Non-cultured cell transplantation in an ovine model of non-ischemic heart failure.

OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. METHODS: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure.     

Enantiomeric Resolution of Drug Compounds by Liquid Chromatography

Novel techniques have recently emerged to separate chiral drug compounds into pure enantiomers. The mechanism, experimental difficulties, and applicability of these methods can vary greatly, and the choices involved are not straightforward. The most significant new advances in the field of chiral separations have come from work done with liquid chromatographic systems and chiral stationary-phase columns. This review describes several commonly used approaches to chiral separation, diastereomeric derivatization, chiral mobile-phase additives, and three major types of chiral stationary phases. Although no single method can be judged superior for every drug application, it appears that chiral stationary phases have received the most attention recently and they are emphasized here.     

Preparation,characterization and catalytic application of nano-Fe3O4@SiO2@(CH2)3OCO2Na as a novel basic magnetic nanocatalyst for the synthesis of new pyranocoumarin derivatives

We present a study on the synthesis, characterization and application of sodium carbonate tag silica-coated nano-Fe₃O₄ (Fe₃O₄@SiO₂@(CH₂)₃OCO₂Na) as a novel and efficient heterogeneous basic catalyst. The described catalyst was fully characterized via FT-IR, X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), and field emission scanning electron microscopy (FE-SEM). The reported novel magnetic nanocatalyst presents an excellent activity and catalytic performance for the synthesis of a novel series of pyranocoumarins through the reaction of dialkyl acetylenedicarboxylates and 5,7-dihydroxy coumarin derivatives at 100 °C under solvent-free conditions.

We present a study on the synthesis, characterization and application of sodium carbonate tag silica-coated nano-Fe₃O₄ (Fe₃O₄@SiO₂@(CH₂)₃OCO₂Na) as a novel and efficient heterogeneous basic catalyst.     

A Novel Protocol to Differentiate Induced Pluripotent Stem Cells by Neuronal microRNAs to Provide a Suitable Cellular Model

Neurodegenerative diseases are one of the most challenging subjects in medicine. Investigation of their underlying genetic or epigenetic factors is hampered by lack of suitable models. Patient‐specific induced pluripotent stem cells (iPS cells) represent a valuable approach to provide a proper model for poorly understood mechanisms of neuronal diseases and the related drug screenings. miR‐124 and miR‐128 are the two brain‐enriched miRNAs with different time‐points of expression during neuronal development. Herein, we transduced human iPS cells with miR‐124 and miR‐128 harboring lentiviruses sequentially. The transduced plasmids contained GFP and puromycin antibiotic‐resistant genes for easier selection and identification. Morphological assessment and immunocytochemistry (overexpressions of beta‐tubulin and neuron‐specific enolase) confirmed that induced hiPS cells by miR‐124 and miR‐128 represent similar characteristics to those of mature neurons. In addition, the upregulation of neuron‐specific enolase, beta‐tubulin, Map2, GFAP, and BDNF was detected by quantitative real‐time PCR. In conclusion, it seems that our novel protocol remarks the combinatorial effect of miR‐124 and miR‐128 on neural differentiation in the absence of any extrinsic factor. Moreover, such cellular models could be used in personalized drug screening and applied for more effective therapies.     

Epitope mapping of PR81 anti-MUC1 monoclonal antibody following PEPSCAN and phage display techniques

PR81 is an anti-MUC1 monoclonal antibody (MAb) which was generated against human MUC1 mucin that reacted with breast cancerous tissue, MUC1 positive cell line (MCF-7, BT-20, and T-4 7 D), and synthetic peptide, including the tandem repeat sequence of MUC1. Here we characterized the binding properties of PR81 against the tandem repeat of MUC1 by two different epitope mapping techniques, namely, PEPSCAN and phage display. Epitope mapping of PR81 MAb by PEPSCAN revealed a minimal consensus binding sequence, PDTRP, which is found on MUC1 peptide as the most important epitope. Using the phage display peptide library, we identified the motif PD(T/S/G)RP as an epitope and the motif AVGLSPDGSRGV as a mimotope recognized by PR81. Results of these two methods showed that the two residues, arginine and aspartic acid, have important roles in antibody binding and threonine can be substituted by either glycine or serine. These results may be of importance in tailor making antigens used in immunoassay.     

Susceptibility of Phlebotomus papatasi (Diptera: Psychodidae) to DDT in some foci of cutaneous leishmaniasis in Iran.

The susceptibility of Phlebotomus papatasi to DDT was studied in field surveys at localities in different areas of Iran during 1985-88. In many parts of Iran houses had been treated with DDT for malaria control (1950-68). Tests were carried out in localities where the application of DDT had been discontinued since 1969. This investigation showed that P. papatasi from Isfahan is more tolerant to DDT than flies from other areas, probably a manifestation of DDT resistance.