Moleküler Biyoloji ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/209

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Akut Myeloid Lösemi Tedavisi için Hedgehog Ve Otofaji Yolaklarının Düzenlenmesi
(TUBİTAK, 2019) EL KHATIB, Mona; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; EL KHATIB, Mona
Akut myeloid lösemi (AML) çeşitli moleküler aberasyonlar ve sinyal yolaklarındaki bozuklukları içeren klonal hastalıklar ile karakterize edilen bir grup heterojen malignanttır. Hedgehog (HH) sinyal yolağı birçok kanserde deregüle edilen evrimsel olarak korunan bir sinyal yolağıdır. HH sinyal yolağı lizozomal degradasyon prosesi otofajinin temel regülatörü olan PI3K/AKT/mTOR aksesini de içeren diğer sinyal yolakları ile karşılıklı iletişim halindedir. Bu sinyal yolakları AML’de deregüle edilmiştir. Birçok çalışmada otofajinin AML için bir kaçış mekanizması olabileceği ortaya konulmuştur. Bizim çalışmamızda, HH ve otofaji yolaklarının farklı AML türleri üzerine etkileri incelenmiştir. Çalışmamızda KML hücresi olan K562 ve CMK, MV4-11, MOLM-13 ve NB4 AML hücreleri GLI1 inhibitörü GANT61 ve farklı otofaji modülatörleri ile muamele edilmiştir.MTT sonuçları NB4, MOLM-13 ve MV4-11hücre proliferasyonun GLI inhibisyonu sonrasında düştüğünü ancak CMK’nin diğer AML hücre hatlarına kıyasla GLI inhibisyonuna daha az sensitif olduğunu ortaya koymuştur. Daha sonra, otofaji modülasyonunun farklı AML hücre hatlarının proliferasyonu üzerine etkileri incelenmiştir. Otofajinin gerek otofagozom-lizozom füzyonu aşamasında gerekse otofagolizozomal degradasyon aşamasında inhibisyonunun ilaç konsantrasyonu ve muamele süresine bağlı olarak AML sağkalımını azalttığı gözlemlenmiştir. Otofaji modülatörleri ve GANT61’in kombinasyonunun MOLM-13 hücre hattı üzerinde sinerjistik bir etkisinin olduğu fakat CMK hücre hattı üzerinde sinerjistik etkisinin olmadığı gözlemlenmiştir. GANT61 muamelesinin AML hücre hatlarında otofajiyi artırdığı LC3II ekspresyonu ile western blot yöntemi ile ortaya konulmuştur. Buna ek olarak, kombinasyonun MOLM-13 hücresinde LC3II’yi artırdığı gözlenirken, bu oran CMK hücre hattında daha düşüktür. AKT proteinin ekspresyonu ilaca ve hücre hattına gore farklılık göstermektedir. Sonuç olarak, HH ve otofaji sinyal yolaklarının hedeflenmesi MOLM-13 hücre hattı için umut vaatedici bir terapi iken, CMK hücre hattında benzer sonuçlara ulaşılamamıştır.
Amelioration potential of synthetic oxime chemical cores against multiple sclerosis and Alzheimer's diseases: Evaluation in aspects of in silico and in vitro experiments
(ELSEVIER, 2024) Yilmaz, Anil; Koca, Murat; Ercan, Selami; Acar, Ozden Ozgun; Boga, Mehmet; Sen, Alaattin; Kurt, Adnan; 0000-0002-8444-376X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Sen, Alaattin
Alzheimer disease (AD) and multiple sclerosis (MS) are inflammatory neurological disorders. The main symptom of AD is dementia, and the main symptoms of MS are vertigo, sexual dysfunction, cognitive problems, and fatigue. Today, millions of people are affected by AD and MS, and the number is growing day by day. However, there are not any accurate remedies for both disorders. For this reason, discovering novel drug molecules against neurological disorders such as AD and MS is essential and precious. Oximes and benzofurans exhibit many pharmacological effects including anti-inflammatory and neurological activities. Thus, several novel compounds bearing oxime and benzofuran chemical cores were designed and synthesized, and their in vitro anticholinesterase activities were investigated in our previous study. A number of the synthesized molecules showed excellent anticholinesterase activity against both AChE and BChE enzymes. The mentioned study constituted a background for this study. In this study, we picked different chemical skeletons among all the synthesized molecules to conduct further in silico and in vitro experiments. In order to support our in vitro anticholinesterase findings, we also examined in silico anti-Alzheimer activity of the selected molecules. In addition, in silico and in vitro activities against MS disease of the synthesized molecules were investigated. Molecule 4 extraordinarily showed outstanding activity against AD disease both in silico and in vitro, as well as in silico activity against MS disease. This feature makes molecule 4 a possible drug lead molecule which is very limited in the market. On the other hand, molecule 1, a less substituted oxime skeleton, demonstrated the strongest in vitro activity against MS disease through in vitro anti-inflammatory effect. As an observation, molecule 4 was determined to be the most promising molecule to focus on in the further steps.
An answer to colon cancer treatment by mesenchymal stem cell originated from adipose tissue
(MASHHAD UNIV MED SCIENCES, VICE-CHANCELLOR FOR RES CTR OFF IJBMS, DANESHGAH ST, PO BOX 9138813944 - 445, MASHHAD, 00000, IRAN, 2018) Iplik, Elif; Ertugrul, Baris; Kozanoglu, İlknur; Baran, Yusuf; Cakmakoglu, Bedia; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü;
Objective(s): Colon cancer is risen up with its complex mechanism that directly impacts on its treatment as well as its common prevalence. Mesenchymal stem cells (MSCs) have been considered as a therapeutic candidate for conventional disease including cancer. In this research, we have focused on apoptotic effects of adipose tissue-derived MSCs in colon cancer. Materials and Methods: MSCs were obtained from adipose tissue and characterized by Flowcytometer using suitable antibodies. MSCs, HT-29, HCT-116, RKO and healthy cell line MRC5 were cultured by different seeding procedure. After cell viability assay, changes in caspase 3 enzyme activity and the level of phosphatidylserine were measured. Results: For cell viability assay, a 48 hr incubation period was chosen to seed all cells together. There was a 1.36-fold decrease in caspase 3 enzyme activity by co-treatment of RKO and MSCs in addition to 2.02-fold decrease in HT-29 and MSCs co-treatment, and 1.103-fold increase in HCT-116 and MSCs. The results demonstrated that HCT-116 led to the highest rate of apoptotic cell death (7.5%) compared with other cells. Conclusion: We suggest that MSCs might remain a new treatment option for cancer by its differentiation and repair capacity.
Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions
(KARE PUBLCONCORD ISTANBUL, DUMLUPINAR MAH, CIHAN SK NO 15, B BLOK 162 KADIKOY, ISTANBUL, TURKEY, 2021) Kavakcioglu Yardimci, Berna; Ozgun Acar, Ozden; Semiz, Asli; Sen, Alaattin; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Sen, Alaattin
OBJECTIVE Defects in apoptotic cell death which restrict the success of conventional cytotoxic therapies have pivotal roles in a number of pathological conditions including cancer. However, a novel drug class targeting pro-survival Bcl-2 protein family members has been developed with the understanding of the structures and interactions of Bcl-2 proteins. Within this new class, Bcl-2/Bcl-xL inhibitor Navitoclax and Bcl-2 specific inhibitor Venetoclax have been shown to demonstrate strong anticancer activities on several types of cancers. But their low affinity to other anti-apoptotic proteins limits their clinical usage. Here, we investigated the cytotoxic and apoptotic effects of Navitoclax/Venetoclax and their combinations with specific tyrosine kinase inhibitor Apatinib on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cell lines. METHODS MTT assay was used for the evaluation of the inhibition of cancer cell proliferation. ELISA test and Quantitative real-time PCR assay was performed to determine the role of caspase-3, Bak, Bax, Bcl-2, Bcl-xL and Mcl-1 proteins in the inhibition of cell proliferation triggered by the tested agents. RESULTS We found that aggressive MDA-MB-231 cell line was more sensitive to all tested agents. Apatinib significantly enhanced Navitoclax/Venetoclax mediated inhibition of cell viability in both cancer cell lines despite up-regulation in the expression levels of Bcl-2 and Mcl-1 genes. We further demonstrated significant Bak/Bax and caspase-3 expression in less aggressive MCF-7 cells. CONCLUSION Our findings have impacts on Navitoclax/Venetoclax plus Apatinib based therapy for breast adenocarcinoma. On the other hand, further studies should be conducted to elucidate the mechanisms underlying synergistic effects of Navitoclax/Venetoclax plus Apatinib combinations.
Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells
(SAGE PUBLICATIONS LTD, 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2016) Kiraz, Yagmur; Neergheen-Bhujun, Vidushi S.; Rummun, Nawraj; Baran, Yusuf; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü;
Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.
Aurora Kinases: Their Role in Cancer and Cellular Processes
(Bingöl Üniversitesi Fen Bilimleri Enstitüsü, 2024) Sarı, Sibel; Özsoy, Elif Rumeysa; 0000-0002-2505-5804; 0009-0008-6040-9875; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Sarı, Sibel; Özsoy, Elif Rumeysa
Aurora kinases, belonging to a highly conserved family of serine/threonine kinases with critical roles in the regulation of the cell cycle, comprise three members: Aurora kinase A, B, and C, which serve as key mitotic regulators essential for maintaining chromosome stability. Aurora kinases play crucial roles in multiple events in mitotic such as the coordination of chromosomal and cytoskeletal events, regulation of the spindle assembly checkpoint pathway and cytokinesis to ensure the smooth progression of the cell cycle. Besides their mitotic functions, Aurora kinases are also involved in the regulation of meiosis. Gene amplification/mutation and overexpression of Aurora kinases have been detected in various solid and haematological cancers. In human tumours, Aurora kinases exhibit oncogenic roles associated with their mitotic roles, which drive the cancer cell proliferation and survival. Deregulation of Aurora kinase activity causes failure in centrosome function, spindle assembly, chromosomal alignment, and cytokinesis, eventually resulting in the mitotic abnormalities and genetic instability. These findings emphasize the crucial functions of Aurora kinases in cancer, prompting their recognition as valuable targets for cancer therapy. This review provides an overview of the structures and functions of Aurora kinases and sheds light on their oncogenic roles in cancer.
Biochemical, pharmacological, and toxicological attributes of caper (Capparis ovata) flowering buds and berries pickles
(WILEY, 2022) Ozgun-Acar, Ozden; Celik-Turgut, Gurbet; Guner, Huseyin; Sezer, Serdar; Sen, Alaattin; 0000-0002-8444-376X; 0000-0002-0220-5224; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Güner, Hüseyin; Şen, Alaattin
Capparis ovata is a natural plant that grows widely in Turkey and its flowering buds and berry pickle are used in traditional medicine. Thus, the current study was expanded to evaluate the biochemical, pharmacological, and toxicological aspects of the Capparis ovata water extract (COWE). To determine the biochemical properties of COWE, mineral and fatty acid content, elemental analysis, flavonoid/phenolic content, radicalscavenging capacity, and pesticide analysis were performed. Furthermore, to find out whether it had anti-inflammatory properties, reverse transcription-polymerase chain reaction (RT-PCR) and nuclear factor kappa B (NF-κB) luciferase activity tests were conducted. Whole-genome transcriptomic profiling was carried out at a dose level of 500 mg/kg COWE to understand its pharmacological effect. Transaminases in serum were tested, and quantitative polymerase chain reaction (qPCR) was done using a custom design array that included the stress and molecular toxicology pathway to establish its toxicological qualities. As a result of the evaluations, it was observed that COWE has a high mineral and unsaturated fatty acid content, flavonoid/phenolic content, and radical-scavenging ability. It significantly inhibited NF-κB transcriptional activity as well as inflammatory cytokine expression in T-lymphoblast cells. Wholegenome transcriptomic profiling depicted that COWE modulates immune responses by upregulating natural killer cell activation, cellular response to type I interferon, B-cell proliferation and differentiation, and Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathways. Molecular Toxicology Pathfinder RT2 Profiler PCR array analysis revealed that COWE at or lower dose of 500 mg/kg/day did not cause a comparatively adverse effect. According to the findings, COWE is a rich source of nutrients and can be used as an adjunct therapy for various inflammatory diseases
Cell Proliferation and Cytotoxicity Assays
(BENTHAM SCIENCE PUBL LTDEXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES, 2016) Adan, Aysun; Kiraz, Yagmur; Baran, Yusuf; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Adan, Aysun; Kiraz, Yagmur; Baran, Yusuf
Cell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes.
Ceramide is a key factor that regulates the crosstalk between TGF-beta and sonic hedgehog signaling at the basal cilia to control cell migration and tumor metastasis
(ELSEVIER SCI LTDTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND, 2016) Gencer, Salih; Ogretmen, Besim; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Gencer, Salih
Ceramide is a key factor that regulates the crosstalk between TGF-beta and sonic hedgehog signaling at the basal cilia to control cell migration and tumor metastasis
Ceramide is A Key Factor That Regulates The Crosstalk Between TGF-beta and Sonic Hedgehog Signaling at The Basal Cilia To Control Cell Migration and Tumor Metastasis
(WILEY111 RIVER ST, HOBOKEN 07030-5774, NJ, 2016) Gencer, Salih; Oleinik, Natalia; Dany, Mohammed; Ogretmen, Besim; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Gencer, Salih
Ceramide is A Key Factor That Regulates The Crosstalk Between TGF-beta and Sonic Hedgehog Signaling at The Basal Cilia To Control Cell Migration and Tumor Metastasis
Cerium Oxide Nanoparticles Biosynthesized Using Fresh Green Walnut Shell in Microwave Environment and their Anticancer Effect on Breast Cancer Cells
(John Wiley and Sons Inc, 2022) Sulak, Mine; Turgut, Gurbet Celik; Sen, Alaattin; 0000-0002-8444-376X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Sen, Alaattin
In this study, cerium oxide nanoparticles (CONPs) were synthesized using fresh green walnut shell extract in microwave environment. The morphology and structure of the CONPs were determined using ultraviolet-visible (UV/VIS), attenuated total reflection-Fourier transform infrared (ATR-FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and scanning electron microscopy (SEM). Crystal purple staining, Annexin V-FITC detection, RT-PCR, P53, and NF-κB luciferase reporter assays were performed to evaluate the mechanism of action of CONPs in breast cancer cell lines (MCF7). The biosynthesized CONPs showed cytotoxic effects and induced apoptosis in MCF7 cells. Furthermore, CONPs induced P53 expression and suppressed NF-κB gene expression, both of which were confirmed using reporter assays. Based on the present results, it was concluded that CONPs can induce apoptosis by acting on P53 at the transcriptional level and may cause cell death by suppressing NF-κB-mediated transcription.
CilioGenics: an integrated method and database for predicting novel ciliary genes
(Oxford University Press, 2024) Pir, Mustafa Samet; Begar, Efe; Yenisert, Ferhan; Demirci, Hasan C.; Korkmaz, Mustafa E.; Karaman, Asli; Tsiropoulou, Sofia; Firat-Karalar, Elif Nur; Blacque, Oliver E.; Oner, Sukru S.; Doluca, Osman; Cevik, Sebiha; Kaplan, Oktay Ismail; 0000-0002-4645-7626; 0000-0002-0935-1929; 0000-0002-8733-0920; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Pir, Mustafa Samet; Yenisert, Ferhan; Demirci, Hasan C.; Korkmaz, Mustafa E.; Cevik, Sebiha; Kaplan, Oktay Ismail
Uncovering the full list of human ciliary genes holds enormous promise for the diagnosis of cilia-related human diseases, collectively known as ciliopathies. Currently, genetic diagnoses of many ciliopathies remain incomplete (1–3). While various independent approaches theoretically have the potential to reveal the entire list of ciliary genes, approximately 30% of the genes on the ciliary gene list still stand as ciliary candidates (4,5). These methods, however, have mainly relied on a single strategy to uncover ciliary candidate genes, making the categorization challenging due to variations in quality and distinct capabilities demonstrated by different methodologies. Here, we develop a method called CilioGenics that combines several methodologies (single-cell RNA sequencing, protein-protein interactions (PPIs), comparative genomics, transcription factor (TF) network analysis, and text mining) to predict the ciliary capacity of each human gene. Our combined approach provides a CilioGenics score for every human gene that represents the probability that it will become a ciliary gene. Compared to methods that rely on a single method, CilioGenics performs better in its capacity to predict ciliary genes. Our top 500 gene list includes 258 new ciliary candidates, with 31 validated experimentally by us and others. Users may explore the whole list of human genes and CilioGenics scores on the CilioGenics database (https://ciliogenics.com /).
Classification of Breast Cancer Molecular Subtypes with Grouping-Scoring-Modeling Approach that Incorporates Disease-Disease Association Information
(IEEE Xplore, 2024) Qumsiyeh, Emma; Bakir-Gungor, Burcu; Yousef, Malik; 0000-0002-2272-6270; AGÜ, Mühendislik Fakültesi, Bilgisayar Mühendisliği Bölümü; Bakir-Gungor, Burcu
This study uses modern sequencing technology and large biological databases to investigate the molecular intricacies of complicated diseases like cancer. Using gene expression databases and biomarkers, the research aims to improve breast cancer molecular subtype identification for better patient outcomes. Using BRCA LumAB_ Her2Basal dataset, this study compares an integrative machine learning-based strategy (GediNET) to traditional feature selection approaches across machine learning classifiers. GediNET excels at uncovering crucial disease-disease connections and potential biomarkers using the Grouping-Scoring-Modeling (GSM) approach, which favors gene groupings above individual genes. Our comparative analysis highlights GediNET's exceptional performance, notably in terms of accuracy and Area Under the Curve metrics, underscoring its effectiveness in uncovering the genetic intricacies of breast cancer. GediNET's promise to improve disease classification and biomarker identification by improving biological mechanism understanding goes beyond exceeding traditional approaches. The work shows that GediNET's integrative method can promote bioinformatics research by identifying the most informative genes associated with certain diseases, enabling focused and customized medicine.
Combined effect of midostaurin and sphingosine kinase-1 inhibitor on FMS-like tyrosine kinase 3 (FLT3) wild type acute myeloid leukemia cells
(De Gruyter, 2022) Adan, Aysun; Şahin, Hande Nur; 0000-0002-3747-8580; 0000-0002-2382-3160; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Adan, Aysun; Şahin, Hande Nur
Objectives Therapeutic potential of clinically approved FLT3 inhibitor midostaurin has been neglected in wild-type FLT3 positive acute myeloid leukemia (AML). Sphingosine kinase-1 (SK-1) having anti-proliferative functions is studied in various cancers, but not in FLT3 wild-type AML. We aimed to develop new therapeutic strategies to combat FLT3 wild-type AML by combining midostaurin with SK-1 inhibitor (SKI II) in THP1 cells. Methods The anti-proliferative effects of midostaurin, SKI II and in combination on THP1 cells were determined by MTT assay. The combination indexes were calculated using calcusyn software. SK-1 expression and PARP cleavage were checked by western blot. Cell cycle distributions (PI staining) and apoptosis (annexin-V/PI dual staining) were assessed by flow cytometry for each agent alone and in combinations. Results Midostaurin decreased SK-1 protein level. Midostaurin, SKI II and certain combinations decreased cell viability in a dose dependent manner. The combined anti-leukemic effects of the aforementioned drug combination afforded additive effect. Co-administration induced both necrosis and apoptosis via phosphatidylserine externalization, PARP cleavage and cell cycle arrest at G0/G1 and S phases. Conclusions Targeting sphingosine kinase-1 together with FLT3 inhibition could be a novel mechanism to increase limited clinic response to midostaurin in wild-type FLT3 overexpressing AML after further pre-clinical studies.
Common miRNA signatures in a group of rare neuromuscular disorders
(WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2018) Aksu, E; Akkaya-Ulum, Y. Z; Balci-Peynircioglu, B.; Dayangac-Erden, D.; Yuzbasioglu, A.; Bakir-Gungor, B.; Talim, B.; Balci-Hayta, B.; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü
Common miRNA signatures in a group of rare neuromuscular disorders
Comparative Genomics of Lentilactobacillus parabuchneri isolated from dairy, KEM complex, Makgeolli, and Saliva Microbiomes
(BMC, 2022) Gumustop, Ismail; Ortakci, Fatih; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Ortakçı, Fatih; Gümüştop, İsmail
Background: Lentilactobacillus parabuchneri is of particular concern in fermented food bioprocessing due to causing unwanted gas formation, cracks, and off-flavor in fermented dairy foods. This species is also a known culprit of histamine poisonings because of decarboxylating histidine to histamine in ripening cheese. Twenty-eight genomes in NCBI GenBank were evaluated via comparative analysis to determine genomic diversity within this species and identify potential avenues for reducing health associated risks and economic losses in the food industry caused by these organisms. Result: Core genome-based phylogenetic analysis revealed four distinct major clades. Eight dairy isolates, two strains from an unknown source, and a saliva isolate formed the first clade. Three out of five strains clustered on clade 2 belonged to dairy, and the remaining two strains were isolated from the makgeolli and Korean effective microorganisms (KEM) complex. The third and fourth clade members were isolated from Tete de Moine and dairy-associated niches, respectively. Whole genome analysis on twenty-eight genomes showed similar to 40% of all CDS were conserved across entire strains proposing a considerable diversity among L. parabuchneri strains analyzed. After assigning CDS to their corresponding function, similar to 79% of all strains were predicted to carry putative intact prophages, and similar to 43% of the strains harbored at least one plasmid; however, all the strains were predicted to encode genomic island, insertion sequence, and CRISPR-Cas system. A type I-E CRISPR-Cas subgroup was identified in all the strains, with the exception of DSM15352, which carried a type II-A CRISPR-Cas system. Twenty strains were predicted to encode histidine decarboxylase gene cluster that belongs to not only dairy but also saliva, KEM complex, and unknown source. No bacteriocin-encoding gene(s) or antibiotic resistome was found in any of the L. parabuchneri strains screened. Conclusion: The findings of the present work provide in-depth knowledge of the genomics of L. parabuchneri by comparing twenty-eight genomes available to date. For example, the hdc gene cluster was generally reported in cheese isolates; however, our findings in the current work indicated that it could also be encoded in those strains isolated from saliva, KEM complex, and unknown source. We think prophages are critical mobile elements of L. parabuchneri genomes that could pave the way for developing novel tools to reduce the occurrence of this unwanted species in the food industry.
A comparative study on normal and obese mice indicates that the secretome of mesenchymal stromal cells is influenced by tissue environment and physiopathological conditions
(BMC, CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, 2020) Ayaz-Guner, Serife; Alessio, Nicola; Acar, Mustafa B.; Aprile, Domenico; Ozcan, Servet; Di Bernardo, Giovanni; Peluso, Gianfranco; Galderisi, Umberto; 0000-0002-1052-0961; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü
Background: The term mesenchymal stromal cells (MSCs) designates an assorted cell population comprised of stem cells, progenitor cells, fibroblasts, and stromal cells. MSCs contribute to the homeostatic maintenance of many organs through paracrine and long-distance signaling. Tissue environment, in both physiological and pathological conditions, may affect the intercellular communication of MSCs. Methods: We performed a secretome analysis of MSCs isolated from subcutaneous adipose tissue (sWAT) and visceral adipose tissue (vWAT), and from bone marrow (BM), of normal and obese mice. Results: The MSCs isolated from tissues of healthy mice share a common core of released factors: components of cytoskeletal and extracellular structures; regulators of basic cellular functions, such as protein synthesis and degradation; modulators of endoplasmic reticulum stress; and counteracting oxidative stress. It can be hypothesized that MSC secretome beneficially affects target cells by the horizontal transfer of many released factors. Each type of MSC may exert specific signaling functions, which could be determined by looking at the many factors that are exclusively released from every MSC type. The vWAT-MSCs release factors that play a role in detoxification activity in response to toxic substances and drugs. The sWAT-MSC secretome contains proteins involved in in chondrogenesis, osteogenesis, and angiogenesis. Analysis of BM-MSC secretome revealed that these cells exert a signaling function by remodeling extracellular matrix structures, such as those containing glycosaminoglycans. Obesity status profoundly modified the secretome content of MSCs, impairing the above-described activity and promoting the release of inflammatory factors. Conclusion: We demonstrated that the content of MSC secretomes depends on tissue microenvironment and that pathological condition may profoundly alter its composition.
Complementary medicines used in ulcerative colitis and unintended interactions with cytochrome P450-dependent drug-metabolizing enzymes
(TUBİTAK, 2022) Şen, Alaattin; 0000-0002-8444-376X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Şen, Alaattin
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease with multiple genetic and a variety of environmental risk factors. Although current drugs significantly aid in controlling the disease, many people have led to the application of complementary therapies due to the common belief that they are natural and safe, as well as due to the consideration of the side effect of current drugs. Curcumin, cannabinoids, wheatgrass, Boswellia, wormwood and Aloe vera are among the most commonly used complementary medicines in UC. However, these treatments may have adverse and toxic effects due to unintended interactions with drugs or drugmetabolizing enzymes such as cytochrome P450s; thus, being ignorant of these interactions might cause deleterious effects with severe consequences. In addition, the lack of complete and controlled long-term studies with the use of these complementary medicines regarding drug metabolism pose additional risk and unsafety. Thus, this review aims to give an overview of the potential interactions of drug-metabolizing enzymes with the complementary botanical medicines used in UC, drawing attention to possible adverse effects.
Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection
(PEERJ INC, 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND, 2020) Demirci, Muserref Duygu Sacar; Adan, Aysun; 0000-0003-2012-0598; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression found in more than 200 diverse organisms. Although it is still not fully established if RNA viruses could generate miRNAs, there are examples of miRNA like sequences from RNA viruses with regulatory functions. In the case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with viral replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA-based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Overall, 950 hairpin structured sequences were extracted from the virus genome and based on the prediction results, 29 of them could be precursor miRNAs. Targeting analysis showed that 30 viral mature miRNA-like sequences could target 1,367 different human genes. PANTHER gene function analysis results indicated that viral derived miRNA candidates could target various human genes involved in crucial cellular processes including transcription, metabolism, defense system and several signaling pathways such as Wnt and EGFR signalings. Protein class-based grouping of targeted human genes showed that host transcription might be one of the main targets of the virus since 96 genes involved in transcriptional processes were potential targets of predicted viral miRNAs. For instance, basal transcription machinery elements including several components of human mediator complex (MED1, MED9, MED 12L, MED 19), basal transcription factors such as TAF4, TAF5, TAF7L and site-specific transcription factors such as STATI were found to be targeted. In addition, many known human miRNAs appeared to be able to target viral genes involved in viral life cycle such as S, M, N, E proteins and ORF lab, ORF3a, ORF8, ORF7a and ORF10. Considering the fact that miRNA-based therapies have been paid attention, based on the findings of this study, comprehending mode of actions of miRNAs and their possible roles during SARS-CoV-2 infections could create new opportunities for the development and improvement of new therapeutics.
COMPUTATIONAL IDENTIFICATION OF MICRORNAS FROM SSDNA VIRUSES
(Eskişehir Teknik Üniversitesi, 2018) Saçar Demirci, Müşerref Duygu; 0000-0003-2012-0598; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Saçar Demirci, Müşerref Duygu
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and the fact that they are associated with various disease phenotypes is one of the main reasons for their importance. The complexity of experimental detection of miRNAs due to their characteristics led to the development of computational methods. In this work, a machine learning based approach was applied to identify and analyze potential miRNAs that might be originated from 60 single strand DNA (ssDNA) viruses’ genomes. The results suggest that 53 of these viruses may possibly produce proper miRNA precursors. Moreover, the possibility of these candidate miRNA precursors’ ability to generate mature miRNAs that could target human genes and viral genomes has been tested. Overall, the outcomes of this research indicate that there might be another level of host-virus interaction through miRNAs which requires further experimental confirmation.

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