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Biomedical subjects

Liang Zhou

Publications and source records attributed to Liang Zhou.

At least 19 recordsLinked to original sources

[Expression, loss of heterozygosity, and methylation of GNAT1 gene in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: In nasopharyngeal carcinoma (NPC), chromosome 3p21.3 is a high frequency deletion region. Evidences from both loss of heterozygosity (LOH) and functional studies showed that there may exists NPC-related tumor suppressor genes on 3p21.3. This study was to investigate the expression, LOH, and methylation of GNAT1 gene, which locates at 3p21.3, in NPC. METHODS: The expression of GNAT1 in 33 specimens of primary NPC and 15 specimens of chronic nasopharyngitis tissue was detected by reverse transcription-polymerase chain reaction (RT-PCR). LOH and promoter methylation status of GNAT1 were examined by microsatellites analysis and methylation-specific polymerase chain reaction (MSP). RESULTS: GNAT1 was expressed stably in all chronic nasopharyngitis tissues, while absent or down-regulated in 24 (72.7%) specimens of NPC (P=0.022). LOH analysis showed allele loss of GNAT1 in 3 (15%) specimens of NPC. LOH of GNAT1 was correlated to its expression level (P=0.016). Methylation analysis showed hypermethylation of GNAT1 promoter in all primary NPC tissues and in 12 (80%) specimens of chronic nasopharyngitis tissues. CONCLUSIONS: Expression of GNAT1 gene is down-regulated or absent in NPC tissues, which may relate to allele loss of GNAT1 in NPC, but not relate to its promoter hypermethylation. Hypermethylation of GNAT1 may not be oncogenic mechanisms of NPC.

Adult↗

Relationship between hs-CRP, proMMP-1, TIMP-1 and coronary plaque morphology: intravascular ultrasound study.

BACKGROUND: Rupture of unstable plaque with subsequent thrombus formation is the common pathophysiological substrate of the acute coronary syndrome (ACS). It is of potential significance to explore the blood indexes predicting plaque characteristics. Little studies have focused on this field. Therefore we investigated the relationship between hypersensitive C-reactive protein (hs-CRP), pro-matrix metalloproteinase-1 (proMMP-1), tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and coronary plaque morphology. METHODS: Intravascular ultrasound (IVUS) examination was done in 152 patients with confirmed coronary heart disease before percutaneous coronary intervention from February 2003 to July 2005. Plasma samples of arterial blood were collected prior to the procedure. The level of hs-CRP, proMMP-1 and TIMP-1 were respectively measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Unstable and ruptured plaque were found more frequently in patients with acute myocardial infarction and unstable angina. External elastic membrane cross-sectional area (EEM CSA), plaque area, lipid pool area and plaque burden were significantly larger in ruptured and unstable plaque group. Positive remolding, thinner fabric-cap, smaller minimal lumen cross-sectional area (MLA), dissection and thrombus were significantly more frequent in ruptured and unstable plaque group. The levels of plasma hs-CRP, proMMP-1 and TIMP-1 were higher in ruptured plaque group. hs-CRP > 8.94 mg/L was used to predict ruptured plaque with a ROC curve area of 0.76 [95% confidence interval (CI), 67.0% - 85.8%], sensitivity of 71.8%, specificity of 77.0% and accuracy of 69.2% (P < 0.01), similarly for proMMP-1 > 0.12 ng/ml with a ROC curve area of 0.69 [95% CI, 58.2% - 80.2%], sensitivity of 69.2%, specificity of 75.2% and accuracy of 66.2% (P < 0.01), and TIMP-1 > 83.45 ng/ml with a ROC curve area of 0.67 [95% CI, 56.2% - 78.3%], sensitivity of 66.7%, specificity of 61.9% and accuracy of 66.2% (P < 0.01). CONCLUSION: The plaque characteristics correlate with the clinical presentation. The elevation of hs-CRP, proMMP-1 and TIMP-1 are related to the plaque instability and rupture.

Aged↗

Expression and characterization of RNA-dependent RNA polymerase of Dendrolimus punctatus tetravirus.

Dendrolimus punctatus tetravirus (DpTV) has been identified as a new member of the genus Omegatetravirus of the family Tetraviridae that may be related serologically to Nudaurelia capensis virus (NomegaV). To establish the function of DpTV RNA genome and to better understand the mechanism of viral replication, the putative RNA-dependent RNA polymerase (RdRp) domain has been cloned and expressed in Escherichia coli. The recombinant protein was purified on a Ni-chelating HisTrap affinity column and demonstrated to initiate viral RNA synthesis in a primer-independent manner but not by terminal nucleotidyle transferase activity in the presence of Mg2+ and RNA template. Mutation of the GDD to GAA interferes with the residues at the polymerase active site and metal ions, and thus renders the polymerase inactive.

Amino Acid Sequence↗

The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.

IL-17-producing T lymphocytes have been recently shown to comprise a distinct lineage of proinflammatory T helper cells, termed Th17 cells, that are major contributors to autoimmune disease. We show here that the orphan nuclear receptor RORgammat is the key transcription factor that orchestrates the differentiation of this effector cell lineage. RORgammat induces transcription of the genes encoding IL-17 and the related cytokine IL-17F in naïve CD4(+) T helper cells and is required for their expression in response to IL-6 and TGF-beta, the cytokines known to induce IL-17. Th17 cells are constitutively present throughout the intestinal lamina propria, express RORgammat, and are absent in mice deficient for RORgammat or IL-6. Mice with RORgammat-deficient T cells have attenuated autoimmune disease and lack tissue-infiltrating Th17 cells. Together, these studies suggest that RORgammat is a key regulator of immune homeostasis and highlight its potential as a therapeutic target in inflammatory diseases.

Animals↗

ZNF325, a novel human zinc finger protein with a RBaK-like RB-binding domain, inhibits AP-1- and SRE-mediated transcriptional activity.

Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of eukaryotic cell regulation. The zinc-finger-containing transcription factors have been previously revealed to be involved in the regulation of the MAPK signaling pathways. Here, we have identified a novel human zinc-finger transcriptional repressor, ZNF325, that contains a RBaK-like RB-binding domain and 15 tandem repeated C2H2 type zinc fingers. Northern blot analysis indicates that a 2.7 kb transcript specific for ZNF325 is widely expressed in all tissues examined at adult stage and in most of the embryonic tissues. Overexpression of ZNF325 in COS-7 cells inhibits the transcriptional activities of AP-1 and SRE. The deletion and RNAi analysis indicate that the C2H2 zinc finger motifs represent the basal transcriptional repressive activity. These results indicate that the ZNF325 protein may act as a novel transcription repressor in MAPK signaling pathway to mediate cellular functions.

Amino Acid Sequence↗

[Preliminary study of serum proteome biomarkers of hypopharyngeal squamous cell carcinoma].

OBJECTIVE: To screen the serum proteome biomarkers of hypopharyngeal squamous cell carcinoma (HSCC) and to establish a predictive model for early detection of HSCC. METHODS: Serum samples were collected from 48 HSCC patients before surgery and 52 age and sex-matched individuals without cancer used as controls. The samples were divided into 2 sets: training set (including 36 HSCC patients and 36 controls) and blind testing set (including 12 HSCC patients and 16 controls). With WCX2 and IMAC3 protein chips, surface-enhanced laser desorption/ionization (SELDI) was used to analyze the serum protein profiling. 72 samples of the training set were analyzed by a decision tree algorithm to be able to differentiate HSCC patients from controls. Double-blind test was used to determine the sensitivity and specificity of the classification model. RESULTS: Ranging from 2000 - 50000 (M/Z), 11 potential biomarkers on WCX2 and 19 biomarkers on IMAC3 protein chip could differentiate HSCC patients from the control set (P < 10(-5)). Among them 4 candidate protein peaks with the m/z values of 7796, 4216, 5927, and 5361 were selected to be used to establish a predictive model by Biomarker Pattern Software. The model separated effectively the HSCC samples from the control samples, achieving a sensitivity of 94.44%, and a specificity of 88.89%. An accuracy of 85.71% (24/28), sensitivity of 91.67% (11/12), specificity of 81.25% (13/16), positive predictive value of 78.57%% (11/14), and negative predictive value of 92.85% (13/14) were validated in the double-blind testing set. CONCLUSION: The SELDI-TOF-MS Protein Chip combined with artificial intelligence classification algorithm helps find serum proteome biomarkers and establish predictive model for early diagnosis of HSCC. This technique has potential for the development of a screening test for the detection of HSCC.

Adult↗

Synthesis and antitumor activity of icogenin and its analogue.

Natural saponin icogenin, namely 25(S)-22-O-methyl-furost-5-en-3beta,26-dio-3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->3)]-beta-D-glucopyranoside, and one of its analogues, 25(S)-22-O-methyl-furost-5-en-3beta,26-dio-3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->3)]-alpha-D-glucopyranoside, were first synthesized via line strategy and convergent approach, respectively. It was observed that icogenin and its analogue show potent antitumor activity in vitro.

Antineoplastic Agents↗

Establishment and applications of epstein-barr virus-based episomal vectors in human embryonic stem cells.

Human embryonic stem (hES) cells are capable of unlimited cell proliferation yet maintain the potential to differentiate into many cell types. Here we reported an Epstein-Barr virus (EBV)-based vector system used to improve transfection efficiency in hES cells. Plasmids containing oriP, the latent replication origin of EBV, can be propagated stably as episomal DNA in human cells that express the EBV nuclear antigen 1 (EBNA1), which binds to oriP and functions as the trans-acting replication initiator. It was reported that the EBV replicon could harbor a DNA fragment of up to 330 kilobase pairs. Plasmids containing an enhanced green fluorescent protein (EGFP)/puromycin resistance gene cassette along with or without oriP were used to transfect hES cells that stably express EBNA1. The presence of oriP moderately increased the transient transfection efficiency and more importantly it elevated the stable transfection efficiency by approximately 1,000-fold as compared with oriP-minus plasmids. The oriP plasmid as episomal DNA and green fluorescent protein expression in hES cells was maintained for months in the presence of drug selection and gradually lost (2%-4% per cell doubling) in the absence of selection. The presence of EBNA1 did not interfere with the hES cell properties or differentiation we tested and could maintain stable EGFP expression during differentiation. In addition to transgene expression, the EBV vector system could effectively enhance the RNA interference efficiency in hES cells. Thus, the EBV vector system that allows a large DNA insert and sustained expression of transgene or small hairpin RNA will enhance basic and translational research using hES cells.

Bone Morphogenetic Protein 4↗

Detection of hypopharyngeal squamous cell carcinoma using serum proteomics.

CONCLUSIONS: The combination of surface-enhanced laser desorption/ionization (SELDI) with bioinformatics tools could help find serum proteome biomarkers and establish a predictive model for early detection of hypopharyngeal squamous cell carcinoma (HSCC). OBJECTIVES: Proteomic profiling of serum using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is an emerging technique to identify new biomarkers in biological fluids and to establish clinically useful diagnostic computational models. We used it to find new potential biomarkers and to establish a predictive model for early detection of HSCC. MATERIALS AND METHODS: One hundred serum samples including 48 from HSCC patients and 52 from normal controls which were divided into a training set and a blind testing set were treated on WCX2 and IMAC3 protein chip, and serum protein or peptide patterns were detected by SELDI-TOF-MS. The data of spectra were analyzed by Biomarker Wizard software to screen serum proteome biomarkers of HSCC. A decision tree classification algorithm and blind validation were determined by Biomarker Pattern Software (BPS). RESULTS: Ranging from 2 to 30 kDa, 45 potential biomarkers could differentiate HSCC patients from normal controls (p < 0.05). Among them four candidate protein peaks with m/z values of 7796, 4216, 5927, and 5361Da were selected to establish a predictive model by BPS with sensitivity of 94% and specificity of 89%. A sensitivity of 92% and specificity of 82% were validated in the blind testing set.

Adult↗

A new labdane type diterpenoid from Trollius ledebouri.

A new labdane type diterpenoid, (8alpha,13R)-epoxy-14-labden-6beta,7beta-diol-7-beta-D-(4'-acetyl) fucopyranoside, named ledebourene 1, was isolated from the flowers of Trollius ledebouri. The absolute stereostructure was elucidated on the basis of the spectroscopic analysis.

China↗

Anti-cancer activity and mechanisms of 25-anhydrocimigenol-3-O-beta-D-xylopyranoside isolated from Souliea vaginata on hepatomas.

Our previous study first revealed the cytotoxicity and relative selectivity of 25-anhydrocimigenol-3-O-beta-D-xylopyranoside (ACX) on HepG2 and R-HepG2 cells. In the present study, the anti-cancer activity and mechanisms of ACX isolated from S. vaginata were investigated both in vitro and in vivo. ACX showed significant, consistent anti-proliferative activity on hepatoma bel-7402 cells by MTT and clone formation assays with an IC50 value of 18 mumol/l. Morphological observation and flow cytometry results showed that apoptosis and G0/G1 cell cycle arrest contributed to the cytotoxic and cytostatic effects. Further studies showed that Bax and p21 protein expression were upregulated, Bcl-2 protein expression was downregulated, and poly(ADP-ribose) polymerase protein was cleaved. Moreover, ACX also exhibited a dose-dependent inhibition of tumor growth on mice implanted with H22 in vivo. These findings implicate ACX as a promising anti-cancer agent for chemotherapy of certain cancers.

Animals↗

67-kDa laminin receptor in human laryngeal squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Abnormal interaction of epithelial cells with laminin component of basement membrane may account for altered biological behavior of cells, influencing proliferation, adhesion, and motility. In the current study, we investigated the role of 67-kDa laminin receptor (67LR), a high affinity receptor for laminin, in aggressiveness of laryngeal squamous cell carcinoma. METHODS: Thirty paraffin-embedded specimens and 20 fresh tissues of patients with laryngeal squamous cell carcinoma were analyzed using immunohistologic and reverse-transcriptase polymerase chain reaction techniques, respectively. Expression of 67LR on the surface of AMC-HN-8 cells was examined by flow cytometry. The effect of 67LR monoclonal antibody (MLuC5) on the adhesive and invasive abilities of AMC-HN-8 cells was determined by adherence and invasion inhibition assay in vitro. RESULTS: Both at the mRNA and protein level, laryngeal carcinoma cells expressed higher level of 67LR than normal epithelial cells (P < .01). The expression of 67LR correlated inversely with differentiation extent of tumor (P < .05). 67LR level was significantly increased in patients with lymph node metastases than those without lymph node involvement (P < .05). Flow cytometry showed 80.9 +/- 0.9% of AMC-HN-8 cells expressed 67LR. After 60 minutes and 120 minutes of incubation, MluC5 induced 57.1 +/- 3.6% and 63.2 +/- 2.8% inhibition of adhesion, respectively. The invasive ability of AMC-HN-8 cells to matrigel was reduced by MLuC5. CONCLUSIONS: Laryngeal carcinoma cells over-expressing 67LR have a stronger aggressive potential, which might make 67LR a promising target for the treatment of metastatic tumor.

Biomarkers, Tumor↗

Nonlinear effects in varactor-tuned resonators.

This paper describes the effects of RF power level on the performance of varactor-tuned resonator circuits. A variety of topologies are considered, including series and parallel resonators operating in both unbalanced and balanced modes. As these resonators were designed to produce oscillators with minimum phase noise, the initial small signal insertion loss was set to 6 dB and, hence, QL/Q0 = 1/2. To enable accurate analysis and simulation, S parameter and PSPICE models for the varactors were optimized and developed. It is shown that these resonators start to demonstrate nonlinear operation at very low power levels demonstrating saturation and lowering of the resonant frequency. On occasion squegging is observed for modified bias conditions. The nonlinear effects are dependent on the unloaded Q (Q0), the ratio of loaded to unloaded Q (QL/Q0), the bias voltage, and circuit configurations with typical nonlinear effects occurring at -8 dBm in a circuit with a loaded Q of 63 and a varactor bias voltage of 3 V. Analysis, simulation, and measurements that show close correlation are presented.

Journal Article↗

Genetic and epigenetic alterations of DLC-1, a candidate tumor suppressor gene, in nasopharyngeal carcinoma.

The DLC-1 gene, located at the human chromosome region 8p22, behaves like a tumor suppressor gene and is frequently deleted in diverse tumors. The deletion of 8p22 is not an uncommon event in nasopharyngeal carcinoma (NPC), therefore we explored the expression levels of the DLC-1 gene in NPCs and NPC cell lines by reverse transcription-polymerase chain reaction. The results showed the mRNA level of DLC-1 was downregulated. To identify the mechanism of DLC-1 downregulation in NPC, we investigated the methylation status of the DLC-1 gene using methylation-specific PCR, and found that 79% (31 of 39) of the NPC tissues and two DLC-1 nonexpressing NPC cell lines, 6-10B and 5-8F, were methylated in the DLC-1 CpG island. Microsatellite PCR was also carried out, and loss of heterozygosity was found at four microsatellite sites (D8S552, D8S1754, D8S1790 and D8S549) covering the whole DLC-1 gene with ratios of 33% (4 of 12 informative cases), 18% (2 of 11), 5% (1 of 18), and 25% (3 of 12), respectively. Taken together, our results suggest that DLC-1 might be an NPC-related tumor suppressor gene affected by aberrant promoter methylation and gene deletion.

Adult↗

Cyclolanostane triterpene glycosides from Souliea vaginata.

Five new cyclolanostane triterpene glycosides, 12-deacetyloxy-15alpha-hydroxy-23-epi-26-deoxyactein, 12-deacetyloxy-23-epi-26-deoxyactein, 24-O-acetyldahurinol-3-O-beta-D-xylopyranoside, 12beta-hydroxycimigenol-3-O-beta-D-xylopyranosyl-(1-->3)-beta-D-xylopyranoside, 25-anhydrocimicigenol-3-O-beta-D-(2'-O-acetyl)xylopyranoside, were isolated from the rhizome of Souliea vaginata collected in China. Their structures were elucidated by spectroscopic techniques, including 2D NMR spectra, and in the case of 5, by chemical correlation.

Actaea↗

Late angiographic stent thrombosis in a drug-eluting stent that occurred 20 months after premature discontinuation of clopidogrel administration.

Late angiographic stent thrombosis (LAST) in a drug-eluting stent has been reported in several studies. Most LAST occur just after discontinuation of antiplatelet therapy. We report the first case of LAST that occurred 21 months after implantation of a Cypher stent and 20 months after discontinuation of clopidogrel, results that suggest a mechanism other than the discontinuation of antiplatelet therapy might be responsible for LAST.

Adult↗

Effects of levobupivacaine and bupivacaine on rat myometrium.

OBJECTIVE: To study the effect of levobupivacaine and bupivacaine on the contractility of isolated uterine muscle strips from pregnant and non-pregnant female rats. METHODS: Full-thick myometrial strips were prepared from 18- to 21-day pregnant (n=8) and non-pregnant rats (n=7). After contractions became regular, strips were exposed to cumulative concentrations of the two drugs from 10(-8) to 10(-4) mol/L, amplitude and frequency of the uterine contraction was recorded. RESULTS: Two local anesthetics caused a concentration dependent inhibition on contractility of myometrial strips from pregnant and non-pregnant rats. In the myometrium from non-pregnant rats, -logIC(50) of levobupivacaine and bupivacaine were 4.85 and 4.25 respectively. In the myometrium from pregnant rats, similar concentrations of levobupivacaine and bupivacaine were observed, -logIC(50) were 2.7 and 2.9 respectively. Levobupivacaine produced an increase in amplitude of contractions, while bupivacaine showed an increased trend in frequency. CONCLUSION: These results demonstrate that levobupivacaine and bupivacaine may inhibit myometrium contractility. The inhibitory effect of levobupivacaine or bupivacaine is not enhanced by gestation in rat. Levobupivacaine may have more positive influence than bupivacaine in pregnant myometrium.

Anesthetics, Local↗