Quantitative,high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans

Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypomethylation while those outside CpG islands showed mid-high methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period.Key words: cord blood, birth weight, folic acid, homocysteine, BeadArray, hierarchical clustering, Illumina     

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.     

Increasing the expression of programmed death ligand 2 (PD-L2) but not 4-1BB ligand in colorectal cancer cells

Molecular Biology Reports - Immune checkpoint (ICP) molecules modulate the immune response by either inducing or preventing T cell activation. Over-expression of some ICPs on malignant cells has...     

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...     

Opportunistic Fungal Infections in the Epidemic Area of COVID-19: A Clinical and Diagnostic Perspective from Iran

Mycopathologia - The coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China, in late 2109, and has rapidly spread around the world. Until May 25, 2020, there were 133,521 confirmed...     

Comparison of Trace Element Concentrations in Ambient Air of Industrial and Residential Areas in Tehran City

Tehran is densely populated possessing unhealthy and polluted air. There are 22 municipality districts in Tehran, and considerable numbers of industries are located within each district. Due to adverse environmental and health effects of trace elements in urban air, this study has been carried out to measure and compare concentration of trace elements including Ag, As, Br, Ce, Co, Cr, Cs, Cu, Mn, Hf, La, Sb, Sc, Sm, Th, and Zn in industrial (district 21) and residential (district 22) areas. For this purpose, total suspended particles were collected in two different time intervals in the year 2008. As a result, maximum and minimum concentrations in residential area associated with Mn (2.9 μg/m³) and Hf (2.92 × 10⁻⁴ μg/m³), respectively. Also, in industrial sites, these concentrations are higher for Mn (4.79 × 10⁻¹ μg/m³) and Hf (6.65 × 10⁻⁴ μg/m³). The concentrations of Mn (2.07 μg/m³) and Hf (7.46 × 10⁻⁴ μg/m³) in traffic zone are close to residential values. General, concentrations of Ce, Co, Cs, La, Sc, Sm, Th, Br, and Hf in industrial area were higher than in residential area. The source of these elements in Tehran's air is mainly anthropogenic. According to the achieved results, the concentration levels of As, Cr, and Zn were close together in both residential and industrial zones. Therefore, these elements could have been originated from natural sources. Also, results show that levels of Ag, Mn, Sb, and Cu in residential area were higher than in industrial area. Finally, obtained data indicated that the trends of average concentration of trace elements in industrial area (from low to high) follow as Hf<Cs<Sm<Th<La<Ce<Sc<Co<Ag<As<Sb<Cr<Br<Zn<Cu<Mn and, in residential area, are in order of Hf<Cs<La<Th<Ce<Sc<Sm<Co<As<Ag<Br<Sb<Cr<Zn<Cu<Mn.     

In Vitro Interaction of Geldanamycin with Triazoles and Echinocandins Against Common and Emerging Candida Species

Mycopathologia - The aim of this study was to determine the in vitro interactions of geldanamycin (Hsp90-inhibitor) with triazoles and echinocandins against common and emerging Candida species....     

Mesenchymal stem cells as the game-changing tools in the treatment of various organs disorders: Mirage or reality?

Recently a growing attention in scientific community has been gathered on potential application of mesenchymal stem cells (MSCs) in various fields of medicine. Owing to the fact that they can be easily isolated from different sources, and simply proliferated in large quantities while keeping their original biological characteristics, they can be successfully used as cell-based therapeutics. Engineering MSCs and other type of stem cells to be carriers of therapeutic agents is a new tactic in the targeted gene and cell therapy of cancers and degenerative diseases. Various useful properties of MSCs including tropism toward tumor/injury site(s), weakly immunogenic, production of anti-inflammatory molecules, and safety against normal tissues have made them prone for regenerative medicine, targeted therapy and treating injured tissues, and immunological abnormalities. In this review, we introduce latest advances, methods, and applications of MSCs in gene therapy of various malignant organ disorders. Additionally, we will cover the problems and challenges which researchers have faced with when trying to translate their basic experimental findings in MSCs research to clinically applicable therapeutics.