Yaşam ve Doğa Bilimleri Fakültesi

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3-Sulfopropyl methacrylate based cryogels as potential tissue engineering scaffolds
(TAYLOR & FRANCIS LTD, 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND, 2019) Durukan, Adile Yuruk; Isoglu, Ismail Alper; 0000-0001-6428-4207; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
In this study, we developed cryogels containing 3-sulfopropyl methacrylate (SPMA) and 4-vinyl pyridine (4-VP) as a potential scaffold for tissue engineering applications. Cryogels with varying monomer ratios were synthesised by chemical cross-linking under cryogelation conditions. Effect of initiators and cross-linker amount (0.025-0.15 g MBA; 0.012-0.05 g APS; 2.5-12.5 mu l TEMED) and also freezing temperature (-20 and -80oC) were investigated, and the conditions were optimised according to the morphological structures examined by SEM. The functional groups of the materials were characterised by FT-IR. Compression test and swelling were applied to investigate mechanical properties and water absorption ability, respectively. As a preliminary study, selected materials were tested for cell cytotoxicity with MTT. According to our results, the ionic and biocompatible cryogels prepared in this study possessing a highly porous and interconnective structure with good mechanical characteristics and swelling properties can be suitable as tissue scaffolds for many applications.
Advances in Micelle-based Drug Delivery: Cross-linked Systems
(BENTHAM SCIENCE PUBL LTDEXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES, 2017) Isoglu, Ismail Alper; Ozsoy, Yildiz; Isoglu, Sevil Dincer; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
There are several barriers that drug molecules encounter in body beginning from kidney filtration and reticulo-endothelial system (RES) clearance to cellular trafficking. Multifunctional nanocarriers have a great potential for the delivery of drugs by enhancing therapeutic activity of existing methodologies. A variety of nanocarriers are constructed by different material types, which have unique physicochemical properties for drug delivery applications. Micelles formed by amphiphilic polymers are one of the most important drug/nanocarrier formulation products, in which the core part is suitable for encapsulation of hydrophobic agent whereas the outer shell can be utilized for targeting the drug to the disease area. Micelles as self-assembled nanostructures may encounter difficulties in biodistribution of encapsulated drugs because they have a tendency to be dissociated in dilution or high ionic strength. Therefore, therapeutic efficiency is decreased and it requires high amount of drug to be administered to achieve more efficient result. To overcome this problem, covalently stabilized structures produced by cross-linking in core or shell part, which can prevent the micelle dissociation and regulate drug release, have been proposed. These systems can be designed as responsive systems in which cross-links are degradable or hydrolysable under specific conditions such as low pH or reductive environment. These are enhancing characteristics in drug delivery because their cleavage allows the release of bioactive agent encapsulated in the carrier at a certain site or time. This review describes the chemical methodologies for the preparation of cross-linked micelles, and reports an update of latest studies in literature.
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.
Alantolactone ameliorates graft versus host disease in mice
(ELSEVIER, 2024) Odabas, Gul Pelin; Aslan, Kubra; Suna, Pinar Alisan; Kendirli, Perihan Kader; Erdem, Şerife; Çakır, Mustafa; Özcan, Alper; Yılmaz, Ebru; Karakukcu, Musa; Donmez-Altuntas, Hamiyet; Yay, Arzu Hanim; Deniz, Kemal; Altay, Derya; Arslan, Duran; Canatan, Halit; Eken, Ahmet; Unal, Ekrem; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Kendirli, Perihan Kader
The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naïve (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2–18 (n = 4) and non-GVHD patients between ages 2–50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naïve phenotype (CD62L+ CD44− ). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in proinflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.
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.
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.
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.
Antibacterial Bilayered Skin Patches Made of HPMA and Quaternary Poly(4-vinyl pyridine)
(KOREAN FIBER SOC, KOREA SCIENCE TECHNOLOGY CTR #501 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA, 2018) Isoglu, I. Alper; Demirkan, Cemre; Seker, Mine Gul; uzlakoglu, Kadriye; Isoglu, Sevil Dincer; 0000-0002-6887-6549; 0000-0002-6226-7507; 0000-0002-7564-9213; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
This study aimed to produce poly(4-vinyl pyridine) and hydroxypropyl methacrylamide (HPMA)-based bilayer wound dressings materials enhancing healing mechanism for the wounds which have self-healing problem and high infection risk. These materials were designed to protect wound from secondary traumas caused microorganism invasion and do not have toxic substance release problem. Synthesis of quaternary poly(4-vinyl pyridine) (poly(Q4-VP)) which is the antibacterial layer of wound dressing material was carried out in two stages. At first stage, poly(4-vinyl pyridine) polymer was synthesized from 4-vinyl pyridine monomer by free radical polymerization. Then, poly(Q4-VP) was synthesized from poly(4-VP) by alkylation reaction with 6-bromocaproic acid. Resulted polymer was structurally characterized by FT-IR. The macroporous spongy structure, as the lower layer of wound dressing material, was prepared by cryogelation of HPMA. Then, the antibacterial polymer was electrospun onto the cryogel structure and bilayered material was obtained. Cryogel structure, fiber morphology and layer integration was examined by SEM. In order to enhance wound healing process, ascorbic acid (vitamin C) was loaded to cryogel layer and release was followed by spectrophotometrically. The antimicrobial properties of the materials were examined against Escherichia coli, Staphylococcus aureus and Candida albicans, respectively. According to the results, bilayered, antibacterial and antifungal against Staphylococcus aureus and Candida albicans, temporary wound dressings which can stimulate wound healing and have high swelling capacity were obtained successfully.
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.
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.
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.
Berberine-containing natural-medicine with boiled peanut-OIT induces sustained peanut-tolerance associated with distinct microbiota signature
(FRONTIERS MEDIA SA, 2023) Srivastava, Kamal; Cao, Mingzhuo; Fidan, Ozkan; Shi, Yanmei; Yang, Nan; Nowak-Wegrzyn, Anna; Miao, Mingsan; Zhan, Jixun; Sampson, Hugh A.; Li, Xiu-Min; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, Ozkan
BackgroundGut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function. ObjectiveWe sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes. MethodsPeanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE(+)B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms. ResultsBNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE(+) B cells (p <0.001 vs Sham for all). Significant differences were observed for Firmicutes/Bacteroidetes ratio across treatment groups. Bacterial genera positively correlated with post-challenge histamine and PN-IgE included Lachnospiraceae, Ruminococcaceae, and Hydrogenanaerobacterium (all Firmicutes) while Verrucromicrobiacea. Caproiciproducens, Enterobacteriaceae, and Bacteroidales were negatively correlated. ConclusionsBNP is a promising regimen for food allergy treatment and its benefits in a murine model are associated with a distinct microbiota signature.
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
Biodiversity, drug discovery, and the future of global health: Introducing the biodiversity to biomedicine consortium, a call to action
(UNIV EDINBURGH, GLOBAL HEALTH SOC, CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG, SCOTLAND, 2017) Neergheen-Bhujun, Vidushi; Awan, Almas Taj; Baran, Yusuf; Bunnefeld, Nils; Chan, Kit; Edison Dela Cruz, Thomas; Egamberdieva, Dilfuza; Elsasser, Simon; Johnson, Mari-Vaughn V.; Komai, Shoji; Konevega, Andrey L.; Malone, John H.; Mason, Paul; Nguon, Rothsophal; Piper, Ross; Shrestha, Uttam Babu; Pesic, Milica; Kagansky, Alexander; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü;
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Biosynthesis of Novel Naphthoquinone Derivatives in the Commonly-used Chassis Cells Saccharomyces cerevisiae and Escherichia coli
(Pleiades journals, 2021) Wu W.; Wang S.; Zhang H.; Guo W.; Lu H.; Xu H.; Zhan R.; Fidan O.; Sun L.; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Fidan, O.
Naphthoquinones harboring 1,4-naphthoquinone pharmacophore are considered as privileged structures in medicinal chemistry. In pharmaceutical industry and fundamental research, polyketide naphthoquinones were widely produced by heterologous expression of polyketide synthases in microbial chassis cells, such as Saccharomyces cerevisiae and Escherichia coli. Nevertheless, these cell factories still remain, to a great degree, black boxes that often exceed engineers’ expectations. In this work, the biotransformation of juglone or 1,4-naphthoquinone was conducted to generate novel derivatives and it was revealed that these two naphthoquinones can indeed be modified by the chassis cells. Seventeen derivatives, including 6 novel compounds, were isolated and their structural characterizations indicated the attachment of certain metabolites of chassis cells to naphthoquinones. Some of these biosynthesized derivatives were reported as potent antimicrobial agents with reduced cytotoxic activities. Additionally, molecular docking as simple and quick in silico approach was performed to screen the biosynthesized compounds for their potential antiviral activity. It was found that compound 11 and 17 showed the most promising binding affinities against Nsp9 of SARS-CoV-2, demonstrating their potential antiviral activities. Overall, this work provides a new approach to generate novel molecules in the commonly used chassis cells, which would expand the chemical diversity for the drug development pipeline. It also reveals a novel insight into the potential of the catalytic power of the most widely used chassis cells. © 2021, Pleiades Publishing, Inc.
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.
Can mesenchymal stem/stromal cells and their secretomes combat bacterial persisters?
(SPRINGER, 2023) Bicer-Çalışkan, Mesude; Fidan, Ozkan; 0000-0001-5312-4742; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Bicer-Çalışkan, Mesude; Fidan, Ozkan
The increasing number of life-threatening infections caused by persister bacteria is associated with various issues, including antimicrobial resistance and biofilm formation. Infections due to persister cells are often difficult to suppress without the use of last-resort antibiotics. Throughout the world, bacterial persistence and resistance create an unmet clinical demand for the exploration of newly introduced therapeutic approaches. Mesenchymal stem / stromal cells (MSCs) have an antimicrobial activity to protect against bacterial infections, including those caused by bacterial persisters. MSCs have substantial potential to secrete antimicrobial peptides (AMPs), including cathelicidin, beta-defensins, lipocalin-2, hepcidin, indoleamine 2,3-dioxygenase (IDO), cysteine proteases, and inducible nitric oxide synthases (iNOS). MSCs possess the potential to contribute to innate immunity by regulating the immune response. Recently, MSCs and their secreted components have been reported to improve antimicrobial activity. Bactericidal activity by MSCs and their secretomes has been shown to be mediated in part by the secretion of AMPs. Even though they were discovered more than 80 years ago, therapeutic options for persisters are restricted, and there is an urgent need for alternative treatment regimens. Hence, this review intends to critically assess the current literature on the effects of MSCs and their secretomes on persister bacteria. MSCs and their secretome-based therapies could be preferred as an up-and-coming approach to reinforce the antimicrobial efficiency in persister infections.
CC2D1A AS A NOVEL CILIOPATHY GENE
(SPRINGERNATURE, CAMPUS, 4 CRINAN ST, LONDON, N1 9XW, ENGLAND, 2020) Sakin, I.; Tuncel, G.; Sag, S. Ozemri; Kaplan, O. I.; Khokha, M. K.; Ergoren, M. C.; Deniz, E.; Temel, S. G.; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
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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.

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