Immunoinformatics studies and design of a novel multi-epitope peptide vaccine against Toxoplasma gondiibased on calcium-dependent protein kinases antigens through an in-silico analysis

Ghaffari Ali Dalir,Rahimi Fardin 대한백신학회 2024 Clinical and Experimental Vaccine Research Vol.13 No.2

Purpose: Infection by the intracellular apicomplexan parasite Toxoplasma gondii has serious clinical consequences in humans and veterinarians around the world. Although about a third of the world’s population is infected with T. gondii, there is still no effective vaccine against this disease. The aim of this study was to develop and evaluate a multimeric vaccine against T. gondii using the proteins calcium-dependent protein kinase (CDPK)1, CDPK2, CDPK3, and CDPK5. Materials and Methods: Top-ranked major histocompatibility complex (MHC)-I and MHC-II binding as well as shared, immunodominant linear B-cell epitopes were predicted and linked using appropriate linkers. Moreover, the 50S ribosomal protein L7/L12 (adjuvant) was mixed with the construct’s N-terminal to increase the immunogenicity. Then, the vaccine’s physicochemical characteristics, antigenicity, allergenicity, secondary and tertiary structure were predicted. Results: The finally-engineered chimeric vaccine had a length of 680 amino acids with a molecular weight of 74.66 kDa. Analyses of immunogenicity, allergenicity, and multiple physiochemical parameters indicated that the constructed vaccine candidate was soluble, nonallergenic, and immunogenic, making it compatible with humans and hence, a potentially viable and safe vaccine candidate against T. gondii parasite. Conclusion: In silico, the vaccine construct was able to trigger primary immune responses. However, further laboratory studies are needed to confirm its effectiveness and safety.

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.

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.

Effect of Turmeric Supplementation on Blood Pressure and Serum Levels of Sirtuin 1 and Adiponectin in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind, Randomized, Placebo-Controlled Trial

Ali Kalhori,Maryam Rafraf,Roya Navekar,Aida Ghaffari,Mohammad Asghari Jafarabadi 한국식품영양과학회 2022 Preventive Nutrition and Food Science Vol.27 No.1

Nonalcoholic fatty liver disease (NAFLD) is commonly associated with obesity. This randomized, double-blind, placebo-controlled trial aimed to evaluate the effects of turmeric on serum adiponectin and sirtuin 1 (SIRT1) levels, blood pressure, and body mass index (BMI) in patients with NAFLD. A total of 46 eligible patients with NAFLD (BMI, 25.0∼39.9 kg/m²) were randomly allocated to turmeric and placebo groups using block randomization. The turmeric group (n=23) was administered 3,000 mg/d turmeric powder in six 500-mg capsules for 12 weeks, whereas the placebo group (n=23) was administered six placebo capsules/d for 12 weeks. Body weight, BMI, serum SIRT1 and adiponectin levels, and systolic and diastolic blood pressures were measured at baseline and 12 weeks after intervention. Serum SIRT1 levels increased significantly in the turmeric group compared with the placebo group. Additionally, participants in the turmeric group exhibited lower weight, BMI, and systolic blood pressure after 12 weeks of intervention compared with the baseline. Turmeric effectively improved SIRT1 levels in patients with NAFLD compared with the placebo. The efficacy of turmeric might increase with long-term use at higher doses.

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.

On χ⊗η-Strong Connes Amenability of Certain Dual Banach Algebras

Ebrahim Tamimi,Ali Ghaffari 한국수학교육학회 2024 純粹 및 應用數學 Vol.31 No.1

In this paper, the notions of strong Connes amenability for certain products of Banach algebras and module extension of dual Banach algebras is investigated. We characterize χ ⊗ η-strong Connes amenability of projective tensor product K⨶H via χ ⊗ η-σwc virtual diagonals, where χ ∈ K∗ and η ∈ H∗ are linear functionals on dual Banach algebras K and H, respectively. Also, we present some conditions for the existence of (χ, θ)-σwc virtual diagonals in the θ-Lau product of K ×_θ H. Finally, we characterize the notion of (χ, 0)-strong Connes amenability for module extension of dual Banach algebras K ⊕ X, where X is a normal Banach K-bimodule.

Identifying a simplified model for heavy duty gas turbine

Saeed Bahrami,Ali Ghaffari,S.Hossein Sadati,Marcus Thern 대한기계학회 2014 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.28 No.6

A dynamic model was developed for long-term simulation of a heavy duty gas turbine. The model includes the essential control algorithmof the gas turbine as well as the most common outputs and other important intermediate variables. Control algorithm details, suchas wind up protection and load limiter algorithm which have large effect on gas turbine transient behavior, are included. The model parametersare identified by applying genetic algorithm and least squares algorithm on regular operational data from a real plant to bettermatch the model response to the real plant. The simulation results have been validated with real plant data and shown to have valid accuracyfor many engineering applications.

MODELING OF DOUBLE LANE CHANGE MANEUVER OF VEHICLES

Sadegh Arefnezhad,Ali Ghaffari,Alireza Khodayari,Sina Nosoudi 한국자동차공학회 2018 International journal of automotive technology Vol.19 No.2

Lane change maneuver is one of most riskiest driving tasks. In order to increase the safety level of the vehicles during this maneuver, design of lane change assist systems which are based on dynamics behavior of driver-vehicle unit is necessary. Therefore, modeling of the maneuver is the first step to design the driver assistance system. In this paper, a novel method for modeling of lateral motion of vehicles in the standard double-lane-change (DLC) maneuver is proposed. A neurofuzzy model is suggested consisting of both the vehicle orientation and its lateral position. The inputs of the model are the current orientation, lateral position and steering wheel angle, while the predicted lateral position and orientation of the vehicle are the outputs. The efficiency of the proposed method is verified using both simulation results and experimental tests. The simulation and experimental maneuvers are performed in different velocities. It is shown that the proposed method can effectively reduce the undesirable effects of environmental disturbances and is significantly more accurate in comparisons with the results in the recent available papers. This method can be used to personalize the advanced driver assistance systems.

In-depth computational analysis of calcium-dependent protein kinase 3 of Toxoplasma gondii provides promising targets for vaccination

Hamidreza Majidiani,Shahrzad Soltani,Ali Dalir Ghaffari,Mohamad Sabaghan,Ali Taghipour,Masoud Foroutan 대한백신학회 2020 Clinical and Experimental Vaccine Research Vol.9 No.2

Purpose: The Toxoplasma gondii calcium-dependent protein kinase-3 (CDPK3) is a key enzyme for parasite egress, control of calcium-dependent permeabilization in parasitophorous vacuole membrane and tissue cyst formation. In this study, we comprehensively explored the bioinformatics features of this protein to improve vaccine design against T. gondii. Materials and Methods: Various web servers were employed for the analysis of physico-chemical properties, post-translational modifications, localization in the subcellular milieu, secondary and tertiary structures, as well as B-cell, major histocompatibility complex (MHC)-binding and cytotoxic T-lymphocyte (CTL) epitopes. Results: This protein was a 537 amino acid antigenic and non-allergenic molecule with a molecular weight of 60.42 kDa, a grand average of hydropathicity score of -0.508, and aliphatic index of 79.50. There exists 46.74% alpha helix, 12.48% extended strand, and 40.78% random coil in the secondary structure. Ramachandran plot of the refined model demonstrated 99.3%, 0.7%, and 0.0% of residues in the favored, allowed and outlier areas, respectively. Besides, various potential B-cell (continuous and conformational), MHC-binding and CTL epitopes were predicted for Toxoplasma CDPK3 protein. Conclusion: This article provides a foundation for further investigations, and laid a theoretical basis for the development of an appropriate vaccine against T. gondii infection.