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Background: Cancer cells restrain apoptotic and senescence pathways through intracellular heat shock protein 70 (Hsp 70). These cells aid stimulus-independent growth, and their higher metabolism rate requires Hsps. Hsps compensate abnormally increased substrate protein folding rate of cancer cells. Objective: Misfolding of substrate proteins especially signaling substrate proteins, may not function properly. Therefore, Hsp70 folds these substrate proteins into their native-fully functional states, and this mode of action helps cancer cell survival. Method: Targeting Hsps is promising cancer therapy, and in this study, 6,8,9-trisubstituted purine derivatives were designed and synthesized to inhibit Hsp70 and drive cancer cells to apoptosis. Further, oncogenic stimuli through inhibitors can induce an irreversible senescent state and senescence is a barrier to transformation. Results: Hsp70 helps cancer cells to bypass the cellular senescence program, however, binding of N6-(4- isopropylaniline) analogue (7) depletes Hsp70 function as evidenced by aggregation assay and Hsp70 depletion induces senescence pathway. Conclusion: The purine-based inhibitor-compound 7 effectively inhibits MCF-7 cell line. Moreover, the therapeutic potential with regard to the senescence-associated secretory phenotype has complementary action. Dual action of the inhibitor not only drives the cells to apoptosis but also force the cells to be in the senescence state and provides promising results specially for luminal A type breast cancer therapy.

Objectives: Recently, studies have demonstrated that serotonin type 7 receptors (5-HT7) have conflincting effects on neuronal excitability in different brain regions. However, the effect of 5-HT7 on seizures has not been exactly elucidated yet. Therefore, our aim in this study was to investigate the effects of 5-HT7 antagonist SB-269970 on pentylenetetrazole (PTZ) induced fully kindled rats. Methods: In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. Rats were injected with PTZ (35 mg/kg) intraperitoneally every other day to generate kindling model. 5-CT (0.1 mg/kg) and SB-269970 (1 mg/kg) were administered 30 min before acute seizure induction with PTZ (35 mg/kg). Seizure stages were determined according to the Racine scale. After electrocorticography (ECoG) recordings of seizure-induced rats were obtained, the animals were sacrificed by decapitation. The hippocampal GABA levels were determined by ELISA kit and the number of c-Fos positive neurons in the hippocampal dentate gyrus (DG), CA1 and CA3 areas were measured by immunohistochemical method. Results: The results showed that SB-269970 reduced the number of spikes, percent seizure duration and duration of generalized tonic-clonic seizures (dGTCS), while increasing the onset time of generalized tonic-clonic seizures (oGTCS). The hippocampal GABA levels were significantly increased in the SB-269970 group compared with the PTZ group. In addition, SB-269970 reduced the number of c-Fos positive cells in hippocampal CA1 area. Discussion: 5-HT7 antagonist SB-269970 displays anticonvulsant effects on PTZ-induced seizures in fully kindled rats and these effects may be related to GABAergic activity in the hippocampus.

A non-toxic nano system using a cleverly designed dual light can be an important treatment strategy in cancer therapy. Here, we propose a unique concept of synergistic non-toxic nanoplatform, which operates with dual light. An apoferritin nano-platform whose surface was modified with Verteporfin (Visudyne (R)) and with ultra-small CuS nanoparticles in the center demonstrated the synergistic effect of photodynamic therapy (PDT) and photothermal therapy (PTT). The synergistic effect of PDT and PTT were achieved with 808 nm laser light and 690 nm LED light, respectively. These results not only give a new horizon to multifunctional nanostructures for biological applications but also show a new way to design the novel PDT and PTT agents.

Recent studies have shown that proton pump inhibitors have positive effects on the nervous system. However, its effect on epileptic seizure and neuronal damage are still unclear. In this study, it was aimed to investigate the effect of pantoprazole on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y cell line. Animals were divided into three groups: control, saline (1 mL/kg serum physiologic), and pantoprazole (10 mg/kg). Pentylenetetrazole (45 mg/kg) was given to induce a seizure and a passive avoidance test trial was carried out to evaluate memory function. 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and brain-derived neurotrophic factor (BDNF) levels were measured in the brain by commercial kits. SH-SY5Y cells were treated with saline or pantoprazole for one hour, and then pentylenetetrazole (30 µm) was added to the medium to induce neurotoxicity. After 24 h, cell viability, total antioxidant, total oxidant status, and apoptosis were measured in SH-SY5Y cells. It was found that pantoprazole treatment postponed epileptic seizure onset, protected memory, reduced 8-OHdG, caspase-3, and also increased BDNF in the brain. In addition, it blocked pentylenetetrazole toxicity, apoptosis, increased antioxidant, and decreased oxidant status in SH-SY5Y cells. Pantoprazole significantly improved seizure, oxidative stress, and apoptosis. Thus, pantoprazole could be used as a supportive therapeutic agent in epilepsy.

Objective: This study was aimed to investigate the in vitro antioxidant, antimicrobial, cytotoxicity, and enzyme inhibition activities of Tragopogon porrifolius and Polygonum cognatum which are naturally grown and consumed intensively by people in Sivas, Turkey. Methods: Plant materials were extracted with aqueous ethanol by maceration method. The components of the extracts were determined using the Gas Chromatography Mass Spectrometry. Antimicrobial, cytotoxic and enzyme inhibition activities of the extracts were investigated by micro dilution, XTT assay and 96-micro-well plate methods, respectively. The antioxidant activity evaluated using the DPPH radical scavenging, thiobarbituric acid and reducing power methods. The total phenol and total flavonoid content was also examined. Results: GC–MS analysis revealed the presence of 31 compounds inP. cognatum extract and 29 compounds in T. porrifolius extract. According to the results, T. porrifolius extract showed high level of antioxidant activity in comparison to P. Cognatum extract. T. porrifolius exhibited higher ?-glucosidase inhibitory activity, and both extract showed strong ?-amylase inhibition activity compared to reference drug acarbose. T. porrifolius and P. cognatum ethanolic extracts exhibited antimicrobial activity in the concentration range of 0.039–2.5 mg/ml. Both extracts also exhibited significant anticancer effect on MDA-MB-231 breast cancer cells. The IC50 values of T. porrifolius and P. cognatum extracts in MDA-MB-231 cells were determined as 0.0625 mg/mL and 0.053 mg/mL, respectively. Conclusion: Our findings demonstrated that T. porrifolius and P. cognatum ethanolic extracts have promising effect on antioxidant, antimicrobial and cytotoxic activity as well as enzyme inhibition activity, and hence further studies required to identify specific compounds responsible for these activities. © 2019, Sivas Cumhuriyet Ãœniversitesi, The authors would like to acknowledge the C?BAP project (NO: ECZ20 and ECZ26) for financial support to the realization of these studies. The authors also would like to thank the Sivas Cumhuriyet University Advanced Technology Applications and Research Center for providing laboratory facilities to conducting these studies.

A new series of thiosemicarbazone derivatives (1–11) were prepared from various aldehydes and isocyanates with high yields and practical methods. The structures of these compounds were elucidated by Fourier transform infrared, 1H‐nuclear magnetic resonance (NMR), 13C‐NMR spectroscopic methods and elemental analysis. Cytotoxic effects of target compounds were determined by 2,3‐bis‐(2‐methoxy‐4‐ nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide assay and compound 1 showed significant cytotoxic activity against both MCF‐7 and MDA‐MB‐231 cells, with halfmaximal inhibitory concentration values of 2.97 μM and 6.57 μM, respectively. Moreover, in this study, the anticholinergic and antidiabetic potentials of these compounds were investigated. To this aim, the effect of the newly synthesized thiosemicarbazone derivatives on the activities of acetylcholinesterase (AChE) and αglycosidase (α‐Gly) was evaluated spectrophotometrically. The title compounds demonstrated high inhibitory activities compared to standard inhibitors with Ki values in the range of 122.15–333.61 nM for α‐Gly (Ki value for standard inhibitor = 75.48 nM), 1.93–12.36 nM for AChE (Ki value for standard inhibitor = 17.45 nM). Antiproliferative activity and enzyme inhibition at the molecular level were performed molecular docking studies for thiosemicarbazone derivatives. 1M17, 5FI2, and 4EY6, 4J5T target proteins with protein data bank identification with (1–11) compounds were docked for anticancer and enzyme inhibition, respectively., Scientific Research Project Fund of Sivas Cumhuriyet University, Grant/Award Numbers: ECZ079, RGD‐020

Cancer is a group of diseases that are caused by uncontrolled proliferation of cells in various parts of the body and it is one of the most studied diseases worldwide. Photodynamic therapy (PDT) is a treatment that uses photosensitizers called photosensitizing agents in addition to light to kill cancer cells. Photosensitizers work only after they have been activated by certain types of light. PDT contains three basic components, these are a photosensitizer, visible light and molecular oxygen (3O2). The efficiency of the therapeutic action is directly related to the property of the photosensitizer. In this study, chitosan and BODIPY based nanoparticles that were capable of carrying out drug delivery and producing singlet oxygen (1O2) were synthesized for the first time. For this purpose, organic nanoparticles showed PDT feature were synthesized via the formation of ionic complexes formed with opposite charged ionic interactions between the synthesized BODIPY derivative (PDT agent) and chitosan hydrochloride at appropriate pH (pH=6). Later, during the formation of this ionic complex, a chemotherapeutic model drug (Doxorubicin) was added to the medium and chemotherapeutic drug-loaded chitosan and BODIPY-based nanoparticles were synthesized. Finally, while drug-free (Y1-Chitosan nanoparticles) and drug-loaded organic nanoparticles (Y1-Chitosan-Dox nanoparticles) showed very good PDT properties, they were found to be effective on MCF7 cancer cells and less toxic to L929 cells.

Objectives The present study aimed to investigate the inhibitory activities of enzymes related to diabetes mellitus and Alzheimer's disease of the methanol and water extracts of Ficus carica leaf extracts. The bioactive compounds and anticancer, antioxidant, and antimicrobial effects of the extracts were also investigated. Materials and methods The bioactive compounds in the extracts were determined by gas chromatography-mass spectrometry. The antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6 sulphonic acid) (ABTS) radical scavenging, total phenol and flavonoid content, ferric reducing power, and iron chelating method. The anticancer, anticholinesterase, and antimicrobial effects were investigated using the XTT assay, Ellman method, and microdilution, respectively. Results Our results showed that between the water and methanol extracts there was a difference in terms of chemical composition. The antioxidant results suggested that both extracts have strong antioxidant activity. Similarly, both extracts showed strong α-glucosidase and α-amylase inhibition activity, while the water extract had higher inhibition activity than the methanol extract against acetylcholinesterase and butyrylcholinesterase. The methanol extract of F. carica exhibited significant anticancer activity on MDA-MB-231 cells and showed moderate antimicrobial activities against Escherichia coli and Staphylococcus aureus. Conclusion Our results suggest that F. carica leaves could be a valuable source for developing a promising therapeutic agent in cancer, diabetes, and Alzheimer's disease.

In recent years, using of plants to develop combine therapies for treatment of certain diseases such as cancer, Alzheimer's disease, and diabetes mellitus is extremely plausible approach. Perhaps, the definitive treatment of some of these diseases is hidden in the complex content of a plant in nature. Thus, in the present study, we decided to determine the biological activities of methanol and water extracts of the endemic Sideritis libanotica. To the best of our knowledge, the present study is the first investigation on antioxidant, enzyme inhibitory activity, antimicrobial activity, and in vitro cytotoxicity of S. libanotica. According to results, while the methanol extract shows better anti-cholinesterase, α-glucosidase, and α-amylase inhibition activity and cytotoxicity than the water extract, the tyrosinase inhibitory activity of the water extract was found to be better than the methanol extract. This study provides valuable information on how the biological activity of endemic S. libanotica changes in different solvent extractions such as water and methanol.

This work examined the cytotoxic effects of colchicine on PC3 cells and elucidated the possible underlying mechanisms of its cytotoxicity. The cells were exposed to colchicine at different concentrations ranging from 1 to 100 ng/mL for 24 h, and it showed considerable cytotoxicity with an IC50 value of 22.99 ng/mL. Mechanistic studies also exhibited that colchicine treatment results in cell cycle arrest at the G2/M phase as well as decreased mitochondrial membrane potential and increased early and late apoptotic cells. The apoptotic and DNA-damaging effects of colchicine have also been verified by fluorescence imaging and ELISA experiments, and they revealed that while colchicine treatment significantly modulated expression as increases in Bax, cleaved caspase 3, cleaved PARP, and 8-hydroxy-desoxyguanosine levels and as a decrease of BCL-2 protein expression. Besides, colchicine treatment significantly increased the total oxidant (TOS) level, which is a signal of oxidative stress and potential cause of DNA damage. Finally, the results of quantitative real-time PCR experiments demonstrated that colchicine treatment concentration-dependently suppressed MMP-9 mRNA expression. Overall, colchicine provides meaningful cytotoxicity on PC3 cells due to induced oxidative stress, reduced mitochondrial membrane potential, increased DNA damage, and finally increased apoptosis in PC3 cells. Nevertheless, further research needs to be conducted to assess the potential of colchicine as an anticancer drug for the treatment of prostate cancer.

Polo-like kinase 1 (PLK1) is a prominent mediatory player during the cell cycle, mitosis, and cytokinesis in eukaryotic cells. Besides its physiological roles, PLK1 expression is upregulated in a wide range of human malignant tumors and its overexpression worsens prognosis, therefore, specific inhibition of PLK1 in tumor cells is a fascinating approach for the development of novel chemotherapeutics. The present study elucidated the potential cytotoxic effects of a PLK1 inhibitor, GSK461364A, in five cancer cell lines including Raji, K562, PC3, MCF-7, MDA-MB-231, along with noncancerous L929 cells by XTT assay. The cells were treated for 24 h with GSK461364A at different concentrations ranged between 0.5 and 40 μM and significant cytotoxicity was observed in all treated groups with the IC50 values between 2.36 and 4.08 μM. GSK461364A was also found to be safer with lower cytotoxicity against L929 cells and the IC50 value was found to be greater than 40 μM. Raji cells were identified as the most sensitive cell line against GSK461364A with the lowest IC50 values, hence it was selected for further studies to evaluate the underlying mechanism of cytotoxic activity. The treatment of Raji cells with GSK461364A caused a cell cycle arrest at the G2/M phase, also altered TOS, which is an indicator of oxidative stress, and DNA damage response, significantly. The Annexin V binding assay revealed that GSK461364A treatment significantly increased in the percentage of early and late apoptotic cells. Fluorescence imaging also showed that GSK461364A treatment significantly induced apoptosis of Raji cells. The apoptotic effect of the compound has also been confirmed by increased expressions of Bax and cleaved caspase 3 and along with the decreased expression of BCL-2. The results demonstrated that GSK461364A induced anticancer effects which was mainly promoted by cell cycle arrest, oxidative stress, DNA damage, and finally apoptosis in Burkitt's lymphoma cells. Taken together, the present results emphasized that GSK461364A could be a useful therapeutic agent in patients with Burkitt's lymphoma. However, further studies are required to consolidate the anticancer activity of this promising compound.

4-Thiazolidinones and phenylaminopyrimidines are known as anticancer agents. Imatinib is the pioneer phenylaminopyrimidine derivative kinase inhibitor, which is used for the treatment of chronic myeloid leukemia. With a hybrid approach, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives containing phenylaminopyrimidine core were designed, synthesized, and tested for their anticancer activity on K562 (chronic myeloid leukemia), PC3 (prostat cancer), and SHSY-5Y (neuroblastoma) cells. Since superior anticancer activity was observed on K562 cells, further biological studies of selected compounds (8, 15, and 34) were performed on K562 cells. For the synthesis of designed compounds, thiourea compounds were converted to 2-imino-1,3-thiazolidin-4-ones with α-chloroacetic acid in the presence of sodium acetate. 5-Benzylidene-2-imino-1,3-thiazolidin-4-one derivatives were obtained by Knoevenagel condensation of 2-imino-1,3-thiazolidin-4-ones with related aldehydes. Compounds 8, 15, and 34 were evaluated for cell viability, apoptosis studies, cell cycle experiments, and DNA damage assays. IC50 values of compounds 8, 15, and 34 were found as 5.26 ± 1.03, 3.52 ± 0.91, and 8.16 ± 1.27 μM, respectively, in K562 cells. Preferably, these compounds showed less toxicity towards L929 cells compared to imatinib. Furthermore, compounds 8 and 15 significantly induced early and late apoptosis in a time-dependent manner. Compounds 15 and 34 induced cell cycle arrest at G0/G1 phase and compound 8 caused cell cycle arrest at G2/M phase. Based on DNA damage assay, compounds 8 and 15 were found to be more genotoxic than imatinib towards K562 cells. To put more molecular insight, possible Abl inhibition mechanisms of most active compounds were predicted by molecular docking studies. In conclusion, a novel series of 5-benzylidene-2-arylimino-4-thiazolidinone derivatives and their promising anticancer activities were reported herein.

Background: As a member of serine/threonine-protein kinase, Polo‐like kinase 1 (PLK1) plays crucial roles during mitosis and also contributes to DNA damage response and repair. PLK1 is aberrantly expressed in many types of tumor cells and increased levels of PLK1 is closely related to tumorigenesis and poor clinical outcomes. Therefore, PLK1 is accepted as one of the potential targets for the discovery of novel anticancer agents. The objective of this study was to assess the cytotoxic effects of a novel PLK1 inhibitor, RO3280, against MCF-7, human breast cancer cells; HepG2, human hepatocellular carcinoma cells; and PC3, human prostate cancer cells, as well as non-cancerous L929 fibroblast cells. Methods: Antiproliferative activity of RO3280 was examined using the XTT assay. Flow cytometry assay was performed to evaluate cell cycle distribution, apoptosis, multicaspase activity, mitochondrial membrane potential, and DNA damage response. We also examined apoptosis with fluorescence imaging studies. Results: According to the results of XTT assay, although RO3280 displayed potent cytotoxicity in all treated cancer cells, the most sensitive cell line was identified as MCF-7 cells that were selected for further studies. The compound induced a cell cycle arrest in MCF-7 cells at G2/M phase and significantly induced apoptosis, multicaspase activity, DNA damage response, and decreased mitochondrial membrane potential of MCF-7 cells. Conclusion: Overall, RO3280 induces anticancer effects promoted mainly by DNA damage, cell cycle arrest, and apoptosis in breast cancer cells. Further studies are needed to assess its usability as an anticancer agent with specific cancer types.

Accumulating evidences indicate that thiamine plays a vital role in the nervous system. However, questions exist as to how it causes epilepsy, neuronal damage, and antiepileptic mechanisms. The study looked at how the thiamine supplement impacted pentylenetetrazole (PTZ)-induced seizures in rats and pentylenetetrazole-induced neurotoxicity in the SH-SY5Y cell line. We used twenty-four male rats and they were randomly divided into 4 groups as control, saline (1 mL/kg/day serum physiologic) + PTZ, thiamine (50 mg/kg/day) + PTZ, and thiamine (50 mg/kg/day) for 10 days. PTZ (45 mg/kg) was given to activate the seizure on day 10. Memory efficiency was measured by using passive avoidance. The brain levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), caspase-3, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) were analyzed by using ELISA kits. SH-SY5Y cells were treated with/without thiamine for 1 h, followed by PTZ (30 μm) at a medium level to trigger neurotoxicity. Cell viability, total antioxidant status, total oxidant status, and apoptosis were assayed in the SH-SY5Y cells. Thiamine delayed the initiation of epileptic seizures and increased memory damage. In addition, 8-OHdG, caspase-3, NO, and cGMP levels were significantly reduced in the brain and prevented pentylenetetrazole-induced neurotoxicity, apoptosis, enhanced antioxidant, and reduced oxidant in SH-SY5Y cells. Thiamine dramatically altered seizures, memory loss, oxidative stress, and apoptosis. Thiamine has a preventative effect on PTZ-induced seizures in rats and PTZ-induced neurotoxicity in SH-SY5Y neuroblastoma cells. It could prevent oxidative stress and signaling of NO/cGMP. Thiamine supplement could be used as an additional therapeutic agent in epilepsy.

Epilepsy is one of the most common neurological disorders that severely affect the life quality of many people worldwide. Excitatory-inhibitory mechanisms, oxidative stress, and also inflammation systems have been implicated in the pathogenesis of epilepsy. Recent studies have shown that salmon calcitonin (sCT) has positive effects on the nervous system. However, its relation with epilepsy is still unclear. This study aimed to investigate the effect of sCT on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole (PTZ)-induced epilepsy model in rats. The study was performed in two steps. In the first step, the effect of sCT on epileptic seizures was evaluated by using electroencephalography (EEG) in fully kindled rats. In the second step, the effect of sCT on epileptogenesis was evaluated by using the kindling process. Glutamate and gamma-aminobutyric acid (GABA), thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1 β), and interleukin 6 (IL-6) were measured in the second group in the brain and serum. Hippocampal regions were stained with hematoxylin-eosin and toluidine blue to evaluate hippocampal neuronal damage histopathologically. Salmon calcitonin showed an antiepileptic effect in fully kindled rats and also prevented the development of epileptogenesis in the kindling process. Besides, sCT decreased glutamate and increased GABA levels. Furthermore, it reduced TBARS levels and increased SOD and CAT levels. On the other hand, it decreased TNF-α levels, IL-1 β levels, and IL-6 levels. Histopathologically, sCT decreased neuronal damage in all hippocampal regions. Our findings are the first preclinical report to show the positive effect of sCT on epileptic seizures and epileptogenesis. Further investigation is required to answer the questions raised about the probable mechanisms involved.

Graphical abstract, Objective This study was aimed to investigate the in vitro antioxidant, antimicrobial, cytotoxicity, and enzyme inhibition activities of Tragopogon porrifolius and Polygonum cognatum which are naturally grown and consumed intensively by people in Sivas, Turkey. Methods Plant materials were extracted with aqueous ethanol by maceration method. The components of the extracts were determined using the Gas Chromatography Mass Spectrometry. Antimicrobial, cytotoxic and enzyme inhibition activities of the extracts were investigated by micro dilution, XTT assay and 96-micro-well plate methods, respectively. The antioxidant activity evaluated using the DPPH radical scavenging, thiobarbituric acid and reducing power methods. The total phenol and total flavonoid content was also examined. Results GC–MS analysis revealed the presence of 31 compounds inP. cognatum extract and 29 compounds in T. porrifolius extract. According to the results, T. porrifolius extract showed high level of antioxidant activity in comparison to P. Cognatum extract. T. porrifolius exhibited higher α-glucosidase inhibitory activity, and both extract showed strong α-amylase inhibition activity compared to reference drug acarbose. T. porrifolius and P. cognatum ethanolic extracts exhibited antimicrobial activity in the concentration range of 0.039–2.5 mg/ml. Both extracts also exhibited significant anticancer effect on MDA-MB-231 breast cancer cells. The IC50 values of T. porrifolius and P. cognatum extracts in MDA-MB-231 cells were determined as 0.0625 mg/mL and 0.053 mg/mL, respectively. Conclusion Our findings demonstrated that T. porrifolius and P. cognatum ethanolic extracts have promising effect on antioxidant, antimicrobial and cytotoxic activity as well as enzyme inhibition activity, and hence further studies required to identify specific compounds responsible for these activities.

WOS: 000444259700003, PubMed ID: 30213283, Plane tree (Platanus orientalis L.) leaves have been employed for centuries in various countries due to their pharmacological value. Therefore, determination of the biological activity of the leaves is of interest. The aim of the study was to evaluate the inhibitory effects against Alzheimer's disease-related enzymes Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE), diabetes mellitus related enzymes alpha-glucosidase and alpha-amylase. The antioxidant, anticancer, and antimicrobial activities of the leaves were also studied. According to the results, both water and methanol extracts of P. orientalis demonstrated more alpha-glucosidase and alpha-amylase inhibition activity than the antidiabetic drug-acarbose at the same concentration level. In addition, extracts showed good inhibition activity against AChE and BuChE. Significant results were obtained regarding antioxidant, anticancer, and antimicrobial activities. These results are very promising especially for the improvement of pharmaceutical formulations to treat various diseases such as age-related diseases, cancer, diabetes etc. and it is necessary to conduct further experiments.

Anomaly detection (AD) is an important application for target detection in remotely sensed hyperspectral data. Therefore, variety kinds of methods with different advantages and drawbacks have been proposed for past two decades. Recently, the kernelized support vector data description (SVDD) based anomaly detection approaches has become popular as these methods avoid prior assumptions about the distribution of data and provides better generalization to characterize the background. The global SVDD needs a training set for the background modeling; however, it is sensitive to outliers in the data; so the training set has to be generated with pure background spectra. In general, the training data is selected by random selection of the pixels spectra in entire image. In this study, we propose an approach for better selection of the training data based on principal component analysis (PCA). A valid assumption for remotely sensed images is that the principal components (PCs) with higher variance include substantial amount of background information. For this reason, a subspace composed of several of the highest variance PCs of cluttered data can be defined as background subspace. Thus, with the proposed algorithm, the selection of background pixels is achieved by projecting all pixels in the image into the background subspace and thresholding them with respect to the relative energy on the background subspace. Experimental results verify that the proposed algorithm has promising results in terms of accuracy and speed during the detection of anomalies.

Aim. The treatment of pain has been one of the most important objectives of medicine. We aimed to investigate antinociceptive effects and mechanisms of magnetic field (MF) on the hyperalgesia produced by S-Nitroso N-acetyl penicillamine (SNAP). Method. Study has been made in two sections. In the first section, rats were divided four groups (six in each). The first group was determined as sham group and administrated 0.3 mL, 0.9% NaCl intraperitoneally (i.p) before assessing tail flick latencies (TFLs) (Sham group). In the second group, 2 mg/kg SNAP administrated i.p. and TFLs were assessed at the same time points with first group (SNAP group). In the third group, rats were repeatedly exposed to MF for 6 consecutive days (MF group). In the fourth group, SNAP was administrated i.p everyday shortly before MF exposure (SNAP+MF group). In the second section, animals divided to the same groups with the first section. Same procedures have been performed with the first section groups and blood samples were collected to determine plasma levels of β-endorphin and substance P. Results. SNAP (2 mg/kg) produced hyperalgesic effect with i.p. administration. MF application (5 mT and 165 min per day) produced a strong antinociception in Days 3 and 4. Tail flick values of SNAP+MF in Days 3 and 4 were found to be significantly low as compared to MF and Sham groups. In SNAP group, substance P levels were found to be significantly high. Plasma β-endorphin levels in MF and SNAP+MF groups were significantly high as compared to the Sham group. Conclusion. MF may be an alternative antinociceptive approach for pain treatment. There is need for further studies to overcome the tolerance to antinociceptive effects of MF.Keywords: Hyperalgesia, magnetic field, snap, substance p, β-endorphin, tail flick ÖzetAmaç. Ağrı tedavisi tıbbın en önemli hedeflerinden biridir. Bu araştırmada manyetik alan uygulamasının S-Nitroso N-acetyl penicillamine (SNAP) tarafından oluşturulan ağrı üzerindeki etkilerini ve etki mekanizmasını araştırmayı amaçladık. Yöntem. Çalışma iki kısım olacak şekilde tasarlandı. Birindi kısımda hayvanlar her birinde altı hayvan olacak şekilde 4 gruba bölündü. Birinci grup sham grubu olarak belirlendi ve bu hayvanlara 0,3 mL %0,9 NaCl tail flick latensleri ölçülmeden once uygulandı. İkinci gruba (SNAP grubu) 2 mg/kg SNAP i.p. olarak enjekte edildi ve sham grubu ile aynı zaman noktalarında tail flick ölçümleri yapıldı. Üçüncü grup (MF grubu) tekrarlayan altı gün boyunca manyetik alana maruz bırakıldı. Dördüncü grupta (SNAP+MF) hayvanlara manyetik alan uygulaması yapılmadan hemen önce 2 mg/kg SNAP i.p. olarak uygulandı. Çalışmanın ikinci kısmında ratlardan kan örnekleri alınarak kanlarında supstance p ve B-endorfin seviyelerine ELISA yöntemi ile bakıldı. Bulgular. SNAP (2 mg/kg) anlamlı bir hiperaljezi meydana getirerek tail flick latenleslerini kısalttı. Manyeteik alan uygulaması (5 mT ve 165 dakika/gün) özellikle 3. ve 4. günlerde anlamlı bir analjezi meydana getirdi. SNAP grubunda substance p seviyeleri yüksek bulunurken, manyetik alan grubunda B-endorfin seviyelerinin yüksek olduğu tespit edildi. Sonuç. Bu sonuçlar manyetik alan uygulamasının ağrı tedavisinde alternatif bir yaklaşım olabileceğini göstermektedir. Fakat bu yöntemin kullanılabilmesi için gelişen toleransın üstesinden gelmenin yollarının bulunması ve bunun içinde ileri araştırmalara gereksinim vardır.Anahtar sözcükler: Hiperaljezi, manyetik alan, snap, p maddesi, β-endorfin, tail flick, Amaç. Ağrı tedavisi tıbbın en önemli hedeflerinden biridir. Bu araştırmada manyetik alan uygulamasının S-Nitroso N-acetyl penicillamine (SNAP) tarafından oluşturulan ağrı üzerindeki etkilerini ve etki mekanizmasını araştırmayı amaçladık. Yöntem. Çalışma iki kısım olacak şekilde tasarlandı. Birindi kısımda hayvanlar her birinde altı hayvan olacak şekilde 4 gruba bölündü. Birinci grup sham grubu olarak belirlendi ve bu hayvanlara 0,3 mL %0,9 NaCl tail flick latensleri ölçülmeden once uygulandı. İkinci gruba (SNAP grubu) 2 mg/kg SNAP i.p. olarak enjekte edildi ve sham grubu ile aynı zaman noktalarında tail flick ölçümleri yapıldı. Üçüncü grup (MF grubu) tekrarlayan altı gün boyunca manyetik alana maruz bırakıldı. Dördüncü grupta (SNAP+MF) hayvanlara manyetik alan uygulaması yapılmadan hemen önce 2 mg/kg SNAP i.p. olarak uygulandı. Çalışmanın ikinci kısmında ratlardan kan örnekleri alınarak kanlarında supstance p ve B-endorfin seviyelerine ELISA yöntemi ile bakıldı. Bulgular. SNAP (2 mg/kg) anlamlı bir hiperaljezi meydana getirerek tail flick latenleslerini kısalttı. Manyeteik alan uygulaması (5 mT ve 165 dakika/gün) özellikle 3. ve 4. günlerde anlamlı bir analjezi meydana getirdi. SNAP grubunda substance p seviyeleri yüksek bulunurken, manyetik alan grubunda B-endorfin seviyelerinin yüksek olduğu tespit edildi. Sonuç. Bu sonuçlar manyetik alan uygulamasının ağrı tedavisinde alternatif bir yaklaşım olabileceğini göstermektedir. Fakat bu yöntemin kullanılabilmesi için gelişen toleransın üstesinden gelmenin yollarının bulunması ve bunun içinde ileri araştırmalara gereksinim vardır.

This paper proposes a novel automatic geo-spatial object recognition algorithm for high resolution satellite imaging. The proposed algorithm consists of two main steps; a hypothesis generation step with a local feature-based algorithm and a verification step with a shape-based approach. In the hypothesis generation step, a set of hypothesis for possible object locations is generated, aiming lower missed detections and higher false-positives by using a Bag of Visual Words type approach. In the verification step, the foreground objects are first extracted by a semi-supervised image segmentation algorithm, utilizing detection results from the previous step, and then, the shape descriptors for segmented objects are utilized to prune out the false positives. Based on simulation results, it can be argued that the proposed algorithm achieves both high precision and high recall rates as a result of taking advantage of both the local feature-based and the shape-based object detection approaches. The superiority of the proposed method is due to the ability of minimization of false alarm rate and since most of the object shapes contain more characteristic and discriminative information about their identity and functionality.

In this paper, a novel automatic geo-spatial object recognition algorithm from high resolution satellite imagery is proposed. The proposed algorithm consists of two main steps; the generation of hypothesis with a local feature based algorithm and verification step with a shape based approach. The superiority of this method is the ability of minimization of false alarm number in the recognition and this is because object shape includes more characteristic and discriminative information about object identity and functionality. Furthermore, the location information can be extracted for the detected objects completely and precisely. Experimental results reveal that the proposed algorithm has promising results in terms of accuracy in recognizing geospatial objects, such as airplane etc., from high resolution satellite imagery.

WOS: 000331099700007, Cancer is one of the most important health problems in the world and the treatment approaches are still challenging and generally not at desirable levels. Conventional anti-cancer agents may cause systemic toxicity, have poor solubility, and lack of selectivity. In order to overcome these hurdles, nanoparticle based therapeutics have been widely employed to enhance therapeutic efficacies and reduce systemic toxicity of pharmaceutical agents. In recent years, nanoparticulate carrier systems (NPCs) in medicine have attracted considerable scientific attention and interest in the worldwide because of their unique properties in the diagnosis and therapy of many diseases including cancer. One of the therapeutic strategies of NPCs is protein based nanoparticles. Human serum albumin (HSA) and bovine serum albumin (BSA) are the most frequently used materials for this purpose due to their remarkable advantages. In this review article, we focused on protein based nanoparticles and summarized their important applications including anti-cancer drug delivery, photodynamic therapy, and gene delivery.