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Book Part Citation Count: 13Experimental MicroRNA Detection Methods(Humana Press Inc., 2022) Akgül, Bünyamin; Akgül,B.MicroRNAs (miRNAs) are considerably small yet highly important riboregulators involved in nearly all cellular processes. Due to their critical roles in posttranscriptional regulation of gene expression, they have the potential to be used as biomarkers in addition to their use as drug targets. Although computational approaches speed up the initial genomewide identification of putative miRNAs, experimental approaches are essential for further validation and functional analyses of differentially expressed miRNAs. Therefore, sensitive, specific, and cost-effective microRNA detection methods are imperative for both individual and multiplex analysis of miRNA expression in different tissues and during different developmental stages. There are a number of well-established miRNA detection methods that can be exploited depending on the comprehensiveness of the study (individual miRNA versus multiplex analysis), the availability of the sample and the location and intracellular concentration of miRNAs. This review aims to highlight not only traditional but also novel strategies that are widely used in experimental identification and quantification of microRNAs. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.Book Part Citation Count: 1Epitranscriptomics Changes the Play: m6A RNA Modifications in Apoptosis(Springer, 2022) Akçaöz,A.; Akgül, Bünyamin; Akgül,B.Apoptosis is a form of programmed cell death that is essential for cellular and organismal homeostasis. Any irregularities that disturb the balance between apoptosis and cell survival have severe implications, such as improper development or life-threatening diseases. Thus, it is highly critical to maintain a proper rate of apoptosis throughout development. In fact, several complex transcriptional and posttranscriptional mechanisms exist in eukaryotes to critically regulate the rate of apoptotic processes. Recent studies suggest that not only RNA sequences but also their modifications, such as m6A methylation, play a fundamental role in these transcriptional and posttranscriptional processes. A specific set of proteins, called writer, eraser, and reader of m6A marks, modulate the rate of apoptosis by determining the m6A repertoire and the fate of certain transcripts associated with apoptosis. In this Review, we will cover the dynamic m6A RNA modifications and their impact on modulation of apoptosis. © 2022, Springer Nature Switzerland AG.Book Part Citation Count: 38Endogenous miRNA Sponges(Humana Press Inc., 2022) Akgül, Bünyamin; Akgül,B.MicroRNAs (miRNAs) are a class of noncoding RNAs of 17–22 nucleotides in length with a critical function in posttranscriptional gene regulation. These master regulators are themselves subject to regulation both transcriptionally and posttranscriptionally. Recently, miRNA function has been shown to be modulated by exogenous RNA molecules that function as miRNA sponges. Interestingly, endogenous transcripts such as transcribed pseudogenes, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and mRNAs may serve as natural miRNA sponges. These transcripts, which bind to miRNAs and competitively sequester them away from their targets, are naturally existing endogenous miRNA sponges, called competing endogenous RNAs (ceRNAs). Here we present a historical background of miRNAs, exogenous and endogenous miRNA sponges as well as some examples of endogenous miRNA sponges involved in regulatory mechanisms associated with various diseases, developmental stages, and other cellular processes. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.Article Citation Count: 5Transcriptomics Profiling Identifies Cisplatin-Inducible Death Receptor 5 Antisense Long Non-coding RNA as a Modulator of Proliferation and Metastasis in HeLa Cells(Frontiers Media Sa, 2021) Gurer, Dilek Cansu; Erdogan, Ipek; Ahmadov, Ulvi; Basol, Merve; Sweef, Osama; Cakan-Akdogan, Gulcin; Akgul, Bunyamin; Akgül, BünyaminCisplatin is a well-known cancer chemotherapeutic agent but how extensively long non-coding RNA (lncRNA) expression is modulated by cisplatin is unknown. It is imperative to employ a comprehensive approach to obtain a better account of cisplatin-mediated changes in the expression of lncRNAs. In this study, we used a transcriptomics approach to profile lncRNAs in cisplatin-treated HeLa cells, which resulted in identification of 10,214 differentially expressed lncRNAs, of which 2,500 were antisense lncRNAs. For functional analyses, we knocked down one of the cisplatin inducible lncRNAs, death receptor 5 antisense (DR5-AS) lncRNA, which resulted in a morphological change in HeLa cell shape without inducing any cell death. A second round of transcriptomics-based profiling revealed differential expression of genes associated with immune system, motility and cell cycle in DR5-AS knockdown HeLa cells. Cellular analyses showed that DR5-AS reduced cell proliferation and caused a cell cycle arrest at S and G2/M phases. Moreover, DR5-AS knockdown reduced the invasive capacity of HeLa cells in zebrafish xenograft model. These results suggest that cisplatin-mediated pleiotropic effects, such as reduction in cell proliferation, metastasis and cell cycle arrest, may be mediated by lncRNAs.Review Citation Count: 3Noncoding RNAs in apoptosis: identification and function(Tubitak Scientific & Technological Research Council Turkey, 2022) Tuncel, Ozge; Kara, Merve; Yaylak, Bilge; Erdogan, Ipek; Akgul, Bunyamin; Akgül, BünyaminApoptosis is a vital cellular process that is critical for the maintenance of homeostasis in health and disease. The derailment of apoptotic mechanisms has severe consequences such as abnormal development, cancer, and neurodegenerative diseases. Thus, there exist complex regulatory mechanisms in eukaryotes to preserve the balance between cell growth and cell death. Initially, protein coding genes were prioritized in the search for such regulatory macromolecules involved in the regulation of apoptosis. However, recent genome annotations and transcriptomics studies have uncovered a plethora of regulatory noncoding RNAs that have the ability to modulate not only apoptosis but also many other biochemical processes in eukaryotes. In this review article, we will cover a brief summary of apoptosis and detection methods followed by an extensive discussion on microRNAs, circular RNAs, and long noncoding RNAs in apoptosis.Article Citation Count: 5Deep sequencing reveals two jurkat subpopulations with distinct miRNA profiles during camptothecin-induced apoptosis(Tubitak Scientific & Technological Research Council Turkey, 2018) Erdogan, Ipek; Cosacak, Mehmet Ilyas; Nalbant, Ayten; Akgul, Bunyamin; Akgül, BünyaminMicroRNAs (miRNAs) are small noncoding RNAs of about 19-25 nt that regulate gene expression posttranscriptionally under various cellular conditions, including apoptosis. The miRNAs involved in modulation of apoptotic events in T cells are partially known. However, heterogeneity associated with cell lines makes it difficult to interpret gene expression signatures, especially in cancer-related cell lines. Treatment of the Jurkat T-cell leukemia cell line with the universal apoptotic drug, camptothecin, resulted in identification of two Jurkat subpopulations: one that is sensitive to camptothecin and another that is rather intrinsically resistant. We sorted apoptotic Jurkat cells from nonapoptotic ones prior to profiling miRNAs through deep sequencing. Our data showed that a total of 184 miRNAs were dysregulated. Interestingly, the apoptotic and nonapoptotic subpopulations exhibited distinct miRNA expression profiles. In particular, 6 miRNAs were inversely expressed in these two subpopulations. The pyrosequencing results were validated by real-time qPCR. Altogether, these results suggest that miRNAs modulate apoptotic events in T cells and that cellular heterogeneity requires careful interpretation of miRNA expression profiles obtained from drug-treated cell lines.Review Citation Count: 10Intracytoplasmic Re-localization of miRISC Complexes(Frontiers Media Sa, 2018) Akgul, Bunyamin; Erdogan, Ipek; Akgül, BünyaminMicroRNAs (miRNAs) are a conserved class of non-coding RNAs of 22 nucleotides that post-transcriptionally regulate gene expression through translational repression and/or mRNA degradation. A great progress has been made regarding miRNA biogenesis and miRNA-mediated gene regulation. Additionally, an ample amount of information exists with respect to the regulation of miRNAs. However, the cytoplasmic localization of miRNAs and its effect on gene regulatory output is still in progress. We provide a current review of the cytoplasmic miRNA localization in metazoans. We then discuss the dynamic changes in the intracytoplasmic localization of miRNAs as a means to regulate their silencing activity. We then conclude our discussion with the potential molecules that could modulate miRNA localization.Article Citation Count: 6Transcriptomics Analysis of Circular RNAs Differentially Expressed in Apoptotic HeLa Cells(Frontiers Media Sa, 2019) Yaylak, Bilge; Erdogan, Ipek; Akgul, Bunyamin; Akgül, BünyaminApoptosis is a form of regulated cell death that plays a critical role in survival and developmental homeostasis. There are numerous reports on regulation of apoptosis by protein-coding genes as well as small non-coding RNAs, such as microRNAs. However, there is no comprehensive investigation of circular RNAs (circRNA) that are differentially expressed under apoptotic conditions. We have performed a transcriptomics study in which we first triggered apoptosis in HeLa cells through treatment with four different agents, namely cisplatin, doxorubicin, TNF-alpha and anti-Fas mAb. Total RNAs isolated from control as well as treated cells were treated with RNAse R to eliminate the linear RNAs. The remaining RNAs were then subjected to deep-sequencing to identify differentially expressed circRNAs. Interestingly, some of the dys-regulated circRNAs were found to originate from protein-coding genes well-documented to regulate apoptosis. A number of candidate circRNAs were validated with qPCR with or without RNAse R treatment as well. We then took advantage of bioinformatics tools to investigate the coding potential of differentially expressed RNAs. Additionally, we examined the candidate circRNAs for the putative miRNA-binding sites and their putative target mRNAs. Our analyses point to a potential for circRNA-mediated sponging of miRNAs known to regulate apoptosis. In conclusion, this is the first transcriptomics study that provides a complete circRNA profile of apoptotic cells that might shed light onto the potential role of circRNAs in apoptosis.Article Citation Count: 1Genomewide m6A Mapping Uncovers Dynamic Changes in the m6A Epitranscriptome of Cisplatin-Treated Apoptotic HeLa Cells(Mdpi, 2022) Alasar, Azime Akcaoz; Tuncel, Ozge; Gelmez, Ayse Bengisu; Saglam, Buket; Vatansever, Ipek Erdogan; Akgul, Bunyamin; Akgül, BünyaminCisplatin (CP), which is a conventional cancer chemotherapeutic drug, induces apoptosis by modulating a diverse array of gene regulatory mechanisms. However, cisplatin-mediated changes in the m(6)A methylome are unknown. We employed an m(6)A miCLIP-seq approach to investigate the effect of m(6)A methylation marks under cisplatin-mediated apoptotic conditions on HeLa cells. Our high-resolution approach revealed numerous m(6)A marks on 972 target mRNAs with an enrichment on 132 apoptotic mRNAs. We tracked the fate of differentially methylated candidate mRNAs under METTL3 knockdown and cisplatin treatment conditions. Polysome profile analyses revealed perturbations in the translational efficiency of PMAIP1 and PHLDA1 transcripts. Congruently, PMAIP1 amounts were dependent on METTL3. Additionally, cisplatin-mediated apoptosis was sensitized by METTL3 knockdown. These results suggest that apoptotic pathways are modulated by m(6)A methylation events and that the METTL3-PMAIP1 axis modulates cisplatin-mediated apoptosis in HeLa cells.Book Part Citation Count: 4Master Regulators of Posttranscriptional Gene Expression Are Subject to Regulation(Humana Press inc, 2014) Hamid, Syed Muhammad; Akgul, Bunyamin; Akgül, BünyaminMicroRNAs (miRNAs) are small noncoding RNAs of 17-25 nt in length that control gene expression posttranscriptionally. As master regulators of posttranscriptional gene expression, miRNAs themselves are subject to tight regulation at multiple steps. The most common mechanisms include miRNA transcription, processing, and localization. Additionally, intricate feedback loops between miRNAs and transcription factors result in unidirectional, reciprocal, or self-directed elegant control mechanisms. In this chapter, we focus on the posttranscriptional regulatory mechanisms that generate miRNAs whose sequence might be slightly different from the miRNA-coding sequences. Hopefully, this information will be helpful in the discovery of novel miRNAs as well as in the analysis of deep-sequencing data and ab initio prediction of miRNAs.Book Part Citation Count: 3Gene Reporter Assay to Validate MicroRNA Targets in Drosophila S2 Cells(Humana Press inc, 2014) Akgul, Bunyamin; Goktas, Cagdas; Akgül, BünyaminBioinformatics programs have helped tremendously in identifying the targets of microRNAs, which are small noncoding RNAs that regulate gene expression posttranscriptionally. However, the partial complementarity between miRNAs and their targets hinders the accuracy of target prediction, necessitating the use of experimental validation procedures. Here, we describe a gene reporter assay typically used in our lab to validate putative miRNA-mRNA interactions in Drosophila S2 cells.Article Citation Count: 0Knockdown of death receptor 5 antisense long noncoding RNA and cisplatin treatment modulate similar macromolecular and metabolic changes in HeLa cells(Tubitak Scientific & Technological Research Council Turkey, 2022) Gurer, Dilek Cansu; Erdogan Vatansever, Ipek; Ceylan, Cagatay; Akgul, Bunyamin; Akgül, BünyaminBackground/aim: Despite great progress in complex gene regulatory mechanisms in the dynamic tumor microenvironment, the potential contribution of long noncoding RNAs (lncRNAs) to cancer cell metabolism is poorly understood. Death receptor 5 antisense (DR5-AS) is a cisplatin inducible lncRNA whose knockdown modulates cell morphology. However, its effect on cell metabolism is unknown. The aim of this study is to examine metabolic changes modulated by cisplatin and DR5-AS lncRNA in HeLa cells.Materials and methods: We used cisplatin as a universal cancer therapeutic drug to modulate metabolic changes in HeLa cervix cancer cells. We then examined the extent of metabolic changes by Fourier transform infrared spectroscopy (FTIR). We also performed transcriptomics analyses by generating new RNA-seq data with total RNAs isolated from cisplatin-treated HeLa cells. Then, we compared cisplatin-mediated transcriptomics and macromolecular changes with those mediated by DR5-AS knockdown.Results: Cisplatin treatment caused changes in the unsaturated fatty acid and lipid-to-protein ratios and the glycogen content. These observations in altered cellular metabolism were supported by transcriptomics analyses. FTIR spectroscopy analyses have revealed that DR5-AS knockdown causes a 20.9% elevation in the lipid/protein ratio and a 76.6% decrease in lipid peroxidation. Furthermore, we detected a 3.42% increase in the chain length of the aliphatic lipids, a higher content of RNA, and a lower amount of glycogen indicating relatively lower metabolic activity in the DR5-AS knockdown HeLa cells. Interestingly, we observed a similar gene expression pattern under cisplatin treatment and DR5-AS knockdown HeLa cells. Conclusion: These results suggest that DR5-AS lncRNA appears to account for a fraction of cisplatin-mediated macromolecular and metabolic changes in HeLa cervix cancer cells.Article Citation Count: 3Small RNA data set that includes tRNA-derived fragments from Jurkat cells treated with camptothecin(Elsevier Science Bv, 2018) Cosacak, Mehmet Ilyas; Erdogan, Ipek; Nalbant, Ayten; Akgul, Bunyamin; Akgül, BünyaminIn this article, we report a small RNA data set obtained from human T cell acute leukemia Jurkat cells, which were treated with the universal apoptotic agent camptothecin. Based on the Annexin-V labeling pattern, we sorted two Jurkat subpopulations in treated cells: one that is sensitive to the drug and the other being relatively more resistant. We report new original data that include the frequency of tRNA-derived fragments (tRF) in drug-sensitive and resistant cells. We also present partially analyzed data to show the origin of reads on tRNAs as well as the borders of the fragments. We believe that this data can benefit the science community working in the field of tRF and/or apoptosis. (C) 2018 The Authors. Published by Elsevier Inc.Review Citation Count: 5Long Noncoding RNAs in Human Cancer and Apoptosis(Bentham Science Publ Ltd, 2023) Erdogan, Ipek; Sweef, Osama; Akgul, Bunyamin; Akgül, BünyaminGenome annotations have uncovered the production of at least one transcript from nearly all loci in the genome at some given time throughout the development. Surprisingly, many of these transcripts do not code for proteins and are relatively long in size, thus called long noncoding RNAs (lncRNAs). Next- and third-generation sequencing technologies have amassed numerous lncRNAs expressed under different phenotypic conditions, yet many remain to be functionally characterized. LncRNAs regulate gene expression by functioning as scaffold, decoy, signaling, and guide molecules both at the transcriptional and post-transcriptional levels, interacting with different types of macromolecules, such as proteins, DNA, and RNA. Here, we review the potential regulatory role of lncRNAs in apoptosis and cancer as some of these lncRNAs may have the diagnostic and therapeutic potential in cancer.Review Citation Count: 1Noncoding RNAs: A New Layer of Functional RNAs(Bentham Science Publ Ltd, 2023) Gurer, Dilek Cansu; Akgul, Bunyamin; Akgül, BünyaminThe conventional central dogma of molecular biology dictates that the genetic information contained within deoxyribonucleic acid (DNA) is passed onto messenger ribonucleic acids (mRNAs), which are then used as templates to synthesize proteins. Although these types of protein-coding genes have been historically prioritized in typical phenotype-genotype studies with a parallel disregard to the rest of the genome, the completion of genome projects has unveiled a surprising layer of genetic information that can play critical roles in cellular processes without coding for proteins. These types of genes are called noncoding genes as they do not code for proteins. Noncoding genes come in different sizes and shapes, and they are just as versatile in carrying out cellular biochemical processes as proteins. In this review, we cover a comprehensive review of housekeeping and regulatory noncoding genes and their mode of action.Article Citation Count: 3Regulation of mRNA stability through a pentobarbital-responsive element(Elsevier Science inc, 2007) Akgul, Bunyamin; Tu, Chen-Pei D.; Akgül, BünyaminPentobarbital, a general anesthetic and non-genotoxic carcinogen, can induce gene expression by activating transcription. In the Drosophila glutathione S-transferase D21 (gstD21) gene, pentobarbital's regulatory influence extends to the level of mRNA turnover. Transcribed from an intronless gene, gstD21 mRNA is intrinsically very labile. But exposure to pentobarbital renders it stabilized beyond what can be attributed to transcriptional activation. We aim here to identify cis-acting element(s) of gstD21 mRNA as contributors to the molecule's pentobarbital-mediated stabilization. In the context of hsp70 5'UTR and the 3'UTR of act5C, gstD21 mRNA, minus its native UTRs, is stable. Maintaining the same context of heterologous UTRs, we can reconstitute using the full-length gstD21 sequence the inherent instability of gstD21 mRNA and its stabilization by pentobarbital. Transgenic flies that express these chimeric gstD21 mRNA exhibit decay intermediates lacking 3'UTR, which are not stabilized by PB treatment. The 3'UTR sequence, when inserted downstream from a reporter transcript, stabilizes it 1.6-fold under PB treatment. The analysis of the decay intermediates suggests a polysome-associated decay pattern. We propose a regulatory model that features a 59-nucleotide pentobarbital-responsive element (PBRE) in the 3'UTR of gstD21 mRNA. (c) 2006 Elsevier Inc. All rights reserved.Article Citation Count: 0Development of AB3-Type Novel Phthalocyanine and Porphyrin Photosensitizers Conjugated with Triphenylphosphonium for Higher Photodynamic Efficacy(Amer Chemical Soc, 2022) Onal, Emel; Tuncel, Ozge; Vatansever, Ipek Erdogan; Albakour, Mohamad; Celik, Gizem Gumusgoz; Kucuk, Tugba; Ozcelik, SerdarThere are a number of lipophilic cations that can be chosen; the triphenylphosphonium (TPP) ion is particularly unique for mitochondrion targeting, mainly due to its simplicity in structure and ease to be linked to the target molecules. In this work, mitochondrion-targeted AB3-type novel phthalocyanine and porphyrin photosensitizers (PSs) were synthesized and their photophysical photochemical properties were defined. Fluores-cence quantum yields (phi F) are 0.009, 0.14, 0.13, and 0.13, and the singlet-oxygen quantum yields (phi Delta) are 0.27, 0.75, 0.57, and 0.58 for LuPcPox(OAc), AB3TPP-Pc, AB3TPP-Por-C4, and AB3TPP-Por-C6, respectively. To evaluate the photodynamic efficacy of the TPP-conjugated PS cell viabilities of A549 and BEAS-2B lung cells were comparatively measured and IC-50 values were determined. AB3TPP-Por-C4, AB3TPP-Por-C6, and AB3TPP-Pc compounds compared to the reference molecules ZnPc and H2TPP were found to be highly cytotoxic (sub-micromolar concentration) under the light. LuPcPox(OAc) is the most effective molecule regarding cell killing (the activity). The cell killing of the TPP-conjugated porphyrin derivatives exhibits a similar response compared to LuPcPox(OAc) when the light absorbing factor of the PS is normalized at 660 nm: TPP-conjugated porphyrins absorb less light (lower extinction coefficient) but produce more radical species (higher singlet-oxygen quantum yield) and therefore effectively kill the cells. The singlet oxygen-producing capacity of AB3TPP-Pc is almost 3 times higher compared to LuPcPox(OAc) and 50% more efficient with respect to ZnPc, suggesting that TPP-conjugated phthalocyanine may serve as a good photosensitizer for photodynamic therapy (PDT). The high singlet oxygen generation capacity of these novel TPP-conjugated porphyrin and phthalocyanine PS suggests that they might be useful for PDT requiring lower photosensitizer concentration and reduced energy deposited through less light exposure.Article Citation Count: 10Garlic Accelerates Red Blood Cell Turnover and Splenic Erythropoietic Gene Expression in Mice: Evidence for Erythropoietin-Independent Erythropoiesis(Public Library Science, 2010) Akgul, Bunyamin; Lin, Kai-Wei; Yang, Hui-Mei Ou; Chen, Yen-Hui; Lu, Tzu-Huan; Chen, Chien-Hsiun; Tu, Chen-Pei D.; Akgül, BünyaminGarlic (Allium sativum) has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic's other physiological effects.Article Citation Count: 15Aggregatibacter actinomycetemcomitans GroEL Protein Promotes Conversion of Human CD4+T Cells into IFNγ IL10 Producing Tbet+Th1 Cells(Public Library Science, 2012) Saygili, Tahsin; Akincilar, Semih Can; Akgul, Bunyamin; Nalbant, Ayten; Akgül, BünyaminOne of the heat shock family protein (Hsp) expressing bacteria is the gram negative, periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa). A. actinomycetemcomitans' Hsp is a 64-kDa GroEL-protein, which has been shown to influence the host cells. In this study we used recombinant A. actinomycetemcomitans GroEL (rAaGroEL) protein as a model antigen to study GroEL-mediated T cell immune response. Human peripheral mononuclear cells (PBMCs), when stimulated with recombinant rAaGroEL, expressed early activation marker CD69 and IL-2R (CD25). CD25 and CD69 expressions were higher in CD4+ T cells compared to CD8+ T cells. rAaGroEL-responding CD4+ T cells expressed IL-10, IFN gamma and TNF alpha cytokines. Interestingly, there were also IL-10 and IFN gamma double cytokine producing CD4+ T cells. Additionally, IFN gamma expressing CD4+ T cells were also T-bet positive. Altogether the results suggest that rAaGroEL protein affects CD4+ T cells to differentiate into IFN gamma IL10-secreting T-bet+ Th1 cells.Article Citation Count: 0Evaluation of Blood Pressure Status and Mortality in Turkey: Findings from Chronic Diseases and Risk Factors Cohort Study(Multidisciplinary Digital Publishing Institute (MDPI), 2023) Sozmen,K.; Ergor,G.; Sakarya,S.; Dinc Horasan,G.; Sahan,C.; Ekinci,B.; Unal,B.Background and objectives: An important Non-Communicable Disease risk factor, hypertension (HT), is highly prevalent and controlled HT rates are not sufficient which increases the risk of developing premature deaths. The purpose of the study is to evaluate differences in all-cause and cardiovascular-related mortality according to HT status by using national data from Chronic Diseases and Risk Factors Survey in Turkey (2011–2017). Materials and Methods: Cox regression models were used to estimate hazard ratios (HR) for predicting the all-cause and cardiovascular system-related mortalities. Median follow-up period was 6.2 years. Results: Among individuals with HT, 41.8% was untreated, 30.1% received treatment and had controlled blood pressure, and 28.1% were under treatment but had uncontrolled BP levels. The hazard for mortality among treated & uncontrolled hypertensive participants was significantly higher for all-cause (HR = 1.32, 95% CI = 1.06–1.65), cardiovascular (HR = 2.11, 95% CI = 1.46–3.06), heart disease (HR = 2.24, 95% CI = 1.46–3.43), and Coronary Heart Disease mortality (HR = 2.66, 95% CI = 1.56–4.53) compared to normotensive participants. Conclusions: Individuals with HT who were treated but do not have controlled blood pressure in Turkey had a significantly increased risk of Cardiovascular Disease and all-cause mortality. Along with studies investigating the causes of uncontrolled blood pressure despite initiation of treatment, support should be provided to patients in cases of non-adherence to antihypertensive medication or life change recommendations. © 2023 by the authors.
