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

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

Potential therapeutic options for celiac Disease: An update on Current evidence from Gluten-Free diet to cell therapy.

Celiac disease (CD) is a chronic autoimmune enteropathy and multifactorial disease caused by inappropriate immune responses to gluten in the small intestine. Weight loss, anemia, osteoporosis, arthritis, and hepatitis are among the extraintestinal manifestations of active CD. Currently, a strict lifelong gluten-free diet (GFD) is the only safe, effective, and available treatment. Despite the social burden, high expenses, and challenges of following a GFD, 2 to 5 percent of patients do not demonstrate clinical or pathophysiological improvement. Therefore, we need novel and alternative therapeutic approaches for patients. Innovative approaches encompass a broad spectrum of strategies, including enzymatic degradation of gluten, inhibition of intestinal permeability, modulation of the immune response, inhibition of the transglutaminase 2 (TG2) enzyme, blocking antigen presentation by HLA-DQ2/8, and induction of tolerance. Hence, this review is focused on comprehensive therapeutic strategies ranging from dietary approaches to novel methods such as antigen-based immunotherapy, cell and gene therapy, and the usage of nanoparticles for CD treatment.

Protective effects of L-arginine on Alzheimer's disease: Modulating hippocampal nitric oxide levels and memory deficits in aluminum chloride-induced rat model.

There is evidence that high daily intake of aluminum (Al) is associated with an increased risk of dementia or cognitive decline. We injected L-arginine into the dorsal hippocampus (DH) of an AlCl3-induced Alzheimer's model and studied memory deficit, ß-amyloid (ßA) accumulation, neurodegeneration, and molecular changes. Male Wistar rats were cannulated unilaterally in the DH under a stereotaxic apparatus and a dose of AlCl3 (1-200 µg/rat) was injected into the CA1. After recovery, L-arginine and L-NAME (0.05-25 µg/rat) were injected into CA1 and animals were tested in novelty seeking task. One group received ßA (2 µg/rat, intra CA1) as a reference group. Control groups received saline (1 µL/rat, intra-CA1) and galantamine (25 µg/rat, intra-CA1), respectively. Finally, rats were anesthetized and hippocampal tissues were isolated on ice. Levels of neuronal NO synthase (nNOS), ß-secretase and soluble guanylyl cyclase (sGC) were measured by western blotting. ßA formation and the number of CA1 neurons were assessed by Congo red and Nissl staining. NOS activation by NADPH-diaphorase (NADPH-d) was investigated. All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. Like ßA, AlCl3 (25 µg/rat) caused accumulation of ßA in the DH and increased stopping of the animal on the novel side (indicating a recall deficit). CA1 neurons decreased, and nNOS and ß-secretase, but not sGC, showed a change consistent with Alzheimer's. However, prophylactic intervention of L-arginine at 3-9 µg/rat was protective, probably by nNOS stimulation in DH, as shown by NADPH-d assay. L-arginine may protect against Alzheimer's by increasing hippocampal NO levels.

Prognosticating the effect of temperature and pH parameters on size and stability of the nanoliposome system based on thermodynamic modeling.

The main challenge of using nanoliposome systems is controlling their size and stability. In order to overcome this challenge, according to the research conducted at the Research Centre for New Technologies of Biological Engineering, University of Tehran, a model for predicting the size and stability of nanoliposome systems based on thermodynamic relations has been presented. In this model, by using the presented equations and without performing many experiments in the laboratory environment, the effect of temperature, ionic power and different pH can be considered simultaneously whereas examining the components of size, stability and any feature were considered before. Synthesis and application of liposomal nanocarriers in different operating conditions can be investigated and predicted, and due to the change in temperature and pH, the smallest size of th system can be obtained. In this study, we were able to model the synthesis and storage conditions of liposomal nanocarriers at different temperatures and acidic, neutral and alkaline pHs, based on the calculation of mathematical equations. This model also indicates that with increasing temperature, the radius increases but with increasing pH, the radius first increases and then decreases. Therefore, this model can be used to predict size and stability in different operating conditions. In fact, with this modelling method, there is no need to study through laboratory methods and analysis to determine the size, stability and surface loads, and in terms of Accuracy, time and cost savings are affordable.

The effect of Nano-liposomal sodium nitrite on smooth muscle cell growth in a tissue-engineered small-diameter vascular graft.

BACKGROUND: Nitric oxide is a chemical agent produced by endothelial cells in a healthy blood vessel, inhibiting the overgrowth of vascular smooth muscle cells and regulating vessel tone. Liposomes are biocompatible and biodegradable drug carriers with a similar structure to cell bilayer phospholipid membrane that can be used as useful nitric oxide carriers in vascular grafts. METHOD: Using a custom-designed apparatus, the sheep carotid arteries were decellularized while still maintaining important components of the vascular extracellular matrix (ECM), allowing them to be used as small-diameter vascular grafts. A chemical signal of sodium nitrite was applied to control smooth muscle cells' behavior under static and dynamic cell culture conditions. The thin film hydration approach was used to create nano-liposomes, which were then used as sodium nitrite carriers to control the drug release rate and enhance the amount of drug loaded into the liposomes. RESULTS: The ratio of 80:20:2 for DPPC: Cholesterol: PEG was determined as the optimum formulation of the liposome structure with high drug encapsulation efficiency (98%) and optimum drug release rate (the drug release rate was 40%, 65%, and 83% after 24, 48, and 72 h, respectively). MTT assay results showed an improvement in endothelial cell proliferation in the presence of nano-liposomal sodium nitrite (LNS) at the concentration of 0.5 µg/mL. Using a suitable concentration of liposomal sodium nitrite (0.5 µg/mL) put onto the constructed scaffold resulted in the controllable development of smooth muscle cells in the experiment. The culture of smooth muscle cells in a pulsatile perfusion bioreactor indicated that in the presence of synthesized liposomal sodium nitrite, the overgrowth of smooth muscle cells was inhibited in dynamic cell culture conditions. The mechanical properties of ECM graft were measured, and a multi-scale model with an accuracy of 83% was proposed to predict mechanical properties successfully. CONCLUSION: The liposomal drug-loaded small-diameter vascular graft can prevent the overgrowth of SMCs and the formation of intimal hyperplasia in the graft. Aside from that, the effect of LNS on endothelial has the potential to stimulate endothelial cell proliferation and re-endothelialization.

Fungal Infected Adipose Stem Cells: The Effects of Novel Lipo-Niosome Nanoparticles Loaded with Amphotericin B and Thymus Essential Oil.

OBJECTIVE: In this study, we aimed to develop new Lipo-niosomes based nanoparticles loaded with Amphotericin B (AmB) and Thymus Essential Oil (TEO) and test their effectiveness in the treatment of fungal-infected human adipose stem cells (hASCs). MATERIALS AND METHODS: In this experimental study, optimal formulation of AmB and TEO loaded lipo-niosome (based on lipid-surfactant thin-film hydration method) was chemically, and biologically characterized. Therefore, encapsulation capacity, drug release, size, and the survival rate of cells with different concentrations of free and encapsulated AmB/ TEO were evaluated using the MTT method, and its antifungal activity was compared with conventional AmB. RESULTS: Lipo-Niosome containing Tween 60 surfactant: cholesterol: Dipalmitoyl phosphatidylcholine (DPPC): Polyethylene glycol (PEG) with a ratio of 20:40:60:3 were chosen as optimal formulation. Lipo-Niosomes entrapment efficiency was 94.15%. The drug release rate after 24 hours was 52%, 54%, and 48% for Lipo-AmB, Lipo-TEO, and Lipo-AmB/TEO, respectively. Physical and chemical characteristics of the Lipo-Niosomes particles indicated size of 200 nm and a dispersion index of 0.32 with a Zeta potential of -24.56 mv. Furthermore, no chemical interaction between drugs and nano-carriers was observed. The cell viability of adipose mesenchymal stem cells exposed to 50 µg/ml of free AmB, free TEO, and free AmB/TEO was 13.4, 58, and 36.9%, respectively. Whereas the toxicity of the encapsulated formulas of these drugs was 48.9, 70.8, and 58.3% respectively. The toxicity of nanoparticles was very low (8.5%) at this concentration. Fluorescence microscopic images showed that the antifungal activity of Lipo-AmB/ TEO was significantly higher than free formulas of AmB, TEO, and AmB/TEO. CONCLUSION: In this study, we investigated the efficacy of the TEO/AmB combination, in both free and encapsulatedniosomal form, on the growth of fungal infected-hASCs. The results showed that the AmB/TEO-loaded Lipo-Niosomes can be suggested as a new efficient anti-fungal nano-system for patients treated with hASCs.

Psychometric Properties of the Intensive Care Unit Nurses' Perceptions Questionnaire of Self-Performance With Families of Critically Ill Patients (Persian Version).

BACKGROUND AND PURPOSE: Nurses' self-perception of their performance toward family members of patients is one of the most important issues in predicting family adaptive behaviors. This study analyzed the psychometric properties of the Persian version of intensive care unit (ICU) nurses' perceptions questionnaire of self-performance with families of critically ill patients. METHODS: Among 135 intensive care nurses, to determine face validity, 10 nurses were asked to comment on, comprehensibility, grammar, and writing of items. Exploratory factor analysis was used to assess construct validity. RESULTS: The intra-cluster correlation coefficient (ICC) was 0.82 and Cronbach's alpha was 0.74. Exploratory factor analysis showed the first nine related factors have 65.22% variance. CONCLUSION: Persian version of ICU nurses' perceptions of self-performance with families of critically ill patients had good reliability and validity.

Psychometric Evaluation of the Sex After Myocardial Infarction Knowledge Test in Iranian Context.

PURPOSE: To translate, adapt, and assess the psychometric properties of the Sex After MI Knowledge Test in Iranian context (where MI is myocardial infarction). DESIGN AND METHODS: A cross-sectional descriptive survey was performed. The sample comprised 250 patients with MI. Confirmatory factor analysis was applied to extract three indicators. FINDINGS: The Sex After MI Knowledge Test indicated good reproducibility (Cronbach's α = .76, Intraclass correlation (ICC) = 0.729, CI = 0.7280-0.781, p < .001 ICC: Intraclass correlation). Nonnormed and normed fit indices (FI) were 0.89, and incremental and comparative FIs were 0.90. Goodness-of-fit index (GFI) and adjusted GFI were below the criteria. After a varimax rotation, the first six items of the instrument explained 58.71% of total variance. PRACTICE IMPLICATIONS: The instrument showed acceptable psychometric properties in terms of construct validity and internal consistency. The instrument might be used to stimulate conversations patients with MI regarding sexual knowledge and concerns.