ABSTRACT
Diabetes mellitus (DM) is a major worldwide public health challenge, for which gene therapy offers a potential therapeutic approach. To date, no systematic review or meta-analysis has been published in this area, so we examined all relevant published studies on rodents to elucidate the overall effects of gene therapy on bodyweight, intraperitoneal glucose tolerance test (IPGTT), fasting blood glucose, and insulin in animals with type 1 DM. The Cochrane Library, PubMed, Embase, ISI Web of Science, SCOPUS, and Google Scholar were systematically searched for potentially relevant studies. Mean±standard deviation (SD) was pooled using a random-effects model. After the primary search, out of 528 studies identified, 16 studies were in concordance with predefined criteria and selected for the final assessment. Of these, 12 studies used viral manipulation, and 4 employed non-viral vectors for gene delivery. The meta-analysis showed gene therapy with a viral vector decreased mean IPGTT (-12.69 mmol/l, P<0.001), fasting blood glucose (-13.51 mmol/l, P<0.001), insulin (398.28 pmol/l, P<0.001), and bodyweight (24.22 g, P<0.001), whereas non-viral vectors reduced fasting glucose (-29.95 mmol/l, P<0.001) and elevated insulin (114.92 pmol/l, P<0.001). Gene therapy has favorable effects on alleviating type 1 DM related factors in diabetic rodents.
ABSTRACT
Immobilization of methotrexate (MTX) anticancer drug onto the graphene surface is reported through three methods, including either covalent linkage via (a) EDC/NHS organic activators and (b) electrografting of MTX diazonium salt, or (c) noncovalent bonding, resulting in three different systems. To evaluate the interaction ability of the immobilized MTX with biological species, calf thymus DNA (ctDNA), mouse 4T1 breast tumor, and Human foreskin fibroblast (hFF) cells as models of the primary intracellular target of anticancer drugs, cancer and normal cells, respectively, are examined. The features of the constructed systems and their interactions with ctDNA are followed by surface analysis techniques and electrochemical methods. The results indicate that (i) the amount of the immobilized MTX on the graphene surface is affected by type of the immobilization method; and a maximum value of (Γ=9.3±0.9pmolcm-2) is found via electrografting method, (ii) graphene-modified-MTX has high affinity for ctDNA in a wide dynamic range of concentrations, and (iii) the nature of the interaction is of electrostatic and/or hydrogen bonding type, formed most probably between OH, NH and CO groups of MTX and different DNA functions. Finally, electrochemical impedance spectroscopy results approved the high affinity of the systems for 4T1 cancer cells.
