in BBSome dependent manner in Caenorhabditis elegans
(CELL PRESS, 2025) Turan, Merve Gul; Kantarci, Hanife; Cevik, Sebiha; Kaplan, Oktay I.; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Turan, Merve Gul; Kantarci, Hanife; Cevik, Sebiha; Kaplan, Oktay I.
The interaction of cilia with various cellular compartments, such as axons, has emerged as a new form of cellular communication. Cilia often extend in proximity to cilia from neighboring cells. However, the mechanisms driving this process termed juxtaposed cilia-cilia elongation (JCE) remain unclear. We use fluorescence-based visualization to study the mechanisms of coordinated cilia elongation in sensory neurons of Caenorhabditis elegans. Conducting a selective gene-based screening strategy reveals that ARL-13/ARL13B and MKS-5/RPGRIP1L are essential for JCE. We demonstrate that ARL-13 modulates JCE independently of cilia length. Loss of NPHP-2/inversin along with HDAC-6 enhances the cilia misdirection phenotype of arl-13 mutants, while disruption of the BBSome complex, but not microtubule components, partially suppresses the JCE defects in arl-13 mutants. We further show changes in the phospholipid compositions in arl-13 mutants. We suggest that ARL-13 contributes to JCE, in part, through the modulation of the ciliary membrane.
Emerging DNA Methylome Targets in FLT3-ITD-Positive Acute Myeloid Leukemia: Combination Therapy with Clinically Approved FLT3 Inhibitors
(SPRINGER LINK, 2024) Tecik, Melisa; Adan, Aysun; 0000-0002-3747-8580; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Tecik, Melisa; Adan, Aysun
The internal tandem duplication (ITD) mutation of the FMS-like receptor tyrosine kinase 3 (FLT3-ITD) is the most common mutation observed in approximately 30% of acute myeloid leukemia (AML) patients. It represents poor prognosis due to continuous activation of downstream growth-promoting signaling pathways such as STAT5 and PI3K/AKT. Hence, FLT3 is considered an attractive druggable target; selective small FLT3 inhibitors (FLT3Is), such as midostaurin and quizartinib, have been clinically approved. However, patients possess generally poor remission rates and acquired resistance when FLT3I used alone. Various factors in patients could cause these adverse effects including altered epigenetic regulation, causing mainly abnormal gene expression patterns. Epigenetic modifications are required for hematopoietic stem cell (HSC) self-renewal and differentiation; however, critical driver mutations have been identified in genes controlling DNA methylation (such as DNMT3A, TET2, IDH1/2). These regulators cause leukemia pathogenesis and affect disease diagnosis and prognosis when they co-occur with FLT3-ITD mutation. Therefore, understanding the role of different epigenetic alterations in FLT3-ITD AML pathogenesis and how they modulate FLT3I’s activity is important to rationalize combinational treatment approaches including FLT3Is and modulators of methylation regulators or pathways. Data from ongoing pre-clinical and clinical studies will further precisely define the potential use of epigenetic therapy together with FLT3Is especially after characterized patients’ mutational status in terms of FLT3 and DNA methlome regulators.
Draft genome of carotenoid-producing endophytic Pseudomonas sp. 102515 from Taxus chinensis
(American Society for Microbiology, 2024) Fidan, Ozkan; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
Here, we report the draft genome sequence of endophytic Pseudomonas sp. 102515 isolated from Taxus chinensis collected from Logan, UT, USA. The genome is composed of 36 contigs and around 4.9 Mbp in size. The GC content is 66% with an N50 length of 918.9 kbp and L50 count of 2.
Elucidating the complex membrane binding of a protein with multiple anchoring domains using extHMMM
(Public Library of Science, 2024) Madsen, Jesper J.; Ohkubo, Y. Zenmei; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Ohkubo, Y. Zenmei
Membrane binding is a crucial mechanism for many proteins, but understanding the specific interactions between proteins and membranes remains a challenging endeavor. Coagulation factor Va (FVa) is a large protein whose membrane interactions are complicated due to the presence of multiple anchoring domains that individually can bind to lipid membranes. Using molecular dynamics simulations, we investigate the membrane binding of FVa and identify the key mechanisms that govern its interaction with membranes. Our results reveal that FVa can either adopt an upright or a tilted molecular orientation upon membrane binding. We further find that the domain organization of FVa deviates (sometimes significantly) from its crystallographic reference structure, and that the molecular orientation of the protein matches with domain reorganization to align the C2 domain toward its favored membranenormal orientation. We identify specific amino acid residues that exhibit contact preference with phosphatidylserine lipids over phosphatidylcholine lipids, and we observe that mostly electrostatic effects contribute to this preference. The observed lipid-binding process and characteristics, specific to FVa or common among other membrane proteins, in concert with domain reorganization and molecular tilt, elucidate the complex membrane binding dynamics of FVa and provide important insights into the molecular mechanisms of protein-membrane interactions. An updated version of the HMMM model, termed extHMMM, is successfully employed for efficiently observing membrane bindings of systems containing the whole FVa molecule.
Computational Detection of Pre-microRNAs
(Humana Press Inc., 2022) Saçar Demirci, Müşerref Duygu; 0000-0003-2012-0598; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Saçar Demirci, Müşerref Duygu
MicroRNA (miRNA) studies have been one of the most popular research areas in recent years. Although thousands of miRNAs have been detected in several species, the majority remains unidentified. Thus, finding novel miRNAs is a vital element for investigating miRNA mediated posttranscriptional gene regulation machineries. Furthermore, experimental methods have challenging inadequacies in their capability to detect rare miRNAs, and are also limited to the state of the organism under examination (e.g., tissue type, developmental stage, stress-disease conditions). These issues have initiated the creation of high-level computational methodologies endeavoring to distinguish potential miRNAs in silico. On the other hand, most of these tools suffer from high numbers of false positives and/or false negatives and as a result they do not provide enough confidence for validating all their predictions experimentally. In this chapter, computational difficulties in detection of pre-miRNAs are discussed and a machine learning based approach that has been designed to address these issues is reviewed.
Integrative analyses in omics data: Machine learning perspective
(Deutsche Gesellschaft fur Medizinische Informatik, Biometrie und Epidemiologie e.V., 2023) Yazici, Miray Unlu; Bakir-Gungor, Burcu; Yousef, Malik; 0000-0001-8165-6164; 0000-0002-2272-6270; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Yazici, Miray Unlu; Bakir-Gungor, Burcu
Developments in the high throughput technologies have enabled the production of an immense amount of knowledge at the multi-omics level. Considering complex diseases which are affected by multi-factors, single omics datasets might not be sufficient to unveil the molecular mechanisms of heterogeneous diseases. Providing a comprehensive and systematic overview to explain disease hallmarks in significant depth is critical. Utilizing multi-omics datasets has led to the development of a variety of tools and platforms. Machine learning models are utilized in a wide variety of tools to tackle the complexity of disorders and to identify new biomolecular signatures and potential markers. Underlying aspects of these approaches are based on training the models for making predictions and classification of the given data. In this review, we describe current machine learning-based approaches and available implementations. Challenges in the enlightenment of disease mechanisms of onset and progression and future development of the field of medicine will be discussed. The prominence of biological interpretation of model output with corresponding biological knowledge will be also covered in this review.
In silico Evaluation of the Potential of Natural Products from Chili Pepper as Antiviral Agents Against Dna-Directed Rna Polymerase of the Monkeypox Virus
(Bitlis Eren Üniversitesi, 2024) Fidan, Özkan; Mujwar, Somdutt; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Özkan
This study focused on the discovery of new drug candidates effective against the monkeypox virus. Virtual screening was performed to evaluate the potential of chili pepper natural products against homology-modeled DNA-directed RNA polymerase of the monkeypox virus using molecular docking. Our findings revealed that structurally similar triterpenes such as α-amyrin, β-amyrin, and β-sitosterol had strong binding affinities towards the DNA-directed RNA polymerase and can inhibit this pivotal viral enzyme. The stability of one of the drug candidate molecules, α-amyrin with the strongest binding affinity towards the binding cavity of the enzyme was also confirmed via molecular dynamics simulation. This study showed that α-amyrin is a promising DNA-directed RNA polymerase inhibitor to treat monkeypox disease. It also paves the way for the idea of the potential dietary supplement candidate for monkeypox patients.
Identifying Taxonomic Biomarkers of Colorectal Cancer in Human Intestinal Microbiota Using Multiple Feature Selection Methods
(Institute of Electrical and Electronics Engineers Inc., 2022) Jabeer, Amhar; Kocak, Aysegul; Akkas, Huseyin; Yenisert, Ferhan; Nalbantoglu, Ozkan Ufuk; Yousef, Malik; Bakir Gungor, Burcu; 0000-0002-6367-7823; 0000-0002-2272-6270; AGÜ, Mühendislik Fakültesi, Bilgisayar Mühendisliği Bölümü; Jabeer, Amhar; Kocak, Aysegul; Akkas, Huseyin; Yenisert, Ferhan; Bakir Gungor, Burcu
A variety of bacterial species called gut microbiota work together to maintain a steady intestinal environment. The gastrointestinal tract contains tremendous amount of different species including archaea, bacteria, fungi, and viruses. While these organisms are crucial immune system stabilizers, the dysbiosis of the intestinal flora has been related to gastrointestinal disorders including Colorectal cancer (CRC), intestinal cancer, irritable bowel syndrome and inflammatory bowel disease. In the last decade, next-generation sequencing (NGS) methods have accelerated the identification of human gut flora. CRC is a deathly condition that has been on the rise in the last century, affecting half a million people each year. Since early CRC diagnosis is critical for an effective treatment, there is an immediate requirement for a classification system that can expedite CRC diagnosis. In this study, via analyzing the available metagenomics data on CRC, we aim to facilitate the CRC diagnosis via finding biomarkers linked with CRC, and via building a classification model. We have obtained the metagenomic sequencing data of the healthy individuals and CRC patients from a metagenome-wide association analysis and we have classified this data according to the disease stages. Conditional Mutual Information Maximization (CMIM), Fast Correlation Based Filter (FCBF), Extreme Gradient Boosting (XGBoost), min redundancy max relevance (mRMR), Information Gain (IG) and Select K Best (SKB) feature selection algorithms were utilized to cope with the complexity of the features. We observed that the SKB, IG, and XGBoost techniques made significant contributions to decrease the microbiota in use for CRC diagnosis, thereby reducing cost and time. We realized that our Random Forest classifier outperformed Adaboost, Support Vector Machine, Decision Tree, Logitboost and stacking ensemble classifiers in terms of CRC classification performance. Our results reiterated some known and some potential microbiome associated mechanisms in CRC, which could aid the design of new diagnostics based on the microbiome.
Protocol for cell surface biotinylation of magnetic labeled and captured human peripheral blood mononuclear cells
(Cell Press, 2022) Ayaz-Guner, Serife; Acar, Mustafa Burak; Boyvat, Dudu; Guner, Huseyin; Bozalan, Habibe; Güzel, Melis; Yıldır, Selin Kübra; Altınsoy, Nilay; Fındık, Fatma; Karakükçü, Musa; Özcan, Servet; 0000-0002-1052-0961; 0000-0002-0220-5224; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Boyvat, Dudu; Ayaz-Guner, Şerife; Guner, Huseyin
Analysis of the surfaceome of a blood cell subset requires cell sorting, followed by surface protein enrichment. Here, we present a protocol combining magnetically activated cell sorting (MACS) and surface biotinylation of the target cell subset from human peripheral blood mononuclear cells (PBMCs). We describe the steps for isolating target cells and their in-column surface biotinylation, followed by isolation and mass spectrometry analysis of biotinylated proteins. The protocol enables in-column surface biotinylation of specific cell subsets with minimal membrane disruption.
Genomic, probiotic, and metabolic potentials of Liquorilactobacillus nagelii AGA58, a novel bacteriocinogenic motile strain isolated from lactic acid-fermented shalgam
(ELSEVIER, 2023) Yetiman, Ahmet Evren; Ortakci, Fatih; 0000-0003-1319-0854; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Ortakci, Fatih
This study aimed to perform genomic, probiotic, and metabolic characterization of a novel Liquorilactobacillus nagelii AGA58 isolated from a lactic acid-fermented shalgam beverage to understand its metabolic potentials and probiotic features. AGA58 is gram-positive, motile, catalase-negative and appears as short rods under the light-microscope. The AGA58 chromosome comprises a single linear chromosome of 2,294,635 bp that is predicted to carry 2135 coding sequences, including 45 tRNA genes, 3 mRNA, and 3 rRNA operons. The genome has a G+C content of 36.9%, including 55 pseudogenes and a single intact prophage. AGA58 is micro-anaerobic due to achieving a shorter doubling time and faster growth rate than micro-aerophilic conditions. It carries flagellar biosynthesis protein-encoding genes predicting motile behavior, which was confirmed with the in vitro motility test. AGA58 is an obligatory homofermentative lactobacillus that can ferment hexose sugars such as galactose, glucose, fructose, sucrose, mannose, N-acetyl glucosamine, maltose, and trehalose to lactate through glycolysis. No acid production from pentoses implies that five-carbon sugars are being utilized for purine and pyrimidine synthesis. Putative pyruvate metabolism revealed formate, malate, oxaloacetate, acetate, acetaldehyde, acetoin, and lactate forms from pyruvate. AGA58 is predicted to encode the LuxS gene and biosynthesis of class IIa and Blp family class-II bacteriocins suggesting this bacterium's antimicrobial potential, linked to antagonism tests that AGA58 can inhibit Escherichia coli ATCC 43895, Salmonella enterica serovar Typhimurium ATCC 14028, and Klebsiella pneumonia ATCC 13883. Moreover, AGA58 is tolerant to acid and bile concentrations simulating the human gastrointestinal conditions depicting the probiotic potential of the organism as the first report in literature within the same species.
Exploring the binding capacity of lactic acid bacteria derived bacteriocins against RBD of SARS-CoV-2 Omicron variant by molecular simulations
(2023) Erol, Ismail; Kotil, Seyfullah Enes; Ortakci, Fatih; Durdagi, Serdar; 0000-0003-1319-0854; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Ortakci, Fatih
The changes in the SARS-CoV-2 genome have resulted in the emergence of new variants. Some of the variants have been classified as variants of concern (VOC). These strains have higher transmission rate and improved fitness. One of the prevalent were the Omicron variant. Unlike previous VOCs, the Omicron possesses fifteen mutations on the spike protein’s receptor binding domain (RBD). The modifications of spike protein’s key amino acid residues facilitate the virus’ binding capability against ACE2, resulting in an increase in the infectiousness of Omicron variant. Consequently, investigating the prevention and treatment of the Omicron variant is crucial. In the present study, we aim to explore the binding capacity of twenty-two bacteriocins derived from Lactic Acid Bacteria (LAB) against the Omicron variant by using protein-peptidedocking and molecular dynamics (MD) simulations. The Omicron variant RBD was prepared by introducing fifteen mutations using PyMol. The protein-peptide complexes were obtained using HADDOCK v2.4 docking webserver. Top scoring complexes obtained from HADDOCK webserver were retrieved and submitted to the PRODIGY server for the prediction of binding energies. RBD-bacteriocin complexes were subjected to MD simulations. We discovered promising peptide-based therapeutic candidates for the inhibition of Omicron variant for example Salivaricin B, Pediocin PA 1, Plantaricin W, Lactococcin mmfii and Enterocin A. The lead bacteriocins, except Enterocin A, are biosynthesized by food-grade lactic acid bacteria. Our study puts forth a preliminary information regarding potential utilization of food-grade LAB-derived bacteriocins, particularly Salivaricin B and Pediocin PA 1, for Covid-19 treatment and prophylaxis.
Investigation of the Interaction of Adipose-Derived Mesenchymal Stem Cells with ε-Polycaprolactone and Egg White Scaffolds
(GAZİ ÜNİVERSİTESİ, 2023) Oztel, Olga N.; Yilmaz, Hilal; Isoglu, Ismail Alper; Allahverdiyev, Adil; 0000-0001-6428-4207; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Isoglu, Ismail Alper
The development of three-dimensional (3D) cell culture models is becoming increasingly important due to their numerous advantages over conventional monolayer culture. This study aimed to examine the interaction of adipose tissue-derived mesenchymal stem cells (AD-MSCs) with scaffolds composed of ε-polycaprolactone (ε-PCL) and egg white. In our study, ε-PCL and egg white scaffolds were produced from their monomers by tin octoate catalyzed and heat polymerization, respectively. Characterization of ε-PCL was carried out by Gel Permeation Chromatography (GPC), Fourier Transform Infrared Spectrophotometry (FTIR), Proton Nuclear Magnetic Resonance (H-NMR), Differential Scanning Calorimetry (DSC) and Scanning Electron Microscopy (SEM). AD-MSCs labeled with red fluorescent CellTracker CM-DiI were cultured on egg white and ε-PCL scaffolds for 12 days. Cell viability was determined using 3-(4.5- Dimethylthiazol-2yl)-2.5-diphenyltetrazolium bromide (MTT) and nitric oxide (NO) level was evaluated for toxicity. The results showed that the number of AD-MSCs in the egg white scaffold increased periodically for 12 days compared to the other groups. Although the number of ADMSCs in the ε-PCL scaffold increased until day 6 of the culture, the number of cells started to decrease after day 6. These results were associated with the toxic effect of lactic acid release on cells resulting from the decomposition of ε-PCL scaffolds through catabolic reactions. Therefore, these results indicated that the egg white scaffold enhanced and maintained cell adhesion and cell viability more than the ε-Polycaprolactone scaffold and could be used as a scaffold in tissue engineering studies involving stem cells.
miRcorrNetPro: Unraveling Algorithmic Insights through Cross-Validation in Multi-Omics Integration for Comprehensive Data Analysis
(Institute of Electrical and Electronics Engineers Inc., 2023) Yazici, Miray Unlu; Yousef, Malik; Marron J.S.; Bakir-Gungor, Burcu; 0000-0001-8165-6164; 0000-0002-2272-6270; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Yazici, Miray Unlu; Bakir-Gungor, Burcu
High throughput -omics technologies facilitate the investigation of regulatory mechanisms of complex diseases. Along this line, scientists develop promising tools and methods to extend our understanding at the molecular and functional levels. To this end, miRcorrNet tool performs integrative analysis of microRNA (miRNA) and gene expression profiles via machine learning (ML) approach to identify significant miRNA groups and their associated target genes. In this study, we propose miRcorrNetPro tool, which extends miRcorrNet by tracking group scoring, ranking and other information through the cross-validation iterations. Heatmap visualizations enable deep novel insights into the collective behavior of clusters of groups in cellular signaling and hence facilitate detection of potential biomarkers for the disease under investigation. Although miRcorrNetPro is designed as a generic tool, here we present our findings and potential miRNA biomarkers for Breast Cancer (BRCA). The miRcorrNetPro tool and all other supplementary files are available at https://github.com/MirayUnlu/miRcorrNetPro.
Analyzing the genetic diversity and biotechnological potential of Leuconostoc pseudomesenteroides by comparative genomics
(Frontiers Media S.A., 2023) Gumustop, Ismail; Ortakci, Fatih; 0000-0003-1319-0854; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Gumustop, Ismail; Ortakci, Fatih
Leuconostoc pseudomesenteroides is a lactic acid bacteria species widely exist in fermented dairy foods, cane juice, sourdough, kimchi, apple dumpster, caecum, and human adenoid. In the dairy industry, Ln. pseudomesenteroides strains are usually found in mesophilic starter cultures with lactococci. This species plays a crucial role in the production of aroma compounds such as acetoin, acetaldehyde, and diacetyl, thus beneficially affecting dairy technology. We performed genomic characterization of 38 Ln. pseudomesenteroides from diverse ecological niches to evaluate this species’ genetic diversity and biotechnological potential. A mere ~12% of genes conserved across 38 Ln. pseudomesenteroides genomes indicate that accessory genes are the driving force for genotypic distinction in this species. Seven main clades were formed with variable content surrounding mobile genetic elements, namely plasmids, transposable elements, IS elements, prophages, and CRISPR-Cas. All but three genomes carried CRISPR-Cas system. Furthermore, a type IIA CRISPR-Cas system was found in 80% of the CRISPR-Cas positive strains. AMBR10, CBA3630, and MGBC116435 were predicted to encode bacteriocins. Genes responsible for citrate metabolism were found in all but five strains belonging to cane juice, sourdough, and unknown origin. On the contrary, arabinose metabolism genes were only available in nine strains isolated from plant-related systems. We found that Ln. pseudomesenteroides genomes show evolutionary adaptation to their ecological environment due to niche-specific carbon metabolism and forming closely related phylogenetic clades based on their isolation source. This species was found to be a reservoir of type IIA CRISPR-Cas system. The outcomes of this study provide a framework for uncovering the biotechnological potential of Ln. pseudomesenteroides and its future development as starter or adjunct culture for dairy industry.

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