Mesenchymal stem cells engineered by modified polyethylenimine polymer for targeted cancer gene therapy,in vitro and in vivo

Cell-based delivery system is a promising strategy to protect therapeutic agents from the immune system and provide targeted delivery. Mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in cell-based gene therapy due to their unique features including tumor-tropic property and migratory ability. However, gene transfer into MSCs is limited due to low efficiency and cytotoxicity of carriers. In this study, we designed a novel delivery system based on polyethylenimine (PEI₂₅) to improve these features of carrier and transfect plasmid encoding TRAIL to MSCs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand of TNF family with selective effect on cancerous cells. Then, death induction and migration ability of TRAIL-expressing MSCs was studied in melanoma cells. The effect of engineered-MSCs as an antitumor vehicle was also investigated in mice bearing melanoma cells. Our findings indicated that heterocyclic amine derivative of PEI₂₅ showed significant improvement in MSCs viability determined by MTT assay and gene expression using fluorescent microscopy, flow cytometry, and Western blot analysis. We observed that engineered-MSCs could migrate toward and induce cell death in B16F0 cells in vitro. The single administration of TRAIL-expressing MSCs could delay tumor appearance and efficiently reduce tumor weights. Hematoxylin and eosin staining of tumor sections revealed extensive neoplastic cells necrosis. Furthermore, engineered-MSCs could migrate and localize to tumors sites within 5 days. Our results indicated that MSCs engineered by modified-PEI/TRAIL complexes could be considered as a promising cellular vehicle for targeted tumor suppression.     

Isolation,Selection and Characterization of Root-Associated Rock Phosphate Solubilizing Bacteria in Moroccan Wheat (Triticum aestivum L.)

Abstract

Phosphorus (P) is the most important macronutrient next to nitrogen for the growth and development of plants. But often unavailable for plants because of its high reactivity with many soil constituents. Thus, the use of phosphate solubilizing bacteria (PSBs) as biofertilizers seems to be an effective way to resolve the soluble phosphorus availability in soil. The present study was conducted to isolate and characterize rock PSB associated with the rhizosphere of wheat (Triticum aestivum L.) from fourteen different wheat-growing sites of Meknes region in Morocco. A total of one hundred ninety-eight (198) rock PSBs were isolated employing NBRIP medium amended with rock phosphate (RP), out of which five strains (A17, A81, B26, B106, and B107) were selected for their strong ability to dissolve RP and were tested in vitro for plant growth-promoting (PGP) traits including production of indole acetic acid (IAA), siderophores, hydrogen cyanide (HCN), and antifungal activity, as well as their response to the effect of extrinsic and intrinsic stress. The 16S rRNA gene sequencing and phylogenetic analysis identified these isolates belong to four genera, Pantoea, Pseudomonas, Serratia, and Enterobacter. The phosphate solubilization index (SI) of selected isolates ranged between 2.3 and 2.7, and the amount of solubilized phosphorus in the liquid medium varied from 59.1 to 90.2 µg mL^?1. HPLC analysis revealed that all the selected isolates produced multiple organic acids (oxalic, citric, gluconic succinic, and fumaric acids) from glucose under aerobic conditions. Except for the A81 strain, all selected isolates were able to produce IAA ranging between 2.9 and 21.2 µg mL^?1. The isolates A17, B26, and B107 showed the ability to produce siderophores ranging from 79.3 to 20.8% siderophore units. Only two strains (A17 and B26) were able to produce HCN. All selected isolates showed good resistance against different environmental stresses like 10–50?°C temperature, 0.5–2?g L^?1 salt concentration and 4.5–9?pH range, and against different antibiotics. The antagonistic effect showed that among the five selected strains, only two strains (B26 and A17) were able to suppress the growth of tested fungi. This study clearly indicates that our selected rock PSBs can be used as biofertilizers for grain crops after studying their interaction with the host crop and field evaluation.     

Aquaporin 4 in Traumatic Brain Injury: From Molecular Pathways to Therapeutic Target

Traumatic brain injury (TBI) is known as an acute degenerative pathology of the central nervous system, and has been shown to increase brain aquaporin 4 (AQP4) expression. Various molecular mechanisms affect AQP4 expression, including neuronal high mobility group box 1, forkhead box O3a, vascular endothelial growth factor, hypoxia-inducible factor-1 α (HIF-1 α) sirtuin 2, NF-κB, Malat1, nerve growth factor and Angiotensin II receptor type 1. In addition, inhibition of AQP4 with FK-506, MK-801 (indirectly by targeting N-methyl-d-aspartate receptor), inactivation of adenosine A2A receptor, levetiracetam, adjudin, progesterone, estrogen, V1aR inhibitor, hypertonic saline, erythropoietin, poloxamer 188, brilliant blue G, HIF-1alpha inhibitor, normobaric oxygen therapy, astaxanthin, epigallocatechin-3-gallate, sesamin, thaliporphine, magnesium, prebiotic fiber, resveratrol and omega-3, as well as AQP4 gene silencing lead to reduced edema upon TBI. This review summarizes current knowledge and evidence on the relationship between AQP4 and TBI, and the potential mechanisms involved.

     

Cytotoxicity,apoptosis inducing activity and Western blot analysis of tanshinone derivatives from Stachys parviflora on prostate and breast cancer cells

Molecular Biology Reports - Cytotoxic activities of methanolic crude extract of Stachys parviflora (Lamiaceae family) and its sub-fractions were primarily evaluated against human breast...     

Differentiation of multipotent stem cells to insulin-producing cells for treatment of diabetes mellitus: bone marrow- and adipose tissue-derived cells comparison

Molecular Biology Reports - Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and...     

Nebkhas of Salvadora persica and their effect on the growth and survival of Prosopis cineraria,Tamarix aphylla,and Capparis decidua trees and shrubs

Few studies were published on the effect of nebkhas (phytogenic mounds) on species diversity and soil resources, but no detailed study has been conducted yet on possible specific influence of nebkhas on growth and survival of the plants associated with them. We studied the nebkhas of Salvadora persica and their effect on growth and survival of three woody species (Prosopis cineraria, Tamarix aphylla, and Capparis decidua) in the Ommanian coast of Hormozgan Province in the south of Iran. The results showed that mean height and mean canopy diameter of P. cineraria and T. aphylla trees and shrubs inhabiting nebkhas of Salvadora persica were considerably higher than those of plants of these species growing outside nebkhas. The reverse occurred in the case of C. decidua. Generally, the percentages of stems with dead parts were significantly lower in plants inhabiting the nebkha sites in comparison to comparable ones growing outside the nebkhas. Salvadora persica nebkhas are enriched with more soil nutrients in comparison to inter-nebkha sites. Soil accumulated per each hectare in the nebkhas of the study area dominated by trees of Salvadora persica amounted to 237.6 m³. This indicates the great importance of nebkhas in the protection of soil and the associating species.     

First report of computational protein–ligand docking to evaluate susceptibility to HIV integrase inhibitors in HIV-infected Iranian patients

BackgroundIran has recently included integrase (INT) inhibitors (INTIs) in the first‐line treatment regimen in human immunodeficiency virus (HIV)-infected patients. However, there is no bioinformatics data to elaborate the impact of resistance-associated mutations (RAMs) and naturally occurring polymorphisms (NOPs) on INTIs treatment outcome in Iranian patients.MethodIn this cross-sectional survey, 850 HIV-1-infected patients enrolled; of them, 78 samples had successful sequencing results for INT gene. Several analyses were performed including docking screening, genotypic resistance, secondary/tertiary structures, post-translational modification (PTM), immune epitopes, etc.ResultThe average docking energy (E value) of different samples with elvitegravir (EVG) and raltegravir (RAL) was more than other INTIs. Phylogenetic tree analysis and Stanford HIV Subtyping program revealed HIV-1 CRF35-AD was the predominant subtype (94.9%) in our cases; in any event, online subtyping tools confirmed A1 as the most frequent subtype. For the first time, CRF-01B and BF were identified as new subtypes in Iran. Decreased CD4 count was associated with several factors: poor or unstable adherence, naïve treatment, and drug user status.ConclusionAs the first bioinformatic report on HIV-integrase from Iran, this study indicates that EVG and RAL are the optimal INTIs in first-line antiretroviral therapy (ART) in Iranian patients. Some conserved motifs and specific amino acids in INT-protein binding sites have characterized that mutation(s) in them may disrupt INT-drugs interaction and cause a significant loss in susceptibility to INTIs. Good adherence, treatment of naïve patients, and monitoring injection drug users are fundamental factors to control HIV infection in Iran effectively.     

Selenium nano-particle induced alterations in expression patterns of heat shock factor A4A (HSFA4A), and high molecular weight glutenin subunit 1Bx (Glu-1Bx) and enhanced nitrate reductase activity in wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.)

Taking account of heat shock factor A4A (HSFA4A) as a hydrogen peroxide sensor, anti-apoptosis agent, and crosslink component with critical signaling cascades, the current study was carried out to monitor possible changes in expression of this gene as well as some other important characteristics in wheat plants exposed to selenium nano-particle (nSe). Wheat seedlings were treated with nSe (0, 5, 10, and 50 mgl^?1). In germinating stage, plant fresh weights were reduced in nSe-treated seedlings, among which the nSe of 50 provoked roots turned brown. The nSe triggered the increases in the expressions of HSFA4A, in the plate. In the pot condition, shoot fresh weights in nSe-supplemented seedlings were decreased by approximately 22%. The nSe of 5 and 10 mgl^?1, respectively induced the expression of HSFA4A by 3.4- and 9.15-folds, contrasted with nSe50. Increasing times of sprays caused the dramatic reductions of the expression of HSFA4A in the nSe-supplemented groups. Moreover, the treatment of nSe stimulated expression of high molecular weight glutenin subunit 1Bx (Glu-1Bx) by fourfold, over the control. While the dramatic decrease in the expression of Glu-1Bx was recorded with increasing times of spray. Nitrate reductase activities were significantly improved by approximately 47% in nSe-fortified seedlings. Also, the foliar supplementation of nSe of 5 mgl^?1 provoked the significant inductions in peroxidase activity by 8%, whereas two other nSe treatments declined it. It may be stated that the nSe may modify the expression of HSFA4A, thereby triggering specific signaling and altering metabolism.     

Silicon and Plants: Current Knowledge and Future Prospects

Journal of Plant Growth Regulation - Silicon (Si) is the most copious element of existence in the lithosphere but still it has not been added into the essential element list. The imperative role of...     

Tragacanth-mediate synthesis of NiO nanosheets for cytotoxicity and photocatalytic degradation of organic dyes

Bioprocess and Biosystems Engineering - In this study, NiO nanosheets have been manufactured using a co-precipitation approach that involved the usage of nickel nitrate (Ni (NO3)2.6H2O) as the raw...