Water-Soluble Flexible Organic Frameworks That Include and Deliver Proteins.

Four water-soluble hydrazone-based three-dimensional (3D) flexible organic frameworks FOF-1-4 have been synthesized from a semirigid tetracationic tetraaldehyde and four flexible dihydrazides. 1H NMR spectroscopy indicated the quantitative formation of FOF-1-4 in D2O, while dynamic light scattering experiments revealed that, depending on the concentration, these porous frameworks display hydrodynamic diameters ranging from 50 to 120 nm. The porosity of the frameworks is confirmed by ethanol vapor adsorption experiments of the solid samples as well as the high loading capacity for a 2.3 nm porphyrin guest in water. The new water-soluble frameworks exhibit low cytotoxicity and form inherent pores with diameters of 5.3 or 6.7 nm, allowing rapid inclusion of proteins such as bovine serum albumin and green and orange fluorescent proteins, and efficient delivery of the proteins into normal and cancer cells. Flow cytometric analysis reveals percentages of the delivered cells up to 99.8%

Structural, stereochemical, and bioactive studies of cembranoids from Chinese soft coral Sarcophyton trocheliophorum

LBK

15-Deoxy-Δ 12,14

It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) have capacity to migrate to the damaged liver and contribute to fibrogenesis in chronic liver diseases. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARγ), is considered a new inhibitor of cell migration. However, the actions of 15d-PGJ2 on BMSC migration remain unknown. In this study, we investigated the effects of 15d-PGJ2 on the migration of BMSCs using a mouse model of chronic liver fibrosis and primary mouse BMSCs. Our results demonstrated that in vivo, 15d-PGJ2 administration inhibited the homing of BMSCs to injured liver by flow cytometric analysis and, in vitro, 15d-PGJ2 suppressed primary BMSC migration in a dose-dependent manner determined by Boyden chamber assay. Furthermore, the repressive effect of 15d-PGJ2 was blocked by reactive oxygen species (ROS) inhibitor, but not PPARγ antagonist, and action of 15d-PGJ2 was not reproduced by PPARγ synthetic ligands. In addition, 15d-PGJ2 triggered a significant ROS production and cytoskeletal remodeling in BMSCs. In conclusion, our results suggest that 15d-PGJ2 plays a crucial role in homing of BMSCs to the injured liver dependent on ROS production, independently of PPARγ, which may represent a new strategy in the treatment of liver fibrosis

Identification of four novel small non-coding RNAs from Xanthomonas campestris pathovar campestris

<p>Abstract</p> <p>Background</p> <p>In bacteria, small non-coding RNAs (sRNAs) have been recognized as important regulators of various cellular processes. Approximately 200 bacterial sRNAs in total have been reported. However, very few sRNAs have been identified from phytopathogenic bacteria.</p> <p>Results</p> <p><it>Xanthomons campestris </it>pathovar <it>campestris </it>(<it>Xcc</it>) is the causal agent of black rot disease of cruciferous crops. In this study, a cDNA library was constructed from the low-molecular weight RNA isolated from the <it>Xcc </it>strain 8004 grown to exponential phase in the minimal medium XVM2. Seven sRNA candidates were obtained by sequencing screen of 2,500 clones from the library and four of them were confirmed to be sRNAs by Northern hybridization, which were named sRNA-<it>Xcc</it>1, sRNA-<it>Xcc</it>2, sRNA-<it>Xcc</it>3, and sRNA-<it>Xcc</it>4. The transcription start and stop sites of these sRNAs were further determined. BLAST analysis revealed that the four sRNAs are novel. Bioinformatics prediction showed that a large number of genes with various known or unknown functions in <it>Xcc </it>8004 are potential targets of sRNA-<it>Xcc</it>1, sRNA-<it>Xcc</it>3 and sRNA-<it>Xcc</it>4. In contrast, only a few genes were predicted to be potential targets of sRNA-<it>Xcc</it>2.</p> <p>Conclusion</p> <p>We have identified four novel sRNAs from <it>Xcc </it>by a large-scale screen. Bioinformatics analysis suggests that they may perform various functions. This work provides the first step toward understanding the role of sRNAs in the molecular mechanisms of <it>Xanthomonas campestris </it>pathogenesis.</p

Efficacy and short-term side effects of sitagliptin, vildagliptin and saxagliptin in Chinese diabetes: a randomized clinical trial

Aims: To investigate the difference in the efficacy among dipeptidyl peptidase-4 (DPP-4) inhibitors in Chinese adults with newly diagnosed diabetes. Materials and methods: In a multicenter, randomized study, we enrolled adults who were either treatment naive or off prior anti-hyperglycemic therapy for at least 3 months. Eligible patients had hemoglobin A1c (HbA1c) concentrations of 6.5–9.5%. Three hundred patients had been randomly allocated to sitagliptin 100 mg, once daily; vildagliptin 50 mg, twice daily and saxagliptin 5 mg, once daily for 12 weeks. Patients and investigators were masked to treatment assignment. The primary endpoint was change from baseline in HbA1c at week 12. This study was completed and registered with ClinicalTrials.gov, number NCT 01703637. Results: Totally 277 patients were enrolled in the final analysis, and 9 3 patients received sitagliptin, 94 received vildagliptin and 90 received saxagliptin. Compared with baseline, adjusted mean differences in change from baseline HbA1c at week 12 were −0.50% (95% CI: −0.20 to −0.90), −0.65% (95% CI: −0.40 to −1.40), −0.70 (95% CI: −0.50 to −1.00) for sitagliptin, vildagliptin and saxagliptin group, respectively. The overall HbA1c-lowering effect was similar for all three selected DPP-4 inhibitors after adjustment for age and baseline HbA1c. Notably, in secondary outcome analysis, patients in vildagliptin group showed a significant decrease in total cholesterol levels, compared with participants in sitagliptin and saxagliptin groups. No significant between-group difference was shown in adverse events (AE). Conclusions: The overall HbA1c-lowering effect and incidence of AE were similar for sitagliptin, vildagliptin and saxagliptin in Chinese adults with newly diagnosed diabetes