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The effect of young blood plasma administration on dysbiosis and intestinal tissue gene expression involved in pathogen response in the middle-aged
Fen Bilimleri Enstitüsü, Biyoloji Ana Bilim Dalı, Biyoloji Bilim DalıYaşlanmayla birlikte bağırsak mikrobiyotasında disbiyozis meydana gelmektedir. Ayrıca bağırsak dokusundaki deformasyonlar bağırsak epitel hücreleri tarafından patojen yanıtta rol alan genlerin ekspresyonunun azalmasına neden olmaktadır. Bu durum ise bağırsak geçirgenliği, enflamatuar bağırsak hastalıkları, doku ve organlarda kronik iltihaplanmanın meydana gelmesi gibi birçok rahatsızlıkla birlikte davranışsal ve bilişsel durumlar üzerinde de etki gösterebilmektedir. Dolayısıyla özellikle yaşlanmayla birlikte meydana gelen disbiyozu geri çevirebilecek ve patojen yanıtta rol alan genlerin ifadesinin düzenlenmesinde rol alabilecek farklı biyolojik yaklaşımlar oldukça önem kazanmaktadır. Genç kan plazma uygulamasının işaret edilen sorunların giderilmesinde alternatif bir tedavi yöntemi olarak kullanılabilme potansiyeline sahip olduğu görülmektedir. Bu doğrultuda gerçekleştirilen bu tez çalışmasının amacı genç plazma transferinin yaşlı bağırsak mikrobiyotası ve patojen yanıtta rol alan gen ifadelerinin düzenlenmesi üzerine olan etkilerinin araştırılmasıdır. Bu amaç doğrultusunda 5 haftalık genç erkek Wistar ratlardan alınan kan plazması 12 aylık erkek orta yaşlı Wistar ratlara 30 gün boyunca her bir hayvana 05ml aktarıldı. Plazma transferi sonrasında Kontrol ve deney grubunda bulunan ratlar feda edildi. Feda edilen ratlardan alınan çekuç içeriğine metagenom uygulanarak bağırsak mikrobiyotası profilleri belirlendi. Bağırsak ileum dokularına gerçekleştirilen RNAseq analizi sonrasında önemli derecede arttığı görülen E3 ubiquitin-protein ligase TRIM56, CD209 antigen-like protein C, complement component C7 ve collectin-12 gen ekspresyonlarının arttığı syndecan-1 genlerin artan ve azalan değerleri RT-qPCR yöntemi ile belirlendi. Ayrıntılı metagenom analizi sonrasında, alfa çeşitlilik indeksleri, plazma uygulanan raların mikrobiyotasında kontrol grubuna göre daha fazla bakteri zenginliği göstermiştir. Ek olarak, Firmicutes/Bacteroidetes oranı plazma grubu mikrobiyotasında önemli derecede azalmıştır, bu da genç plazmanın olası gençleştirme özelliklerini doğrulamaktadır. Ayrıca, plazma uygulanan sıçanlarda Bifidobacterium longum, Coprococcus catus ve Romboutsia ilealis türlerinde artmış sayımlar ölçülmüştür. RT-qPCR ile elde sonuçlar RNAseq verileri ile uyumlu şekilde E3 ubiquitin-protein ligase TRIM56, CD209 antigen-like protein C, complement component C7 ve collectin-12 gen ekspresyonlarının öneli derecede arttığını syndecan-1 gen ifadesinin ise azaldığını bulmuştur. Çalışma sonuçları genç plazma transferinin yaşlı bağırsak mikrobiyotasında meydana gelen disbiyozisi geriye doğru çevirilmesinde ve bağırsak dokusunda patojen yanıtta rol alan genlerin düzenlenmesinde önemli derecede rol alabildiğini göstermektedir.Aging is associated with dysbiosis of the gut microbiota. Additionally, deformations in the intestinal tissue cause a reduction in the expression of genes in intestinal epithelial cells, which play a role in the pathogen response. This situation can have various repercussions, such as increased gut permeability, inflammatory bowel diseases, and chronic inflammation in tissues and organs, and can also affect behavioral and cognitive states. Therefore, various biological approaches that can reverse dysbiosis, especially with aging, and regulate the expression of genes involved in pathogen response are becoming increasingly important. Young blood plasma treatment appears to have the potential to be an alternative treatment method for addressing these problems. The aim of this thesis was to investigate the effects of young plasma transfer on the gut microbiota of the elderly and the regulation of gene expression involved in the pathogen response. To this end, blood plasma taken from 5-week-old male Wistar rats was transferred to 12-month-old middle-aged male Wistar rats, with each animal receiving 0.5 ml over 30 days. After plasma transfer, the rats from both the control and test groups were sacrificed. The cecal contents of the sacrificed rats were subjected to metagenomic analysis to determine the gut microbiota profiles. After RNA-seq analysis of the ileum tissues of the intestines, significant increases in the expression of E3 ubiquitin-protein ligase TRIM56, CD209 antigen-like protein C, complement component C7, and collectin-12 genes, and the increased and decreased values of syndecan-1 genes were determined by RT-qPCR. After detailed metagenome analysis, alpha diversity indices showed greater bacterial richness in the microbiota of plasma-administered rats than in the control group. Additionally, the Firmicutes/Bacteroidetes ratio significantly decreased in the plasma group microbiota, confirming the possible rejuvenating properties of young plasma. Furthermore, increased counts of Bifidobacterium longum, Coprococcus catus, and Romboutsia ilealis were observed in plasma-administered rats. Results obtained from RT-qPCR, consistent with RNAseq data, showed a significant increase in the expression of E3 ubiquitin-protein ligase TRIM56, CD209 antigen-like protein C, complement component C7, and collectin-12 genes, and a decrease in the syndecan-1 gene expression. The study results indicate that young plasma transfer plays a significant role in reversing the dysbiosis that occurs in the gut microbiota of the elderly and in regulating the genes involved in the pathogenic response of intestinal tissue
Aşırı yağlı diyet beslenen hamile dişi sıçan yavrularının hipotalamus damarlarında görülen değişiklilerin incelenmesi.
Obesity is a medical condition that carries increased risk for the onset of metabolic disorders and many other chronic diseases. However, etiology of obesity and how obsegenic traits are emerged remain to be elucidated. Investigations about this issue focused on one of the brain regions, hypothalamus,where energy homeostasis,food intake and appetite are regulated. Under the condition of hypothalamic inflammation and/or because of the passage of toxic substances from the circulating blood to the hypothalamus, hypothalamic cells are disrupted and metabolic deregulations might initiate, risk factors for obesity and other cluster of metabolic disordersmight increase. Recent studies have shown that the maternal obesity and/or obesogenic diet consumption during pregnancy may initiate hypothalamic inflammation which may permanently alter hypothalamic structures and functions in the offspring. Based on evidences that neuro-vascular changes, especially changes in brain blood barrier (BBB) integrity arenot only results in passage of toxic substances from circulating bloods but also may initiate or contribute to hypothalamic inflammation and affect microvessel density. In this study, we investigated changes in BBB integrity of 20 days-old Wistar rat offspring whose mothers were fed with HFD. Our results shows thatoffspringwhose mothers fed with HFD (cafeteria diet) hypothalamicBBB integritywas increased significantly compare to controls.Our results suggest that maternal obesity has impacts on hypothalamicBBB integrity and such changes can inhibit certain crutial signals to reach hypothalamus and initiate cascade of disease conditions as blocking signal homeostasisduring development.M.S. - Master of Scienc
Annenin metabolik hastalıklarının yavru antimikrobiyal peptitlerin ifadesine etkisi: antimikrobiyal savunma sistemindeki değişiklikler
Birth is a traumatic and stressful event for all living organisms. Neonate
meets a world full of microbes and has to adapt the new external environment.
Throughout all developmental periods and adulthood stages, balanced microbiota
crucial for the health of offspring. Antimicrobial peptides (AMP) have enormous
impacts on the establishment of the microbiome and determining the specific
composition of the bacterial community as well as its spatial organization. This thesis
investigated the effects of maternal metabolic disorders on antimicrobial protein
(AMP) expression, which is crucial for establishment of gastrointestinal system
(GIS) probiotic composition and mucin expression on offspring intestinal cells. As
Using whole-genome microarray analysis, changes in AMP expressions were
detected and also ceratin gene expressions were validated by RT-PCR. Besides,
changes in probiotic bacterial species populations were determined in those regions.
Our results might reflect how maternal metabolic disorders fluctuate offspring
mainly mucosal immunology parameters for the future microbiome establishment.
Finally, tight junction proteins of intestinal cells were investigated to understand the
pathogenic bacterial translocations that might be essential for chronic inflammation
and obesity tendency of offspring.Doğum tüm canlı organizmalar için travmatik ve stresli bir olaydır. Yeni
doğan yavru, mikroplarla dolu dünyayla tanışır ve yeni dış çevreye uyum sağlamak
zorundadır. Tüm gelişim dönemleri ve yetişkinlik aşamasında, dengeli mikrobiyota
yavruların sağlığı için çok önemlidir. Antimikrobiyal peptidler (AMP) mikrobiyom
yerleşmesinin yanı sıra bu bölgeye yerleşebilecek bakterilere karar vererek bakteri
topluluğunun organizasyonu üzerinde etkileri vardır. Bu tezde, maternal metabolik
bozuklukların; yavru bağırsak hücreleri tarafından ifade edilen müsin ve
gastrointestinal sistem (GIS) probiyotik bileşimi için önemli olan AMP ekspresyonu
üzerindeki etkileri araştırılmıştır. Tüm genom mikrodizi analizi kullanılarak AMP
ekspresyonlarında değişiklikler saptanmıştır ve seçilen belli genlerin ifadeleri RTPCR ile doğrulanmıştır. Ayrıca bu bölgelerde belirli probiyotik bakteri türleri
popülasyonlarında gerçekleşen değişimler belirlenmiştir. Sonuçlarımız, maternal
metabolik bozukluklarla beraber mukozal immünolojide gerçekleşen değişikliklerin
yavru gelişim sırasında yerleşmesi beklenen mikrobiyomu nasıl etkileyebileceğini
yansıtabilir. Son olarak, bağırsak hücrelerinin sıkı bağ proteinlerinin analizi
sonucunda azalan sıkı bağ proteinleri patojenik bakteriyel translokasyonlarına neden
olarak gelecekte yavru için kronik inflamasyon ve obezite oluşturabilme
potansiyelini taşıyabilir.Ph.D. - Doctoral Progra
KARBOKSİPEPTİDAZ E (CPE) 'NİN SIÇANLARDA GEBELİK DÖNEMİNDEKİ GEN İFADELERİNİN İNCELENMESİ
KARBOKSİPEPTİDAZ E (CPE) 'NİN SIÇANLARDA GEBELİK DÖNEMİNDEKİ GEN İFADELERİNİN İNCELENMES
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
INVESTIGATION OF THE EFFECTS OF PLASMA APPLICATIONS ON AGE-RELATED LIVER TISSUE AND ENZYMES FOR YOUNG AND OLD
Genç ve Yaşlı Plazma Uygulamalarının Yaşlanmayla İlişkili Karaciğer Dokusu ve Enzimleri Üzerindeki Etkilerinin İncelenmesi
INVESTIGATION OF THE EFFECTS OFYOUNG AND OLD PLASMA ADMINISTRATIONS ON AGE-RELATED LIVER TISSUE AND ENZYMES Hikmet Taner Teker 1,Taha Ceylani 2, Seda Keskin 3, EdaAçıkgöz 4ORCID ID: https://orcid.org/0000-0002-4726-982X1Ankara Medipol University,Department of Medical Biology, Ankara, 06050, Turkey, E-mail: [email protected] Muş Alparslan University,Department of Food Quality Control and Analysis, Muş, 49250, Turkey, E-mail: [email protected] Van Yüzüncü Yıl University, Facultyof Medicine, Department of Medical Histology and Embryology, Van, 65090,Turkey, E-mail: [email protected], [email protected] 4 Van Yüzüncü Yıl University, Facultyof Medicine, Department of Medical Histology and Embryology, Van, 65090,Turkey, E-mail: [email protected], [email protected]: Young plasma administration is oneof the effective treatment methods in delaying the burden of aging-relateddisease and promoting healthy aging. Our understanding of the effects of such alternativetherapies on organs associated with aging-related metabolism is limited. Thisstudy aimed to reveal the histological and biochemical results of the effectsof plasma applications on and young rats on cell and tissue architecture in therat liver.Materials and Methods: Sprague Dawley male aged rats (24months) were treated with pooled plasma (30 days, 0.5 ml, i.v) collected from5-week-old young rats. Young 5-week-old rats were treated with pooled plasma(30 days, 0.25 ml, i.v) collected from aged rats (24 months). At the end of theexperiment, 5µm sections were taken from the paraffin blocks prepared afterfixation in buffered formalin for liver samples from all groups. H&Estaining was performed for histopathological analysis and PAS staining was usedto determine glycogen density in all sections and then evaluated with the lightmicroscope. In addition, serum concentrations of liver enzymes AST, ALT, ALP,LDH, and ALB were measured using commercial kits in an automatic analyzer. Alldata were analyzed with the SPSS program using an unpaired t-test. Results: In the histopathologicalevaluations, we determined that young plasma administration improved hepaticfibrosis as well as other cellular degenerations in aged rat livers, andsignificantly reduced the amount of adipose tissue and lymphatic infiltrationdensity. There was a significant increase in glycogen accumulation in thehepatocytes of aged rats given young plasma. Young rats given aged plasma had asignificant increase in AST levels, while aged rats had significantly increasedALT levels compared to young controls. ALP levels were significantly increasedin the young control group compared to the other groups. Aged rats receivingyoung plasma had a significant increase in albumin levels.Discussion and Conclusion: Considering young plasma treatments displayedprotective and curative effects on aging-related liver enzymes and cellarchitecture, plasma exchanges can provide supportive data that may guidetreatment in the clinic and alternative solutions for the treatment ofaging-related metabolic diseases. Keywords: Young plasma; Aging; Inflammation;Oxidative stress; Liver Ethical Statement: This study was carried out withthe approval of the Ethics Committee (2021/03) obtained from the Saki YenilliExperimental Animal Production and Application Laboratory.</p
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