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Öğe 1,4-Substituted 4-(1H)-pyridylene-hydrazone-type inhibitors of AChE, BuChE, and amyloid-beta aggregation crossing the blood-brain barrier(Elsevier Science Bv, 2013) Prinz, Michaela; Parlar, Sulunay; Bayraktar, Gulsah; Alptuzun, Vildan; Erciyas, Ercin; Fallarero, Adyary; Karlsson, Daniela; Vuorela, Pia; Burek, Malgorzata; Foerster, Carola; Turunc, Ezgi; Armagan, Guliz; Yalcin, Ayfer; Schiller, Carola; Leuner, Kristina; Krug, Manuel; Sotriffer, Christoph A.; Holzgrabe, UlrikeGiven the fundamentally multifactorial character of Alzheimer's disease (AD), addressing more than one target for disease modification or therapy is expected to be highly advantageous. Here, following the cholinergic hypothesis, we aimed to inhibit both acetyl- and butyrylcholinesterase (AChE and BuChE) in order to increase the concentration of acetylcholine in the synaptic cleft. In addition, the formation of the amyloid p fibrils should be inhibited and already preformed fibrils should be destroyed. Based on a recently identified AChE inhibitor with a 1,4-substituted 4-(1H)-pyridylene-hydrazone skeleton, a substance library has been generated and tested for inhibition of AChE, BuChE, and fibril formation. Blood-brain barrier mobility was ensured by a transwell assay. Whereas the p-nitrosubstituted compound 18C shows an anti-AChE activity in the nanomolar range of concentration (IC50 = 90 nM), the bisnaphthyl substituted compound 20L was found to be the best overall inhibitor of AChE/BuChE and enhances the fibril destruction. (C) 2013 Elsevier B.V. All rights reserved.Öğe Changes in the cannabinoid (CB1) receptor expression level and G-protein activation in kainic acid induced seizures(Elsevier Science Bv, 2012) Bojnik, Engin; Turunc, Ezgi; Armagan, Guliz; Kanit, Lutfiye; Benyhe, Sandor; Yalcin, Ayfer; Borsodi, AnnaIt has been known for centuries that exogenous cannabinoids, such as tetrahydrocannabinol have anticonvulsant activity. Recent studies have advanced our understanding of the endogenous cannabinoid system and renewed the interest in cannabinoids as a potential treatment for epilepsy. The endogenous cannabinoid system is rapidly activated after seizure activity but still little is known about the molecular mechanisms underlying the role of the cannabinoid system in epilepsy. In this study epileptiform activity was induced by kainic acid (KA) and effects of the CB1 receptor agonists N-(2-Chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA) on G-protein signaling using the agonist-stimulated [S-35]GTP gamma S binding assay were evaluated. Control and KA treated rat hippocampus and cortex membranes were used. Our results showed that the ACEA displayed a high potency and efficacy in stimulating the G-proteins and when compared to the control animals, significant enhancements were observed in tissues from the KA treated animals. Potency and efficacy values were in particular increased in the hippocampus tissues. Furthermore, gene expression levels of the cannabinoid receptor 1 (CB1) receptor and cannabinoid receptor interacting protein 1 (CRIP1) were measured by RT-PCR, where both CB1 and CRIP1 expressions were found to be elevated in the KA treated animals. (C) 2011 Elsevier B.V. All rights reserved.Öğe Changes in the cannabinoid (CB1) receptor expression level and G-protein activation in the kainic acid model of epilepsy(Polish Acad Sciences Inst Pharmacology, 2011) Bojnik, Engin; Turunc, Ezgi; Armagan, Guliz; Kanit, Lutfiye; Benyhe, Sandor; Yalcin, Ayfer; Borsodi, AnnaÖğe The Comparison of Electrochemical Assay and Agarose Gel Electrophoresis for the Determination of DNA Damage Induced by Kainic Acid(Wiley-V C H Verlag Gmbh, 2009) Karadeniz, Hakan; Armagan, Guliz; Erdem, Arzum; Turunc, Ezgi; Caliskan, Ayfer; Kanit, Lutfiye; Yalcin, AyferA possible DNA damage after interaction of kainic acid (KA) with calf thymus double stranded DNA and genomic DNA was herein determined in in vitro and in vivo conditions using; electrochemical assay and agarose gel electrophoresis. The changes in guanine signal were detected as an indicator of DNA damage in genomic DNA samples isolated from 1 or 10 mg/kg KA-treated animals. The decreased levels of guanine signal were found as 29% and 33% by 1 and 10 mg/kg KA treatment when compared to controls, respectively. The results of gel electrophoresis confirmed DNA damage obtained in identical samples by electrochemical method.Öğe The Comparison of Electrochemical Assay and Agarose Gel Electrophoresis for the Determination of DNA Damage Induced by Kainic Acid(Wiley-V C H Verlag Gmbh, 2009) Karadeniz, Hakan; Armagan, Guliz; Erdem, Arzum; Turunc, Ezgi; Caliskan, Ayfer; Kanit, Lutfiye; Yalcin, AyferA possible DNA damage after interaction of kainic acid (KA) with calf thymus double stranded DNA and genomic DNA was herein determined in in vitro and in vivo conditions using; electrochemical assay and agarose gel electrophoresis. The changes in guanine signal were detected as an indicator of DNA damage in genomic DNA samples isolated from 1 or 10 mg/kg KA-treated animals. The decreased levels of guanine signal were found as 29% and 33% by 1 and 10 mg/kg KA treatment when compared to controls, respectively. The results of gel electrophoresis confirmed DNA damage obtained in identical samples by electrochemical method.Öğe Development of Ketoprofen Solid Dispersions and Evaluation of Their Protective Effects against DNA Damage and Cytotoxicity Potential(Colegio Farmaceuticos Provincia De Buenos Aires, 2017) Rencber, Seda; Ozyazici, Mine; Turunc, Ezgi; Tascioglu, Alev; Gurer Orhan, Hande; Yalcin, AyferThe purpose of this study was to prepare solid dispersion formulations (SDs) of ketoprofen (KP) in order to increase solubility and dissolution rate. This approach is important because of the potential usage of these formulations for neurodegenerative diseases such as Alzheimer's. SDs of KP in different ratios as drug-polymer system were prepared using melting method and ideal formulation was selected by in vitro and in situ studies. In situ effects of these developed formulations on DNA damage was determined in rat brain cortex homogenates. Our results showed that SDs helped to improve the dissolution rates of KP. These formulations decreased the levels of DNA damage in rat brain cortex when compared to controls. The selected B3 formulation would have a potential protective effect on neurodegenerative processes including inflammation. In addition, cytotoxic potential and long term effect of B3 formulation on cell survival were evaluated via MTT and colony formation assays, respectively. Tested formulation had no cytotoxic effect and did not decrease the cell survival at its pharmacologically relevant and higher concentrations. Overall, newly developed SD formulation of KP is suggested to be a promising candidate for long term use in neurodegenerative diseases because of its improved solubility and dissolution rates, increased beneficial activity against DNA damage and its short and long term safety in cells.Öğe Discovery of selective TYK2 inhibitors: Design, synthesis, in vitro and in silico studies of promising hits with triazolopyrimidinone scaffold(Academic Press Inc Elsevier Science, 2024) Istanbullu, Huseyin; Coban, Gunes; Turunc, Ezgi; Disel, Cagla; Butuner, Bilge DebelecThe Janus kinase (JAK) -signal transducer and activator of transcription (STAT) pathway mediates many cytokine and growth factor signals. Tyrosine kinase 2 (TYK2), one of the members of this pathway and the first described member of the JAK family. TYK2 associates with inflammatory and autoimmune diseases, cancer and diabetes. Here, we present novel compounds as selective inhibitors of the canonical kinase domain of TYK2 enzyme. These compounds were rationally designed and synthesized with appropriate reactions. Molecular modeling techniques were used to design and optimize the candidates for TYK2 inhibition and to determine the estimated binding orientations of them inside JAKs. Designed compounds potently inhibited TYK2 with good selectivity against other JAKs as determined by in vitro assays. In order to verify its selectivity properties, compound A8 was tested against 58 human kinases (KinaseProfilerTM assay). The effects of the selected seven compounds on the protein levels of members of the JAK/STAT family were also detected in THP-1 monocytes although the basal level of these proteins is poorly detectable. Therefore, their expression was induced by lipopolysaccharide treatment and compounds A8, A15, A18, and A19 were found to be potent inhibitors of the TYK2 enzyme, (9.7 nM, 6.0 nM, 5.0 nM and 10.3 nM, respectively), and have high selectivity index for the JAK1, JAK2, and JAK3 enzymes. These findings suggest that triazolo[1,5-a]pyrimidinone derivatives may be lead compounds for developing potent TYK2-selective inhibitors targeting enzymes' active site.Öğe Effect of gamma-glutamylcysteine ethylester on the levels of c-fos mRNA expression, glutathione and reactive oxygen species formation in kainic acid excitotoxicity(Wiley, 2010) Turunc, Ezgi; Kanit, Lutfiye; Yalcin, AyferObjectives The aim of this study was to investigate the effect of gamma-glutamylcysteine ethylester (GCEE), a precursor of glutathione biosynthesis, on the levels of glutathione, formation of reactive oxygen species and c-fos mRNA expression in rat hippocampus and cortex in kainic acid-induced excitotoxicity. Methods Sprague-Dawley rats were used and divided into four groups: control, kainic acid (10 mg/kg), GCEE (10 mg/kg) and kainic acid (10 mg/kg) + GCEE (10 mg/kg). Kainic acid and GCEE were administered to the rats intraperitoneally. The levels of glutathione and the expressions of c-fos mRNA in hippocampus and cortex tissues were determined using spectrophotometric and reverse transcription followed real-time PCR methods, respectively. Formation of reactive oxygen species was determined using dichlorofluorescin fluorescence in brain synaptosomes treated with kainic acid or GCEE in vitro. Key findings Kainic acid treatment significiantly upregulated the expression of c-fos mRNA in the hippocampus and cortex when compared to the control group. GCEE treatment significantly decreased the levels of c-fos mRNA in the cortex when compared to the kainic acid-treated group. GCEE treatment against kainic acid significantly increased the levels of glutathione in the cortex and hippocampus, and decreased the levels of formation of reactive oxygen species when compared to kainic acid-treated synaptosomes. Conclusions The increased levels of glutathione and the reduced levels of reactive oxygen species formation lead us to conclude that GCEE may be beneficial as a potential antioxidant against neurodegenerative processes where excitotoxicity is involved.Öğe Effects of nicotinamide treatment on mRNA expression of various enzymes involved in NAD(+) metabolism in A beta(1-42) induced neurodegeneration(Elsevier Science Inc, 2016) Kilicarslan, Irem; Turunc, Ezgi; Kanit, Lutfiye; Yalcin, AyferÖğe The Effects of Prenatal Stress on Cortical and Hippocampal Gene Expression Profiles of DNA Methyltransferases and Histone Deacetylases in Female Rats(2022) Turunc, Ezgi; Uyanıkgil, Yiğit; Yalçın, Ayfer; Temiz, TijenThe aim of this study was to investigate the effects of prenatal stress (PS) on mRNA levels of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) in cerebral cortex and hippocampus of female rats. PS was induced in rats with dexamethasone (Dex). From gestation day 14 to 21, pregnant rats were injected daily with Dex (100 ?g/kg) or saline. After birth, at 3 months of age, female rats were decapitated (n=5). The effects of Dex on epigenetic mechanisms were investigated by real-time PCR through mRNA levels of DNMT1, DNMT3a, DNMT3b, HDAC1 and HDAC2. Statistical significant differences were determined with one-way analysis of variance. Prenatal Dex exposure caused significant increases in DNMT3a, HDAC1 and HDAC2 mRNA levels in cortex and hippocampus. We further found that DNMT3b mRNA levels significantly increased in hippocampus but decreased in cortex of Dex group. No significant differences were found in DNMT1 mRNA levels. It was concluded that PS may trigger dysregulation of epigenetic mechanisms in cortex and hippocampus of female rats through alterations in gene expression profiles of DNMT3a, DNMT3b, HDAC1 and HDAC2.Öğe Electrochemical Determination of Glutathione in Plasma at Carbon Nanotubes Based Screen Printed Electrodes(Bentham Science Publ Ltd, 2013) Turunc, Ezgi; Karadeniz, Hakan; Armagan, Guliz; Erdem, Arzum; Yalcin, AyferGlutathione (GSH) is a major endogenous antioxidant highly active in human tissues and plays a key role in controlling cellular thiol redox system, maintaining the immune and detoxification system. The determination of GSH levels in tissue is important to estimate endogenous defenses against oxidative stress. In our study, the multi-walled carbon nanotube modified screen-printed electrodes (MWCNT-SPEs) were used to determine the levels of GSH in trichloroacetic acid (TCA)-treated or untreated samples of rat plasma. It was found that the deproteinization of samples with TCA improved the electrochemical detection of GSH particularly in plasma. The oxidation of GSH was measured by using differential pulse voltammetry (DPV) method in combination with MWCNT-SPE (n=3), and the detection limit of GSH was found to be 0.47 mu M (S/N=3). The GSH levels in plasma samples were also measured spectrophotometrically in order to compare the effectiveness of electrochemical method and we obtained a high correlation between the two methods (R-2=0.976).Öğe An examination of carbopol hydrogel/organogel bigels of thymoquinone prepared by microwave irradiation method(Taylor & Francis Ltd, 2020) Yapar, Evren Algin; Tanriverdi, Sakine Tuncay; Tural, Gulsen Aybar; Gumus, Zinar Pinar; Turunc, Ezgi; Gokce, Evren HomanNigella sativa L. is shown wide spread over the world and contains many useful phytochemicals. Much of the biological activity of the seeds has been shown due to the presence of thymoquinone (TQ). Its poor aqueous solubility of TQ hinders its delivery to target site. the aim of this work was to prepare TQ bigels composed of Carbopol 974 P NF (C974) in PEG 400 (organogel) or C974 in water (hydrogel) with microwave heating method. A novel technique, high speed homogenization followed by microwave heating, was used to prepare organogels. the pH, electrical conductivity, differential scanning calorimetry, rheological properties, and morphological structure of the formulations have been evaluated, and the effect of microwave on drug content and TQ antioxidant activity has been investigated. the bigels of TQ were successfully producedviahigh-speed homogenization followed by microwave-assisted heating for the first time in this study. Highly lipophilic TQ was successfully dissolved in organogel, and it was not affected from the microwaves. It can be stated that microwave heating is a promising method to obtain C974 organogels and thus bigels with appropriate above indicated investigated physicochemical characteristics. the time and energy consumption could be decreased with microwave-assisted heating, especially for gel preparation in the field of pharmaceuticals.Öğe Mu opioid receptor mRNA expression, binding, and functional coupling to G-proteins in human epileptic hippocampus(Wiley-Blackwell, 2012) Cuellar-Herrera, Manola; Luisa Velasco, Ana; Velasco, Francisco; Chavez, Laura; Orozco-Suarez, Sandra; Armagan, Guliz; Turunc, Ezgi; Bojnik, Engin; Yalcin, Ayfer; Benyhe, Sandor; Borsodi, Anna; Alonso-Vanegas, Mario; Rocha, LuisaMu opioid receptors (MOR) are known to be involved in seizure activity. The main goal of the present study was to characterize the MOR mRNA expression, binding, as well as G protein activation mediated by these receptors in epileptic hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (TLE). In contrast with autopsy samples, hippocampus obtained from patients with mesial TLE demonstrated enhanced MOR mRNA expression (116%). Saturation binding experiments revealed significantly higher (60%) Bmax values for the mesial TLE group, whereas the Kd values were not statistically different. Although mesial TLE group demonstrated high levels of basal binding for the G proteins (136%), DAMGO-stimulated [35S]GTP?S binding did not demonstrate significant alterations. In conclusion, our present data provide strong evidence that the epileptic hippocampus of patients with pharmacoresistant mesial TLE presents significant alterations in MOR. Such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations. (C) 2010 Wiley Periodicals, Inc.Öğe Potential neuroprotective effect of gamma-glutamylcysteine ethyl ester on rat brain against kainic acid-induced excitotoxicity(Taylor & Francis Ltd, 2010) Yalcin, Ayfer; Armagan, Guliz; Turunc, Ezgi; Konyalioglu, Sibel; Kanit, LutfiyeThe aim of this study was to investigate the effect of gamma-Glutamylcysteine Ethyl Ester (GCEE) on the levels of GSH, caspase-3 activity, DNA damage and the expressions of Bcl-2, Bax and p53 mRNAs in rat hippocampus after status epilepticus (SE) induced by systemic kainic acid (KA). The male rats were divided into four groups as controls, KA (10 mg/kg), GCEE (10 mg/kg) and KA+GCEE. Glutathione (GSH) levels and caspase-3 activity were determined spectrophotometrically and colourimetrically, respectively. DNA damage and Bcl-2, Bax and p53 mRNA expressions were quantified by comet assay and reverse transcription followed by RT-PCR, respectively. KA treatment significantly depleted GSH levels, induced DNA damage, caspase-3 activity and the expressions of p53 and Bax mRNA. GCEE treatment protected GSH levels, decreased DNA damage and the levels of p53 and Bax/Bcl-2 mRNA against KA injection. These results indicate that GCEE treatment at the dose of 10 mg/kg is capable to protect the depleted levels of GSH and shows an anti-apoptotic activity due to the decreased levels of apoptotic biomarkers in the rat hippocampus after SE induced by KA.Öğe Potential neuroprotective effects of 2-hydroxypropyl-? cyclodextrin against amyloid ? (1-42)-induced neurotoxicity on the rat hippocampus(Taylor & Francis Ltd, 2024) Yalcin, Ayfer; Turunc, Ezgi; Kaplan, Mehmet Mahsum; Uyanikgil, Yigit; Erzurumlu, Yalcin; Gavini, Elisabetta; Kanit, LutfiyeThe neurodegenerative mechanisms of Alzheimer's disease (AD) are not fully understood, but it is believed that amyloid beta (A beta) peptide causes oxidative stress, neuroinflammation, and disrupts metabotropic glutamate receptor 5 (mGluR5) signaling by interacting with cholesterol and caveolin-1 (Cav-1) in pathogenic lipid rafts. This study examined the effect of 2-hydroxypropyl-beta-cyclodextrin (HP-CD) on cholesterol, oxidative stress (total oxidant status), neuroinflammation (TNF-alpha), and mGluR5 signaling molecules such as PKC beta 1, PKC beta 2, ERK1/2, CREB, BDNF, and NGF in A beta (1-42)-induced neurotoxicity. The Sprague-Dawley rats were divided into four groups: control (saline), A beta (1-42), HP-CD (100 mg/kg), and A beta (1-42) + HP-CD (100 mg/kg). All groups received bilateral stereotaxic injections of A beta (1-42) or saline into the hippocampus. After surgery, HP-CD was administered intraperitoneally (ip) for 7 days. Cholesterol, TNF-alpha, and TOS levels were measured in synaptosomes isolated from hippocampus tissue using spectrophotometry, fluorometry, and enzyme immunoassay, respectively. The gene expressions of Cav-1, mGluR5, PKC beta 1, PKC beta 2, ERK1/2, CREB, BDNF, and NGF in hippocampus tissue were evaluated using reverse transcription PCR after real-time PCR analysis. Treatment with A beta (1-42) significantly elevated cholesterol, TOS, TNF-alpha, Cav-1, PKC beta 2, and ERK1/2 levels. Additionally, mGluR5, CREB, and BDNF levels were shown to be lowered. HP-CD reduced cholesterol, TOS, and TNF-alpha levels while increasing mGluR5, CREB, and BDNF in response to A beta (1-42) treatment. These findings indicate that HP-CD may have neuroprotective activity due to the decreased levels of cholesterol, oxidative stress, and neuroinflammation, as well as upregulated levels of mGluR5, CREB, and BDNF.Öğe Potential protective effects of hydroxypropyl-beta-cyclodextrin on A beta(1-42)-induced neurotoxicity(Elsevier Science Inc, 2018) Yalcin, Ayfer; Turunc, Ezgi; Uyanikgil, Yigit; Kanit, Lutfiye; Kaplan, Mehmet M.; Erzurumlu, Yalcin; Sevinc, EgeÖğe Prenatal Dexamethasone Exposure in Male Rats Alters Gene Expression Patterns of Epigenetic Enzymes in Hippocampus and Cortex(Aves, 2022) Turunc, Ezgi; Uyanikgil, Yigit; Temiz, Tijen Kaya; Yalcin, AyferObjective: This study aimed to examine the effects of prenatal stress (PS) induced by dexamethasone exposure on gene expression levels of epigenetic enzymes in hippocampus and cerebral cortex of male rats through relative mRNA levels of histone acetyltransferases (activating transcription factor 2, P300), histone deacetylases (HDAC1, HDAC2), and DNA methyltransferases (DNMT1, DNMT3a, DNMT3b). Methods: Pregnant rats were daily injected subcutaneously with dexamethasone (0.2 mg/kg) or saline during the third week of gestation. After birth, male rats were killed at 90 days of age (n = 5 for control and dexamethasone groups). Hippocampal and cortical tissues were used for gene expression analyses. The effects of dexamethasone on epigenetic mechanisms were investigated by real-time polymerase chain reaction through relative mRNA levels of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2. Statistical comparisons were performed with Student's t-test. Results: Prenatal dexamethasone exposure (PDE) caused increased DNMT1, DNMT3a, DNMT3b, activating transcription factor 2 and decreased P300 mRNA levels in hippocampus while increased DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2 mRNA levels were achieved in cortex. Furthermore, no significant differences were obtained in cortical DNMT1 and hippocampal HDAC1 and HDAC2 gene expression levels between control and prenatally stressed rats. Conclusion: Our results emphasize the effect of prenatal dexamethasone exposure on gene expression levels of epigenetic enzymes involved in histone acetylation/deacetylation and DNA methylation in male rats and suggest that prenatal stress may lead to epigenetic dysregulation through alterations in hippocampal and cortical gene expression patterns of DNMT1, DNMT3a, DNMT3b, activating transcription factor 2, P300, HDAC1, and HDAC2.Öğe Rabies virus-mimicking liposomes for targeted gene therapy in Alzheimer's disease(Elsevier, 2024) Erel Akbaba, Gulsah; Akbaba, Hasan; Karaman, Ozan; Tian, Tian; Tannous, Bakhos A.; Turunc, EzgiRNA interference (RNAi) harbors significant potential for treating neurological disorders; nevertheless, limited efficacy has been discerned. The presence of barriers within the central nervous system, coupled with the inherent instability of nucleic acids within biological conditions, poses formidable challenges in advancing effective gene delivery strategies. In this study, we designed and prepared a virus-mimic non-viral gene vector, rabies virus glycoprotein (RVG29)-decorated liposome (f(Lipo)-RVG29), to deliver small interfering RNAs to the brain. Alzheimer's disease (AD) was chosen as a model of neurodegenerative disease in this context, and b-site APP cleaving enzyme silencing siRNA (siBACE1) was used. The developed liposomal delivery system has a particle size of under 80 nm with a spherical shape, positive zeta potential, and the ability to protect siRNA against nucleases. In vitro studies demonstrate that functionalizing the cationic liposome by the RVG29 targeting ligand significantly enhances the effectiveness of gene delivery and silencing. Examination through ex vivo imaging illustrates an increased deposition of fluorescent-labeled f(Lipo)-RVG29 within brain tissue after 12 h post application. Additionally, the in vivo delivery of f(Lipo)-RVG29 carrying siRNA has substantially suppressed BACE1 expression at both mRNA and protein levels within the brain tissue. Our results suggest that the developed non-viral vector could be a promising gene carrier system combining the synergistic effect of virus-mimic RVG29 ligand with bioinspired liposome that imitates the natural lipid bilayers of cell membranes for braintargeted RNAi therapeutics.Öğe Studies on Mefenamic Acid Microparticles: Formulation, In Vitro Release, and In Situ Studies in Rats(Springer, 2009) Sevgi, Ferhan; Yurdasiper, Aysu; Kaynarsoy, Buket; Turunc, Ezgi; Gueneri, Tamer; Yalcin, AyferIn this study, we investigated the in vitro characteristics of mefenamic acid (MA) microparticles as well as their effects on DNA damage. MA-loaded chitosan and alginate beads were prepared by the ionotropic gelation process. Microsponges containing MA and Eudragit RS 100 were prepared by quasi-emulsion solvent diffusion method. The microparticles were characterized in terms of particle size, surface morphology, encapsulation efficiency, and in vitro release profiles. Most of the formulation variables manifested an influence on the physical characteristics of the microparticles at varying degrees. We also studied the effects of MA, MA-loaded microparticles, and three different polymers on rat brain cortex DNA damage. Our results showed that DNA damage was higher in MA-loaded Eudragit microsponges than MA-loaded biodegradable chitosan or alginate microparticles.Öğe Transcoronary Gradients of Mechanosensitive MicroRNAs as Predictors of Collateral Development in Chronic Total Occlusion(Mdpi, 2024) Vural, Mustafa Gokhan; Temel, Hulya Yilmaz; Turunc, Ezgi; Akdemir, Ramazan; Tatli, Ersan; Agac, Mustafa TarikBackground and Objectives: In this present study, we investigated the impact of mechanosensitive microRNAs (mechano-miRs) on the collateral development in 126 chronic total occlusion (CTO) patients, selected from 810 undergoing angiography. Materials and Methods: We quantified the collateral blood supply using the collateral flow index (CFI) and assessed the transcoronary mechano-miR gradients. Results: The patients with favorable collaterals had higher CFI values (0.45 +/- 0.02) than those with poor collaterals (0.38 +/- 0.03, p < 0.001). Significant differences in transcoronary gradients were found for miR-10a, miR-19a, miR-21, miR-23b, miR-26a, miR-92a, miR-126, miR-130a, miR-663, and let7d (p < 0.05). miR-26a and miR-21 showed strong positive correlations with the CFI (r = 0.715 and r = 0.663, respectively), while let7d and miR-663 were negatively correlated (r = -0.684 and r = -0.604, respectively). The correlations between cytokine gradients and mechano-miR gradients were also significant, including Transforming Growth Factor Beta with miR-126 (r = 0.673, p < 0.001) and Vascular Endothelial Growth Factor with miR-10a (r = 0.602, p = 0.002). A regression analysis highlighted the hemoglobin level, smoking, beta-blocker use, miR-26a, and miR-663 as significant CFI determinants, indicating their roles in modulating the collateral vessel development. Conclusions: These findings suggest mechanosensitive microRNAs as predictive biomarkers for collateral circulation, offering new therapeutic perspectives for CTO patients.
