Current Issue : January - March Volume : 2020 Issue Number : 1 Articles : 5 Articles
Ginger is a plant that is native to southern China. In the last decade and research on\nthe components of ginger has significantly increased; of these components, 6-shogaol exhibits\nthe greatest potential antitumor capacity. However, the molecular mechanism through which\n6-shogaol exerts its effects has not yet been elucidated. In this study, the effect of 6-shogaol on\ntumor cells that were derived from human fibrosarcoma (HT1080) was evaluated. Cell viability\nwas determined by a (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay\ntesting different concentrations of 6-shogaol (2.5â??150 microM). Subsequently, the effect of 6-shogaol on\nreactive oxygen species (ROS) production, glucose uptake, and protein expression of the signaling\npathway phosphatase and tensin homolog/ protein kinase B /mammalian target of rapamycin\n(PTEN/Akt/mTOR) was measured. 6-Shogaol reduced the viability of the tumor cells and caused an\nincrease in ROS production, which was attenuated with the addition of N-acetylcysteine, and the\nrecovery of cell viability was observed. The increase in ROS production in response to 6-shogaol was\nassociated with cell death. Similarly, glucose uptake decreased with incremental concentrations of\n6-shogaol, and an increase in the expression of mTOR-p and Akt-p proteins was observed; PTEN was\nactive in all the treatments with 6-shogaol. Thus, the results suggest that cells activate uncontrolled\nsignaling pathways, such as phosphoinositide 3-kinase (PI3K)/Akt/mTOR, among other alternative\nmechanisms of metabolic modulation and of survival in order to counteract the pro-oxidant effect of\n6-shogaol and the decrease in glucose uptake. Interestingly, a differential response was observed\nwhen non-cancerous cells were treated with 6-shogaol....
Topical treatment of wound infections is often a challenge due to limited drug availability\nat the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects,\nprovided that a more selective and sustained local drug delivery is achieved. In this study, a poorly\nwater-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and\nnanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and\nantimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin.\nWounds of 5 mm in diameter were created on 1.5 * 1.5 cm skin blocks and treated with the\ninvestigated materials. While nanofiber mats reached the highest amount of delivered drug after 6\nh, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment\nhad no effect on the overall skin metabolic activity but influenced the wound healing process, as\nobserved using histological analysis. Both delivery systems were efficient in preventing the growth\nof Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 microg of\nciprofloxacin accomplished the complete eradication of biofilm infections with 1 * 109\nbacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats\nare promising delivery systems for the prevention or topical treatment of infected wounds....
The objective of the present work was to characterize the ability of liposomes and\ncyclodextrin (CyD) complexes to modulate the in vivo profile of fluticasone (FTZ). In vitro cell\ncompatibility tests were performed, exposing A549 cells to FTZ in the free form and FTZ associated\nto liposomes and complexed with CyD. The in vivo fate of a selected FTZ liposomal formulation\nand of several FTZ CyD complexes was achieved following intranasal instillation or pulmonary\nadministration in BALB/c mice, respectively. For pulmonary administration, an inhalation chamber\nwas constructed to enable the simultaneously pulmonary administration to six mice. Thirty minutes\nand 3 h after administration, mice were sacrificed, their blood, lungs, livers, and spleens were\nremoved, and FTZ level was determined by HPLC using an extraction procedure. The in vitro\ntests revealed no toxic effects of FTZ formulations, as cellular viability was always superior to 90%\nfor FTZ concentrations ranging from 5 to 60 microM 72 h after incubation. The in vivo biodistribution\nresults showed that FTZ incorporated in liposomes resulted in 20 and 30 times higher accumulation\nin the lungs in comparison with free FTZ, at 0.5 and 3 h after i.n. administration, respectively.\nFTZ associated to Hydroxypropyl-Gamma-cyclodextrin (HP-CyD) was the complex that permitted the\nhigher accumulation of FTZ in the lungs in comparison with the respective free form. The results\nalso suggest that the inhalation chamber apparatus can effectively facilitate the evaluation of in vivo\ninhalation. The establishment of an animal model of asthma allows us to further study the therapeutic\nefficacy of the developed FTZ formulations....
We previously reported that siRNA delivery to the brain is improved by the nose-to-brain\ndelivery route and by conjugation with polyethylene glycol-polycaprolactone (PEG-PCL) polymer\nmicelles and the cell-penetrating peptide, Tat (PEG-PCL-Tat). In this study, we evaluated the\nnose-to-brain delivery of siRNA targeting TNF-Alpha (siTNF-Alpha) conjugated with PEG-PCL-Tat to\ninvestigate its therapeutic effects on a transient middle cerebral artery occlusion (t-MCAO) rat\nmodel of cerebral ischemia-reperfusion injury. Intranasal treatment was provided 30 min after\ninfarction induced via suturing. Two hours after infarction induction, the suture was removed,\nand blood flow was released. At 22 h post-reperfusion, we assessed the infarcted area, TNF-Alpha\nproduction, and neurological score to determine the therapeutic effects. The infarcted area was\nobserved over a wide range in the untreated group, whereas shrinkage of the infarcted area was\nobserved in rats subjected to intranasal administration of siTNF-Alpha with PEG-PCL-Tat micelles.\nMoreover, TNF-Alpha production and neurological score in rats treated by intranasal administration of\nsiTNF-Alpha with PEG-PCL-Tat micelles were significantly lower than those in untreated and naked\nsiTNF-Alpha-treated rats. These results indicate that nose-to-brain delivery of siTNF-Alpha conjugated with\nPEG-PCL-Tat micelles alleviated the symptoms of cerebral ischemia-reperfusion injury....
Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome characterized by\nred blood cell aplasia. Currently, mutations in 19 ribosomal protein genes have been identified in\npatients. However, the pathogenic mechanism of DBA remains unknown. Recently, several DBA\nmodels were generated in zebrafish (Danio rerio) to elucidate the molecular pathogenesis of disease and\nto explore novel treatments. Zebrafish have strong advantages in drug discovery due to their rapid\ndevelopment and transparency during embryogenesis and their applicability to chemical screens.\nTogether with mice, zebrafish have now become a powerful tool for studying disease mechanisms\nand drug discovery. In this review, we introduce recent advances in DBA drug development and\ndiscuss the usefulness of zebrafish as a disease model....
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