Arsenic Trioxide Induces Apoptosis and Incapacitates Proliferation and Invasive Properties of U87MG Glioblastoma Cells through a Possible NF-κB-Mediated Mechanism

Ghaffari, Seyed H.,Yousefi, Meysam,Dizaji, Majid Zaki,Momeny, Majid,Bashash, Davood,Zekri, Ali,Alimoghaddam, Kamran,Ghavamzadeh, Ardeshir Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dose-dependent manner and also inhibited classical NF-${\kappa}B$ signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF-${\kappa}B$ and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF-${\kappa}B$ down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-${\kappa}B$-mediated inhibition of survivin and telomerase activity and NF-${\kappa}B$-dependent suppression of cathepsin B, MMP-2 and MMP-9.

Triple Tooth AlGaN/GaN HEMT on SiC Substrate: A Novel Structure for High-Power Applications

Majid Ghaffari,Ali A. Orouji,Mojtaba Valinataj 한국물리학회 2017 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.71 No.12

In this paper, a AlGaN/AlN/GaN/SiC High Electron Mobility Transistor (HEMT) to reduce the electric field is suggested. The main idea of this work is to improve the Direct Current (DC) and Radio Frequency (RF) properties of device by modifying the depletion region in the channel. The proposed structure consists of a floating metal like a comb with triple tooth which is located in the space between the gate and drain and inside the buffer layer. We called the proposed structure as triple tooth HEMT (TT-HEMT). The RF and DC characteristics of the proposed structure are studied using numerical simulations. The breakdown voltage (VBR) increases to 169.5 V for the proposed structure in comparison with 103 V for the conventional HEMT (C-HEMT) due to the modified electric field distribution in the channel of the TT-HEMT structure. The maximum output power density (Pmax) of the TT-HEMT structure is 60.4% greater than that of the C-HEMT. The optimized results show that the maximum oscillation frequency (fmax) and cut-off frequency (fT ) of the proposed structure improve 111% and 26.5%, respectively compared to the C-HEMT structure. In addition, the maximum available gain (MAG) of the TT-HEMT structure is obtained 8.5 dB higher than that of the C-HEMT structure at the frequency of 40 GHz. The optimal results show that whatever the number of teeth on metal increases, the depletion region in the channel is modified more and the breakdown voltage increases, as well. Besides, the output power density (Pmax) is improved with the increasing number of teeth on metal (N). This characteristic is also true, for the cut-off frequency (fT ), the maximum oscillation frequency (fmax) and the maximum available gain (MAG) of the proposed structure. However, the drain current (ID) of the proposed structure is reduced.

Antigenic properties of dense granule antigen 12 protein using bioinformatics tools in order to improve vaccine design against Toxoplasma gondii

Ali Dalir Ghaffari,Abdolhossein Dalimi,Fatemeh Ghaffarifar,Majid Pirestani 대한백신학회 2020 Clinical and Experimental Vaccine Research Vol.9 No.2

Purpose: Toxoplasma gondii is an opportunistic parasite infecting all warm-blooded animals including humans. The dense granule antigens (GRAs) play an important role in parasite survival and virulence and in forming the parasitophorous vacuole. Identification of protein characteristics increases our knowledge about them and leads to develop the vaccine and diagnostic studies. Materials and Methods: This paper gave a comprehensive definition of the important aspects of GRA12 protein, including physico-chemical features, a transmembrane domain, subcellular position, secondary and tertiary structure, potential epitopes of B-cells and T-cells, and other important features of this protein using different and reliable bioinformatics methods to determine potential epitopes for designing of a high-efficient vaccine. Results: The findings showed that GRA12 protein had 53 potential post-translational modification sites. Also, only one transmembrane domain was recognized for this protein. The secondary structure of GRA12 protein comprises 35.55% alpha-helix, 19.50% extended strand, and 44.95% random coil. Moreover, several potential B- and T-cell epitopes were identified for GRA12. Based on the results of the Ramachandran plot, 79.26% of amino acid residues were located in favored, 11.85% in allowed and 8.89% in outlier regions. Furthermore, the results of the antigenicity and allergenicity assessment noted that GRA12 is immunogenic and non-allergenic. Conclusion: This research provided important basic and conceptual data on GRA12 to develop an effective vaccine against acute and chronic toxoplasmosis for further in vivo investigations. More studies are required on vaccine development using the GRA12 alone or combined with other antigens in the future.

Immunoinformatic analysis of immunogenic B- and T-cell epitopes of MIC4 protein to designing a vaccine candidate against Toxoplasma gondii through an in-silico approach

Ali Dalir Ghaffari,Abdolhossein Dalimi,Fatemeh Ghaffarifar,Majid Pirestani,Hamidreza Majidiani 대한백신학회 2021 Clinical and Experimental Vaccine Research Vol.10 No.1

Purpose: Toxoplasmosis, transmitted by Toxoplasma gondii, is a worldwide parasitic disease that affects approximately one-third of the world’s inhabitants. Today, there are no appropriate drugs to deter tissue cysts from developing in infected hosts. So, developing an effective vaccine would be valuable to avoid from toxoplasmosis. Considering the role of microneme antigens such as microneme protein 4 (MIC4) in T. gondii pathogenesis, it can be used as potential candidates for vaccine against T. gondii. Materials and Methods: In this study several bioinformatics methods were used to assess the different aspects of MIC4 protein such as secondary and tertiary structure, physicochemical characteristics, the transmembrane domains, subcellular localization, B-cell, helper-T lymphocyte, cytotoxic-T lymphocyte epitopes, and other notable characteristic of this protein design a suitable vaccine against T. gondii. Results: The studies revealed that MIC4 protein includes 59 potential post-translational modification sites without any transmembrane domains. Moreover, several probable epitopes of B- and T-cells were detected for MIC4. The secondary structure comprised 55.69% random coil, 5.86% beta-turn, 19.31% extended strand, and 19.14% alpha helix. According to the Ramachandran plot results, 87.42% of the amino acid residues were located in the favored, 9.44% in allowed, and 3.14% in outlier regions. The protein allergenicity and antigenicity revealed that it was non-allergenic and antigenic. Conclusion: This study gives vital basic on MIC4 protein for further research and also established an effective vaccine with different techniques against acute and chronic toxoplasmosis.

Relationship between Urbanization and Cancer Incidence in Iran Using Quantile Regression

Momenyan, Somayeh,Sadeghifar, Majid,Sarvi, Fatemeh,Khodadost, Mahmoud,Mosavi-Jarrahi, Alireza,Ghaffari, Mohammad Ebrahim,Sekhavati, Eghbal Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.no.sup3

Quantile regression is an efficient method for predicting and estimating the relationship between explanatory variables and percentile points of the response distribution, particularly for extreme percentiles of the distribution. To study the relationship between urbanization and cancer morbidity, we here applied quantile regression. This cross-sectional study was conducted for 9 cancers in 345 cities in 2007 in Iran. Data were obtained from the Ministry of Health and Medical Education and the relationship between urbanization and cancer morbidity was investigated using quantile regression and least square regression. Fitting models were compared using AIC criteria. R (3.0.1) software and the Quantreg package were used for statistical analysis. With the quantile regression model all percentiles for breast, colorectal, prostate, lung and pancreas cancers demonstrated increasing incidence rate with urbanization. The maximum increase for breast cancer was in the 90th percentile (${\beta}$=0.13, p-value<0.001), for colorectal cancer was in the 75th percentile (${\beta}$=0.048, p-value<0.001), for prostate cancer the 95th percentile (${\beta}$=0.55, p-value<0.001), for lung cancer was in 95th percentile (${\beta}$=0.52, p-value=0.006), for pancreas cancer was in 10th percentile (${\beta}$=0.011, p-value<0.001). For gastric, esophageal and skin cancers, with increasing urbanization, the incidence rate was decreased. The maximum decrease for gastric cancer was in the 90th percentile(${\beta}$=0.003, p-value<0.001), for esophageal cancer the 95th (${\beta}$=0.04, p-value=0.4) and for skin cancer also the 95th (${\beta}$=0.145, p-value=0.071). The AIC showed that for upper percentiles, the fitting of quantile regression was better than least square regression. According to the results of this study, the significant impact of urbanization on cancer morbidity requirs more effort and planning by policymakers and administrators in order to reduce risk factors such as pollution in urban areas and ensure proper nutrition recommendations are made.