Synthesis of cobalt-based magnetic nanoporous carbon core-shell molecularly imprinted polymers for the solid-phase extraction of phthalate plasticizers in edible oil.

In this work, cobalt magnetic nanoporous carbon (Co-MNPC) is employed as an alternative to intensively used Fe3O4 cores for the preparation of magnetic molecularly imprinted polymers (Co-MNPC@MIPs) for the first time. Co-MNPC was prepared by one-step carbonization of Zeolitic Imidazolate Framework-67 (ZIF-67). Compared with the traditional Fe3O4 core, Co-MNPC showed a high specific surface area and large pore volumes. The prepared adsorbents, which could be rapidly collected from a matrix by external magnetic field, were applied for solid-phase extraction of phthalate plasticizers in edible oil. Several requisite extraction parameters were optimized to achieve desired extraction performance. Under the optimum extraction conditions, Co-MNPC@MIPs displayed better performance than commercialized columns. An analysis method based on Co-MNPC@MIPs coupled with gas chromatography (GC) was established. The linear range was 1-150 µg mL-1, and the detection limit range was 0.010-0.025 µg mL-1. The spiked recovery rate of the five phthalate plasticizers was 81.6-102.2%, with a relative standard deviation of 3.25-12.02%. Finally, the proposed method showed good feasibility for phthalate plasticizer extraction from edible oil.

Identification of target gene and prognostic evaluation for lung adenocarcinoma using gene expression meta-analysis, network analysis and neural network algorithms.

BACKGROUND: Lung adenocarcinoma (LUAD) is a heterogeneous disease with poor survival in the advanced stage and a high incidence rate in the world. Novel drug targets are urgently required to improve patient treatment. Therefore, we aimed to identify therapeutic targets for LUAD based on protein-protein and protein-drug interaction network analysis with neural network algorithms using mRNA expression profiles. RESULTS: A comprehensive meta-analysis of selective non-small cell lung cancer (NSCLC) mRNA expression profile datasets from Gene Expression Omnibus were used to identify potential biomarkers and the molecular mechanisms related to the prognosis of NSCLC patients. Using the Network Analyst tool, based on combined effect size (ES) methods, we recognized 6566 differentially expressed genes (DEGs), which included 3036 downregulated and 3530 upregulated genes linked to NSCLC patient survival. ClueGO, a Cytoscape plugin, was exploited to complete the function and pathway enrichment analysis, which disclosed "regulated exocytosis", "purine nucleotide binding", "pathways in cancer", and "cell cycle" between exceptionally supplemented terms. Enrichr, a web tool examination, demonstrated "early growth response protein 1 (EGR-1)", "hepatocyte nuclear factor 4α (HNF4A)", "mitogen-activated protein kinase 14 (MAP3K14)", and "cyclin-dependent kinase 1 (CDK1)" to be among the most prevalent TFs and kinases associated with NSCLC. Our meta-analysis identified that MAPK1 and aurora kinase (AURKA) are the most obvious class of hub nodes. Furthermore, protein-drug interaction network and neural network algorithms identified candidate drugs such as phosphothreonine and 4-(4-methylpiperazin-1-yl)-n-[5-(2-thienylacetyl)-1,5-dihydropyrrolo[3,4-c]pyrazol-3-yl] benzamide and for the targets MAPK1 and AURKA, respectively. CONCLUSION: Our study has identified novel candidate biomarkers, pathways, transcription factors (TFs), and kinases associated with NSCLC prognosis, as well as drug candidates, which may assist treatment strategy for NSCLC patients.

Nanoliposomes as Vehicles for Astaxanthin: Characterization, In Vitro Release Evaluation and Structure.

Astaxanthin was encapsulated in nanoliposomes by a film dispersion-ultrasonic technique using soybean phosphatidyl choline. The astaxanthin-loaded nanoliposomes displayed advantages in the aspects of high encapsulation efficiency and less particle size with a remarkably homodisperse size distribution. Based on X-ray diffraction and differential scanning calorimetry the analysis, it has been demonstrated that there could be interactions of astaxanthin with the lipid bilayer, resulting in the forming of astaxanthin-loaded nanoliposomes. The thermal gravimetric analysis revealed that the thermal stability of astaxanthin after encapsulation in nanoliposomes was remarkably enhanced as compared to astaxanthin alone. Furthermore, encapsulation could greatly enhance the water dispersibility of astaxanthin. This study also confirmed that encapsulation of astaxanthin in nanoliposomes could be an effective way to supply astaxanthin continuously in the body. The effects of astaxanthin incorporation on structural changes of the liposomal membrane were investigated through steady-state fluorescence measurements. This study revealed that the incorporation of astaxanthin into the lipid bilayer decreased membrane fluidity, but increased micropolarity in the membrane within a certain range of astaxanthin concentrations. Additionally, it indicated that the encapsulation of astaxanthin in the lipid bilayer could be applied to modulate the structural properties of membranes.

Effects of Phytosterol Butyrate Ester on the Characteristics of Soybean Phosphatidylcholine Liposomes.

The nutritional and structural properties of phytosterols (PS)/phytosterol esters (PEs) facilitate their use as substitutes for cholesterol in liposome encapsulation systems designed for oral drugs and health products. The purpose of this study was to determine the effect of phytosterol butyrate ester (PBE) on the properties of liposomes. PBE was encapsulated within liposomes (approximately 60 nm) prepared using soybean phosphatidylcholine using the thin-film hydration method. There was no significant change in the average particle diameter and zeta potential of these liposomal vesicles corresponding to the increasing amounts of encapsulated PBE. The incorporation of PBE increased the polydispersity index (PDI) independent of concentration. Additionally, we observed that the storage stability of PBE liposomes with uniform particle size and approximately spherical shape vesicle was better at low concentration. The results of Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy showed that PBE was positioned at the water interface, which increased the order of hydrophobic alkyl chains in the lipid membranes. The incorporation of PBE led to an increase in the trans conformation of hydrophobic alkyl chain and consequently, the thermal stability of liposomes, which was confirmed by differential scanning calorimetry (DSC). The results of powder X-ray diffraction (XRD) analysis confirmed that PBE was present in an amorphous form in the liposomes. Additionally, the incorporation of PBE reduced the micropolarity of the lipid membrane. Thus, when preparing liposomes using thin-film hydration, the presence of PBE affected the characteristics of liposomes.

Molecular Understanding of Solvents and Glycitein Interaction during Extraction.

Hydrogen bonding interaction plays a crucial role in liquid systems. Methanol, ethanol, and acetone are the most commonly used solvents to extract isoflavones from soybeans. The structural and electronic properties of the molecular clusters of naturally occurring glycitein with solvents were investigated using the density functional theory method employing the B3LYP-D3/cc-pVTZ approach. The influence of the solvent was carried out by using the polarized continuum model (PCM). The geometry optimization, vibrational frequencies, and topological parameters have been assessed at the same level of theory. From the molecular structure and thermodynamic point of view, the most stable structures are formed by the interaction between the carbonyl group of glycitein and MeOH or EtOH. For acetone-glycitein, the strongest interaction is formed by the interaction of the hydroxyl group of glycitein with the carbonyl group of acetone. All the hydrogen bonds in the MeOH/EtOH/acetone-glycitein complexes are closed-shell interactions. This study can help increase the efficiency of extraction.

Prognostic Impact of Tissue Inhibitor of Metalloproteinase-1 in Non- Small Cell Lung Cancer: Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) is a multifunctional natural matrixin inhibitor that is generally considered a negative regulator of cancer metastasis. Clinical studies reporting the prognostic value of TIMP-1 in Non-small Cell Lung Cancer (NSCLC) are inconsistent. Therefore, the present study aimed to determine the prognostic impact of TIMP-1 expression in NSCLC. METHODS: Appropriate studies with full-text articles were identified in searches of the China National Knowledge Infrastructure (CNKI), Cochrane Library, PubMed, and Web of Science databases up to March 7, 2018. The pooled Hazard Ratio (HR) of overall survival with a 95% confidence interval (95% CI) was employed to assess the relationship between the expression of TIMP-1 and NSCLC patient survival. RESULTS: The meta-analysis comprised 40 studies including 3,194 patients. Study outcomes indicated that high TIMP-1 expression is independently associated with poor overall survival (HR: 1.60; 95% CI: 1.50, 1.69; P < 0.00001) with 61% of heterogeneity. In addition, we analyzed subgroups, including ethnicities, histological types, percentage of TIMP-1 expression levels, specimens, and tumor stage. All results were statistically significant. The outcome of our meta-analysis indicates that high expression levels of TIMP-1 are correlated with poor prognosis in patients with NSCLC. CONCLUSION: Expression levels of TIMP-1 represent a potential prognostic biomarker in NSCLC patients in addition to being a possible therapeutic target.

Exploring the Papillomaviral Proteome to Identify Potential Candidates for a Chimeric Vaccine against Cervix Papilloma Using Immunomics and Computational Structural Vaccinology.

The human papillomavirus (HPV) 58 is considered to be the second most predominant genotype in cervical cancer incidents in China. HPV type-restriction, non-targeted delivery, and the highcost of existing vaccines necessitate continuing research on the HPV vaccine. We aimed to explore the papillomaviral proteome in order to identify potential candidates for a chimeric vaccine against cervix papilloma using computational immunology and structural vaccinology approaches. Two overlapped epitope segments (23⁻36) and (29⁻42) from the N-terminal region of the HPV58 minor capsid protein L2 are selected as capable of inducing both cellular and humoral immunity. In total, 318 amino acid lengths of the vaccine construct SGD58 contain adjuvants (Flagellin and RS09), two Th epitopes, and linkers. SGD58 is a stable protein that is soluble, antigenic, and non-allergenic. Homology modeling and the structural refinement of the best models of SGD58 and TLR5 found 96.8% and 93.9% favored regions in Rampage, respectively. The docking results demonstrated a HADDOCK score of -62.5 ± 7.6, the binding energy (-30 kcal/mol) and 44 interacting amino acid residues between SGD58-TLR5 complex. The docked complex are stable in 100 ns of simulation. The coding sequences of SGD58 also show elevated gene expression in Escherichia coli with 1.0 codon adaptation index and 59.92% glycine-cysteine content. We conclude that SGD58 may prompt the creation a vaccine against cervix papilloma.

Viewing the Emphasis on State-of-the-Art Magnetic Nanoparticles: Synthesis, Physical Properties, and Applications in Cancer Theranostics.

Cancer-related mortality is a leading cause of death among both men and women around the world. Target-specific therapeutic drugs, early diagnosis, and treatment are crucial to reducing the mortality rate. One of the recent trends in modern medicine is "Theranostics," a combination of therapeutics and diagnosis. Extensive interest in magnetic nanoparticles (MNPs) and ultrasmall superparamagnetic iron oxide nanoparticles (NPs) has been increasing due to their biocompatibility, superparamagnetism, less-toxicity, enhanced programmed cell death, and auto-phagocytosis on cancer cells. MNPs act as a multifunctional, noninvasive, ligand conjugated nano-imaging vehicle in targeted drug delivery and diagnosis. In this review, we primarily discuss the significance of the crystal structure, magnetic properties, and the most common method for synthesis of the smaller sized MNPs and their limitations. Next, the recent applications of MNPs in cancer therapy and theranostics are discussed, with certain preclinical and clinical experiments. The focus is on implementation and understanding of the mechanism of action of MNPs in cancer therapy through passive and active targeting drug delivery (magnetic drug targeting and targeting ligand conjugated MNPs). In addition, the theranostic application of MNPs with a dual and multimodal imaging system for early diagnosis and treatment of various cancer types including breast, cervical, glioblastoma, and lung cancer is reviewed. In the near future, the theranostic potential of MNPs with multimodality imaging techniques may enhance the acuity of personalized medicine in the diagnosis and treatment of individual patients.

Designing of CD8+ and CD8+-overlapped CD4+ epitope vaccine by targeting late and early proteins of human papillomavirus.

BACKGROUND AND AIM: Human papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools. METHODS: Initially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins. Then, major histocompatibility complex class I-restricted CD8+ T-cell epitopes were selected based on their immunogenicity. In addition, epitope conservancy, population coverage (PC), and target receptor-binding affinity of the immunogenic epitopes were determined. Moreover, we predicted the possible CD8+, nested interferon gamma (IFN-γ)-producing CD4+, and linear B-cell epitopes. Further, antigenicity, allergenicity, immunogenicity, and system biology-based virtual pathway associated with cervical cancer were predicted to confirm the therapeutic efficiency of overlapped epitopes. RESULTS: Twenty-seven immunogenic epitopes were found to exhibit cross-protection (≥55%) against the 15 high-risk HPV strains (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, 68, 69, 73, and 82). The highest PC was observed in Europe (96.30%), North America (93.98%), West Indies (90.34%), North Africa (90.14%), and East Asia (89.47%). Binding affinities of 79 docked complexes observed as global energy ranged from -10.80 to -86.71 kcal/mol. In addition, CD8+ epitope-overlapped segments in CD4+ and B-cell epitopes demonstrated that immunogenicity and IFN-γ-producing efficiency ranged from 0.0483 to 0.5941 and 0.046 to 18, respectively. Further, time core simulation revealed the overlapped epitopes involved in pRb, p53, COX-2, NF-X1, and HPV45 infection signaling pathways. CONCLUSION: Even though the results of this study need to be confirmed by further experimental peptide sensitization studies, the findings on immunogenic and IFN-γ-producing CD8+ and overlapped epitopes provide new insights into HPV vaccine development.

Cancer Immunoinformatics: A Promising Era in the Development of Peptide Vaccines for Human Papillomavirus-induced Cervical Cancer.

Cancer immunoinformatics have led to new directions towards vaccine design from predicted potential epitope candidates, which are able to stimulate the correct cellular or humoral immune responses. They were employed to accomplish an advanced vaccine design through reverse vaccinology by replacing the whole organisms. In this review, computational tools play an essential role in evaluating multiple proteomes to identify and select the potential targeted epitopes or combinations of distinct epitopes, so that candidates may afford a rationale design competent for obtaining suitable cytotoxic T lymphocytes (CTL) or B cell-mediated immune responses. This review is a complete collection of the most beneficial online and user-friendly immunological tools, servers, and databases for the design and development of the peptide vaccine. The mechanism of major histocompatability (MHC)-restricted peptide presentation and how these tools support the vaccine development are also presented. The human papillomavirus (HPV) is taken as a model microbial strain for peptide vaccine design and its sensitization against HPV-induced cervical cancer is discussed.

Structure prediction and functional analyses of a thermostable lipase obtained from Shewanella putrefaciens.

Previous experimental studies on thermostable lipase from Shewanella putrefaciens suggested the maximum activity at higher temperatures, but with little information on its conformational profile. In this study, the three-dimensional structure of lipase was predicted and a 60 ns molecular dynamics (MD) simulation was carried out at temperatures ranging from 300 to 400 K to better understand its thermostable nature at the molecular level. MD simulations were performed in order to predict the optimal activity of thermostable lipase. The results suggested strong conformational temperature dependence. The thermostable lipase maintained its bio-active conformation at 350 K during the 60 ns MD simulations.

Determination of the acid values of edible oils via FTIR spectroscopy based on the OH stretching band.

A new method for determining the acid values (AVs) of edible oils based on the OH stretching band was developed. The oil sample was diluted with carbon tetrachloride and was placed in a quartz cuvette with a thickness of 1cm to record the FTIR spectrum. The peak at 3535cm(-1), which corresponds to the OH stretch of the carboxyl group in free fatty acids, together with the peak valley at 3508cm(-1) and the spectral data in the range of 3340-3390cm(-1) were used to determine the AV of the edible oil. The excellent linear relationship between the AVs measured in this work and those measured using a titration method, with a correlation coefficient (R) of 0.9929, indicates that the present procedure can be applied as an alternative to the classic method for determining the AVs of edible oils.

Current updates on computer aided protein modeling and designing.

Determination of the three dimensional (3D) structure of a protein can provide important details about its biological functions and mechanism of action. However, despite their significance, the precise three-dimensional structures of most of the proteins are not fully determined till date. The main focus of the current review article is to gain a better understanding of the structural features of the proteins using computational techniques, and their relationship with function. Protein modeling and design is the method aimed to fold a primary amino acids sequence into protein structure with the ultimate goal of designing novel function and behavior. Moreover, proteins can also be designed from scratch or by similarity with the known protein structure. In the current article we have tried to cover various computer aided protein modeling and designing via homology and ab initio modeling, folding study using Molecular Dynamics (MD) methods and in silico mutation analysis.

Novel restricted access materials combined to molecularly imprinted polymers for selective solid-phase extraction of organophosphorus pesticides from honey.

A novel restricted access materials (RAM) combined to molecularly imprinted polymers (MIPs), using malathion as template molecule and glycidilmethacrylate (GMA) as pro-hydrophilic co-monomer, were prepared for the first time. RAM-MIPs with hydrophilic external layer were characterized by scanning electron microscopy and recognition and selectivity properties were compared with the restricted access materials-non-molecularly imprinted polymers (RAM-NIPs) and unmodified MIPs. RAM-MIPs were used as the adsorbent enclosed in solid phase extraction column and several important extraction parameters were comprehensively optimized to evaluate the extraction performance. Under the optimum extraction conditions, RAM-MIPs exhibited comparable or even higher selectivity with greater extraction capacity toward six kinds of organophosphorus pesticides (including malathion, ethoprophos, phorate, terbufos, dimethoate, and fenamiphos) compared with the MIPs and commercial solid phase extraction columns. The RAM-MIPs solid phase extraction coupled with gas chromatography was successfully applied to simultaneously determine six kinds of organophosphorus pesticides from honey sample. The new established method showed good linearity in the range of 0.01-1.0 µg mL(-1), low limits of detection (0.0005-0.0019 µg mL(-1)), acceptable reproducibility (RSD, 2.26-4.81%, n = 6), and satisfactory relative recoveries (90.9-97.6%). It was demonstrated that RAM-MIPs solid phase extraction with excellent selectivity and restricted access function was a simple, rapid, selective, and effective sample pretreatment method.