Igniting nanotubes with a flash.
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Comment↗
Biomedical subjects
Wei Shi
Publications and source records attributed to Wei Shi.
Synthesis of natural fragrant molecules cis-3-methyl-4-decanolide and aerangis lactone. General enantioselective routes to beta,gamma-cis-disubstituted gamma-lactones and gamma,delta-cis-disubstituted delta-lactones.
General enantioselective routes to 3,4-cis-dialkyl substituted gamma-lactones and 4,5-cis-dialkyl substituted delta-lactones using TiCl(4)-mediated Evans asymmetric aldolization as the key step are reported. The syntheses are exemplified with two natural fragrant molecules, cis-3-methyl-4-decanolide (1) and aerangis lactone (2). The (R,R) steroegenic centers were established using (S)-phenylalanine-derived 2-oxazolidinone or thiazolidinethione as chiral auxiliary, whereas the (S,S) ones were constructed with auxiliary prepared from (R)-phenylglycine. NaBH(4)/CaCl(2)/THF in the presence of a small amount of EtOH was introduced as a new effective method for reductive cleavage of chiral oxazolidinone auxiliaries. Previously unknown, tricky concentration effects were observed during the monotosylation of diol 7 and BOM protection of Evans aldol 23.
Lactones↗
Molecular pathology parameters in human nasopharyngeal carcinoma.
BACKGROUND: To derive a better understanding of the biologic behavior of nasopharyngeal carcinoma (NPC), the authors evaluated a number of molecular variables to address the hypothesis that p53 dysfunction in NPC is associated with Epstein-Barr virus (EBV), increased tumor angiogenesis, lower likelihood of apoptosis, and poorer clinical outcome. MATERIALS: The biopsy samples from 87 NPC patients were obtained and sections were made to detect EBV, using in-situ hybridization; the authors used immunohistochemistry to assess p53, p21(WAF1/CIP1) expression, and microvessel density count (MVD). In situ end labelling was used to evaluate apoptosis and necrosis. Analyses were conducted on the association between each of these variables as well as clinical outcome, including survival and local control. RESULTS: There was a highly significant association between EBV-encoded RNA (EBER) positivity with p53 over-expression in that only 1 out of 32 p53 over-expressing tumors was EBER negative, as opposed to 19 out of 48 p53 negative tumors being EBER negative (P = 0.001). In addition, EBER positivity was highly associated with World Health Organization (WHO) type 3 NPC, Asian/Chinese ethnicity, a lower apoptotic index, and p21 over-expression. p53 over-expression was associated with a higher MVD count. Controlling for age and nodal status, EBER positivity was associated with both improved overall survival (P = 0.02), and disease-free survival (P = 0.04). In contrast, the presence of tumor necrosis was associated with an inferior local control (P = 0.03). CONCLUSION: p53 protein was over-expressed in approximately one third of NPC samples in the current study, and this correlated significantly with the presence of EBER. Epstein-Barr virus status was also associated with WHO type 3 NPC, Asian/Chinese ethnicity, and induction of p21. The presence of EBV appeared to predict for improved survival, the mechanism of which remains to be elucidated in this biologically complex disease.
Cyclin-Dependent Kinase Inhibitor p21↗
[Polymorphism of the HLA-DMA in Han nationality in Hunan Province].
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Adult↗
Tumor-targeted gene therapy for nasopharyngeal carcinoma.
The unique feature of human nasopharyngeal carcinoma (NPC) is its almost universal association with the EBV, which is expressed in a latent form exclusively in cancer cells, and not in the surrounding tissues. We have exploited this differential by constructing a novel replication-deficient adenovirus vector (ad5.oriP) in which transgene expression is under the transcriptional regulation of the family of repeats domain of the origin of replication (oriP) of EBV. When EBNA1, one of the latent gene products of EBV, binds to the family of repeats sequence, this activates transcription of downstream genes. Vector constructs were made using the beta-galactosidase and luciferase reporter genes (ad5oriP.betagal and ad5oriP.luc) or the p53 tumor suppressor gene (ad5oriP.p53). 5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining demonstrated extensive expression only in EBV-positive NPC cells, specifically in response to the presence of EBNA1. The relative difference in expression between EBV-positive and -negative cell lines is approximately 1000-fold. This selective expression was corroborated in EBV-positive and -negative tumor models, along with an absence of transgene expression in the host liver. Significant cytotoxicity was achieved using the adv.oriP.p53 therapeutic gene only in EBV-positive NPC cells, which was enhanced with the addition of ionizing radiation. Cytotoxicity was mediated primarily by induction of apoptosis. These results demonstrate that the oriP sequence can achieve high levels of gene expression targeted specifically to EBV-positive NPC cells in the context of the adv vector. This has now provided the tumor-specific expression system from which additional interventions can be evaluated in future treatment strategies for patients with nasopharyngeal cancers.
Adenoviridae↗
Microchannel DNA sequencing matrices with switchable viscosities.
We review the variety of thermo-responsive and shear-responsive polymer solutions with "switchable" viscosities that have been proposed for application as DNA sequencing matrices for capillary and microfluidic chip electrophoresis. Generally, highly entangled polymer solutions of high-molar mass polymers are necessary for the attainment of long DNA sequencing read lengths (> 500 bases) with short analysis times (< 3 h). However, these entangled polymer matrices create practical difficulties for microchannel electrophoresis with their extremely high viscosities, necessitating high-pressure loading into capillaries or chips. Shear-responsive (shear-thinning) polymer matrices exhibit a rapid drop in viscosity as the applied shear force is increased, but still require a high initial pressure to initiate flow of the solution into a microchannel. Polymer matrices designed to have thermo-responsive properties display either a lowered (thermo-thinning) or raised (thermo-thickening) viscosity as the temperature of the solution is elevated. These properties are generally designed into the polymers by the incorporation of moderately hydrophobic groups in some part of the polymer structure, which either phase-separate or hydrophobically aggregate at higher temperatures. In their low-viscosity states, these matrices that allow rapid loading of capillary or chip microchannels under low applied pressure. The primary goal of work in this area is to design polymer matrices that exhibit this responsive behavior and hence easy microchannel loading, without a reduction in DNA separation performance compared to conventional matrices. While good progress has been made, thermo-responsive matrices have yet to offer sequencing performance as good as nonthermo-responsive networks. The challenge remains to accomplish this goal through the innovative design of novel polymer structures.
Electrophoresis, Capillary↗
Effect of pendent group structures on the chemical selectivity and performance of sulfonated copolymers as novel pseudophases in electrokinetic chromatography.
Amphiphilic copolymers of 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS) with dihydrocholesteryl acrylate (pDHCHAt) or tert-octyl acrylamide (ptOAm) as comonomers were synthesized, characterized and used as new polymeric pseudostationary phases in electrokinetic chromatography. High-efficiency separations with theoretical plates around 500,000 to 870,000/m were achieved. Linear solvation energy relationships analysis of 20 solutes was performed to investigate the retention mechanism. Polycyclic aromatic hydrocarbons (PAHs) were separated under 30% v/v acetonitrile. The separation of nine aromatic model solutes by pDHCHAt showed significantly different selectivity from that of sodium dodecyl sulfate. Although only minor difference in selectivity was found for small aromatic compounds on pDHCHAt and poly(AMPS-lauryl acrylate), significantly different retention mechanism was found for PAHs and n-dodecanophenone comparing both copolymers. Significant chemical selectivity difference was found for selected small aromatic compounds on ptOAm and poly(AMPS-stearyl acrylamide).
Chromatography, Micellar Electrokinetic Capillary↗
Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals.
We show that methylated lysine 9 of histone H3 (Me9H3) is a marker of heterochromatin in divergent animal species. It localises to both constitutive and facultative heterochromatin and replicates late in S-phase of the cell cycle. Significantly, Me9H3 is enriched in the inactive mammalian X chromosome (Xi) in female cells, as well as in the XY body during meiosis in the male, and forms a G-band pattern along the arms of the autosomes. Me9H3 is a constituent of imprinted chromosomes that are repressed. The paternal and maternal pronuclei in one-cell mouse embryos show a striking non-equivalence in Me9H3: the paternal pronucleus contains no immunocytologically detectable Me9H3. The levels of Me9H3 on the parental chromosomes only become equivalent after the two-cell stage. Finally, we provide evidence that Me9H3 is neither necessary nor sufficient for localisation of heterochromatin protein 1 (HP1) to chromosomal DNA.
Animals↗
Alphaherpesvirus antigen quantitation to optimize the diagnosis of herpes B virus infection.
Standardized, quantified virus antigen stocks are essential for dependable quality control of diagnostic assays. Five simple, rapid and economical direct enzyme linked immunoassays (dELISA) were developed to standardize and optimize antigen from five major cross-reacting alphaherpesviruses: herpes B virus, herpesvirus papio 2, langur monkey herpesvirus, herpes simplex virus-1 and herpes simplex virus-2. Each dELISA relied on pools of convalescent sera from rhesus monkeys, baboons, langurs and humans. Conjugates were prepared from purified IgG preparations, fractionated from the same sera and then labeled with peroxidase. Serum coated microplates could be stored at -70 degrees C for at least 1 year before use. The duration of the test was approximately 2.5 h if plates were prepared at an earlier time. Virus antigen titers could be determined from titration curves or from single dilutions using a standard curve. The sensitivity of detection was approximately 8x10(5) PFU/ml. This sensitivity sufficed for the determination of viral antigen mass in live or detergent treated virus stocks that usually contain at least 1x10(8) PFU/ml. The assays were valuable for quality assurance of diagnostic serological assays for herpes B virus and other alphaherpesviruses.
Alphaherpesvirinae↗
Pharmacodynamics and pharmacogenomics of diverse receptor-mediated effects of methylprednisolone in rats using microarray analysis.
Corticosteroids such as methylprednisolone (MPL) produce many of their anti-inflammatory, immunosuppressive, and exaggerated physiological effects by receptor and gene-mediated mechanisms. The temporal pattern of change in four genes in rat tissues was measured by quantitative Northern hybridization and rtPCR after a single dose of MPL. Two profiles were observed: two genes with enhanced expression showed a slow onset and moderate rate of decline within a 24 hr time frame while two genes with reduced expression exhibited a rapid onset and prolonged suppression over a > or = 72 hr time span. These patterns are consistent with and rationalized by pharmacodynamic expectations based on earlier models. cDNA microarrays used to assess the expression levels of 5200 genes at one optimal time-point showed marked variation in baseline values. Of these, 20 genes showed statistically significant enhanced expression with increases ranging from 130 to 1690%, 31 genes exhibited reduced expression ranging from 31 to 72% of control. Many genes could be categorized as affecting acute phase/immune response, energy metabolism, microsomal metabolism, and hepatic function. These studies provide the first simultaneous assessment of the diversity in pharmacogenomic effects of corticosteroids. They also provide some insight into the advantages and limitations of microarray measurements in regard to the pharmacodynamics of drugs having complex, multi-faceted, and integrated mechanisms of action.
Animals↗
Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice.
Transforming growth factor-beta (TGF-beta) signaling plays an important regulatory role during lung fibrogenesis. Smad3 was identified in the pathway for transducing TGF-beta signals from the cell membrane to the nucleus. Using mice without Smad3 gene expression, we investigated whether Smad3 could regulate bleomycin-induced pulmonary fibrosis in vivo. Mice deficient in Smad3 demonstrated suppressed type I procollagen mRNA expression and reduced hydroxyproline content in the lungs compared with wild-type mice treated with bleomycin. Furthermore, loss of Smad3 greatly attenuated morphological fibrotic responses to bleomycin in the mouse lungs, suggesting that Smad3 is implicated in the pathogenesis of pulmonary fibrosis. These results show that Smad3 contributes to bleomycin-induced lung injury and that Smad3 may serve as a novel target for potential therapeutic treatment of lung fibrosis.
Animals↗
Acupuncture treatment for 34 cases of epiphora with dysfunction of lacrimal duct.
We have treated 34 cases of epiphora due to dysfunction of the lacrimal duct with a warm needle puncturing at the Jingming (UB 1) point. The effect was significantly better than that of the control group treated with lacrimal duct irrigation and norflaxacin eye drops (a total effective rate of 91.07% vs. 54.29%).
Acupuncture Therapy↗
[Sub-acute hepatotoxicity of low doses of microcystins].
In order to study sub-acute hepatotoxicity of low doses of microcystins in vivo, as well as to understand the mechanisms of hepatotoxicity of microcystins, eighty Spague-Dawley rats were injected with microcystins intraperitoneally at the doses of 0, 4, 8 and 12 micrograms.(kg.d)-1, respectively, for 35 days. Then blood and liver samples were used for assay. Several enzymatic levels and pathological changes were detected. Both terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and immunohistochemical methods were employed to study the apoptosis and proliferating cell nuclear antigen (PCNA). It was shown that the activity of serum gamma-glutamyltransferase (GGT) and concentrations of whole blood glutathione (GSH) decreased, serum activities of lactate dehydrogenase (LDH) and aminotransferase (AST) increased after exposure to MC. No significant change of concentration of serum alanine aminotransferase (ALT) was observed in the tested groups. Characteristic morphological alterations and active proliferation as well as apoptosis of hepatotocytes were observed in the treated groups. It was suggested that oxidative injury and apoptosis of hepatocytes induced by microcystins may be the mechanisms of its hepatotoxicity.
Animals↗
[Studies of penicillins by micro Raman spectroscopy].
The Raman spectra of three kinds of penicillins were obtained and investigated by micro Raman technique. By comparing these Raman spectra, we find there are many differences among them, and it can be used as an important criterion in distinguishing different kinds of penicillins. In this paper, the characteristic Raman peaks of penicillins have been given. In other hand, we find there is no much difference in the Raman spectra of same kind of penicillin, even though different plants produce them. So, the Raman spectra can't be used to make sure whether certain plant produces one sample.
Amoxicillin↗
Construction and Characterization of a Mutant of Single-chain Urokinase-type Plasminogen Activator Ser(175)-His(187)-mscu-PA
Single-chain urokinase-type plasminogen activator scu-PA is the precursor of double-chain urokinase tcu-PA , which has a much higher intrinsic catalytic activity than other zymogens of the serine protease family. To restore the "zymogen triad" of Asp-His-Ser in the serine protease family, the mutant gene of scu-PA mscu-PA, Ala(175)right curved arrow Ser(175), Tyr(187)right curved arrow His(187) was constructed by the method of oligonucleotide-directed, site-specific mutagenesis in order to reduce its intrinsic catalytic activity. mscu-PA was expressed in E. coli BL21. After denaturation and renaturation in vitro, the mscu-PA was purified to homogeneity by SP-Sepharose ion-exchange chromatography, Sephacryl S-200 chromatography and Benzamidine-Sepharose affinity adsorption. mscu-PA had the same activity to plasmin as scu-PA. The catalytic efficiency measured by k(cat)/K(m) to synthetic substrate S(2444) was 2.5-fold lower than that of scu-PA, and the activity against Glu-plasminogen was also reduced. After activation by plasmin, mtcu-PA and tcu-PA had similar catalytic efficiency against S(2444) and Glu-plasminogen. The results suggest that the intrinsic catalytic activity of mscu-PA be really reduced after restoring the "zymogen triad".
Journal Article↗
QSAR modeling of in vitro inhibition of cytochrome P450 3A4.
We report the QSAR modeling of cytochrome P450 3A4 (CYP3A4) enzyme inhibition using four large data sets of in vitro data. These data sets consist of marketed drugs and drug-like compounds all tested in four assays measuring the inhibition of the metabolism of four different substrates by the CYP3A4 enzyme. The four probe substrates are benzyloxycoumarin, testosterone, benzyloxyresorufin, and midazolam. We first show that using state-of-the-art QSAR modeling approaches applied to only one of these four data sets does not lead to predictive models that would be useful for in silico filtering of chemical libraries. We then present the development and the testing of a multiple pharmacophore hypothesis (MPH) that is formulated as a conceptual extension of the traditional QSAR approach to modeling the promiscuous binding of a large variety of drugs to CYP3A4. In the simplest form, the MPH approach takes advantage of the multiple substrate data sets and identifies the binding of test compounds as either proximal or distal relative to that of a given substrate. Application of the approach to the in silico filtering of test compounds for potential inhibitors of CYP3A4 is also presented. In addition to an improvement in the QSAR modeling for the inhibition of CYP3A4, the results from this modeling approach provide structural insights into the drug-enzyme interactions. The existence of multiple inhibition data sets in the BioPrint database motivates the original development of the concept of a multiple pharmacophore hypothesis and provides a unique opportunity for formulating alternative strategies of QSAR modeling of the inhibition of the in vitro metabolism of CYP3A4.
Cytochrome P-450 CYP3A↗