PubMed İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397

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High Carbohydrate Diet Decreases Microbial Diversity and Increases Il-1β Levels in Mice Colon
(Korean Society Food Science & Technology-kosfost, 2024) Ulutas, Mehmet Sefa; Aydin, Erkin; Cebeci, Aysun
Western diet is known to contribute to intestinal dysbiosis and the progression of inflammation. Although the Turkish diet has different macronutrient contents, the intestinal inflammatory disease incidences in T & uuml;rkiye are comparable to Western countries. Thus, we hypothesized that high carbohydrate diets also contribute to inflammation of the colon. We compared diets with different macronutrient compositions and investigated their effects on colonic microbiota, cytokine, histology, and tight junction protein levels. High carbohydrate diet caused the lowest microbial diversity and is accompanied by the highest expression of interleukin-1 beta and claudin-1. A low carbohydrate diet with zero fiber resulted in the lowest inflammatory markers as well as the lowest occludin and claudin levels. Overall, our results indicate that carbohydrate and fiber contents of the diets are important contributors to colon health.
Citation - WoS: 8
Citation - Scopus: 8
Involvement of Sphingolipid Metabolism Enzymes in Resveratrol-Mediated Cytotoxicity in Philadelphia-Positive Acute Lymphoblastic Leukemia
(Routledge Journals, Taylor & Francis Ltd, 2022) Oguz, Osman; Adan, Aysun
Targeting the key enzymes of sphingolipid metabolism including serine palmitoyltransferase (SPT), sphingosine kinase (SK) and glucosylceramide synthase (GCS) has a therapeutic importance. However, sphingolipid metabolism-mediated anti-leukemic actions of resveratrol in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Therefore, we explored potential mechanisms behind resveratrol-mediated cytotoxicity in SD1 and SUP-B15 Ph + ALL cells in the context of sphingolipid metabolism and apoptosis induction. The anti-proliferative and apoptotic effects of resveratrol alone and in combination with SPT inhibitor (myriocin), SK inhibitor (SKI II), GCS inhibitor (PDMP) were determined by MTT cell proliferation assay and flow cytometry, respectively. The effects of resveratrol on PARP cleavage, SPT, SK and GCS protein levels were investigated by Western blot. Resveratrol inhibited proliferation and triggered apoptosis via PARP activation and externalization of phosphatidylserine (PS). Resveratrol increased the expression of SPT whereas it downregulated SK and GCS. Resveratrol's combinations with SKI II and PDMP intensified its anti-leukemic activity by increasing the relocalization of PS while its combination with myriocin suppressed apoptosis. Therefore, resveratrol inhibited cell proliferation and induced apoptosis through modulating SK, GCS and SPT expression, which may be considered as novel biomarkers of resveratrol-induced cytotoxicity in Ph + ALL.
Effect of Yttrium/Lanthanum-Doped Ultrasonically Assisted Nano-Hydroxyapatite on Remineralization and Bracket Bond Strength in Artificial Enamel Lesions
(BMC, 2025) Ozturk, Taner; Mammadov, Elshan; Bulduk Karakaya, Humeyra; Yagci, Filiz; Dayan, Serkan; Yagci, Ahmet
Background This in vitro study aimed to evaluate the remineralization efficacy of ultrasonically assisted yttrium fluoride-doped (Ult-YF3-nHAP) and lanthanum fluoride-doped (Ult-LaF3-nHAP) nano-hydroxyapatite (nHAP) on artificially induced enamel lesions (aWSLs), and to compare their performance with acidulated phosphate fluoride (APF) gel, fluoride varnish, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and resin infiltrant (ICON). Methods This in vitro study followed a four-phase design: enamel lesion creation, application of remineralization agents, a 14-day treatment protocol, and post-treatment analyses using QLF, Micro-CT, SEM-EDX, and SBS testing. This study included 168 extracted human premolars, divided into eight experimental groups (n = 21 per group): (1) Demineralized control (no remineralization treatment), (2) Acidulated phosphate fluoride (APF) gel, (3) Fluoride varnish, (4) Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), (5) Ultrasonically assisted nHAP (Control nHAP), (6) Ult-YF3-nHAP, (7) Ult-LaF3-nHAP, and (8) Resin infiltrant (ICON). The aWSLs were created under laboratory conditions. Brackets were bonded to the teeth with composite material, and aWSLs were created under laboratory conditions. After lesion formation and at the end of the experimental process, micro-computed tomography (Micro-CT) and laser-assisted quantitative light fluorescence (QLF) analysis were performed to assess lesion progression and remineralization. Additionally, scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and shear bond strength (SBS) tests were conducted at the end of the study. Statistical analysis was performed using one-way ANOVA, Kruskal-Wallis, and Mann-Whitney U tests, with a significance level of p < 0.05. Results The bracket bond strength test data showed no significant differences between the groups (p = 0.156). Significant differences were found among groups for QLF fluorescence recovery (Delta F, p < 0.001), with the Ult-YF3-nHAP group showing the greatest increase (median: +0.5, IQR: -1.4 to + 0.7), while the control group showed the greatest decrease (median: -12.1, IQR: -12.4 to -10.2). Micro-CT analysis also revealed significant differences between groups (p = 0.008). The APF Gel group showed values comparable to those of all other experimental groups. The highest remineralization values were recorded in the Ult-YF3-nHAP group (6.87 +/- 3.03 mm(3)), whereas the lowest values were found in the Varnish group. The demineralized control group had significantly higher values than the Varnish group, but lower than the Ult-LaF3-nHAP group. SEM-EDX analysis revealed that fluoride weight was significantly lower in the Tooth Mousse and Varnish groups compared to the other experimental groups (p < 0.001). Ca/P ratio was significantly lower in the demineralized control, Varnish, and Ult-YF3-nHAP groups than in other experimental groups (p = 0.002). Conclusion Ult-YF3-nHAP showed higher efficacy in remineralization of aWSLs compared to fluoride-based treatments, CPP-ACP, and resin infiltrant. The highest remineralization was detected in the Ult-YF3-nHAP group by micro-CT and QLF analysis, while fluoride varnish gave the lowest result.
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.
Citation - WoS: 35
Citation - Scopus: 39
Advances in Micelle-Based Drug Delivery: Cross-Linked Systems
(Bentham Science Publ Ltd, 2017) Isoglu, Ismail Alper; Ozsoy, Yildiz; Isoglu, Sevil Dincer
There are several barriers that drug molecules encounter in body beginning from kidney filtration and reticulo-endothelial system (RES) clearance to cellular trafficking. Multifunctional nanocarriers have a great potential for the delivery of drugs by enhancing therapeutic activity of existing methodologies. A variety of nanocarriers are constructed by different material types, which have unique physicochemical properties for drug delivery applications. Micelles formed by amphiphilic polymers are one of the most important drug/nanocarrier formulation products, in which the core part is suitable for encapsulation of hydrophobic agent whereas the outer shell can be utilized for targeting the drug to the disease area. Micelles as self-assembled nanostructures may encounter difficulties in biodistribution of encapsulated drugs because they have a tendency to be dissociated in dilution or high ionic strength. Therefore, therapeutic efficiency is decreased and it requires high amount of drug to be administered to achieve more efficient result. To overcome this problem, covalently stabilized structures produced by cross-linking in core or shell part, which can prevent the micelle dissociation and regulate drug release, have been proposed. These systems can be designed as responsive systems in which cross-links are degradable or hydrolysable under specific conditions such as low pH or reductive environment. These are enhancing characteristics in drug delivery because their cleavage allows the release of bioactive agent encapsulated in the carrier at a certain site or time. This review describes the chemical methodologies for the preparation of cross-linked micelles, and reports an update of latest studies in literature.
Citation - WoS: 1
Citation - Scopus: 1
ConVarT: Search Engine for Missense Variants Between Humans and Other Organisms
(Wiley, 2022) Pir, Mustafa S.; Cevik, Sebiha; Kaplan, Oktay I.
ConVarT (https://convart.org/) is a search engine for searching for conjugate variants between humans and other species. The search engine is based on matching conjugate variants called MatchVars between species. Matching equivalent variants requires correct alignment of orthologous proteins with the use of multiple sequence alignments (MSA). Indeed, the ConVarT pipeline has performed over a million MSAs and integrated variants and variant-specific annotations (pathogenicity, phenotypic variants; etc.) into the corresponding positions on MSAs. When a clinically relevant variant is discovered whose functional relevance is unknown, ConVarT offers clinician scientists the possibility to search for a MatchVar in other species and to look for functional data on that variant. Fortunately, ConVarT enables users to paste a protein sequence in FASTA format to search for human orthologous proteins. A pairwise sequence alignment (PSA) is then performed between the provided protein sequence and the human orthologous protein, allowing users to visualize human variants on the PSA. Here, we describe the step-by-step usage of ConVarT.
Citation - WoS: 21
Citation - Scopus: 23
Photonic-Lantern Coherent LIDAR System
(Optical Soc Amer, 2015) Ozdur, Ibrahim; Toliver, Paul; Woodward, T. K.
In this work, a photonic-lantern-based coherent LIDAR system is experimentally demonstrated and the voltage signal-to-noise ratio improvement is analyzed. A voltage signal-to-noise ratio (SNRV) improvement of 2.8 is demonstrated experimentally for photonic-lantern-based coherent receivers relative to single-mode coherent receivers. The voltage signal-to-noise ratio improvement is obtained when other parameters are kept constant. We have also analyzed the effect of random optical power distribution among the single-mode fibers. We found that the distribution does not significantly impact the SNRV improvement. The mean value of voltage signal-to-noise ratio improvement is found to be similar to 2.4. (C) 2015 Optical Society of America
Citation - WoS: 31
Citation - Scopus: 33
Discovery of Adapalene and Dihydrotachysterol as Antiviral Agents for the Omicron Variant of SARS-CoV-2 Through Computational Drug Repurposing
(Springer, 2023) Fidan, Ozkan; Mujwar, Somdutt; Kciuk, Mateusz
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as "variant of concern" due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a significant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confirmed using MD simulations. The lead compounds were further evaluated for their potential use and side effects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2. [GRAPHICS] .
Citation - WoS: 18
Citation - Scopus: 20
Optimization Study on Surface Roughness and Tribological Behavior of Recycled Cast Iron Reinforced Bronze MMCs Produced by Hot Pressing
(MDPI, 2021) Gunes, Aydin; Sahin, Omer Sinan; Duzcukoglu, Hayrettin; Salur, Emin; Aslan, Abdullah; Kuntoglu, Mustafa; Pimenov, Danil Yurievich
Surface roughness reflects the quality of many operational parameters, namely service life, wear characteristics, working performance and tribological behavior of the produced part. Therefore, tribological performance is critical for the components used as tandem parts, especially for the MMCs (Metal Matrix Composites) which are a unique class of materials having extensive application areas such as aerospace, aeronautics, marine engineering and the defense industry. Current work covers the optimization study of production parameters for surface roughness and tribological indicators of newly produced cast iron reinforced bronze MMCs. In this context, two levels of temperature (400 and 450 degrees C), three levels of pressure (480, 640 and 820 MPa) and seven levels of reinforcement ratios (60/40, 70/30, 80/20, 90/10, 100/0 of GGG40/CuSn10, pure bronze-as received and pure cast iron-as received) are considered. According to the findings obtained by Taguchi's signal-to-noise ratios, the reinforcement ratio has a dominant effect on surface roughness parameters (Ra and Rz), the coefficient of friction and the weight loss in different levels. In addition, 100/0 reinforced GGG40/CuSn10 gives minimum surface roughness, pure cast iron provides the best weight loss and pure bronze offers the desired coefficient of friction. The results showed the importance of material ingredients on mechanical properties by comparing a wide range of samples from starting the production phase, which provides a perspective for manufacturers to meet the market supply as per human requirements.
Citation - WoS: 2
Citation - Scopus: 1
Computational Prediction of MicroRNAs in Histoplasma Capsulatum
(Academic Press Ltd- Elsevier Science Ltd, 2020) Demirci, Mueserref Duygu Sagar
MicroRNAs (miRNAs) are small and non-coding RNAs that regulate gene expression through post-transcriptional regulation. Although, the standard miRNA repository, MiRBase, lists more than 200 organisms having miRNA mediated regulation mechanism and thousands of miRNAs, there is not enough information about miRNAs of fungal species. Considering that there are various fungal pathogens causing disease phenotypes, it is important to search for miRNAs of those organisms. The leading cause of endemic mycosis in the USA is a fungal disease known as histoplasmosis, which is resulted by infection with a fungal intracellular parasite, Histoplasma capsulatum (H. capsulatum). In this work, genomes of H. capsulatum strains NAm1 and G217B were explored for potential miRNA like sequences and structures. Through a complex workflow involving miRNA detection and target prediction, several miRNA candidates of H. capsulatum and their possible targets in human were identified. The results presented here indicate that H. capsulatum might be one of the fungal pathogens having a miRNA based post-transcriptional gene regulation mechanism and it might have a miRNA mediated host - parasite interaction with human.
Citation - WoS: 33
Citation - Scopus: 40
Big Data Acquired by Internet of Things-Enabled Industrial Multichannel Wireless Sensors Networks for Active Monitoring and Control in the Smart Grid Industry 4.0
(Elsevier, 2021) Faheem, Muhammad; Fizza, Ghulam; Ashraf, Muhammad Waqar; Butt, Rizwan Aslam; Ngadi, Md. Asri; Gungor, Vehbi Cagri
Smart Grid Industry 4.0 (SGI4.0) defines a new paradigm to provide high-quality electricity at a low cost by reacting quickly and effectively to changing energy demands in the highly volatile global markets. However, in SGI4.0, the reliable and efficient gathering and transmission of the observed information from the Internet of Things (IoT)-enabled Cyberphysical systems, such as sensors located in remote places to the control center is the biggest challenge for the Industrial Multichannel Wireless Sensors Networks (IMWSNs). This is due to the harsh nature of the smart grid environment that causes high noise, signal fading, multipath effects, heat, and electromagnetic interference, which reduces the transmission quality and trigger errors in the IMWSNs. Thus, an efficient monitoring and real-time control of unexpected changes in the power generation and distribution processes is essential to guarantee the quality of service (QoS) re-quirements in the smart grid. In this context, this paper de-scribes the dataset contains measurements acquired by the IMWSNs during events monitoring and control in the smart grid. This work provides an updated detail comparison of our proposed work, including channel detection, channel assign-ment, and packets forwarding algorithms, collectively called CARP [1] with existing G-RPL [2] and EQSHC [3] schemes in the smart grid. The experimental outcomes show that the dataset and is useful for the design, development, testing, and validation of algorithms for real-time events monitoring and control applications in the smart grid. (C) 2021 The Authors. Published by Elsevier Inc.
A Potential Hemostatic Chitosan/Gelatin Cryogel Impregnated with Verbascum Thapsus Leaf Extract for Noncompressible Hemorrhage Management
(IOP Publishing Ltd, 2025) Uzuner, Hacernur; Yuruk, Adile; Isoglu, Ismail Alper
In this study, we prepared a series of chitosan/gelatin (CS/GEL) cryogels containing Verbascum thapsus (V. thapsus) leaf extract and identified a lead formulation for noncompressible hemorrhage (NCH). Cryogels with average pore diameters ranging from 225 to 478 mu m were fabricated through cryogelation at various CS/GEL ratios. C15 was chosen as the base scaffold due to its homogeneous pore distribution, with a pore size coefficient of variation (CV) of approximately 0.22. Extract loading was 1%, 5%, 10%, and 20% w/v. Functional porosity was reported by the relative accessible void index (RAVI). In PBS, the values relative to neat C15 were 1.00, 0.27, 0.20, 0.13, and 0.09 for concentrations of 0%, 1%, 5%, 10%, and 20% w/v, respectively. In citrated blood, the series was 1.00, 0.29, 0.12, 0.14, and 0.09. After loading, equilibrium swelling decreased and the compressive modulus increased, consistent with partial pore filling in a fixed network. The cryogels maintained an interconnected macroporous network and showed swelling from 300% to 3600% in blood and PBS. Antibacterial activity reached 89% inhibition, and cell viability remained above 80%. Hemolysis was low and within acceptance limits. Clotting improved in whole blood as the blood clotting index decreased from 11.9 to 6.5, and the clotting time was approximately 6 min. The 5% w/v group provided the optimal balance of clotting, antibacterial effects, and biocompatibility. This study presents a novel hemostatic CS/GEL cryogel containing V. thapsus leaf extract that holds strong potential for future applications in NCH management.
Neuroinflammatory Human Brain Organoids Enable Comprehensive Drug Screening Studies: Fingolimod and Its Analogues in Focus
(Bentham Science Publishing Ltd, 2026) Acar, Busra; Pepe, Nihan Aktas; Zivkovic, Aleksandra; Stark, Holger; Sen, Alaattin
Introduction The absence of physiologically relevant models for neuroinflammatory brain disorders, such as multiple sclerosis (MS), highlights the need for improved drug screening platforms. To bridge this gap, this study aimed to develop a human brain organoid (hBO) model incorporating essential neural cell types, including astrocytes, microglia, and oligodendrocytes.Methods hBOs were generated from H9 stem cells, and neuroinflammatory characteristics were elicited by lipopolysaccharide (LPS). The expression of specific neuronal and inflammatory markers was assessed through qRT-PCR, immunofluorescence staining (IFS), and ELISA.Results IFS of mature hBOs with anti-SOX2, anti-SATB2, anti-MAPT, anti-GFAP, anti-MBP, and anti-IBA1 antibodies and images collected with the confocal microscope confirmed the differentiation of H9 cells into cortical neurons, astrocytes, microglia, and oligodendrocyte cell types. Elevated GFAP, IBA1, NF-kappa B, and IL-6 levels, along with reduced CNPase expression with LPS treatment, were considered reflective of MS-like pathology and were used to test fingolimod and its derivatives. Fingolimod and all its derivatives, specifically ST-1505, decreased MAPT (2.1-fold in ELISA, 1.7-fold in IFS), GFAP (1.8-fold in IFS), TNF alpha (5.4-fold in qRT-PCR), and FABP (1.5-fold in ELISA) levels, and increased IL-10 (11-fold in qRT-PCR) and MBP (2.9-fold in IFS) levels.Discussion The present data collectively showed LPS to evoke neuroinflammation in the hBO model, while fingolimod and its derivatives, particularly ST-1505, exhibited significant anti-inflammatory and neuroprotective properties by counteracting these evoked changes in the hBO model.Conclusion The findings supported the applicability of brain organoids as a model system for drug screening studies for neuroinflammatory brain diseases.
Citation - Scopus: 1
The Impact of Knitted Linked Seams on Comfort and Friction Perception
(Taylor & Francis Ltd, 2024) Temel, Mevra; Scott, Eleanor; Cain, Rebecca; Johnson, Andrew A.
Friction from knitted clothing can cause discomfort and skin issues, underscoring the importance of tactile comfort for wearers. Seamless knitted garments are assumed to be comfortable to wear, yet there is little understanding of their tactile comfort in comparison to linked seams - the most common form of knitted garment. This novel study examines the influence of a garments knitted structural architecture on clothing comfort and wearability by investigating skin friction and tactile perception across ten body regions in both male and female participants, using two commonly utilised materials and seam designs: cotton and merino wool with plain and linked seams. The impact of seam design and regional factors on skin friction and tactile perception was analysed, revealing varying levels across tested body regions. Removing seams exposed a greater surface area to skin contact, leading to higher perceived friction levels. As such, structural elements in knitted garments enhance wearer comfort. Seamless knitwear manufacturing offers a more environmentally conscious option compared to traditional cut-and-sew processes. This study investigated the impact of knitted garment material and structure on wearer comfort by analysing skin friction and tactile perception across ten upper body regions. Removing seams increased garment-to-skin contact leading to wearer discomfort.
Citation - Scopus: 1
Image Processing Methodology for Patient-Specific Instrument Design
(Wiley, 2020) Mohammad Sadeghi, Majid; Kececi, Emin Faruk
Background Patient-specific instrumentation (PSI) improves accuracy of surgical operations. PSI needs software for preoperative planning and instrument design. In this study, we explain the methodology of developing a software tool for PSI guide design and preoperative planning in reverse shoulder arthroplasty (RSA). Methods Approaches used to prepare input data, transform them into meaningful features and use of those features to create special guide geometries are explained by describing different algorithms and libraries. Results The developed software is tested on three different patients' data. Preoperative planning is performed and guides designed by software and the patients' bones are manufactured and tested for RSA. The method of building a software is presented to do the preoperative planning and designing specific guides for each patient are shown to be properly functional. Conclusions This study proves processes in the development of the PSI software and the design of a specific guide for RSA.
Citation - WoS: 20
Citation - Scopus: 24
miRdisNET: Discovering MicroRNA Biomarkers That Are Associated With Diseases Utilizing Biological Knowledge-Based Machine Learning
(Frontiers Media S.A., 2023) Jabeer, Amhar; Temiz, Mustafa; Bakir-Gungor, Burcu; Yousef, Malik
During recent years, biological experiments and increasing evidence have shown that MicroRNAs play an important role in the diagnosis and treatment of human complex diseases. Therefore, to diagnose and treat human complex diseases, it is necessary to reveal the associations between a specific disease and related miRNAs. Although current computational models based on machine learning attempt to determine miRNA-disease associations, the accuracy of these models need to be improved, and candidate miRNA-disease relations need to be evaluated from a biological perspective. In this paper, we propose a computational model named miRdisNET to predict potential miRNA-disease associations. Specifically, miRdisNET requires two types of data, i.e., miRNA expression profiles and known disease-miRNA associations as input files. First, we generate subsets of specific diseases by applying the grouping component. These subsets contain miRNA expressions with class labels associated with each specific disease. Then, we assign an importance score to each group by using a machine learning method for classification. Finally, we apply a modeling component and obtain outputs. One of the most important outputs of miRdisNET is the performance of miRNA-disease prediction. Compared with the existing methods, miRdisNET obtained the highest AUC value of .9998. Another output of miRdisNET is a list of significant miRNAs for disease under study. The miRNAs identified by miRdisNET are validated via referring to the gold-standard databases which hold information on experimentally verified MicroRNA-disease associations. miRdisNET has been developed to predict candidate miRNAs for new diseases, where miRNA-disease relation is not yet known. In addition, miRdisNET presents candidate disease-disease associations based on shared miRNA knowledge. The miRdisNET tool and other supplementary files are publicly available at: .
Citation - WoS: 9
Citation - Scopus: 12
Orally Administered Docetaxel-Loaded Chitosan-Decorated Cationic PLGA Nanoparticles for Intestinal Tumors: Formulation, Comprehensive in Vitro Characterization, and Release Kinetics
(Beilstein-Institut, 2022) Unal, Sedat; Dogan, Osman; Aktas, Yesim
Intestinal cancers are the third most lethal cancers globally, beginning as polyps in the intestine and spreading with a severe meta-static tendency. Chemotherapeutic drugs used in the treatment of intestinal tumors are usually formulated for parenteral administra-tion due to poor solubility and bioavailability problems. Pharmaceutically, clinical failure due to a drug's wide biodistribution and non-selective toxicity is one of the major challenges of chemotherapy. In addition, parenteral drug administration in chronic diseases that require long-term drug use, such as intestinal tumors, is challenging in terms of patient compliance and poses a burden in terms of health economy. Especially in the field of chemotherapy research, oral chemotherapy is a subject that has been inten -sively researched in recent years, and developments in this field will provide serious breakthroughs both scientifically and socially. Development of orally applicable nanodrug formulations that can act against diseases seen in the distant region of the gastroin-testinal tract (GIT), such as intestinal tumor, brings with it a series of difficulties depending on the drug and/or GIT physiology. The aim of this study is to develop an oral nanoparticle drug delivery system loaded with docetaxel (DCX) as an anticancer drug, using poly(lactic-co-glycolic acid) (PLGA) as nanoparticle material, and modified with chitosan (CS) to gain mucoadhesive properties. In this context, an innovative nanoparticle formulation that can protect orally administered DCX from GIT conditions and deliver the drug to the intestinal tumoral region by accumulating in mucus has been designed. For this purpose, DCX-PLGA nanoparticles (NPs) and CS/DCX-PLGA NPs were prepared, and their in vitro characteristics were elucidated. Nanoparticles around 250-300 nm were obtained. DCX-PLGA NPs had positive surface charge with CS coating. The formulations have the potential to deliver the encapsulated drug to the bowel according to the in vitro release studies in three different simulated GIT fluids for approximately 72 h. Mucin interaction and penetration into the artificial mucus layer were also investigated in detail, and the mucoadhesive and mucus-penetration characteristics of the formulations were examined. Furthermore, in vitro release kinetic studies of the NPs were elucidated. DCX-PLGA NPs were found to be compatible with the Weibull model, and CS/DCX-PLGA NPs were found to be compatible with the Peppas-Sahlin model. Within the scope of in vitro cytotoxicity studies, the drug-loaded NPs showed signifi-cantly higher cytotoxicity than a DCX solution on the HT-29 colon cell line, and CS/DCX-PLGA showed the highest cytotoxicity (p < 0.05). According to the permeability studies on the Caco-2 cell line, the CS/DCX-PLGA formulation increased permeability by 383% compared to free DCX (p < 0.05). In the light of all results, CS/DCX-PLGA NPs can offer a promising and innovative ap-proach as an oral anticancer drug-loaded nanoformulation for intestinal tumors.
Citation - WoS: 8
Citation - Scopus: 8
Thermo-Responsive Complexes of c-Myc Antisense Oligonucleotide With Block Copolymer of Poly(OEGMA) and Quaternized Poly(4-Vinylpyridine)
(Wiley-VCH Verlag GmbH, 2017) Topuzogullari, Murat; Elalmis, Yeliz Basaran; Isoglu, Sevil Dincer
Solution behavior of thermo-responsive polymers and their complexes with biological macromolecules may be affected by environmental conditions, such as the concentration of macromolecular components, pH, ion concentration, etc. Therefore, a thermo-responsive polymer and its complexes should be characterized in detail to observe their responses against possible environments under physiological conditions before biological applications. To briefly indicate this important issue, thermo-responsive block copolymer of quaternized poly(4-vinylpyridine) and poly(oligoethyleneglycol methyl ether methacrylate) as a potential nonviral vector has been synthesized. Polyelectrolyte complexes of this copolymer with the antisense oligonucleotide of c-Myc oncogene are also thermo-responsive but, have lower LCST (lower critical solution temperature) values compared to individual copolymer. LCST values of complexes decrease with molar ratio of macromolecular components and presence of salt. Dilution of solutions also affects solution behavior of complexes and causes a significant decrease in size and an increase in LCST, which indicates possible effects of severe dilutions in the blood stream.
Citation - WoS: 13
Citation - Scopus: 14
A New Approach for Development of Vaccine Against Visceral Leishmaniasis: Lipophosphoglycan and Polyacrylic Acid Conjugates
(Wolters Kluwer Medknow Publications, 2017) Allahverdiyev, Adil M.; Koc, Rabia Cakir; Bagirova, Melahat; Elcicek, Serhat; Baydar, Serap Yesilkir; Oztel, Olga Nehir; Akdeste, Zeynep
Objective: To determine the antileishmanial vaccine effectiveness of lipophosphoglycan (LPG) and polyacrylic acids (PAA) conjugates on in vivo mice models. Methods: LPG molecule was isolated and purified from large-scale Leishmania donovani parasite culture. Protection efficacies of LPG alone, in combination with Freund's adjuvant, in a physical mixture and in conjugate (consisting of various LPG concentrations) with PAA, were comparatively determined by various techniques, such as cultivation with the micro-culture method, assessment of in vitro infection rates of peritoneal macrophages, determination of parasite load in liver with Leishman-Donovan Units, and detection of cytokine responses. Results: Obtained results demonstrated that the highest vaccine-mediated immune protection was provided by LPG-PAA conjugate due to all parameters investigated. According to the Leishman-Donovan Units results, the sharpest decline in parasite load was seen with a ratio of 81.17% when 35 mg LPG containing conjugate was applied. This value was 44.93% for the control group immunized only with LPG. Moreover, decreases in parasite load were 53.37%, 55.2% and 65.8% for the groups immunized with 10 mg LPG containing LPG-PAA conjugate, a physical mixture of the LPG-PAA, and a mixture of LPG + Freund's adjuvant, respectively. Furthermore, cytokine results supported that Th1 mediated protection occurred when mice were immunized with LPG-PAA conjugate. Conclusions: It has been demonstrated in this study that conjugate of LPG and PAA has an antileishmanial vaccine effect against visceral leishmaniasis. In this respect, the present study may lead to new vaccine approaches based on high immunogenic LPG molecule and adjuvant polymers in fighting against Leishmania infection.
Citation - WoS: 16
Citation - Scopus: 18
Microfluidic Chip Based Direct Triple Antibody Immunoassay for Monitoring Patient Comparative Response to Leukemia Treatment
(Springer, 2020) Icoz, Kutay; Akar, Unal; Unal, Ekrem
We report a time and cost-efficient microfluidic chip for screening the leukemia cells having three specific antigens. In this method, the target blast cells are double sorted with immunomagnetic beads and captured by the 3rd antibody immobilized on the gold surface in a microfluidic chip. The captured blast cells in the chip were imaged using a bright-field optical microscope and images were analyzed to quantify the cells. First sorting was performed with nano size immunomagnetic beads and followed by 2nd sorting where micron size immunomagnetic beads were used. The low-cost microfluidic platform is made of PMMA and glass including micro size gold pads. The developed microfluidic platform was optimized with cultured B type lymphoblast cells and tested with the samples of leukemia patients. The 8 bone marrow samples of 4 leukemia patients on the initial diagnosis and on the 15th day after the start of the chemotherapy treatment were tested both with the developed microfluidic platform and the flow cytometry. A 99% statistical agreement between the two methods shows that the microfluidic chip is able to monitor the decrease in the number of blast cells due to the chemotherapy. The experiments with the patient samples demonstrate that the developed system can perform relative measurements and have a potential to monitor the patient response to the applied therapy and to enable personalized dose adjustment.

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