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Biomedical subjects

Hui Li

Publications and source records attributed to Hui Li.

At least 73 records · Page 4Linked to original sources

Establishment of risk model for pancreatic cancer in Chinese Han population.

AIM: To investigate risk factors for pancreatic cancer and establish a risk model for Han population. METHODS: This population-based case-control study was carried out from January 2002 to April 2004. One hundred and nineteen pancreatic cancer patients and 238 healthy people completed the questionnaire which was used for risk factor analysis. Logistic regression analysis was used to calculate odds ratio (ORs), 95% confidence intervals (Cls) and beta value, which were further used to establish the risk model. RESULTS: According to the study, people who have smoked more than 17 pack-years had a higher risk to develop pancreatic cancer compared to non-smokers or light smokers (not more than 17 pack-years) (OR 1.98; 95% CI 1.11-3.49, P = 0.017). More importantly, heavy smokers in men had increased risk for developing pancreatic cancer (OR 2.11; 95%CI 1.18-3.78, P = 0.012) than women. Heavy alcohol drinkers (>20 cup-years) had increased risk for pancreatic cancer (OR 3.68; 95%CI 1.60-8.44). Daily diet with high meat intake was also linked to pancreatic cancer. Moreover, 18.5% of the pancreatic cancer patients had diabetes mellitus compared to the control group of 5.8% (P = 0.0003). Typical symptoms of pancreatic cancer were anorexia, upper abdominal pain, bloating, jaundice and weight loss. Each risk factor was assigned a value to represent its importance associated with pancreatic cancer. Subsequently by adding all the points together, a risk scoring model was established with a value higher than 45 as being at risk to develop pancreatic cancer. CONCLUSION: Smoking, drinking, high meat diet and diabetes are major risk factors for pancreatic cancer. A risk model for pancreatic cancer in Chinese Han population has been established with an 88.9% sensitivity and a 97.6% specificity.

Adult↗

Analysis of veterinary drug residues in shrimp: a multi-class method by liquid chromatography-quadrupole ion trap mass spectrometry.

A liquid chromatography-mass spectrometry (LC-MS) method was developed to screen and confirm veterinary drug residues in raw shrimp meat. This method simultaneously monitors 18 drugs of different classes, including oxytetracycline (OTC), sulfonamides, quinolones, cationic dyes, and toltrazuril sulfone (TOLS). The homogenized shrimp meat is extracted with 5% trichloroacetic acid. The extract is further cleaned using polymer-based SPE. A 50 mm phenyl column separates the analytes, prior to analysis with an ion trap mass spectrometer interfaced with an atmospheric pressure chemical ionization source. This method is able to confirm oxytetracycline residues at 200 ng/g, toltrazuril sulfone at 50 ng/g, sulfaquinoxaline at 20 ng/g, and the other 15 drugs at 10 ng/g or lower levels. An estimate of the level of residues can also be made so that only confirmed samples above action levels will be sent for quantitation. The method is validated with both fortified and incurred samples, using multiple shrimp species as well. This multi-class method can provide a means to simultaneously monitor for a wide range of illegal drug residues in shrimp.

Animals↗

Alteration of subcellular redox equilibrium and the consequent oxidative modification of nuclear factor kappaB are critical for anticancer cytotoxicity by emodin, a reactive oxygen species-producing agent.

We previously found that emodin produced reactive oxygen species (ROS) intracellularly. In various tumor cells at low doses it enhances the cytotoxicity of As(2)O(3), and at higher doses it renders cytotoxicity independently in vitro and in vivo. The effects involve redox-mediated inhibition of NF-kappaB activation. In this study, we focus on the mechanisms by which emodin inhibits NF-kappaB activation. Results in HeLa cells demonstrated that emodin at high doses or in combination with As(2)O(3), via generation of ROS especially in the nucleus, altered subcellular redox equilibrium and thus oxidized the redox-sensitive site on NF-kappaB and prevented its binding to the target DNA. In vivo study showed that tumors exposed to the arsenic/emodin cotreatment had dramatically smaller sizes and weaker antioxidant capacity, compared with arsenic alone. NF-kappaB binding and transactivation were inhibited in these tumors. These data help in the understanding of the mechanisms by which manipulation of cellular redox and NF-kappaB activation may enhance chemotherapy.

Antineoplastic Agents↗

Role of conserved glycines in pH gating of Kir1.1 (ROMK).

Gating of inward rectifier Kir1.1 potassium channels by internal pH is believed to occur when large hydrophobic leucines, on each of the four subunits, obstruct the permeation path at the cytoplasmic end of the inner transmembrane helices (TM2). In this study, we examined whether closure of the channel at this point involves bending of the inner helix at one or both of two highly conserved glycine residues (corresponding to G134 and G143 in KirBac1.1) that have been proposed as putative "gating hinges" for potassium channels. Replacement of these conserved inner helical glycines by less flexible alanines did not abolish gating but shifted the apparent pKa from 6.6 +/- 0.01 (wild-type) to 7.1 +/- 0.01 for G157A-Kir1.1b, and to 7.3 +/- 0.01 for G148A-Kir1.1b. When both glycines were mutated the effect was additive, shifting the pKa by 1.2 pH units to 7.8 +/- 0.04 for the double mutant: G157A+G148A. At this pKa, the double mutant would remain completely closed under physiological conditions. In contrast, when the glycine at G148 was replaced by a proline, the pKa was shifted in the opposite direction from 6.6 +/- 0.01 (wild-type) to 5.7 +/- 0.01 for G148P. Although conserved glycines at G148 and G157 made it significantly easier to open the channel, they were not an absolute requirement for pH gating in Kir1.1. In addition, none of the glycine mutants produced more than small changes in either the cell-attached or excised single-channel kinetics which, in this channel, argues against changes in the selectivity filter. The putative pH sensor at K61-Kir1.1b, (equivalent to K80-Kir1.1a) was also examined. Mutation of this lysine to an untitratable methionine did not abolish pH gating, but shifted the pKa into an acid range from 6.6 +/- 0.01 to 5.4 +/- 0.04, similar to pH gating in Kir2.1. Hence K61-Kir1.1b cannot function as the exclusive pH sensor for the channel, although it may act as one of multiple pH sensors, or as a link between a cytoplasmic sensor and the channel gate. K61-Kir1.1b also interacted differently with the two glycine mutations. Gating of the double mutant: K61M+G148A was indistinguishable from K61M alone, whereas gating of K61M+G157A was midway between the alkaline pKa of G157A and the acid pKa of K61M. Finally, closure of ROMK, G148A, G157A, and K61M all required the same L160-Kir1.1b residue at the cytoplasmic end of the inner transmembrane helix. Hence in wild-type and mutant channels, closure occurs by steric occlusion of the permeation path by four leucine side chains (L160-Kir1.1b) at the helix bundle crossing. This is facilitated by the conserved glycines on TM2, but pH gating in Kir1.1 does not absolutely require glycine hinges in this region.

Amino Acid Sequence↗

[Study on the methods for detection of Toxoplasma antigen].

A sandwich ELISA was established with monoclonal antibody as detecting antibody and rabbit anti-Toxoplasma polyclonal antibody as capturing antibody. ABC (avidin-biotin-peroxidase complex)-ELISA and immuno-PCR were also used to detect different concentrations of Toxoplasma antigen. The lowest concentration of antigen to be detected by sandwich ELISA, ABC-ELISA and immuno-PCR was 0. 6 microg/ml, 0. 075 microg/ml and 0.1 ng/ml respectively. The immuno-PCR shows a much higher sensitivity than the other two methods.

Animals↗

Involvement of caspase-3 pathway in anti-apoptotic action of methionine enkephalin on CEM x 174 cells in prolonged infection with simian immunodeficiency virus in vitro.

The roles of methionine enkephalin, as an immunomodulator, on immunodeficiency virus-induced apoptosis of lymphocytes during prolonged infection are still unclear. In the present study, we evaluated the effects of methionine enkephalin on the viability, the profile of cell cycle and apoptosis, as well as the expression of apoptosis-related genes in CEM x 174 cells infected with simian immunodeficiency virus for 72 h. Our data demonstrated that methionine enkephalin maintains the viability of cells during the period of prolonged infection. Following co-incubation with the virus, CEM x 174 cells were arrested at S phase, with increased mortality as a result of apoptosis. Methionine enkephalin could abolish virus-induced over-expression of caspase-3. Taken together all findings, we conclude that methionine enkephalin may maintain the viability of SIV-infected cells via suppressing the expression of caspase-3, which may have clinical implications in opioid peptide therapy for AIDS.

Apoptosis↗

High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals.

A body of evidence indicates that expression of the programmed cell death 1 (PD-1) receptor by activated T cells plays an important role in the down-regulation of immune responses; however, the functions of its known ligands, B7-H1 (PD-L1) and B7-dendritic cell (DC; PD-L2), at the effector phase of immune responses are less clear. In the current study, we investigated the roles of B7-H1 in DC-mediated regulation of hapten-activated T cells and the delayed-type contact hypersensitivity response in primed animals. We found that the expression of B7-H1 and B7-DC was induced on activation of DC by hapten stimulation. Blockade of B7-H1, but not B7-DC, enhanced the activity of hapten-specific T cells. Interaction with a DC line that expresses high cell-surface levels of B7-H1 (B7-H1/DC) suppressed the proliferation of, and cytokine production by, activated T cells. In vivo administration of hapten-carrying B7-H1/DC desensitized the response of sensitized animals to hapten challenge, and this desensitization was hapten-specific. These data indicate that B7-H1 expressed by DC mediates inhibitory signals for activated T cells and suppresses the elicitation of immune responses. The ability of B7-H1/DC to inhibit the function of preactivated T cells in vivo suggests novel strategies for the treatment of immune response-mediated disorders.

Allergens↗

Well-aligned arrays of CuO nanoplatelets.

This paper reports well-aligned arrays of CuO nanoplatelets synthesized through a hydrothermal route without template's assistance. The surface of well-aligned arrays of CuO nanoplatelets looks like a wall. These nanoplatelets, possessing four clear edges, are 50-80 nm in thickness, 150-250 nm in width, and 0.8-1.5 microm in length. Electron microscopic detection shows that the nanoplatelet grows along the [010] direction. The Ostwald ripening mechanism has been used to describe the growth of CuO nanoplatelets. In addition, the optic and electrochemical properties of as-obtained products have been discussed. And the arrays of CuO nanoplatelets exhibit the blue shift in UV-visible spectra, a slow capacity fading rate, and a relatively high Coulombic efficiency in charge-discharge process.

Journal Article↗

Enhanced sorption of trichloroethene by smectite clay exchanged with Cs+.

Trichloroethene (TCE) is one of the most common pollutants in groundwater, and Cs+ can be a cocontaminant at nuclear facilities. Smectite clays have large surface areas, are common in soils, have high affinities for some organic contaminants, and hence can potentially influence the transport of organic pollutants entering soils and sediments. The exchangeable cations present near smectite clay surfaces can radically influence the sorption of organic pollutants by soil clays. This research was undertaken to determine the effect of Cs+, and other common interlayer cations, such as K+ and Ca2+, on the sorption of TCE by a reference smectite clay saponite. Cs-saturated clay sorbed the most TCE, up to 3500 mg/kg, while Ca-saturated smectite sorbed the least. We hypothesize that the stronger sorption of TCE by the Cs-smectite can be attributed to the lower hydration energy and hence smaller hydrated radius of Cs+, which expands the lateral clay surface domains available for sorption. Also, Cs-smectite interlayers are only one or two water layers thick, which may drive capillary condensation of TCE. Our results implicate enhanced retention of TCE in aquifer materials containing smectites accompanied by Cs+ cocontamination.

Adsorption↗

Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia.

Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopy demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis.

Animals↗

Linkage disequilibrium sharing and haplotype-tagged SNP portability between populations.

The discovery of the block-like structure of linkage disequilibrium (LD) in human populations holds the promise of delineating the etiology of common diseases. However, understanding the magnitude, mechanism, and utility of between-population LD sharing is critical for future genome-wide association studies. In this study, substantial LD sharing between six non-African populations was observed, although much less between African-American and non-African, based on 20,000 SNPs of chromosome 21. We also demonstrated the respective roles of recombination and demographic events in shaping LD sharing. Furthermore, we showed that the haplotype-tagged SNPs chosen from one population are portable to the others in East Asia. Therefore, we concluded that the magnitude of LD sharing between human populations justifies the use of representative populations for selecting haplotype-tagged SNPs in genome-wide association studies of complex diseases.

Africa↗

Modeling styrene-styrene interactions.

This study is the first step in the systematic investigation of substituted (carboxyl) polystyrene nanoparticles. Understanding the fundamental interactions between the p-carboxyl styrene monomers, where an ethyl group is used instead of a vinyl group (referenced, for convenience, as "p-carboxyl styrene"), provides the basic information needed to construct potentials for nanoparticles composed of these monomers. In this work, low-energy isomers of p-carboxyl styrene dimer were studied. The dimer structures and their relative and binding energies were determined using both Møller-Plesset second-order perturbation theory (MP2) and the general effective fragment potential (EFP2) method. Sections of the intermolecular potential energy surface (PES) of the p-carboxylated styrene dimer in its global minimum orientation were also determined. As expected, double hydrogen bonding between the two carboxylic groups provides the strongest interaction in this system, followed by isomers with a single H-bond and strong benzene ring-benzene ring (pi-pi) type interactions. Generally, the EFP2 method reproduces the MP2 geometries and relative energies with good accuracy, so it appears to be an efficient alternative to the correlated ab initio methods, which are too computationally demanding to be routinely used in the study of the more-complex polymeric systems of interest.

Journal Article↗

Heat shock fusion protein induces both specific and nonspecific anti-tumor immunity.

Mucin 1 (MUC1) is a tumor antigen, and the most important epitopes that can induce cytotoxic T lymphocytes (CTL) reside in the variable-number tandem repeats (VNTR). Heat shock protein (HSP) complexes isolated from tumors have been shown to induce specific anti-tumor immunity. HSP alone can also induce nonspecific immunity. To explore the possibility to utilize the specific anti-tumor immunity induced by MUC1 VNTR and the nonspecific immunity induced by HSP, we constructed a recombinant protein (HSP65-MUC1) by fusing Bacillus Calmette-Guérin-derived HSP65 with the MUC1 VNTR peptide and tested its ability to induce anti-tumor activities in a tumor challenge model. The growth of MUC1-expressing tumors was significantly inhibited in mice immunized with HSP65-MUC1, both before and after tumor challenge. A much larger percentage of immunized mice survived the tumor challenge than non-immunized mice. Correlating with the anti-tumor activity, HSP65-MUC1 was shown to induce MUC1-specific CTL as well as nonspecific anti-tumor immunity. In the human system, HSP65-MUC1-loaded human DC induced the generation of autologous MUC1-specific CTL in vitro. These results suggest that exogenously applied HSP65-MUC1 may be used to treat MUC1 tumors by inducing the epitope-specific CTL as well as nonspecific anti-tumor responses mediated by the HSP part of the fusion protein.

Amino Acid Sequence↗

The polarizable continuum model (PCM) interfaced with the fragment molecular orbital method (FMO).

The polarizable continuum model (PCM) for the description of solvent effects is combined with the fragment molecular orbital (FMO) method at several levels of theory, using a many-body expansion of the electron density and the corresponding electrostatic potential, thereby determining solute (FMO)-solvent (PCM) interactions. The resulting method, denoted FMO/PCM, is applied to a set of model systems, including alpha-helices and beta-strands of alanine consisting of 10, 20, and 40 residues and their mutants to charged arginine and glutamate residues. The FMO/PCM error in reproducing the PCM solvation energy for a full system is found to be below 1 kcal/mol in all cases if a two-body expansion of the electron density is used in the PCM potential calculation and two residues are assigned to each fragment. The scaling of the FMO/PCM method is demonstrated to be nearly linear at all levels for polyalanine systems. A study of the relative stabilities of alpha-helices and beta-strands is performed, and the magnitude of the contributing factors is determined. The method is applied to three proteins consisting of 20, 129, and 245 residues, and the solvation energy and computational efficiency are discussed.

Journal Article↗

Proteomics-based generation and characterization of monoclonal antibodies against human liver mitochondrial proteins.

Monoclonal antibodies (mAbs) have the potential to be a very powerful tool in proteomics research to determine protein expression, quantification, localization and modification, as well as protein-protein interactions, especially when combined with microarray technology. Thus, a large amount of well-characterized and highly qualified antibodies are needed in proteomics. Purified antigen, which is not always available, has proven to be one of the rate-limiting steps in mAb large-scale generation. Here we describe our strategies to establish a murine hybridoma cell bank for human liver mitochondria using unknown native proteins as the immunogens. The antibody-recognized mitochondrial proteins were identified by MS following immunoprecipitation (IP), and by screening of human liver cDNA expression library. We found that the established antibodies reacted specifically with a number of important enzymes in mitochondria. The subcellular localization of these antigens in mitochondria was further confirmed by immunohistocytochemistry. A panel of antibodies was also tested for their ability to capture and deplete the targeting proteins and complexes from the total mitochondrial proteins. We believe these well-characterized antibodies would be useful in various applications for Human Liver Proteome Project (HLPP) when the scale of this hybridoma cell bank is enlarged significantly in the near future.

Antibodies, Monoclonal↗

Correlation analysis between single-nucleotide polymorphism of malate dehydrogenase gene 5'-flanking region and growth and body composition traits in chicken.

Malate dehydrogenase (MD) is a key enzyme that plays an important role in energy metabolism. It catalyzes the oxidative decarboxylation of L-malate to yield CO2 and pyruvate, while simultaneously generating NADPH from NADP+. The NADPH generated can be utilized in de novo synthesis of palmitate, which is the precursor molecule for the formation of other long-chain fatty acids. And high levels of MD will also activate muscle development. The current study was designed to investigate the effects of MD gene on growth and body-composition traits in chicken. The eighth generation population of Northeast Agricultural University broiler lines divergently selected for its abdominal fat and Northeast Agricultural University F2 resource population were used in the research. Polymorphisms were detected by DNA sequencing and PCR-RFLP method was then developed to screen the population. A single mutation at the position of the 235 bp (Accession No. U49693) of MD 5'-flanking region was found. The correlation analysis between the polymorphism of the MD gene and growth and body composition traits was carried out using the appropriate statistic model. Least-square analysis showed that the BB genotype birds had much higher pectoralis major weight and percentage of pectoralis major than AA genotype birds (P<0.05). The abdominal fat weight, percentage of abdominal fat, the liver weight and percentage of liver weight of the AA genotype birds were much higher than those of BB genotype birds (P<0.05). These results indicate that MD gene is the major gene or is linked to the major gene that affects the growth and body composition traits in chicken.

5' Flanking Region↗

Y-chromosome genotyping and genetic structure of Zhuang populations.

Zhuang, the largest ethnic minority population in China, is one of the descendant groups of the ancient Bai-Yue. Linguistically, Zhuang languages are grouped into northern and southern dialects. To characterize its genetic structure, 13 East Asian-specific Y-chromosome biallelic markers and 7 Y-chromosome short tandem repeat (STR) markers were used to infer the haplogroups of Zhuang populations. Our results showed that O*, O2a, and O1 are the predominant haplogroups in Zhuang. Frequency distribution and principal component analysis showed that Zhuang was closely related to groups of Bai-Yue origin and therefore was likely to be the descendant of Bai-Yue. The results of principal component analysis and hierarchical clustering analysis contradicted the linguistically derived north-south division. Interestingly, a west-east clinal trend of haplotype frequency changes was observed, which was supported by AMOVA analysis that showed that between-population variance of east-west division was larger than that of north-south division. O* network suggested that the Hongshuihe branch was the center of Zhuang. Our study suggests that there are three major components in Zhuang. The O* and O2a constituted the original component; later, O1 was brought into Zhuang, especially eastern Zhuang; and finally, northern Han population brought O3 into the Zhuang populations.

Alleles↗

Molecular cloning and assessment of the immunocontraceptive potential of the zona pellucida subunit 3 from Brandt's vole (Microtus brandti).

A full-length cDNA encoding Brandt's vole (Microtus brandti) zona pellucida glycoprotein subunit 3 (vZP3) was isolated using rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The cDNA contains an open reading frame of 1254 nucleotides encoding a polypeptide of 418 amino acid residues. The deduced amino acid sequence of vZP3 revealed high overall homology with hamster (82.1%), mouse (81.3%) and rat (80.6%). A synthetic vZP3 peptide corresponding to amino acid residues 328-343 was conjugated to keyhole limpet hemocyanin (KLH-vZP3(328-343)) and used to immunise female Brandt's voles in order to test the efficacy of this peptide as a contraceptive antigen. High IgG antibody levels to the vZP3(328-343) peptide were present in the sera of female voles immunised with KLH-vZP3(328-343) and these also cross-reacted to the zona pellucida in ovaries of Brandt's vole. The fertility of the KLH-vZP3(328-343) -immunised voles was reduced by 50% compared with controls without evidence of significant ovarian pathology.

Amino Acid Sequence↗