Effects of K+ concentration on inhibition of protein synthesis by trimer and tetramer triphosphates of 2',5'-oligoadenylates in rabbit reticulocyte lysates

The inhibition of protein synthesis by trimer or tetramer triphosphates of 2',5'-oligoadenylates (2-5A) in rabbit reticulocyte lysates is dependent on the concentration of K+ in the assay mixture. Based on studies using mRNA-dependent rabbit reticulocyte lysates and the degradation of [3H] polyadenylated mRNA, the greater inhibitory effects of trimer or tetramer triphosphates at the higher K+ is shown to be due to a more active 2-5A-dependent endoribonuclease (RNase L).     

Impact of IFN-β and LIF overexpression on human adipose-derived stem cells properties

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells that their therapeutic effects in various diseases make them an interesting tool in cell therapy. In the current study, we aimed to overexpress interferon-β (IFN-β) and leukemia inhibitory factor (LIF) cytokines in human ADSCs to evaluate the impact of this overexpression on human ADSCs properties. Here, we designed a construct containing IFN-β and LIF and then, transduced human adipose-derived stem cells (hADSCs) by this construct via a lentiviral vector (PCDH-513B). We assessed the ability of long-term expression of the transgene in transduced cells by western blot analysis and enzyme-linked immunosorbent assay techniques on Days 15, 45, and 75 after transduction. For the evaluation of stem cell properties, flow cytometry and differentiation assays were performed. Finally, the MTT assay was done to assess the proliferation of transduced cells compares to controls. Our results showed high-efficiency transduction with highest expression rates on Day 75 after transduction which were 70 pg/ml for IFN-β and 77.9 pg/ml for LIF in comparison with 25.60 pg/ml and 27.63 pg/ml, respectively, in untransduced cells (p = .0001). Also, transduced cells expressed a high level of ADSCs surface markers and successfully differentiated into adipocytes, chondrocytes, neural cells, and osteocytes besides the preservation rate of proliferation near untreated cells (p = .88). All in all, we successfully constructed an hADSC population stably overexpressed IFN-β and LIF cytokines. Considering the IFN-β and LIF anti-inflammatory and neuroprotective effects as well as immune-regulatory properties of hADSCs, the obtained cells of this study could be subjected for further evaluations in experimental autoimmune encephalomyelitis mice model.     

Trace Element Level in Different Tissues of <Emphasis Type="Italic">Rutilus frisii kutum</Emphasis> Collected from Tajan River,Iran

Tajan River is among the most significant rivers of the Caspian Sea water basin. In this study, the concentration of Cr, Cu, Fe, Mn, Ni, Pb, Cd, and Zn were determined in brain, heart, liver, gill, bile, and muscle of Rutilus frisii kutum which has great economic value in the Mazandaran state. Trace element levels in fish samples were analyzed by means of atomic absorption spectrometry. Nearly all non-essential metals levels (Ni, Pb, Cd) detected in tissues were higher than limits for fish proposed by FAO/WHO, EU, and TFC. Generally, non-essential metals (Ni, Pb) were so much higher in muscle than the essential metals (Cu, Zn, and Mn) except Fe, which was higher than other metals in nearly all parts, except in gills. Fe distribution pattern in tissues was in order of heart > brain > liver > muscle > bile > gill. Distribution patterns of metal concentrations in the muscle of fish as a main edible part followed the sequence: Fe > Pb > Ni > Cu > Mn > Zn > Cd.     

Cloning,expression and dynamic simulation of TRYP6 from <Emphasis Type="Italic">Leishmania major</Emphasis> (MRHO/IR/75/ER)

Leishmania, a digenetic protozoan parasite causes severe diseases in human and animals. Efficient evasion of toxic microbicidal molecules, such as reactive oxygen species and reactive nitrogen species is crucial for Leishmania to survive and replicate in the host cells. Tryparedoxin peroxidase, a member of peroxiredoxins family, is vital for parasite survival in the presence of antioxidant, hence it is one of the most important molecules in Leishmania viability and then, it may be an appropriate goal for challenging against leishmaniasis. After cloning and sub-cloning of TRYP6 from Leishmania major (MRHO/IR/75/ER), homology modeling of the LmTRYP6 was proposed to predict some functional property of this protein. The refined model showed that the core structure consists of a seven β stranded β-sheet and five α helices which are organized as a central 7-stranded β2-β1-β5-β4-β3-β6-β7 surrounded by 2-stranded β-hairpin, α helices A and D on one side, and α helices B, C and E on the other side. The peroxidatic active site is located in a pocket formed by the residue Pro45, Met46, Thr49, Val51, Cys52, Arg128, Met147 and Pro 148. The catalytic Cys52, located in the first turn of helix αB, is in van der Waals with a Pro45, a Thr49 and an Arg128 that are absolutely conserved in all known Prx sequences. In this study, an attractive molecular target was studied. These results might be used in designing of drugs to fight an important human pathogen.     

Mycobacterium avium paratuberculosis and Mycobacterium avium complex and related subspecies as causative agents of zoonotic and occupational diseases

Mycobacterium avium complex (MAC) and Mycobacterium avium paratuberculosis (MAP) cause zoonotic infections transmitted by birds and livestock herds. These pathogens have remained as serious economic and health threats in most areas of the world. As zoonotic diseases, the risk of development of occupational disease and even death outcome necessitate implementation of control strategies to prevent its spread. Zoonotic MAP infections include Crohn’s disease, inflammatory bowel disease, ulcerative colitis, sarcoidosis, diabetes mellitus, and immune-related diseases (such as Hashimoto’s thyroiditis). Paratuberculosis has classified as type B epidemic zoonotic disease according to world health organization which is transmitted to human through consumption of dairy and meat products. In addition, MAC causes pulmonary manifestations and lymphadenitis in normal hosts and human immunodeficiency virus (HIV) progression (by serotypes 1, 4, and 8). Furthermore, other subspecies have caused respiratory abscesses, neck lymph nodes, and disseminated osteomyelitis in children and ulcers. However, the data over the occupational relatedness of these subspecies is rare. These agents can cause occupational infections in susceptible herd breeders. Several molecular methods have been recognized as proper strategies for tracking the infection. In this study, some zoonotic aspects, worldwide prevalence and control strategies regarding infections due to MAP and MAC and related subspecies has been reviewed.     

Current information on the association of Helicobacter pylori with autophagy and gastric cancer

Helicobacter pylori (H. pylori) is a Gram-negative bacterium and causative agent of gastric cancer. H. pylori induce defective autophagy or inhibit it by means of CagA and vacuolating cytotoxin A (VacA) toxins leading to the gastric cancer induction. Impaired or defective autophagy leads to the accumulation of cytotoxic materials, such as ROS and P62 that lead to increased mutations in the DNA, genome instability, and risk of cancer formation. H. pylori CagA may inhibit autophagy through the c-Met-PI3k/Akt-mTOR signaling pathway. However, VacA induces autophagy by some signaling pathways. In the gastric epithelial cells, VacA is a necessary and sufficient factor for the creation of autophagy. While CagA is a negative regulator of this phenomenon, the elimination of this gene from H. pylori has increased autophagy and the production of inflammatory cytokines is reduced. In gastrointestinal cancers, some of the microRNAs (miRNAs) act as tumor suppressors and some other are oncogenes by regulating various genes expression. H. pylori can also modify autophagy through a mechanism that includes the function of miRNAs. In autophagy, oncogenic miRNAs inhibit activation of some tumor suppressor signaling pathways (e.g., ULK1 complex, Beclin-1 function, and Atg4 messaging), whereas tumor suppressor miRNAs can block the activation of oncogenic signaling pathways. For instance, Beclin-1 is negatively regulated by miRNA-376b (oncogenic miRNA) and miRNA-30a (tumor suppressor miRNA). Similarly, Atg4 by miRNA-376b (oncogenic miRNA) and miRNA-101 (tumor suppressor miRNA). So, this apparent paradox can be explained as that both Beclin-1 and Atg4 play different roles in a particular cell or tissue.     

Deep analysis of N-cadherin/ADH-1 interaction: a computational survey

Due to the considerable role of N-cadherin in cancer metastasis, tumor growth, and progression, inhibition of this protein has been highly regarded in recent years. Although ADH-1 has been known as an appropriate inhibitor of N-cadherin in clinical trials, its chemical nature and binding mode with N-cadherin have not been precisely specified yet. Accordingly, in this study, quantum mechanics calculations were used to investigate the chemical nature of ADH-1. These calculations clarify the molecular properties of ADH-1 and determine its reactive sites. Based on the results, the oxygen atoms are suitable for electrophilic reactivity, while the hydrogen atoms that are connected to nitrogen atoms are the favorite sites for nucleophilic reactivity. The higher electronegativity of the oxygen atoms makes them the most reactive portions in this molecule. Molecular docking and molecular dynamics (MD) simulation have also been applied to specify the binding mode of ADH-1 with N-cadherin and determine the important residues of N-cadherin involving in the interaction with ADH-1. Moreover, the verified model by MD simulation has been studied to extract the free energy value and find driving forces. These calculations and molecular electrostatic potential map of ADH-1 indicated that hydrophobic and electrostatic interactions are almost equally involved in the implantation of ADH-1 in the N-cadherin binding site. The presented results not only enable a closer examination of N-cadherin in complex with ADH-1 molecule, but also are very beneficial in designing new inhibitors for N-cadherin and can help to save time and cost in this field.     

Protective effect of selenium on vincristine-induced peripheral neuropathy in PC12 cell line

Cytotechnology - Vincristine-induced peripheral neuropathy (VIPN) is the main side effect and major reason for neuropathic pain in cancer survivors treated with vincristine. Vincristine, a...     

Development of Hydrogels for Entrapment of Vitamin D3: Physicochemical Characterization and Release Study

In this study two carbohydrate biopolymers were used to entrap vitamin D3. In order to optimize the microencapsulation parameters, response surface methodology was applied to evaluate the effects of three independent variables (alginate percentage, vitamin: alginate weight ratio, and ultrasound time) on the efficiency of microencapsulation and loading capacity. According to the results, 0.23% alginate (W/V), 1: 5 weight ratio of vitamin D3: alginate, and 13.7 min ultrasound time were determined as the optimal conditions for obtaining maximum microencapsulation efficiency (92.86%) and loading capacity (30.1%). Then, the optimized carrier was coated by chitosan followed by the examinations of morphological characteristics, mean particle size, Fourier transform infrared (FTIR) spectrometry, in vitro release characteristics, and release modeling. Scanning electron microscopy examinations showed that the alginate and alginate-chitosan microcapsules had irregular and interlacing forms. The average particle sizes of alginate and alginate-chitosan were 11.3 and 23.3, respectively, which decreased to 9.8 and 14.0 μm after drying. Results of FTIR indicated a physical interaction between alginate and vitamin D3. The Weibull II model was found to be the best one to predict vitamin release behavior. The results of this study showed the potential application of developed carriers to encapsulate hydrophobic compounds.     

Rich spectroscopic and molecular dynamic studies on the interaction of cytotoxic Pt(II) and Pd(II) complexes of glycine derivatives with calf thymus DNA

Some amino acid derivatives, such as R-glycine, have been synthesized together with their full spectroscopic characterization. The sodium salts of these bidentate amino acid ligands have been interacted with [M(bpy)(H₂O)₂](NO₃)₂ giving the corresponding some new complexes with formula [M(bpy)(R-gly)]NO₃ (where M is Pt(II) or Pd(II), bpy is 2,2′-bipyridine and R-gly is butyl-, hexyl- and octyl-glycine). Due to less solubility of octyl derivatives, the biological activities of butyl and hexyl derivatives have been tested against chronic myelogenous leukemia cell line, K562. The interaction of these complexes with highly polymerized calf thymus DNA has been extensively studied by means of electronic absorption, fluorescence and other measurements. The experimental results suggest that these complexes positive cooperatively bind to DNA presumably via groove binding. Molecular dynamic results show that the DNA structure is largely maintained its native structure in hexylglycine derivative–water mixtures and at lower temperatures. The simulation data indicates that the more destabilizing effect of butylglycine is induced by preferential accumulation of these molecules around the DNA and due to their more negative free energy of binding via groove binding.