A new multi-epitope peptide vaccine induces immune responses and protection against Leishmania infantum in BALB/c mice.

Visceral leishmaniasis (VL) is a tropical and subtropical disease which is endemic in more than eighty countries around the world. Leishmania infantum is one of the main causative agents of VL disease. Currently, there is no approved-to-market vaccine for VL therapy. In this study, we evaluated cellular and humoral immune responses induced by our newly designed multi-epitope vaccine in BALB/c mice. Four antigenic proteins, including histone H1, sterol 24-c-methyltransferase (SMT), Leishmania-specific hypothetical protein (LiHy), and Leishmania-specific antigenic protein (LSAP) were chosen for the prediction of potential immunodominant epitopes. Moreover, to enhance vaccine immunogenicity, two toll-like receptors 4 (TLR4) agonists, resuscitation-promoting factors of Mycobacterium tuberculosis (RpfE and RpfB), were employed as the built-in adjuvants. Immunization with the designed multi-epitope vaccine elicited a robust Th1-type immune response, compared to other groups, as shown by increased levels of IL-2, IFN-γ, TNF-α, and IgG2a. Furthermore, a significant decrease was observed in Th-2-type-related cytokines such as IL-4 in immunized mice. The designed construct also induced a significant reduction in parasite load (p < 0.0001), conferring protection against L. infantum challenge. This study could be promising in gaining insight towards the potential of peptide epitope-based vaccines as effective protective approaches against Leishmania species.

Proteome-scale identification of Leishmania infantum for novel vaccine candidates: A hierarchical subtractive approach.

Vaccines are one of the most significant achievements in medical science. However, vaccine design is still challenging at all stages. The selection of antigenic peptides as vaccine candidates is the first and most important step for vaccine design. Experimental selection of antigenic peptides for the design of vaccines is a time-consuming, labor-intensive and expensive procedure. More recently, in the light of computer-aided biotechnology and reverse vaccinology, the precise selection of antigenic peptides and rational vaccine design against many pathogens have developed. In this study, the whole proteome of Leishmania infantum was analyzed using a pipeline of algorithms. From the set of 8045 proteins of L. infantum, sixteen novel antigenic proteins were derived using a hierarchical proteome subtractive analysis. These novel vaccine targets can be utilized as top candidates for designing the new prophylactic or therapeutic vaccines against visceral leishmaniasis. Significantly, all the sixteen novel vaccine candidates are non-allergen antigenic proteins that have not been used for the design of vaccines against visceral leishmaniasis until now.

Immunoinformatics-aided design of a potential multi-epitope peptide vaccine against Leishmania infantum.

Visceral leishmaniasis (VL) or kala-azar, the most severe form of the disease, is endemic in more than eighty countries across the world. To date, there is no approved vaccine against VL in the market. Recent advances in reverse vaccinology could be promising approach in designing the efficient vaccine for VL treatment. In this study, an efficient multi-epitope vaccine against Leishmania infantum, the causative agent of VL, was designed using various computational vaccinology methods. Potential immunodominant epitopes were selected from four antigenic proteins, including histone H1, sterol 24-c-methyltransferase (SMT), Leishmania-specific hypothetical protein (LiHy), and Leishmania-specific antigenic protein (LSAP). To enhance vaccine immunogenicity, two resuscitation-promoting factor of Mycobacterium tuberculosis, RpfE and RpfB, were employed as adjuvants. All the aforesaid segments were joined using proper linkers. Homology modeling, followed by refinement and validation was performed to obtain a high-quality 3D structure of designed vaccine. Docking analyses and molecular dynamics (MD) studies indicated vaccine/TLR4 complex was in the stable form during simulation time. In sum, we expect our designed vaccine is able to induce humoral and cellular immune responses against L. infantum, and may be promising medication for VL, after in vitro and in vivo immunological assays.

Application of nanoparticles in cancer detection by Raman scattering based techniques.

In vitro detection technique Raman spectroscopy (Rs), in one number times another Rs  based expert ways of art and so on, are useful instruments for cancer  discovery. top gave greater value to Raman spectroscopy  sers is a relatively new careful way for in vitro  and in vivo discovery that takes away bad points of simple Raman spectroscopy (Rs). Raman spectroscopy (RS) and in particular, multiple RS-based techniques are useful for cancer detection. Surface enhanced Raman spectroscopy (SERS) is a relatively new method for both in vitro and in vivo detection, which eliminates the drawbacks of simple RS. Using nanoparticles has elevated the sensitivity and specificity of SERS. SERS has the potential to increase sensitivity, specificity and spatial resolution in cancer detection, especially in cooperation with other diagnostic imaging tools such as magnetic resonance imaging (MRI) and PET-scan polyethylene terephthalate. Developing a hand held instrument for detecting cancer or other illnesses may also be feasible by using SERS. Frequently, novel nanoparticles are used in SERS. With a focus on nanoparticle utilization, we review the benefits of RS in cancer detection and related biomarkers. With a focus on nanoparticles utilizations, the benefits of RS in cancer detection and related biomarkers were reviewed. In addition, Raman applications to detect some of prevalent were discussed. Also more investigated cancers such as breast and colorectal cancer, multiple nanostructures and their possible special biomarkers, especially as SERS nano-tag have been reviewed. The main purpose of this article is introducing of most popular nanotechnological approaches in cancer detection by using Raman techniques. Moreover, have been caught up on detection and reviewed some of the most prevalent and also more investigated cancers such as breast, colorectal cancer, multiple intriguing nanostructures, especially as SERS nano-tag, special cancer biomarkers and related approaches. The main purpose of this article is to introduce the most popular nanotechnological approaches in cancer detection by using Raman techniques.

Tracing Tellurium and Its Nanostructures in Biology.

Tellurium (Te) is a semimetal rare element in nature. Together with oxygen, sulfur (S), and selenium (Se), Te is considered a member of chalcogen group. Over recent decades, Te applications continued to emerge in different fields including metallurgy, glass industry, electronics, and applied chemical industries. Along these lines, Te has recently attracted research attention in various fields. Though Te exists in biologic organisms such as microbes, yeast, and human body, its importance and role and some of its potential implications have long been ignored. Some promising applications of Te using its inorganic and organic derivatives including novel Te nanostructures are being introduced. Before discovery and straightforward availability of antibiotics, Te had considered and had been used as an antibacterial element. Antilishmaniasis, antiinflammatory, antiatherosclerotic, and immuno-modulating properties of Te have been described for many years, while the innovative applications of Te have started to emerge along with nanotechnological advances over the recent years. Te quantum dots (QDs) and related nanostructures have proposed novel applications in the biological detection systems such as biosensors. In addition, Te nanostructures are used in labeling, imaging, and targeted drug delivery systems and are tested for antibacterial or antifungal properties. In addition, Te nanoparticles show novel lipid-lowering, antioxidant, and free radical scavenging properties. This review presents an overview on the novel forms of Te, their potential applications, as well as related toxicity profiles.

Staphylokinase Enzyme: An Overview of Structure, Function and Engineered Forms.

BACKGROUND: One of the most important causes of death in the modern lifestyle is acute ischemic stroke, which is related to thrombosis in the blood vessels. Staphylokinase (SAK), a fibrinolytic agent, which is produced mainly by Staphylococcus aureus, is an indirect activator of plasminogen and belongs to the third generation of fibrinolytic enzymes. METHODS: Considering the very low level of production and immunogenicity concerns of natural SAK produced by Staphylococcus aureus, attempts have been made to produce recombinant SAKs with high production levels, more fibrinolytic activities and low immunogenicity. RESULTS AND CONCLUSION: In this review, we summarized a number of expression systems based on recombinant DNA technology and protein-engineering approaches, which have been developed for the production of engineered recombinant SAK molecules with higher fibrinolytic activities and lower antigenicity.

Modelface: an Application Programming Interface (API) for Homology Modeling Studies Using Modeller Software.

An interactive application, Modelface, was presented for Modeller software based on windows platform. The application is able to run all steps of homology modeling including pdb to fasta generation, running clustal, model building and loop refinement. Other modules of modeler including energy calculation, energy minimization and the ability to make single point mutations in the PDB structures are also implemented inside Modelface. The API is a simple batch based application with no memory occupation and is free of charge for academic use. The application is also able to repair missing atom types in the PDB structures making it suitable for many molecular modeling studies such as docking and molecular dynamic simulation. Some successful instances of modeling studies using Modelface are also reported.

Neuroprotective and restorative effects of the brain-derived neurotrophic factor in retinal diseases.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin proposed to be implicated in ameliorating the course of some neurodegenerative disorders. Given the fact that retina is considered as an out-pouching of the central nervous system, its related diseases have long been suggested to receive protective influence from this signaling molecule. The role of BDNF in retinal neurorestoration, neuroprotection and oxidative stress has extensively been tested over the past two decades. Nonetheless, almost the entire related literature root in animal studies and clinical research on this topic is lacking. Although much of the evidence have validated the protective properties of BDNF against various retinal cell diseases, bringing such insights into clinical context would depend on further well-designed research. The present review is an attempt to categorize and discuss the available evidence with regard to the BDNF and retinal diseases.

Antifungal activity of biogenic tellurium nanoparticles against Candida albicans and its effects on squalene monooxygenase gene expression.

In this study, we evaluated the antifungal activity of biogenic tellurium nanoparticles (Te NPs) against Candida albicans (ATCC14053). In addition, the effect of these biogenic NPs on squalene monooxygenase activity and the squalene monooxygenase gene (ERG1) expression level was evaluated. Squalene monooxygenase is an important enzyme involved in the synthesis of ergosterol, cholesterol, and phytosterols. Because of the importance of the noted compound, the squalene monooxygenase gene could be considered a good antifungal target. Results showed that biogenic Te NPs had antifungal effect against C. albicans. The minimal fungicidal concentration-minimal inhibitory concentration ratios of the biogenic Te NPs revealed that these NPs exhibited fungicidal effects against the test strain. The results of an enzyme assay using quantitative high-performance liquid chromatography showed squalene accumulation in C. albicans cells because of enzyme inhibition. Real-time PCR analysis showed an increase in the expression of the ERG1 gene in C. albicans cells, which were treated with Te NPs (0.2 mg/mL). It is conclution that Te NPs can inhibit the squalene monooxygenase enzyme, and, as a result, this inhibition phenomenon can cause an increase in the expression level of the ERG1 gene. This is the first report of the anti-Candida effect of biogenic Te NPs and its possible mechanisms.