核仁小RNA源性小RNA

最新研究结果表明,一些与RNA介导基因沉默相关的小RNA由核仁小RNA(small nucleolar RNA,snoRNA)加工产生,这种小RNA被称为核仁小RNA源性小RNA(snoRNA derived small RNA,sdRNA)。sdRNA现象分布物种广;涉及的snoRNA种类全,数量多;产生的小RNA分子大小不一、数量、种类多。表明这种小RNA在生物中存在着广泛的普遍性。sdRNA的发现拓展了snoRNA的功能,揭示了snoRNA与RNA介导的基因沉默之间的紧密关系,增强了snoRNA在RNA调控网络中的重要性,并为进一步研究RNA调控网络开启了一扇门。     

Novel tetrahydrochinoline derived CETP inhibitors

In the course of our efforts to identify orally active cholesteryl ester transfer protein (CETP) inhibitors, we have continued to explore tetrahydrochinoline derivatives. Based on BAY 19-4789 structural modifications led to the discovery of novel cycloalkyl substituted compounds. Thus, example 11b is a highly potent CETP inhibitor both in vitro and in vivo in transgenic mice with favourable pharmacokinetic properties for clinical development.     

Tubulin-polymerization inhibitors derived from thalidomide

2-(2,6-Diisopropylphenyl)-5-hydroxy-1H-isoindole-1,3-dione (5HPP-33), which was obtained during our previous structural development studies on thalidomide, was revealed to possess potent tubulin-polymerization-inhibiting activity, comparable to that of the known tubulin-polymerization inhibitors, rhizoxin and colchicine. A major metabolite of thalidomide, 5-hydroxythalidomide, which possesses a hydroxyl group at the position corresponding to that of 5HPP-33, also showed moderate inhibitory activity.     

Small RNAs derived from snoRNAs

Small nucleolar RNAs (snoRNAs) guide RNA modification and are localized in nucleoli and Cajal bodies in eukaryotic cells. Components of the RNA silencing pathway associate with these structures, and two recent reports have revealed that a human and a protozoan snoRNA can be processed into miRNA-like RNAs. Here we show that small RNAs with evolutionary conservation of size and position are derived from the vast majority of snoRNA loci in animals (human, mouse, chicken, fruit fly), Arabidopsis, and fission yeast. In animals, sno-derived RNAs (sdRNAs) from H/ACA snoRNAs are predominantly 20–24 nucleotides (nt) in length and originate from the 3′ end. Those derived from C/D snoRNAs show a bimodal size distribution at ∼17–19 nt and >27 nt and predominantly originate from the 5′ end. SdRNAs are associated with AGO7 in Arabidopsis and Ago1 in fission yeast with characteristic 5′ nucleotide biases and show altered expression patterns in fly loquacious and Dicer-2 and mouse Dicer1 and Dgcr8 mutants. These findings indicate that there is interplay between the RNA silencing and snoRNA-mediated RNA processing systems, and that sdRNAs comprise a novel and ancient class of small RNAs in eukaryotes.     

Exosomes derived from dendritic cells

Dendritic cells (DC) are potent antigen presenting cells and the only ones capable of inducing primary cytotoxic immune responses both in vivo and vitro. DCs secrete a 60-80 nm membrane vesicle population of endocytic origin, called exosomes. The protein composition of exosomes was analyzed using a systematic proteomic approach. Besides MHC and costimulatory molecules, exosomes bear several adhesion proteins, probably involved in their specific targeting. Exosomes also accumulate several cytosolic factors, most likely involved in exoxome's biogenesis in late endosomes. Like DCs, exosomes induce potent anti tumor immune responses in vivo. Indeed, a single injection of DC-derived exosomes sensitized with tumor peptides induced the eradication of established mouse tumors. Tumor-specific cytotoxic T lymphocytes were found in the spleen of exosome treated mice, and depletion of CD8+ T cells in vivo inhibited the anti tumor effect of exosomes. These results strongly support the implementation of human DC-derived exosomes for cancer immunotherapy.     

Novel macrocycles derived from nucleosides

A novel nucleoside-derived macrocycle formed from three thymidine 5'-carboxylic acid monomer units is described.     

Phospholipid derived mediators and glomerulonephritis

The contributions made by the various eicosanoids, PAF, the HETES and the lipoxins to the pathophysiology of glomerulonephritis is reviewed. A case can be made for clinical trials of PAF, leukotriene and thromboxane antagonists. Combined thromboxane synthetase and thromboxane receptor antagonism would seem to be the more efficacious approach for the various disease entities.     

Amino acids derived from ornithine

Summary The use of copper complexes in the protection of lysine and tyrosine side chains has been extensively described. Based on this work and in order to produre a peptide library consisting of unnatural amino acids, three amino acids were prepared by acylation/sulfonation of the -amino function of ornithine and they were incorporated in a random sequence. Depending upon the acidity of the remaining proton on the -nitrogen, an intramolecular cyclization competed with the amide formation using standard coupling conditions (DIC/HOBt/DIEA). This side reaction could be suppressed by simple removal of the base from the condensation mixture. The obtained peptides were purified on a PLRP-s^® column and their identity was confirmed by mass spectrometry.Abbreviations Fmoc 9-fluorenylmethyloxycarbonyl - Inp isonipecotic acid - Thi -(2-thienylcarbonyl)ornithine - Tos -tosylornithine - Qui -(8-quinolinesulfonyl)ornithine - Ala -alanine - SPPS solid phase peptide synthesis     

Angiogenesis inhibitors derived from thalidomide

5-Hydroxy-2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33: 10), which was obtained during our previous structural development studies on thalidomide, was revealed to possess potent anti-angiogenic activity in a human umbilical vein endothelial cell (HUVEC) assay. Thalidomide (1) and its metabolite, 5-hydroxythalidomide (5-HT: 2), which possesses a hydroxyl group at the position corresponding to that of 5HPP-33, as well as IMiDs (immunomodulatory derivatives of thalidomide: 3 and 5), also showed weak or moderate activity in the same assay.     

Antimicrobial metal-based thiophene derived compounds

A novel series of thiophene derived Schiff bases and their transition metal- [Co(II), Cu(II), Zn(II), Ni(II)] based compounds are reported. The Schiff bases act as tridentate ligands toward metal ions via azomethine-N, deprotonated-N of ammine substituents and S-atom of thienyl moiety. The synthesized ligands along with their metal complexes were screened for their in vitro antibacterial activity against six bacterial pathogens (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and Bacillus subtilis) and for antifungal activity against six fungal pathogens (Trichophytonlongifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata). The results of antimicrobial studies revealed the free ligands to possess potential activity which significantly increased upon chelation.     

Character comparison of abdomen‐derived and eyelid‐derived mesenchymal stem cells

Objectives

While most human adipose tissues, such as those located in the abdomen, hip and thigh, are of mesodermal origin, adipose tissues located in the face are of ectodermal origin. The present study has compared stem cell‐related features of abdomen‐derived adult stem cells (A‐ASCs) with those of eyelid‐derived adult stem cells (E‐ASCs).

Materials and methods

Adipose tissue‐derived cells were maintained in DMEM supplemented with 10% FBS. Before passage 6, cells were analysed using FACS, immunocytochemistry and quantitative real time PCR (qRT‐PCR). To examine multi‐differentiational potential, early passage ASCs were cultivated in each of a commercial Stempro^® Differentiation kit.

Results

Unlike fibroblast‐like morphology of A‐ASCs, E‐ASCs had bipolar morphology. Both types of cell exhibited similar surface antigens, and neuronal cell‐related genes and proteins. However, there were differences in mRNA expression levels of CD90 and CD146; neuron‐specific enolase (NSE) and nuclear receptor‐related protein 1 (Nurr1) were different between the two cell types. There was no difference in multi‐differentiational potential between 3 E‐ASCs lines, however, E‐ASCs had higher expression levels of chondrocyte‐related genes compared to A‐ASCs. These cells underwent senescence and maintained normal karyotypes.

Conclusions

Although isolated from similar adipose tissues, both types of cells displayed many contrasting characteristics. Understanding defining phenotypes of such cells is useful for making suitable choices in differing clinical indications.