TR-Dizin İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/396

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Citation - WoS: 1
Citation - Scopus: 2
Complementary Medicines Used in Ulcerative Colitis and Unintended Interactions With Cytochrome P450-Dependent Drug-Metabolizing Enzymes
(Tubitak Scientific & Technological Research Council Turkey, 2022) Sen, Alaattin
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease with multiple genetic and a variety of environmental risk factors. Although current drugs significantly aid in controlling the disease, many people have led to the application of complementary therapies due to the common belief that they are natural and safe, as well as due to the consideration of the side effect of current drugs. Curcumin, cannabinoids, wheatgrass, Boswellia, wormwood and Aloe vera are among the most commonly used complementary medicines in UC. However, these treatments may have adverse and toxic effects due to unintended interactions with drugs or drug-metabolizing enzymes such as cytochrome P450s; thus, being ignorant of these interactions might cause deleterious effects with severe consequences. In addition, the lack of complete and controlled long-term studies with the use of these complementary medicines regarding drug metabolism pose additional risk and unsafety. Thus, this review aims to give an overview of the potential interactions of drug-metabolizing enzymes with the complementary botanical medicines used in UC, drawing attention to possible adverse effects.
Enlightening the Molecular Mechanisms of Type 2 Diabetes With a Novel Pathway Clustering and Pathway Subnetwork Approach
(Tubitak Scientific & Technological Research Council Turkey, 2022) Bakir-Gungor, Burcu; Yazici, Miray Unlu; Goy, Gokhan; Temiz, Mustafa
Type 2 diabetes mellitus (T2D) constitutes 90% of the diabetes cases, and it is a complex multifactorial disease. In the last decade, genome-wide association studies (GWASs) for T2D successfully pinpointed the genetic variants (typically single nucleotide polymorphisms, SNPs) that associate with disease risk. In order to diminish the burden of multiple testing in GWAS, researchers attempted to evaluate the collective effects of interesting variants. In this regard, pathway-based analyses of GWAS became popular to discover novel multigenic functional associations. Still, to reveal the unaccounted 85 to 90% of T2D variation, which lies hidden in GWAS datasets, new post-GWAS strategies need to be developed. In this respect, here we reanalyze three metaanalysis data of GWAS in T2D, using the methodology that we have developed to identify disease-associated pathways by combining nominally significant evidence of genetic association with the known biochemical pathways, protein-protein interaction (PPI) networks, and the functional information of selected SNPs. In this research effort, to enlighten the molecular mechanisms underlying T2D development and progress, we integrated different in silico approaches that proceed in top-down manner and bottom-up manner, and presented a comprehensive analysis at protein subnetwork, pathway, and pathway subnetwork levels. Using the mutual information based on the shared genes, the identified protein subnetworks and the affected pathways of each dataset were compared. While most of the identified pathways recapitulate the pathophysiology of T2D, our results show that incorporating SNP functional properties, PPI networks into GWAS can dissect leading molecular pathways, and it could offer improvement over traditional enrichment strategies.
Citation - WoS: 3
Citation - Scopus: 3
MicroRNA Prediction Based on 3D Graphical Representation of RNA Secondary Structures
(Tubitak Scientific & Technological Research Council Turkey, 2019) Sacar Demirci, Muserref Duygu
MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. While a miRNA can target hundreds of messenger RNA (mRNAs), an mRNA can be targeted by different miRNAs, not to mention that a single miRNA might have various binding sites in an mRNA sequence. Therefore, it is quite involved to investigate miRNAs experimentally. Thus, machine learning (ML) is frequently used to overcome such challenges. The key parts of a ML analysis largely depend on the quality of input data and the capacity of the features describing the data. Previously, more than 1000 features were suggested for miRNAs. Here, it is shown that using 36 features representing the RNA secondary structure and its dynamic 3D graphical representation provides up to 98% accuracy values. In this study, a new approach for ML-based miRNA prediction is proposed. Thousands of models are generated through classification of known human miRNAs and pseudohairpins with 3 classifiers: decision tree, naive Bayes, and random forest. Although the method is based on human data, the best model was able to correctly assign 96% of nonhuman hairpins from MirGeneDB, suggesting that this approach might be useful for the analysis of miRNAs from other species.
Citation - WoS: 1
Citation - Scopus: 1
RPI-1 (Human DCDC2) Displays Functional Redundancy With Nephronophthisis 4 in Regulating Cilia Biogenesis in C. Elegans
(Tubitak Scientific & Technological Research Council Turkey, 2023) Kaplan, Oktay I.
Projecting from most cell surfaces, cilia serve as important hubs for sensory and signaling processes and have been linked to a variety of human disorders, including Bardet-Biedl Syndrome (BBS), Meckel-Gruber Syndrome (MKS), Nephronophthisis (NPHP), and Joubert Syndrome, and these diseases are collectively known as a ciliopathy. DCDC2 is a ciliopathy protein that localizes to cilia; nevertheless, our understanding of the role of DCDC2 in cilia is still limited. We employed C. elegans to investigate the function of C. elegans RPI-1, a Caenorhabditis elegans ortholog of human DCDC2, in cilia and found that C. elegans RPI-1 localizes to the entire ciliary axoneme, but is not present in the transition zone and basal body. We generated a null mutant of C. elegans rpi-1, and our analysis with a range of fluorescence-based ciliary markers revealed that DCDC2 and nephronophthisis 4 (NPHP-4/NPHP4) display functional redundant roles in regulating cilia length and cilia positions. Taken together, our analysis discovered a novel genetic interaction between two ciliopathy disease genes (RPI-1/DCDC2 and NPHP-4/NPHP4) in C. elegans.
Citation - WoS: 6
Citation - Scopus: 6
Sex Effect on the Correlation of Immunoglobulin G Glycosylation With Rheumatoid Arthritis Disease Activity
(Tubitak Scientific & Technological Research Council Turkey, 2020) Ercan, Altan
Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects females more than males with a presence of autoantibodies. Immunoglobulin G (IgG) produced by adaptive arm has 2 functional domains, Fc and Fab. The Fc domain binds Fc gamma receptors and C1q proteins of the innate arm. Therefore, the IgG Fc domain serves as a bridge between the innate and adaptive arms and is regulated by an evolutionarily conserved N-glycosylation with variable structures. These glycans are classified as agalactosylated G0, monogalactosylated G1, and digalactosylated G2, which are further modified by core-fucosylation (F) and bisecting N-acetylglucosamine (B) moieties such as G0F and G0FB. Interestingly, proinflammatory G0F is shown to be regulated by estrogen in vivo. Here, it is hypothesized that the regulation of G0F by estrogen contributes to sex dichotomy in RA by setting up the level of IgG-dependent inflammation and therefore, RA disease activity (Das28-CRP3). To investigate this hypothesis, IgG glycosylation was characterized in serum samples from active RA patients (n = 232) and healthy controls (n = 232) by serum N-glycan analysis using the high performance liquid chromatography. According to the results, the IgG Fc glycan phenotype originates predominantly from the structure of G0F, and both G0F and G0FB correlate with Das28-CRP3 in females, but not in males. In conclusion, IgG G0F-dependent inflammation differs in males and females, and these differences point to the differential regulation of inflammation by sex hormone estrogen via IgG glycosylation.
Theoretical Investigation of Steric Effects on the S1 Potential Energy Surface of O-Carborane Derivatives
(Tubitak Scientific & Technological Research Council Turkey, 2023) Alkan, Fahri
TDDFT scan calculations were performed for s-carborane-anthracene derivatives (o-CB-X-Ant where X=-H,-CH3,-C2H5 and tert-butyl or-tBu) in order to understand the interplay between the steric effects, S1 potential energy surface (PES) and photophysical properties. The results show that all systems exhibit three local minima on the S1 PES, which correspond to the emissive LE and TICT state, along with the nonemissive CT state respectively. In the case of the unsubstituted system (o-CB-H-Ant), and-CH3 and-C2H5 substituted cases, S1 PES is predicted to be quite flat for certain conformations indicating that it is possible for these systems to reach the nonemissive CT state without a large energy penalty. In comparison, conformational pathways for the nonemissive CT state are predicted to be energetically unfavorable for o-CB-tBu-Ant as a result of both steric and electronic effects. These results provide a mechanism for the enhanced emission of cr-CB-fluorophore molecules with bulky ligands.

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