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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14411/22
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Article Advances in Stabilizing Lipid-Based Nanoparticles: The Central Role of Lyophilization(Elsevier, 2026) Gallego, Idoia; Pedraz, José Luis; Bautista-Lopez, Irene; Enriquez-Rodriguez, Lucia; Maldonado, Iván; Lafuente-Merchan, Markel; Ramalingam, MuruganLipid-based nanoparticles (L-bNPs) have become a key platform in nanomedicine, enabling advances in drug delivery, gene therapy, and vaccine development. However, their widespread clinical application remains limited by their poor long-term stability, especially when stored in aqueous media. This review provides a comprehensive overview of long-term storage strategies for L-bNPs, with a particular focus on lyophilization (freeze-drying), which has emerged as the most widely adopted and effective stabilization method in the biopharmaceutical industry. The review begins with a classification of lipid-based nanoparticles and their medical applications, followed by an analysis of key storage challenges and a detailed exploration of freeze-drying processes, including critical parameters such as cryoprotectant selection, vial type, and the lipid composition of the formulation. Additionally, novel approaches such as spin freeze-drying are discussed for their potential to optimize solvent distribution and product morphology. Other long-term storage methods-including cryopreservation and atomization-based drying techniques such as spray-drying and supercritical fluid drying (SCFD)- are also examined for their potential benefits. Spray congealing, though still under development for L-bNPs, is highlighted for its promising performance in related lipid-based systems. While lyophilization remains the gold standard, the choice of method must be tailored to the physicochemical properties of the L-bNPs and their intended therapeutic use. Future perspectives highlight the need for more standardized protocols and advanced analytical tools to ensure stability and effectiveness across storage and transport conditions.Article Citation - WoS: 1Citation - Scopus: 1Genomic Characterization of Five Novel Salmonella Phages and the Assessment of Their Biocontrol Potential for the Preservation of Chicken Meat(Elsevier, 2026) Cufaoglu, Gizem; Cengiz, Gorkem; Acar, Bahar Onaran; Kardogan, Ozlem; Onmaz, Nurhan Ertas; Unal, Gultekin; Ayaz, Naim Deniz; Onaran Acar, Bahar; Ertas Onmaz, NurhanThe rise of multidrug-resistant Salmonella poses a significant threat to food safety and public health, necessitating novel antimicrobial strategies. The primary objective of this study was to characterize novel bacteriophages and assess their biocontrol potential against predominant Salmonella serotypes. A total of 84 lytic bacteriophages specific to various Salmonella enterica serotypes were isolated from wastewater sources across T & uuml;rkiye. Five phages (S.Hadar 4-5-1, S.Inf 5-2, S.Typ Adana, S.Ent 1-35-3, and S.Kent 1-2-1) demonstrating broad lytic activity to tested major serotypes (S. Enteritidis, S. Typhimurium, S. Infantis, S. Kentucky, S. Newport, S. Hadar, S. Gallinarum and S. Pullorum) and genetic diversity were selected for detailed phenotypic and genomic analysis. These phages, four from Siphoviridae and one from Podoviridae, exhibited tolerance to thermal (up to 60 degrees C) and mildly acidic conditions (pH 4), as well as 12-month stability when stored in Tris-Buffered Saline (TBS) with 20 % (v/v) glycerol at -20 degrees C and - 80 degrees C. Whole-genome sequencing confirmed their novelty and the absence of antimicrobial resistance and virulence genes. A cocktail formulated from these phages was applied against Salmonella Enteritidis both in-vitro (at 37 degrees C) and on artificially contaminated chicken wings (at 4 degrees C). The phage cocktail effectively reduced Salmonella counts in both environments, keeping levels below the detection limit (< 1 log CFU/g) over 24 h. For chicken wings food model, bacterial reductions reached 3.30 log CFU/g and 4.86 log CFU/g. These results underscore the potential of the newly characterized Salmonella phages as effective tools for controlling bacterial contamination on chicken meat, supporting their use as a natural, and antibiotic-free strategy in modern food safety management.Article Citation - WoS: 1Citation - Scopus: 2Outcomes of Gonioscopy-Assisted Transluminal Trabeculotomy in Children with Early-Onset Glaucoma Secondary To Sturge-Weber Syndrome(Elsevier, 2025) Aktas, Zeynep; El Sayed, Yasmine; Ucgul, Ahmet Yucel; Gawdat, Ghada; Elhilali, Hala; Aboalazayem, FayrouzPurpose: To evaluate the effectiveness and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in managing early-onset glaucoma secondary to Sturge-Weber syndrome (SWS). Design: A retrospective interventional case series. Participants: Medical records of 16 patients (22 eyes) diagnosed with early-onset glaucoma secondary to SWS who underwent GATT surgery were reviewed. Methods: All patients underwent GATT surgery using a 5-0 or 6-0 prolene suture under general anesthesia. Main Outcome Measures: The primary outcomes were intraocular pressure (IOP) reduction, complete surgical success (IOP <= 18 mmHg without medications), qualified surgical success (IOP <= 18 mmHg with medications), and postoperative complications. Results: The mean IOP decreased significantly from 25.4 +/- 4.8 mmHg at baseline to 15.7 +/- 4.2 mmHg at the final follow-up (P < 0.001), representing a 38.19% reduction. The mean age at the time of GATT surgery was 33.6 +/- 33.9 months. The mean follow-up duration was 16.3 +/- 6.4 months. Complete surgical success was achieved in 45.4% of eyes (10 out of 22), while qualified success was reached in 81.8% of eyes (18 out of 22). Despite the overall success, 18.1% of eyes (4 eyes) required additional surgical interventions during the follow-up period. These included Ahmed glaucoma valve implantation in 1 eye, trabeculectomy in 2 eyes, and transscleral diode laser cyclophotocoagulation in 1 eye. Transient hyphema was the only reported complication, resolving spontaneously within 1 week without further intervention. Conclusions: Gonioscopy-assisted transluminal trabeculotomy appears to be a promising surgical option for managing early-onset glaucoma in patients with SWS, offering significant IOP reduction and a favorable safety profile within the limitations of our study. However, further studies with longer follow-up periods and comparative groups are necessary to confirm these findings.Article Citation - WoS: 5Citation - Scopus: 6Molecular/Antigenic Mimicry and Immunological Cross-Reactivity Explains Sars-Cov Autoimmunity(Elsevier, 2025) Adiguzel, Yekbun; Bogdanos, Dimitros P.; Shoenfeld, YehudaCOVID-19 pandemic is over, but its effects on chronic illnesses remain a challenging issue. Understanding the influence of SARS-COV-2-mediated autoimmunity and overt autoimmune disease is of paramount importance, as it can provide a critical mass of information regarding both infection-mediated (and vaccination-induced) autoimmune phenomena in susceptible individuals during the disease course, and short or long-term post-disease sequelae. The high prevalence of organ and non-organ specific autoantibody positivity in patients with COVID-19 led to studies attempting to delineate the origin and the underlying mechanism responsible for their induction nature, identifying novel autoantigens, and the self-epitope sequences which could be the impetus for the initiating autoreactive responses. Herein, we provide a meticulous review of the studies reporting those mimicking sequences that have been experimentally validated, based on the assumption that molecular mimicry and immunological crossreactivity may account for autoantibody development. Most reports are based on bioinformatics approaches, and only a disproportionally small number of studies currently demonstrate immunological crossreactivity. We took the opportunity to further review and searched for the linear human epitope sequences of human, through the epitopes deposited at the Immune Epitope Database. This included an analysis of autoimmune disease as the disease data to comprehensively understand the subject matter. The critical overview of the findings underscore the urgent and immense need for further research to gain a comprehensive understanding of the mechanisms involved and the anticipated appraisal that molecular mimicry and immunological crossreactivity is indeed central to the loss of immunological tolerance during SARS-COV-2 infection.Article Citation - WoS: 3Citation - Scopus: 4Microfluidic Rapid Isolation and Electrochemical Detection of S. Pneumonia Via Aptamer-Decorated Surfaces(Elsevier, 2025) Babaie, Zahra; Kibar, Gunes; Yesilkaya, Hasan; Amrani, Yassine; Dogan, Soner; Tuna, Bilge G.; Cetin, Barbaros; Özalp, Veli CengizBackground: S. pneumoniae is widely recognized as a leading cause of respiratory infections worldwide, often resulting in high mortality rates. However, the advent of microfluidic technologies has brought significant advancements, including the simplified, sensitive, cost-effective, and rapid approach to pneumococcal bacteremia detection. In this study, a microfluidic magnetic platform is presented for rapid isolation, and an electrode array is utilized for the electrochemical detection of S. pneumoniae. Aptamer-decorated surfaces were employed for both isolation and detection. For isolation, silica magnetic microparticles were synthesized and decorated with aptamer. Results: Isolation performance was assessed for phosphate-buffered saline (PBS) and blood samples for different concentrations of S. pneumoniae. Electrical impedance spectroscopy (EIS) with fabricated gold interdigitated electrodes (IDEs) decorated with aptamer was implemented for the detection of S. pneumoniae at different bacteria concentrations. The microfluidic platform performed bacteria isolation at comparable isolation efficiency with batch systems but at a much faster rate (isolation took about a minute, and the aptamer-decorated electrode array exhibited a limit of detection (LOD) at 962 CFU/mL and linear range between 104 and 107CFU/mL. Significance: Our method represents a significant advancement compared to previous reports. Our microfluidic platform can efficiently isolate 60 mu L of the bacteria sample within about one minute. The entire process takes about two minutes including the detection step. Furthermore, our method achieves a notable improvement in the detection limit for S. pneumoniae compared to conventional ELISA and magnetic microfluidics ELISA.Article Citation - WoS: 4Citation - Scopus: 4A Novel Injectable Nanotherapeutic Platform Increasing the Bioavailability and Anti-Tumor Efficacy of Arachidonylcyclopropylamide on an Ectopic Non-Small Cell Lung Cancer Xenograft Model: A Randomized Controlled Trial(Elsevier, 2025) Boyacioglu, Ozge; Varan, Cem; Bilensoy, Erem; Aykut, Zaliha Gamze; Recber, Tuba; Nemutlu, Emirhan; Korkusuz, PetekRapid progressing non-small cell lung adenocarcinoma (NSCLC) decreases treatment success. Cannabinoids emerge as drug candidates for NSCLC due to their anti-tumoral capabilities. We previously reported the controlled release of Arachidonylcyclopropylamide (ACPA) selectively targeting cannabinoid 1 (CB1) receptor in NSCLC cells in vitro. Hydrophobic polymers like polycaprolactone (PCL) offer prolonged circulation time and slower drug clearance which is suitable for hydrophobic molecules like ACPA. Thus, the extended circulation time with enhanced bioavailability and half-life of nanoparticular ACPA is crucial for its therapeutic performance in the tumor area. We assumed that a novel high technology-controlled release system increasing the bioavailability of ACPA compared to free ACPA could be transferred to the clinic when validated in vivo. Plasma profile of ACPA and ACPA-loaded PCL-based nanomedicine by LC-MS/MS and complete blood count (CBC) was assessed in wild-type Balb/c mice. Tumor growth in nanomedicine-applied NSCLC-induced athymic nude mice was assessed using bioluminescence imaging (BLI) and caliper measurements, histomorphometry,immunohistochemistry, TUNEL assay, and Western blot on days 7-21. Injectable NanoACPA increased its systemic exposure to tissues 5.5 times and maximum plasma concentration 6 times higher than free ACPA by substantially improving bioavailability. The potent effect of NanoACPA lasted for at least two days on ectopic NSCLC model through Akt/PI3K, Ras/MEK/Erk, and JNK pathways that diminished Ki-67 proliferative and promoted TUNEL apoptotic cell scores on days 7-21. The output reveals that NanoACPA platform could be a chemotherapeutic for NSCLC in the clinic following scale-up GLP/GMP-based phase trials, owing to therapeutic efficacy at a safe low dose window.Article Citation - WoS: 1Citation - Scopus: 1Does Reformer Pilates Exercise Improve Cognitive Functions in Sedentary Women? a Randomized Controlled Study(Elsevier, 2024) Ozeren, Aysenur; Ulug, Naime; Sahan, Nilay; Karahan, Zehra Can; Can Karahan, ZehraBackground: The reformer is an apparatus on which to perform the foot work and the body in a comfortable, nonweight-bearing supine position and keeps the muscles in balance. The aim of this randomized controlled and single-center study was to investigate the effect of reformer Pilates exercises on cognitive functions in sedentary women. Methods: A total of 44 sedentary women aged between 24 and 50 were randomized into two groups. The reformer Pilates group received a 6-week exercise program (45 min/twice per week), while the control group didn't receive any exercise program. Outcomes measured before and after the interventions were, right/left discrimination and scores of two questionnaires: Stroop Test and The Pittsburgh SleepQuality Index. Results: Reformer pilates group showed significant improvement in terms of the Stroop Test (STROOP) "STROOP-B" (t0 = 156; p < 0.05; Cohen d = 0.12), "STROOP-C" (U = 144.5; p < 0.05; Cohen d = 1.13) and "STROOP-D" (U = 165; p < 0.05, Cohen d = 0.40) when compared to control group. In the comparison of the results of the right-left separation in both groups, the difference values were not statistically significant (p > 0.05). Similarly, in the both groups the sleep quality of the individuals improved, but the difference was not statistically significant (p > 0.05). Conclusion: The results of the current study suggest that Reformer Pilates exercises may be more effective on cognitive functions compared to no exercise intervention in sedentary women. Clinical Trial Number: NCT05932004.Article Citation - WoS: 6Citation - Scopus: 7Clinic-Oriented Injectable Smart Material for the Treatment of Diabetic Wounds: Coordinating the Release of Gm-Csf and Vegf(Elsevier, 2024) Kinali, Hurmet; Kalaycioglu, Gokce Dicle; Boyacioglu, Ozge; Korkusuz, Petek; Aydogan, Nihal; Vargel, IbrahimChronic wounds are often caused by diabetes and present a challenging clinical problem due to vascular problems leading to ischemia. This inhibits proper wound healing by delaying inflammatory responses and angiogenesis. To address this problem, we have developed injectable particle-loaded hydrogels which sequentially release Granulocyte-macrophage- colony-stimulating-factor (GM-CSF) and Vascular endothelial growth factor (VEGF) encapsulated in polycaprolactone-lecithin-geleol mono-diglyceride hybrid particles. GM-CSF promotes inflammation, while VEGF facilitates angiogenesis. The hybrid particles (200 -1000 nm) designed within the scope of the study can encapsulate the model proteins Bovine Serum Albumin 65 +/- 5 % and Lysozyme 77 +/- 10 % and can release stably for 21 days. In vivo tests and histological findings revealed that in the hydrogels containing GM-CSF/VEGF-loaded hybrid particles, wound depth decreased, inflammation phase increased, and fibrotic scar tissue decreased, while mature granulation tissue was formed on day 10. These findings confirm that the hybrid particles first initiate the inflammation phase by delivering GM-CSF, followed by VEGF, increasing the number of vascularization and thus increasing the healing rate of wounds. We emphasize the importance of multi-component and sequential release in wound healing and propose a unifying therapeutic strategy to sequentially deliver ligands targeting wound healing stages, which is very important in the treatment of the diabetic wounds.Article Citation - Scopus: 1The Effect of Folic Acid Supplementation and Folate Deficiency on Embryo Implantation(Elsevier, 2024) Ozdemir, Elif Seda; Bulut, Deniz Irem; Saglam, Atiye Seda Yar; Isgor, Belgin; Elmas, CigdemImplantation is a critical stage of pregnancy, which occurs in a short period of interaction between the receptive endometrium and the embryo. Folic acid (FA) is a synthetic derivative of folate and is recommended as a preconceptional supplement. However, the impact of different doses of FA supplementation and folate deficiency during the early stages of pregnancy requires further investigation. The aim of this study was to investigate the possible effects of FA supplementation and folate deficiency on expression of Estrogen Receptor Alpha (ER-alpha), Vascular Endothelial Growth Factor-A (VEGFA), and Integrin alpha V and beta3 (Integrin alpha V beta 3). A total of 32, 6-8-week old Wistar albino rats were divided into four groups of control, folate-deficiency, low-dose, and highdose FA supplement groups. After five weeks of FA supplementation and folate deficiency model formation, mated rats were sacrificed on the 5th gestational day (GD), and implantation sites were collected. The expression of ER- alpha, VEGFA, and Integrin alpha V beta 3 in the implantation sites were examined with immunohistochemistry and real-time PCR. The results revealed that the mRNA levels of ESR1, VEGFA, and Integrin alpha V and beta 3 were significantly increased in the high-dose FA group and significantly decreased in the folate deficiency group compared to the control group (p < 0.05). Based on these results, it can be concluded that FA supplementation before pregnancy has positive effects on the maintenance of pregnancy, and folate deficiency may lead to implantation disorders.Article Citation - WoS: 29Citation - Scopus: 32Effects of Exercise Training on Anxiety in Diabetic Rats(Elsevier, 2019) Caliskan, Hasan; Akat, Firat; Tatar, Yakup; Zaloglu, Nezahet; Dursun, Ali Dogan; Bastug, Metin; Ficicilar, HakanDiabetes mellitus (DM) is a common health problem, which manifests itself with chronic hyperglycemia and impaired insulin action. The prevalence of anxiety disorders tends to be high in the diabetic population. Exercise has a well-known anxiolytic effect, also demonstrated on rodents, but the effect of exercise on the DM-induced anxiety is still unknown. Female, Wistar albino rats were randomly divided into four groups (n=8) (C; EX; DM; DM+EX). DM was induced by injection (i.p.; 50 mg/kg) of Streptozotocin (STZ). Rats exercised in moderate intensity on the treadmill (15m/min; 5 degrees; 30 min) for 5 weeks. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT) and Elevated Plus Maze (EPM). According to OFT, central time and central entry have increased with in EX but not in DM+EX. There was no difference between C and DM. Central latency time didn't differ among groups. Unsupported rearing increased in both EX and DM+EX. There was no significant decrease in DM. Freezing time was significantly increased in the DM group. Exercise training reduced freezing time both in diabetic and non-diabetic animals. EPM results were similar. Time spent in open arm was increased significantly in exercise groups compared to their sedentary matches, and freezing time data were also parallel to OFT. Our study revealed that diabetes had shown an anxiogenic effect, which was not severe, and it only manifested itself on some behavioral parameters. Exercise training was reduced anxiety-like behavior both in diabetic and non-diabetic rats. However, because of the nature of exercise studies, it is hard to separate the anxiolytic effect of exercise from the alteration of locomotion.