Biomedical subjects

Gang Lu

Publications and source records attributed to Gang Lu.

At least 19 recordsLinked to original sources

PubMed2006

Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine.

The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (-)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation.

Adenocarcinoma↗

PubMed2006

High-performance transparent inorganic-organic hybrid thin-film n-type transistors.

High-performance thin-film transistors (TFTs) that can be fabricated at low temperature and are mechanically flexible, optically transparent and compatible with diverse substrate materials are of great current interest. To function at low biases to minimize power consumption, such devices must also contain a high-mobility semiconductor and/or a high-capacitance gate dielectric. Here we report transparent inorganic-organic hybrid n-type TFTs fabricated at room temperature by combining In2O3 thin films grown by ion-assisted deposition, with nanoscale organic dielectrics self-assembled in a solution-phase process. Such TFTs combine the advantages of a high-mobility transparent inorganic semiconductor with an ultrathin high-capacitance/low-leakage organic gate dielectric. The resulting, completely transparent TFTs exhibit excellent operating characteristics near 1.0 V with large field-effect mobilities of >120 cm2 V(-1) s(-1), drain-source current on/off modulation ratio (I(on)/I(off)) approximately 10(5), near-zero threshold voltages and sub-threshold gate voltage swings of 90 mV per decade. The results suggest new strategies for achieving 'invisible' optoelectronics.

Journal Article↗

PubMed2006

Dithienosilole- and dibenzosilole-thiophene copolymers as semiconductors for organic thin-film transistors.

The synthesis and physicochemical properties of a new class of thiophene/arenesilole-containing pi-conjugated polymers are reported. Examples of this new polymer class include the following: poly(2,5-bis(3',3' '-dihexylsilylene-2',2' '-bithieno)thiophene) (TS6T1), poly(2,5'-bis(3' ',3' ''-dihexylsilylene-2' ',2' ''-bithieno)bithiophene) (TS6T2), poly(2,5'-bis(2' ',2' ''-dioctylsilylene-1' ',1' ''-biphenyl)thiophene) (BS8T1), and poly(2,5'-bis(2' ',2' ''-dioctylsilylene-1' ',1' ''-biphenyl)bithiophene) (BS8T2). Organic field-effect transistors (OFETs) with hole carrier mobilities as high as 0.02-0.06 cm2/V s in air, low turn-on voltages, and current on/off ratios >105-106 are fabricated using solution processing techniques with the above polymers as the active channel layer. OFETs based on this polymer class exhibit excellent ambient operational stability.

Journal Article↗

PubMed2006

CYP2A13 in human respiratory tissues and lung cancers: an immunohistochemical study with a new peptide-specific antibody.

Human cytochrome P450 2A13 (CYP2A13) is highly efficient in the metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and another potent carcinogen, aflatoxin B1 (AFB1). Although previous studies demonstrated that CYP2A13 mRNA is predominantly expressed in human respiratory tissues, expression of CYP2A13 protein in these tissues and the involved cell types have not been determined because of the lack of CYP2A13-specific antibodies. To explore the toxicological and physiological function of CYP2A13, it is important to understand the tissue/cellular distribution of CYP2A13 protein. In this study, we generated a peptide-specific antibody against human CYP2A13 and demonstrated by immunoblot analysis that this antibody does not cross-react with heterologously expressed human CYP2A6 and mouse CYP2A5 proteins, both sharing a high degree of amino acid sequence similarity with CYP2A13. Nor does the antibody cross-react with heterologously expressed human CYP3A4, CYP2S1, or any of the cytochrome P450 enzymes present in the human liver microsomes. Using this highly specific antibody for immunohistochemical staining, we detected a high level of CYP2A13 protein expression in the epithelial cells of human bronchus and trachea, but a rare distribution in the alveolar cells. There was little expression of CYP2A13 protein in different types of lung cancers. In consideration of the high efficiency of CYP2A13 in NNK metabolic activation, our result is consistent with the reported observations that most smoking-related human lung cancers are bronchogenic and supports that CYP2A13-catalyzed in situ activation may play a critical role in human lung carcinogenesis related to NNK and AFB1 exposure.

Animals↗

PubMed2006

Expression and characterization of lactate dehydrogenase from Schistosoma japonicum.

Some effective antiparasitic drugs for chemotherapy schistosomiasis, such as praziquantel and artemether, are proved to act on lactate dehydrogenase (LDH) in vitro, but detailed molecular action mechanisms of these have not yet been elucidated. To this end, the sequence encoding LDH of Schistosoma japonicum (SjLDH) was amplified from the cDNA library of the adult parasite. Sequence analysis revealed an open reading frame (ORF) of 999 bp, encoding 332 amino acids with a molecular weight of 36.120 kDa. It has three transmembrane regions and may be located in the cytoplasm membrane. The encoding ORF was inserted into pET-28a vector and expressed in Escherichia coli (E. coli) induced by IPTG. A 36-kDa protein with 6xHis-tag was purified by metal affinity column and identified by SDS-PAGE and Western blot, which had high LDH activity of 379 U/mg. Characterization such as Michaelis constant (K (m)) and maximum velocity (V (max)), optimum pH, and temperature of the protein were assayed. It provides a model for drug screening on SjLDH.

Amino Acid Sequence↗

PubMed2006

Molecular evidence of the neuroprotective effect of Ginkgo biloba (EGb761) using bax/bcl-2 ratio after brain ischemia in senescence-accelerated mice, strain prone-8.

In the present studies, we investigated the molecular mechanism of one of the active ingredients of Ginkgo biloba, EGb761, to affect the levels of several apoptotic markers in six brain regions following global ischemia in senescence-accelerated mice. A 4-day treatment with EGb761 significantly decreased bax/bcl-2 ratios in all brain regions in both young and aged mice. Our findings indicate that the bax/bcl-2 ratio provides a suitable index of apoptosis and modulation of these markers may explain the neuroprotective action of EGb761.

Aging↗

PubMed2006

Serotonin 5-HT2A and 5-HT6 receptors in the prefrontal cortex of Alzheimer and normal aging patients.

BACKGROUND: It has been hypothesized that alterations of the serotonergic system contribute to neuropsychiatric symptoms in Alzheimer disease (AD). Cellular expressions of the two serotonergic receptors 5-HT2A and 5-HT6 have therefore been determined by immunohistochemistry in the prefrontal cortex of patients with AD (n=6) and normal age-matched controls (n = 7). RESULTS: In normal aging patients, 5-HT2A label was mainly observed in large pyramidal cells, but to a lesser extent also in small pyramidal cells and in stellate cells of cortical layers II-VI. In AD, a similar distribution was observed, but density of positive cells was significantly reduced by 33%. In aging control patients, the 5-HT6 receptor was expressed by pyramidal cells and occasional stellate cells, not only of layers II-V, but also of layer I, where a distinct label was observed in neurons and surrounding fibers. 5-HT6 receptor expression in AD patients had the same pattern, but was significantly decreased by 40%. CONCLUSION: Our results indicate that a decline in neurons expressing 5-HT2A, but also 5-HT6 receptors may play a role in the etiopathology of neuropsychiatric symptoms in AD.

Aged↗

PubMed2006

General but discriminating fluorescent chemosensor for aliphatic amines.

Aliphatic amines are sensitively and discriminatively detected through binding with demethylated naphthol AS-BI (7-bromo-3-hydroxy-2-naphth-o-hydroxyanilide, 2) and fluorescence of the resulting complex. Recognition of the amine by the chemosensor 2 occurs via proton transfer of the naphtholic proton to the amine and is facilitated by the presence of the phenol group. Amine basicity is the primary controller of detection. Poorly basic aromatic and conjugated amines such as pyridine and aniline are not detected. Hydrogen bonding within the complex allows further differentiation of aliphatic amines. Doubly primary, conformationally flexible diamines are the most sensitive to detection, followed by secondary amines.

Amines↗

PubMed2006

Molecular targets for the cancer preventive activity of tea polyphenols.

Inhibition of carcinogenesis by tea and tea polyphenols has been demonstrated in many animal models. The mechanisms of action have been extensively investigated mostly in cell culture systems with (-)-epigallocatechin-3-gallate (EGCG), the most active and major polyphenolic compound from green tea. However, the mechanisms of cancer preventive activity by tea and tea polyphenols are not clearly understood. This article discusses some of the reported mechanisms and possible targets for the action of EGCG. The difficulties and major issues in extrapolating data from studies in cancer cell lines to cancer prevention mechanisms are discussed. Activities observed in cell culture with high concentrations of EGCG may not be relevant because of the limited systemic bioavailability of EGCG. In addition, possible artifacts due to the auto-oxidation of EGCG may complicate this issue. Some recent studies revealed high-affinity EGCG binding proteins as possible direct targets for the action of EGCG. Validating the related cancer preventive mechanisms found in in vitro studies in animal models and human samples would be exciting.

Animals↗

PubMed2006

Possible mechanisms of the cancer-preventive activities of green tea.

The cancer-preventive activities of tea and some tea constituents, such as caffeine and (-)-epigallocatechin-3-gallate (EGCG), have been demonstrated in animal models. The mechanisms of action of the tea constituents have been extensively investigated, but the mechanisms for the cancer-preventive activity of tea are not clearly understood. This chapter discusses some of the reported studies on the green tea polyphenol, EGCG, and the major issues in the interpretation of these data. Among the different activities of EGCG observed in cell culture systems, we need to select the physiologically relevant ones based on the biological importance of the target as well as the effective concentration and whether the reaction can take place in vivo because of the limited bioavailability of EGCG. We also need to distinguish between primary and subsequent events. Possible artifacts should be recognized. The cancer-preventive mechanisms need to be validated in animal models or human samples.

Animals↗

PubMed2006

Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin.

Adiponectin is a fat cell-secreted hormone with antidiabetic and anti-inflammatory activities. The reduced adiponectin levels are associated with obesity-related metabolic syndrome. Replenishment of this hormone into animal models can improve insulin sensitivity, decrease blood glucose and lipid levels, and prevent the development of atherosclerosis and fatty liver injury. Despite these findings, the underlying molecular mechanisms remain largely unknown. Here, we have used affinity chromatography to purify the protein complexes that are associated with adiponectin in human serum. The nature of these adiponectin-binding proteins was analyzed by MS/MS. Eight proteins from the adiponectin-containing protein mixtures have been identified. Many of them, including thrombospondin-1 (TSP-1), histidine-rich glycoprotein, kininogen 1, and alpha 2 macroglobulin (alpha2M), are well-known glycoproteins involved in the regulation of inflammation, angiogenesis, and tissue remodeling. Coimmunoprecipitation and radioligand competitive-binding assays confirmed the direct interactions between adiponectin and alpha2M, or TSP-1. Moreover, these specific bindings were also detected in the serum samples derived from both healthy human subjects and patients with type 2 diabetes. In summary, our study demonstrated that, in the circulation, adiponectin forms protein complexes with other serum proteins. These proteins might serve as the physiological-binding partners of adiponectin and regulate its bioavailability and biological activities.

Adiponectin↗

PubMed2006

[Patient-controlled intravenous analgesia with sufentanil and fentanyl after thoracotomy: a comparative study].

OBJECTIVE: To evaluate the clinical efficacy of sufentanil and fentanyl at equivalent dose for patient-controlled intravenous analgesia (PCIA) after thoracotomy. METHODS: Sixty ASA I-II patients (20-60 years of age) undergoing radical operation for lung or esophageal cancer were randomly divided into sufentanil intravenous analgesia group (group S, with sufentanil 1 microg/ml) and fentanyl intravenous analgesia group (group F, fentanyl 10 microg/ml). PCIA was administered with background infusion of 2.5 ml/h, bolus injection of 2.5 ml and lockout time of 15 min. The pain intensity according to visual analogue scale (VAS), cumulative analgesic consumption (CAC), sedative scores and side effects at 24 and 48 h after administration were recorded. SpO(2), respiratory rate (RR), blood pressure (BP) and ECG were continuously monitored. RESULTS: There were no significant differences in CAC between the two groups, but he VAS was lower in group S than in group F (P<0.05) and the sedative efficacy was superior in group S (P<0.05). The incidence of nausea and vomiting in group S was lower than that in group F (P<0.05). No significant differences were observed in SpO(2), RR, heart rate and mean arterial pressure between the two groups. CONCLUSION: PCIA with sufentanil provides better efficacy of analgesia and sedation with lower incidence of nausea and vomiting than with fentanyl in postoperative patients with thoracotomy.

Adult↗

PubMed2005

TAB-1 modulates intracellular localization of p38 MAP kinase and downstream signaling.

Stress-activated mitogen-activated protein (MAP) kinase p38 mediates stress signaling in mammalian cells via threonine and tyrosine phosphorylation in its conserved TGY motif by upstream MAP kinase kinases (MKKs). In addition, p38 MAP kinase can also be activated by an MKK-independent mechanism involving TAB-1 (TAK-1-binding protein)-mediated autophosphorylation. Although TAB-1-mediated p38 activation has been implicated in ischemic heart, the biological consequences and downstream signaling of TAB-1-mediated p38 activation in cardiomyocytes is largely unknown. We show here that TAB-1 expression leads to a significant induction of p38 autophosphorylation and consequent kinase activation in cultured neonatal cardiomyocytes. In contrast to MKK3-induced p38 kinase downstream effects, TAB-1-induced p38 kinase activation does not induce expression of pro-inflammatory genes, cardiac marker gene expression, or changes in cellular morphology. Rather, TAB-1 binds to p38 and prevents p38 nuclear localization. Furthermore, TAB-1 disrupts p38 interaction with MKK3 and redirects p38 localization in the cytosol. Consequently, TAB-1 expression antagonizes the downstream activity of p38 kinase induced by MKK3 and attenuates interleukin-1beta-induced inflammatory gene induction in cardiomyocytes. These data suggest that TAB-1 can mediate MKK-independent p38 kinase activation while negatively modulating MKK-dependent p38 function. Our study not only redefines the functional role of TAB-1 in p38 kinase-mediated signaling pathways but also provides the first evidence that intracellular localization of p38 kinase and complex interaction dictates its downstream effects. These results suggest a previously unknown mechanism for stress-MAP kinase regulation in mammalian cells.

Animals↗

PubMed2005

ATP hydrolysis is required to reset the ATP-binding cassette dimer into the resting-state conformation.

ATP-binding cassette (ABC) transporters couple ATP binding and hydrolysis to the movement of substances across the membrane; conformational changes clearly play an important role in the transporter mechanism. Previously, we have shown that a dimer of MalK, the ATPase subunit of the maltose transporter from Escherichia coli, undergoes a tweezers-like motion in a transport cycle. The MalK monomer consists of an N-terminal nucleotide binding domain and a C-terminal regulatory domain. The two nucleotide-binding domains in a dimer are either open or closed, depending on whether ATP is present, while the regulatory domains maintain contacts to hold the dimer together. In this work, the structure of MalK in a posthydrolysis state is presented, obtained by cocrystallizing MalK with ATP-Mg(2+). ATP was hydrolyzed in the crystallization drop, and ADP-Mg(2+) was found in the resulting crystal structure. In contrast to the ATP-bound form where two ATP molecules are buried in a closed interface between the nucleotide-binding domains, the two nucleotide-binding domains of the ADP-bound form are open, indicating that ADP, unlike ATP, cannot stabilize the closed form. This conclusion is further supported by oligomerization studies of MalK in solution. At low protein concentrations, ATP promotes dimerization of MalK, whereas ADP does not. The structures of dimeric MalK in the nucleotide-free, ATP-bound, and ADP-bound forms provide a framework for understanding the nature of the conformational changes that occur in an ATP-binding cassette transporter hydrolysis cycle, as well as how conformational changes in MalK are coupled to solute transport.

ATP-Binding Cassette Transporters↗

PubMed2005

Ki67 and doublecortin positive cells in the human prefrontal cortices of normal aging and vascular dementia.

Immunohistochemical localizing of the proliferation of Ki67 nuclei and doublecortin positive cells were performed in the prefrontal cortex of normal aged and vascular dementia (multiple infarct dementia) patients. Positive Ki67 nuclei and doublecortin positive cells were observed in both groups, with slightly higher density in the prefrontal cortex of vascular dementia. When the Ki67 sites were superimposed with the neuronal specific enolase localizations, only about 5% of the cells was doubly labeled, indicating few proliferating cells were neurons. This percentage did not vary between specimens of normal aging and those of vascular dementia.

Aged, 80 and over↗

PubMed2005

Hypoxia-induced differential apoptosis in the central nervous system of the sturgeon (Acipenser shrenckii).

Hypoxia is a frequent challenge to aquatic vertebrates as compared with that for their terrestrial counterparts. All vertebrates respond to hypoxia in a similar, but not identical manner, indicating that these responses appeared early in the evolution of vertebrates. The aim of this study is to find out the effects of hypoxia on apoptosis in the central nervous system (CNS) of sturgeon, an archaic fish. With the regional specialization of the CNS, we hypothesize that if cell death does occur, the response will vary between regions, i.e., some CNS areas will be more susceptible to hypoxia than the others would. Sturgeons (Acipenser shrenckii) were subjected to hypoxia by exposure to either air or hypoxic water. After 6- or 30-h recovery they were sacrificed and the following regions of the CNS: retina, olfactory lobe, optic tectum, pituitary, cerebellum, pons/medulla, and spinal cord were examined by the terminal transferase mediated dUTP nick end labeling technique and for the cleaved fragment of activated caspase-3 by Western blotting. In hypoxia-treated sturgeons, the retina, optic tectum, pituitary, and spinal cord were found to have significantly more apoptotic cells than did untreated sturgeons at both 6 and 30 h after the hypoxic insults, indicating prolonged damage. Apoptosis was confirmed by Western blotting of the cleaved fragment of activated caspase-3. Olfactory lobe, cerebellum, and pons/medulla had relatively few apoptotic cells. The CNS of sturgeon showed a differential pattern of apoptosis in response to hypoxia.

Animals↗

PubMed2005

Simple sequence repeat-based consensus linkage map of Bombyx mori.

We established a genetic linkage map employing 518 simple sequence repeat (SSR, or microsatellite) markers for Bombyx mori (silkworm), the economically and culturally important lepidopteran insect, as part of an international genomics program. A survey of six representative silkworm strains using 2,500 (CA)n- and (CT)n-based SSR markers revealed 17-24% polymorphism, indicating a high degree of homozygosity resulting from a long history of inbreeding. Twenty-nine SSR linkage groups were established in well characterized Dazao and C108 strains based on genotyping of 189 backcross progeny derived from an F(1) male mated with a C108 female. The clustering was further focused to 28 groups by genotyping 22 backcross progeny derived from an F(1) female mated with a C108 male. This set of SSR linkage groups was further assigned to the 28 chromosomes (established linkage groups) of silkworm aided by visible mutations and cleaved amplified polymorphic sequence markers developed from previously mapped genes, cDNA sequences, and cloned random amplified polymorphic DNAs. By integrating a visible mutation p (plain, larval marking) and 29 well conserved genes of insects onto this SSR-based linkage map, a second generation consensus silkworm genetic map with a range of 7-40 markers per linkage group and a total map length of approximately 3431.9 cM was constructed and its high efficiency for genotyping and potential application for synteny studies of Lepidoptera and other insects was demonstrated.

Animals↗

PubMed2005

Comparative and functional genomic analyses of the pathogenicity of phytopathogen Xanthomonas campestris pv. campestris.

Xanthomonas campestris pathovar campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield world-wide. This bacterium is a model organism for studying plant-bacteria interactions. We sequenced the complete genome of Xcc 8004 (5,148,708 bp), which is highly conserved relative to that of Xcc ATCC 33913. Comparative genomics analysis indicated that, in addition to a significant genomic-scale rearrangement cross the replication axis between two IS1478 elements, loss and acquisition of blocks of genes, rather than point mutations, constitute the main genetic variation between the two Xcc strains. Screening of a high-density transposon insertional mutant library (16,512 clones) of Xcc 8004 against a host plant (Brassica oleraceae) identified 75 nonredundant, single-copy insertions in protein-coding sequences (CDSs) and intergenic regions. In addition to known virulence factors, full virulence was found to require several additional metabolic pathways and regulatory systems, such as fatty acid degradation, type IV secretion system, cell signaling, and amino acids and nucleotide metabolism. Among the identified pathogenicity-related genes, three of unknown function were found in Xcc 8004-specific chromosomal segments, revealing a direct correlation between genomic dynamics and Xcc virulence. The present combination of comparative and functional genomic analyses provides valuable information about the genetic basis of Xcc pathogenicity, which may offer novel insight toward the development of efficient methods for prevention of this important plant disease.

Bacterial Proteins↗