Nano-based drug delivery systems are increasingly used for diagnosis, prevention and treatment of several diseases, thanks to several beneficial properties, including the ability to target specific cells or organs, allowing to reduce treatment costs and side effects frequently associated with chemotherapeutic medications, thereby improving treatment compliance of patients. In the field of communicable diseases, especially those caused by intracellular bacteria, the delivery of antibiotics targeting specific cells is of critical importance to maximize their treatment efficacy. Brucella melitensis, an intracellular obligate bacterium surviving and replicating inside macrophages is hard to be eradicated, mainly because of the low ability of antibiotics to enter these phagocityc cells . Although different antibiotics regimens including gentamicin, doxycycline and rifampicin are in fact used against the Brucellosis, no efficient treatment has been attained yet, due to the intracellular life of the respective pathogen. Nano-medicines responding to environmental stimuli allow to maximize drug delivery targeting macropages, thereby boosting treatment efficacy. Several drug delivery nano-technologies, including solid lipid nanoparticles, liposomes, chitosan, niosomes, and their combinations with chitosan sodium alginate can be employed in combination of antibiotics to successfully eradicate Brucellosis infection from patients.

CRISPR/Cas9 technology is one of the common methods of genome editing and targeted gene mutation, which has recently been used for manipulating microalgae such as Chlamydomonas reinhardtii . Besides, this technology can play a role in the fight against greenhouse gases (e.g., carbon dioxide) production by studying genetic pathways to improve algal strains. Among several genes in algae that respond to CO 2 and regulators control the expression of each; Cia5 is one of the most critical transcriptional regulators. In this research, we knocked out the Cia5 gene using the CRISPR/Cas9 technique and analysed the ability of C. reinhardtii to perform CO 2 sequestration. Our results showed that C. reinhardtii has better performance (i.e., response to CO 2 treatment) in both control and mutant species at 0.5% CO 2 concentration than other concentrations. However, the difference between the control microalgae species and the mutant species was in the CO 2 removal efficiency. Additionally, our findings revealed that the control type isolate in CO 2 concentrations of 0.04%, 0.5% and 1% had removal efficiencies of 27%, 37% and 21%, respectively. Nevertheless, for mutant species in the same concentrations, the observed removal efficiencies were 16%, 23% and 9%.

PURPOSE:Chitosan is a natural polymer that has excellent properties include biocompatibility, biodegradability, no cytotoxicity, high charge density, low cost, mucoadhesive, permeation enhancing (ability to cross tight junction), and immunomodulating ability that makes the spectrum of its applicability much broader. This study was conducted to investigate the stabilizing, preservative and immunogenicity properties of N-trimethyl chitosan nanospheres (N-TMCNS).MATERIALS AND METHODS:The tetanus toxoid (TT) was encapsulated into N-TMCNS and then characterized by scanning electron microscope, atomic force microscope, and dynamic light scattering. For stabilizer assay of N-TMCNS after storage of TT-N-TMCNS at different temperatures for 3 weeks, they were used for immunization of mice and different temperatures groups' anti-TT-N-TMCNS production compared with other groups. Finally, the immunized mice were challenged with tetanus toxin. The preservation activity of TT-N-TMCNS against Escherichia coli was compared with thimerosal formulated TT.RESULTS:Our results revealed that heat-treated TT-N-TMCNS could induce higher titer of neutralizing immunoglobulin G in compared to TT vaccine and was able to protect the mice better than TT vaccine in challenge test. Furthermore, N-TMCNS as a preservative inhibited the growth of E. coli more effective than thimerosal.CONCLUSION:Overall, the obtained results indicated that the N-TMCNS is one of the best stabilizer and preservative agent that can be used in the formulation of TT vaccine.

Introduction The current study examined the clinical impacts of phosphatase and tensin (PTEN) expression in prostate cancer (PCa) using immunohistochemistry. Methods 50 patients with mean age of 66.4±7.3 years who had undergone prostatectomy surgery with the diagnosis of PCa, were enrolled in the study. We collected 50 paraffin blocks from the malignant part and 50 paraffin blocks from the healthy part of each patient’s prostate. We considered malignant and healthy parts as the case and the control, respectively. Clinical and pathological information of the patients were gathered and their associations with PTEN status were assessed using odds ratios (ORs) analysis. Results The significant associations between tumor stage, perivascular invasion, perineural invasion, marginal involvement, extraprostatic extension, and biochemical recurrence (as assed by post-surgical prostate-specific antigen (PSA)) and PTEN expression were detected. For patients negative for PTEN, the odds ratio of the higher stage, perivascular invasion, perineural invasion, marginal involvement, and extraprostatic extension in comparison to patients positive for PTEN were estimated 7.5 (95%CI: 2.01,27.86), (95%CI: 1.65-25.57), 7.8 (95%CI:1.54-40.09), 9.78 (95%CI:2.33-41.08), and 4.84 (95%CI:1.07-21.84), respectively. Concerning biochemical recurrence, ORs was calculated 0.30 (95%CI:0.09-1.02) for PTEN positive patients compare to PTEN negative patients. Conclusions Since PTEN loss was associated with fe­atures of aggressive PCa, it can be concluded that loss of PTEN would lead to more aggressive PCa and thereby, lower clinical outcomes.

The article's abstract is no available.

The article's abstract is not available.

Along with robust immunogenicity, an ideal vaccine candidate should be able to produce a long lasting protection. In this regard, the frequency of memory B-cells is possibly an important factor in memory B-cell persistency and duration of immunological memory. On this basis, binding domains of tetanus toxin (HcT), botulinum type A1 toxin (HcA), and heat-labile toxin (LTB) were selected as antigen models that induced long-term, midterm and short-term immune memory, respectively. In the present study, the frequency of total memory B-cells after immunization with HcT, HcA and LTB antigens after 90 and 180 days, and also after one booster, in 190 days, was evaluated. The results showed a significant correlation between frequency of total memory B-cells and duration of humoral immunity. Compared to other antigens, the HcT antibody titers and HcT total memory B-cell populations were greater and persistent even after 6 months. At 6 months after the final immunization, all HcT- and HcA-immunized mice survived against tetanus and botulinum toxins, and also LT toxin binding to GM1 ganglioside was blocked in LTB-immunized mice. We conclude the frequency of memory B-cells and their duration are likely a key factor for vaccine memory duration.

Tenodera angustipennis is an Asian praying mantis, whose crude extracts have long been used for the prevention and treatment of bacterial and viral diseases. Despite significant progress in obtaining biomaterials from praying mantis, antiherpetic activity of T. angustipennis eggs is not well defined. In this study, we characterized the crude extracts from T. angustipennis eggs using high performance liquid chromatography (HPLC), gas chromatography (GC), and gas chromatography-mass spectrometry (GC/MS) methods. Inhibition of cell proliferation by mantis egg extracts and isolated components was investigated on lymphocytes in a MTT assay. Furthermore, the effects of egg extracts against the herpes simplex virus type 1 (HSV-1) strain KOS (HSV-1 KOS) were evaluated in a mouse model. The HPLC and GC/MS results showed that the extracts are mainly composed of stearic acid monoterpenes, octadecanoic acid, hexadecanoic acid, and propionic acid. Investigation on the immunomodulatory effects of the extracted components following infection of mice with HSV-1 KOS virus showed an increase in serum interferon-gamma level (26.01 ± 5.21 vs. 18.67 ± 3.23 pg/mL, respectively) and interleukin-10 level (106.64 ± 4.13 vs. 48.04 ± 3.12 pg/mL, respectively) in test and control groups (for both p < 0.05). It indicates that the mantis egg components have shifted the cytokines induction to the anti-inflammatory arm and probably truncated inflammation caused by HSV-1 KOS virus. Our findings can be considered as an early attempt to reveal the comprehensive biological properties of T. angustipennis eggs as new anti-inflammatory components in future pharmaceutical investigations.

Background: Shigella flexneri is a pathogen responsible for shigellosis around the world, especially in developing countries. Many immunogenic antigens have been introduced as candidate vaccines against Shigella, including N-terminal region of IpaD antigen (NIpaD). Objective: To evaluate the efficiency of O-metylated free trimethyl chitosan nanoparticles (TMC NPs) in the oral delivery of NIpaD. Methods: TMC was synthesized by a two-step method from high molecular weight chitosan. The recombinant NIpaD protein was used as the immunogen. The protein was overexpressed in E. coli BL21 (DE3) and characterized by gel electrophoresis. The NIpaD-loaded TMC NPs were synthesized by ionic gelation method and were characterized by electron microscopy. NPs were orally administered to guinea pigs and specific humoral and mucosal immune responses were assessed by serum IgG and secretory IgA, respectively. The protectivity of the formulation was assessed by keratoconjunctivitis (Sereny) test. Results: The immunized guinea pigs showed a significant raise in rNIpaD-specific serum IgG and faecal IgA titers. Specific secretory IgA was detected in eye-washes. Sereny test results showed that immunized animals vaccinated with IpaD-loaded TMC NPS tolerated the wild type of Shigella flexneri 2a in Sereny test. However, in the group immunized with NIpaD antigen and non-immunized group, no increase was observed in antibody titer against NIpaD. These animals were infected following the challenge with Shigella flexneri 2a (p<0.0152). Conclusion: The recombinant rNIpaD formulated with TMC obtained from high molecular weight chitosan, can be considered as a mucosal vaccine against Shigella flexneri through oral route.

Background: Final elimination of some intracellular bacterial agents, such as Brucella, is often a complex issue and impossible to achieve, primarily due to the presence and survival of the bacteria within phagocytic cells. By penetrating into the cell membrane, drug delivery nanosystems can reduce the number of intracellular bacteria. The aim of this study was to assess the efficacy of chitosan nanoparticles on the delivery of gentamicin into Brucella infected J774A.1 murine cells in vitro. Materials and Methods: Chitosan nanoparticles (NPs) were synthesized using ionic gelation technique. The shape, size and charge of NPs, loading rate and release of the drug were investigated. Finally, the effects of gentamicin-loaded chitosan NPs (Gen-Cs) and free gentamicin on J774A.1 murine cells infected with these bacteria were examined. Results: The mean size and charge of NPs were computed as 100 nm and +28mV, respectively. The loading capacity of NPs was 22%. About 70% of the drug was released from NPs during the first 8 hours. Antimicrobial activity of the two formulations showed that MIC (minimum inhibitory concentration) of the Gen-Cs and free drug was 3.1 and 6.25 µg, respectively. The minimum bactericidal concentration of the NPs-loaded drug and free drug was 6.25 and 12.5 µg, respectively. Cell culture analysis revealed that there was a significant reduction in the load of the intercellular bacteria in J774A.1 murine cells in both formulations. Conclusion: Our results showed the Gen-Cs have a proper potential for optimal treatment of intracellular bacterial agents. [GMJ.2019;8:e1296]Â

OBJECTIVES:The present study was aimed at comparing tetanus toxoid (TT)‑loaded-chitosan nanoparticles with aluminum hydroxide as a common vaccine adjuvant.BACKGROUND:Tetanus remains to be a major public health problem. Nanoparticles have been extensively used as immune adjuvants. Tetanus toxoid (TT) encapsulated in chitosan nanoparticles is considered to be a promising tetanus vaccine candidate.METHODS:TT‑loaded chitosan nanoparticles were prepared by the ionic gelation method. The nanoparticles were studied by SEM for their size and morphology. In vivo study was conducted to evaluate the immunity response using mice divided into 4 groups and injected with encapsulated toxoid. The immune responses were then measured using indirect ELISA.RESULTS:The purity and integrity of antigen were confirmed by SDS-PAGE electrophoresis. The size of nanoparticles was estimated at 100 nm. As a result, the IgG antibody levels were 1.9, 1.76, and 0.87 in chitosan nanoparticles, aluminum hydroxide, and TT alone groups, respectively. Also, the immune responses were significantly higher in immunized groups compared to control groups vaccinated with free adjuvant vaccines (p < 0.05).CONCLUSIONS:The quality and efficacy of toxoid‑loaded chitosan nanoparticles were reasonable. It enhanced the immune responses as much as aluminum hydroxide adjuvant does and thus may be a good alternative candidate (Tab. 1, Fig. 3, Ref. 16).

In order to overcome complexities and survive in an intense competitive environment ,todays organizations have no choice but to rely on knowledge rather than on some advantage –making factors like land, capital, and work force. accordingly , considering the existing complexities and expanding rang of threats , defense organizations also need to move toward knowledge- base organizations. Superiority in the upcoming battle scenes depend on knowledge superiority over enemies. This research, which has been done using descriptive survey method, aims to offer a model of knowledge – based defense organizations as well as their components, indices and the relationship between them. First, 19 factors were identified using authentic literature and experts advices. Then, the mentioned factors were divided into four major categories namely organizational structure, organizational culture , human capital , end leadership. After that the components and indices were ranked according to friedman test. Finally , the model was tested using structural equation modeling. All the identified factors and relationship in the proposed model were approved with high reliability.

Background and purpose: In recent years nanotechnology has a significant impact on various fields of human life, especially in pharmaceutical and medical needs. Some biopolymers such as chitosan which is also biocompatible are low cost and abundantly found, so, their application for vaccine production is cost benefit. Trimethyl chitosan is a deacetylated derivative of chitosan that could be used to increase the induction of immune response. In this study, trimethyl chitosan nanoparticles containing tetanus protein were used to stimulate the immune system. Materials and methods: In this experimental study, synthesis of the tetanus toxoid loaded nanoparticles was done by ion gelation method. Physical features of the nanoparticles were investigated using scanning electron microscopy (SEM). The nanoparticles were then injected subcutaneously into mice. After the sampling process, the immune system stimulation was evaluated using indirect ELISA. Data was analyzed using one-way ANOVA and significance level of P< 0.05. Results: The purity of protein was confirmed by SDS-PAGE and encapsulated proteins were loaded up to 80 percent. ELISA results showed that the immune system was stimulated significantly compared with Freund adjuvant, and antibody titer increased. Conclusion: Tetanus toxoid loaded Trimethyl chitosan nanoparticles increase the stimulation of immune system and are more effective in comparison with Freund's adjuvant.

Despite significant progresses in the development and emergence of new antibiotics, it is still a major problem to treat intracellular bacterial pathogens in human infections. Concentration in specific doses of antibiotics is often dependent on the type of treatment and some drugs may be prescribed in large doses for more efficiency. This is important not only economically, but also may cause localized or side effects in individual patients. On the other hand the emergence of antimicrobial resistance caused that treatment of inner celullar bacteria has not been successfully completed. The use of nanoparticles for drug delivery systems caused to optimize the effectiveness of the treatment process and subsequently better in this kind of infections. polymeric nanoparticles are of particular importance due to biodegradability and biocompatibility. On the other hand, the nanoparticles particularly increase the phagocytic activity and operate as desired in drug delivery systems. Due to great efforts in recent years in the field, there is no doubt that the nanoparticles improve the treatment of intracellular bacterial agents, optimize the chronic infections and minimize their side effects. In this review, applicaions of drug delivery systems are used, leading to effective performance on target bacteria.

Lung cancer, the leading cause of cancer mortality, needs urgent development of newly qualified diagnostic and therapeutic biomarkers. Recently, Human Endogenous Retroviruses (HERVs) have been introduced for cancer diagnosis. In this case-control study, we have collected blood samples from 60 lung cancer patients and 20 healthy controls. Quantitative gene expression analysis of various HERV env genes, including HERV-R, HERV-H, HERV-K, and HERV-P was performed by real-time PCR. Results indicate that expression of all four HERV env mRNAs is significantly increased in the blood of lung cancer patients than healthy controls (P-values<0.01). Furthermore, we have observed a positive and significant pairwise correlation between the expressions of four HERV env genes. The level of HERV env transcript in the blood of adenocarcinoma patients was generally much higher than squamous cell carcinoma (SCC) and small-cell lung cancer (SCLC) patients. Also, the expression of three HERV P, HERV H, and HERV K in the blood of lung cancer patients could significantly differentiate between adenocarcinoma and other types of lung cancer. In conclusion, these four HERV families could be considered as promising non-invasive blood-based biomarkers for prognosis, early detection, and monitoring of lung cancer.

Background and Objectives: Tetanus is a deadly zoonotic infectious disease. For nearly a century, tetanus vaccine has been produced and used. This study was carried out with the aim of preparation and evaluation of immunogenicity of chitosan nanoparticles containing tetanotoxin in comparison with Freund's adjuvant in mouse model for improvement of tetanus vaccine after subcutaneous onjection. Methods: In this experimental study, chitosan nanoparticles synthesis containing tetanus toxoid was performed using ionic gelation method. The morphology of nanoparticles was investigated using SEM and AFM, then, the nanoparticles were subcutaneously injected into mice and two weeks after the end of injection, blood was taken. Antibody titer was measured by indirect ELISA. Data were analyzed using one-way one-way ANOVA and Tukey test at significance level of p<0.05. Results: High-load antigen (uniform spherical morphology and the mean size of 144), were encapsulated in chitosan nanoparticles. After serum analysis, IgG antibody titer was significantly different between the mice that received antigen as nanoparticle and the control group, but no significant difference was observed in the antigen with Freund’s adjuvant group. Conclusion: Based on the results of this study, tetanus toxoid injection using nanoproces is able to induce humoral immune response almost equal to Freund’s adjuvant and can be an appropriate alternative.

A simple and sensitive nanobiosensor was developed for diagnosing label-free, PCR-free of rfbE gene in Escherichia coli O157:H7 real sample. The Au nanoparticles modified electrode (AunanoME) was prepared by electrodeposition technique. The single-stranded DNA probes were immobilized through the chemisorptions process on AunanoME (ssDNA/AunanoME). Electrochemical impedance spectroscopy (EIS) technique has been used to investigate the hybridization and sensing properties. Using electrochemical impedance spectroscopy (EIS) technique, the charge-transfer resistance (R-ct) values were raised by immobilization of the DNA probe and after the hybridization with the complementary oligonucleotide for ssDNA/Au electrode from 2.81 +/- 0.1 to 7.62 +/- 0.2 k Omega and for ssDNA/AunanoME from 2.58 +/- 0.1 to 9.95 +/- 0.2 kW. The results showed that the immobilization and hybridization of DNA on the AunanoME increases effectively the nanobiosensor response compared with the Au bare electrode. In addition, the electrochemical DNA biosensor showed a good selectivity toward the detection of the complementary oligonucleotides of the rfbE gene of E. coli O157. The nanobiosensor response showed a linear dynamic range 1.0 X 10(-13) to 1.0 X 10(-6) molL(-1) with a detection limit of 9.1 X 10(-14) molL(-1) and was able to detect E. coli O157:H7 real sample corresponding to 10(2) cells per ml. Our results suggest that, the nanobiosensor is promising for environmental and clinical applications.

Background: Physical exercise and herbal treatment with antioxidant property induce a favorable effect on glucose metabolism in diabetic patients. Objective: The aim of the present study was to investigate the effects of resistance training combined with green tea extract consumption on blood glucose and lipid profile in diabetic rats. Methods: Forty male Wistar diabetic rats aged 5 months and weights 290 ± 20 were divided into 4 groups named as: resistance training, resistance training + green tea, green tea and control. The resistance training and resistance training + green tea groups engaged in exercise for 5 weeks with three times per week moving up the ladder with weight hanging their tail. Green tea extract (100 mg/kg) was gavaged once a day for 5 weeks. Forty eight hours after the last training session and green tea gavages, the fasting blood samples was collected for determination of blood glucose, cholesterol, LDL-C, HDL-C and triglyceride levels. Results: Fasting blood glucose level significantly decreased in all three groups compared with control group, where as triglyceride, cholesterol and LDL-C level significantly decrease in resistance training + green tea group compared to control group. Conclusion: Green tea extract and resistance training improve hyperglycemia and in combination improve lipid profile in diabetic rats.