Anti-angiogenic effects of ethanolic extract of Artemisia sieberi compared to its active substance, artemisinin

AbstractAngiogenesis plays a key role in tumor growth, invasion and metastasis of cancer diseases and therefore, the inhibition of angiogenesis can provide an important therapeutic approach in cancer diseases. This study was designed to compare the anti-angiogenic activities of the ethanolic extract of Artemisia sieberi Besser, Asteraceae, and its active substance, artemisinin in both in vitro and in vivo models. To compare cytotoxicity level of ethanolic extract of A. sieberi with artemisinin, different concentrations (1–100μg/ml) were tested using MTT assay on human umbilical vein endothelial cells. The anti-angiogenic properties of serial concentrations of ethanolic extract of A. sieberi and artemisinin were examined on human umbilical vein endothelial cells using a three-dimensional angiogenesis assay (in vitro model) and in the chick chorioallantoic membrane assay as in vivo model. The effects of ethanolic extract of A. sieberi and artemisinin were also tested on the expression of VEGFR-1, VEGFR-2 and CD34 genes using real-time PCR. Ethanolic extract of A. sieberi and artemisinin significantly (p<0.001) inhibited the angiogenesis in the human umbilical vein endothelial cells culture whilst the ethanolic extract of A. sieberi showed higher effect in a concentration-dependent fashion (p<0.001). The chick chorioallantoic membrane angiogenesis was also completely inhibited by ethanolic extract of A. sieberi at concentration of 33ng/100μl/egg. The gene expression analysis showed that the ethanolic extract of A. sieberi and artemisinin reduced the transcription of VEGFR-1, VEGFR-2 and CD34 genes in a concentration-dependent manner. This study demonstrated that the ethanolic extract of A. sieberi is strongly able to inhibit the angiogenesis in human umbilical vein endothelial cells and chick chorioallantoic membrane models compared to the artemisinin

Groundwater Vulnerability Assessment Using DRASTIC and SINTACS Models in GIS (Case Study: Karun Township)

Existence of important sources of pollutants and points of human activities on the ground and the penetration of these pollutants into aquifers, reduces the quality of groundwater, so in the management of groundwater resources, pollution prevention these waters are essential. The groundwater of Karun Township in Khuzestan province is always exposed to pollution due to the prosperity of agricultural and industrial activities in that area. Therefore, the aim of this study is to evaluate and zoning the aquifer vulnerability of the region using DRASTIC and SINTACS models. By mapping and combining hydrogeological parameters effective in the transfer of contamination to the aquifer, vulnerability maps of the two models were prepared in GIS software environment. To validate the models used, the measured amounts of nitrate in the wells in the area were used and the Pearson correlation coefficient between the models and the nitrate layer was calculated and determined. The results showed that the vulnerability index of the DRASTIC model varies Between 68 to 215 and the vulnerability index of the SINTACS model varies between 52 and 195. In the DRASTIC method, 485.2 hectares of the area without risk of pollution, 751.6 hectares with very low vulnerability, 3305.5 hectares with low vulnerability, 12411.7 hectares with moderate vulnerability, 11191.2 hectares with Moderate to high vulnerability, 9427.3 hectares with high vulnerability, 58861 hectares with very high vulnerability and 478.5 hectares are completely susceptible to infection. In the SINTACS method, 455.4 hectares of the area without risk of pollution, 789.1 hectares with very low vulnerability, 32281 hectares with low vulnerability, 12426.7 hectares with medium vulnerability, 11169.4 hectares with Moderate to high vulnerability, 9449.3 hectares with high vulnerability, 5844.2 hectares with very high vulnerability and 495.7 hectares are completely susceptible to infection. Also, the correlation of groundwater nitrate map with DRASTIC and SINTACS models was 0.68 and 0.51, respectively, which indicates the higher capability of the DRASTIC model than the SINTACS model for the aquifer in the study area

The pivotal role of angiogenesis in a multi-scale modeling of tumor growth exhibiting the avascular and vascular phases

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.mvr.2018.05.001 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/The mechanisms involved in tumor growth mainly occur at the microenvironment, where the interactions between the intracellular, intercellular and extracellular scales mediate the dynamics of tumor. In this work, we present a multi-scale model of solid tumor dynamics to simulate the avascular and vascular growth as well as tumor-induced angiogenesis. The extracellular and intercellular scales are modeled using partial differential equations and cellular Potts model, respectively. Also, few biochemical and biophysical rules control the dynamics of intracellular level. On the other hand, the growth of melanoma tumors is modeled in an animal in-vivo study to evaluate the simulation. The simulation shows that the model successfully reproduces a completed image of processes involved in tumor growth such as avascular and vascular growth as well as angiogenesis. The model incorporates the phenotypes of cancerous cells including proliferating, quiescent and necrotic cells, as well as endothelial cells during angiogenesis. The results clearly demonstrate the pivotal effect of angiogenesis on the progression of cancerous cells. Also, the model exhibits important events in tumor-induced angiogenesis like anastomosis. Moreover, the computational trend of tumor growth closely follows the observations in the experimental study

Antibacterial effects of <em>Solanum tuberosum</em> peel ethanol extract in vitro

Introduction: Today, medicinal plants are being widely used due to being natural, available, and cheaper than synthetic drugs and having minimum side effects. Since there were reports about the antibacterial properties of Solanum tuberosum (SE), the aim of this study was to investigate the antibacterial effects of SE ethanol extract in vitro condition on Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae Methods: Ethanol extract of SE peel was prepared by maceration method. Initially, antibacterial activity of ethanol extract of SE was qualitatively determined by disk diffusion test; then, the minimum inhibitory concentration and minimum bactericidal concentration were qualitatively determined by micro-dilution method. Results: SE peel extract had antibacterial properties and its effect was more pronounced on gram-positive bacteria, especially S. aureus (0.62&plusmn;0.00 mg/ml). The extract had antibacterial activity on gram-negative bacteria, P. aeruginosa, too (8.33&plusmn;2.88 mg/ml). Conclusion: SE peel extract has antibacterial activity and its effect on gram-positive bacteria was more pronounced than the investigated gram-negative bacteria. Therefore, it is suggested that SE peel constituent compounds be determined and to determine the exact mechanism of its antibacterial properties, and more comprehensive research be done to apply it, clinically.</p

AGS cell line xenograft tumor as a suitable gastric adenocarcinoma model: growth kinetic characterization and immunohistochemistry analysis

Objective(s): Gastric cancer is the third leading cause of cancer-related death worldwide. The overall survival rate of patients is poor because gastric cancers are usually diagnosed at the late stages. Therefore, further research is needed and appropriate research tools are required to develop novel therapeutic approaches.Materials and Methods: Eight female athymic nude mice with a C57BL/6 background were used in this study. AGS cells were inoculated into the flank. The tumor volumes were calculated and growth curves were drawn. When the volume of the tumors reached 1000 mm3, the animals were humanely euthanized with CO2 gas. After harvesting, tumors were analyzed with Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC). A pathologist confirmed tumor entity through H&E staining. Tumors were evaluated for expression of HER-2, P53, Ki-67, CD34, cytokeratin 8 (CK8), vimentin, estrogen receptor (ER), and progesterone receptor (PR) utilizing immunohistochemistry.Results: The tumor take rate was 62.5%, mean doubling time was 40.984 d, and the latency period was 30.62 days. The H&E staining results showed highly malignant hyperchromatin epithelial cells. IHC assessment showed the mutation status of P53 gene. The expression score of the CK8 protein in the tumor cells was +3. Vimentin protein was not expressed and changes in mesenchymal phenotype were not observed. Ki-67 IHC indicated that the proliferation rate was >43% and angiogenesis was defined as high MVD.Conclusion: The respective AGS xenograft model provides an opportunity to understand the pattern of tumor growth as well as to evaluate new gastric cancer therapies in in vivo studies

Transforming Growth Factor Beta-Induced Factor 2-Linked X (TGIF2LX) Regulates Two Morphogenesis Genes, Nir1 and Nir2 in Human Colorectal

Abstract- A member of homeodomain protein namely TGIF2LX has been implicated as a tumor suppressor gene in human malignancy as well as in spermatogenesis. However, to our knowledge, dynamic functional evidence of the TGIF2LX has not yet been provided. The aim of the present study was to investigate the human TGIF2LX target gene(s) using a cDNA-AFLP as a differential display method. A pEGFP-TGIF2LX construct containing the wild-type TGIF2LX cDNA was stably transfected into SW48 cells. UV microscopic analysis and Real-time RT-PCR were used to confirm TGIF2LX expression. The mRNA expressions of TGIF2LX in transfected SW48 cells, the cells containing empty vector (pEGFP-N), and untransfected cells were compared. Also, a Real-time PCR technique was applied to validate cDNA-AFLP results. The results revealed a significant down-regulation and up-regulationby TGIF2LX of Nir1 and Nir2 genes, respectively. The genes are engaged in the cell morphogenesis process. Our findings may provide new insight into the complex molecular pathways underlying colorectal cancer development

In vivo identification of novel TGIF2LX target genes in colorectal adenocarcinoma using the cDNA-AFLP method

Background and study aims: Homeobox-containing genes are composed of a group of regulatory genes encoding transcription factors involved in the control of developmental processes. The homeodomain proteins could activate or repress the expression of downstream target genes. This study was conducted to in vivo identify the potential target gene(s) of TGIF2LX in colorectal adenocarcinoma. Methods: A human colorectal adenocarcinoma cell line, SW48, was transfected with the recombinant pEGFPN1-TGIF2LX. The cells were injected subcutaneously into the flank of the three groups of 6-week-old female athymic C56BL/6 nude mice (n = 6 per group). The transcript profiles in the developed tumours were investigated using the cDNA amplified fragment length polymorphism (cDNA-AFLP) technique. Results: The real-time RT-PCR and DNA sequencing data for the identified genes indicated that the N-terminal domain-interacting receptor 1 (Nir1) gene was suppressed whereas Nir2 and fragile histidine triad (FHIT) genes were upregulated followed by the overexpression of TGIF2LX gene. Conclusion: Downregulation of Nir1 and upregulation of Nir2 and FHIT genes due to the overexpression of TGIF2LX suggests that the gene plays an important role as a suppressor in colorectal adenocarcinoma. � 2018 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved

Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma.

BACKGROUND: Transforming growth factor-β (TGF-β) pathway is involved in primary tumor progression and in promoting metastasis in a considerable proportion of human cancers such as colorectal cancer (CRC). Therefore, blockage of TGF-β pathway signaling via an inhibitor could be a valuable tool in CRC treatment. METHODS: To evaluate the efficacy of systemic targeting of the TGF-β pathway for therapeutic effects on CRC, we investigated the effects of a TGβRI (TGF-β receptor 1) or TβRI kinase inhibitor, SD-208, on SW-48, colon adenocarcinoma cells. In this work, in vitro cell proliferation was studied by methyl thiazolyl tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Also, the histopathological and immunohistochemical evaluations were conducted by hematoxylin and eosin, and Ki-67 and CD34 markers were stained, respectively. RESULTS: Our results showed no significant reduction in cell proliferation and vessel formation (170 ± 70 and 165 ± 70, P > 0.05) in treated SW-48 cells with SD-208 compared to controls. CONCLUSION: Our data suggested that SD-208 could not significantly reduce tumor growth and angiogenesis in human colorectal cancer model at least using SW-48 cells

Qualitative analysis of using particle swarm optimization for multi robot agents in three dimensional space

In the field of multi robot systems, algorithms that control communication and movement of multi robot agents has became an interesting arena for researchers recently. A big challenge in this area is to design an effective algorithm which make multi robots to work as a team of robots to perform their task and reach to their goal. In this article we use a Modified version of Particle Swarm Optimization Algorithm that is called MPSA. This algorithm allow us to use a virtual multi robot search to find optima in a three dimensional function space. The presented model has the advantages of being capable to change parameters and number of robots or agents, in order to improve the functionality of the multi agent system. In order to avoid collision with obstacles, we use the "leader follower" technique which can help to change the direction of swarm movement to avoid collision with obstacles while trying to get closer to their target. Simulation results show that with this algorithm, our team of robots can perform a swarm movement to reach the target while avoiding collision among themselves or with the obstacles that may be in the environment