A chiral [2]catenane precursor of the antiarthritic gold(I) drug auranofin.
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Anthracenes↗
Biomedical subjects
Rong Chen
Publications and source records attributed to Rong Chen.
A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis.
A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes.
Adolescent↗
Proteomic analysis of the mode of antibacterial action of silver nanoparticles.
Silver nanoparticles (nano-Ag) are potent and broad-spectrum antimicrobial agents. In this study, spherical nano-Ag (average diameter = 9.3 nm) particles were synthesized using a borohydride reduction method and the mode of their antibacterial action against E. coli was investigated by proteomic approaches (2-DE and MS identification), conducted in parallel to analyses involving solutions of Ag(+) ions. The proteomic data revealed that a short exposure of E. coli cells to antibacterial concentrations of nano-Ag resulted in an accumulation of envelope protein precursors, indicative of the dissipation of proton motive force. Consistent with these proteomic findings, nano-Ag were shown to destabilize the outer membrane, collapse the plasma membrane potential and deplete the levels of intracellular ATP. The mode of action of nano-Ag was also found to be similar to that of Ag(+) ions (e.g., Dibrov, P. et al, Antimicrob. Agents Chemother. 2002, 46, 2668-2670); however, the effective concentrations of nano-Ag and Ag(+) ions were at nanomolar and micromolar levels, respectively. Nano-Ag appear to be an efficient physicochemical system conferring antimicrobial silver activities.
Anti-Bacterial Agents↗
[Experimental research on antagonistic effect of heme oxygenase-1 on acute mercury chloride induced renal impairment].
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Animals↗
[Fluorescence spectral characteristics of human blood and its endogenous fluorophores].
The three-dimensional fluorescence spectra and excitation-emission matrix of human blood were measured, and an attempt was made to exploit the endogenous fluorophores of major peaks in the UV and visible. The result indicates that the absorption peaks of human blood appear at 274, 345, 415, 541 and 576 nm. Based on the analysis of fluorescence excitation-emission matrix, the major emission peaks of human blood occur at excitation-emission wavelength pairs of 260-630, 280-340, 340-460 and 450-520 nm, which are attributed to endogenous porphyrins, tryptophan, reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH), and flavin adenine dinucleotide (FAD), respectively. These results can be used to analyze and explain the effect of blood on the distortion of fluorescence signal of human tissues for optical diagnosis.
Blood Chemical Analysis↗
[Changes of mitochondrial membrane potential (delta psi m) and calcium concentration in cultured glomerular mesangial cells of rats with obstructive jaundice].
OBJECTIVE: To explore the effect of mitochondrial membrane potential (delta psi m) and calcium concentration on the kidney injury of rats with obstructive jaundice and to probe into the underlying mechanism. METHODS: Sixty male Sprague-Dowley rats, weighing 200 g to 250 g were randomly divided into three groups: control group; sham operation group; experiment group. And the rats of experiment group were subdivided into two groups according to the time (15 d, 21 d) after the common bile duct ligation. The experiment groups were rendered jaundiced by doubly ligating the common bile duct. Glomeruli were isolated, the glomerular mesangial cells (GMCs) were cultured. The mitochondrial membrane potential (delta psi m) was measured by flow cytometry; the concentration of calcium was measured by confocal microscopes. RESULTS: The amount of mitochondrial membrane potential (delta psi m) was decreased (P < 0.05) in the rats with obstructive jaundice, compared with the control; the concentration of calcium was increased (P < 0.05) in the rats with obstructive jaundice, compared with the control. Conclusion The calcium incurrent that leads to changes in amount of mitochondrial membrane potential (delta psi m) has significant effect on the kidney injury of the rats with obstructive jaundice.
Animals↗
Novel derivatives of chitosan and their antifungal activities in vitro.
Three kinds of Schiff bases of carboxymethyl chitosan (CMCTS) were prepared, and their antifungal activities were assessed according to Jasso de Rodríguez's method. The results indicated that 2-(2-hydroxybenzylideneamino)-6-carboxymethylchitosan (HNCMCTS) and 2-(5-chloro-2-hydroxybenzylideneamino)-6-carboxymethylchitosan (HCCMCTS) had better inhibitory effects than those of chitosan or CMCTS against Fusarium oxysporium f. sp. vasinfectum, Alternaria solani, and Valsa mali.
Alternaria↗
Molecular cloning and functional characterization of the dopamine transporter from Eloria noyesi, a caterpillar pest of cocaine-rich coca plants.
Cocaine is produced by coca plants as a chemical defense to deter feeding by insects. It has been shown that cocaine sprayed on tomato leaves reduces insect feeding, causes abnormal behaviors at low doses and kills feeding insects at doses equivalent to that in coca leaves [Nathanson, J.A., Hunnicutt, E.J., Kantham, L., Scavone, C., 1993. Cocaine as a naturally occurring insecticide. Proc. Natl. Acad. Sci. U. S. A. 90, 9645-9648.]. Most insects avoid coca leaves except the larvae of Eloria noyesi, a caterpillar pest of coca plants, which feeds preferentially on coca leaves. In the current study, we cloned and characterized the dopamine transporters (DATs) from caterpillars of E. noyesi (enDAT) and the silkworm, Bombyx mori (B. mori, bmDAT). The two insect DATs shared 88% amino acid sequence homology and functional similarity. Although enDAT and bmDAT showed the highest affinity for dopamine among endogenous amines, they were more sensitive to mammalian NET-selective inhibitors than to mammalian DAT-selective inhibitors. Despite a high cocaine content in the food source for E. noyesi, cocaine sensitivity of enDAT was similar to that of bmDAT, suggesting that mechanisms other than DAT insensitivity to cocaine, such as cocaine sequestration, might be responsible for cocaine resistance in this species. Given the significant differences in pharmacological profile from mammalian DATs, invertebrate DATs provide excellent tools for identifying regions and residues in the transporters that contribute to high-affinity binding of psychostimulants and antidepressants.
Amino Acid Sequence↗
Antioxidant activity of different sulfate content derivatives of polysaccharide extracted from Ulva pertusa (Chlorophyta) in vitro.
Polysaccharide extracted from Ulva pertusa (Chlorophyta) is a group of sulfated heteropolysaccharide; for simplicity, the sulfated polysaccharide is referred to as ulvan in this paper. In this study, different sulfate content ulvans were prepared with sulfur trioxide/N,N-dimethylformamide (SO3-DMF) in formamide, and their antioxidant activities were investigated including scavenging activity of superoxide and hydroxyl radicals, reducing power and metal chelating ability. As expected, we obtained several satisfying results, as follows: firstly, high sulfate content ulvans had more effective scavenging activity on hydroxyl radical than natural ulvan. Secondly, comparing with natural ulvan, high sulfate content ulvans exhibited stronger reducing power. Thirdly, HU4 (sulfate content, 30.8%) and HU5 (sulfate content, 32.8%) showed more pronounce chelating ability on ferrous ion at high concentration than other samples.
Antioxidants↗
Network analysis of mild cognitive impairment.
We present a network analysis of a cross-sectional study of mild cognitive impairment (MCI). Network analysis, as opposed to univariate analysis, accounts for interactions among brain structures in explaining a clinical outcome. In this context, we analyze structural magnetic resonance (MR) data based on a Bayesian network representation of variables in the problem domain. The Bayesian network resulting from this analysis reveals complex, nonlinear multivariate associations among morphological changes in the left hippocampus and in the right thalamus and the presence of mild cognitive impairment. This Bayesian network could be used to predict the presence of mild cognitive impairment from structural MR scans.
Aged↗
The properties of CpG islands in the putative promoter regions of human immunoglobulin (Ig) genes.
CpG island is a GC-rich motif occurred in gene promoter region, which can play important roles in gene silencing and imprinting. Here, we present a set of discriminant functions that can recognize the structural and compositional features of CpG islands in the putative promoter regions (PPRs) of human and mouse immunoglobulin (Ig) genes. We showed that the PPRs of both human and mouse Ig genes irrespective of gene chromosomal localization are apparently CpG island poor, with a low percentage of the CpG islands overlapped with the transcription start site (TSS). The human Ig genes that have CpG islands in the PPRs show a very narrow range of CpG densities. 47% of the Ig genes fall in the range of 3.5-4 CpGs/100 bp. In contrast, the non-Ig genes examined have a wide range of the density of CpG island, with 10.5% having the density of 8.1-15 CpGs/100 bp. Meantime, five patterns of the CpG distributions within the CpG islands have been classified: Pat A, B, C, D, and E. 21.6% and 10.8% of the Ig genes fall into the Pat B and Pat D groups, respectively, which were significantly higher than the non-Ig genes examined (8.2% and 3.8%). Moreover, the length of CpG islands is shorter in human Ig genes than in non-Ig genes but is much longer than in mouse orthologues. These findings provide a clear picture of non-neutral and nonrandom occurrence of the CpG islands in the PPRs of human and mouse Ig genes, which facilitate rational recommendations regarding their nomenclature.
Animals↗
Silver nanoparticles fabricated in Hepes buffer exhibit cytoprotective activities toward HIV-1 infected cells.
Silver nanoparticles fabricated in Hepes buffer exhibit potent cytoprotective and post-infected anti-HIV-1 activities toward Hut/CCR5 cells.
Apoptosis↗
ZDOCK and RDOCK performance in CAPRI rounds 3, 4, and 5.
We present an evaluation of the results of our ZDOCK and RDOCK algorithms in Rounds 3, 4, and 5 of the protein docking challenge CAPRI. ZDOCK is a Fast Fourier Transform (FFT)-based, initial-stage rigid-body docking algorithm, and RDOCK is an energy minimization algorithm for refining and reranking ZDOCK results. Of the 9 targets for which we submitted predictions, we attained at least acceptable accuracy for 7, at least medium accuracy for 6, and high accuracy for 3. These results are evidence that ZDOCK in combination with RDOCK is capable of making accurate predictions on a diverse set of protein complexes.
Algorithms↗
Protein-Protein Docking Benchmark 2.0: an update.
We present a new version of the Protein-Protein Docking Benchmark, reconstructed from the bottom up to include more complexes, particularly focusing on more unbound-unbound test cases. SCOP (Structural Classification of Proteins) was used to assess redundancy between the complexes in this version. The new benchmark consists of 72 unbound-unbound cases, with 52 rigid-body cases, 13 medium-difficulty cases, and 7 high-difficulty cases with substantial conformational change. In addition, we retained 12 antibody-antigen test cases with the antibody structure in the bound form. The new benchmark provides a platform for evaluating the progress of docking methods on a wide variety of targets. The new version of the benchmark is available to the public at http://zlab.bu.edu/benchmark2.
Algorithms↗
Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death.
Flavopiridol is active against chronic lymphocytic leukemia (CLL) cells in vitro and in the treatment of advanced stage disease, but the mechanisms of these actions remain unclear. Originally developed as a general cyclin-dependent kinase inhibitor, flavopiridol is a potent transcriptional suppressor through the inhibition of positive transcription elongation factor b (P-TEFb; CDK9/cyclin T). P-TEFb phosphorylates the C-terminal domain (CTD) of RNA polymerase II to promote transcriptional elongation. Because most CLL cells are not actively cycling, and their viability is dependent upon the continuous expression of antiapoptotic proteins, we hypothesized that flavopiridol induces apoptosis in CLL cells through the transcriptional down-regulation of such proteins. This study demonstrated that flavopiridol inhibited the phosphorylation of the CTD of RNA polymerase II in primary CLL cells and reduced RNA synthesis. This was associated with a decline of the transcripts and the levels of short-lived antiapoptotic proteins such as myeloid cell leukemia 1 (Mcl-1), and resulted in the induction of apoptosis. The B-cell lymphoma 2 (Bcl-2) protein level remained stable, although its mRNA was consistently reduced, suggesting that the outcome of transcriptional inhibition by flavopiridol is governed by the intrinsic stability of the individual transcripts and proteins. The dependence of CLL-cell survival on short-lived oncoproteins may provide the biochemical basis for the therapeutic index in response to flavopiridol.
Antineoplastic Agents↗
Human T helper (Th) cell lineage commitment is not directly linked to the secretion of IFN-gamma or IL-4: characterization of Th cells isolated by FACS based on IFN-gamma and IL-4 secretion.
Upon activation in vitro, only a fraction of the bulk human T helper cell cultures secret the hallmark Th1/2 cytokines (IFN-gamma for Th1 and IL-4 for Th2, respectively). It is uncertain whether these IFN-gamma-/IL-4- cells are differentiated Th1 or Th2 cells. Here, we have characterized live IFN-gamma+, IL-4+ and IFN-gamma-/IL-4- cells isolated from Th cell cultures treated under Th1 or Th2 polarizing conditions by employing affinity matrix capture technology. RNA samples from the sorted cells were analyzed by real time RT-PCR and microarrays. The double negative cells from either Th1 or Th2 cultures expressed lower levels of Th1/Th2 marker cytokine genes (IFNgamma, IL4, and IL5). However, they were comparable with the IFN-gamma+ or IL-4+ cells in the expression levels of other Th1/Th2 marker genes (GATA3, Tbet, and IL12Rbeta2). Most importantly, these double negative cells were already committed in their Th1/Th2 lineages. Gene expression profiling analysis showed that very few previously identified Th1/Th2 marker genes were differentially expressed between the IFN-gamma or IL-4 producers and the non-producers, further underscoring the similarity between these two groups.
Cell Differentiation↗
Differential effects of angiotensin II on atherogenesis at the aortic sinus and descending aorta of apolipoprotein-E-deficient mice.
Angiotensin (Ang) II infusion increases atherosclerosis and leads to the formation of abdominal aortic aneurysms in apolipoprotein E-deficient (ApoE-/-) mice. Conversely, blockade of the renin-angiotensin system (RAS) decreases atherosclerosis in this model. However, there are conflicting data in the literature concerning responses to both Ang II infusion and RAS blockade which may depend on age, sex, dose, duration of treatment, and the site at which lesion area was measured. In the present study we examined the effects of Ang II infusion on lesion formation in male ApoE-/- mice both at the aortic sinus and in the descending aorta, starting at different ages, and varying in duration. We also tested the effects of the Ang II receptor antagonist losartan at different doses in both males and females. Blood pressure and plasma renin concentration (PRC) were measured as indicators of the hemodynamic and neurohormonal effects of these treatments. Administration of Ang II increased lesion area much more in the descending aorta than at the aortic sinus. However, spontaneous lesion development at the aortic sinus was much greater than in more distal regions of the aorta. Aneurysms were observed in all treatment groups but were less severe in animals treated from 4 weeks age, possibly because of protective remodeling. Losartan treatment reduced lesion area at the aortic sinus, although differences were only significant in female mice. These findings demonstrate regional and temporal differences in the sensitivity of the aorta to the effects of RAS stimulation and blockade, and may help to explain some of the discrepancies between previous reports from other laboratories.
Angiotensin II↗
cDNA cloning and mRNA expression of neuropeptide Y in orange spotted grouper, Epinephelus coioides.
A full-length cDNA encoding the neuropeptide Y (NPY) was cloned from the hypothalamus of orange spotted grouper (Epinephelus coioides) by rapid amplification of cDNA ends approaches. The NPY cDNA sequence is 688 bp long and has an open reading frame of 300 bp encoding prepro-NPY with 99 amino acids. The deduced amino acid sequences contain a 28-amino-acids signal peptide followed by a 36-amino-acids mature NPY peptide. mRNA expression of NPY was determined using semi-quantitative RT-PCR followed by Southern blot analysis. NPY mRNA was expressed in olfactory bulb, telencephalon, pituitary, hypothalamus, optic tectum-thalamus, medulla oblongata, cerebellum and spinal cord. Low levels of NPY mRNA expression were found in retina, ovary and stomach, while much lower levels of expression were detected in liver, heart, gill, skin, anterior intestine, thymus and blood. No NPY mRNA expression was observed in unfertilized eggs, newly fertilized eggs, 16-cells stage and morula stage of the embryo and lower levels of expression were detected in the blastula, gastrula and neurula stages. It was highly expressed from lens formation stage to 52-day-old larval stage. NPY might be involved in the late embryonic and larval development of the orange spotted grouper.
Amino Acid Sequence↗