29 results on '"Yazar, Volkan"'
Search Results
2. 3D-MSCs A151 ODN-loaded exosomes are immunomodulatory and reveal a proteomic cargo that sustains wound resolution
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Camões, Sérgio P., Bulut, Ozlem, Yazar, Volkan, Gaspar, Maria M., Simões, Sandra, Ferreira, Rita, Vitorino, Rui, Santos, Jorge M., Gursel, Ihsan, and Miranda, Joana P.
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- 2022
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3. Immunogenicity and protective capacity of a CpG ODN adjuvanted alum adsorbed bivalent meningococcal outer membrane vesicle vaccine.
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Yildirim, Tugce Canavar, Ozsurekci, Yasemin, Yildirim, Muzaffer, Evcili, Irem, Yazar, Volkan, Aykac, Kubra, Guler, Ulku, Salih, Bekir, Gursel, Mayda, and Gursel, Ihsan
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MENINGOCOCCAL infections ,EXTRACELLULAR vesicles ,IMMUNE response ,MENINGOCOCCAL vaccines ,ENZYME-linked immunosorbent assay ,NEISSERIA meningitidis - Abstract
Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis , with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N. meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and the Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal activity (SBA) assay-based protective coverage of OMV vaccine to the X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W + B OMV vaccine, either adjuvanted with Alum, CpG ODN, or their combinations, and compared with a MenACYW conjugate vaccine (Nimenrix
TM , Pfizer), and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through enzyme-linked immunosorbent assay (ELISA) and SBA assay. Antibody responses and SBA titers were significantly higher in the W + B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W + B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W + B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation
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Yazar, Volkan, Kang, Sung-Ung, Ha, Shinwon, Dawson, Valina L., and Dawson, Ted M.
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- 2021
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5. Impaired ATF3 Signaling Involves SNAP25 in SOD1 Mutant ALS Patients
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Yazar, Volkan, primary, Kühlwein, Julia K., additional, Knehr, Antje, additional, Grozdanov, Veselin, additional, Ekici, Arif B., additional, Ludoplph, Albert C., additional, and Danzer, Karin M., additional
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- 2023
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6. Gene network landscape of mouse splenocytes reveals integrin complex as the A151 ODN-responsive hub molecule in the immune transcriptome
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Yazar, Volkan, primary, Yilmaz, Ismail Cem, additional, Bulbul, Artun, additional, Klinman, Dennis M., additional, and Gursel, Ihsan, additional
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- 2023
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7. DNA Methylation Signature of Aging: Potential Impact on the Pathogenesis of Parkinson’s Disease
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Yazar, Volkan, primary, Dawson, Valina L., additional, Dawson, Ted M., additional, and Kang, Sung-Ung, additional
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- 2023
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8. DNA Methylation Analysis in Monozygotic Twins Discordant for ALS in Blood Cells
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Yazar, Volkan, primary, Ruf, Wolfgang P, additional, Knehr, Antje, additional, Günther, Kornelia, additional, Ammerpohl, Ole, additional, Danzer, Karin M, additional, and Ludolph, Albert C, additional
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- 2023
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9. sj-docx-1-gae-10.1177_25168657231172159 – Supplemental material for DNA Methylation Analysis in Monozygotic Twins Discordant for ALS in Blood Cells
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Yazar, Volkan, Ruf, Wolfgang P, Knehr, Antje, Günther, Kornelia, Ammerpohl, Ole, Danzer, Karin M, and Ludolph, Albert C
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Cell Biology - Abstract
Supplemental material, sj-docx-1-gae-10.1177_25168657231172159 for DNA Methylation Analysis in Monozygotic Twins Discordant for ALS in Blood Cells by Volkan Yazar, Wolfgang P Ruf, Antje Knehr, Kornelia Günther, Ole Ammerpohl, Karin M Danzer and Albert C Ludolph in Epigenetics Insights
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- 2023
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10. The Secretome of Human Neonatal Mesenchymal Stem Cells Modulates Doxorubicin-Induced Cytotoxicity: Impact in Non-Tumor Cells
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Serras, Ana S., primary, Camões, Sérgio P., additional, Antunes, Bernardo, additional, Costa, Vera M., additional, Dionísio, Flávio, additional, Yazar, Volkan, additional, Vitorino, Rui, additional, Remião, Fernando, additional, Castro, Matilde, additional, Oliveira, Nuno G., additional, and Miranda, Joana P., additional
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- 2021
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11. Circulating extracellular vesicles of patients with steroid-sensitive nephrotic syndrome have higher RAC1 and induce recapitulation of nephrotic syndrome phenotype in podocytes
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Eroglu, Fehime K., primary, Yazar, Volkan, additional, Guler, Ulku, additional, Yıldırım, Muzaffer, additional, Yildirim, Tugce, additional, Gungor, Tulin, additional, Celikkaya, Evra, additional, Karakaya, Deniz, additional, Turay, Nilsu, additional, Ciftci Dede, Eda, additional, Korkusuz, Petek, additional, Salih, Bekir, additional, Bulbul, Mehmet, additional, and Gursel, Ihsan, additional
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- 2021
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12. Verem aşısı uygulayan ülkelerin bireyleri SARS-CoV-2 virüsünün yol açtığı enfeksiyona karşı daha dirençli olabilir mi?
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Ayanoğlu, İ. C., İpekoğlu, E. M., Yazar, Volkan, Yılmaz, İ. C., Gürsel, İhsan, Gürsel, M., Yazar, Volkan, and Gürsel, İhsan
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Protection ,virus diseases ,COVID-19 ,BCG ,SARS-CoV-2 infections - Abstract
The lower than expected number of SARS-CoV-2 cases in countries with fragile health systems is puzzling. Herein, we hypothesize that BCG vaccination policies and vaccine strain preferences adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated morbidity and mortality. We also postulate that until a specific vaccine is developed, SARS-CoV-2 vulnerable populations could be immunized with BCG vaccines to attain heterologous nonspecific protection from the new coronavirus. In the lights of our investigations the most resistant countries appear to be the ones using Group I BCG strain. Within these countries, however, those who employs Russian strain is even more protected against COVID-19 infection.
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- 2020
13. Human Gut Commensal Membrane Vesicles Modulate Inflammation by Generating M2-like Macrophages and Myeloid-Derived Suppressor Cells
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Alpdundar Bulut, Esin, primary, Bayyurt Kocabas, Banu, additional, Yazar, Volkan, additional, Aykut, Gamze, additional, Guler, Ulku, additional, Salih, Bekir, additional, Surucu Yilmaz, Naz, additional, Ayanoglu, Ihsan Cihan, additional, Polat, Muammer Merve, additional, Akcali, Kamil Can, additional, Gursel, Ihsan, additional, and Gursel, Mayda, additional
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- 2020
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14. Verem Aşısı Uygulayan Ülkelerin Bireyleri SARS-CoV-2 Virüsünün Yol Açtığı Enfeksiyona Karşı Daha Dirençli Olabilir mi?
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Ayanoğlu, İhsan Cihan, primary, İpekoğlu, Emre Mert, additional, Yazar, Volkan, additional, Yılmaz, İsmail Cem, additional, Gürsel, İhsan, additional, and Gürsel, Mayda, additional
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- 2020
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15. A suppressive oligodeoxynucleotide expressing TTAGGG motifs modulates cellular energetics through the mTOR signaling pathway
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Yazar, Volkan, primary, Kilic, Gizem, additional, Bulut, Ozlem, additional, Canavar Yildirim, Tugce, additional, Yagci, Fuat C, additional, Aykut, Gamze, additional, Klinman, Dennis M, additional, Gursel, Mayda, additional, and Gursel, Ihsan, additional
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- 2019
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16. Circulating extracellular vesicles of patients with steroid-sensitive nephrotic syndrome have higher RAC1 and induce recapitulation of nephrotic syndrome phenotype in podocytes.
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Eroglu, Fehime K., Yazar, Volkan, Guler, Ulku, Yıldırım, Muzaffer, Yildirim, Tugce, Gungor, Tulin, Celikkaya, Evra, Karakaya, Deniz, Turay, Nilsu, Dede, Eda Ciftci, Korkusuz, Petek, Salih, Bekir, Bulbul, Mehmet, and Gursel, Ihsan
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EXTRACELLULAR vesicles , *NEPHROTIC syndrome , *PHENOTYPES , *WESTERN immunoblotting , *DISEASE remission - Abstract
Since previous research suggests a role of a circulating factor in the pathogenesis of steroid-sensitive nephrotic syndrome (NS), we speculated that circulating plasma extracellular vesicles (EVs) are a candidate source of such a soluble mediator. Here, we aimed to characterize and try to delineate the effects of these EVs in vitro. Plasma EVs from 20 children with steroid-sensitive NS in relapse and remission, 10 healthy controls, and 6 disease controls were obtained by serial ultracentrifugation. Characterization of these EVs was performed by electron microscopy, flow cytometry, and Western blot analysis. Major proteins from plasma EVs were identified via mass spectrometry. Gene Ontology classification analysis and Ingenuity Pathway Analysis were performed on selectively expressed EV proteins during relapse. Immortalized human podocyte culture was used to detect the effects of EVs on podocytes. The protein content and particle number of plasma EVs were significantly increased during NS relapse. Relapse NS EVs selectively expressed proteins that involved actin cytoskeleton rearrangement. Among these, the level of RAC-GTP was significantly increased in relapse EVs compared with remission and disease control EVs. Relapse EVs were efficiently internalized by podocytes and induced significantly enhanced motility and albumin permeability. Moreover, relapse EVs induced significantly higher levels of RAC-GTP and phospho-p38 and decreased the levels of synaptopodin in podocytes. Circulating relapse EVs are biologically active molecules that carry active RAC1 as cargo and induce recapitulation of the NS phenotype in podocytes in vitro. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Elucidating immunomodulatory effects of telomeric repeat mimicking synthetic A151 oligodeoxynucleotide on immune cell transcriptome
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Yazar, Volkan, Gürsel, İhsan, Alkan, Can, and Moleküler Biyokimya ve Genetik Anabilim Dalı
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Innate immunity ,CpG ODN ,Suppressive ODN A151 ,Molecular biology ,Biyoistatistik ,mTOR signaling ,Cellular metabolism ,Transcriptome analysis ,Microarray ,Biostatistics ,Differential gene expression ,Intracellular trafficking - Abstract
Yapılan son çalışmalar DNA'nın, yaşamın mavi baskısı olmasının ötesinde bağışıklık sisteminidüzenleyici etkisini göstermiştir. Prokaryotik DNA'ya ait metil grubu içermeyen Sitozin-fosfat-Guanin(CpG) motifleri Toll-benzeri reseptör 9 (TLR9) ile etkileşerek bağışıklığı uyarır. Bu etkileşim, insandaaşılamanın kazandırdığı bağışıklığı artırmak amacıyla benzer DNA motifleri ihtiva eden sentetikoligodeoksinükleotidler (ODN) kullanılarak hayata geçirilmektedir. Öte yandan, tekrarlayan TTAGGGdizini içeren memeli kromozomlarının telomerik uçları bağışıklığı baskılayabilmekte ve hassas bağışıklıkdengesinin ayarlanmasında katkı sağlamaktadır. Bu bağlamda, esasen G-zengini telomer dizini olanbaskılayıcı ODN A151'in bağışıklığı baskılamada etkili olduğu kanıtlamıştır; otoimmün hastalıklardaolduğu gibi, aşırı boyutta etkin bir bağışıklık cevabı da kişiye zarar vermektedir. CpG ODN ve A151hâlihazırda klinik faz/klinik öncesi test kapsamlarında kanser ve bulaşıcı hastalıklardan otoimmün veotoenflammatuvar hastalıklara kadar birçok tıbbi bozukluğun tedavisi için denenmektedir. CpGODN'nin aksine, A151 literatürü çok sınırlıdır ve gen seviyesinde çalışma prensibi bilinmemektedir.Buna ek olarak, A151'in bağışıklık transkriptomunda yaptığı değişikliklerin boyutu ve süresi tamanlamıyla aydınlatılamamıştır. A151'in hücreye ait `öz` bir molekül olarak tıbbi anlamda taşıdığıpotansiyel göz önüne alındığında, A151'e ait işleyiş mekanizmasının aydınlatılması önem arzetmektedir. Bu amaçla, A151'in bağışıklık hücre transkriptomu üzerindeki bağışıklık düzenleyicietkilerinin anlaşılması adına birleşik mikroarray veri analizi tekniği kullanılarak bu tez çalışmasıhazırlanmıştır. A151'in hücre içi trafiği engellemesinin akabinde enerji zengini moleküllerin hücre içinealımını baskılamak suretiyle hücreleri enerjiden mahrum bıraktığını göstermiş olduk. Başka bir deyişle,A151 bağışıklık hücrelerini doğrudan etkilememektedir, bunun yerine hücre içi trafiği engelleyerekglikoz, glutamin gibi moleküllerin hücreye alınıp içeride yıkımını yavaşlatır ve böylece hücremetabolizmasını baskılar. Bağışıklığın baskılanması ise, bizim sonuçlarımıza göre, bu büyük etkinindolaylı bir sonucudur. Yaptığımız çalışmalar bu gözlemin bağışıklık hücrelerin CpG ODN ileetkinleştirilmesinden bağımsız ve zamana bağlı bir şekilde ortaya çıktığını göstermiştir. Hücrelerinfizyolojik olarak uygun miktardaki A151 ile inkübasyonu sonucu hücre içi trafik, kesecik sinyalizasyonuve zar proteinlerinin taşınmasında görevli birçok denetleyici genin baskılandığını ispatladık. Ancak,A151'in bağışıklık hücre transkriptomu üzerindeki baskılayıcı etkilerinin bununla da sınırlı kalmadığınıgördük; Lncpint, Malat1 ve H2-T10 gibi uzun protein kodlamayan RNA (lncRNA)'ların A151 tarafındandenetlenen elementler arasında olduğunu bu çalışma kapsamında göstermiş olduk. lncRNA'larınbağışıklık denetlemesiyle olan ilişkisi hâlihazırda bilinmektedir. Son olarak, sonuçlarımız A151'inbağışıklık hücrelerindeki enerji döngüsü, büyüme, bölünme ve hayatta kalma işlevlerinden sorumlubirincil yolak olan mTOR sinyal yolağına büyük bir etkisi olduğunu ima etmiştir. mTOR yolağınıetkinleştiren ve bu yolağın temel parçası olan birçok genin ifade miktarındaki değişimler farklı birtakımbelirteç (marker) gen ve fonksiyonel incelemeler kullanılmak suretiyle gösterilmiş olup, bu da A151'inmakrofajlarda ve B-hücrelerinde metabolik dinamikleri şekillendirmede hayati rolünü gözler önünesermektedir. Bu bulgular A151 ODN'in klinik uygulamalarının genişletilmesine ve hayata geçirilmesinekatkılar sağlayacak niteliktedir. Recent evidence revealed that DNA is beyond just the blueprint of life; it is also involved inimmunomodulation. Unmethylated Cytosine-phosphate-Guanine (CpG) motifs of prokaryotic DNAstimulate immune response by interacting with Toll-like receptor 9 (TLR9). This interaction is mimickedusing synthetic oligodeoxynucleotides (ODN) bearing similar DNA motifs to boost vaccine-drivenimmune response in human. Conversely, mammalian telomeric ends expressing TTAGGG repeatssuppress immune response and contribute to fine-tuning of delicate immune balance. In this respect,suppressive ODN A151 with such G-rich telomeric repeats has proven useful in downregulatingimmune response; an overly active immune response is just as harmful to the host, as in the case ofautoimmune disorders. Both CpG ODN and A151 are currently under preclinical/clinical trials with theaim of averting or medically treating a wide range of conditions from cancer to infectious disease orfrom autoimmune to autoinflammatory conditions. Contrary to CpG ODN, A151 literature is verylimited and its modus operandi at gene level remains more of a mystery. Additionally, the degree,duration and breath of A151-induced alterations in immune transcriptome appear partiallyunderstood. Given the medical potential A151 holds for immunosuppressive therapy in human as a`self-molecule`, understanding the underlying molecular mechanisms via which A151 operates isinvaluable. Toward this end, we attempted to uncover the unidentified features lying behind A151ODNs immunosuppressive effects on immune cell transcriptome using a combined analysis approachof microarray data in this thesis. We demonstrated for the first time that A151 ODN deprives the cellsenergy by ceasing cellular uptake of fundamental molecules into the immune cells after derailing theentire intracellular trafficking. Putting it another way, A151 does not directly act on immune systemcells but actually suffocates the cells by messing with intracellular trafficking, thereby blocking cellularuptake of fundamental molecules like glucose and glutamine. As such, immune suppression is just an indirect consequence of this larger cellular chaos. Our results indicated that this phenomenon occursindependent of CpG ODN stimulation of the cells and in a timely manner. Most, if not all, regulators ofintracellular trafficking, vesicle signaling, and membrane protein transportation were founddownregulated after incubation of cells with A151 at a physiologically relevant concentration, as well,implying full-blown entry to this intracellular turmoil at cellular level. The A151 effect on immunetranscriptome was not just restricted to setting off a chaos for intracellular dynamics; novel long noncodingRNAs (lncRNAs) with immunometabolic activities were identified within the scope of this studyamong elements potentially regulated by A151, such as Lncpint, Malat1 and H2-T10 just to name afew. The involvement of lncRNAs in immune regulation is a well-documented phenomenon. Finally,our data showed that as an epiphenomenon of the intracellular turmoil mentioned above A151 has adeep impact in immune cells on mTOR network, the cardinal network of cellular energetics, growth,proliferation, and survival. A major shift in expression profile of relevant genes, i.e. downregulation ofmany activators of mTOR signaling along with core mTOR components, was validated on the benchtopafter different layers of experimental validation using a wide range of marker genes and functionalassays, reflecting A151's ability to vastly shape dynamics of metabolism in favor of a metabolically inertstate in macrophages and in B-cells. This knowledge will expand the breadth of A151 therapy in theclinics. 207
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- 2019
18. A suppressive oligodeoxynucleotide expressing TTAGGG motifs modulates cellular energetics through the mTOR signaling pathway.
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Yazar, Volkan, Kilic, Gizem, Bulut, Ozlem, Yildirim, Tugce Canavar, Yagci, Fuat C, Aykut, Gamze, Klinman, Dennis M, Gursel, Mayda, and Gursel, Ihsan
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TISSUE remodeling , *IMMUNOSUPPRESSION , *IMMUNE system , *IMMUNE response , *MTOR inhibitors , *OXYGEN consumption , *WARBURG Effect (Oncology) - Abstract
Abstract Immune-mediated inflammation must be down-regulated to facilitate tissue remodeling during homeostatic restoration of an inflammatory response. Uncontrolled or over-exuberant immune activation can cause autoimmune diseases, as well as tissue destruction. A151, the archetypal example of a chemically synthesized suppressive oligodeoxynucleotide (ODN) based on repetitive telomere-derived TTAGGG sequences, was shown to successfully down-regulate a variety of immune responses. However, the degree, duration and breadth of A151-induced transcriptome alterations remain elusive. Here, we performed a comprehensive microarray analysis in combination with Ingenuity Pathway Analysis (IPA) using murine splenocytes to investigate the underlying mechanism of A151-dependent immune suppression. Our results revealed that A151 significantly down-regulates critical mammalian target of rapamycin (mTOR) activators (Pi3kcd , Pdpk1 and Rheb), elements downstream of mTOR signaling (Rps6ka1 , Myc , Stat3 and Slc2a1), an important component of the mTORC2 protein complex (Rictor) and Mtor itself. The effects of A151 on mTOR signaling were dose- and time-dependent. Moreover, flow cytometry and immunoblotting analyses demonstrated that A151 is able to reverse mTOR phosphorylation comparably to the well-known mTOR inhibitor rapamycin. Furthermore, Seahorse metabolic assays showed an A151 ODN-induced decrease in both oxygen consumption and glycolysis implying that a metabolically inert state in macrophages could be triggered by A151 treatment. Overall, our findings suggested novel insights into the mechanism by which the immune system is metabolically modulated by A151 ODN. [ABSTRACT FROM AUTHOR]
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- 2020
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19. Novel insights into the molecular pathogenesis ofCYP4V2‐associated Bietti's retinal dystrophy
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Astuti, Galuh D. N., primary, Sun, Vincent, additional, Bauwens, Miriam, additional, Zobor, Ditta, additional, Leroy, Bart P., additional, Omar, Amer, additional, Jurklies, Bernhard, additional, Lopez, Irma, additional, Ren, Huanan, additional, Yazar, Volkan, additional, Hamel, Christian, additional, Kellner, Ulrich, additional, Wissinger, Bernd, additional, Kohl, Susanne, additional, De Baere, Elfride, additional, Collin, Rob W. J., additional, and Koenekoop, Robert K., additional
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- 2014
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20. Kemeraltı ticaretinde işportacılığın sosyolojik boyutları
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Yazar, Volkan, Tatlıdil, Ercan, Ege Üniversitesi, Sosyal Bilimler Enstitüsü, and Diğer
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İzmir-Kemeraltı ,Marginal sector ,Sociology ,Migrations ,Peddlers ,Urbanization ,Work life ,Uygulamalı Sosyoloji Anabilim Dalı ,Sosyoloji - Abstract
120 ÖZET Bu araştırmanın amacı ` işportacı` olarak nitelenen marjinal işler kapsamında değerlendirilen ; ` işportacılık` faaliyeti ile uğraşan kesimin.izmir metropolü, Kemeraltı Bölgesi örneğinde, içinde yer aldığı sosyal, ekonomik ilişkilerini, demografik özelliklerini ve kentlileşme tutumlarını incelemek, bilimsel öngörülerde bulunmak ve öneriler oluşturmaktır. Çalışma bölgesi olarak Kemeraltı'nın seçilme nedeni, bu bölgenin yüzyıllardır ticari bir alan olma özelliğinin yanı sıra, İzmir metropol yapısı içerisinde bu bölgede çok sayıda işportacının bulunuyor olması ve bu kesimin kendi aralarında geliştirmiş oldukları sosyal ve ticari ilişkilerin sosyoljik önem sergiliyor olmasıdır. Araştırmada gönüllülük esasına dayalı bir biçimde tesadüfi olarak Kemeraltı'nın değişik bölgelerinden seçilmiş yüz işportacı ile alanda ön denemesi yapılarak yeniden yapılandırılmış soru formu çerçevesinde görüşmeler yapılmış ve aşağıdaki bulgular tespit edilmiştir. İşportacıların yaklaşık yarıya yakın bir kesiminin İzmir doğumlu oldukları ancak, ebeveynlerinin İzmir çevresi il ve ilçelerden göç ederek İzmir'e yerleşmiş oldukları ortaya çıkmaktadır. Ayrıca işportacıların %60 lık bir kesiminin halen göç ettikleri yerler ile ilişkilerini sürdürdükleri görülmektedir. Buradan hareketle, ` kentlileşme ` sürecinin geniş bir zaman dilimine yayılan çok yönlü bir süreç olduğu görülmektedir. İşportacılık faaliyetinin, İzmir'e dışarıdan gelenlere akraba, hemşehri ve arkadaş yardımı ile edindirilmiş bir ticari faaliyet olduğu, göç süreci ve sonrasında da geleneksel ilişkilerin devam ettirildiği izlenmektedir, izmir doğumlu işportacıların genellikle daha önce mesleki beceri gerektirmeyen işlerle uğraştıktan sonra işportacılık yapmaya başladıkları görülmektedir. İşportacıların %60 lık bir kesiminin İzmir'e gelmeden önceki yaşamları ile şimdiki yaşamlarını karşılaştırdıklarında `daha kötü ` olarak nitelemektedirler. İşportacıların kentsel boş zaman faaliyetlerinin dışında yer aldıkları, genellikle hiçbir örgüte üye olmadıkları izlenmektedir. SUMMARY The aim of the present study is to investigate the social.economic relations and demogrphic features of ` street sellers` in Kemeraltı, İzmir and forming a scientific foresight about this distinct community. Kemeraltı was chosen for this research, because this area had been a main commercial area in Izmir for centuries which included a huge number of `street sellers ` and social and commercial connections between themselves have got a sociologic importance. A hundred `street sellers ` who had been chosen voluntarily were interwiewed by using a questionary form and following results were obtained. Almost half of them were borned in Izmir but their parents were immigrants from other towns and villages surronding Izmir. Additionaly 60 percent of whole group have still got close connections with this towns. So it can be said that urbanization is a complicated and multidirectional process which occurs in a long time period. Non-Izmir borned `street sellers` said that they found their positions as `street seller` by help of their friends, relatives and fellow-citizens. Also they preserved their contacts even long time after they immigrated to İzmir. İzmir borned ones generally had been working in some other jobs as non-qualified workers before they became street seller. When non-Izmir borned ones were asked to compare their life quality before and after they come to Izmir, sixty percent of them said `it's getting worse after they come. It was understood that the street sellers do not join to the spare time activities in the city, also they are not members of any civil organization. 127
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- 2001
21. High-Resolution Homozygosity Mapping Is a Powerful Tool to Detect Novel Mutations Causative of Autosomal Recessive RP in the Dutch Population
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Collin, Rob W. J., primary, van den Born, L. Ingeborgh, additional, Klevering, B. Jeroen, additional, de Castro-Miró, Marta, additional, Littink, Karin W., additional, Arimadyo, Kentar, additional, Azam, Maleeha, additional, Yazar, Volkan, additional, Zonneveld, Marijke N., additional, Paun, Codrut C., additional, Siemiatkowska, Anna M., additional, Strom, Tim M., additional, Hehir-Kwa, Jayne Y., additional, Kroes, Hester Y., additional, de Faber, Jan-Tjeerd H. N., additional, van Schooneveld, Mary J., additional, Heckenlively, John R., additional, Hoyng, Carel B., additional, den Hollander, Anneke I., additional, and Cremers, Frans P. M., additional
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- 2011
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22. Novel insights into the molecular pathogenesis of CYP4V2-associated Bietti's retinal dystrophy.
- Author
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Astuti, Galuh D. N., Sun, Vincent, Bauwens, Miriam, Zobor, Ditta, Leroy, Bart P., Omar, Amer, Jurklies, Bernhard, Lopez, Irma, Ren, Huanan, Yazar, Volkan, Hamel, Christian, Kellner, Ulrich, Wissinger, Bernd, Kohl, Susanne, De Baere, Elfride, Collin, Rob W. J., and Koenekoop, Robert K.
- Subjects
RETINAL degeneration ,DEGENERATION (Pathology) ,DIAGNOSIS ,RETINAL diseases ,MEDICAL care - Abstract
Bietti's crystalline dystrophy (BCD) is a rare, autosomal recessive retinal degenerative disease associated with mutations in CYP4V2. In this study, we describe the genetic and clinical findings in 19 unrelated BCD patients recruited from five international retinal dystrophy clinics. Patients underwent ophthalmic examinations and were screened for CYP4V2 mutations by Sanger sequencing and quantitative polymerase chain reaction ( qPCR) copy number variation screening. Eight CYP4V2 mutations were found in 10/19 patients, including three patients in whom only monoallelic mutations were detected. Four novel mutations were identified: c.604G>A; p.(Glu202Lys), c.242C>G; p.(Thr81Arg), c.604+4A>G; p.(?), and c.1249dup; p.(Thr417Asnfs*2). In addition, we identified a heterozygous paternally inherited genomic deletion of at least 3.8 Mb, encompassing the complete CYP4V2 gene and several other genes, which is novel. Clinically, patients demonstrated phenotypic variability, predominantly showing choroidal sclerosis, attenuated vessels, and crystalline deposits of varying degrees of severity. To our knowledge, our study reports the first heterozygous CYP4V2 deletion and hence a novel mutational mechanism underlying BCD. Our results emphasize the importance of copy number screening in BCD. Finally, the identification of CYP4V2-negative patients with indistinguishable phenotypes from CYP4V2-positive patients might suggest the presence of mutations outside the coding regions of CYP4V2, or locus heterogeneity, which is unreported so far. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
23. Circulating extracellular vesicles of steroid sensitive nephrotic syndrome patients have higher RAC1 and induce recapitulation of nephrotic syndrome phenotype in podocytes
- Author
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Eroglu, Fehime Kara, Yazar, Volkan, Guler, Ulku, Yıldırım, Muzaffer, Yildirim, Tugce, Gungor, Tulin, Celikkaya, Evra, Karakaya, Deniz, Turay, Nilsu, Ciftci Dede, Eda, Korkusuz, Petek, Salih, Bekir, Bulbul, Mehmet, and Gursel, Ihsan
- Abstract
Since previous research suggests a role of a circulating factor in the pathogenesis of steroid-sensitive nephrotic syndrome (SSNS), we speculated that circulating plasma extracellular vesicles (EVs) are a candidate source of such a soluble mediator. Here, we aimed to characterize and try to delineate the effects of these EVs in vitro. Plasma EVs from 20 children with SSNS in relapse and remission, 10 healthy controls and 6 disease controls were obtained by serial ultracentrifugation. Characterization of these EVs was performed by electron microscopy, flow cytometry and western blotting. The major proteins from the plasma EVs were identified via mass spectrometry. A Gene Ontology classification analysis and integuinity pathway analysis were performed on selectively expressed EV proteins during relapse. Immortalized human podocyte culture was used to detect the effects of EVs on podocytes. The protein content and the particle number of plasma EVs were significantly increased during NS relapse. Relapse NS EVs selectively express proteins which involved actin cytoskeleton rearrangement. Among these, the level of RAC-GTP was significantly increased in relapse EVs compared to remission and disease control EVs. Relapse EVs were efficiently internalized by podocytes and induced significantly enhanced motility and albumin permeability. Moreover, relapse EVs induced significantly higher levels of RAC-GTP and phospho p38 (p-p38) and decreased levels of synaptopodin in podocytes. Circulating relapse EVs are biologically active molecules that carry active RAC1 as cargo and induce recapitulation of the nephrotic syndrome phenotype in podocytes in vitro.
- Published
- 2021
- Full Text
- View/download PDF
24. Human Gut Commensal Membrane Vesicles Modulate Inflammation by Generating M2-like Macrophages and Myeloid-Derived Suppressor Cells.
- Author
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Bulut, Esin Alpdundar, Kocabas, Banu Bayyurt, Yazar, Volkan, Aykut, Gamze, Guler, Ulku, Salih, Bekir, Yilmaz, Naz Surucu, Ayanoglu, Ihsan Cihan, Polat, Muammer Merve, Akcali, Kamil Can, Gursel, Ihsan, and Gursel, Mayda
- Subjects
- *
MYELOID-derived suppressor cells , *PROGRAMMED cell death 1 receptors , *MYELOID cells , *LACTIC acid bacteria , *MACROPHAGES , *T cells , *EXERCISE tolerance - Abstract
Immunomodulatory commensal bacteria modify host immunity through delivery of regulatory microbial-derived products to host cells. Extracellular membrane vesicles (MVs) secreted from symbiont commensals represent one such transport mechanism. How MVs exert their anti-inflammatory effects or whether their tolerance-inducing potential can be used for therapeutic purposes remains poorly defined. In this study, we show that MVs isolated from the human lactic acid commensal bacteria Pediococcus pentosaceus suppressed Ag-specific humoral and cellular responses. MV treatment of bone marrow–derived macrophages and bone marrow progenitors promoted M2-like macrophage polarization and myeloid-derived suppressor cell differentiation, respectively, most likely in a TLR2-dependent manner. Consistent with their immunomodulatory activity, MV-differentiated cells upregulated expression of IL-10, arginase-1, and PD-L1 and suppressed the proliferation of activated T cells. MVs’ anti-inflammatory effects were further tested in acute inflammation models in mice. In carbon tetrachloride–induced fibrosis and zymosan-induced peritonitis models, MVs ameliorated inflammation. In the dextran sodium sulfate–induced acute colitis model, systemic treatment with MVs prevented colon shortening and loss of crypt architecture. In an excisional wound healing model, i.p. MV administration accelerated wound closure through recruitment of PD-L1–expressing myeloid cells to the wound site. Collectively, these results indicate that P. pentosaceus–derived MVs hold promise as therapeutic agents in management/treatment of inflammatory conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
25. Circulating extracellular vesicles of patients with steroid-sensitive nephrotic syndrome have higher RAC1 and induce recapitulation of nephrotic syndrome phenotype in podocytes
- Author
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Ulku Guler, Muzaffer Yildirim, Volkan Yazar, Deniz Karakaya, Tugce Yildirim, Eda Çiftci Dede, Fehime Kara Eroglu, Ihsan Gursel, Tülin Güngör, Evra Çelikkaya, Nilsu Turay, Mehmet Bülbül, Petek Korkusuz, Bekir Salih, Kara Eroğlu, Fehime, Yazar, Volkan, Yıldırım, Muzaffer, Yıldırım, Tuğçe, Turay, Nilsu, and Gürsel, İhsan
- Subjects
Male ,rac1 GTP-Binding Protein ,medicine.medical_specialty ,Nephrotic Syndrome ,Adolescent ,Physiology ,Steroid-sensitive nephrotic syndrome ,Nephrotic syndrome ,RAC1 ,p38 Mitogen-Activated Protein Kinases ,Extracellular vesicles ,Cell Line ,Pathogenesis ,Extracellular Vesicles ,Recurrence ,Internal medicine ,Humans ,Medicine ,Phosphorylation ,Child ,Children ,Phospho-p38 ,Podocytes ,business.industry ,Microfilament Proteins ,Remission Induction ,medicine.disease ,Phenotype ,Treatment Outcome ,Endocrinology ,Case-Control Studies ,Child, Preschool ,Female ,Steroids ,business - Abstract
Since previous research suggests a role of a circulating factor in the pathogenesis of steroid-sensitive nephrotic syndrome (NS), we speculated that circulating plasma extracellular vesicles (EVs) are a candidate source of such a soluble mediator. Here, we aimed to characterize and try to delineate the effects of these EVs in vitro. Plasma EVs from 20 children with steroid-sensitive NS in relapse and remission, 10 healthy controls, and 6 disease controls were obtained by serial ultracentrifugation. Characterization of these EVs was performed by electron microscopy, flow cytometry, and Western blot analysis. Major proteins from plasma EVs were identified via mass spectrometry. Gene Ontology classification analysis and Ingenuity Pathway Analysis were performed on selectively expressed EV proteins during relapse. Immortalized human podocyte culture was used to detect the effects of EVs on podocytes. The protein content and particle number of plasma EVs were significantly increased during NS relapse. Relapse NS EVs selectively expressed proteins that involved actin cytoskeleton rearrangement. Among these, the level of RAC-GTP was significantly increased in relapse EVs compared with remission and disease control EVs. Relapse EVs were efficiently internalized by podocytes and induced significantly enhanced motility and albumin permeability. Moreover, relapse EVs induced significantly higher levels of RAC-GTP and phospho-p38 and decreased the levels of synaptopodin in podocytes. Circulating relapse EVs are biologically active molecules that carry active RAC1 as cargo and induce recapitulation of the NS phenotype in podocytes in vitro.
- Published
- 2021
26. A suppressive oligodeoxynucleotide expressing TTAGGG motifs modulates cellular energetics through the mTOR signaling pathway
- Author
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Gamze Aykut, Mayda Gursel, Fuat Cem Yagci, Volkan Yazar, Ozlem Bulut, Ihsan Gursel, Dennis M. Klinman, Tugce Yildirim, Gizem Kilic, Yazar, Volkan, Kılıç, Gizem, Bulut, Özlem, Canavar-Yıldırım, Tuğçe, Yağcı, Fuat C., Gamze, Aykut, and Gürsel, İhsan
- Subjects
Amino Acid Motifs ,Immunology ,Inflammation ,Microarray ,mTORC2 ,A151 ODN ,Mice ,Immune system ,medicine ,Animals ,Immunology and Allergy ,Phosphorylation ,STAT3 ,Cells, Cultured ,PI3K/AKT/mTOR pathway ,Original Research ,Immunometabolism ,biology ,Chemistry ,TOR Serine-Threonine Kinases ,General Medicine ,Cell biology ,Mice, Inbred C57BL ,Oligodeoxyribonucleotides ,biology.protein ,medicine.symptom ,Signal transduction ,Immunosuppression ,Immunosuppressive Agents ,Signal Transduction ,RHEB - Abstract
Immune-mediated inflammation must be down-regulated to facilitate tissue remodeling during homeostatic restoration of an inflammatory response. Uncontrolled or over-exuberant immune activation can cause autoimmune diseases, as well as tissue destruction. A151, the archetypal example of a chemically synthesized suppressive oligodeoxynucleotide (ODN) based on repetitive telomere-derived TTAGGG sequences, was shown to successfully down-regulate a variety of immune responses. However, the degree, duration and breadth of A151-induced transcriptome alterations remain elusive. Here, we performed a comprehensive microarray analysis in combination with Ingenuity Pathway Analysis (IPA) using murine splenocytes to investigate the underlying mechanism of A151-dependent immune suppression. Our results revealed that A151 significantly down-regulates critical mammalian target of rapamycin (mTOR) activators (Pi3kcd, Pdpk1 and Rheb), elements downstream of mTOR signaling (Rps6ka1, Myc, Stat3 and Slc2a1), an important component of the mTORC2 protein complex (Rictor) and Mtor itself. The effects of A151 on mTOR signaling were doseand time-dependent. Moreover, flow cytometry and immunoblotting analyses demonstrated that A151 is able to reverse mTOR phosphorylation comparably to the well-known mTOR inhibitor rapamycin. Furthermore, Seahorse metabolic assays showed an A151 ODN-induced decrease in both oxygen consumption and glycolysis implying that a metabolically inert state in macrophages could be triggered by A151 treatment. Overall, our findings suggested novel insights into the mechanism by which the immune system is metabolically modulated by A151 ODN. This work was partially supported by the Scientific and Technological Research Council of Turkey (TUBITAK) (grant number: 115S492 to I.G.), (grant number: 115S837 to I.G.) and the Ministry of Development (grant name: UMRAM-ASI, project #: 2015BSV302 to I.G.).
- Published
- 2019
27. Human gut commensal membrane vesicles modulate inflammation by generating m2-like macrophages and myeloid-derived suppressor cells
- Author
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Ihsan Gursel, Ulku Guler, Naz Surucu Yilmaz, Banu Bayyurt Kocabas, Mayda Gursel, Gamze Aykut, Ihsan Cihan Ayanoglu, Volkan Yazar, Muammer Merve Polat, Kamil Can Akcali, Bekir Salih, Esin Alpdundar Bulut, Kocabaş, Banu Bayyurt, Yazar, Volkan, Aykut, Gamze, Güler, Ülkü, and Gürsel, İhsan
- Subjects
Ovalbumin ,Immunology ,Anti-Inflammatory Agents ,Macrophage polarization ,Inflammation ,T-Lymphocytes, Regulatory ,Mice ,Downregulation and upregulation ,Cell-Derived Microparticles ,Fibrosis ,Extracellular ,medicine ,Animals ,Humans ,Immunology and Allergy ,Progenitor cell ,Biological Products ,Pediococcus pentosaceus ,Chemistry ,Macrophages ,Myeloid-Derived Suppressor Cells ,Cell Membrane ,Macrophage Activation ,medicine.disease ,Gastrointestinal Microbiome ,Cell biology ,Disease Models, Animal ,medicine.anatomical_structure ,Ligilactobacillus salivarius ,Myeloid-derived Suppressor Cell ,Female ,Bone marrow ,medicine.symptom - Abstract
Immunomodulatory commensal bacteria modify host immunity through delivery of regulatory microbial-derived products to host cells. Extracellular membrane vesicles (MVs) secreted from symbiont commensals represent one such transport mechanism. How MVs exert their anti-inflammatory effects or whether their tolerance-inducing potential can be used for therapeutic purposes remains poorly defined. In this study, we show that MVs isolated from the human lactic acid commensal bacteria Pediococcus pentosaceus suppressed Ag-specific humoral and cellular responses. MV treatment of bone marrow–derived macrophages and bone marrow progenitors promoted M2-like macrophage polarization and myeloid-derived suppressor cell differentiation, respectively, most likely in a TLR2-dependent manner. Consistent with their immunomodulatory activity, MV-differentiated cells upregulated expression of IL-10, arginase-1, and PD-L1 and suppressed the proliferation of activated T cells. MVs’ anti-inflammatory effects were further tested in acute inflammation models in mice. In carbon tetrachloride–induced fibrosis and zymosan-induced peritonitis models, MVs ameliorated inflammation. In the dextran sodium sulfate–induced acute colitis model, systemic treatment with MVs prevented colon shortening and loss of crypt architecture. In an excisional wound healing model, i.p. MV administration accelerated wound closure through recruitment of PD-L1–expressing myeloid cells to the wound site. Collectively, these results indicate that P. pentosaceus–derived MVs hold promise as therapeutic agents in management/treatment of inflammatory conditions.
- Published
- 2020
28. Immunogenicity and protective capacity of a CpG ODN adjuvanted alum adsorbed bivalent meningococcal outer membrane vesicle vaccine.
- Author
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Canavar Yildirim T, Ozsurekci Y, Yildirim M, Evcili I, Yazar V, Aykac K, Guler U, Salih B, Gursel M, and Gursel I
- Subjects
- Animals, Mice, Female, Adjuvants, Immunologic administration & dosage, Adjuvants, Immunologic pharmacology, Antibodies, Bacterial immunology, Antibodies, Bacterial blood, Immunogenicity, Vaccine, Bacterial Outer Membrane immunology, Meningococcal Vaccines immunology, Meningococcal Vaccines administration & dosage, Mice, Inbred BALB C, Neisseria meningitidis immunology, Alum Compounds administration & dosage, Oligodeoxyribonucleotides immunology, Oligodeoxyribonucleotides administration & dosage, Meningococcal Infections prevention & control, Meningococcal Infections immunology
- Abstract
Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N. meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and the Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal activity (SBA) assay-based protective coverage of OMV vaccine to the X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the W + B OMV vaccine, either adjuvanted with Alum, CpG ODN, or their combinations, and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer), and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through enzyme-linked immunosorbent assay (ELISA) and SBA assay. Antibody responses and SBA titers were significantly higher in the W + B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the W + B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the W + B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
29. Gene network landscape of mouse splenocytes reveals integrin complex as the A151 ODN-responsive hub molecule in the immune transcriptome.
- Author
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Yazar V, Yilmaz IC, Bulbul A, Klinman DM, and Gursel I
- Abstract
Homeostatic restoration of an inflammatory response requires quenching of the immune system after pathogen threats vanish. A continued assault orchestrated by host defense results in tissue destruction or autoimmunity. A151 is the epitome of synthetic oligodeoxynucleotides (ODNs) that curb the immune response by a subset of white corpuscles through repetitive telomere-derived TTAGGG sequences. Currently, the genuine effect of A151 on the immune cell transcriptome remains unknown. Here, we leveraged an integrative approach where weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and gene set enrichment analysis (GSEA) of our in-house microarray datasets aided our understanding of how A151 ODN suppresses the immune response in mouse splenocytes. Our bioinformatics results, together with experimental validations, indicated that A151 ODN acts on components of integrin complexes, Itgam and Itga6 , to interfere with immune cell adhesion and thereby suppresses the immune response in mice. Moreover, independent lines of evidence in this work converged on the observation that cell adhesion by integrin complexes serves as a focal point for cellular response to A151 ODN treatment in immune cells. Taken together, the outcome of this study sheds light on the molecular basis of immune suppression by a clinically useful DNA-based therapeutic agent., Competing Interests: The funding bodies played no role in study design, data collection, decision to publish, or preparation of the manuscript. I.G. and D.M.K. declare that they have the inventor rights on A151 ODN-related patents., (© 2023 The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
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