Three-dimensional differentiation of adipose-derived mesenchymal stem cells into insulin-producing cells

The aim of this study is to evaluate the collagen/hyaluronic acid (Col/HA) scaffold effect on the differentiation of insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ASCs). In this experimental study, ASCs were cultured and seeded in a Col/HA scaffold (3D culture) and then treated with induction media. After induction, the presence of IPCs was evaluated using gene expression (PDX-1, GLUT-2 and insulin) analysis and immunocytochemistry, while functional maturity was determined by measuring insulin release in response to low- and high-glucose media. The induced IPCs were morphologically similar to pancreatic islet-like cells. Expression of the islet-associated genes PDX-1, GLUT-2 and insulin genes in 3D-cultured cells was markedly higher than the 2D-cultured cells exposure differentiation media. Compared to the 2D culture of ASCs-derived IPCs, the insulin release from 3D ASCs-derived IPCs showed a nearly 4-fold (p?<?0.05) increase when exposed to a high glucose (25 mmol) medium. The percentage of insulin-positive cells in the 3D experimental group showed an approximately 4-fold increase compared to the 2D experimental culture cells. The results of this study demonstrated that the COL/HA scaffold can enhance the differentiation of IPCs from rat ASCs.     

Co-delivery of miRNA-15a and miRNA-16–1 using cationic PEGylated niosomes downregulates Bcl-2 and induces apoptosis in prostate cancer cells

Biotechnology Letters - Tumor suppressor miRNAs, miR-15a and miR-16–1, with high-specificity and oncogenic targeting of Bcl-2, can target tumor tissues. Disadvantages of the clinical...     

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.     

A new ATP7B gene mutation with severe condition in two unrelated Iranian families with Wilson disease

Wilson disease is associated with a defect in copper metabolism and caused by different mutations in ATP7B gene. The aim of this study was to determine mutation frequency of ATP7B exons 8 and 14 in Wilson disease patients from the south of Iran. The exons 8 and 14 of ATP7B gene were analyzed in 65 unrelated Wilson disease patients by Denaturing High Performance Liquid Chromatography, and samples with abnormal peak profile were selected for direct DNA sequencing. Seven out of 65 (10.8%) patients had mutations at exon 14, including c.3061-1G>A in four and c.3207C>A in three patients. In addition, four different mutations were identified at exon 8 of six patients (9.2%). Three of these mutations have been previously reported, including c.2304delC in two patients, c.2293G>A and 2304dupC each in one patient. Furthermore, a novel mutation, c.2335T>G (p.Trp779Gly), was identified in two unrelated patients. The patients with this novel mutation demonstrated severe neuropsychiatric condition. All together, 13 out of 65 (20%) patients had mutations within exons 8 and 14. We also identified a lower frequency of the most common mutations of exons 8 and 14 in the southern Iranian population.     

Evaluating Drug Resistant Mutations to HCV NS3 Protease Inhibitors in Iranian Naïve Patients

International Journal of Peptide Research and Therapeutics - Hepatitis C virus (HCV) is an important causative agent of acute and chronic hepatitis. The non-structural protein 3 (NS3) of HCV...     

Correction to: Variation in Blood and Colorectal Epithelia’s Key Trace Elements along with Expression of Mismatch Repair Proteins from Localized and Metastatic Colorectal Cancer Patients

Biological Trace Element Research - The original version of this article unfortunately contained a mistake. The name of “Ali Ghorbani Ranjbary” is now corrected in the author group of...     

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&nbsp;study&nbsp;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.