PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 8The Effects of Halofuginone on Wound Healing in the Rat Nasal Mucosa(Sage Publications Inc, 2020) Ceylan, Seyit Mehmet; Uysal, Erdal; Sokucu, Mehmet; Sezgin, Efe; Kanmaz, Mahmut Alper; Yurtseven, Duygu Gok; Bilal, NagihanBackground Halofuginone is an alkaloid febrifugine analogue and bioactive molecule that was isolated incidentally from the Dichroa febrifuga plant. The therapeutic efficacy of halofuginone in parasitic infections, scleroderma, inflammation, and fibrosis-related diseases, as well as in some types of cancer, has been previously reported. The effects of halofuginone on nasal mucosal damage are not yet known. Objective The aim of this study was to investigate the potential effect of topically applied halofuginone on wound healing in the mechanically injured nasal mucosa of rats. Methods A unilateral mucosal wound was created in the nasal cavity of 32 rats (aged 4 weeks) using the brushing technique. These rats were randomly divided into 4 groups. Although the control group did not receive an intervention, a dry pad, a saline-impregnated pad, or a pad impregnated with halofuginone were placed in the rats of the other 3 groups and left for 5 minutes. Rats were sacrificed on the 14th day, and a histological examination was performed. The nasal mucosa was assessed via hematoxylin-eosin and Masson's trichrome staining. Results There were no statistically significant differences in epithelial thickness, inflammation, goblet cell formation, and epithelial disarray values between the halofuginone group and the control group (P > .05). The subepithelial thickness was significantly decreased in the saline-treated group and the halofuginone-treated group (P < .05), but a significantly lower level of subepithelial fibrosis was only observed in the halofuginone group compared to the other groups (P < .05). Conclusions Topical halofuginone administration reduces the development of fibrosis and subepithelial edema after experimentally induced nasal mucosal injury, but it does not exert therapeutic or preventive effects on epithelial damage, inflammation, and goblet cell hyperplasia.Article Citation - WoS: 1Citation - Scopus: 1A Pragmatic Grouping Model for Bone-Only De Novo Metastatic Breast Cancer (MetS Protocol MF22-03)(MDPI, 2025) Goktepe, Berk; Demirors, Berkay; Senol, Kazim; Ozbas, Serdar; Sezgin, Efe; Lucci, Anthony; Soran, AtillaDe novo metastatic breast cancer (dnMBC) accounts for 3-10% of newly diagnosed cases, with 20-40% presenting as a bone-only metastatic disease, which can achieve survival outcomes exceeding 10 years with multimodal therapy. However, the role of multimodal therapy remains controversial in the guidelines. Objective: This study aims to identify dnBOMBC subgroups to develop a pragmatic staging system for guiding locoregional therapy decisions. Materials and Methods: Data from the MF07-01 phase III randomized trial (2021, median follow-up time (mFT): 40 months (range 1-131)) and the BOMET prospective multi-institutional registry trial (2021, mFT: 34 months (range 25-45)) were combined for analysis, including only patients who presented with bone-only metastases. Exclusion criteria were patients under 18 and those with a history of prior cancer or cancer metastases. Patients with missing data and positive surgical margins were excluded. Out of 770 patients, 589 were included. Survival analyses were first conducted according to molecular subgroups, after which patients were further stratified by hormone receptor status, human epidermal human epidermal growth factor receptor 2 (HER2) status, tumor grade, and clinical T (cT) stage. Group A (GrA) included hormone receptor (HR)-positive, low- or intermediate-grade tumors at any cT; HR-positive, high-grade tumors with cT0-3; or any HER2-positive tumors. Group B (GrB) included HR-positive, high-grade tumors with cT4 disease or any triple-negative (TN) tumors. Results: The hazard of death (HoD) was 43% lower in GrA than in GrB. Median OS was 65 months (39-104) for GrA patients and 44 months (28-72) for GrB patients (HR 0.57, 95% CI 0.41-0.78, p = 0.0003). Primary tumor surgery (PTS) significantly improved OS in GrA patients, regardless of the number of metastases (solitary: HR, 0.375, 95% CI 0.259-0.543, p < 0.001; multiple: HR 0.435, 95% CI 0.334-0.615, p < 0.001). Conversely, GrB patients did not experience a significant benefit from PTS. Conclusions: This study demonstrates that GrA patients have better OS than GrB patients, and PTS reduces the HoD in GrA patients compared to systemic therapy alone. These findings support using a modified staging system in dnBOBMC to identify patients who may benefit from multimodal therapy including PTS.Article Plasma Proteomic Markers of Interleukin-1β Pathway Associated With Incident Age-Related Macular Degeneration in Persons With Aids(Elsevier, 2025) Hunt, Peter W.; Olshen, Adam B.; Murad, Natalia; Ambayec, Gabrielle C.; Sezgin, Efe; Schneider, Michael F.; Jabs, Douglas A.Objective To evaluate the associations of plasma inflammatory proteins with age-related macular degeneration (AMD) in persons with the AIDS, using a discovery-based proteomics approach. Design A nested case-control study (analysis 1) and nested cohort study (analysis 2). Participants Persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications with AIDS (LSOCA). Methods Cryopreserved plasma specimens obtained at baseline were assayed for inflammatory proteins using the Olink Inflammation Explore Panel 1. In analysis 1, baseline proteomic profiles for 26 persons with AIDS and incident intermediate-stage AMD 5 to 10 years after baseline and 49 matched controls (matched for age, biologic sex, race/ethnicity, and follow-up) without AMD were compared. In analysis 2, 475 persons from LSOCA with baseline plasma inflammatory proteomic profile measurements were followed for incident cataract and mortality. Main Outcome Measures Incident intermediate-stage AMD; incident cataract; and mortality. Results Of 365 measurable plasma inflammatory proteins, 118 (32%) were associated with incident intermediate-stage AMD at the false discovery rate-adjusted Q < 0.05 level after adjustment for smoking, CD4+ T count, and plasma human immunodeficiency virus RNA level. Gene ontology pathway enrichment analysis identified the interleukin (IL)-1 beta pathway and wound healing pathways, including tissue inhibitor of metalloproteinase 3, as significantly associated with incident AMD. These associations were qualitatively different from those associated with incident cataracts, where elevated levels of inflammatory proteins were associated with a decreased risk of cataracts. A much broader number of inflammatory pathways, including those related to the adaptive immune system, were associated with mortality. Conclusions Upregulation of the IL-1 beta pathway appears to be associated with an increased risk of incident AMD in persons with AIDS. Given the availability of inhibitors of this pathway, inhibition of the IL-1 beta pathway may provide a therapeutic avenue for treatment of AMD. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2025;5:100794 (c) 2025 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Article Citation - WoS: 1Citation - Scopus: 1Comparison of Magnetic Seed and Rfid Methods in the Localization of Non-Palpable Breast Lesions(Wolters Kluwer Medknow Publications, 2024) Sanli, Ahmet Necati; Sanli, Deniz E. Tekcan; Golshan, Mehra; Sezgin, Efe; Celik, Varol; Aydogan, FatihBackground: Many methods have been developed for localizing non-palpable breast lesions. This study investigated the success rate and surgical results of the magnetic seed (Magseed) and radiofrequency identification (RFID) method, which are relatively new compared to standard wire-guided localizations. Materials and Methods: 20 simulation (10 Magseed, 10 RFID) models were created using turkey breasts and raisins. Raisins containing magnetic seed and RFID tags were placed on the turkey breast. Sentimag (R) probe was used for the Magseed group, and Faxitron LOCalizer (TM) System device was used in the RFID group. Both methods were evaluated in terms of accuracy in detecting breast lesion localization, operation times, excised tissue weights, total resection volume, surgical margin negativity, and re-excision rates. Results: Lesion localization success in both techniques was 100%. While procedure times were statistically significantly shorter in the Magseed group, incision lengths were shorter in the RFID group (P = 0.013, P = 0.007, respectively). No statistically significant difference was found between the groups for the weight of the removed parts, total resection volume, and surgical margin distance (P > 0.05). Conclusion: In this feasibility study, it was concluded that neither the RFID nor Magseed methods had a significant advantage over each other, in terms of localization detection and surgical margin negativity, and both methods could be used successfully for localization.Article Citation - WoS: 1Citation - Scopus: 1Altitude Shapes Gut Microbiome Composition Accounting for Diet, Thyroid Hormone Levels, and Host Genetics in a Subterranean Blind Mole Rat(Frontiers Media Sa, 2024) Solak, Halil Mert; Kreisinger, Jakub; Cizkova, Dagmar; Sezgin, Efe; Schmiedova, Lucie; Murtskhvaladze, Marine; Yanchukov, AlexeyThe animal gut microbiome acts as a crucial link between the host and its environment, playing a vital role in digestion, metabolism, physiology, and fitness. Using 16S rRNA metabarcoding, we investigated the effect of altitude on the microbiome composition of Anatolian Blind Mole Rats (Nannospalax xanthodon) across six locations and three altitudinal groups. We also factored in the host diet, as well as host microsatellite genotypes and thyroid hormone levels. The altitude had a major effect on microbiome composition, with notable differences in the relative abundance of several bacterial taxa across elevations. Contrary to prior research, we found no significant difference in strictly anaerobic bacteria abundance among altitudinal groups, though facultatively anaerobic bacteria were more prevalent at higher altitudes. Microbiome alpha diversity peaked at mid-altitude, comprising elements from both low and high elevations. The beta diversity showed significant association with the altitude. Altitude had a significant effect on the diet composition but not on its alpha diversity. No distinct altitude-related genetic structure was evident among the host populations, and no correlation was revealed between the host genetic relatedness and microbiome composition nor between the host microbiome and the diet. Free thyroxine (FT4) levels increased almost linearly with the altitude but none of the bacterial ASVs were found to be specifically associated with hormone levels. Total thyroxine (TT4) levels correlated positively with microbiome diversity. Although we detected correlation between certain components of the thyroid hormone levels and the microbiome beta diversity, the pattern of their relationship remains inconclusive.Article Genetic Factors Associated With Age-Related Macular Degeneration Modulating Plasma Inflammatory Biomarker Levels in Patients With Aids(Taylor & Francis inc, 2024) Sezgin, Efe; Schneider, Michael F.; Hunt, Peter W.; Beck-Engeser, Gabriele; Ambayac, Gabriele C.; Jabs, Douglas A.IntroductionPatients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS.Materials and MethodsCryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C x 3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C x 3motif chemokine receptor 1 (CX3CR1).ResultsIn Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels.ConclusionsGenetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS.Article Mitotyping of Random Bred Cats and Pure Breed Cats (turkish Angora and Turkish Van) Using Non-Repetitive Mitochondrial Dna Control Region(Elsevier, 2024) Bilgen, Nuket; Guvendi, Mervenur; Sezgin, Efe; Can, Huseyin; Koseoglu, Ahmet Efe; Alak, Sedef Erkunt; Un, CemalThe Fertile Crescent appears to be the most plausible region where the domestication of cats commenced through a mutually beneficial relationship between wild cats and early agrarian societies. These domesticated cats then journeyed across the globe mirroring the paths of human migration. An examination of mitochondrial DNA (mtDNA) control region-based mitotyping suggested that a significant majority, exceeding 80%, of globally sampled random-bred and pure-bred cats could be categorized into 12 predominant mitotypes. However, the extent of mitotype diversity within random-bred cats from regions proximate to the Fertile Crescent remains inadequately explored. In light of this we aimed to investigate the mitotype diversity in random bred cats sampled from various regions across Turkey. Additionally, we sought to establish a comparison with the mito-type profiles of locally recognized pure breeds, namely the Turkish Angora and Turkish Van. To unravel their evolutionary narratives, we engaged in comprehensive population genetics analyses at both the individual and mitotype-based levels. Our study encompassed a sample size of 240 specimens, forming the basis for both mitotyping and population genetics scrutiny. Our analysis yielded the identification of nine 'universal' mitotypes (A-J), alongside an 'outlier' mitotype group I. Notably mitotypes A and D emerged as particularly prevalent in contrast to the lesser occurrence mitotypes C, G, and H. With the realm of random bred cats the structure of haplotypes exhibited remarkable diversity presenting distinctions from Turkish Angora and Van breeds. Nucleotide diversity was higher compared to previous reports from Turkey and was one of the highest among reported world cat population estimates. Intriguingly, our investigations did not unveil any pronounced instances of strong selection, population expansions or contractions within any specific population or mitotype. To conclude, our study represents a pioneering effort in uncovering the mitotype profiles and haplotype structures inherent to both random-bred and pure breed cats in Turkey. This endeavor not only broadens our understanding of the feline genetic landscape within the region but also lays the foundation for future inquiries into the evolutionary trajectories and genetic legacies of these feline populations.Article Citation - WoS: 6Citation - Scopus: 5Basidiomycota Species in Drosophila Gut Are Associated With Host Fat Metabolism(Nature Research, 2023) Bozkurt, Berkay; Terlemez, Gamze; Sezgin, EfeThe importance of bacterial microbiota on host metabolism and obesity risk is well documented. However, the role of fungal microbiota on host storage metabolite pools is largely unexplored. We aimed to investigate the role of microbiota on D. melanogaster fat metabolism, and examine interrelatedness between fungal and bacterial microbiota, and major metabolic pools. Fungal and bacterial microbiota profiles, fat, glycogen, and trehalose metabolic pools are measured in a context of genetic variation represented by whole genome sequenced inbred Drosophila Genetic Reference Panel (DGRP) samples. Increasing Basidiomycota, Acetobacter persici, Acetobacter pomorum, and Lactobacillus brevis levels correlated with decreasing triglyceride levels. Host genes and biological pathways, identified via genome-wide scans, associated with Basidiomycota and triglyceride levels were different suggesting the effect of Basidiomycota on fat metabolism is independent of host biological pathways that control fungal microbiota or host fat metabolism. Although triglyceride, glycogen and trehalose levels were highly correlated, microorganisms’ effect on triglyceride pool were independent of glycogen and trehalose levels. Multivariate analyses suggested positive interactions between Basidiomycota, A. persici, and L. brevis that collectively correlated negatively with fat and glycogen pools. In conclusion, fungal microbiota can be a major player in host fat metabolism. Interactions between fungal and bacterial microbiota may exert substantial control over host storage metabolite pools and influence obesity risk. © 2023, Springer Nature Limited.Article Citation - WoS: 6Citation - Scopus: 4Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared With Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms(Mary Ann Liebert, 2023) Soran, Atilla; Bengur, Fuat Barış; Rodriguez, Wendy; Chroneos, Maria Z.; Sezgin, EfeIntroduction: The reported incidences of breast cancer-related lymphedema (LE) affecting the arms vary greatly. Reason for this variability includes different diagnostic techniques used across studies. In the current study, we compared the accuracy of indocyanine green lymphography (ICG_L) and bioimpedance spectroscopy (BIS) in detecting LE before presentation of clinical signs.Methods and Results: Patients with no initial detectable signs of clinical LE of their arms after axillary lymph node dissection or removal of >5 lymph nodes on sentinel lymph node biopsy were included. Subclinical LE was defined as BIS values outside the normal range [(>= 7 units (or >10 units)] or a 7-unit (or 10 unit) change between two measurements. We tracked ICG_L and BIS measurements for 133 potentially affected arms (n = 123). ICG_L detected signs of lymphatic flow disruption in 63 arms (47%). Based on the BIS value of 7 units, 60 arms (45%) had values outside the normal range. When using ICG_L-identified LE cases as true positives, BIS had a 54% accuracy (area under the curve [AUC] = 0.54) in detecting LE. Accuracy was 61% for subclinical LE symptoms when compared with ICG_L (AUC = 0.62). Both BIS and subclinical LE symptoms had <0.70 AUC-receiver characteristic operator curve, suggesting that BIS and development of subclinical LE symptoms are not adequate for identifying patients with subclinical LE.Conclusion: ICG_L is a reliable diagnostic tool for detecting early signs of lymphatic flow disruption in subclinical LE. Utilizing ICG_L to diagnose subclinical LE followed by a personalized treatment plan may provide patients the best chance of preventing disease progression.Article Citation - WoS: 11Citation - Scopus: 10Molecular Evolution and Population Genetics of Glutamate Decarboxylase Acid Resistance Pathway in Lactic Acid Bacteria(Frontiers Media S.A., 2023) Sezgin, Efe; Tekin, BurcuGlutamate decarboxylase (GAD) pathway (GDP) is a major acid resistance mechanism enabling microorganisms’ survival in low pH environments. We aimed to study the molecular evolution and population genetics of GDP in Lactic Acid Bacteria (LAB) to understand evolutionary processes shaping adaptation to acidic environments comparing species where the GDP genes are organized in an operon structure (Levilactobacillus brevis) versus lack of an operon structure (Lactiplantibacillus plantarum). Within species molecular population genetic analyses of GDP genes in L. brevis and L. plantarum sampled from diverse fermented food and other environments showed abundant synonymous and non-synonymous nucleotide diversity, mostly driven by low frequency changes, distributed throughout the coding regions for all genes in both species. GAD genes showed higher level of replacement polymorphism compared to transporter genes (gadC and YjeM) for both species, and GAD genes that are outside of an operon structure showed even higher level of replacement polymorphism. Population genetic tests suggest negative selection against replacement changes in all genes. Molecular structure and amino acid characteristics analyses showed that in none of the GDP genes replacement changes alter 3D structure or charge distribution supporting negative selection against non-conservative amino acid changes. Phylogenetic and between species divergence analyses suggested adaptive protein evolution on GDP genes comparing phylogenetically distant species, but conservative evolution comparing closely related species. GDP genes within an operon structure showed slower molecular evolution and higher conservation. All GAD and transporter genes showed high codon usage bias in examined LAB species suggesting high expression and utilization of acid resistance genes. Substantial discordances between species, GAD, and transporter gene tree topologies were observed suggesting molecular evolution of GDP genes do not follow speciation events. Distribution of operon structure on the species tree suggested multiple independent gain or loss of operon structure in LABs. In conclusion, GDP genes in LABs exhibit a dynamic molecular evolutionary history shaped by gene loss, gene transfer, negative and positive selection to maintain its active role in acid resistance mechanism, and enable organisms to thrive in acidic environments.