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Effects of Iron Ion Ratios on the Synthesis and Adsorption Capacity of the Magnetic Graphene Oxide Nanomaterials

ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING 2025年第6期50卷 4137-4150页

作者： Konuk, H. Hamiyet Alp, Erdem Ozaydin, Zeynep Koyuncu, Dilsad Dolunay Eslek Arbag, Huseyin Gazi Univ Dept Chem Engn TR-06570 Ankara Turkiye Turkish Med & Med Devices Agcy TR-06520 Ankara Turkiye

Nanocomposites consisting of graphene oxide (GO) and Fe3O4 nanoparticles are significant structures due to their high absorption and magnetic properties, and they are promising materials for various application areas from drug delivery to dye removal. In this study, the effect of adding iron salts with different Fe2+/Fe3+ ratios during the synthesis of magnetic graphene oxide (MNGO) nanocomposites on size distribution, magnetic properties, morphology, and adsorption-desorption behavior was investigated. Characterization results indicated that superparamagnetic iron oxide nanoparticles (SPIONs) were successfully integrated into MNGO nanocomposites, and the surface area increased when SPIONs were synthesized on GO significantly, especially with increasing Fe2+/Fe3+ ratio. MNGO nanocomposites were tested for the removal of methylene blue (MB). Moreover, the effects of initial pH, dye concentration, and temperature on the adsorption process of MB were also studied. As a result, it is shown that the Fe2+/Fe3+ ratio has a crucial effect on the adsorption-desorption behavior of MNGO nanocomposites, which are promising nanomaterials for dye removal studies.

关键词： 2D materials SPIONs Graphene Nanostructure Adsorption

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SGLT2 inhibitors: how do they affect the cardiac cells

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MOLECULAR AND CELLULAR BIOCHEMISTRY 2025年第3期480卷 1359-1379页

作者： Erdogan, Betul Rabia Arioglu-Inan, Ebru Turkish Med & Med Devices Agcy Ankara Turkiye Ankara Univ Fac Pharm Dept Pharmacol Dogol St4 Yenimahalle TR-06560 Ankara Turkiye

The first sodium-glucose cotransporter-2 inhibitor (SGLT2I), canagliflozin, was approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes in 2013. Since then, other members of this drug class (such as dapagliflozin, empagliflozin, and ertugliflozin) have become widely used. Unlike classical antidiabetic agents, these drugs do not interfere with insulin secretion or action, but instead promote renal glucose excretion. Since their approval, many preclinical and clinical studies have been conducted to investigate the diverse effects of SGLT2Is. While originally introduced as antidiabetic agents, the SGLT2Is are now recognized as pillars in the treatment of heart failure and chronic kidney disease, in patients with or without diabetes. The beneficial cardiac effects of this class have been attributed to several mechanisms. Among these, SGLT2Is inhibit fibrosis, hypertrophy, apoptosis, inflammation, and oxidative stress. They regulate mitochondrial function and ion transport, and stimulate autophagy through several underlying mechanisms. This review details the potential effects of SGLT2Is on cardiac cells.

关键词： Apoptosis Cardiac cells Fibrosis Inflammation Ion transport SGLT2 inhibitors

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An RP-HPLC Method for the Simultaneous Analysis of Selected Antiviral Drugs

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CHROMATOGRAPHIA 2025年第3期88卷 179-191页

作者： Ozdemirhan, Mehmet Emre Ozen, Guerkan Nemutlu, Emirhan Turkish Med & Med Devices Agcy Dept Anal & Control Labs Ankara Turkiye Baskent Univ Fac Pharm Dept Analyt Chem Etimesgut Ankara Turkiye Hacettepe Univ Fac Pharm Dept Analyt Chem Ankara Turkiye

A rapid and efficient reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the simultaneous determination of six antiviral drugs: emtricitabine (EMT), entecavir (ENT), favipiravir (FAV), ganciclovir (GAN), valaciclovir (VAL), and valganciclovir (VLG). Chromatographic separation was achieved on an ExsilTM Mono 100 C18 column using a mobile phase of 50 mM phosphate buffer (pH 4): acetonitrile (90:10, v/v) at a flow rate of 0.5 mL/min. UV detection was performed at 215 nm. The method was validated according to ICH Q2(R2) guidelines, demonstrating excellent linearity (R-2 > 0.9938) across the concentration ranges of 1.0-150 mu g/mL for EMT, ENT and VLG, and 5.0-200 mu g/mL for FAV, GAN and VAL. The LOD and LOQ values ranged from 0.02 to 0.48 mu g/mL and 0.05 to 1.45 mu g/mL, respectively. Intra-day and inter-day precision, expressed as relative standard deviation (RSD), were less than 1.82%, while accuracy, expressed as relative error (RE), was within +/- 1.34%. Recovery studies yielded values ranging from 98.12% to 101.60%, further confirming method accuracy. The method proved to be selective, robust, and suitable for the quantitative analysis of these antiviral drugs in pharmaceutical formulations, with results obtained for commercially available tablets demonstrating excellent agreement with labeled contents. Notably, stability studies revealed the susceptibility of EMT, ENT, and FAV to degradation under refrigerated storage, highlighting the need for timely analysis of these compounds. In addition, the greenness, blueness, and whiteness of the method were evaluated, and the developed method performs strongly across environmental (AGREE score: 0.79), practical (BAGI index: 85), and sustainability (whiteness value: 74.7) criteria, reinforcing its viability as a sustainable approach for antiviral analysis. This validated RP-HPLC method provides a reliable and efficient tool for the quality control of these essential ant

关键词： Antivirals HPLC Validation Pharmaceuticals

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THE effect of P2X7 receptor activation on functional responses of human left internal mammary artery

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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2025年第2期398卷 2027-2037页

作者： Bayram, Zeliha Akcabag, Esra Ozbey, Gul Nacitarhan, Cahit Ozdem, Sebahat Turkay, Cengiz Ozdem, Sadi S. Turkish Med & Med Devices Agcy Ankara Turkiye Akdeniz Univ Med Fac Dept Med Pharmacol Dumlupinar Ave TR-07070 Antalya Turkiye Akdeniz Univ Med Fac Dept Med Biochem Antalya Turkiye Akdeniz Univ Med Fac Dept Cardiovasc Surg Antalya Turkiye

The Purinoreceptor 7 (P2X7R) has become a promising drug target in many cardiovascular diseases, including coronary artery disease, since prolonged activation of P2X7R could promote vascular dysfunction, atherosclerosis, and thrombosis. Thus, we aimed to study the effects of P2X7R activation on vascular relaxation responses of the human left internal mammary artery (LIMA). Sections of redundant human LIMA were cut into 3-mm wide rings,, suspended in 20-mL organ baths containing physiologic salt solution, and attached to an isometric force transducer connected to a computer-based data acquisition system. Long-term (60 min) incubation with specific P2X7R agonist Bz-ATP caused significant reductions in relaxation responses of LIMA to ATP and acetylcholine, which were reversed by selective P2X7R antagonists Brilliant Blue G or AZ11645373, whereas there were no changes in relaxation responses to endothelium-independent vasodilators isoprenaline, cAMP analog 8-Br-cAMP, and nitric oxide donor sodium nitroprusside. The impairment in relaxant responses of LIMA to endothelium-dependent vasodilators following activation of P2X7R for the long-term may contribute to postoperative LIMA vasospasm and hypertension. Modulation of P2X7R activity with selective agents may represent a new potential therapeutic approach in patients undergoing coronary artery bypass grafting surgery.

关键词： ATP Acetylcholine Human left internal mammary artery Endothelium Vasorelaxation

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Trimethylamine N-oxide as a potential prognostic biomarker for mortality in patients with COVID-19 disease

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ADVANCES IN medICAL SCIENCES 2025年第1期70卷 174-183页

作者： Aksoyalp, Zinnet Sevval Erdogan, Beti Rabia Aksun, Saliha Sozmen, Melih Kaan Aksun, Murat Buharalioglu, Cineyt Kemal Altinci-Karahan, Nagihan Turgut, Nergiz Hacer Kaya-Temizh, Tijen Izmir Katip Celebi Univ Dept Pharmacol Izmir Turkiye Turkish Med & Med Devices Agcy Ankara Turkiye Izmir Katip Celebi Univ Dept Med Biochem Izmir Turkiye Izmir Katip Celebi Univ Dept Publ Hlth Izmir Turkiye Harvard TH Chan Sch Publ Hlth Dept Global Hlth & Populat Boston MA USA Izmir Katip Celebi Univ Dept Anesthesiol & Reanimat Izmir Turkiye Ataturk Training & Res Hosp Dept Anesthesiol & Reanimat Izmir Turkiye Izmir Katip Celebi Univ Dept Med Pharmacol Izmir Turkiye

Purpose Trimethylamine N-oxide (TMAO) is suggested as a biomarker for inflammatory and cardiovascular diseases which are identified as risk factors for severe cases of coronavirus disease 2019 (COVID-19). Our primary aim was to assess prognostic potential of serum TMAO levels in predicting COVID-19-related mortality. The secondary aim was to examine the potential of various biochemical parameters, particularly those associated with inflammation or thrombosis, as predictors of mortality. Patients and methods In this prospective and single-centre study, COVID-19 patients were categorized as death (group 1) or discharged (group 2) based on their in-hospital mortality status. The characteristics of participants were documented, and clinical data, including TMAO, angiotensin-converting enzyme-2 (ACE2), and neutrophil to lymphocyte ratio (NLR), were determined. The association of these independent variables with the COVID-19-related mortality, was assessed by calculation of crude odds ratios (OR) in bivariate and logistic regression analysis. Receiver operation characteristic (ROC) analysis was used for cut-off values. Results The serum levels of TMAO, ACE2 and NLR were markedly higher in group 1 on the days of hospital admission (p < 0.05, p < 0.05, and p < 0.01, respectively). Serum TMAO levels (OR 1.422;95 % CI [1.067-1.894];p = 0.016) and NLR (OR 1.166;95 % CI [1.012-1.343];p = 0.033) were determined as independent predictors for COVID-19-related mortality with after multivariate logistic regression analysis. The optimal cut-off values were detected as 7.9 ng/ml for TMAO (71 % sensitivity, 68 % specificity, AUC = 0.701). Conclusions The findings of this initial study indicate that serum TMAO levels and NLR may be useful in predicting mortality in the early stages of COVID-19.

关键词： Biomarker Inflammation Mortality Prognosis SARS-CoV-2

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Formulation Optimization and in Vitro-in Vivo Evaluation of Alpha Lipoic Acid-Loaded Lipid-Polymer Hybrid Nanoparticles Via Design of Experiments

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JOURNAL OF PHARMACEUTICAL INNOVATION 2025年第2期20卷 1-15页

作者： Coban, Ozlem Demirtas, Hatice Kaya-Yasar, Yesim Engin, Seckin Yildirim, Sercan Morsali, Mohammed Reza Karadeniz Tech Univ Fac Pharm Dept Pharmaceut Technol TR-61080 Trabzon Turkiye Karadeniz Tech Univ Drug & Pharmaceut Technol Applicat & Res Ctr TR-61080 Trabzon Turkiye Karadeniz Tech Univ Fac Pharm Dept Pharmacol TR-61080 Trabzon Turkiye Karadeniz Tech Univ Fac Pharm Dept Analyt Chem TR-61080 Trabzon Turkiye Karadeniz Tech Univ Fac Pharm TR-61080 Trabzon Turkiye Turkish Med & Med Devices Agcy Ankara Turkiye

PurposeAlpha lipoic acid (ALA) is a natural compound that has recently gained attention for its anti-inflammatory potential. ALA has a low bioavailability and in vitro stability, making its clinical use a challenge. Lipid-polymer hybrid nanoparticles (LPHNPs), a newly discovered core-shell nanostructures, are derived from liposomes and polymeric nanoparticles, and they were commonly used to improve in vivo efficiency and stability of active *** current study aimed to prepare ALA-loaded LPHNPs via the design of experiments (DoE) approach to improve oral bioavailability and in vitro stability of ALA. The Plackett-Burman design was used to select independent variables by evaluating the effects of drug amount, stirring rate, polymer amount, lipid/polymer ratio, water/organic solvent (W/Os) ratio, and polyvinyl alcohol (PVA) concentration on formulation properties. Afterward, statistically significant formulation parameters were optimized using the Box-Behnken design (BBD). Finally, the in vitro properties were evaluated, and the in vivo anti-inflammatory effect of the optimized formulation was tested using formalin-induced paw edema in *** main factors affecting the mean particle size (mPS), polydispersity index (PdI), and zeta potential (ZP) values of ALA-loaded LPHNPs were the stirring rate, W/Os ratio, and PVA concentration;however, the independent variables had no significant effect on encapsulation efficiency (EE). Furthermore, optimized ALA-loaded LPHNPs also significantly reduced paw edema thickness and volume with a prolonged duration of action compared to ALA solution during 6 h after formalin *** optimized ALA-loaded LPHNPs with core-shell structure had sustained control release up to day 17 and exhibited superior colloidal and chemical stability under various in vitro conditions and prolonged and robust in vivo anti-inflammatory effect.

关键词： Design of experiments (DoE) Alpha lipoic acid (ALA) Lipid-polymer hybrid nanoparticles (LPHNPs) Plackett-burman Box-behnken design (BBD) in vivo anti-inflammatory

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Investigation of paraspecific effects of polyvalent snake antivenom on the venom of three vipers (Vipera berus berus;Linnaeus 1758, Vipera ammodytes ammodytes;Linnaeus, 1758 and Montivipera raddei;Boettger, 1890)

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TOXICON 2025年 260卷 108349页

作者： Cevik, Yasemin Numanoglu Altun, Derya Serin, Metin Bozkurt, Edibe Nurzen Namli Bozyigit, Ilhan Icigen, Halit Ozkan Kanat, Mehmet Ali Republ Turkish Minist Hlth Gen Directorate Publ Hl Biol Prod Dept Microbiol & Reference Lab TR-06430 Ankara Turkiye Republ Turkish Minist Hlth Gen Directorate Publ Hl TB Dept Ankara Turkiye Republ Turkish Minist Hlth Turkish Med & Med Devices Agcy TR-06430 Ankara Turkiye

Objective: The aim was to investigate the paraspecific efficiacy of the National HSGM-polyvalent snake anti-venom, which is used in the treatment of snakebite poisoning cases in Turkey, on Vipera ammodytes ammodytes and Vipera berus berus snakes that live widely in Europe and Montivipera raddei venoms that live in Turkey and Armenia. Method: The paraspecific efficiacy of the antivenom on these three venoms were determined using the test method for neutralization of the lethal effect of the venom in mice specified in the European pharmacopoeia. Conclusion: It was observed that HSGM-PVSAV produced using Vipera ammodytes montandoni, Macrovipera lebetina obtusa and Montivipera xanthina venoms showed an effect above the European pharmacopoeia limits against all three snake venoms.

关键词： Paraspecific neutralization Polyvalent snake antivenom Vipera ammodytes ammodytes Vipera berus berus Montivipera raddei

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Off-label use of immune checkpoint inhibitors for the treatment of solid tumors: analysis of a nationwide patient sample

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JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 2023年第11期149卷 8655-8662页

作者： Kandemir, Esin Aysel Karaomerlioglu, Irem Yaradilmis, Ibrahim Muaz Turkish Med & Med Devices Agcy Ankara Turkiye

PurposeImmune checkpoint inhibitors (ICIs) have become an indispensable part of clinical practice;however, off-label use of these agents is unknown. We aimed to define the patterns of off-label use of ICIs in a nationwide sample of *** online database (Recetem) was retrospectively searched for off-label use cases related to ICIs approved during a 6-month period. Adult patients with metastatic solid tumors were included. Ethics approval was obtained. Reasons for off-label use were recorded in eight categories and cases were assessed for adherence to current guidelines. Statistical analysis was performed with GNU PSPP version *** hundred seventy-seven reasons for use were recorded for 538 cases related to 527 patients (67.5% male). Non-small-cell lung cancer (NSCLC) (35.9%) was the most common cancer type. Nivolumab (49%), pembrolizumab (25.5%), and atezolizumab (25%) were commonly used. The top reason for off-label use was lack of approval for the cancer type (37.1%), followed by use beyond the approved treatment line (21%). Nivolumab was more frequently used than atezolizumab and/or pembrolizumab in patients with malignant melanoma, kidney cancer, head and neck cancer, and hepatocellular carcinoma (Chi-square goodness-of-fit test, p < 0.001). The guideline adherence rate was 60.5%.ConclusionOff-label use of ICIs was primarily related to (NSCLC), and most patients were treatment-naive in contrast to the acceptance that off-label use results from exhausted treatment options. Lack of approval is a significant reason for the off-label use of ICIs.

关键词： Solid tumors Immunotherapy Immune checkpoint inhibitors Off-label Clinical practice

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Review of novel and supplemental approvals of the targeted cancer drugs by the Food and Drug Administration in 2021

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JOURNAL OF ONCOLOGY PHARMACY PRACTICE 2023年第1期29卷 191-207页

作者： Kandemir, Esin Aysel Turkish Med & Med Devices Agcy TR-06520 Ankara Turkey

Objective This review aims to present the most recent results from clinical trials of targeted cancer drugs that led to the Food and Drug Administration approval in 2021 and reflect the changing treatment landscape of solid malignancies. Data Sources Novel approvals and supplemental approvals in 2021 were retrieved from the official web page of the Food and Drug Administration (Drugs@FDA). This review did not include approvals for generics, biosimilars, imaging, and diagnostics agents. Data Summary This review included 10 novel drugs approved for 11 indications and 10 already-approved drugs approved for 21 indications by the Food and Drug Administration in 2021. Novel approvals mainly were related to treating an orphan disease. In addition, one-third of the supplemental approvals were given for neoadjuvant or adjuvant treatment, while the number of indications for each tumor site was as follows: gastrointestinal (7), genitourinary (5), skin (3), lung (2), breast (2), thyroid (1), and cervix (1). Conclusions Targeted cancer treatments are gaining more importance than ever in treating malignant diseases. As the approval of targeted cancer drugs provides a possibility for patients and this trend is expected to continue in the future, it remains vital for healthcare providers to stay up-to-date with newer therapeutic options.

关键词： Cancer targeted drugs novel approvals supplemental approvals food and drug administration

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A model study by using polymeric molecular imprinting nanomaterials for removal of penicillin G

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ENVIRONMENTAL MONITORING AND ASSESSMENT 2020年第6期192卷 367-367页

作者： Kuru, Cansu Ilke Ulucan, Fulden Kusat, Keyser Akgol, Sinan Ege Univ Dept Biochem Fac Sci Izmir Turkey Turkish Hlth Minist Turkish Med & Med Devices Agcy Ankara Turkey

We aimed to develop a molecularly imprinted polymeric systems with using penicillin G as a template molecule for removal of the antibiotic residues from environmental samples. Firstly, Pen-G-imprinted poly (2-hydroxyethyl methacrylate-N-methacryloyl-l-alanine) [p(HEMA-MAAL)] nanopolymers were synthesized by surfactant-free emulsion polymerization method. Then, template molecule (Pen-G) was extracted from nanopolymers. Synthesized nanopolymers were characterized by different methods such as Fourier-transform infrared spectroscopy (FTIR), elemental and zeta-size analysis, scanning electron microscope (SEM), and surface area calculations. Nanopolymers have 60.38 nm average size and 1034.22 m(2)/g specific surface area. System parameters on Pen-G adsorption onto Pen-G imprint nanopolymers were investigated at different conditions. The specific adsorption value (Q(max)) of molecularly impirinted p(HEMA-MAAL) nanopolymers was found 71.91 g/g for Pen-G in 5 mg/mL Pen-G initial concentration. Pen-G adsorption of molecularly imprinted nanopolymers was 15 times more than non-imprinted polymer. It is shown that obtained p(HEMA-MAAL) nanopolymer was a reuseable product which protected its adsorption capacity of 98.9% after 5th adsorption-desorption cycle. In conclusion, we suggest a method to develop a nanostructure, selective, low-cost molecularly imprinted polymeric systems with using penicillin G as a template molecule for removal of the antibiotic residues.

关键词： Moleculer imprinted polymers Nanopolymers beta-Lactam antibiotics Removal of penicillin G

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