Nanoconfined polymers: modelling and simulation approaches

In this article, application of molecular simulation methods for studying molecular pictures of nanoconfined polymers is reviewed and discussed. The simulation methods, covering a range from atomistic to systematically parameterised coarse-grained models, employed in the literature to study nanoconfined polymers are reviewed and their results are compared together. The effect of polymer–surface interactions, surface curvature and surface area on the alteration of polymer structure and dynamics from the unperturbed (bulk) polymer properties are discussed. The length scales over which the surface influences the polymer structure and dynamics and the magnitude of surface effect on dynamics deceleration in the interphase are addressed in terms of different local and global chain properties.     

Chemical disinfection of high-consequence transboundary animal disease viruses on nonporous surfaces

Disinfection is a critical part of the response to transboundary animal disease virus (TADV) outbreaks by inactivating viruses on fomites to help control infection. To model the inactivation of TADV on fomites, we tested selected chemicals to inactivate Foot and Mouth Disease virus (FMDV), African Swine Fever virus (ASFV), and Classical Swine Fever virus (CSFV) dried on steel and plastic surfaces. For each of these viruses, we observed a 2 to 3 log reduction of infectivity due to drying alone. We applied a modified surface disinfection method to determine the efficacy of selected disinfectants to inactivate surface-dried high-titer stocks of these three structurally different TADV. ASFV and FMDV were susceptible to sodium hypochlorite (500 and 1000 ppm, respectively) and citric acid (1%) resulting in complete disinfection. Sodium carbonate (4%), while able to reduce FMDV infectivity by greater than 4-log units, only reduced ASFV by 3 logs. Citric acid (2%) did not totally inactivate dried CSFV, suggesting it may not be completely effective for disinfection in the field. Based on these data we recommend disinfectants be formulated with a minimum of 1000 ppm sodium hypochlorite for ASFV and CSFV disinfection, and a minimum of 1% citric acid for FMDV disinfection.     

In silico analysis of six known Leishmania major antigens and in vitro evaluation of specific epitopes eliciting HLA-A2 restricted CD8 T cell response

Background

As a potent CD8⁺ T cell activator, peptide vaccine has found its way in vaccine development against intracellular infections and cancer, but not against leishmaniasis. The first step toward a peptide vaccine is epitope mapping of different proteins according to the most frequent HLA types in a population.

Methods and Findings

Six Leishmania (L.) major-related candidate antigens (CPB,CPC,LmsTI-1,TSA,LeIF and LPG-3) were screened for potential CD8⁺ T cell activating 9-mer epitopes presented by HLA-A*0201 (the most frequent HLA-A allele). Online software including SYFPEITHI, BIMAS, EpiJen, Rankpep, nHLApred, NetCTL and Multipred were used. Peptides were selected only if predicted by almost all programs, according to their predictive scores. Pan-A2 presentation of selected peptides was confirmed by NetMHCPan1.1. Selected peptides were pooled in four peptide groups and the immunogenicity was evaluated by in vitro stimulation and intracellular cytokine assay of PBMCs from HLA-A2⁺ individuals recovered from L. major. HLA-A2⁻ individuals recovered from L. major and HLA-A2⁺ healthy donors were included as control groups. Individual response of HLA-A2⁺ recovered volunteers as percent of CD8⁺/IFN-γ⁺ T cells after in vitro stimulation against peptide pools II and IV was notably higher than that of HLA-A2⁻ recovered individuals. Based on cutoff scores calculated from the response of HLA-A2⁻ recovered individuals, 31.6% and 13.3% of HLA-A2⁺ recovered persons responded above cutoff in pools II and IV, respectively. ELISpot and ELISA results confirmed flow cytometry analysis. The response of HLA-A2⁻ recovered individuals against peptide pools I and III was detected similar and even higher than HLA-A2⁺ recovered individuals.

Conclusion

Using in silico prediction we demonstrated specific response to LmsTI-1 (pool II) and LPG-3- (pool IV) related peptides specifically presented in HLA-A*0201 context. This is among the very few reports mapping L. major epitopes for human HLA types. Studies like this will speed up polytope vaccine idea towards leishmaniasis.     

Hybrid of niosomes and bio-synthesized selenium nanoparticles as a novel approach in drug delivery for cancer treatment

Molecular Biology Reports - The current study intends to investigate a novel drug delivery system (DDS) based on niosomes structure (NISM) and bovine serum albumin (BSA) which was...     

Potential antigen candidates for subunit vaccine development against Helicobacter pylori infection

Helicobacter pylori (H. pylori) is a resident bacterium in the stomach that accounts for 75% cases of gastric cancer. In this review, we comprehensively studied published papers on H. pylori vaccines using Google Scholar and NCBI databases to gather information about vaccines against H. pylori. Considering the pivotal roles of the enzyme urease (in production of NH₃ and neutralization of the acidic medium of the stomach), cytotoxin-associated gene A, and vacuolating cytotoxin A proteins in H. pylori infection, they could be the best candidates for the construction of recombinant vaccines. The outer membrane porins (Hop), blood group antigen-binding adhesin (BabA), sialic acid-binding adhesin (SabA), and outer inflammatory protein A, play significant roles in binding of bacterium to human gastric tissues, and because binding is the first step in bacterial fixation and colonization, these antigens also can be considered as suitable candidates for designing vaccines. Likely, other significant bacterial antigens, such as NapA (chemotactic factor for recruitment of human neutrophils and monocytes to the site of infection), duodenal ulcer promoting protein A (to promote duodenal ulcer), and Hsp60 (as a molecular chaperon for activation of urease enzyme), can be used in the construction of subunit vaccines. New vaccines in use currently, such as DNA vaccines and subunit vaccines, can efficiently replace the dead and attenuated vaccines. Nonetheless, the results show that urease enzyme is most used compared with bacterial components in the designing and construction of recombinant vaccines. The BabA and SabA antigens belong to the outer membrane porins family in H. pylori and are required for binding and fixation of the bacterium to the human gastric tissues.     

Improved cellular response on functionalized polypyrrole interfaces

Neuroregeneration strategies involve multiple factors to stimulate nerve regeneration. Neural support with chemical and physical cues to optimize neural growth and replacing the lesion neuron and axons are crucial for designing neural scaffolds, which is a promising treatment approach. In this study, polypyrrole polymerization and its functionalization at the interface developed by glycine and gelatin for further optimization of cellular response. Nanofibrous scaffolds were fabricated by electrospinning of polyvinyl alcohol and chitosan solutions. The electrospun scaffolds were polymerized on the surface by pyrrole monomers to form an electroactive interface for further applications in neural tissue engineering. The polymerized polypyrrole showed a positive zeta potential value of 57.5 ± 5.46 mV. The in vitro and in vivo biocompatibility of the glycine and gelatin-functionalized polypyrrole-coated scaffolds were evaluated. No inflammatory cells were observed for the implanted scaffolds. Further, DAPI nucleus staining showed a superior cell attachment on the gelatin-functionalized polypyrrole-coated scaffolds. The topography and tuned positively charged polypyrrole interface with gelatin functionalization is expected to be particularly efficient physical and chemical simultaneous factors for promoting neural cell adhesion.     

Importance of probiotics in the prevention and treatment of colorectal cancer

Colorectal cancer (CRC) remains one of the most common and deadly cancers. Intestinal gut microflora is important to maintain and contributes to several intestinal functions, including the development of the mucosal immune system, absorption of complex macromolecules, synthesis of amino acids/vitamins and the protection against pathogenic microorganisms. It is well known that the gut microbiota changes or dysbiosis may have an essential impact in the initiation and promotion of chronic inflammatory pathways and also have a profound different genetic and epigenetic alterations leading to dysplasia, clonal expansion, and malignant transformation. Probiotic bacteria has antitumor activity with various mechanisms such as nonspecific physiological and immunological mechanisms. This review evaluates the effects of microbiota and probiotics in clinical trials, in vitro and animal model studies that have explored how probiotic against cancer development and also discusses the possible immunomodulatory mechanisms. Several mechanisms alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host's immune response; antiproliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase; reduces the enteropathogenic complications before and after colon cancer surgery and improve diarrhea and it's have been able to create the integrity of gut mucosal and have stimulatory effects on the systemic immune system and prevent the CRC metastasis. Research in clinical trials encouraging findings that support a role of probiotics in CRC prevention and improve the safety and effectiveness of cancer therapy even though additional clinical research is still necessary.     

Biological evaluations of newly-designed Pt(II) and Pd(II) complexes using spectroscopic and molecular docking approaches

To perform biological evaluations of newly-designed Pt(II) and Pd(II) complexes, the present study was conducted with targeted protein human serum albumin (HSA) and HCT116 cell line as model of human colorectal carcinoma. The binding of Pt(II) and Pd(II) complexes to HSA was analyzed using fluorescence spectroscopy and molecular docking. The thermal stability and alterations in the secondary structure of HSA in the presence of Pt(II) and Pd(II) complexes were investigated using the thermal denaturation method and circular dichroism (CD) spectroscopy. The cytotoxicity of the Pt(II) and Pd(II) complexes was studied against the HCT116 cell line using MTT assay. The binding analysis revealed that the fluorescence findings were well in agreement with docking results such that there is only one binding site for each complex on HSA. Binding constants of 8.7?×?10³ M^?1, 2.65?×?10³ M^?1, 0.3?×?10³ M^?1, and 4.4?×?10³ M^?1 were determined for Pd(II) and Pt(II) complexes (I–IV) at temperature of 25?°C, respectively. Also, binding constants of 1.9?×?10³ M^?1, 15.17?×?10³ M^?1, 1.9?×?10³ M^?1, and 13.1?×?10³ M^?1 were determined for Pd(II) and Pt(II) complexes (I–IV) at temperature of 37?°C, respectively. The results of CD and thermal denaturation showed that the molecular structure of HSA affected by interaction with Pt(II) and Pd(II) complexes is stable. Cytotoxicity studies represented the growth suppression effect of the Pt(II) and Pd(II) complexes toward the human colorectal carcinoma cell line. Therefore, the results suggest that the new designed Pt(II) and Pd(II) complexes are well promising candidates for use in cancer treatment, particularly for human colorectal cancer.

Communicated by Ramaswamy H. Sarma     

Quercetin protects human granulosa cells against oxidative stress via thioredoxin system

Granulosa Cells (GCs) are sensitive to excessive production of reactive oxygen species (ROS). Quercetin (QUR) is a free radical scavenger which can alleviate oxidative stress through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) pathway and thioredoxin (Trx) system. We aimed to explore the probable protective role of QUR on cultured human GCs treated with hydrogen peroxide (H₂O₂) as an inducer of oxidative stress. MTT assay was applied for evaluating the cell cytotoxicity of QUR and H₂O₂. The rate of apoptotic cells and intracellular ROS generation were determined by Annexin V-FITC/PI staining and 2′-7′-dichlorodihydro?uorescein diacetate ?uorescent probes (DCFH-DA), respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blot analysis were used to evaluate the gene and protein expression of Nrf2 and kelch-like ech-associated protein 1 (Keap1)1. The Nrf2 and Trx activities were measured by Enzyme-linked Immunosorbent Assay (ELISA). The results indicated that QUR pretreatment can decrease ROS production and apoptosis induced by H₂O₂. In addition, QUR increased Nrf2 gene and protein expression, as well as its nuclear translocation. Moreover, in QUR-treated group, a lower level of Keap1 protein was observed, which was not reported as significant. The results also indicated a significant correlation between the expression of Nrf2 and Keap1 in QUR-treated group. Further, QUR protected GCs from oxidative stress by increasing Trx gene expression and activity. This study suggests that QUR as a supplementary factor may protect GCs from oxidative stress in diseases related to this condition.