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Biomedical subjects

Qun Zhou

Publications and source records attributed to Qun Zhou.

At least 19 recordsLinked to original sources

Histone deacetylase inhibitor LBH589 reactivates silenced estrogen receptor alpha (ER) gene expression without loss of DNA hypermethylation.

Our previous studies demonstrated that inhibition of histone deacetylases (HDACs) by trichostatin A reactivates estrogen receptor alpha (ER) gene expression in ER-negative breast cancer cells. Here, we use the clinically relevant HDAC inhibitor, LBH589 (LBH) to explore the roles of HDAC in ER gene silencing. In the ER-negative human breast cancer lines, MDA-MB-231 and MDA-MB-435, treatment with LBH for 24 hours restored ER mRNA and protein expression without a concomitant demethylation of the CpG island at the ER promoter. The expression of ER mRNA was sustained at least 96 hours after withdrawal of LBH treatment. Restoration of ER expression by LBH enhanced 4-hydroxy-tamoxifen sensitivity in MDA-MB-231 cells. The molecular mechanisms by which LBH reactivated silenced ER gene in MDA-MB-231 cells were examined with emphasis on chromatin structure reorganization. By chromatin immunoprecipitation analysis, LBH treatment released DNMT1, HDAC1, and the H3 lysine 9 (H3-K9) methyltransferase SUV39H 1 from the ER promoter. Such changes were associated with an active chromatin formation manifested as accumulation of acetylated histones H3 and H4, a decrease in methylated H3-K9, and an impaired binding of heterochromatin protein 1 (HP1 alpha) at the promoter. Our findings suggest that HDAC inhibitors could restore expression of the silenced ER gene by reorganizing the heterochromatin-associated proteins without alteration in promoter DNA hypermethylation.

Breast Neoplasms↗

Effect of substrate on surface-enhanced Raman scattering of molecules adsorbed on immobilized silver nanoparticles.

Silver nanoparticles were assembled on polyvinylpyridine (PVP) derivatized glass slides. Charge transfer between the adsorbed 4-aminothiophenol (PATP) and the immobilized silver nanoparticles was studied by surface-enhanced Raman spectroscopy with 1064 nm excitation, and compared with that of the silver nanoparticles in the colloid. It was demonstrated that the positive charges of the PVP layer could alter the charge distribution in the immobilized nanoparticles and induce the formation of the dipole in the nanoparticles, leading to less charge transfer from the metal to the adsorbed molecules. The coadsorption of chloride ions on the surface of the immobilized silver nanoparticles resulted in the redistribution of the charges in the nanoparticles and, in turn, altered the charge transfer between the adsorbed PATP molecules and the silver nanoparticles.

Journal Article↗

Sequence requirements and an optimization strategy for short antimicrobial peptides.

Short antimicrobial host-defense peptides represent a possible alternative as lead structures to fight antibiotic resistant bacterial infections. Bac2A is a 12-mer linear variant of the naturally occurring bovine host defense peptide, bactenecin, and demonstrates moderate, broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria as well as against the yeast Candida albicans. With the assistance of a method involving peptide synthesis on a cellulose support, the primary sequence requirements for antimicrobial activity against the human pathogen Pseudomonas aeruginosa of 277 Bac2A variants were investigated by using a luciferase-based assay. Sequence scrambling of Bac2A led to activities ranging from superior or equivalent to Bac2A to inactive, indicating that good activity was not solely dependent on the composition of amino acids or the overall charge or hydrophobicity, but rather required particular linear sequence patterns. A QSAR computational analysis was applied to analyze the data resulting in a model that supported this sequence pattern hypothesis. The activity of selected peptides was confirmed by conventional minimal inhibitory concentration (MIC) analyses with a panel of human pathogen bacteria and fungi. Circular-dichroism (CD) spectroscopy with selected peptides in liposomes and membrane depolarization assays were consistent with a relationship between structure and activity. An additional optimization process was performed involving systematic amino acid substitutions of one of the optimal scrambled peptide variants, resulting in superior active peptide variants. This process provides a cost and time effective enrichment of new candidates for drug development, increasing the chances of finding pharmacologically relevant peptides.

Amino Acid Sequence↗

[Determination of geographical origins of Chinese medical herbs by NIR and pattern recognition].

Geographical origin of medical herbs is an important factor of the quality of many traditional Chinese herbal medicines. The objective of the present study is to investigate whether NIR spectroscopy coupled with pattern recognition techniques could effectively discriminate geographical origins of medical herbs. Nearest neighbor method (NNM) and a SVM-based multiclass classifier were employed to discriminate 269 Angelicae Dahuricae Radix (ADR) samples from 4 provinces and 380 Salviae Miltiorrhizae Radix (SMR) samples from 6 provinces in China. The multiclass classifier achieves leave-one-out cross-validation accuracy of 99% for (ADR) and 95% (SMR). This classification scheme can be a highly accurate approach to the rapid and nondestructive discrimination of medical herbs of different origins.

China↗

[Analysis and discrimination of infant powdered milk via FTIR spectroscopy].

Six kinds of infant powdered milk were identified by Fourier transform infrared spectra (FTIR) and their corresponding second derivative infrared spectra. The main nutritious components such as lipid (1,747, 2,854 and 2,926 cm(-1)), protein (1,658 and 1,540 cm(-1)), and carbohydrate(1,200-900 cm(-1)) of had distinct fingerprint characteristics of FTIR spectra. Maltodextrin, sucrose and lactose also had obvious spectral characteristics, which changed with different added content. For the samples from the same factory but with different sorts, there was some dissimilarity in the relative intensities of infrared absorption peaks due to the difference in fat, protein and carbohydrate. For the samples of the same sort but from different factories, there are certain similarities in the IR spectra, however, the second derivative infrared spectra present different fingerprint characteristics. This analytical method is fast and direct for evaluating the quality of infant powdered milk.

Carbohydrates↗

[Identification study of different Flos Trollii by IR].

OBJECTIVE: To establish a method to identify different Flos Trollii with IR spectra and to provide a new technique for their science estimation and quality identification. METHODS: Their IR spectra were obtained by the method of intuitionistic analysis-selecting point to normalization. RESULTS: Differences on the shape, the position, the height and the relative intensity of absorption peaks were shown in IR spectra of the ten samples. CONCLUSIONS: Different Flos Trollii can be identified using IR spectra obtained by the method of intuitionistic analysis-selecting point to normalization. This new method can be used to study the identification features of the influence factors of Traditional Chinese Medicine quality.

Desiccation↗

[Analysis and characterization of fingerprint infrared spectra for ecology-planted Coptis chinensis].

The fingerprint features of infrared spectra for Coptis chinensis in different shading conditions (shelf, firry wood, corn wood) and with different ages (one year to five years) were studied. According to the ratio of characteristic peaks, the rules of the influence of shadings and ages on Coptis chinensis growth were illustrated, which confirms the feasibility of ecological planting technique for Coptis chinensis. Fourier transform infrared (FTIR) spectroscopy was used to analyze the influence of growing conditions on the growth of Coptis chinensis. The shadings and ages have no obvious influence on the quality of Coptis chinensis root, which is consistent with the results of HPLC. The quality of Coptis chinensis with ecological planting is identical with those in shelves. Infrared technique provides a meaningful guide to standardized planting of medicinal plants.

Agriculture↗

[Study on the identification of standard and false Gancao by Fourier transform infrared spectroscopy].

Standard Gancao (Glycyrrhiza uralensis Fisch) and false Ciguogancao (Glycyrrhiza pallidiflata Batal) were identified fast, nondestructively by Fourier transform infrared spectroscopy (FTIR) combined with derivative spectra and two-dimensional correlation spectroscopy (2D) in the present article. The result shows that although the two kinds of Gancao belong to one genus, there are some certain differences in their chemical components that are reflected in the IR spectra, but with some similarity and dissimilarity in the IR spectra. The two kinds of Gancao are quite different from each other in second derivative spectra and 2D spectra. Based on the differences reflected in the IR and 2D IR, the standard gancao can be identified from the false easily and clearly. The result also proved that there is a relationship between the IR spectra and the chemical components of the herbs. This method is fast, accurate and nondestructive, and the wastage of sample is less. The fast, accurate property of 2D spectroscopy makes it a powerful and new approach to evaluating medicinal herbs impersonally.

Glycyrrhiza↗

[Analysis and discrimination of Collocalia esculenta L. via FTIR spectroscopy].

Collocalia esculenta L. is called Yanwo in China. Thirty kinds of dry yanwo were identified by Fourier transform infrared spectroscopy (FTIR) . The results indicated that there were some obvious differences in FTIR between the dry yanwo and the natural yanwo, mainly represented in some absorption peaks of protein, amino acid (1 634, 1 535 cm(-1)) and amylase (1 034 cm9-1)). Meanwhile, the shape, position and intensity of the peaks from methylene (2 935 cm(-1)), protein and amino acid (1 647, 1 533, 1 447 cm(-1)) in dry yanwo were similar to those of the glutin. Therefore, different amounts of glutin were added in dry yanwo samples. The content of candy in some dry candy yanwo products was as high as 99%, but the content of yanwo was only 1%. The characteristic peaks of yanwo in these products even could not be found. So the quality of yanwo in the market could not be guaranteed from these results. FTIR is fast and direct to analyse and evaluate the quality of yanwo product.

Animals↗

Study of traditional Chinese animal drugs using FT-IR and 2D-IR correlation spectroscopy.

Using FT-IR and 2D-IR correlation spectroscopy, the intensity changes and their sequence of amide I and II bands of four traditional Chinese animal drugs (Cornu Cervi Pantotrichum, Cornu Saigae Tataricae, Scorpio and Hirud) under thermal perturbation are studied, and component of Ca(3)(PO(4))(2) in the drug of Cornu Cervi Pantotrichum and sulfates components in the drug of scorpion are identified. The drug of Cornu Cervi Pantotrichum contains inorganic salt Ca(3)(PO(4))(2) and the drug of Scorpio contains sulfates. It is assigned that the bands of 604 and 561 cm(-1) belong to the component of Ca(3)(PO(4))(2), and the bands of 637 and 615 cm(-1) belong to sulfates. Organic components of these drugs respond to the thermal perturbation far stronger than that of the inorganic components. The intensities of amide I and II bands in the drugs, except for amide II band in drug Scorpio, change strongly. For the drugs of Cornu Cervi Pantotrichum, Cornu Saigae Tataricae and Hirudo, the intensity changes of amide II band occurs prior to that of amide I band. The C-N bond in the product operator(3)(4) conjugative system converts from double bond to single bond, but the C=O bond remains double bond during the heating process. On the other hand, amide II vibrations, which may involve much more of the hydrogen bonded local structures of amide groups in the system compared to the C=O dominated amide I vibration, may undergo thermally induced changes at a temperature much lower than the other mode. The traditional Chinese animal drugs can be identified rapidly and non-separately by using FT-IR and 2D-IR correlation spectroscopy.

Amides↗

Protein phosphatase 2A regulates estrogen receptor alpha (ER) expression through modulation of ER mRNA stability.

Protein phosphatase 2A (PP2A) is a ubiquitously expressed member of the serine-threonine phosphatase family that is involved in regulation of many cellular processes including transcription, translation, cellular metabolism, and apoptosis. Because of a correlation between PP2A and estrogen receptor alpha (ER) expression in several human breast cancer cell lines, the effect of PP2A on regulation of ER expression in the human breast cancer cell line MCF-7 was studied. Inhibition of PP2A using the pharmacologic inhibitor okadaic acid at 250 nm for 16 h resulted in a 60% reduction in PP2A activity in MCF-7 cells concurrent with a 75% reduction in ER mRNA and protein expression. Similar results were obtained with a small interfering RNA probe that specifically inhibited PP2A expression. ER promoter studies showed that regulation of ER through the PP2A pathway did not occur through transcriptional activation. Rather, PP2A mediated ER expression through modulation of ER mRNA stability through degradation of ER mRNA, reversible with concomitant treatment with the proteasomal inhibitor MG 132. These data suggest a novel pathway controlling ER expression resulting from the activation of PP2A, potentially providing a novel therapeutic target.

3' Untranslated Regions↗

Effect of genetic background on glycosylation heterogeneity in human antithrombin produced in the mammary gland of transgenic goats.

Glycosylation is involved in the correct folding, targeting, bioactivity and clearance of therapeutic glycoproteins. With the development of transgenic animals as expression systems it is important to understand the impact of different genetic backgrounds and lactations on glycosylation. We have evaluated the glycosylation of recombinant antithrombin produced in several transgenic goat lines, from cloned animals and from different types of lactation including induced lactations. Our results show glycosylation patterns from the protein expressed in animals, derived from the same founder goat, are mostly comparable. Furthermore, the protein expressed in two cloned goats had highly consistent oligosaccharide profiles and similar carbohydrate composition. However, there were significantly different oligosaccharide profiles from the proteins derived from different founder goats. Artificial induction of lactation did not have significant effects on overall carbohydrate structures when compared to natural lactation. The only major difference was that recombinant antithrombin from induced lactations contained a slightly higher ratio of N-acetylneuraminic acid to N-glycolylneuraminic acid and less amount of oligosaccharides containing N-glycolylneuraminic acid. The oligosaccharides from all animals were a mixture of high mannose-, hybrid- and complex-type oligosaccharides. Sialic acid was present as alpha-2,6-linkage and no alpha-1,3-linked galactose was observed. These results indicate that transgenic animals with closely related genetic backgrounds express recombinant protein with comparable glycosylation.

Animals↗

Research on processing medicinal herbs with multi-steps infrared macro-fingerprint method.

How to apply rapid and effective method to research medicinal herbs, the representative of complicated mixture system, is the current study focus for analysts. The functions of non-processed and processed medicinal herbs are greatly different, so controlling the processing procedure is highly important for guarantee of the curative effect. Almost, the conventional criteria of processing are based on personal sensory experience. There is no scientific and impersonal benchmark. In this article, we take Rehmannia for example, conducting a systematic study on the process of braising Rehmannia with yellow wine by using the multi-steps infrared (IR) macro-fingerprint method. The method combines three steps: conventional Fourier transform infrared spectroscopy (FT-IR), second derivative spectroscopy, and two-dimensional infrared (2D-IR) correlation spectroscopy. Based on the changes in different types of IR spectra during the process, we can infer the optimal end-point of processing Rehmannia and the main transformations during the process. The result provides a scientific explanation to the traditional sensory experience based recipe: the end-point product is "dark as night and sweet as malt sugar". In conclusion, the multi-steps IR macro-fingerprint method, which is rapid and reasonable, can play an important role in controlling the processing of medicinal herbs.

Carbohydrate Conformation↗

Viral vectors for cancer gene therapy: viral dissemination and tumor targeting.

Cancer gene therapy is the most promising and active field in gene therapy treatment. Although previous experimental and clinical trials have brought forward some exciting cases, in general, the clinical benefits have been limited. A major difference between virus-mediated gene therapy and other therapies is the poor physical diffusibility of viral vectors, which is also one of the major obstacles in cancer gene therapy. As safety is a prerequisite to enhanced viral dissemination, tumor-specific targeting becomes crucial. The present review focuses on questions related to efficient viral dissemination in tumor masses and how to sustain a high level of oncolytic virus targeting of tumor cells only. We will first consider two common reasons for limited virus spread in tumor masses and then discuss strategies for improving the tumor-specific oncolysis of currently used viral vectors and to comment on their advantages and potential problems.

Animals↗

[Use of FTIR and pattern recognition to determine geographical origins of Chinese medical herbs].

Geographical origin of medical herbs is an important factor of the quality of many traditional Chinese herbal medicines. The objective of this study is to investigate whether FTIR spectroscopy coupled with pattern recognition techniques could effectively discriminate geographical origins of medical herbs. Nearest neighbor method (NNM) and a SVM-based multiclass classifier were employed to discriminate 269 angelicae dahuricae radix (ADR) samples from 4 provinces in China and 380 salviae miltiorrhizae radix (SMR) samples from 6 provinces. A leave-one-out cross-validation accuracy of 99% was achieved by the multiclass classifier. The study shows this classification scheme can be a highly accurate approach for the discrimination of medical herbs of different origins.

Algorithms↗