Cancer chemopreventive effects can be exerted through the induction of phase II detoxification enzymes and the inhibition of inflammatory responses. In this study, the cancer chemopreventive effects and anti-inflammatory responses of 30 seaweed extracts were examined. The extracts of Dictyota coriacea and Cutleria cylindrica exhibited the high chemoprevention index, having 4.36 and 4.66, respectively. They also activated antioxidant response element at $100\;{\mu}g/mL$ by about 3-fold while did not activate xenobiotic response element. Seven seaweed extracts, Ishige okamurae, Desmarestia ligulata, Desmarestia viridis, Dictyopteris divaricata, D. coriacea, Sargassum horneri, and Sargassum yezoense, showed significant inhibition on nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production in a dose-dependant manner in $5-20\;{\mu}g/mL$. These seaweed extracts could be used as food materials for cancer chemoprevention. D. coriacea could contain potential chemopreventive agents not only that regulate genes via an ARE-dependent mechanism but also prevent the inflammation through inhibition of NO and $PGE_2$ production.
Type 304SS coatings were performed at 200$\square$ onto AISI 1045 carbon steel substrate using unbalanced magnetron sputtering (UBMS) with an austenitic AISI 304 stainless steel (SS) target of 100mm diameter. The total deposition pressure in the active Ar gas was 2$\times$10$^{-3}$ Torr. Coatings were done at various target power densities and bias voltages. Chemical compositions of metallic elements of the coatings were measured by energy dispersive X-rays spectroscopy (EDS). The structure and the morphology of Type 304SS coatings were investigated by means of X-ray diffraction (XRD) and scanning electron microscopy (SEM). Corrosion properties of the coated specimens were examined using electrochemical polarization measurements and electrochemical impedance spectroscopy in a deaerated 3.5% NaCl solution. The porosity rate was obtained from a comparison of the dc polarization resistance of the uncoated and coated substrates. Scratch adhesion testing was used to compare the critical loads for different coatings. XRD results showed that the sputtered films exhibit a ferritic b.c.c. $\alpha$-phase. Potentiodynamic polarization curves indicated that all samples had much higher corrosion potential and better corrosion resistance than the bare steel substrate. The corrosion performance increased with increasing power density and the adhesion was enhanced at the bias voltage of -50V. An improvement in the corrosion resistance can be obtained with a better coating adhesion. Finally, an optimized deposition condition for corrosion protection was found as $40W/cm^2$ and -50V.
In the present paper, a numerical simulation method based on mesoscopic composite structure of concrete, the truss network model, is developed to evaluate the diffusivity of concrete in order to account for the microstructure of concrete, the binding effect of chloride ions and the chloride concentration dependence. In the model, concrete is described as a three-phase composite, consisting of mortar, coarse aggregates and the interfacial transition zones (ITZs) between them. The advantage of the current model is that it can easily represent the movement of mass (e.g. water or chloride ions) through ITZs or the potential cracks within concrete. An analytical method to estimate the chloride diffusivity of mortar and ITZ, which are both treated as homogenious materials in the model, is introduced in terms of water-to-cement ratio (w/c) and sand volume fraction. Using the newly developed approaches, the effect of cracking of concrete on chloride diffusion is reflected by means of the similar process as that in the test. The results of calculation give close match with experimental observations. Furthermore, with consideration of the binding capacity of chloride ions to cement paste and the concentration dependence for diffusivity, the one-dimensional nonlinear diffusion equation is established, as well as its finite difference form in terms of the truss network model. A series of numerical analysises performed on the model find that the chloride diffusion is substantially influenced by the binding capacity and concentration dependence, which is same as that revealed in some experimental investigations. This indicates the necessity to take into account the binding capacity and chloride concentration dependence in the durability analysis and service life prediction of concrete structures.
A novel strategy for the synthesis of $CoSb_2$ nanoparticles is demonstrated via preparation of novel organometallic complexes. Hydrated cobalt oleate (CoOl) and non-hydrated antimony oleate (SbOl) complexes are synthesized as precursors. The $CoSb_2$ nanoparticles are prepared by hot injection, which involves thermolysis of CoOl and SbOl in a non-coordinating solvent at $320^{\circ}C$. The coordination modes and distinct thermal behaviors of the intermediate non-hydrated SbOl complexes are comparatively investigated by thermo-analytical techniques. When the reaction temperature is increased, the particle size is found to increase linearly. The crystallinity of the $CoSb_2$ nanoparticles prepared at $250^{\circ}C$ is amorphous phase without any peaks. $CoSb_2$ structural peaks start to appear at $300^{\circ}C$ and dominant peaks with high crystallinity are synthesized at $320^{\circ}C$. The potential chemical structures of non-hydrated SbOl and their reaction mechanisms by thermolysis are elucidated. The elemental composition and crystallographic structure of $CoSb_2$ nanoparticles suggest a bimodal interaction of the organic shell and the nanoparticle surface, with a chemical absorbed inner layer and physically absorbed outer layer of carboxylic acid.
Objectives : This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells. Methods : U937 cells were exposed to DST and growth inhibition was measured by MTT assay. Results : Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-${\gamma}1$, ${\beta}$-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3. Conclusions : These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.
This study analyzed the observation characteristics with the subject of observation data through defining the change of the observation degree as attention /conscious observation /visual understanding. Furthermore, by obtaining the formular with which to estimate the subjects' observation amount, this study suggests a potential method for easier analysis of observation characteristics. The conclusions from the study are as the followings. First, the observation frequency was being generated with wide deviation among subjects while there was a flow-on characteristics depending on the degree of observation. These characteristics enabled the study to obtain the formular with which to estimate the observation amount. Second, the study could establish the area frequency by grade from the entire observation data. The area I was at most 4% for the area frequency but accounted for 18.2% of the entire effective observation time, and the area II 16% and 38.7% respectively. Accordingly, only considering the observation area distribution of the area I or the areas I and II shows which position of the space the subjects were observing. Third, with the subject of the relatively higher observation time at at the subject's observation characteristics, as the observation phase was getting higher, the observation time decreased more. Forth, by obtaining the formular to estimate the observation amount for observation data according to the change of observation degree, the study could find the estimating observation characteristics of additional subjects. The formular shortens the analysis time and facilitates the analysis process.
Introduction: Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from ${\varepsilon}$-N-acetyl lysine amino acids of histone proteins. Their action is opposite to that of histone acetyltransferase that adds acetyl groups to these lysines. Only few HDAC inhibitors are approved and used as anti-cancer therapeutics. Thus, discovery of new and potential HDAC inhibitors are necessary in the effective treatment of cancer. Materials and Methods: This study proposed a method using support vector machine (SVM) to classify HDAC8 inhibitors and non-inhibitors in early-phase virtual compound filtering and screening. The 100 experimentally known HDAC8 inhibitors including 52 inhibitors and 48 non-inhibitors were used in this study. A set of molecular descriptors was calculated for all compounds in the dataset using ADRIANA. Code of Molecular Networks. Different kernel functions available from SVM Tools of free support vector machine software and training and test sets of varying size were used in model generation and validation. Results and Conclusion: The best model obtained using kernel functions has shown 75% of accuracy on test set prediction. The other models have also displayed good prediction over the test set compounds. The results of this study can be used as simple and effective filters in the drug discovery process.
Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.
Background: Ovarian cancer is the third most common cause of cancer in Indian women. Despite an initial 70-80% response rate, most patients relapse within 1-2 years and develop chemoresistance. Hence, identification or repositioning of drugs to resensitise ovarian cancer cells to existing chemotherapy is needed. Traditionally immortalized cell lines have been used in research, but these may contain genetic aberrations and chromosomal abnormalities serving as poor indicators of normal cell phenotype and progression of early-stage disease. The use of primary cells, maintained for only short periods of time in vitro, may serve as the best representative for studying in vivo conditions of the tissues from which they are derived. In this study we have attempted to evaluate the effect of metformin (an antidiabetic drug) in primary ovarian cancer cells because of its promising effect in other solid tumours. Materials and Methods: Primary cultures of epithelial ovarian cancer cells established from ascitic fluid of untreated ovarian cancer patients were used. The cells were treated with metformin at doses standardized by MTT assay and its ability to induce apoptosis was studied. The cells were analysed for apoptosis and apoptosis related proteins by flow cytometry and western blotting respectively. Results: Metformin induced apoptosis in ovarian cancer cells, provoking cell cycle arrest in the G0/G1 and S phase. It induced apoptosis in ovarian cancer cells by, down-regulating Bcl-2 and up-regulating Bax expression. Conclusions: Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins. These data are relevant to ongoing translational research efforts exploring the chemotherapeutic potential of metformin.
Purpose: The chemoresistance of human hepatocellular carcinoma (HCC) to cytotoxic drugs, especially intrinsic or acquired multidrug resistance (MDR), still remains a major challenge in the management of HCC. In the present study, possible mechanisms involved in MDR of HCC were identified using a 5-fluorouracil (5-FU)-resistant human HCC cell line. Methods: BEL-7402/5-FU cells were established through continuous culturing parental BEL-7402 cells, imitating the pattern of chemotherapy clinically. Growth curves and chemosensitivity to cytotoxic drugs were determined by MTT assay. Doubling times, colony formation and adherence rates were calculated after cell counting. Morphological alteration, karyotype morphology, and untrastructure were assessed under optical and electron microscopes. The distribution in the cell cycle and drug efflux pump activity were measured by flow cytometry. Furthermore, expression of potential genes involved in MDR of BEL-7402/5-FU cells were detected by immunocytochemistry. Results: Compared to its parental cells, BEL-7402/5-FU cells had a prolonged doubling time, a lower mitotic index, colony efficiency and adhesive ability, and a decreased drug efflux pump activity. The resistant cells tended to grow in clusters and apparent changes of ultrastructures occurred. BEL-7402/5-FU cells presented with an increased proportion in S and G2/M phases with a concomitant decrease in G0/G1 phase. The MDR phenotype of BEL-7402/5-FU might be partly attributed to increased drug efflux pump activity via multidrug resistance protein 1 (MRP1), overexpression of thymidylate synthase (TS), resistance to apoptosis by augmentation of the Bcl-xl/Bax ratio, and intracellular adhesion medicated by E-cadherin (E-cad). P-glycoprotein (P-gp) might play a limited role in the MDR of BEL-7402/5-FU. Conclusion: Increased activity or expression of MRP1, Bcl-xl, TS, and E-cad appear to be involved in the MDR mechanism of BEL-7402/5-FU.
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