Application of Nanoparticles as New Therapeutic Methods on Monitoring and Treating Obesity: a Systematic Review

Introduction: Nowadays, obesity has become a major global health challenge and it is closely linked with many metabolic disorders like diabetes and hypertension. Although various types of drugs have been developed, the prevalence of obesity is increasing worldwide. One of the effective way to treat obesity and prevent metabolic disorders coming after, is using nanoparticles as new therapeutic methods.  This study reviewed nanoparticles effects on monitoring and treating obesity. Methods and Results: In this systematic review, based on PRISMA guidelines, two persons independently searched MeSH terms “nanoparticles”, “drugs” and “obesity” and some other relevant terms in databases including PubMed, Medline, Scopus, and Cochrane library up to July 2017, and all the articles with considered inclusion criteria were added to the study. 145 articles were obtained by primary searching. After removing 12 irrelevant and 57 duplicate articles, 76 with inclusion criteria were added to this study. Nanoparticles could be used on both monitoring and treating obesity. These nanoceria when conjugated with antibodies are used for monitoring proteins involve in inflammation and insulin signaling without cell lysis. For example, due to TNF- α inflammatory cytokine that has an important role in insulin resistance in obesity, these nanoceria can be applied on monitoring some proteins like multiple kinases that ameliorate insulin resistance in obesity. Drug delivery via nanoparticles made it more possible to have better effects on regulating lipase cycle in adipose cells and tissues. Furthermore, application of nanoparticles conjugated with some agents can affect intracellular signaling or mechanisms in order to treat obesity. For example, silica nanoparticle has anti-brown adipogenic effect via regulation of p38 phosphorylation which involves in obesity. Conclusions: Application of nanoparticles increases the accessibility of adipose targeting cells. these nanoceria might be used to detect and treat many metabolic disorders like obesity. Producing more efficient and complicated nanoparticles in sizes depended manner, provides more opportunities to access better on targeted cells for treatment, however,  their side effects on normal cells should be considered

Synthesis, characterization, molecular docking studies and biological evaluation of some novel hybrids based on quinazolinone, benzofuran and imidazolium moieties as potential cytotoxic and antimicrobial agents

Objective(s): Hybridization of bioactive natural and synthetic compounds is one of the most promising novel approaches for the design of hit and lead compounds with new molecular structures. In this investigation, a series of novel hybrid structures bearing quinazolinone, benzofuran and imidazolium moieties were designed and synthesized. Materials and Methods:Novel hybrid compounds were prepared and their structures were characterized by spectral and analytical data. In order to evaluate the biological activities, the synthesized hybrid compounds were studied for in vitro antibacterial activity against three Gram positive bacteria (Staphylococcus aureu, Bacillus subtilis, Listeria monocitogenes) and three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella entritidis) and also, Candida albicans as one yeast-like fungi strain. Cytotoxic activities of the synthesized compounds were also evaluated by the MTT assay in the human breast cancer cell line (MCF-7) and finally docking studies of cytotoxic derivatives were performed on aromatase enzyme. Results:The results of antimicrobial activity showed that compound 14e, with two halogen atoms on quinazolinone and benzofuran was the most active against all the tested strains of microorganisms with the MIC value 16-128 µg/ml. Some of the tested compounds showed good cytotoxicity on MCF-7, and compound 14c with IC50=0.59 micromolar (μM) was found to be the most cytotoxic compound among the studied hybrid derivatives. The docking analysis showed acceptable binding interactions for these compounds. Conclusion: Based on the obtained results, the hybrid derivatives of quinazolinone, benzofuran and imidazolium could be regarded as efficient candidates for further molecular developments of anticancer and antimicrobial agents

Recombinant expression and purification of functional vascular endothelial growth factor-121 in the baculovirus expression system

AbstractObjectiveTo express human vascular endothelial growth factor121 (VEGF121) in insect cells.MethodsA gene construct containing VEGF was cloned in the pFastBac-HTA vector, followed by transformation in DH10BAC. The recombinant bacmid was then extracted, and transfected into Sf9 insect cells. The transfected cells were harvested, and then VEGF expression was confirmed by western blotting using specific antibodies. The tube formation assay was used for functional assessment of VEGF.ResultsOur results showed that VEGF could be successfully expressed in the baculovirus system. Purified VEGF was able to stimulate in vitro tube formation of human endothelial cells.ConclusionsResults from this study demonstrated that the recombinantly-produced VEGF can be considered as a promising candidate for therapeutic purposes

High-levelexpression of functional recombinant human coagulation factor VII in insect cells

Abstract: Recombinant coagulation factor VII (FVII) is used as a potential therapeutic intervention in hemophilia patients who produce antibodies against the coagulation factors. Mammalian cell lines provide low levels of expression, however, the Spodoptera frugiperda Sf9 cell line and baculovirus expression system are powerful systems for high-level expression of recombinant proteins, but due to the lack of endogenous vitamin K-dependent carboxylase, expression of functional FVII using this system is impossible. In the present study, we report a simple but versatile method to overcome the defect for high-level expression of the functional recombinant coagulation FVII in Sf9 cells. This method involves simultaneous expression of both human γ-carboxylase (hGC) and human FVII genes in the host. It may be possible to express other vitamin K-dependent coagulation factors using this method in the future. Keywords: Baculovirus; γ-carboxylase; Coagulation FVII; Factor VII; Insect cel

Optimization of the Expression of DT386-BR2 Fusion Protein in Escherichia coli using Response Surface Methodology

Background: The aim of this study was to determine the best condition for the production of DT386-BR2 fusion protein, an immunotoxin consisting of catalytic and translocation domains of diphtheria toxin fused to BR2, a cancer specific cell penetrating peptide, for targeted eradication of cancer cells, in terms of the host, cultivation condition, and culture medium. Materials and Methods: Recombinant pET28a vector containing the codons optimized for the expression of the DT386-BR2 gene was transformed to different strains of Escherichia coli (E. coli BL21 DE3, E. coli Rosetta DE3 and E. coli Rosetta-gami 2 DE3), followed by the induction of expression using 1 mM IPTG. Then, the strain with the highest ability to produce recombinant protein was selected and used to determine the best expression condition using response surface methodology (RSM). Finally, the best culture medium was selected. Results: Densitometry analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the expressed fusion protein showed that E. coli Rosetta DE3 produced the highest amounts of the recombinant fusion protein when quantified by 1 mg/ml bovine serum albumin (178.07 μg/ml). Results of RSM also showed the best condition for the production of the recombinant fusion protein was induction with 1 mM IPTG for 2 h at 37°C. Finally, it was established that terrific broth could produce higher amounts of the fusion protein when compared to other culture media. Conclusion: In this study, we expressed the recombinant DT386-BR2 fusion protein in large amounts by optimizing the expression host, cultivation condition, and culture medium. This fusion protein will be subjected to purification and evaluation of its cytotoxic effects in future studies

Artificial Blood Substitutes: First Steps on the Long Route to Clinical Utility

The 21st century is challenging for human beings. Increased population growth, population aging, generation of new infectious agents, and natural disasters are some threatening factors for the current state of blood transfusion. However, it seems that science and technology not only could overcome these challenges but also would turn many human dreams to reality in this regard. Scientists believe that one of the future evolutionary innovations could be artificial blood substitutes that might pave the way to a new era in transfusion medicine. In this review, recent status and progresses in artificial blood substitutes, focusing on red blood cells substitutes, are summarized. In addition, steps taken toward the development of artificial blood technology and some of their promises and hurdles will be highlighted. However, it must be noted that artificial blood is still at the preliminary stages of development, and to fulfill this dream, ie, to routinely transfuse artificial blood into human vessels, we still have to strengthen our knowledge and be patient

Formulation of Herbal Gel of Antirrhinum majus Extract and Evaluation of its Anti- Propionibacterium acne Effects

Background: Antirrhinum majus contains aurone with excellent antibacterial and antifungal activities. In addition, visible light activates the endogenous porphyrins of Propionibacterium acne, which results in bacterial death. Therefore, considering the above-mentioned facts, the aim of the present study was to prepare a topical herbal gel of A. majus hydroalcoholic extract and to evaluate its antiacne effects with or without blue light combination as an activator of the porphyrins. Materials and Methods: Antibacterial activity of the shoot or petal extracts was evaluated by disc diffusion method and the minimum inhibitory concentration (MIC) was calculated. Various gel formulations were developed by the Experimental Design software. The obtained gel formulations were prepared and tested for pharmaceutical parameters including organoleptic features, pH, viscosity, drug content, and release studies. Finally, the antibacterial activity was evaluated against (P. acnes) with or without blue light. Results: The MIC of the extracts showed to be 0.25 μg/ml. Evaluation of the gel formulation showed acceptable properties of the best formulation in comparison to a gel in the market. Pharmaceutical parameters were also in accordance with the standard parameters of the marketed gel. Furthermore, statistical analyses showed significant antibacterial effect for gel when compared to negative control. However, combination of blue light with gel did not show any significant difference on the observed antibacterial effect. Conclusion: Because of the statistically significant in vitro antiacne effects of the formulated gel, further clinical studies for evaluation of the healing effects of the prepared gel formulation on acne lesions must be performed

Theoretical design of a new chimeric protein for the treatment of breast cancer

p28 and NRC peptides are two anticancer peptides with various mechanisms have shown to be effective against breast cancer. Therefore, it seems that construction of a chimeric protein containing the two peptides might cause synergistic cytotoxic effects. However, since the two peptides bear opposite charges, production of a chimeric protein in which the two moieties do not intervene each other is difficult. In this study, our goal was to find a suitable peptide linker for the new chimeric protein in a manner that none of the peptides intervene the other’s function. We selected some linkers with different characteristics and lengths and created a small library of the chimeric proteins harboring these linkers. Homology modeling and molecular dynamic simulation revealed that (PA)5P and (EAAAK)3 linkers can separate the p28 and NRC peptides effectively. Thus, the chimeric protein linked with (PA)5P or (EAAAK)3 linkers might show synergistic and stronger anticancer effects than the separate peptide moieties because they could exert their cytotoxic effects freely which is not influenced by the other part

HESA-A Exerts Its Cytoprotective Effects through Scavenging of Free Radicals: An in Vitro Study

Background: Natural medicines have been recently considered more reasonable for human use most notably due to their safety and tolerance. HESA-A is a marine-originated herbal medicine with a variety of healing effects. However, its exact biological mechanism is not clear. The present study aimed at the evaluation of the HESA-A antioxidant effect.Methods: Chinese hamster ovary (CHO) and human embryonic kidney (HEK293T) cells were treated with different concentrations of HESA-A and H2O2 followed by cell proliferation assays. The antioxidant effect of the HESA-A preparations was evaluated by an antioxidant assay kit.Results: The viability of CHO and HEK293T cells were about 89% following their incubation with 100 and 200 ng/ml HESA-A, respectively for 1.5 hrs. However, when the cells were incubated with concentrations of 300 ng/ml or more, the cell viability significantly decreased to 48% compare to the control cells. The cytotoxic effects of H2O2 were observed after 2 hrs of incubation of the HEK293T or CHO cells with 10 mM or 16 mM H2O2, respectively, while in the presence of HESA-A the cytotoxicity was significantly decreased. Antioxidant assay revealed that HESA-A scavenges free radicals. Conclusion: The findings indicate that HESA-A had cytoprotective effects in vitro, and that such an effect might be due to antioxidant properties

The Expression of Heme Oxygenase-1 in Human-Derived Cancer Cell Lines

Background: Heme oxygenase-1 (HO-1) is a cytoprotective and antiapoptotic enzyme, which has been involved in maintaining cellular homeostasis, and plays an important protective role by modulating oxidative injury. Up-regulation of (HO-1) has contributed to tumorogenicity of some cancers. In this study we investigated the expression pattern of the HO-1, in five different human-derived cancer cell lines with high incidence in Iran. Methods: Total cell RNA were extracted from HepG2 (hepato carcinoma), A549 (lung adenocarcinoma), MCF-7 (breast cancer), K562 (myeloid leukemia) and LS174T (colon cancer) cell lines. Human embryonic kidney (HEK293) cell line was used as a control. cDNAs were synthesized and expression of HO-1 was examined using RT-PCR. Results: The expression of HO-1 was not detected in the control cell line (HEK293), but it was observed to express following ultraviolet (UV) exposure indicating that HO-1 is not constantly expressed. The examined cancer cell lines constitutively expressed different variety of HO-1 on mRNA level. Strong expression of HO-1 was observed in HepG2, MCF-7 and A549 cells. A moderate expression of HO-1 was observed in K562 cells, and LS174T cells showed no expression of HO-1. Conclusion: Heme oxygenase-1 could be considered as a new marker in the diagnosis of some cancers, especially hepatomacarcinoma. Our results also suggest that up-regulation of HO-1 may contribute to tumorogenicity of some cancers. Therefore, the combination of gene-silencing effect of HO-1 and chemo-therapy might be considered as a new modality for the treatment of cancers in which the expression HO-1 is up-regulated