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Öğe Edaravone’s hepatoprotective effects against oxidative stress in valproic acid–induced rat model(2024) Hacıhasanoğlu Çakmak, Neziha; Yanardağ, RefiyeIn this experimental study, the effect of edaravone (EDA) on liver damage caused by valproic acid (VPA) was investigated. The antioxidant, oxidative stress, and inflammation indicators such as glutathione (GSH), total lipid (TL), sialic acid (SA), aspartate (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were examined. Male Sprague Dawley rats were used in the experiment and randomly divided into 4 groups. The experiment lasted for 7 days. Group I: control group rats; Group II: rats receiving 0.5 g/kg VPA intraperitoneally daily. Group III: rats receiving 30 mg/kg EDA intraperitoneally daily. Group IV: rats receiving 0.5 g/kg VPA and 30 mg/kg EDA intraperitoneally daily (at the same time). On day 8, all animals were sacrificed under anesthesia, and liver tissues were removed. VPA caused the decreases in GSH, CAT, SOD, GPx, GR, and GST values and the increases in AST, ALT, ALP, GGT, sialic acid, and total lipid values. EDA reversed the in all values. These results suggest that EDA administration potentially reduces liver injury in VPA-induced hepatotoxicity.Öğe Ameliorative effects of edaravone against valproic acid-induced kidney damage(2025) Bayrak, Bertan Boran; Sancar, Serap; Hacıhasanoğlu Çakmak, Neziha; Bolkent, Şehnaz; Yanardağ, RefiyeValproic acid (VPA) is a well-known and increasingly documented antiepileptic drug that has been widely used in the treatment of epilepsy and/or epilepsy-related disorders. Prolonged clinical use of VPA has been reported to cause side effects such as nephrotoxicity. Edaravone (EDA) is a powerful free radical scavenger. The aim of the study was to investigate the protective effects of EDA against VPA-induced oxidative renal injury. Four experimental groups were formed by randomly assigning thirty-eight male Sprague Dawley rats. The first group, (Control Group, n = 8), consisted of healthy rats. The second group, (Group II, n = 10), comprised control rats given intraperitoneally EDA (30 mg/kg/day) for seven days. The third group (Group III, n = 10) was administered intraperitoneally only VPA (500 mg/kg/day) for seven days. The last group (Group IV, n = 10) was treated with VPA + EDA for seven days. On the 8th day, kidney tissues were immediately removed from rats. In kidney homogenates, reduced glutathione levels and Na/K+-ATPase, paraoxonase1 and prolidase activities were remarkably decreased while catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, myeloperoxidase, and xanthine oxidase activities and lipid peroxidation, protein carbonyl, advanced oxidized protein products, and hydroxyproline contents were notably elevated in VPA given group. Consistently, administration of EDA decreased renal degenerative changes seen in the kidney tissue of VPA given rats. Treatment with EDA in the VPA group significantly resulted in the recovery of both biochemical and histopathological alterations. As a result, EDA is potentially beneficial to revert oxidative renal damage induced by VPA.Öğe Optimization of inulin extraction from chicory roots and an ultrafiltration application to obtain purified inulin and hydrolyzed fructooligosaccharides(Ankara University, 2024) Sağcan, Nihan; Sağcan, Hasan; Bozkurt, Fatih; Bulut Güneş, Ayşe Nur; Fakir, Hüseyin; Dertli, Enes; Sağdıç, OsmanInulin and fructooligosaccharides (FOS) are prominent functional components in the food industry due to prebiotic and other pharmaceutical properties. Inulin is a storage polysaccharide in various plants. FOS are naturally present in various plants and can be obtained by partial hydrolysis of inulin. In this study, ground and sieved chicory roots (Cichorium intybus L.) were used as starting material for inulin extraction under optimized conditions determined by Response Surface Methodology (RSM) with a Box-Behnken design. Optimum inulin extraction conditions from chicory roots were; temperature of 90 °C, extraction time of 30 min., and liquid-to-solid (LS) ratio of 10:1 mL/g. Inulin extract was further hydrolyzed to FOS by enzymatic or acid treatment, separately. Purification of inulin extract and FOS hydrolysate was performed by ultrafiltration with a 10 kDa membrane under the pressure of 2 bar with continuous stirring. As a result, inulin and FOS were obtained at 90% and 76% purity, respectively.Öğe Analysis of the prechiasmatic sulcus in chiari malformation type I(Elsevier Science Inc., 2023) Özalp, Hakan; Özgüral, Onur; Alpergin, Baran Can; İnceoğlu, Ayşenur; Özalp, Sibel; Armağan, Ercan; Uçar, Hadice; Beger, OrhanOBJECTIVE: To assess morphologic features of the pre-chiasmatic sulcus (PS) in Chiari malformation type I (CM-I).-METHODS: Computed tomography images were ob-tained in patients with CM-1 (mean age: 21.26 & PLUSMN; 16.46 years; sex: 25 females and 17 males) and 58 healthy control subjects (mean age: 28.12 & PLUSMN; 22.60 years; sex: 29 females and 29 males). The following parameters were measured to determine the anatomy of the PS: planum length, sulcal length, sulcal angle (SA), and interoptic distance. Consid-ering sulcal length and SA measurements, 4 types of PS were identified: narrow-steep-groove (NSG), narrow-flat -groove (NFG), wide-steep-groove, and wide-flat-groove.-RESULTS: SA was greater in the CM-I group (32.80 & PLUSMN; 18.21 & DEG;) compared with the control group (23.05 & PLUSMN; 14.53 & DEG;) (P = 0.004), but the other parameters were similar in both groups. Distribution ranking of PS types was as follows: NFG (31%) > NSG (26.20%) > wide-steep-groove (23.80%) > wide-flat-groove (19%) in the CM-I group; wide-flat-groove (37.90%) > wide-steep-groove (20.70%) = NFG (20.70%) = NSG (20.70%) in the control group. Distribution rate of PS types relative to both groups showed that the classification system was not affected by CM-I (P = 0.226).-CONCLUSIONS: SA value was approximately 25% greater in the CM-I group than in the control group; thus, CM-I patients had more vertical groove. The percentage of narrow-type (NSG D NFG) PS in the CM-I group was higher than in the control group.Öğe Surface characterization, electrochemical properties and in vitro biological properties of Zn-deposited TiO2 nanotube surfaces(Nature Research, 2023) Durdu, Salih; Cihan, Gizem; Yalçın, Emine; Çavuşoğlu, Kültigin; Altınkök, Atılgan; Sağcan, Hasan; Yurtsever, İlknur; Usta, MetinIn this work, to improve antibacterial, biocompatible and bioactive properties of commercial pure titanium (cp-Ti) for implant applications, the Zn-deposited nanotube surfaces were fabricated on cp-Ti by using combined anodic oxidation (AO) and physical vapor deposition (PVD-TE) methods. Homogenous elemental distributions were observed through all surfaces. Moreover, Zn-deposited surfaces exhibited hydrophobic character while bare Ti surfaces were hydrophilic. Due to the biodegradable behavior of Zn on the nanotube surface, Zn-deposited nanotube surfaces showed higher corrosion current density than bare cp-Ti surface in SBF conditions as expected. In vitro biological properties such as cell viability, ALP activity, protein adsorption, hemolytic activity and antibacterial activity for Gram-positive and Gram-negative bacteria of all surfaces were investigated in detail. Cell viability, ALP activity and antibacterial properties of Zn-deposited nanotube surfaces were significantly improved with respect to bare cp-Ti. Moreover, hemolytic activity and protein adsorption of Zn-deposited nanotube surfaces were decreased. According to these results; a bioactive, biocompatible and antibacterial Zn-deposited nanotube surfaces produced on cp-Ti by using combined AO and PVD techniques can have potential for orthopedic and dental implant applications.Öğe The optimal method to measure polyamines in serum by using HPLC fluorescence detector(Istanbul Medipol University, 2023) Çakan, Orhan; Hacıhasanoğlu Çakmak, Neziha; Bayramoğlu, Feyza; Yiğitbaşı, TürkanMeasurement of polyamines (putrescine, spermidine and spermine) is important in the monitoring of many metabolic events, as well as in cancer prognosis. However, the lack of method standardization and validation for the measurement of poly-amines is a major obstacle. In this study, sample preparation, gradient program, chromatography column, sample concentration studies were attempted and an analysis method was developed for the detection of polyamines in serum by using HPLC fluorescence detector in order to reduce the difficulties experienced with the existing methodologies. This method was validated analytically in accordance with EMA and FDA’s guidelines. In this study, Waters Nova-Pak C18 A chromatography column with 3.9 mm, 150 mm and 4 µm specifications was used for the first time. Acetonitrile was used instead of methanol. Thanks to the newly developed gradient, peak purity and sufficient peak separation were ensured and accurate, sensitive, reliable and reproducible method was developed and validated.Öğe Synthesis of novel hybrid lonidamine-coumarin derivatives and their anticancer activities(Elsevier B.V., 2023) Şavluğ İpek, Özgecan; Onur Sucu, Bilgesu; Gül, Şeref; Yolaçan, Çiğdem; Güzel, MustafaIn order to develop drugs against cancer, which is one of the deadliest diseases in the world, hybridizing structures with known anticancer activity can provide a dual activity for the treatment of cancer cases. For this purpose, a series of novel hybrid compounds combining lonidamine and 7-hydroxy-4-methylcoumarin via different linker modifications have been synthesized in this study. The chemical structures of the novel compound were elucidated with 1H and 13C NMR and mass spectrometry (HRMS) methods. All the synthesized compounds were screened for anticancer activity against MCF-7 and A549 cells. Among them, compound 2 appeared to be the most potent compound on MCF-7 lines; and IC50 dose was determined as 33.12 µM. IC50 of Compound 6 was determined as 139.6 µM for A549 cells. Considering anticancer activity studies, compounds 2 and 6 have potential to lead to the development of novel hybrid compounds for cancer therapy. Further studies to identify mechanistic explanations of the bioactivity of these molecules are ongoing and will be reported in due course.Öğe Biological evaluation of imidazopyridine derivatives as potential anticancer agents against breast cancer cells(Springer, 2022) Sucu, Bilgesu OnurImidazo[1,2-a]pyridine cores have increasing importance in the pharmaceutical industry with their wide range pharmacological activities. In this study, two series of imidazopyridine derivatives were synthesized. It was planned to integrate the pyrimidine ring or N-acylhydrazone (NAH) to the carbon atom at the 3 position of the imidazo[1,2-a]pyridine scaffold. Pyrimidine-containing compounds (9-12) were obtained by palladium-catalyzed coupling reaction (Suzuki reaction), and NAH compounds (13-19) were obtained from the aldehyde intermediate synthesized as a result of the Vilsmeier-Haack reaction. All of the derivatives were evaluated in breast cancer cells for their antiproliferative potential. The pyrimidine-containing compounds did not show active results in both breast cancer cell lines, while the NAH derivatives showed significant results. Among the novel derivatives, compound 15 exhibited the most potent activity against the MCF7 and MDA-MB-231 cell lines with IC50 values of 1.6 and 22.4 mu M, respectively. The current study demonstrated that these compounds have anticancer activity and would be useful in developing more effective compounds for treating breast cancer.Öğe Characterization and investigation of properties of copper nanoparticle coated TiO2 nanotube surfaces on Ti6Al4V alloy(Elsevier Ltd, 2022) Durdu, Salih; Tosun, Sergen; Yalçın, Emine; Cavuşoğlu, Kültigin; Altınkök, Atılgan; Sağcan, Hasan; Yurtsever, İlknur; Usta, MetinIn this work, to investigate surface, corrosion and in vitro biological properties of the CuNPs-coated nanotube surfaces, antibacterial, bioactive and biocompatible nanoparticle-coated nanotube surfaces were produced on Ti6Al4V alloys by combined anodic oxidation (AO) and electrodeposition (ED) techniques for implant applications. All surfaces were characterized by SEM, EDX-mapping and -area, XRD, AFM and contact angle measurement techniques. The electrochemical and biological properties such as antibacterial activities, protein adsorption, ALP activity, hemolytic activity and cell viability of the surfaces were investigated in detail. Electrochemical corrosion resistance of CuNPs-coated nanotube surfaces were enhanced respect to uncoated Ti6Al4V alloy under simulated body fluid (SBF) conditions. Antibacterial properties, cell viability and ALP activity of CuNPs-coated nanotube surfaces were improved with compared to uncoated Ti6Al4V alloys. In addition, protein adsorption and hemolytic activity of CuNPs-coated nanotube surfaces were reduced. This work indicates a potential to precisely fabricate an antibacterial, bioactive and biocompatible CuNPs-coated nanotube surfaces on Ti6Al4V to fulfill orthopedic and dental implant needs by using combined AO and ED processes.Öğe Synthesis of novel oxadiazole derivatives and their cytotoxic activity against various cancer cell lines(TUBITAK, 2022) Sucu, Bilgesu Onur; Koç, Elif BeyzaCaffeic acid (CA), ferulic acid (FA) and caffeic acid phenethyl ester (CAPE) have a broad anticancer effect on various cell lines. In this study, nine ferulic and caffeic acid-based 1,2,4 and 1,3,4 oxadiazole molecular hybrids were synthesized and their cytotoxic activity was evaluated mainly against Glioblastoma (GBM) cell lines. Compounds 1 and 5 exhibited the highest inhibitory activity against three different GBM cell lines (LN229, T98G, and U87), without toxicity to healthy human mesenchymal stem cells (hMSC). In addition, their cytotoxicity was also evaluated against three additional cancer cell lines and more inhibitory results were found than GBM cell lines. The IC50 values of compound 5 in U87, T98G, LN229, SKOV3, MCF7, and A549 cells were determined as 35.1, 34.4, 37.9, 14.2, 30.9, and 18.3 µM. In the light of biological activity studies, the developed compounds have a high potential to lead studies for the development of new drug candidates for the treatment of cancer.Öğe Rapid molecular diagnosis of group a streptococcus with a novel loop mediated isothermal amplification method(Verlag Klinisches Labor GmbH, 2022) Toptan, Hande; Ağel, Esra; Sağcan, Hasan; Ertunç, Yiğit M.; Elmas, Bahri; Köroğlu, Mehmet; Şengil, Ahmet Zeki; Altındiş, MustafaBackground: Group A Streptococcus (GAS) is the most common bacterial cause of acute tonsillopharyngitis. In this study, it was aimed to evaluate the performance of a novel Loop Mediated Isothermal Amplification (LAMP) method in the rapid diagnosis of GAS in samples taken from children with a pre-diagnosis of acute bacterial tonsillopharyngitis by comparing it with culture and rapid antigen test (RAT) methods. Methods: A total of 100 throat swab samples taken from children at the pediatrics outpatient clinic with suspected tonsillopharyngitis were included in the study. Throat swab samples were analyzed by RAT, throat culture, and LAMP method. GAS suspected colonies were identified with MALDI-TOF MS system. The isothermal amplification reaction for LAMP was conducted by a novel LAMP instrument. Results: According to the results of throat cultures; 53 of them were positive and 47 were negative in terms of GAS. Six (11.32%) of the culture positive samples were found to be negative by the RAT (sensitivity; 88.68%, specificity 100%). While the antigen test was positive, no culture negative sample was detected. One of the culture positive samples was found negative by LAMP. In two samples, while throat culture was negative, it was observed that LAMP was positive (sensitivity; 98.11%, specificity; 95.74%). In one of these samples, the bacteria grown in the culture were identified as Streptococcus dysgalactiae by mass spectrophotometry. Conclusions: In this study, it was determined that the LAMP method used in the diagnosis of throat infections caused by GAS has high sensitivity and specificity. We believe that the instrument is easy to use, low cost, portable, and adaptable to point of care tests. There are very few studies in the literature regarding the use of the instrument in this field, and it should be evaluated in terms of its usability in daily practice with new studies.Öğe Potential of novel methyl jasmonate analogs as anticancer agents to metabolically target HK-2 activity in glioblastoma cells(Frontiers Media S.A., 2022) Uludağ, Damla; Bay, Sadık; Onur Sucu, Bilgesu; Şavluğ İpek, Özgecan; Mohr, Thomas; Güzel, Mustafa; Karakaş, NihalChange in the energy metabolism of cancer cells, which display significant differences compared to normal cells, is a rising phenomenon in developing new therapeutic approaches against cancers. One of the metabolic enzymes, hexokinase-II (HK-II) is involved in glycolysis, and inhibiting the HK-II activity may be a potential metabolic target for cancer therapy as most of the drugs in clinical use act on DNA damage. Methyl jasmonate (MJ) is one of the compounds blocking HK-II activity in cancer cells. In a previous study, we showed that the novel MJ analogs inhibit HK-II activity through VDAC detachment from the mitochondria. In this study, to evaluate the potential of targeting HK-2 activity, through patient cohort analysis, we first determined HK-2 expression levels and prognostic significance in highly lethal glioblastoma (GBM) brain tumor. We then examined the in vitro therapeutic effects of the novel analogs in the GBM cells. Here, we report that, among all, compound-10 (C-10) showed significant in vitro therapeutic efficacy as compared to MJ which is in use for preclinical and clinical studies. Afterward, we analyzed cell death triggered by C-10 in two different GBM cell lines. We found that C-10 treatment increased the apoptotic/necrotic cells and autophagy in GBM cells. The newly developed analog, C-10, was found to be lethal against GBM by the activation of cell death authorities, mostly in a necrotic and autophagic fashion at the early stages of the treatment. Considering that possibly decreased intracellular ATP levels by C-10 mediated inhibition of HK-2 activity and disabled VDAC interaction, a more detailed analysis of HK-2 inhibition-mediated cell death can provide a deep understanding of the mechanism of action on the oncosis/necroptosis axis. These findings provide an option to design clinically relevant and effective novel HK-II inhibitors and suggest novel MJ analogs to further study them as potential anticancer agents against GBM.Öğe Design and synthesis of novel caffeic acid phenethyl ester (CAPE) derivatives and their biological activity studies in glioblastoma multiforme (GBM) cancer cell lines(Elsevier Inc., 2022) Onur Sucu, Bilgesu; Koç, Elif Beyza; Şavluğ İpek, Özgecan; Mirat, Afranur; Almas, Furkan; Güzel, Melike Aybala; Doğan, Berna; Uludağ, Damla; Karakaş, Nihal; Durdağı, Serdar; Güzel, MustafaGlioblastoma Multiforme (GBM) is the most aggressive brain tumor and classified as one of the deadliest cancers. The current treatment plans for GBM remains to be ineffective because of its rapid progress and inability of the drugs used to cross the blood-brain barrier (BBB). Thus, developing more effective and potent medicines for GBM are needed. There have been several reports demonstrating that CAPE presents reasonably good anti-cancer activity in certain cancer cell lines and can penetrate the blood-brain barrier. Accordingly, in this study we synthesized several novel CAPE analogs with the addition of more druggable handles and solubilizing entities and subsequently evaluated their in vitro therapeutic efficacies in GBM cell lines (T98G and LN229). The most potent compound was then examined extensively and results showed that the 50 ?M novel CAPE analog (compound 10) significantly decreases the viability of both T98G and LN229 GBM cells as compared to CAPE itself. Moreover, the compound 10 was not cytotoxic to healthy human cells (fibroblast-like mesenchymal stem cells) at the same concentration. Apoptotic (32.8%, and 44.6%) cell populations were detected in the compound 10 treated groups for LN229 and T98G, respectively. As an indication of apotosis, significantly increased PARP cleavage was detected in compound 10 versus CAPE treated LN229. In addition, we conducted molecular docking and molecular dynamics (MD) simulations studies on certain targets playing roles on GBM disease pathway such as NF-?B, EGFR, TNF-?, ERK2, PAPR1, hCA IX and hCA XII. Our findings demonstrated that designed CAPE analogs have anti-cancer activity on GBM cells and in silico studies also demonstrate the inhibitory ability of suggested compounds via interactions with critical residues in binding pockets of studied targets. Here, we suggest the novel CAPE analog to study further against GBM. Therefore, identification of the compound related molecular signature may provide more to understand the mechanism of action.Öğe Antileishmanial activity of BNIPdaoct- and BNIPdanon-loaded emulsomes on leishmania infantum parasites(Frontiers Media S.A., 2022) İşlek, Zeynep; Üçışık, Mehmet Hikmet; Keskin, Elif; Onur Sucu, Bilgesu; Gomes-Alves, Ana G.; Tomás, Ana M.; Güzel, Mustafa; Şahin, FikrettinAmong bisnaphthalimidopropyl (BNIP) derivatives, BNIPDaoct and BNIPDanon recently came forward with antileishmanial activities beyond the standard, commercialized antileishmanial therapies. However, high-level toxicity on macrophages plus poor aqueous solubility and poor bioavailability of the compounds limit their application in therapies. Addressing these limitations, the present study introduces BNIPDaoct- and BNIPDanon-loaded emulsomes as lipid-based nanocarrier systems. Accordingly, emulsome formulations were prepared with the presence of BNIP compounds. The average diameters of BNIPDaoct- and BNIPDanon-loaded emulsomes were found as 363.1 and 337.4 nm, respectively; while empty emulsomes differed with a smaller average particle diameter, i.e., 239.1 nm. All formulations exhibited a negative zeta potential value. The formulations achieved the encapsulation of BNIPDaoct and BNIPDanon at approximately 0.31 mg/ml (501 µM) and 0.24 mg/ml (387 µM), respectively. The delivery of BNIP within the emulsomes improved the antileishmanial activity of the compounds. BNIPDaoct-loaded emulsome with 50% inhibitory concentration (IC50) value of 0.59 ± 0.08 µM was in particular effective against Leishmania infantum promastigotes compared to free BNIPDaoct (0.84 ± 0.09 µM), free BNIPDanon (1.85 ± 0.01 µM), and BNIPDanon-loaded emulsome (1.73 ± 0.02 µM). Indicated by at least ? 2-fold higher 50% cytotoxic concentration (CC50) values, the incorporation of BNIP into emulsomes significantly reduced the toxicity of BNIPs against macrophages, corresponding to up to 16-fold improvement in selectivity index (CC50/IC50) for L. infantum promastigotes. The infection rates of macrophages were determined using dual-fluorescent flow cytometry as 68.6%. Both BNIP formulations at concentration of 1.87 µM reduced the parasitic load nearly to 40%, whereas BNIPDaoct-loaded emulosmes could further decrease the parasitic load below 20% at 7.5 µM and above. In conclusion, the incorporation of BNIPDaoct and BNIPDanon into emulsomes results in water-soluble dispersed emulsome formulations that do not only successfully facilitate the delivery of BNIP compounds into the parasites and the Leishmania-infected macrophages in vitro but also enhance antileishmanial efficacy as proven by the decline in IC50 values. The selectivity of the formulation for L. infantum parasites further contributes to the challenging safety profile of the compounds. The promising in vitro antileishmanial efficacy of BNIP-loaded emulsomes highlights the potential of the system for the future in vivo studies.Öğe Novel ??hydroxy ketones: Synthesis, spectroscopic characterization, molecular docking, and anticancer activity studies(Elsevier B. V., 2022) Başpınar Küçük, Hatice; Kantürk, Gökhan; Yerlikaya, Şerife; Yıldız, Tülay; Şentürk, Ahmet Mesut; Güzel, MustafaIn this study, a series of novel ??hydroxy ketone derivatives 3a-o were designed, synthesized, and evaluated for their anticancer activity. The structure of these compounds were characterized by IR, 1H and 13C NMR, mass spectrometry and elemental analysis methods. All the synthesized compounds were screened for anticancer activity against MCF-7 and U87 cells. Among them, compound 3l was appeared to be the most potent compound on both cancer cells; and IC50 dose was determined as 145 µM for MCF-7 cells and 6,6 µM for U87 cells. DNA ladder and Annexin V apoptotic marker tests were used and as a result, 3l caused the initiation of apoptosis on U87 cells. VDAC protein expression increased dramatically after U87 glioblastoma brain cancer cells were treated with compound 3l Additionally, the molecular modeling of these compounds was studied in FLT3 receptor, Estrogen receptor, and PARP2 receptor for the treatment of Acute Myeloid Leukemia (AML), breast cancer, and Glioblastoma (GBM) respectively. Their binding motifs and drug-like properties were investigated, and the results are highlighted in the discussion. Based on the results, compound 3l may have a potential drug candidate profile that can reverse the drug resistance profile.Öğe Antiproliferative properties and structural analysis of newly synthesized Schiff bases bearing pyrazole derivatives and molecular docking studies(Elsevier, 2021) Şener, Nesrin; Özkınalı, Sevil; Çelik Altunoğlu, Yasemin; Yerlikaya, Şerife; Gökçe, Halil; Zurnacı, Merve; Gür, Mahmut; Baloğlu, Mehmet Cengiz; Şener, İzzetNew pyrazole Schiffbases containing azo groups were synthesized using the condensation reaction between p-nitrobenzaldehyde and (E)-4-(phenyl)-1-H-pyrazole-3,5-diamine in the molar ratio of 1:2. Characterization of the compounds was performed by spectroscopic techniques, including IR, UV-Vis, H-1-NMR and C-13-NMR. Biological activity of the compounds was evaluated by analyzing DNA protection, antimicrobial and anticancer properties. Compound 4 was effective for Salmonella typhimurium with the MIC concentration of 62.5 mu g/mL. Moreover, this compound had the highest protection activity on DNA. Cytotoxic activity of compound 4 was determined on the HeLa cancer cell line with the IC50 concentration of 976.6 mu M. The anti-cancer characteristic of compounds 4 and 5 for HeLa cancer was theoretically analyzed by molecular docking study as well. Among the tested compounds, compound 4 possessed significant results due to its in vitro cytotoxic properties. Therefore, it may be considered as a potential bioactive agent for cancer treatment studies. In addition, further in vivo analysis can be performed to indicate its anticancer property.Öğe Evaluation of antidiabetic activities of scorzonera species on alloxan-induced diabetic mice(Marmara University Faculty of Health Sciences, 2021) Şakul, Ayşe Arzu; Kurtul, Ekin; Özbek, Hanefi; Kırmızı, Neriman İpek; Bahtiyar, Bade Cevriye; Saltan, Hayriye; Bahadır Acıkara, ÖzlemObjective: In Turkish folk medicine, different species of Scorzonera (Asteraceae) have been used in the treatment of various disorders. The study aimed to investigate antidiabetic activity of Scorzonera species and if rutin is the primary component responsible of this activity. Methods: The extracts of aerial parts of Scorzonera tomentosa, S. mollis ssp. szowitsii, S. suberosa ssp. suberosa, S. eriophora, S. acuminata, S. sublanata and S. cana var. jacquiniana were used in the experiment. Additionally, rutin, which has been analysed and detected by using HPLC qualitatively and quantitatively in some Scorzonera species, was also tested for its antidiabetic activity in the same conditions. An alloxan-induced diabetic mice test model was used in order to verify antidiabetic activity. Antidiabetic activities of the 9 groups (n=5; each) were measured at four different times: before Scorzonera extracts and rutin treatment and after 1, 2 and 4 hours of treatments. Results: S. sublanata extract exhibited the highest antidiabetic activity and at 100 mg/kg dose, it significantly reduced blood glucose levels measured after 1, 2 and 4 hours of treatments when compared to isotonic saline solution group (diabetic control group). S. cana var. jacquiniana extract also displayed notable decrease after 4 hours of treatment. Significant lowering effect on blood glucose level was also observed by treatment with rutin in all tested times at 100 mg/kg i.p. injection. According to the HPLC analyses the highest rutin content was determined in the S. acuminata aerial parts. Conclusion: Rutin content and the antidiabetic activity of the plant extracts were not correlated as displayed in this present study. Further studies should be performed to reveal responsible compunds for antidiabetic activity.Öğe A single center cohort of 40 severe COVID-19 patients who were treated with convalescent plasma(Tübitak Scientific & Technical Research Council Turkey, 2020) Gemici, Aliihsan; Bilgen, Hülya; Erdoğan, Cem; Kansu, Abdullah; Olmuşçelik, Oktay; Beköz, Hüseyin Saffet; Dinleyici, Rümeysa; Mert, Ali; Sevindik, Ömür GökmenBackground/aim: A SARS-Cov2 infection which was first arised from Wuhan in December 2019 and named as COVID-19. Still there lacks either a specific treatment or a vaccine to treat COVID-19. Convalescent plasma (CP) was previously used successfully to treat SARS-CoV-1 and MERS infections. Health authority in Turkey has published a guideline to integrate this promising option in the treatment process of patients who are prone to high risk of developing severe COVID-19.Materials and Methods: Forty consecutive patients who had received CP at our center were included in the study. Demographics, COVID-19 specific parameters, biomarkers to detect the severity of COVID-19 infection and outcome variables were collected retrospectively. The correlation between outcome variables and the independent predictors of the outcome were reported.Results: Median age of the patients was 57.5 and 72.5% were male. At least one COVID-19 PCR test was confirmed to be positive in 75% of patients. Remaining 25% had a Chest-CT which was reported to be compatible with an ongoing COVID-19. All patients (100%) were classified as having severe COVID-19 infection. Over a half of the patients harbored an oxygen saturation of less than 90 despite of a continuous 5 L/min support of O-2. 82.5% of the patients had a need for mechanical ventilation and 45.5% had a need for invasive mechanical ventilation. Nine out of 10 patients who have received CP outside ICU have totally recovered from COVID-19 at a median of 9 days, and a half of the patients who needed invasive mechanical ventilation were successfully free of mechanical ventilation support and managed to recover from COVID-19.Conclusion: According to the results of this study, CP is an efficient conjunct to conventional therapy against COVID-19 with a favorable safety profile.Öğe Optimization of isothermal amplification method for Mycobacterium tuberculosis detection and visualization method for fieldwork(Türkiye Klinikleri, 2020) A?el, Esra; Sağcan, Hasan; Ceyhan, İsmail; Durmaz, RızaBackground/aim: Tuberculosis is still one of the most contagious diseases around the world. Key factors of tuberculosis control are rapid diagnostic, efficient treatment, and prevention of contamination by surveillance and monitoring. However, culture is the gold standard method for laboratory diagnosis of tuberculosis; the results are several weeks to obtain. In order to prevent contamination of tuberculosis, diagnosis must be made in short time and treatment should be started as soon as possible. The aim of this study is to optimize the loop-mediated isothermal amplification (LAMP) method, which provides a much faster and more sensitive result than the polymerase chain reaction (PCR) method and allows the replication of target nucleic acid sequences under isothermal conditions without the need for laboratory infrastructure. Materials and methods: Sputum samples were homogenized with 5% trypsin solution in CaCl2 to obtain DNA. DNA was purified using QIAGEN QIAamp DNA mini kit. LAMP primers were design using Primer explorer V5 program according to IS6110 gene of Mycobacterium tuberculosis. NEB Bst 3.0 DNA polymerase kit was used for LAMP reactions. Besides, LAMP reactions were compared with TaqMan based RT-PCR method using NEB’s Taq polymerase kit. Finally, for visualization of LAMP products, lateral flow dipsticks that produced by Milenia Biotec, colorimetric 2X LAMP master mix that produced by NEB and 2% w/v agarose gel electrophoresis methods were used. Results: Optimum amplification temperature for LAMP was found to be 71.4 °C. The detection limit of the method was 102 CFU/mL and sensitivity was determined 100% compared to five different Mycobacterium species. Conclusion: The current study indicated that the LAMP-LFD and colorimetric LAMP protocol optimized with sputum samples can be reliable used as a rapid, sensitive and specific assay in the diagnosis of tuberculosis in the field.Öğe Optimization of lyophilized LAMP and RT-PCR reaction mixes for detection of tuberculosis(Sciendo, 2020) Ağel, Esra; Sağcan, HasanUndoubtedly, one of the most infectious diseases in the world is tuberculosis. Key factor for tuberculosis control is to prevent possible contagion with rapid diagnosis and effective treatment. The culture method, which it takes several weeks to obtain results, is the gold standard method for laboratory diagnosis of tuberculosis. In order to prevent possible contagion of tuberculosis, diagnosis must be made in short time and treatment should be started as soon as possible. Normally, clinical samples are studied in advanced laboratories designed for this purpose. However, especially after the screening in rural areas, the transmission of the samples to the centers has many negative effects on the clinical material. Therefore, the latest trend molecular techniques in microbiological diagnosis are developing into point of care systems that can be applied in the field without laboratory infrastructure. The major challenge for molecular-based point-of-care tests is the need to store polymerase enzymes and some of the ingredients used in the cold chain. The aim of this study is to increase the resistance of the amplification reaction mixtures by lyophilizing the tuberculosis diagnosis. Lyophilization was performed on Loop-mediated isothermal amplification (LAMP) and Real-time PCR mixtures. For the lyophilization of LAMP and RT-PCR mixtures, two different experimental setups were tried from the literature except for the developed content. Chemicals such as stachyose, trehalose, glycerol and PEG 8000 are widely using as cryoprotectants. As a result, the developed content (0.5% PEG 8000, 2.0 % Stachyose) was determined the best cryoprotectant mixture. Accordingly, amplification mixtures can be produced with the developed lyophilization method and point of care kits can be developed.
