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Öğe Aberrant crypt foci are regionally affected by zinc treatment in a 1,2-dimethylhydrazine induced colon carcinogenesis model(Elsevier Gmbh, Urban & Fischer Verlag, 2018) Moulahoum, Hichem; Boumaza, Belkacem Mohamed Amine; Ferrat, Meriem; Nagy, Andras-Laszlo; Olteanu, Diana Elena; Bounaama, Abdelkader; Clichici, SimonaZinc is a trace element widely known for its marked antioxidant properties. To gain more insight into the site and time- specific mechanisms by which it induces chemoprevention, this study was elaborated over a pre-cancerous model of colon carcinogenesis. Colon cancer was induced by 1,2-dimethylhydrazine (DMH) in mice (20 mg/kg for 2 weeks) and groups of animals were supplemented with or without zinc sulfate (ZnSO4, 200 mg/L) in drinking water for 4, 10 or 14 weeks. Colon tissues were collected for pathological observation, analyzing aberrant crypt (AC) and aberrant crypt foci (ACF) formations, multiplicity and distribution. Similarly, histological assessment and mucin production, as well as oxidative stress markers estimation was performed for the different groups. Results showed a significant increase in ACF and AC numbers, ACF multiplicity and demonstrated stronger distal occurrence than in the proximal after DHM administration. Histopathological analysis presented marked structural alterations and mucin loss in the distal than the proximal colons. A significant increase in myeloperoxidase (MPO), nitric oxide (NO), L-omithine and malondialdehyde (MDA) levels was observed followed by a significant decrease in antioxidant markers (superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH)). Oral ZnSO4 supplementation (continuous or partial) induced significant decrease in ACF, AC numbers and multiplicity, restored histological architecture and mucin production, and a significant decrease in proinflammatory markers while it reduced antioxidants to normal levels. From this study, insight was obtained on the use of ZnSO4 as a chemopreventive agent and shed light on its potential, as a supplement in nutraceutical approaches.Öğe Activity-guided purification and identification of endogenous bioactive peptides from barley sprouts (Hordeum vulgare L.) with diabetes treatment potential(Wiley, 2022) Gumus, Zinar Pinar; Moulahoum, Hichem; Tok, Kerem; Kocadag Kocazorbaz, Ebru; Zihnioglu, FigenMetabolic-associated disorders such as blood pressure and type 2 diabetes (T2D) are some of modern society's widespread problems. While there are many beneficial treatments, the quest for safe alternatives using natural products (e.g., cereals) is of great promise, especially plant-based peptides containing inherently endogenous bioactivities that can provide multiple health-promoting effects. Here, we aimed to purify and identify potential endogenous peptides of barley sprouts through an activity-guided process with a potential T2D therapeutical effect. Barley seeds were germinated, and sprouts were fractionated through ultrafiltration followed by RP-HPLC. All peptide fractions were examined for various bioactivities (alpha-glucosidase/DPP4 inhibition, antiglycation, antioxidant and metal chelation activities). LC-Q-TOF-MS/MS was employed for sequence identification of the fraction with the highest activity level. The data demonstrated that fractions with molecular weights lower than 3 kDa were the only ones with antiglycation activities. The RP-HPLC of the 3 kDa fraction resulted in 11 fractions, including 4 having significant IC50/EC50 levels. F11 demonstrated the highest potential as T2D treatment, and the sequence identification provided the sequences SQQENELTSLIVESNNRFNNASNT. Natural bioactive peptides from easy to procure and cheap sources are promising molecules for therapeutic applications. Further in vivo and clinical testing are necessary to validate the current findings.Öğe Application of Biofunctionalized Magnetic Nanoparticles Based-Sensing in Abused Drugs Diagnostics(Amer Chemical Soc, 2020) Sanli, Serdar; Ghorbani-Zamani, Faezeh; Moulahoum, Hichem; Gumus, Zinar Pinar; Coskunol, Hakan; Demirkol, Dilek Odaci; Timur, SunaReal-time detection of substance use is an approach of high interest leading to the optimization of behavioral interventions and drug abuse intervention. the current methods in use suffer many limitations and need high logistical and laboratory requirements. Biosensors have shown a great potential in overcoming these limitations. in the present study, the electrochemical biosensor composed of a screen-printed electrode (SPE) was designed for the detection of synthetic cannabinoid (SC). Antibody-immobilized magnetic nanoparticles were also used to create a surface on the transducer with magnetic interactions in order to detect JWH-073 as a SC model. the use of immobilized magnetic nanoparticles to create working surfaces makes the electrode a reusable SPE which can be reutilized after the cleansing. To examine and observe any possible changes on the surface due to its interaction with the analyte, different electrochemical techniques such as differential pulse voltammetry, cyclic voltammetry, and electrochemical impedance spectrometry were applied. Based on the obtained results, the linearity of the biosensor was found between 5 and 400 ng/mL, and the detection limit was calculated as 22 ng/mL (n = 6) using the 3 Sb/m formula. the biosensor functionality was studied in the presence of some related interferents that showed lower responses than JWH-073, thus demonstrating the good selectivity of the prepared biosensor. Finally, the sensory platform was used to test synthetic urine sample, and the results were compared with obtained results from liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS), which showed that the proposed method could be utilized to identify abuse drugs.Öğe Arsenic trioxide ameliorates murine colon inflammation through inflammatory cell enzymatic modulation(Springer, 2019) Moulahoum, Hichem; Boumaza, Belkacem Mohamed Amine; Ferrat, Meriem; Bounaama, Abdelkader; Djerdjouri, BahiaArsenic trioxide (As2O3) is a trending subject in recent therapy approaches despite its described toxicity. In this work, we have investigated the use of arsenic trioxide in a murine model of chemically induced inflammatory bowel disease colitis. Male mice were randomly separated into four different groups. Controls received vehicle, arsenic group had a daily injection of As2O3 (2.5mg/kg, i.p.) for 2days. Colitis was induced through intra-rectal instillation of 4% (v/v) solution of acetic acid in the second day. The treatment group (As2O3 + acetic acid) received the same treatment as the two previous groups. Twenty-four hours after colitis challenge, animals were sacrificed and organs (colons, livers, and kidneys) were taken for analysis. Disease-related macroscopic and microscopic symptoms, as well as histologic observations, showed a high index in the colitis group, which was greatly reduced by the As2O3 pretreatment. Similarly, colon length was reduced during colon inflammation, which was prevented in the presence of As2O3. Inflammatory cells and oxidative stress markers significantly increased during inflammation accompanied by a considerable reduction of antioxidants. As2O3 treatment managed to reverse these observations to normal levels. Mitochondrial implication was observed through mPTP opening phenomena and semi-quantitative cell death estimation. Low-dose As2O3 use as a mean of preventing the acute phase of colitis can be seen as an interesting approach which counts as a great addition to IBD available treatments.Öğe Arsenic trioxide exposure accelerates colon preneoplasic aberrant crypt foci induction regionally through mitochondrial dysfunction(Royal Soc Chemistry, 2018) Moulahoum, Hichem; Boumaza, Betkacem Mohamed Amine; Ferrat, Meriem; Djerdjouri, BahiaArsenic poisoning is a worldwide problem. Thus, we studied the effects of arsenic trioxide (ATO) administration on a 1,2-dimethylhydrazine (DMH)-induced preneoplasic colon carcinogenesis model. Mice were separated into four study groups; the control group received only vehicles. The ATO group received daily a 2.5 mg kg(-1) dose for 4 weeks. The DMH group received DMH (20 mg kg(-1)) twice in two weeks. The third group (D-ATO) had the same as the DMH group with ATO administration starting at week 10. At the end of 14 weeks, colons from sacrificed mice were taken, segmented into distal and proximal and subjected to aberrant crypt foci (ACF), aberrant crypt (AC) counting, alcian blue, H&E and Hoechst histological study and lastly oxidative stress marker analysis as well as mitochondrial swelling assessment. Data showed a significant increase in ACF and AC after DMH treatment, which was further increased after ATO addition. A perturbed histological structure was observed and loss of mucin producing cells in the colon tissue was observed. An important impact on the distal colon compared to the proximal one was noticed. The oxidative stress balance showed a similar pattern with an increase in MPO, NO/L-ornithine balance and MDA, while a decrease was observed in the antioxidant enzymes (CAT, SOD and GSH). In all parameters analyzed, the distal colons showed higher values than proximal. Furthermore, histological cell death analysis in combination with mitochondrial permeability pore opening suggested ATO contribution in the pathological effect. Our study has shown that ATO administration accelerated colon cancer development suggesting the heaviness of such treatments and the need to explore combinations and cycle type formulas.Öğe Arsenic trioxide exposure accelerates colon preneoplasic aberrant crypt foci induction regionally through mitochondrial dysfunction (vol 7, pg 182, 2017)(Royal Soc Chemistry, 2018) Moulahoum, Hichem; Boumaza, Belkacem Mohamed Amine; Ferrat, MeriemÖğe Artemisia alleviates AGE-induced liver complications via MAPK and RAGE signaling pathways modulation: a combinatorial study(Springer, 2022) Moulahoum, Hichem; Ghorbanizamani, Faezeh; Khiari, Zineb; Toumi, Mohamed; Benazzoug, Yasmina; Tok, Kerem; Timur, SunaArtemisia herba-alba (AHA) is a traditionally used plant to treat various diseases, including diabetes and metabolic dysfunctions. Plant extracts are generally explored empirically without a deeper assessment of their mechanism of action. Here, we describe a combinatorial study of biochemical, molecular, and bioinformatic (metabolite-protein pharmacology network) analyses to elucidate the mechanism of action of AHA and shed light on its multilevel effects in the treatment of diabetes-related advanced glycation end-products (AGE)-induced liver damages. The extract's polyphenols and flavonoids content were measured and then identified via LC-Q-TOF-MS/MS. Active compounds were used to generate a metabolite-target interaction network via Swiss Target Prediction and other databases. The extract was tested for its antiglycation and aggregation properties. Next, THLE-2 liver cells were challenged with AGEs, and the mechanistic markers were measured [TNF-alpha, IL-6, nitric oxide, total antioxidant capacity, lipid peroxidation (LPO), and caspase 3]. Metabolite and network screening showed the involvement of AHA in diabetes, glycation, liver diseases, aging, and apoptosis. Experimental confirmation showed that AHA inhibited protein modification and AGE formation. Additionally, AHA reduced inflammatory mediators (IL-6, TNF alpha), oxidative stress markers (NO, LPO), and apoptosis (Caspase 3). On the other hand, cellular total antioxidant capacity was restored to normal levels. The combinatorial study showed that AHA regulates AGE-induced liver damages through MAPK-AKT and AGE-RAGE signaling pathways. This report highlights the combination of experimental and network pharmacology for the exact elucidation of AHA mechanism of action as a multitarget option in the therapy of diabetes and AGEs-related diseases.Öğe Bioactive peptides with multiple activities extracted from Barley (Hordeum vulgare L.) grain protein hydrolysates: Biochemical analysis and computational identification(Wiley, 2020) Tok, Kerem; Moulahoum, Hichem; Kocadag Kocazorbaz, Ebru; Zihnioglu, FigenPlant-derived bioactive peptides demonstrate great potential given their availability and cost-effectiveness. in this study, barley (Hordeum vulgare L.) grain proteins were explored for bioactive peptides with potential health applications. Gross grain proteins were obtained through aqueous extraction, after which, trypsin hydrolysis was performed. the hydrolysis process provided high peptide yields reaching 11%. the peptide hydrolysates were evaluated for their antioxidant and metal chelating activities, DPP4 inhibition, deglycation, and antimicrobial activity. the obtained results demonstrated biological activity levels of great importance and comparable to reference molecules. To confirm the experimental results, barley grain protein sequences were simulated for hydrolysis and explored for potential bioactive peptides using the FeptideDB. Indeed, barley grain proteins contain a great diversity of bioactive peptides with various biological activities. the current data highlights the promising therapeutic application of barley-derived bioactive peptides. Further molecular and sequencing approaches are necessary to identify and characterize these peptides. Practical applications Barley (Hordeum vulgare L.) grain proteins are widely used cereals for nutrition and beverages. Their availability and low-cost make them good sources for functional food exploration. We have described the potential of bioactive peptides obtained from barley grain proteins that have various activities including DPP4 inhibitory, antioxidant, antimicrobial, metal chelating, and deglycation activities. This data supports the potential of these peptides in biomedicine applications as a treatment option or as food supplement. Hence, the described peptide sequences could be exploited and industrialized by artificial synthesis and be proposed as food supplements or included in protein mixes for athletes.Öğe Carbon dots and curcumin-loaded CD44-Targeted liposomes for imaging and tracking cancer chemotherapy: A multi-purpose tool for theranostics(Elsevier, 2021) Demir, Bilal; Moulahoum, Hichem; Ghorbanizamani, Faezeh; Barlas, F. Baris; Yesiltepe, Ozan; Gumus, Z. Pinar; Timur, SunaGrowing needs in biomedical applications have driven the development of multifunctional nanoparticles towards theranostically-engineered multimodal platforms. Many strategies for point-effective cellular uptake of theranostics have been described. in this report, multifunctional nanostructures were designed and synthesized as a novel theranostic platform. Liposomes were loaded with curcumin as a therapeutic agent and carbon dots (CDs) as a contrast molecule. Anti-CD44 antibodies were bioconjugated on the liposomal surface to obtain an active targeting nanocarrier. After synthesis, the relative characterization of the vesicles was performed using DLS and TEM techniques. in vitro analysis was conducted to investigate the multimodal properties of the theranostic via testing its toxicity, cell uptake, bioimaging, and chemo/radiotherapy applications on two different cell lines. 3D holographic microscopy was employed to track the treatment effects during experimentation. Results indicated that these particles are efficient tools for clinical applications due to their fluorescent characteristic and increased bioperformance.Öğe Combination of LC-Q-TOF-MS/MS, network pharmacology, and nanoemulsion approaches identifies active compounds of two Artemisia species responsible for tackling early diabetes-related metabolic complications in the liver(Wiley, 2022) Moulahoum, Hichem; Ghorbanizamani, Faezeh; Khiari, Zineb; Toumi, Mohamed; Benazzoug, Yasmina; Timur, Suna; Zihnioglu, FigenIntroduction The chronicity of advanced glycation end-products (AGEs) imparts various damages resulting in metabolic dysfunction and diseases involving inflammation and oxidative stress. The use of plant extracts is of high interest in complementary medicine. Yet, extracts are multicomponent mixtures, and difficult to pinpoint their exact mechanism. Objectives We hypothesise that network pharmacology and bioinformatics can help experimental findings depict the exact active components and mechanism of action by which they induce their effects. Additionally, the toxicity and variability can be lowered and standardised with proper encapsulation methods. Methodology Here, we propose the formulation of phytoniosomes encapsulating two Artemisia species (Artemisia dracunculus and Artemisia absinthium) to mitigate AGEs and their induced cell redox dysregulation in the liver. Extracts from different solvents were identified via liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS/MS). Phytoniosomes were explored for their anti-glycating effect and modulation of AGE-induced damages in THLE-2 liver cells. Network pharmacology tools were used to identify possible targets and signalling pathways implicated. Results Data demonstrated that A. absinthium phytoniosomes had a significant anti-AGE effect comparable to reference molecules and higher than A. dracunculus. They were able to restore cell dysfunction through the restoration of tumour necrosis alpha (TNF-alpha), interleukin 6 (IL-6), nitric oxide, and total antioxidant capacity. Phytoniosomes were able to protect cells from apoptosis by decreasing caspase 3 activity. Network pharmacology and bioinformatic analysis confirmed the induction of the effect via Akt-PI3K-MAPK and AGE-RAGE signalling pathways through quercetin and luteolin actions. Conclusion The current report highlights the potential of Artemisia phytoniosomes as strong contenders in AGE-related disease therapy.Öğe Current trends in the development of conducting polymers-based biosensors(Elsevier Sci Ltd, 2019) Zamani, Faezeh Ghorbani; Moulahoum, Hichem; Ak, Metin; Demirkol, Dilek Odaci; Timur, SunaBioelectronics devices are seeing great improvement. After the earliest generations of sensors and biosensors, the current generation is attracting great interest due to the advantages that it showed. Despite the positive advantages, some drawbacks linked to the technologies used in the construction process are still seen. Therefore, the scientific community is giving its best to further develop the current biosensor knowledge and bypass the disadvantages seen before. In this review, we will be examining the current approaches taken by research in order to avoid the already seen drawbacks in sensors development. Many tools and methodologies are being used ranging from conducting polymers, conducting polymer nanowires, embedded metal nanoparticles in polymeric films, to conducting polymers synthesis in ionic liquids and polymeric ionic liquids. These approaches permitted the fabrication of highly simplistic and low-cost biosensors stressing on their potential in biological samples detection. The dynamic seen between polymers and protein opens the door to many possibilities to use novel materials or devising new techniques for the next generation biosensor systems. Despite all the efforts been made, the subject of modification of electrodes by chemical reactions is still a remarkable area of research activity. Hence, in this review, the considerable emphasis has been placed on the recent approaches of electrical active polymer modified electrodes specialized for application in biosensing devices and in particular amper-ometric biosensors. (C) 2019 Elsevier B.V. All rights reserved.Öğe Design of Polymeric Surfaces as Platforms for Streamlined Cancer Diagnostics in Liquid Biopsies(MDPI, 2023) Ghorbanizamani, Faezeh; Moulahoum, Hichem; Celik, Emine Guler; Zihnioglu, Figen; Beduk, Tutku; Goksel, Tuncay; Turhan, KutsalMinimally invasive approaches for cancer diagnosis are an integral step in the quest to improve cancer survival. Liquid biopsies such as blood samples are matrices explored to extract valuable information about the tumor and its state through various indicators, such as proteins, peptides, tumor DNA, or circulating tumor cells. Although these markers are scarce, making their isolation and detection in complex matrices challenging, the development in polymer chemistry producing interesting structures, including molecularly imprinted polymers, branched polymers, nanopolymer composites, and hybrids, allowed the development of enhanced platforms with impressive performance for liquid biopsies analysis. This review describes the latest advances and developments in polymer synthesis and their application for minimally invasive cancer diagnosis. The polymer structures improve the operational performances of biosensors through various processes, such as increased affinity for enhanced sensitivity, improved binding, and avoidance of non-specific interactions for enhanced specificity. Furthermore, polymer-based materials can be a tremendous help in signal amplification of usually low-concentrated targets in the sample. The pros and cons of these materials, how the synthesis process affects their performance, and the device applications for liquid biopsies diagnosis will be critically reviewed to show the essentiality of this technology in oncology and clinical biomedicine.Öğe Discarded CHO cells as a valuable source of bioactive peptides for sustainable biotechnological applications(Elsevier, 2024) Yilmaz, Sude; Moulahoum, Hichem; Tok, Kerem; Zihnioglu, FigenRepurposing discarded cells stands as a groundbreaking paradigm shift in sustainable biotechnology, with profound implications across diverse industrial sectors. Our study proposes a transformative concept by harnessing histone proteins from discarded CHO cells to produce bioactive peptides. We systematically isolated and hydrolyzed histones using Trypsin and Neutrase enzymes, optimizing reaction conditions. Ultrafiltration yielded distinct peptide fractions (<3 kDa and 3-10 kDa), which we analyzed for DPP-IV inhibition, antioxidant potential, and other activities. Furthermore, LC-Q-TOF-MS analysis and in silico tools unveiled the structural composition of bioactive peptides within these fractions. Three peptide sequences with high bioactivity potential were identified: KLPFQR, VNRFLR, and LSSCAPVFL. Our findings demonstrated exceptional DPP-IV inhibition, potent antioxidant effects, and effective anti-lipid peroxidation activities, surpassing reference compounds. Hemolytic activity assessment indicated promising biocompatibility, enhancing therapeutic application prospects. Pioneering the strategic repurposing of discarded cells, this research addresses cost-efficiency in cell-based studies and promotes sustainable use of biological resources across sectors. This novel approach offers an efficient, eco-friendly method for bioactive molecule procurement and resource management, revolutionizing cell culture studies and biotechnological applications.Öğe Dual Chromatic Laser-Printed Microfluidic Paper-Based Analytical Device (?PAD) for the Detection of Atrazine in Water(Amer Chemical Soc, 2023) Moulahoum, HichemWater pollution caused by pesticides is a significant threat to the environment and human health. Silver and gold nanoparticle (AgNPs, AuNPs)-based biosensors are affordable tools, ideal for environmental monitoring. Microfluidic paper-based devices (mu PADs) are a promising approach for on-site testing, but few studies have explored the use of laser printing (LP) for mu PAD-based biosensors. This study investigates the feasibility of using laser printing to fabricate paper-based biosensors for pesticide detection in water samples. The mu PAD was designed and optimized by using different filter paper porosities, patterns, and channel thicknesses. The developed LP-mu PAD was used to sense the pesticide atrazine in water through colorimetric assessments using a smartphone-assisted image analysis. The analytical assessment showed a limit of detection (LOD) of 3.5 and 10.9 mu M for AgNPs and AuNPs, respectively. The sensor had high repeatability and reproducibility. The LP-mu PAD also demonstrated good recovery and functionality in simulated contaminated water. Furthermore, the detection of pesticides was found to be specific under the influence of interferents, such as NaCl and pH levels. By combining laser printing and nanoparticles, the proposed sensor could contribute to developing effective and low-cost solutions for monitoring water quality that are widely accessible.Öğe Dye-Loaded Polymersome-Based Lateral Flow Assay: Rational Design of a COVID-19 Testing Platform by Repurposing SARS-CoV-2 Antibody Cocktail and Antigens Obtained from Positive Human Samples(Amer Chemical Soc, 2021) Ghorbanizamani, Faezeh; Tok, Kerem; Moulahoum, Hichem; Harmanci, Duygu; Hanoglu, Simge Balaban; Durmus, Ceren; Zihnioglu, FigenThe global pandemic of COVID-19 continues to be an important threat, especially with the fast transmission rate observed after the discovery of novel mutations. In this perspective, prompt diagnosis requires massive economical and human resources to mitigate the disease. The current study proposes a rational design of a colorimetric lateral flow immunoassay (LFA) based on the repurposing of human samples to produce COVID-19-specific antigens and antibodies in combination with a novel dye-loaded polymersome for naked-eye detection. A group of 121 human samples (61 serums and 60 nasal swabs) were obtained and analyzed by RT-PCR and ELISA. Pooled samples were used to purify antibodies using affinity chromatography, while antigens were purified via magnetic nanoparticles-based affinity. The purified proteins were confirmed for their specificity to COVID-19 via commercial LFA, ELISA, and electrochemical tests in addition to sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Polymersomes were prepared using methoxy polyethylene glycol-b-polycaprolactone (mPEG-b-PCL) diblock copolymers and loaded with a Coomassie Blue dye. The polymersomes were then functionalized with the purified antibodies and applied for the preparation of two types of LFA (antigen test and antibody test). Overall, the proposed diagnostic tests demonstrated 93 and 92.2% sensitivity for antigen and antibody tests, respectively. The repeatability (92-94%) and reproducibility (96-98%) of the tests highlight the potential of the proposed LFA. The LFA test was also analyzed for stability, and after 4 weeks, 91-97% correct diagnosis was observed. The current LFA platform is a valuable assay that has great economical and analytical potential for widespread applications.Öğe Emerging trends in nanomaterial design for the development of point-of-care platforms and practical applications(Elsevier, 2023) Moulahoum, Hichem; Ghorbanizamani, Faezeh; Beduk, Tutku; Bedük, Duygu; Özufuklar, Özge; Güler Çelik, Emine; Timur, SunaNanomaterials and nanotechnology offer promising opportunities in point-of-care (POC) diagnostics and therapeutics due to their unique physical and chemical properties. POC platforms aim to provide rapid and portable diagnostic and therapeutic capabilities at the site of patient care, offering cost-effective solutions. Incorporating nanomaterials with distinct optical, electrical, and magnetic properties can revolutionize the POC industry, significantly enhancing the effectiveness and efficiency of diagnostic and theragnostic devices. By leveraging nanoparticles and nanofibers in POC devices, nanomaterials have the potential to improve the accuracy and speed of diagnostic tests, making them more practical for POC settings. Technological advancements, such as smartphone integration, imagery instruments, and attachments, complement and expand the application scope of POCs, reducing invasiveness by enabling analysis of various matrices like saliva and breath. These integrated testing platforms facilitate procedures without compromising diagnosis quality. This review provides a summary of recent trends in POC technologies utilizing nanomaterials and nanotechnologies for analyzing disease biomarkers. It highlights advances in device development, nanomaterial design, and their applications in POC. Additionally, complementary tools used in POC and nanomaterials are discussed, followed by critical analysis of challenges and future directions for these technologies.Öğe Extraction and characterization of novel multifunctional peptides from Trachinus Draco (greater weever) myofibrillar proteins with ACE/DPP4 inhibitory, antioxidant, and metal chelating activities(Wiley, 2020) Kula, Elif; Kocazorbaz, Ebru Kocadag; Moulahoum, Hichem; Alpat, Senol; Zihnioglu, FigenMarine organisms represent a great source of natural bioactive molecules, from which bioactive peptides are of great importance in biomedicine application in many diseases such as diabetes and its related complications. in this study, greater weever (Trachinus Draco) myofibrillar proteins were sequentially hydrolyzed and the different RP-HPLC purified fractions were tested for potential inhibitory activities of ACE and DPP4, in addition to metal chelation and antioxidant activities. Four fractions were found to have high levels of activity (with two peptides being multifunctional) and were subsequently sequenced using the de novo sequencing method. the results indicate that the peptides are novel and highly effective for each related activity compared to reference molecules. the current findings suggest these multifunctional peptides as promising therapeutics against oxidative stress, hypertension, and diabetes. Practical applications We have described the finding of two multifunctional bioactive peptides from Trachinus Draco (greater weever) myofibrillar proteins having two or more activities. They have ACE inhibitory, DPP4 inhibitory, antioxidant, and metal chelation activities. These new peptides could be used for future biomedicine applications as a stand-alone treatment, in combination with other molecules, or as a supplement. Furthermore, after identification of their sequence in our work, it would have a great potential to be artificially synthesized. the field of food supplements could be explored further.Öğe Fluorescent bioassay for SARS-CoV-2 detection using polypyrene-g-poly(epsilon-caprolactone) prepared by simultaneous photoinduced step-growth and ring-opening polymerizations(Springer Wien, 2022) Celiker, Tugba; Ghorbanizamani, Faezeh; Moulahoum, Hichem; Guler Celik, Emine; Tok, Kerem; Zihnioglu, Figen; Cicek, CandanThe construction of a rapid and easy immunofluorescence bioassay for SARS-CoV-2 detection is described. We report for the first time a novel one-pot synthetic approach for simultaneous photoinduced step-growth polymerization of pyrene (Py) and ring-opening polymerization of epsilon-caprolactone (PCL) to produce a graft fluorescent copolymer PPy-g-PCL that was conjugated to SARS-CoV-2-specific antibodies using EDC/NHS chemistry. The synthesis steps and conjugation products were fully characterized using standard spectral analysis. Next, the PPy-g-PCL was used for the construction of a dot-blot assay which was calibrated for applications to human nasopharyngeal samples. The analytical features of the proposed sensor showed a detection range of 6.03-8.7 LOG viral copy mL(-1) (Ct Scores: 8-25), the limit of detection (LOD), and quantification (LOQ) of 1.84 and 6.16 LOG viral copy mL(-1), respectively. The repeatability and reproducibility of the platform had a coefficient of variation (CV) ranging between 1.2 and 5.9%. The fluorescence-based dot-blot assay was tested with human samples. Significant differences were observed between the fluorescence intensity of the negative and positive samples, with an overall correct response of 93.33%. The assay demonstrated a high correlation with RT-PCR data. This strategy opens new insights into simplified synthesis procedures of the reporter molecules and their high potential sensing and diagnosis applications.Öğe Glutathione Encapsulation in Core-Shell Drug Nanocarriers (Polymersomes and Niosomes) Prevents Advanced Glycation End-products Toxicities(Springer, 2021) Ghorbanizamani, Faezeh; Moulahoum, Hichem; Bayir, Ece; Zihnioglu, Figen; Timur, SunaThe clinical application of some natural molecules in therapy is usually limited due to the lack of feasible delivery systems. Core-shell nanocarriers (polymersomes and niosomes) are interesting stable nanocarriers that are biocompatible, biodegradable, and able to produce sustainable delivery. They can be modified and functionalized according to the application needed. In this report, we describe the synthesis of a smart and pH-responsive poly(ethylene oxide)-poly(lactide) polymersome (PEO-PL) and niosomes (NIO) loaded with GSH for efficient peptide delivery and potent application against advanced glycation end-products-related damages and toxicities. PEO-PL was constructed using the one-pot sequential anionic ring-opening polymerization method, while the niosomes were prepared via the thin film layer technique. The nanocarriers were characterized for their size and morphology by DLS and SEM. The formulations demonstrated a high encapsulation rate reaching 95% and showed increased sensitivity to release their content in acidic conditions (pH 5.5) compared with physiological media. PEO-PL showed a higher retention rate compared with the NIO. The nanocarriers showed no apparent toxicity even at high concentrations (400 mu g/mL). The MTT test demonstrated that HeLa cell lines were more sensitive to GSH than U87 cell lines starting from 100 and 400 mu g/mL, respectively. Testing the synthesized core-shell nanocarriers on altered proteins showed prolonged and high prevention rates of glycation, aggregation, and oxidation without hindering the effect of GSH. These bioresponsive nanocarriers appear as an interesting platform for biomedicine and therapy.Öğe How should diagnostic kits development adapt quickly in COVID 19-like pandemic models? Pros and cons of sensory platforms used in COVID-19 sensing(Elsevier, 2021) Moulahoum, Hichem; Ghorbanizamani, Faezeh; Zihnioglu, Figen; Turhan, Kutsal; Timur, SunaAs COVID-19 has reached pandemic status and the number of cases continues to grow, widespread availability of diagnostic testing is critical in helping identify and control the emergence of this rapidly spreading and serious illness. However, a lacking in making a quick reaction to the threat and starting early development of diagnostic sensing tools has had an important impact globally. in this regard, here we will review critically the current developed diagnostic tools in response to the COVID-19 pandemic and compare the different types through the discussion of their pros and cons such as nucleic acid detection tests (including PCR and CRISPR), antibody and protein-based diagnosis tests. in addition, potential technologies that are under development such as on-site diagnosis platforms, lateral flow, and portable PCR units are discussed. Data collection and epidemiological analysis could also be an interesting factor to incorporate with the emerging technologies especially with the wide access to smartphones. Lastly, a SWOT analysis and perspectives on how the development of novel sensory platforms should be treated by the different decision-makers are analyzed.
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