Simultaneous impact of atorvastatin and mesenchymal stem cells for glioblastoma multiform suppression in rat glioblastoma multiform model

Glioblastoma multiform (GBM) is known as an aggressive glial neoplasm. Recently incorporation of mesenchymal stem cells with anti-tumor drugs have been used due to lack of immunological responses and their easy accessibility. In this study, we have investigated the anti-proliferative and apoptotic activity of atorvastatin (Ator) in combination of mesenchymal stem cells (MSCs) on GBM cells in vitro and in vivo. The MSCs isolated from rats and characterized for their multi-potency features. The anti-proliferative and migration inhibition of Ator and MSCs were evaluated by MTT and scratch migration assays. The annexin/PI percentage and cell cycle arrest of treated C6 cells were evaluated until 72 h incubation. The animal model was established via injection of C6 cells in the brain of rats and subsequent injection of Ator each 3 days and single injection of MSCs until 12 days. The growth rate, migrational phenotype and cell cycle progression of C6 cells decreased and inhibited by the interplay of different factors in the presence of Ator and MSCs. The effect of Ator and MSCs on animal models displayed a significant reduction in tumor size and weight. Furthermore, histopathology evaluation proved low hypercellularity and mitosis index as well as mild invasive tumor cells for perivascular cuffing without pseudopalisading necrosis and small delicate vessels in Ator?+?MSCs condition. In summary, Ator and MSCs delivery to GBM model provides an effective strategy for targeted therapy of brain tumor.

     

Synthesis, crystal structure, NMR and ab initio molecular-orbital studies of some magnesium(II) macrocyclic Schiff-base complexes, with two 2-aminoethyl pendant arms

Three new Mg(II) bis(pendant arm) macrocyclic Schiff-base complexes, [MgLⁿ]²⁺(n=5, 6, 7), have been prepared via cyclocondensation of 2,6-diacetylpyridine with branched hexaamines and characterised spectroscopically. In addition, for [MgL⁵](ClO₄)₂ the crystal structure is reported. This is the first X-ray structural determination of an Mg(II) complex coordinated by seven nitrogen atoms. The ligands, L, are 15-, 16- and 17-membered pentaaza macrocycles having two 2-aminoethyl pendant arms [L⁵; 2,13-dimethyl-6,9-bis(aminoethyl)-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18), 2, 12, 14, 16-pentaene, L⁶; 2,14-dimethyl-6,10-bis(aminoethyl)-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19), 2, 13, 15, 17-pentaene and L⁷; 2,15-dimethyl-6,11-bis(aminoethyl)-3,6,11,14,20-pentaazabicyclo[14.3.1]eicosa-1(20),2,14,16,18-pentaene]. The crystal structure of [MgL⁵](ClO₄)₂, was determined by X-ray diffraction and showed that the complex cation that had formed consisted of a pentagonal bipyramidally coordinated Mg(II) ion. All complexes were characterised by IR, ¹H NMR,¹³C NMR, COSY(H,H) and HETCOR(H,C) spectroscopy, and the data indicate that the structure is approximately pentagonal bipyramidal in each case. This structural assignment is also supported by ab initio HF-MO calculations made using the standard 3-21G* basis set.     

Synthesis and characterization of Mg(II), Mn(II), Zn(II) and Cd(II) complexes with a new heptaaza Schiff base pendant-armed macrocycle: X-ray crystal structure, NMR and computational study

New 2-aminoethyl pendant-armed Schiff base macrocyclic complexes, [ML⁷]²⁺ (M = Mn(II), Mg(II), Zn(II) and Cd(II)), have been prepared via M(II) templated [1 + 1] cyclocondensation of 2,6-diacetylpyridine with a new branched hexamine, N,N,N′,N′-tetrakis(2-aminoethyl)-2,2-dimethylpropane-1,3-diamine. The ligand is a 16-membered pentaaza macrocycle having two 2-aminoethyl pendant arms [L⁷ is 2,14-dimethyl-6,10-bis(2-aminoethyl)-3,6,10,13,19-pentaazabicyclo[13.3.1]8,8-dimethylnonadeca-1(19),2,13,15,17-pentaene]. The crystal structures of [MnL⁷]²⁺ and [MgL⁷]²⁺ were determined from X-ray diffraction data. The geometry of the coordination sphere of complexes is a slightly distorted pentagonal bipyramid with the metal ion located within a pentaaza macrocycle and two pendant amines coordinating on opposite sides. All complexes were characterized by IR, microanalysis and except of [MnL⁷]²⁺ by ¹H NMR, ¹³C NMR, DEPT135, COSY(H, H) and HMQC spectroscopy. The data indicate that the structure is pentagonal bipyramidal in each case. The structure of all complexes has also been theoretically studied by ab initio Hartree-Fock and density functional theory methods.     

Teeth-derived stem cells: A source for cell therapy

Cell therapy is one of the important therapeutic approaches in the treatment of many diseases such as cancer, degenerative diseases, and cardiovascular diseases. Among various cell types, which could be used as cell therapies, stem cell therapy has emerged as powerful tools in the treatment of several diseases. Multipotent stem cells are one of the main classes of stem cells that could originate from different parts of the body such as bone marrow, adipose, placenta, and tooth. Among several types of multipotent stem cells, tooth-derived stem cells (TDSCs) are associated with special properties such as accessible, easy isolation, and low invasive, which have introduced them as a good source for using in the treatment of several diseases such as neural injuries, liver fibrosis, and Cohrn’s disease. Here, we provided an overview of TDSCs particular stem cells from human exfoliated deciduous teeth and clinical application of them. Moreover, we highlighted molecular mechanisms involved in the regulation of dental stem cells fate.     

Synthesis, crystal structures and ab initio studies of some heptaaza manganese(II) macrocyclic Schiff-base complexes with two 2-aminoethyl pendant arms

Two new heptaaza Mn(II) macrocyclic bis(pendant donor) Schiff-base complexes, [MnL⁶]²⁺ and [MnL⁷]²⁺, have been prepared via Mn(II) templated [1 + 1] cyclocondensation of 2,6-diacetylpyridine with an appropriate branched hexaamine, and characterized by X-ray crystallography and spectroscopic methods. The ligands are 16- and 17-membered pentaaza macrocycles with two 2-aminoethyl pendant arms [L⁶ = 2,14-dimethyl-6,10-bis(2-aminoethyl)-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19),2,13,15,17-pentaene and L⁷ = 2,15-dimethyl-6,11-bis(2-aminoethyl)-3,6,11,14,20-pentaazabicyclo[14.3.1]eicosa-1(20),2,14,16,18-pentaene]. The crystal structures of [MnL⁷]²⁺ and another related complex, [MnL⁵]²⁺ [L⁵ = 2,13-dimethyl-6,9-bis(2-aminoethyl)-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene] were determined from X-ray diffraction data and the structure of each complex indicates that the geometry of the coordination sphere is that of a slightly distorted pentagonal bipyramid with the Mn(II) ion located within a pentaaza macrocycle and two pendant amines coordinating on opposite sides. The increased macrocycle ring size in [MnL⁷]²⁺ introduces an unusual seven-membered chelate ring and leads to long Mn-N bond lengths within the macrocycle, but to shorter pendant amine-Mn(II) bond lengths. Ab initio HF-MO calculations produce structures for the two complexes which are in close agreement with experimental findings and predict a similar structure for [MnL⁶]²⁺, but with the longest pendant amine-Mn(II) bond lengths of the three structures.     

Long non-coding RNA as a novel biomarker and therapeutic target in aggressive B-cell non-Hodgkin lymphoma: A systematic review

Cancer initiation and progression have been associated with dysregulated long non-coding RNA (lncRNA) expression. However, the lncRNA expression profile in aggressive B-cell non-Hodgkin lymphoma (NHL) has not been comprehensively characterized. This systematic review aims to evaluate the role of lncRNAs as a biomarker to investigate their future potential in the diagnosis, real-time measurement of response to therapy and prognosis in aggressive B-cell NHL. We searched PubMed, Web of Science, Embase and Scopus databases using the keywords “long non-coding RNA”, “Diffuse large B-cell lymphoma”, “Burkitt's lymphoma” and “Mantle cell lymphoma”. We included studies on human subjects that measured the level of lncRNAs in samples from patients with aggressive B-cell NHL. We screened 608 papers, and 51 papers were included. The most studied aggressive B-cell NHL was diffuse large B-cell lymphoma (DLBCL). At least 79 lncRNAs were involved in the pathogenesis of aggressive B-cell NHL. Targeting lncRNAs could affect cell proliferation, viability, apoptosis, migration and invasion in aggressive B-cell NHL cell lines. Dysregulation of lncRNAs had prognostic (e.g. overall survival) and diagnostic values in patients with DLBCL, Burkitt's lymphoma (BL), or mantle cell lymphoma (MCL). Furthermore, dysregulation of lncRNAs was associated with response to treatments, such as CHOP-like chemotherapy regimens, in these patients. LncRNAs could be promising biomarkers for the diagnosis, prognosis and response to therapy in patients with aggressive B-cell NHL. Additionally, lncRNAs could be potential therapeutic targets for patients with aggressive B-cell NHL like DLBCL, MCL or BL.