Chem-bioinformatics and QSAR: a review of QSAR lacking positive hydrophobic terms.
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Animals↗
Biomedical subjects
H Gao
Publications and source records attributed to H Gao.
Temporal gene expression analysis of monolayer cultured rat hepatocytes.
The use of cultured primary hepatocytes within toxicology has proven to be a valuable tool for researchers, however, questions remain with regard to functional differences observed in these hepatocytes relative to the intact liver. Cultured hepatocytes have typically been described as dedifferentiated, a classification based upon the investigation of a few key cellular processes or hepatocellular markers. In the present study, parallel expression monitoring of approximately 8700 rat genes was used to characterize mRNA changes over time in hepatocyte cultures using Affymetrix microarrays. We isolated and labeled mRNA from whole rat livers, hepatocyte-enriched cell pellets, and primary cultured hepatocytes (4, 12, 24, 48, and 72 h postplating), and hybridized these samples to microarrays. From these data, several pairwise and temporal gene expression comparisons were made. Gene expression changes were confirmed by RT/PCR and by performing replicate experiments and repeated hybridizations using a rat toxicology sub-array that contained a 900-gene subset of the 8700-gene rat genomic microarray. PCR data qualitatively reproduced the temporal patterns of gene expression observed with microarrays. Cluster analysis of time course data using self-organizing maps (SOM) revealed a classic hepatocyte dedifferentiation response. Functional grouping of genes with similar transcriptional patterns showed time-dependent regulation of phase I and phase II metabolizing enzymes. In general, cytochrome P450 mRNA expression was repressed, but expression of phase II metabolizing enzymes varied by class (upregulation of glucuronidation, downregulation of sulfation). Potential metabolic targets for toxic insult, such as glutathione metabolism, gluconeogenesis, and glycolysis, were also affected at the transcriptional level. Progressive induction of several genes associated with the cellular cytoskeleton and extracellular matrix was observed in accord with physical changes in cell shape and connectivity associated with cellular adhesion. Finally, many transcriptional changes of genes involved in critical checkpoints throughout the hepatocyte cell cycle and differentiation process were observed. In total, these data establish a more comprehensive understanding of hepatocellular dedifferentiation and reveal many novel aspects of physiological and morphological hepatocyte adaptation. An assembly of all transcripts that demonstrated differential expression in this study can be found in the Supporting Information.
Animals↗
Synthesis of a novel series of cationic lipids that can act as efficient gene delivery vehicles through systematic heterocyclic substitution of cholesterol derivatives.
The synthesis of a series of novel cationic lipids through the systematic substitution of cholesterol derivatives that could greatly enhance the delivery and expression of plasmid DNA in vitro and in vivo is described. Two of the newly synthesized lipids, designated as NCC4 and NCC10, were chosen to be studied in detail and gave much higher levels of gene expression than that which could be obtained with some of the conventional cationic polymers and cationic liposomes. In vivo studies with both NCC4 and NCC10 also showed better ability in delivering the reporter gene to the target cells through intrasplenic injection. In addition, by varying the DNA/lipid charge ratios, NCC4 and NCC10 can withstand serum inactivation in vitro. However, this does not correlate with the corresponding increase in the level of gene expression following systemic gene delivery with NCC4 and NCC10 in vivo.
Adenoviridae↗
Apoptosis, proliferation and p53 gene expression of H. pylori associated gastric epithelial lesions.
AIM: To study the relationship between Helicobacter pylori (H. pylori) and gastric carcinoma and its possible pathogenesis by H. pylori. METHODS: DNEL technique and immunohistochemical technique were used to study the state of apoptosis, proliferation and p53 gene expression. A total of 100 gastric mucosal biopsy specimens, including 20 normal mucosa, 30 H. pylori-negative and 30 H. pylori-positive gastric precancerous lesions along with 20 gastric carcinomas were studied. RESULTS: There were several apoptotic cells in the superficial epithelium and a few proliferative cells within the neck of gastric glands, and no p53 protein expression in normal mucosa. In gastric carcinoma, there were few apoptotic cells, while there were a large number of proliferative cells, and expression of p53 protein significantly was increased. In the phase of metaplasia, the apoptotic index (AI, 4.36%+/-1.95%), proliferative index (PI, 19.11%+/-6.79%) and positivity of p53 expression (46.7%) in H. pylori-positive group were higher than those in normal mucosa (P<0.01). AI in H. pylori-positive group was higher than that in H. pylori-negative group (3.81%+/-1.76%), PI in H. pylori-positive group was higher than that in H. pylori-negative group (12.25%+/-5.63%, P<0.01). In the phase of dysplasia, AI (2.31%+/-1.10%) in H. pylori-positive group was lower (3.05%+/-1.29%) than that in H. pylori-negative group, but PI (33.89%+/-11.65%) was significantly higher (22.09+/-8018%, P<0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. pylori-positive group, AIs had an evidently graduall decreasing trend (P<0.01), while PIs had an evidently gradual increasing trend (P<0.05 or P<0.01), and there was also a trend of gradual increase in the expression of p53 gene. CONCLUSION: In the course of the formation of gastric carcinoma, proliferation of gastric mucosa can be greatly increased by H. pylori, and H. pylori can induce apoptosis in the phase of metaplasia, but in the phase of dysplasia H. pylori can inhibit cellular apoptosis. And H. pylori infection can strengthen the expression of mutated p53 gene.
Apoptosis↗
[Expression of tumor suppressor genes p16, p21 and p53 in a pair of lung adenocarcinoma cell lines with different metastasis potentials: Anip973 and AGZY83-a].
OBJECTIVE: In order to investigate the suppression effect of tumor suppressor genes in lung adenocarcinoma. METHODS: p16 and p21 expression vectors were transfected into a pair of lung adenocarcinoma cell lines with different metastasis potentials: Anip973(high metastasis potential)and AGZY83-a (low metastasis potential). In the mean time, AGZY83-a, Anip973, AGZY83-ap16 and Anip973p16 were infected with recombinant adenovirus encoding wild- type p53 gene. The suppression effects of these genes were evaluated by cell growth curve, MTT, cloning efficiency assay, flow cytometric analysis and TUNEL technique. RESULTS: Overexpression of p16 gene in Anip973 and AGZY83-a could only lengthen the G(1) phase while increased expression of p21 in both of the cell lines was associated with significant lengthening of G(1) phase, decreased proliferation potential and decreased cloning efficiency. High efficient expression of wild-type p53 gene in AGZY83-a, Anip973, Anip973p16 and AGZY83-ap16 inhibited the growth of these four kinds of lung cancer cells and killed the cells in the end. Apoptosis was detected in all the four kinds of cells. The suppression effect of p53 gene was higher in Anip973 and Anip973p16 than in AGZY83-a and AGZY83-ap16 while co-expression of p53 and p16 in this pair of cell lines inhibited the cells more efficiently as compared with the expression of p53 gene. CONCLUSION: Increased expression of p21 gene suppressed the lung adenocarcinoma cells by G(1) arrest and the co-transfection of tumor suppressor genes p16 and p53 into the lung adenocarcinoma cell line proved more effective in lung cancer gene therapy.
Adenocarcinoma↗
Clinical study on treatment of senile vascular dementia by acupuncture.
63 patients with senile vascular dementia were randomly divided into the treatment group (treated by acupuncture) and the control group (treated with piracetam). The authors observed the changes in the score of Hasegawa's dementia scale (HDS), p300, rheoencephalogram, topographic EEG, superoxide dismutase (SOD) activity in erythrocytes, and lipid peroxide (LPO) level in plasma before and after treatment. The statistical data showed that the total effective rate in the treatment group (80.6%) was significantly higher than that in the control group (25%), and the differences in the observed indexes before and after treatment were significant (P < 0.05 or P < 0.01) in the treatment group but not in the control group (P > 0.05), indicating that the acupuncture treatment was superior in immediate therapeutic effect on senile vascular dementia to drug treatment.
Acupuncture Therapy↗
[Effects of nitric oxide and prostaglandin on gastric mucosal perfusion in rats with portal hypertensive gastropathy].
OBJECTIVE: To observe the effects of nitric oxide (NO) and prostaglandin on gastric mucosal perfusion in rats with portal hypertensive gastropathy (PHG). METHODS: Two weeks after partial portal vein ligation, gastric mucosal blood flow (GMBF) was measured with the neutral red clearance method and the changes of portal venous pressure (PVP) were observed. RESULTS: GMBF and PVP were significantly higher in rats with PHG than in sham operated rats (P<0.01). Low dose inhibitor of NO synthesis N(-nitro-L-arginine methyl ester (L-NAME 1mg/kg, 4mg/kg) caused a significant and dose dependent reduction in GMBF in PHG rats, but had no effect on sham operated rats. High dose L-NAME (12 mg/kg) significantly decreased GMBF in both PHG and sham operated rats. The inhibition of prostaglandin synthesis with indomethacin significantly decreased GMBF in rats with PHG, but had no effect in sham operated rats. In sham operated rats pretreated with indomethacin, GMBF was not modified after and before injection of low dose L-NAME (4mg/kg); likewise, high dose of L-NAME (12mg/kg) did not alter the significant reduction in GMBF as compared with pretreatment without indomethacin. In PHG rats the significant dose dependent reduction in GMBF induced by L-NAME (4mg/kg, 12mg/kg) was not significantly different between pretreatment with and without indomethacin. CONCLUSIONS: NO and prostaglandins play an important role in the regulation of GMBF in rats with PHG, but no synergistic interactions between them.
Animals↗
[Genescan analysis of the loss of heterozygosity on the long arm of chromosome 6 in non-small cell lung cancer].
To investigate if there are microsatellite loci in the long arm of chromosome 6 that have close relationship with non-small cell lung cancer, Multiple PCR approach was used to analyze the 36 loci in the long arm of chromosome 6. The PCR products were analyzed in PAGE and then the electrophoresis maps were analyzed with Genescan and Genotyper. There is different LOH frequency in different loci. The total frequency of LOH in 41 lung cancers was 78%(32/41), with the highest frequency of LOH was detected on the locus D6S302(75%). There are 14 loci which have LOH frequency more than 20% and the loci are mainly located in 2 regions: 6q16.3-q21 [6 loci D6S458 (21.43%), D6S1694 (26.92%), D6S1717 (35.71%), D6S1565 (40%), D6S302 (75%), D6S1706 (36.36%) and 6q26-q27 (5 loci D6S1550 (38.46%), D6S264 (20%), D6S1585 (25%), D6S446 (33.33%), D6S281 (30.77%)], There may be tumor suppressor genes located in the two regions, which have a close relationship with non-small cell lung cancer.
Carcinoma, Non-Small-Cell Lung↗
[Analysis of loss of heterozygosity on 19p in primary gastric cancer].
OBJECTIVE: To investigate the loss of heterozygosity (LOH) frequency of microsatellite loci in primary gastric cancer samples and locate the deleted regions on 19p in which might exist human gastric cancer related genes. METHODS: The LOH of microsatellite loci on chromosome 19p was analyzed using PCR-SSLP-silver stain method in 43 primary gastric cancers and their paired normal tissues. RESULTS: In 43 primary gastric tumors, LOH was detected on the site for D19S424(29.63%), D19S216(11.53%), D19S406 (33.33%), D19S413(8.57%), D19S221(13.15%), D19S226(8.00%), D19S411(6.45%), D19S883(6.89%), and D19S886(10.71%), microsatellite instability (MSI) was found at the same time at locus D19S886 (17.85%). CONCLUSION: The most common LOH occurrence at D19S406 and D19S424 might imply the existence of the potential genes related to the tumorigenesis of gastric cancer in these loci.
Chromosome Mapping↗
Role of beta-adrenoceptor at different stages of bronchial asthma.
OBJECTIVE: To investigate the changes of beta-adrenergic receptor (beta AR) in peripheral lymphocytes and beta 2AR mRNA levels at different stages of bronchial asthma. METHODS: beta 2AR density and beta 2AR mRNA level in peripheral lymphocytes, cAMP and cGMP levels in blood plasma were estimated by radioligand binding assay, radioimmunoassay and RT-PCR. RESULTS: (1) Maximum bound volume (Bmax) and equilibrium dissociation constant (Kd) of beta 2AR of lymphocyte in asthma patients at remission stage were markedly higher than that in normal subjects, while cAMP levels in blood plasma showed no difference. Bmax of beta 2AR and cAMP levels in asthma patients at acute exacerbation stage were significantly lower than that in normal subjects, and Kds between these two groups were not much different. (2) Expression of beta 2ARmRNA in peripheral lymphocytes of asthmatics at remission stage was not significantly different compared with that in normals. CONCLUSIONS: Amount and function of beta AR and beta 2ARmRNA levels are related to asthmatic conditions. Changes of beta AR and beta 2ARmRNA in asthma might rather be a pathological change accompanied by the course of the disease than a primary defect.
Adult↗
[Analysis of parameters for optimum of ergosterol fermentation].
Parameters in the process of ergosterol fermentation are studied. The relationship between biomass, ergosterol content in Saccharomyces cerevisiae and parameters such as DO, pH, OUR, glucose concentration, are discussed. Because of its good manipulation in yeast fermentation process, Do can thus serve as an effective control parameter. DO at about 12% (+/- 1%) can enhance the total yield of ergosterol considerably.
Ergosterol↗
[The development of an automatic dialyser reuse device by microcomputer].
This article introduces the principles, composition and main functions of an automatic dialyser reuse device by microcomputer. It Ras more practical uses, better reliability, easier operations and greater effect than previous ones, and it's an ideal dialyser ruse device.
Dialysis↗
Potentiation of docetaxel antitumor activity by batimastat against mouse forestomach carcinoma.
OBJECTIVE: To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat (BB-94) on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. METHODS AND RESULTS: In vitro, growth curve analysis, MTT assay and clonogenic assay used to determine the cytotoxic effect of docetaxel or/and BB-94 on MFC cell showed that docetaxel but not BB-94 had a significant cytotoxicity, and the effect of docetaxel wasn't enhanced by BB-94. In early stage MFC tumor model, obvious antitumor effect of docetaxel or doxorubicin given i.v. at maximum tolerated dose (MTD, docetaxel: 20 mg/kg; doxorubicin: 6 mg/kg) every 4 days for 3 injections (q4d x 3), even that of BB-94 (30 mg/kg i. p. qd x 20) was observed. Tumor growth inhibition was greater for docetaxel-batimastat (96.0%) than for doxorubicin-batimastat (88.0%), docetaxel (89.0%), doxorubicin (68.0%) and BB-94 (33.0%), and the effect of docetaxel could be potentiated by BB-94. Docetaxel also showed activity against advanced stage MFC tumor in dose-dependent manner, and was more effective at MTD than doxorubicin with 4/5 regressions, 46.5 days tumor growth delay and 2.8log(10) tumor cell kill. CONCLUSION: Our results suggest that in the MFC model with dose and schedule used, docetaxel is an effective cytotoxic new drug against MFC tumor and BB-94 enchances the antitumor activity of docetaxel.
Animals↗
[Study on the interactions between a 3H-indole probe molecule and Triton X-100 micelles by spectral methods].
The interactions between a fluorescent molecule, [2-(p-hexylamino) phenyl-3,3-dimethyl-5-ethoxycarbonyl-3H-indole] methyldiioctadecylammonium iodide (A), with Triton X-100 micelle are investigated by absorption and fluorescence spectra. The relatively large binding constant Ks shows that strong interactions between A and micelles do exist. The polarity parameter confirms that the polarity of the environment of A in the micelle is similar to that of methanol. According to the spectral characteristics and pH effects, the various sites of different groups of A in micelles are suggested. Lifetime measurements indicate that A can recognize two sites with Triton X-100 micelle at lower surfactant concentration. However, in the Triton X-100 micelle at higher surfactant concentration, A can only recognize one site.
English Abstract↗
[On the characteristics of velocity modulation laser spectroscopy].
The technical properties of velocity modulation laser spectroscopy were investigated using the spectrum of A2 pi u-X2 sigma g+ (2-0) band of Meinel system of N2+. The dependence of spectral intensity on discharge current, the pressure of the gas mixture and the pump velocity of the vacuum pump were studied. Making uses of the results of these studies, the sensitivity and resolution of the spectrometer are improved by above 3 times, and economized the experimental expenses can be reduced to as 3/4 time as normal, which confirms that the results of this paper is of considerable uses.
Lasers↗
[Ethyl acetate synthesis on-line measurement by Raman spectroscopy].
We report an on-line Raman spectroscopy measurement with fiber probe. In the experiment, the real-time spectrum measurement of ethyl acetate synthesis reaction with ethanol and acetic acid was carried out by using a homemade Raman spectrometer. The time variation of integrated spectrum peak intensities of reaction product and raw materials are obtained. From the integrated peak intensities, the concentrations of the reactants can be deduced and the ending point of reaction under this experimental condition can be determined.
Acetates↗
Determination of the enaminone DM5, an anti-epileptic agent, in mouse plasma and brain tissue by high-performance liquid chromatography with ultraviolet detection.
Enaminone derivatives of the 4-carbomethoxy-5-methylcyclohexane-1,3-dione series represent a new and potentially active series of compounds for the treatment of Epilepsy. Enaminone esters have been previously evaluated as compounds with potent oral anticonvulsant activity similar to class 1 anticonvulsants phenytoin, carbamazepine, and lamotrigine. DM5, a member of this class with -Cl in the para-substituted position, has been assessed to have the most potent pharmacological activity (ED50) in both the mouse and rat. A selective and specific high-performance liquid chromatography method was developed to quantitate DM5 in plasma and brain tissue in mice. Reverse phase chromatography with ultraviolet (lambda = 307 nm) detection was utilized to quantitate eluate. A C18 analytical column was used and the mobile phase consisted of acetonitrile and 0.05 M NaH2PO4 buffer (60:40; v/v). Liquid-liquid extraction with ether was used to extract the DM5 from plasma or brain homogenates. DM5 and carbamazepine (internal standard) eluted at approximately 6.0 and 9.0 min without any interfering peaks. The calibration curves were found to be linear (r > or = 0.9999) in the range of 0.1-5.0 microg/ml or microg/g. Intra-run precision's were in all in the range of 90%. The absolute recovery of the analyte in brain and plasma samples was < or = 90%. The valid method accurately quantified DM5 in plasma and brain tissue samples collected from a pharmacokinetic study consisting of an intravenous bolus in the tail vein of wild type and genetically altered mice.
Aniline Compounds↗
Significant down-regulation of alpha-albumin in human hepatoma and its implication.
The potential association of alpha-albumin (ALF) with hepatocellular carcinoma (HCC) was investigated. Expression of ALF was significantly reduced in HCC tumor tissue as compared with the paired peritumor tissue from 16 patients and in four HCC cell lines as compared with normal hepatocytes. ALF mRNA was also down-expressed in circulating HCC cells compared to circulating normal hepatocytes. The proliferation of Hep3B cells was inhibited by over-expression of ALF. Taken together, ALF is significantly down-regulated in HCC, and this might facilitate the proliferation of HCC. Thus, detection of ALF mRNA, in addition to that of alpha-fetoprotein (AFP) mRNA, might help to distinguish normal or malignant hepatocytes in peripheral blood.
Albumins↗