Gene Transfer into the Lung by Nanoparticle Dextran-Spermine/Plasmid DNA Complexes

A novel cationic polymer, dextran-spermine (D-SPM), has been found to mediate gene expression in a wide variety of cell lines and in vivo through systemic delivery. Here, we extended the observations by determining the optimal conditions for gene expression of D-SPM/plasmid DNA (D-SPM/pDNA) in cell lines and in the lungs of BALB/c mice via instillation delivery. In vitro studies showed that D-SPM could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency at D-SPM to pDNA weight-mixing ratio of 12. In the lungs of mice, the levels of gene expression generated by D-SPM/pDNA are highly dependent on the weight-mixing ratio of D-SPM to pDNA, amount of pDNA in the complex, and the assay time postdelivery. Readministration of the complex at day 1 following the first dosing showed no significant effect on the retention and duration of gene expression. The study also showed that there was a clear trend of increasing size of the complexes as the amount of pDNA was increased, where the sizes of the D-SPM/pDNA complexes were within the nanometer range

The association between acylcarnitine and amino acids profile and metabolic syndrome and its components in Iranian adults: Data from STEPs 2016

BackgroundEvidence, albeit with conflicting results, has suggested that cardiometabolic risk factors, including obesity, type 2 diabetes (T2D), dyslipidemia, and hypertension, are highly associated with changes in metabolic signature, especially plasma amino acids and acylcarnitines levels. Here, we aimed to evaluate the association of circulating levels of amino acids and acylcarnitines with metabolic syndrome (MetS) and its components in Iranian adults.MethodsThis cross-sectional study was performed on 1192 participants from the large–scale cross-sectional study of Surveillance of Risk Factors of non-communicable diseases (NCDs) in Iran (STEP 2016). The circulating levels of amino acids and acylcarnitines were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in individuals with MetS (n=529) and without MetS (n=663).ResultsThe higher plasma levels of branched-chain amino acids (Val, Leu), aromatic amino acids (Phe, Tyr), Pro, Ala, Glu, and the ratio of Asp to Asn were significantly associated with MetS, whereas lower circulating levels of Gly, Ser, His, Asn, and citrulline were significantly associated with MetS. As for plasma levels of free carnitine and acylcarnitines, higher levels of short-chain acylcarnitines (C2, C3, C4DC), free carnitine (C0), and long-chain acylcarnitines (C16, C18OH) were significantly associated with MetS. Principal component analysis (PCA) showed that factor 3 (Tyr, Leu, Val, Met, Trp, Phe, Thr) [OR:1.165, 95% CI: 1.121-1.210, P<0.001], factor 7 (C0, C3, C4) [OR:1.257, 95% CI: 1.150-1.374, P<0.001], factor 8 (Gly, Ser) [OR:0.718, 95% CI: 0.651-0.793, P< 0.001], factor 9 (Ala, Pro, C4DC) [OR:1.883, 95% CI: 1.669-2.124, P<0.001], factor 10 (Glu, Asp, C18:2OH) [OR:1.132, 95% CI: 1.032-1.242, P= 0.009], factor 11 (citrulline, ornithine) [OR:0.862, 95% CI: 0.778-0.955, P= 0.004] and 13 (C18OH, C18:1 OH) [OR: 1.242, 95% CI: 1.042-1.480, P= 0.016] were independently correlated with metabolic syndrome.ConclusionChange in amino acid, and acylcarnitines profiles were seen in patients with MetS. Moreover, the alteration in the circulating levels of amino acids and acylcarnitines is along with an increase in MetS component number. It also seems that amino acid and acylcarnitines profiles can provide valuable information on evaluating and monitoring MetS risk. However, further studies are needed to establish this concept

トリコスタチン A ワ サル ハイセイ カンサイボウ ノ シンキン エ ノ ブンカ オ ソクシンスル

京都大学0048新制・課程博士博士(医学)甲第13295号医博第3136号新制||医||955(附属図書館)UT51-2007-H660京都大学大学院医学研究科内科系専攻(主査)教授 篠原 隆司, 教授 野間 昭典, 教授 山中 伸弥学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Tissue Regeneration through Self-Assembled Peptide Amphiphile Nanofibers

Introduction: In the present study, we hypothesized that a novelapproach to promote vascularization would be to create injectablethree dimensional (3-D) scaffolds within growth factor that enhancethe sustained release of growth factor and induce the angiogenesis.Material and Methods: We demonstrate that a 3-D scaffold can beformed by mixing of peptide-amphiphile (PA) aqueous solution withhepatocyte growth factor (HGF) solution. PA was synthesized bystandard solid phase chemistry that ends with the alkylation of theNH2 terminus of the peptide. The sequence of arginine-glycineasparticacid (RGD) was included in peptide design as well. A 3-Dnetwork of nanofibers was formed by mixing HGF suspensions withdilute aqueous solution of PA.Results: Scanning electron microscopy (SEM) examination revealedthe formation of fibrous assemblies with an extremely high aspectratio and high surface areas with mean diameter of less than 200 nm.In vitro HGF release profile of 3-D nanofibers was investigated whileangiogenesis induced by the released HGF was being assessed. Invivo potential ability of PA nanofibers to induce angiogenesis wasassessed through subcutaneous injection of PA solution, HGFsolution, and PA in combination with HGF solutions. Injection of PAwith HGF induced significant angiogenesis around the injected site,in marked contrast to HGF injection alone and PA injection alone.Conclusion: The combination of HGF-induced angiogenesis is apromising procedure to improve tissue regeneration