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This paper investigates resource management in device-to-device (D2D) networks coexisting with cellular user equipment (CUEs). We introduce a novel model for joint scheduling and resource management in D2D networks, taking into account environmental constraints. To preserve information freshness, measured by minimizing the average age of information (AoI), and to effectively utilize energy harvesting (EH) technology to satisfy the network's energy needs, we formulate an online optimization problem. This formulation considers factors such as the quality of service (QoS) for both CUEs and D2Ds, available power, information freshness, and environmental sensing requirements. Due to the mixed-integer nonlinear nature and online characteristics of the problem, we propose a deep reinforcement learning (DRL) approach to solve it effectively. Numerical results show that the proposed joint scheduling and resource management strategy, utilizing the soft actor-critic (SAC) algorithm, reduces the average AoI by 20% compared to other baseline methods.

Objective(s): In this study, the adjuvant activity of aqueous and alcoholic extracts of propolis was examined on the inactivated herpes simplex virus-1 (HSV-1).Materials and Methods: BALB/C mice were administered with inactivated (HSV-1; the KOS strain) plus alcoholic and aqueous extracts, followed by assessment of the cellular and humoral immune responses. Results: Alcoholic and aqueous extracts, as an adjuvant, revealed a significant increase in lymphocyte proliferation and cytotoxic T lymphocyte (CTL) responses versus the HSV-1 group. In addition, HSV-1 plus alcoholic extract showed a remarkable increase in IFN-γ cytokine and IFN-γ/IL-4 ratio. On the other hand, both alcoholic and aqueous extracts in the HSV-1 vaccine suppressed the IL-4 cytokine response as compared with the HSV-1 vaccine. In addition, HSV-1 plus alcoholic extract showed a significant increment in IgG1, IgG2a, and IgG2b isotypes as compared with the HSV-1 vaccine.Conclusion: Propolis extracts seem to modulate the immune response against inactivated HSV-1 model and can be used as a suitable vaccine adjuvant or a component of a complex adjuvant against infectious diseases.

Considering the uncertainties associated with earthquake, seismic response of structures, damage caused by the response and the repair costs, determining Earthquake Insurance Premium (EIP) is a challenging task that requires a framework for modeling all inherent risks. Most of the models proposed for EIP determination have two basic components. The first component indicates the probability of seismic hazard (generally obtained from the probabilistic seismic hazard analysis), and the second component indicates the probability of occurrence of a given damage to the structure with respect to different seismic hazard levels (generally obtained from the fragility curves). These two components are interconnected through an intermediate parameter, known as the Intensity Measure (IM), which is of great importance in calculations and has hardly been considered so far. In this study, the dependency of EIP on the IM used in the probabilistic seismic hazard analysis and the fragility curves is analyzed. To this end, the EIP was determined for five types of buildings at low, medium and high seismic hazard levels using two IMs (peak ground acceleration and first mode spectral acceleration). The results of this study warn that the EIP can be highly dependent on the IM, so that for all studied structures, the EIP determined based on peak ground acceleration at a high seismic hazard level is nearly three times as many as the one determined by the first mode spectral acceleration. A significant finding is that when the first mode spectral acceleration is used as the IM, the ratio of EIP at different seismic hazard levels closely matches the ratio of IM at the same levels. This result can be valuable in developing insurance codes and regulations. However, this is not the case for the currently used IM, i.e., peak ground acceleration.

Mycobacterium bovis (M. bovis) is a slow-growing bacteria that can intracellularly reduce selenium ions to elemental selenium nanoparticles (SeNPs). We used bacterial lysates along with vitamin C to help the synthesis of SeNPs coated with M. bovis Bacille Calmette-Guérin (BCG) crude hydrophobic materials. However, the large-scale fabrication, separation, extraction, and purification of intercellular SeNPs which are prepared by using M. bovis, have many complexities. So, we developed a simple method for preparation of above BCG-coated nanoparticles and tested its potential immune-modulatory effects. In the current investigation, we cultivated the M. bovis in conventional media and prepared total cell lysates from this bacterium by just applying freeze and thaw and ultra-sonication. The resulting cell lysates were added to the solution containing selenium ions before adding the ascorbic acid as a reducing agent. At the end of the process, the fabricated selenium nanoparticles were separated by centrifugation and characterized by different instrumentation methods. In the next step, to evaluate the immune-modulatory effects of the hepatitis B surface antigen (HBsAg) vaccine alone, and in combination with plain SeNPs or SeNPs-BCG lysate, the serum level of interferon-gamma (IFN-γ) was determined in different groups by enzyme-linked immunosorbent assay (ELISA). This study showed adjuvant effects of prepared nanoparticles (in both 10 μg/300 μL and 100 μg/300 μL doses) in increasing the level of interferon-gamma (IFN-γ) in comparison with vaccine alone. Moreover, in both doses of SeNPs-BCG lysate, the level of interferon-gamma (IFN-γ) was remarkably higher than the same doses of plain SeNPs. As a result, synthesized SeNPs in the presence of whole-cell lysates of M. bovis indicated a greater ability to induce the interferon-gamma (IFN-γ) compared with other groups. Additionally, its easy fabrication procedure can be considered its superiority.

Objective(s): HBsAg vaccine is unable to induce Th1 immune responses. Here, immune responses and long-lived IgG responses of HBsAg-Alum, HBsAg-MF59, as well as HBsAg-MF59 were compared when formulated with PPD. Materials and Methods: BALB/c mice were injected with the vaccines subcutaneously three times with a two-week interval. Then, specific IgG, long-lived IgG responses up to 220 days, and also IgG1 and IgG2a isotypes were assessed using ELISA. Furthermore, IFN-γ and IL-4 were assessed on spleen cell culture supernatant by ELISA. Results: IFN-γ cytokine response between MF59- and Alum-adjuvanted vaccines did not show a significant difference. HBsAg-Alum vaccine revealed an increase in IL-4 cytokine, as compared with those immunized with HBsAg-MF59 at borderline (P=0.0553). In addition, HBsAg-MF59+PPD 10 µg showed a significant decrease in IL-4 and IFN-γ cytokines, as compared with HBsAg-MF59. Furthermore, the HBsAg-MF59+PPD10 µg group showed a significant increase in the IL-2/IL-4 ratio, as compared with HBsAg-MF59 (P=0.0339). Specific IgG antibody showed a significant increase in HBsAg-MF59, as compared with HBsAg-Alum. Furthermore, HBsAg-MF59 plus PPD showed a significant increase in IgG responses, as compared with HBsAg-MF59 and HBsAg-Alum groups. Long-lived IgG responses up to 220 days after the final shot showed a significant increase in HBsAgMF59 versus HBsAg-Alum group and PPD in the HBsAg-MF59 vaccine formulation, resulting in a significant increase in IgG responses versus HBsAg-MF59 group. In addition, PPD in the HBsAg-MF59 vaccine formulation suppressed IgG1 response versus HBsAg-Alum. However, HBsAg-MF59 showed a significant increase in IgG2α versus the HBsAg-Alum group (P=0.0190). Immunization with HBsAg-MF59+PPD (10 µg) showed a significant increase versus the HBsAg-MF59 group (P=0.0040). Results from the IgG2a/IgG1 ratio in HBsAg-MF59+PPD1µg and HBsAg-MF59+PPD10 µg groups showed a significant increase as compared with HBsAg-MF59 groups (P

Objective(s): SARS-CoV-2, emerging as a major threat to public health, has to be controlled through vaccination. Naloxone (NLX), an opioid receptor antagonist, demonstrated its adjuvant activity for microbial vaccines. In this study, inactivated SARS-CoV-2 was developed in the Alum/NLX adjuvant to increase the potency of the inactivated SARS-CoV-2 vaccine. Materials and Methods: BALB/c mice were immunized on days 0 and 14 with inactivated SARS-CoV-2-Alum, -Alum + NLX 3 mg/kg, -Alum + NLX 10 mg/kg, and -Freund adjuvant, as well as PBS. IFN-γ and IL-4 cytokines and Granzyme-B release were assessed with ELISA. In addition, specific total IgG, IgG1/IgG2a isotypes, and ratio as well as anti-RBD IgG responses were assessed with an optimized ELISA. Results: SARS-CoV-2-Alum-NLX10 group showed a significant increase in the IFN-γ cytokine response versus SARS-CoV-2-Alum, SARS-CoV-2-Alum-NLX3, and PBS groups. The SARS-CoV-2-Alum-NLX3 group exhibited a significant decrease in IL-4 cytokine versus SARS-CoV-2-Alum. The mice immunized with SARS-CoV-2-Alum-NLX10 showed a significant increase in CTL activity versus SARS-CoV-2-Alum and PBS. In addition, mice immunized with SARS-CoV-2-Alum-NLX3, SARS-CoV-2-Alum-NLX10 and SARS-CoV-2-Freund demonstrated an increase in IgG response, as compared with SARS-CoV-2-Alum and PBS group. Furthermore, all formulations of SARS-CoV-2 vaccines could induce both IgG1 and IgG2a isotypes. But, the IgG2a/IgG1 ratio in SARS-CoV-2-Freund and SARS-CoV-2-Alum-NLX10 revealed an increase as compared with that of the SARS-CoV-2-Alum group. Anti-RBD IgG response in the SARS-CoV-2-Alum-NLX10 group showed a significant increase as compared with the Alum-based vaccine. Conclusion: Formulation of inactivated SARS-CoV-2 virus in NLX/alum adjuvant improved the potency of humoral and, especially, cellular responses.

Objective(s): Methicillin-resistant Staphylococcus aureus (MRSA) reasons extreme infections, can resist various conventional antimicrobial agents, and cause morbidity and mortality worldwide. Vaccination seems to help modulate MRSA infections. Nanovaccine is considered a novel strategy in vaccine technology. The primary purpose of the present study was to develop a conjugate vaccine based on recombinant PBP2a and MRSA autolysin formulated in PLGA as a nanoparticle capable of enhancing protective responses against MRSA in the murine model.Materials and Methods: Recombinant PBP2a and autolysin have been expressed and purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity column and characterized by SDS-PAGE and western blot. PLGA was bound to recombinant proteins by using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) and adipic acid dihydrazide (ADH) as a linker and spacer, respectively. Conjugation of recombinant proteins to PLGA was confirmed by the AFM assay, zeta potential, and size distribution, and its efficacy was evaluated in mice. Total IgG, IgG1, IgG2a, IgG2b, and IgM titers were analyzed to assess immune responses. Lastly, the bioactivity of antibodies was tested by using the opsonophagocytosis assay. Results: Mice immunized with the r-PBP2a-r-autolysin–PLGA nanovaccine led to increased levels of opsonic antibodies and IgG1, IgG2a, IgG2b, and IgM when compared with other experimental groups. Our results confirmed that vaccination with nanovaccine could reduce the mortality rate against the sub-lethal dose of MRSA challenge. Furthermore, the nanovaccine could eliminate MRSA from the kidney of infected mice. Conclusion: This study may provide valuable insights into the protective power of the r-PBP2a-r-autolysin–PLGA conjugate vaccine against MRSA infection.

Background and purpose: Acinetobacter baumannii (A. baumannii) is known as a pathogen with antibiotic resistance, causing respiratory infections. PLGA has been approved for use in vaccines as well as drug delivery. This study was performed to evaluate PLGA nanoparticles containing the outer membrane proteins (OMPs) of A. baumannii in stimulating the mice’s immune system and improving pneumonia. Experimental approach: Double emulsion solvent evaporation technique was used. The properties of the obtained nanospheres were determined using a zetasizer, FTIR, and AFM devices. Nanoparticles were administered to mice BALB/c by applying the intramuscular route. ELISA was used to measure the amounts of immunoglobulins produced; also, an opsonophagocytic killing assay was used to measure the effectiveness of immunoglobulins. Immunized mice were then challenged with live A. baumannii through the lungs; their internal organs were also removed for bacteriological studies. Findings/Results: The prepared particles were 550 nm in diameter with a negative surface charge. The production of the OMPs specific IgG was much higher in the group receiving nanoparticles containing antigen as compared to those getting pure antigen. The immunoglobulins produced against nanoparticles were superior to those developed against pure antigens. Mice that received the new nanovaccine were more resistant to pneumonia caused by this bacterium than those that received pure antigen. Conclusion and implication: Overall, it can be said that PLGA nanoparticles could deliver their internal antigens (OMPs) well to the immune system of mice and stimulate humoral immunity in these animals, thus protecting them against pneumonia caused by A. baumannii.

Objective(s): Influenza is a highly contagious disease, which affects the respiratory system and seasonal influenza is common throughout the world. Influenza vaccination is an effective way to reduce the risk of death and hospitalization. This study aims at the expression of swine recombinant hemagglutinin protein in the baculovirus expression system and it offers a comparison of the immunologic parameters with the commercial vaccine. Materials and Methods: The HA gene from the swine H1N1 strain of the Influenza virus was cloned into the Bac-To-Bac expression system in pFastBAC HTA vector and was transformed into Escherichia coli TOP10 strain. After the confirmation, the vector was transfected into the SF9 insect cell line. The recombinant HA was evaluated by SDS-PAGE and western blot. After formulation in Montanide ISA71 adjuvant, the immunization test was performed comparatively with Alum adjuvant, commercial vaccine in four groups of BALB/c mice, of which one group was control without any vaccination. Two weeks after the last immunization, the antibody response was assessed with HI assay, and experimental mice were challenged with mouse-adapted Influenza A/PR8/34 (H1N1) virus through nasal inhalation. Results: The immunoassay results revealed that the candidate vaccine induced the antibody response as the commercial one did but it did not significantly reduce the mortality rate, body loss, and severe fever. Conclusion: To summarize, the results showed that the recombinant protein with the MontanideTM ISA- 71 adjuvant developed a more appropriate level of immunity than Alum adjuvant, so it might be used as a safe and reliable vaccine against H1N1 virus for further research.

Introduction: Intravesical Mycobacterium Bovis bacillus Calmette-Guérin (BCG) therapy for non-muscle invasive bladder cancer has been successfully applied to prevent metastasis and disease progression. However, some studies have reported a percentage of treatment failure and recurrence along with possible side effects. Therefore, this study has evaluated the effect of administration of synthetic (SSeNPs) and biogenic selenium nanoparticles (BSeNPs) as an adjuvant drug in combination with intravesical BCG for the treatment of mice-bearing bladder tumors. Methods: Orthotopic bladder cancer model mice were established by 12 weeks of N-butyl-N-(4-hydroxybutyl) nitrosamine oral gavage. Mice-bearing bladder cancer was treated by sequential intravesical treatments with SSeNPs, BCG, BCG/SSeNPs, and BCG/SSeNPs. After immunotherapy, the status of the immune system was evaluated by quantitatively measuring mRNA expression of cytokines by Real-time qRT-PCR in the spleen samples and measuring cytokines protein level by enzyme-linked immunosorbent assay in the serum samples. As well, in the tumor microenvironment, the mRNA expression level of autophagic molecules (Beclin-1, ATG2B, and ATG5), apoptotic molecule (Caspase-3), iNOS, HMGB1, and PD-L1 were evaluated in all groups. Results: Immunotherapy with BCG/SSeNPs and BCG/BSeNPs elicited a considerable immune response by increasing the expression of IFN-γ, IL-12, and IL-6 and inhibiting the expression of IL-10 and TGF-β cytokines. As well, BCG/SSeNPs and BCG/BSeNPs could increase Caspase-3 expression and decrease autophagic genes as well as PD-L1. Conclusion: Our results showed that synthetic and biogenic SeNPs as an effective adjuvant could enhance intravesical BCG's efficacy and therapeutic effect for bladder cancer treatment with almost the same function.

Objective(s): Though immunization with HBsAg has been routine since the 1980s, it has numerous limitations such as low or none humoral immune responses. Today, nanotechnology is used in vaccinology to achieve higher potency. The present study deals with the achievement of fast antibody response of humoral immune responses using immune-targeting through mannosylated nanocarriers of the vaccine.Materials and Methods: Mannose sugar and HBsAg were attached to the surface of iron oxide nanoparticles. Mannosylated iron oxide nanoparticles conjugated HBsAg (HBsAg +MLCMNP), iron oxide nanoparticles conjugated HBsAg (HBsAg +LCMNP), hepatitis B vaccine, and mere HBsAg were injected twice to BALB/c mice subcutaneously, while suitable control groups were considered. Specific total IgG antibodies were evaluated on the 7th and 14th days after the final immunization. The avidity maturation of the humoral immune response was assessed with an optimized ELISA. Graph pad prism software was used to analyze statistical data. Results: Results showed that on the seventh day of the final shooting, the mannosylated nano-vaccine caused higher antibody response induction than nano-vaccine without mannose and commercial vaccine groups. After 14 days of the second injection, a significant difference was seen versus the nano-vaccine without mannose but not the commercial vaccine group. In addition, the avidity index in mannosylated nano-vaccine showed a significant increase compared with the nano-vaccine without mannose and mere HBsAg group but not compared with the commercial vaccine.Conclusion: It seems that mannosylated nano-vaccine has more potency to achieve fast antibody responses and also higher quality of humoral immune response.

Every year, the phenomenon of earthquake causes a lot of human, financial and environmental losses. Transmission pipelines are one of the vital arteries that are very important, however, in the event of an earthquake can cause devastating damages. Safeguarding urban and interurban facilities, including electricity, water supply, oil and gas transmission lines, against these loads requires careful studies and engineering designs. Given that traditional methods for seismic design of pipelines such as FEM modeling and experimental methods are so expensive, a new combined method for predicting the strain of pipes based on the Artificial Neural Network (ANN) is proposed. For this purpose, the parameters of the pipeline including pipe and soil type, length, discharge, path slope, depth, etc. and earthquake-induced characteristics including earthquake acceleration, earthquake occurrence time, Peak ground acceleration (PGA), etc. were included in the model. Earthquake input parameters were considered as input parameters and pipe strains and stresses were considered as output parameter. ANSYS finite element software has also been used to simulate the pipeline and produce training data. The results of finite element software were used as input and output parameters for training and validating artificial neural network. 753 models created using ANSYS and its input/output data divided into three parts to creat ANN model. 70% of the total data were used for training, 15% for validating and 15% for testing the ANN model. Results show that the proposed Method provides a very good agreement with the computational results of the ANSYS with accuracy of 96 percent.

Careful estimation of global ductility will certainly lead to greater accuracy in the design of structural members. In this paper, a new and optimal intelligent model is proposed to predict the roof ductility (μR) of EBF steel frames exposed to the near-fault pulse-like earthquakes, using the Adaptive Neuro-Fuzzy Inference System (ANFIS). To achieve this goal, a databank consisting of 12960 data is created. To establish different geometrical properties of models, 3-,6-, 9-, 12-, 15, 20-stories, steel EBF frames are considered with 3 different types of link beam, column stiffness, and brace slenderness. All models are analysed to reach 4 different performance levels using nonlinear time history under 20 near-fault earthquakes. About 6769 data are applied as ANFIS training data. Subtractive clustering and Fuzzy C-Mean clustering (FCM) methods are applied to generate the purposed model. The results show that FCM provides more accurate outcomes. Moreover, to validate the model, 2257 data are applied (as test data) in order to calculate the correlation coefficient (R) and mean squared error (MSE) between the predicted values of (μR) and the real values. The results of correlation analysis show the high accuracy of the proposed intelligent model.

Introduction The Robaie copper area is located 95 kilometers South of Damghan in the Semnan province. The study area has coordinates between 54˚30΄37˝to 54˚30΄42.71˝ latitude and 35˚22΄29.41˝ to 35˚23΄47.54˝ longitude. Geotectonically, the study area is located in the central Iran and in the northern part of the Torud-Chahshirin volcanic-plutonic belt (Houshmandzadeh et al., 1978). The Torud-Chahshirin volcanic-plutonic belt is a Tertiary magmatism in central Iran which is composed of volcanic rocks with dominant andesite composition and granodiorite intrusive with dominant diorite composition (Fard et al., 2001). Torud-Chahshirin volcanic-plutonic belt has created a favorable geological situation for base metals such as copper, lead, zinc, gold, silver and other precious and base metals, such as the Robaie copper area, Chah Messi (Cu±Pb-Zn; Imamjome et al., 2009), Kuh-Zar (Cu-Au; Rohbakhsh et al., 2018) and other instances. The main objective of this study is geology, petrography, U-Pb zircon dating and Sr-Nd isotope and also alteration, mineralization, geochemistry and fluid inclusion in the study area. Materials and methods 60 samples were collected from the study area. Petrographic studies were done on 40 thin sections. Mineralization and paragnesis of the system were studied based on 10 polished-thin sections and 6 polished sections. The measurements were conducted on a Linkam THMSG 600 at the Ferdowsi University of Mashhad. REE (ICP-MS method-ACME Laboratory in Vancouver, Canada) elements were analyzed for 3 samples of diorite dykes. Eight sampels for geochemistry and four samples for fire assay were analyzed at the Zar Azma Company. U-Pb dating in zircon of diorite dyke was conducted by the ICP-MS method in the Arizona LaserChron Center. Sr and Nd isotopic compositions were determined at the Laboratório de Geologia Isotópica da Universidade de Aveiro, Portugal. Results The geology of the area is dominated by volcanic rocks (andesite and trachyandesite), which were intruded by diorite dykes. Alteration zones are propylitic, argillic, sericitic and carbonate. The Copper deposit in the study area occurs as ore veins situated along fault zone with NS-SW trending. Vein thickness varies from 1-5m. Vein thickness varies from 1-5m. The primary minerals are chalcopyrite, pyrite and chalcocite, covellite, bornite, malachite, azurite, hematite, goethite and limonite are secondary minerals. The amount of Cu is between 0.01 to 5.6 % and amount of Ag, Sb, Pb, Zn, As elements is low. The homogenization temperature (Th) values ranged from 165 to 300 oC. Salinities of ore-forming fluids ranged from 7 to 16 wt. % NaCl equivalents. Diorite dykes in the Robaie area have characteristics of enrichment in LREE versus HREE, enrichment of LILE and depletion in HFSE. The initial 87Sr/86Sr and 143Nd/144Nd ratios of biotite-hornblende diorite are 0.705664 and 0.512486, respectively. The εNdI value is -1.7. In the εNdI versus initial 87Sr/86Sr diagram diorite dykes of the Robaie area plot to the right part of the mantle array. The mean age of diorite dyke is 50.49±0.49 Ma. Therefore, the U-Th-Pb zircon dating indicates that diorite dyke formed in the early Eocene (Ypresian) era. Discussion Diorite dykes originated from mantle-derived magmas. The parental melt would have originated in a non-depleted mantle source. Isotopic data from diorite dykes show that subduction source with contamination to continental crust. In tectonic setting diagrams (Pearce et al., 1984) diorite dykes plot on the fields of the volcanic arc granites (VAG). In the Dy/Yb vs. Dy system (Shaw, 1970) diorite dykes of Robaie area were formed by 15-20% partial melting of spinel-phlogopite lherzolite. According to Yh/Yb vs. Ta/Yb (Pearce et al., 1984) and Ba/La vs. Th/Nd diagrams (Shaw, 1970) diorite dykes were formed from slab-drive fluid in the active continental margins. Fluid inclusions data of the Robaie area manifest that the ore-forming fluids were medium to low temperature and medium to low salinity. The pressure determined for the Robaie area was approximately < 10 MPa, which is equivalent to a depth of approximately < 1 km assuming lithostatic pressure. Fluid inclusion studies indicate that there is a positive correlation between homogenization temperature and fluid salinity, similar to the process of fluid mixing. The decrease in salinity has been the most important factor in the precipitation of copper in the area. All of evidence shows that mineralization in the Robaie area is of epithermal type deposit. Acknowledgment The financial support provided by grant no. 42842.3, date: 3 Jan 2017 is greatly appreciated. We would like to thank Mr. Ehsan Azizian of the Zamin Pouyan Fraz Assia Company for the generous support and the access to mine data.

Purpose – Perfume is arguably one of the most challenging experience products offered online. This article explores how the associations between the human senses of olfaction and audition can help consumers recognize the characteristics of the scent in the absence of the real scent. Method – Given the scarcity of contributions regarding online shopping behavior for perfume, an exploratory qualitative approach was implemented. Twenty-seven in-depth interviews were conducted among individuals from three countries with prior experience of purchasing perfume online. Results –The study highlights the associations made by the interviewees between the types of sounds/voice and types of scents and the complementary role of these cues in online shopping for perfume. Practical implications – Both e-sellers and e-buyers can benefit from the findings of this research. In fact, it is likely that e-shoppers decide to either consider or ignore an unknown perfume for purchase based on the scent signals perceived from sounds, which can provide guidance for e-sellers as well.

Background: The H1N1 influenza virus is a highly pathogenic virus that threatens human life. Vaccination is an effective way of preventing and controlling influenza. Production of recombinant hemagglutinin in the baculovirus expression system, in the insect eukaryotic cell substrate (Sf9), has been suggested as an effective strategy. Methods: The H1N1 influenza virus hemagglutinin gene sequence was prepared from National Center for Biotechnology Information (NCBI). After designing a specific primer, the sequence was provided using restriction digestion, cloned into pFastBacHTA plasmid, and transferred to the DH10Bac cell to produce a recombinant bacmid. After extracting the relevant plasmid, it was transfused into the insect cell; and after the expression of the protein by Sf9 cell, the presence of recombinant protein was confirmed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot methods. Findings: The hemagglutinin gene (654 bp) was cloned in pFastBacHTA plasmid using the two enzymes of BamHI and Xhol. Sf9 cell expressed a protein weighing approximately 60 kDa after receiving the recombinant bacmid protein. The extracted protein was identified and confirmed using SDS-PAGE and Western blot methods; and protein concentration was measured by Lowry method. Conclusion: The baculovirus system is useful for the production of proteins with complex structures. Generally, it can be concluded that this protein is highly expressed in insect cells. Due to the similarity of this system with the human system, it can be a suitable alternative for embryonic eggs in the future, and can be used in vaccination.

Background: Pseudomonas aeruginosa has an important role in nosocomial infections. Objective: To evaluate biological activity of the detoxified LPS (D-LPS) entrapped into Poly lactic-co-glycolic acid (PLGA) nanoparticles. Materials: LPS was extracted and detoxified from the P. aeruginosa strain PAO1. The D-LPS, conjugated to the PLGA nanoparticles with 1-ethyl-3-dimethyl aminopropyl carbodiimide (EDAC) and N-hydroxy-succinimide (NHS). The connection was evaluated by FTIR (Fourier transform infrared), Zetasizer, and Atomic Force Microscope (AFM). The BALB/c mice injected intramuscularly with the D-LPS-PLGA with two-week intervals and then challenged two weeks after the last immunization. The bioactivity of the induced specific antisera and cytokines responses against D-LPS-PLGA antigen was assessed by ELISA. Results: D-LPS-PLGA conjugation was confirmed by FTIR, Zetasizer, and AFM. The ELISA results showed that D-LPS was successful in the stimulation of the humoral immune response. The immune responses raised against the D-LPS-PLGA, significantly decreased bacterial titer in the spleen of the immunized mice after challenge with PAO1 strain in comparison with the control groups. Conclusion: The conjugation of the bacterial LPS to the PLGA nanoparticle increased their functional activity by decrease in bacterial dissemination and increase the killing of opsonized bacteria.

Konjac glucomannan (KGM) is a water-soluble polysaccharide derived from the Amorphophallus’s tuber and, as herbal medicine has shown, can suppress tumor growth or improve health. However, there has been no investigation into the effects of KGM on breast tumor-bearing mice. Therefore, in two cohort experiments, we assessed the effect of glucomannan at daily doses of 2 and 4 mg for 28 days as a dietary supplement and also glucomannan in combination with tumor lysate vaccine as an adjuvant. Tumor volume was monitored twice weekly. In addition, TNF-α cytokines and granzyme B (Gr–B) release were measured with ELISA kits, and IL-2, IL-4, IL-17, and IFN-γ were used as an index for cytotoxic T lymphocyte activity. Moreover, TGF-β and Foxp3 gene expression were assessed in a real-time PCR test. The results show that glucomannan as a dietary supplement increased the IFN-γ cytokine and Th1 responses to suppress tumor growth. Glucomannan as a dietary supplement at the 4 mg dose increased the IL-4 cytokine response compared to control groups. In addition, cell lysate immunization with 2 or 4 mg of glucomannan suppressed tumor growth. As an adjuvant, glucomannan at both doses showed 41.53% and 52.10% tumor suppression compared with the PBS group. Furthermore, the administration of glucomannan as a dietary supplement or adjuvant reduced regulatory T cell response through decreasing TGF-β and Foxp3 gene expression in the tumor microenvironment. In conclusion, glucomannan as a dietary supplement or adjuvant enhanced the immune responses of tumor-bearing mice and decreased immune response suppression in the tumor milieu, making it a potentially excellent therapeutic agent for lowering breast tumor growth.

The rocks of the Robaie area located in the Torud-Chahshirin belt and south of Damghan, includes the Eocene andesite and trachyandesite rocks in which subvolcanic igneous rocks as stoke and dyke with diorite, monzonite and monzodiorite porphyry composition are intruded. The main textures of volcanic rocks are porphyritic characterized by plagioclase, hornblende and biotite phenocrysts as well as apatite and zircon as minor minerals. The rocks studied are mainly of shoshonitic nature and only one sample is considered as high-K calc-alkaline. Several line of evidence including LILE and LREE enrichment, HREE and HFSE depletion, high Th/Yb with negative anomalies of Ti, Nb and the position of the samples on the tectonic discrimination diagrams indicate that the volcanic rocks in discussion were emplaced into the subduction zone related to an active continental margin setting. The initial 87Sr/86Sr, 143Nd/144Nd ratios and (εNd)i value of andesite are 0.704445, 0.512691 and 2.29, respectively. All of these evidences confirm that the studied volcanic rocks were generated from partial melting of the mantle wedge above the subduction zone. Petrographic observations along with geochemistry of rare earth and trace elements suggest that the calc-alkaline affinity of the rocks studied and their parent magma from a subducted-related environment as well as crustal assimilation and fractional crystallization

Mannosylation of nanovaccine is an appropriate strategy for targeting the mannose receptors on DCs. Here, HBsAg and mannose loaded on the surface of iron oxide nanoparticles to increases HBsAg vaccine potency. Nanoparticles are made by co-precipitation method and bonded to the HBsAg and mannose by chemical bonding. The physicochemical properties of nano-vaccines, their toxicity and antigenicity were determined. The synthesized nano-vaccine showed spherical shape with a mean particle size of 60 nm, a zeta potential of −44 mV, an antigen-binding efficiency of around 100% and for mannose 78%. In vitro release of nanoparticles exhibited about 30% at the first day and about 60% until the third day. SDSPAGE analysis confirmed structural integrity of HBsAg loaded on nanoparticles. The HBsAg-loaded LCMNP and MLCMNP nanoparticles had no toxic effects on HEK293 cell line. The quantification of the intracellular Fe by ICP-OES as a criterion of nano-vaccine uptake revealed mannose intensify uptake of MLCMNP. In addition, mannose in the structure of MLCMNP improved IL-6, TNF-α and IFN-γ (>16 fold) cytokines genes expression by macrophage/dendritic cells after exposure in 12 h. Immunization of experimental mice (subcutaneously, two times with 2-week intervals) with 5 µg of HBsAg loaded on MLCMNP nanoparticles increased specific total IgG and IgG2a/IgG1 ratio. In addition, TNF-α, IL-12, IL-2 and IL-4 cytokines in mannosylated nano-vaccine increased versus nano-vaccine group while lymphocyte proliferation and IFN-γ responses in the targeted nano-vaccine group show a tiny increase versus the nano-vaccine group. The results show that mannosylated nano-vaccine promotes higher level of cellular and humoural immune responses against HBsAg nano-vaccine.

The H1N1 influenza virus is known as a serious pandemic threat across the globe. Vaccination is one of the most effective methods of protection against this virus and the way to reduce the seasonal pandemic risk. The commercial vaccine does not adequately respond to pandemic strains. This study examines the potential function of formulated H1N1 hemagglutinin with MF59 adjuvant against A/PR/8/34 (H1N1). To this end, a recombinant hemagglutinin (rHA) gene of influenza A virus was designed and expressed in SF9 cell by the Baculovirus expression system. Four groups of mice were immunized by rHA in combination with MF59, Alum adjuvant, and virus split only. The immunized mice subsequently used for the humoral immune assay and the results compared with untreated mice (negative group). Besides, both treated and control mice groups were challenged with mouse-adapted influenza virus A/PR/8/34(H1N1) through the intranasal drop. Bodyweight, survival, temperature variation, and the medical conditions of the samples were assessed. Mice immunized with the recombinant protein demonstrated a humoral response to the influenza A virus. Upon virus challenging, co-administration of rHA with MF59 adjuvant could lead to 92% survival of the vaccinated mice within 10 days. The MF59-treated group showed slight weight loss and high-temperature body two weeks after infection. This group also displayed a higher hemagglutination inhibition (HI) antibody titer as compared to the group vaccinated with virus split, and Alum adjuvant. Altogether, the results showed that the recombinant protein with the MF59 adjuvant created better safety than the Alum adjuvant, thereby can be considered as a safe and reliable vaccine against the H1N1 virus for further investigations.

Background: Leukemia is a kind of blood cancer diseases which are generally known as neoplasm. There are two types of blood cancer called acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). This type of leukemia targets plasma cells and prevents the production of antibodies in the body and makes the immune system vulnerable to infections. Methods: Blood samples from 10 people with AML and 10 normal individuals were collected who were defined as the case and control groups, respectively. PBMCs were isolated by Ficoll hypaque and cultured in order to the MTT assay. Then, the cell wall of Bifidobacterium bifidum bacterium was treated in five concentrations on these cells and the MTT test was performed at 24, 48 and 72hrs. Also, K562 leukemia cell was cultured then after; the MTT test was performed in the same protocol. The expression of BAX, Bcl2, β-actin genes were assessed by real-time PCR after 48 and 72hrs of treatment. Results: The results of MTT test could not show any significant differences in extracted PBMCs from individuals as compared to control group. But, K562 cell line in treatment with the cell wall of Bifidobacterium bifidum showed a significant cell toxicity effect at 48 and 72hrs versus non-treated K562 cells. BAX gene expression was significantly increased versus β-actin gene control only on K562 cell line, but not on AML derived leukemic cells. Conclusion: According to the obtained results, Bifidobacterium bifidum, as a probiotic bacterial species, can impact the growth and/or proliferation of cancer cells; however, it could depend on the type of cancer cells.

The most important feature of the behavior factor is that it allows the structural designer to be able to evaluate the structural seismic demand, using an elastic analysis, based on force-based principles quickly. In most seismic codes, this coefficient is merely dependent on the type of lateral resistance system and is introduced with a fixed number. However, there is a relationship between the behavior factor, ductility (performance level), structural geometric properties, and type of earthquake (near and far). In this paper, a new and accurate correlation is attempted to predict the behavior factor (q) of EBF steel frames, under near-fault earthquakes, using the genetic algorithm (GA). For this purpose, a databank consisting of 12960 data is created. To establish different geometrical properties of models, 3−, 6−, 9−, 12−, 15, and 20− story steel EBF frames were considered with 3 different types of link beam, 3 different types of column stiffness, and 3 different types of brace slenderness. Using nonlinear time history under 20 near-fault earthquake, all models were analyzed to reach 4 different performance levels. 6769 data were used as GA training data. Moreover, to validate the correlation, 2257 data were used as test data for calculating mean squared error (MSE) and correlation coefficient (R) between the predicted values of (q) and the real values. In addition, the MSE and R were calculated for correlation in the train and test data. Also, the comparison of the response of maximum inelastic displacement of 5 stories EBF from the proposed correlation and the mean inelastic time-history analysis confirms the accuracy of the estimate relationship.

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that causes various inflammatory local infections, from those of the skin to postinfectious glomerulonephritis. These infections could result in serious threats, putting the life of the patient in danger. Antibiotic-resistant S. aureus could lead to dramatic increases in human mortality. Antibiotic resistance would explicate the failure of current antibiotic therapies. So, it is obvious that an effective vaccine against S. aureus infections would significantly reduce costs related to care in hospitals. Bacterial vaccines have important impacts on morbidity and mortality caused by several common pathogens, however, a prophylactic vaccine against staphylococci has not yet been produced. During the last decades, the efforts to develop an S. aureus vaccine have faced two major failures in clinical trials. New strategies for vaccine development against S. aureus has supported the use of multiple antigens, the inclusion of adjuvants, and the focus on various virulence mechanisms. We aimed to present a compressive review of different antigens of S. aureus and also to introduce vaccine candidates undergoing clinical trials, from which can help us to choose a suitable and effective candidate for vaccine development against S. aureus.

Introduction: Hepatitis is a systemic diseasethat causes liver inflammation. The prevention of this infection is a vaccination. The commonly used vaccine to fight this disease is to use the vaccine formulated with Alum. This vaccine cannot provide immune response and complete productivity in some people. In this study, cellular and humoral immune responses of hepatitis B vaccine were compared with hepatitis B vaccine formulated in MF59 adjuvant. Methods: In this experimental study, Balb/c mice received different formulations of the vaccine subcutaneously three times with a two-week interval. Then, the mice were bled and the levels of anti-HBs Ag were determined by the ELISA method. IFN-γ, IL-4, IL-2 and IFN-γ / IL-4 cytokines were examined by the ELISA method from the soup of spleen cells culture. The data were analyzed using the GraphPad prism software ANOVA. Results: IL-4 levels were significantly higher in alum vaccine than the vaccine formulated in MF59, also the IFN-γ cytokine level showed no significant difference between two main groups. TNF-α cytokine shows that alum vaccine is more secreted due to the high inflammation compared with the vaccine with MF59. Total antibody in the third injection, in some dilutions of the commercial vaccine was more than vaccine with MF59. Conclusion: Significant decrease in IL-4 and antibodies indicates that the tendency of vaccine formulated in MF59 to induce cellular immune responses is higher than humoral immune responses. In addition, the safety and lack of side effects of the MF59 adjuvant can also be considered as another advantage.

Introduction: Pseudomonas aeruginosa is a particular importance due to the numerous factors of pathogenicity and the prevalence of multi-resistance strains throughout the world. Therefore, the need to prevent and produce an effective vaccine seems necessary. The aim of this study was to use PLGA nanoparticles in the design of vaccine with alginate antigens, lipopolysaccharide, and exotoxin, A Pseudomonas aeruginosa. In this study, strain PAO1 of Pseudomonas aeruginosa is used. Then, antigens including, alginate, lipopolysaccharide, and exotoxin A were extracted. Then, lipopolysaccharide was detoxified by hot phenol method. Exotoxin A was purified by chromatography and detoxified with formalin. Then, antigens separately conjugated to PLGA. FT-IR and AFM methods were usedto confirm conjugation with nanoparticles. A rabbit model was used to study the pyrogenic effects of conjugates. The mortality effect of conjugates on mouse model was tested. Materials and methods: The success of conjugation based on the size and charge of the nanoparticle was confirmed. The presence of antigenic functional groups in the structure of the nanoparticle and the formation of a steric bond confirmed with FT-IR results and the corresponding courier form. Results: The 3D conjugate images of nanoparticles before and after conjugation showed an increase in the height of nanoparticle binding sites. The change from initial sharpness to puff after the conjugation confirmed the success of conjugation. Failure to observe the pyrogenic effects in the rabbit and no mortality observed in mice was proved. Discussion and conclusion: All of the results showed that conjugates were effective in immunization. Therefore, it can be a candidate vaccine with a great potential against Pseudomonas causing diseases.

Objective(s): Leishmaniasis is endemic in 88 countries. Amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection. Monoclonal antibodies are key reagents used in the diagnosis of infectious and non-infectious diseases. The aim of this study was to produce monoclonal antibodies against axenic amastigotes of the Leishmania infantum strain in Iran.Materials and Methods: First, standard strains were cultured and axenic amastigote antigens of L. infantum were obtained. Since then, BALB/c mice were immunized and antibody titers were determined. For hybridoma cell formation, lymphocytes isolated from spleen of immunized mice and myeloma cells were fused at a ratio of 10 to 1 in the presence of polyethylene glycol, followed by limiting dilution for the isolation of monoclones. Subsequently, antibody isotypes were determined by using the isotyping kit. The best clone was injected intraperitoneally to pristane-primed mice for large scale production of monoclonal antibodies. The specificity of antibody was determined with Western blotting.Results: Approximately 25 positive monoclones were obtained, of which four hybrids producing anti-amastigotes L. infantum monoclonal antibodies with high optical density (OD), selected and designated as 8D2 FVI6, 8D2 FVI3, 6G2 FV4 and 6G2 FV3. Results from isotype determination showed the IgG2b sub-class in 6G2FV2 and 8D2FVI6 monoclones. Conclusion: This study produced monoclonal antibody against amastigotes of Iranian strain of L. infantum for the first time. These antibodies have reactivity against Iranian strain of L. infantum and can be used in the diagnosis of Kala-azar.

In cognitive radio (CR) networks coexistence between primary and secondary networks is allowed to exploit the spectrum bands more efficiently. To have a green CR network, energy efficiency (EE) as well as collision probability between such networks are vital key performance. While, it is desired to improve EE, the latter should be decreased as much as possible. Therefore, interference between the primary user (PU) and secondary user (SU) is of high importance. Two kinds of interference are unavoidable. They are sensing error and PU re-occupancies interferences. While most studies focus on the sensing error interference, with the dynamic PU, the latter is also quite intense. Moreover, a precise investigation on the effect of such interference necessitates considering the PU and SU traffic behavior. Therefore, in this paper a new analytical framework is proposed in which the EE and collision probability are formulated. The traffic behaviors of PU and a general SU traffic are also considered. Using renewal reward theory, EE, and collision probability are then extracted and investigated for different dynamic rates of the PU traffic. For this, sensing error interference, PU-re-occupancy interference, and total energy consumption are derived in closed form expressions. The queue stability of SU's buffer is also investigated. Finally, simulation results are provided to justify the theoretical results. Suitable values for sensing and transmission times are obtained to maximize the EE under collision and queue stability constraints.

Abstract Background Surfactant protein D (SP-D) is a member of the collectin family and is an important component of the pulmonary innate host defense. To find the relationship between exercise training and SP-D in diabetes, we examined the possible effects of a 10-week endurance exercise-training program on serum levels of SP-D, leptin, lipid profile and insulin resistance in obese women with type-2 diabetes mellitus (T2DM). Methods Twenty-two obese women with T2DM were randomly assigned to either exercise training (ET) or control (C) group. A subject dropped from ET group due to personal reasons and 1 subject dropped from C group due to commitment to experiments conditions. A total of twenty obese women with T2DM were randomly assigned into endurance exercise training (ET = 10) and control (C = 10) groups. The training group underwent a progressive endurance-training program for 10 weeks (running on a treadmill for 30–55 min/day at 50–75% heart rate reserve) and the control group did not participate in any exercise program. Venous blood samples were collected from both groups before and 72 h after the last session of exercise training for analysis of serum SP-D, leptin, lipid profile, glucose and insulin. Data were analyzed using 2 (group: control, endurance training) × 2 (time: pre, post) ANOVA with repeated measures on the second factor. Absolute changes from rest (∆ baseline) values were calculated according to the following formula: ((measure-baseline)·baseline-1)·100. Percent change between groups was analyzed using independent t-tests (p

Objective(s): Infection with Pseudomonas aeruginosa has been a long-standing obstacle for clinical therapy due to the complexity of the genetics and pathogenesis, as well for widespread resistance to antibiotics, thus attaching great importance to explore effective vaccines for prevention and treatment. This paper focuses on the introduction of novel Pseudomonas aeruginosa type IV pili (T4P)-based fusion protein containing the secretin domain of PilQ and tandem PilA-related peptides. Materials and Methods: We surveyed the expression of the PilQ380-705-PilA fusion protein in-frame with pET26b vector in which a rigid linker was used between two polypeptides and flexible linkers were inserted between the three tandem repeats and each pilA domains. The transformants were expressed in Escherichia coli BL21. The reactivity of specific antisera to the fusion protein was assessed by ELISA. The biological activities of this candidate vaccine were evaluated by western blotting, opsonophagocytosis, and twitching inhibition assays. Results: The fusion protein was purified in high yield by osmotic shock method using HisTrap affinity column. The protein was confirmed by immunoblot analysis. The checkerboard titration showed that the optimal dilution of the antibody to react with antigen is 1:128. Results of opsonophagocytosis assay revealed that the antibodies elevated to the fusion protein promoted phagocytosis of the PAO1 and 6266E strains, so that the twitching immobilization test confirmed these results. Conclusion: Due to excellent killing activity mediated by opsonic antibodies and efficient immobilization of the strains, it seems that PilQ380-705-PilA fusion protein could be a reliable candidate vaccine against P. aeruginosa infection.

Background & Objective: Tuberculosis (TB) is a zoonotic disease which is caused by Mycobacterium tuberculosis. Because of common structural and secretory antigens between pathogen and nonpathogenic mycobacterium, the specific diagnosis of TB is difficult. Therefore, it is very important to find a new method with high specificity and sensitivity for accurate and rapid diagnosis of tuberculosis. In this study, the serodiagnostic potential of Mycobacterium tuberculosis recombinant ESAT-6 in TB infected patients was evaluated by Enzyme Linked Immunosorbent Assay (ELISA). Materials & Methods: 55 TB patients with active disease and 28 healthy controls have been collected and evaluated in different dilutions in ELISA methods for the presence of specific anti-ESAT-6 antibody. The specificity and the sensitivity of this method was compared with the culture test. Results: TB patients have high levels of specific antibody against ESAT-6 antigens. The specificity and the sensitivity of this method was calculated as 80.90% and 85.45%, respectively. Conclusion: These findings provide useful information on the importance of ESAT-6 protein and suggested this serologic test as a good alternative method for rapid and prefect diagnosis of tuberculosis.

Current licensed and commercially available prophylactic human papillomavirus (HPV) vaccines (Cervarix and quadrivalent/nine valents Gardasil) are based on major capsid protein L1 virus-like particles (VLPs) production which are expensive and type specific. Minor capsid L2-RG1 linear epitope (17-36) is a known candidate for induction of cross-neutralizing antibodies to develop low-cost pan-HPV vaccines. Herein, we report construction and expression of a three tandem repeats of L2-RG1 derived from HPV16 and 18 fused with the same head to tail pattern (HPV16:17-36×3+ HPV18:17-36×3; hereafter termed dual-type fusion L2 peptide) in E. coli and provide the results of its immunogenicity in mice. SDS-PAGE and western blot analyses indicated proper expression of the peptide that could be further purified by Ni-NTA affinity chromatography via the located C-terminal 6xHis-tag. Mice immunized by formulation of the purified peptide and Freund adjuvant raised neutralizing antibodies which showed proper cross reactivity to HPV L2 (11-200) of types: 18, 16, 31 and 45 (which totally are responsible for 90% of cervical cancers) and efficiently neutralized HPV18/16 pseudoviruses in vitro. Our results imply the possibility of development of a simple, low-cost preventive HPV vaccine based on this dual-type fusion L2 peptide in bacterial expression system with broad spectrum.

Summary: Hepatitis B virus (HBV) infection is known as a life-threatening liver infection and leads to chronic liver disease if left untreated. Nevertheless, the prevalence of HBV infection has been reduced by an approved vaccination approach using recombinant Hepatitis B surface Antigen (HBsAg) and Alum, known as the HBV vaccine. Alum can be used as an adjuvant to increase HBsAg immunogenicity as a strong Th2 stimulator. There is a vital need to stimulate Th1 immunity by HBsAg vaccination; however, the present vaccine does not induce a prophylactic immune response in some groups. The main aim of the present study was to induce a Th1 cytokine pattern and stimulate an immune response after HBsAg vaccination. Experimental mice were fed selenium nanoparticles (SeNPs) and were later immunized with 5 μg of Hepatitis B Vaccine. After a period of 30 days, the experimental animals were given two booster doses of SeNPs during their vaccination course. Group one, i.e., the control vaccine group, was only administered the HBsAg vaccine. The two treated groups, Groups 2 and 3, were daily fed different doses of SeNPs (100 μg and 200 μg, respectively) via gavage. Group four was considered the control group and was only given phosphate buffered saline (PBS). Lymphocyte proliferation, IFN-γ and IL-4 levels, total antibody and the isotypes of IgG1, IgG2a, IgG2b, and IgM were measured by Enzyme Linked Immunosorbent Assay (ELISA). The administration of SeNPs and the HBs antigen vaccine affected the lymphocyte proliferation; moreover, the total antibody responses also increased the IFN-γ level and induced a Th1 response. Conclusions: The present study proposed that the administration of SeNPs with a conventional HBs antigen vaccine induces a better immune response with a Th1 bias. Keywords: Selenium nanoparticles, Hepatitis B vaccine, IFN-γ, Th1 immune response

Nanoparticles have comprehensively affected various sights of human life. Through the wide range of claims about nanosized particles and their functions, biomedical applications are of much interest among health care researchers due to the nanoparticles' potential for use in the process of disease diagnosis, control and treatment. In this regard, inorganic nanoparticles, which have high potential in diagnostic and therapeutic systems, have recently received much attention in oncology. Although inorganic nanoparticles initially seemed an appropriate tool for cancer imaging and diagnosis, their ability to attack cancerous cells as anticancer drugs or carriers in other drugs has also demonstrated promising results. The present review primarily provides a brief survey of various studies in which metal nanoparticles such as gold, silver, iron oxide, and metalloid nanoparticles viz. tellurium and bismuth were exploited for therapeutic or diagnostic purposes in oncology. Then the application of selenium nanoparticles as a therapeutic agent against cancer in in vitro and in vivo studies is reviewed in detail. Although inorganic nanoparticles seem to be useful tools for cancer imaging and diagnosis, their potential for attacking cancerous cells as anticancer substances or even carriers for anticancer medications should not be underestimated.

Background & Objective: Tuberculosis (TB) is a zoonotic disease which is caused by Mycobacterium tuberculosis. Because of common structural and secretory antigens between pathogen and nonpathogenic mycobacterium, the specific diagnosis of TB is difficult. Therefore, it is very important to find a new method with high specificity and sensitivity for accurate and rapid diagnosis of tuberculosis. In this study, the serodiagnostic potential of Mycobacterium tuberculosis recombinant ESAT-6 in TB infected patients was evaluated by Enzyme Linked Immunosorbent Assay (ELISA). Materials & Methods: 55 TB patients with active disease and 28 healthy controls have been collected and evaluated in different dilutions in ELISA methods for the presence of specific anti-ESAT-6 antibody. The specificity and the sensitivity of this method was compared with the culture test. Results: TB patients have high levels of specific antibody against ESAT-6 antigens. The specificity and the sensitivity of this method was calculated as 80.90% and 85.45%, respectively. Conclusion: These findings provide useful information on the importance of ESAT-6 protein and suggested this serologic test as a good alternative method for rapid and prefect diagnosis of tuberculosis.

Objective(s): Many types of human papillomaviruses (HPVs) have been identified, with some leading to cancer and others to skin lesions such as anogenital warts. Studies have demonstrated an association between oncogenic HPV and cervical cancer and many researchers have focused on therapeutic vaccines development. At present, the modulatory effect of opioids on the innate and acquired immune system is characterized. Antagonists of opioid receptors such as naloxone (NLX) can contribute to the shifting Th2 response toward Th1. Herein; we studied the adjuvant activity of NLX/Alum mixture for improvement of the immunogenicity of HPV-16E7d vaccine. Materials and Methods: The mice were administered different regimens of vaccine; E7d, E7d-NLX, E7d-Alum, E7d-NLX-Alum, NLX, alum and PBS via subcutaneous route for three times with two weeks interval. Two weeks after the last immunization, the sera were assessed for total antibody, IgG1 and IgG2a with an optimized ELISA method. The splenocytes culture supernatant was analyzed by ELISA for the presence of IL-4, IFN-g and IL-17 cytokines and lymphocyte proliferation was evaluated with Brdu method. Results: Immunization of mice with HPV-16 E7d vaccine formulated in NLX/Alum mixture significantly increased lymphocyte proliferation and Th1 and Th17 cytokines responses compared to other experimental groups. Analysis of humoral immune responses revealed that administration of vaccine with NLX/Alum mixture significantly increased specific IgG responses and also isotypes compared to control groups. Conclusion: NLX/Alum mixture as an adjuvant could improve cellular and humoral immune responses and the adjuvant maybe useful for HPV vaccines model for further studies in human clinical trial.

Background: Brain tumors can be serious and life-threatening when they are treated effectively. Many therapeutic approaches, such as chemotherapy, radiotherapy, and surgery have been used to treat brain tumors. In this regard, selenium supplements have been reported effective. Methods: Selenium Nanoparticles (SeNPs) were produced in two forms of synthetic and biogenic to evaluate their cytotoxicity on brain glioblastoma cell lines. A-172 cell line was cultured in DMEM medium. The cytotoxicity of the synthetic and biogenic SeNP was assessed by MTT assay. Results: There was a significant difference between the group treated with biogenic and synthetic SeNP compared with non-treated cells after 24, 48, and 72 h. Both biogenic and synthetic SeNP increased Bax gene and decreased Bcl-2 gene expression. Conclusion: It seems that biogenic SeNP was more lethal than its synthetic form. Therefore, it should be considered that the method of NP construction may be an important parameter for its bioactivity.

Background: Human papilloma virus is a DNA virus from the papillomavirus family that is most prevalent in human cervical cancers and many studies showed the E6 and E7 proteins are present in the majority of cervical cancer cases. Development of universal HPV peptide-based vaccine with more serotypes coverage has considerable value. The aim of the study was to design a multi-epitope universal vaccine for major HPV based on E6 and E7 proteins and optimization the expression of polytopic construct contains E6 and E7 genes from different genotypes of human papilloma virus as a candid vaccine. Methods: In this experimental study that was carried out in Pasteur Institute of Iran, Virology Department from October 2013 to November 2014. In order to design the polytypic construct, we predicted the most probable immunogenic epitopes of E6 and E7 from common high risk HPV16, 18, 31, 45 along with high prevalent type 6 and 11 using bioinformatics methods. The synthetic pET28a expression vector harboring E6 and E7 protein was transformed into Escherichia coli hosts and its expression was analyzed by SDS-PAGE and western blotting. Finally, in order to expression optimization of recombinant protein, cell density, induction time, growth temperature, IPTG (Isopropyl β-D-1-thiogalactopyranoside) concentration and cultures media were studied. Results: In the present study the recombinant fusion protein was expressed successfully and the highest expression of target protein was achieved in super broth medium containing 0.1% glucose and 0.2% L-arabinose. In Super broth medium, the optimum condition for recombinant protein expression was occurred at OD600 of 0.8, 0.1mM IPTG, one hour’s incubation time at 37 °C and BL21 (A1) host. Conclusion: The results of this study show that the optimum expression of E6 and E7 proteins from different genotypes of human papilloma virus can be performed. Moreover, by purification of recombinant protein and evaluation of its immunogenicity in mice, it can be used as a vaccine candidate against the human papilloma virus.

Objective(s):Multi-epitopic protein vaccines and direction of vaccine delivery to dendritic cells (DCs) are promising approaches for enhancing immune responses against mutable pathogens. Escherichia coli is current host for expression of recombinant proteins, and it is important to optimize expression condition. The aim of this study was the optimization of multi-epitopic HIV-1 tat/pol/gag/env recombinant protein (HIVtop4) expression by E. coli and conjugation of purified protein to anti DEC-205 monoclonal antibody as candidate vaccine. Materials and Methods: In this study, expression was induced in BL21 (DE3) E. coli cells by optimization of induction condition, post induction incubation time, temperature and culture medium formula. Some culture mediums were used for cell culture, and isopropyl-beta-D-thiogalactopyranoside was used for induction of expression. Protein was purified by Ni-NTA column chromatography and confirmed against anti-His antibody in western-blotting. To exploit DCs properties for immunization purposes, recombinant protein chemically coupled to αDEC-205 monoclonal antibody and confirmed against anti-His antibody in western-blotting. Results: The optimum condition for expression was 1 mM IPTG during 4 hr cultures in 2XYT medium, and final protein produced in soluble form. Conjugation of purified protein to αDEC-205 antibody resulted in smears of protein: antibodies conjugate in different molecular weights. [AGA1] . Conclusion: The best cultivation condition for production of HIVtop4 protein is induction by 1 mM IPTG during 4 hr in 2XYT medium. [AGA2] The final concentration of purified protein was 500 µg/ml.

Introduction : Designing an effective vaccine against human immunodeficiency virus (HIV)-1 is a global health priority . Multi-epitope vaccines offer several potential advantages that may be promising in case of mutable divergent pathogens such as HIV-1. Herein, a multiepitopic recombinant protein containing various HIV-1 antigens was expressed in E. coli cells and its immunogenicity in combination with different adjuvants was initially evaluated in BALB/c mouse. Methods: HIVtop4 sequence spanning the junction of six amino acid fragments (Gag158-186, Pol150-190, ENV296-323, ENV577-610, Tat1-20 and Tat44-61) was designed based on immunoinformatic analysis to reduce the creation of junctional epitopes, improve the cleavage of proteasome and avoid the local accumulation of hydrophobic regions. Synthesized nucleotide sequence corresponding to HIVtop4 was cloned into pET23a plasmid. Expression of pET-HIVtop4 plasmid was induced in BL21 (DE3) E. coli cells by addition of 1 mM IPTG during 3 h culture and the protein was purified by Ni-NTA column chromatography and further confirmed against anti-His antibody in western-blotting. Groups of BALB/c mice (n=6) were immunized three times with 2 weeks interval, subcutaneously with 10 m g of candidate vaccine adjuvanted in Complete Freund’s adjuvant , Montanide ISA70 and Alum with suitable control groups. Two weeks after last immunization lymphocyte proliferation was measured with Brdu, IL-4 and IFN- g cytokines with ELISA, total antibody and IgG1, IgG2a isotypes with indirect ELISA methods. Results: Results showed that Immunization with HIV-1 tat/pol/gag/env led to a significant increase in the proliferative responses of lymphocytes, IL-4 and IFN-γ cytokine production and humoral immune response in comparison with the control groups. Conclusion: In this study we concluded that Tat, Env, Pol, Gag with adjuvants (Montanide, Alum and CFA) has potentials as a candidate vaccine against the HIV-1 virus. Vac Res, 2014, 1 (1): 10-15

Background & Objective: Invasive Aspergillosis is a fatal infection in immunocompromised patients. The aim of this study was to evaluate the interaction of infectious with Aspergillus and tumor on immune response and cytokine network in Aspergillus infected tumor-bearing mice. Materials and Methods: Mice were implanted by sterile pieces of mouse mammary tumor and then infected by Aspergillus conidia by IV injection. Control groups mice were infected with Aspergillus conidia and/or implanted by sterile funga pieces of mouse mammary tumor. Seven days after Aspergillus infection, cytokine production of extracted splenocytes was analyzed by ELISA method. Results: Tumor bearing mice which were infected with Aspergillus conidia showed remarkable increase in IL-4 production. Conversely, the levels of IFN-γ and IL-10 were decreased and TNF-α was increased moderately. Conclution: Probably, Aspergillus infection could change cytokine production from CD4+ T helper cells and acquired immunity of tumor bearing mice. This point may be considered for better management of Aspergillus-infected patients suffering from cancer.

The present study explores parents’ educational styles (or ‘parenting styles’ as used by previous researchers) as perceived by their pre-university-aged children. Sample size formula was administered to determine the number of participants; accordingly, 800 (380 males and 420 female) students studying at Tehran pre-university schools were selected through stratified random sampling. Participants were given a researcher-made, 35-item questionnaire devised to measure parenting styles. Data was then analyzed using the Factor Analysis method. Findings revealed four distinguished parenting styles, i.e. Decisive-kind, Decisive-unkind, Permissive-kind & Permissive-unkind styles.

Recent studies have indicated the profound anti-tumor activity of artemisinin's compounds, among which; arteether is an oil-soluble derivative of artemisinin with an endoperoxide bridge that can induce apoptosis in tumor cells but not in the normal cells. An experiment was carried out on tumor-bearing Balb/c mice to estimate the effects of Arteether on tumor growth and antitumor immune responses. Briefly, 6mg/kg/day of Arteether and diluents were administered to two groups of mice. Tumor sizes were measured using digital verniercallipers. Mice were sacrificed and splenocytes were harvested for lymphocyte proliferation assay, the level of IL-4 and IFN-γ cytokines, and the percentage of splenic T regulatory cells were measured. According to the findings, there were no statistical differences between the groups with respect to the level of IFN-γ, IL-4 and proliferation assay; while our results showed that Arteether is effective in the reduction of tumor growth rate. In general, intra-tumoral injection of Arteether as an oil-soluble derivative of artemisinin brings to light some antitumor properties that may aid in development of more effective antitumor agents.

Breast cancer patients are susceptible to infections such as candidiasis. Due to the importance and the role of matrix metalloproteinases (MMP) in breast cancer progression and its correlation with tumor metastasis, we analyzed the serum level of MMPs -2, -3, -9 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in breast cancer bearing mice in the presence of systemic Candida albicans infection. Female BALB/c mice were divided into 4 groups: group I had tumor + candidiasis; group II, tumor only; group III, candidiasis only and group IV as negative control. Tumor tissue was separated from stock breast cancer bearing mice and transplanted subcutaneously into the groups I and II mice. Two weeks after tumor transplantation, groups I and III were infected with Candida albicans by intravenous injection. One week after systemic infection, the sera of the experimental groups were prepared and analyzed with ELISA for MMP-2, -3, -9 and TIMP-1 levels. The results showed that the levels of MMP-3, MMP-9 and TIMP-1 were increased in groups I, II and III, as compared to the control group. However, the level of MMP-2 was decreased in mice infected with Candida albicans and in infected mice bearing tumor. These data suggest that candidiasis may have a positive effect on tumor progression and metastasis.

Lactic acid bacteria which are used as probiotics have ability to modulate immune responses and modify immune mechanisms. It has also been indicated that some strains of this family can affect the immune responses against solid tumors. In the present work, we proposed to study the effects of oral administration of L.cacesi ssp casei on the NK cells cytotoxicity and also production of cytokines in spleen cells culture of BALB/c mice bearing invasive ductal carcinoma. 30 female In-bred BALB/c mice, were used and divided in two groups of test and control each containing 15 mice. Every day from 2 weeks before tumor transplantation 0.5 ml of PBS containing 2.7×108 CFU/ml of L.casei spp casei was orally administered to the test mice and it was followed 3 weeks after transplantation as well with 3 days interval between each week. Control mice received an equal volume of PBS in a same manner. Results showed that oral administration of L. casei significantly increased the production of IL-12 and IFN-γ (P

Background: Fusion of Hepatitis B virus surface antigen (HBsAg) to a DNA construct might be considered as a strategy to enhance cellular and cytotoxic T-lymphocytes (CTL) responses of a Hepatitis C Virus core protein (HCVcp)-based DNA vaccine comparable to that of adjuvanted protein (subunit) immunization. Materials and Methods: pCHCORE vector harboring coding sequence of HBsAg and HCVcp (amino acids 2-120) in tandem within the pCDNA3.1 backbone was constructed. The corresponding recombinant HCVcp was also expressed and purified in Escherichia coli. Mice were immunized either by adjuvanted HCVcp (pluronic acid + protein) or by pCHCORE vector primed/protein boosted immunization regimen. The cellular immune responses (proliferation, In vivo CTL assay and IFN-g/IL-4 ELISpot) against a strong and dominant H2-d restricted, CD8 + -epitopic peptide (C39) (core 39-48; RRGPRLGVRA) of HCVcp were compared in immunized animals. Result: Proper expression of the fused protein by pCHCORE in transiently transfected HEK 293T cells and in the expected size (around 50 kDa) was confirmed by western blotting. The immunization results indicated that the pCHCORE shifted the immune responses pathway to Th1 by enhancing the IFN-g cytokine level much higher than protein immunization while the proliferative and CTL responses were comparable (or slightly in favor of DNA immunization). Conclusion: Fusion of HBsAg to HCVcp in the context of a DNA vaccine modality could augment Th1-oriented cellular and CTL responses toward a protective epitope, comparable to that of HCVcp (subunit HCV vaccine) immunization.