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Biomedical subjects

Hong Guo

Publications and source records attributed to Hong Guo.

At least 37 records · Page 2Linked to original sources
PubMed2006

Effects of Transcutol P on the corneal permeability of drugs and evaluation of its ocular irritation of rabbit eyes.

Our purpose was to explore the use of Transcutol P (Trans) in an ocular drug delivery system. The effect of Trans on the corneal permeability of drugs was investigated in-vitro, using isolated rabbit corneas. The ocular irritation of Trans was also tested in rabbits in-vivo. In the presence of Trans, at a concentration of 0.005-0.03%, the maximum increase in the apparent permeability coefficient (P(app)) was 1.5, 1.5, 3.0 and 3.3 fold for ribavirin, gatifloxacin, levofloxacin hydrochloride and enoxacin, respectively. However, the P(app) value of oxaprozin was reduced in the presence of Trans. The maximum reduction was found to be 2.8 fold at a concentration of 0.03% Trans. The results of the ocular irritation studies showed that Trans was non-irritant at the concentrations studied (0.005-0.03%), while it produced slight irritation at a concentration of 0.05%. It was also found that Trans did not cause any visible ocular damage or abnormal clinical signs involving the cornea, iris or conjunctivae at all concentrations. We concluded that Trans may have potential clinical benefits in improving the ocular drug delivery of hydrophilic compounds.

1-Octanol↗
PubMed2006

Effects of isopropyl palmitate on the skin permeation of drugs.

The model penetrants oxaprozin, nimesulide, gliclazide, and ribavirin, because of their different lipophilicities, were selected to assess the enhancing activity of pre-treatment solutions consisting of isopropyl palmitate (IP) in ethanol (5%, 10%, 15%and 20%, w/w, respectively) across excised rat skin using Franz diffusion cells and HPLC detection. All pre-treatment solutions produced a significant increase in the flux and permeation of all four penetrants (p<0.001) and a relationship between penetrant lipophilicity and enhancement effect was observed. The general order of IP effectiveness at concentration was 20%>15%>10%>5% (w/w). The lag-time of drugs did not significantly change except for ribavirin.

Abdomen↗
PubMed2006

[A preliminary study on anti-liver cancer immunity of the virus-like particulate peptide-nucleic acid vaccine].

OBJECTIVES: To construct a novel virus-like particulate peptide-nucleic acid vaccine (VPNV) of human telomerase reverse transcriptase (hTERT), and to study its anti-liver cancer immunity. METHODS: A cationic antigenic peptide was synthesized and purified, and then human granulocyte macrophage colony stimulating factor (hGM-CSF) and TERT gene were cloned into the eukaryotic expression vector pTCAE. The peptide was combined with the nucleic acid vaccine to make a VPNV, which was transfected into eukaryotic cell COS-7. The immunogenicity of hGM-CSF and hTERT were detected using ELISA and Western blot. The efficacy of VPNV for inducing antigen specific CTL response was determined using the lactate dehydrogenase release method. RESULTS: VPNV was verified capable to trigger specific CTL responses and has shown a specific cytolytic activity to liver cancer cell HepG2. CONCLUSION: A VPNV which can stimulate antigen specific CTL response was successfully constructed. This paves the way for our further investigation of anti-liver cancer immunity in mice.

Animals↗
PubMed2006

[Apoptosis of K562 cells induced by nociceptin/orphanin FQ].

The study was to investigate the proliferation and apoptosis effect of nociceptin/orphanin FQ (OFQ) on 562 cells in vitro. Inhibition of K562 cells proliferation was measured by MTT assay. Morphological assessment of apoptosis was performed with Wright staining and transmission electron microscope. The apoptosis peak was measured by flow cytometry. DNA fragmentation was visualized by agarose gel electrophoresis. The results showed that OFQ time-dependently and no-dose-dependently inhibited the proliferation of K562 cells at concentrations of 10(-6) - 10(-13) mol/L. Discrete maximum of cytolytic activity was detected at concentrations of 10(-6) - 10(-7), 10(-9), 10(-12) mol/L. Compared with the control group K562 cells, the cells treated with OFQ at concentration of 10(-9) mol/L for 72 hours showed typical characteristics of apoptosis under transmission electron microscope. Apoptosis peak was found by FCM at concentration of 0, 10(-7), 10(-8), 10(-9) mol/L of OFQ for 72 hours, apoptosis rates were 0%, 22.8%, 23.8% and 26.5% respectively. DNA agarose gel electrophoresis revealed nuclear fragmentation (DNA ladder). It is concluded that OFQ can inhibit the proliferation of K562 cells and induce the apoptosis in K562 cells.

Apoptosis↗
PubMed2005

Global analysis of protein phosphorylation in yeast.

Protein phosphorylation is estimated to affect 30% of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.

Eukaryotic Cells↗
PubMed2005

Conductance of an ensemble of molecular wires: a statistical analysis.

We report on a first principles analysis of quantum transport through molecular wires made of 4,4'bipyridine and 6-alkanedithiol contacted by Au electrodes. We investigate how charge transport is altered due to small structure changes at the molecule-electrode contacts. These changes include distance between the molecule and the contact, extra metal atoms at the Au surface, binding sites, molecular orientation, and bias voltages. By investigating hundreds of wires we extract a statistical picture on transport properties of the two different molecules. We compare quantitatively with the corresponding experimental data.

Journal Article↗
PubMed2005

Ab initio analysis of electron-phonon coupling in molecular devices.

We report a first principles analysis of electron-phonon coupling in molecular devices under external bias voltage and during current flow. Our theory and computational framework are based on carrying out density functional theory within the Keldysh nonequilibrium Green's function formalism. Using a molecular tunnel junction of a 1,4-benzenedithiolate molecule contacted by two aluminum leads as an example, we analyze which molecular vibrational modes are most relevant to charge transport under nonequilibrium conditions. We find that the low-lying modes are most important. As a function of bias voltage, the electron-phonon coupling strength can change drastically while the vibrational spectrum changes at a few percent level.

Journal Article↗
PubMed2005

Novel antiglaucoma prodrugs and codrugs of ethacrynic acid.

The purpose of this study was to synthesize a novel prodrug of ethacrynic acid (ECA) with short chain polyethylene glycols (PEGs) and codrugs of ECA with the beta-adrenergic blocking agent atenolol (ATL) or timolol (TML) to overcome the adverse effects of ECA and to enhance its physicochemical properties.

Adrenergic beta-Antagonists↗
PubMed2005

Defects in SUMO (small ubiquitin-related modifier) conjugation and deconjugation alter cell sensitivity to DNA topoisomerase I-induced DNA damage.

Eukaryotic DNA topoisomerase I (Top1p) has important functions in DNA replication, transcription, and recombination. This enzyme also constitutes the cellular target of camptothecin (CPT), which induces S-phase-dependent cytotoxicity. To define cellular pathways that regulate cell sensitivity to Top1p-induced DNA lesions, we described a yeast genetic screen for conditional tah (top1T722A-hypersensitive) mutants with enhanced sensitivity to low levels of the CPT mimetic mutant top1T722A (Reid, R. J., Fiorani, P., Sugawara, M., and Bjornsti, M. A. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 11440-11445; Fiorani, P., Reid, R. J., Schepis, A., Jacquiau, H. R., Guo, H., Thimmaiah, P., Benedetti, P., and Bjornsti, M. A. (2004) J. Biol. Chem. 279, 21271-21281). Here we report that tah mutant ubc9-10 harbors a hypomorphic allele of UBC9, which encodes the essential SUMO (small ubiquitin-related modifier) E2-conjugating enzyme. The same conditional ubc9P123L mutant was also isolated in an independent screen for enhanced sensitivity to a distinct Top1p poison, Top1N726Hp. The ubc9-10 mutant exhibited a decrease in global protein sumoylation and increased sensitivity to a wide range of DNA-damaging agents independent of Top1p. Deletion of the Ulp2 SUMO protease failed to restore ubc9-10 cell resistance to Top1p poisons or hydroxyurea yet adversely affected wild-type TOP1 cell genetic stability and sensitivity to hydroxyurea. Moreover, although mutation of different consensus SUMO sites in the N terminus and linker region of yeast Top1p failed to recapitulate ubc9-10 mutant phenotypes, they revealed distinct and subtle effects on cell sensitivity to CPT. These results provide insights into the complexities of SUMO conjugation and the confounding effects of SUMO modification on Top1p function and cell sensitivity to genotoxic agents.

DNA Damage↗
PubMed2005

Origin of tight binding of a near-perfect transition-state analogue by cytidine deaminase: implications for enzyme catalysis.

Cytidine deaminase (CDA) is a zinc metalloenzyme that catalyzes the hydrolytic deamination of cytidine to uridine. Zebularine (ZEB) binds to CDA, and the binding process leads to a near-perfect transition-state analogue (TSA) inhibitor at the active site with an estimated K(i) value of 1.2 x 10(-)(12) M. The interaction of CDA with the TSA inhibitor has become a paradigm for studying the tight TSA binding by enzymes. The formation of the TSA is catalyzed by CDA by a mechanism that is similar to the formation of the tetrahedral intermediate during the CDA-catalyzed reaction (i.e., through the nucleophilic attack of a Zn-hydroxide group on C(4)). It is believed that the TSA formed at the active site is zebularine 3,4-hydrate. In this paper, it is shown from QM/MM molecular dynamics and free energy simulations that zebularine 3,4-hydrate may in fact be unstable in the enzyme and that a proton transfer from the Zn-hydroxide group to Glu-104 during the nucleophilic attack could be responsible for the very high affinity. The nucleophilic attack by the Zn-hydroxide on C(4) is found to be concerted with two proton transfers. Such concerted process allows the TSA, an alkoxide-like inhibitor, to be stabilized through a mechanism that is similar to the transition-state stabilization in the general acid-base catalysis. It is suggested that the proton transfer from the Zn-hydroxide to Glu-104, which is required to generate the general acid for protonating the leaving ammonia, may play an important role in lowering the activation barrier during the catalysis.

Cytidine↗
PubMed2005

Microglial expression of the B7 family member B7 homolog 1 confers strong immune inhibition: implications for immune responses and autoimmunity in the CNS.

Inflammation of the CNS is usually locally limited to avoid devastating consequences. Critical players involved in this immune regulatory process are the resident immune cells of the brain, the microglia. Interactions between the growing family of B7 costimulatory ligands and their receptors are increasingly recognized as important pathways for costimulation and/or inhibition of immune responses. Human and mouse microglial cells constitutively express B7 homolog 1 (B7-H1) in vitro. However, under inflammatory conditions [presence of interferon-gamma (IFN-gamma) or T-helper 1 supernatants], a significant upregulation of B7-H1 was detectable. Expression levels of B7-H1 protein on microglial cells were substantially higher compared with astrocytes or splenocytes. Coculture experiments of major histocompatibility complex class II-positive antigen-presenting cells (APC) with syngeneic T cells in the presence of antigen demonstrated the functional consequences of B7-H1 expression on T-cell activation. In the presence of a neutralizing anti-B7-H1 antibody, both the production of inflammatory cytokines (IFN-gamma and interleukin-2) and the upregulation of activation markers (inducible costimulatory signal) by T cells were markedly enhanced. Interestingly, this effect was clearly more pronounced when microglial cells were used as APC, compared with astrocytes or splenocytes. Furthermore, B7-H1 was highly upregulated during the course of myelin oligodendrocyte glycoprotein-induced and proteolipid protein-induced experimental allergic encephalomyelitis in vivo. Expression was predominantly localized to areas of strongest inflammation and could be colocalized with microglial cells/macrophages as well as T cells. Together, our data propose microglial B7-H1 as an important immune inhibitory molecule capable of downregulating T-cell activation in the CNS and thus confining immunopathological damage.

Animals↗
PubMed2005

Detection of single-electron charging in an individual InAs quantum dot by noncontact atomic-force microscopy.

Single-electron charging in an individual InAs quantum dot was observed by electrostatic force measurements with an atomic-force microscope (AFM). The resonant frequency shift and the dissipated energy of an oscillating AFM cantilever were measured as a function of the tip-back electrode voltage, and the resulting spectra show distinct jumps when the tip was positioned above the dot. The observed jumps in the frequency shift, with corresponding peaks in dissipation, are attributed to a single-electron tunneling between the dot and the back electrode governed by the Coulomb blockade effect, and are consistent with a model based on the free energy of the system. The observed phenomenon may be regarded as the "force version" of the Coulomb blockade effect.

Journal Article↗
PubMed2005

Cancer-related symptom assessment in Russia: validation and utility of the Russian M. D. Anderson Symptom Inventory.

This multicenter cross-sectional study (n=226) validated the Russian-language M. D. Anderson Symptom Inventory (MDASI-R) in Russian cancer patients with hematological malignancies or solid tumors. The Russian-language Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36-R) also was used for validation. Factor analysis found three underlying constructs for symptom items--general, treatment-related, and affective symptoms--with Cronbach alphas of 0.86, 0.68, and 0.90, respectively. Convergent validity was established by comparing MDASI-R items with SF-36-R subscales. The MDASI-R detected significant differences in symptom severity and interference levels by performance status, supporting known-group validity. The most prevalent symptoms were fatigue, sleep disturbance, pain, sadness, and poor appetite; 53% of the sample reported one to four moderate-to-severe symptoms (>or=5 on 0-10 scale). Symptoms interfered most with work and general activity. Medical professionals underestimated the severity of pain, fatigue, and distress. The MDASI-R is valid and reliable for measuring symptom severity and interference in Russian cancer patients.

Adolescent↗
PubMed2005

Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies.

Destruction of nigrostriatal dopaminergic (DA) pathway triggers various persistent responses, such as inflammation and increased synthesis of neural growth factors, both in striatum and in substantia nigra. The pathological processes involved in such responses are poorly characterized and could contribute to secondary damage and/or regeneration in the central nervous system (CNS). Cystatin C was previously implicated in the process of neurodegeneration. However, its biological role during neurodegeneration is not understood and remains controversial. The present study identified an increased cystatin C mRNA level in the DA-depleted rat striatum, starting from the second week following a 6-OHDA-induced lesion. Immunohistochemical analysis confirmed the increase in cystatin C protein level in the striatum following DA depletion. Double-labeled fluorescence immunohistochemistry revealed that nigrostriatal neurons, astrocytes, and microglia contributed to the elevated level of cystatin C. Exposure to 6-hydroxydopamine, a DA-specific neurotoxin, resulted in DA neurons loss in the fetal mesencephalic cultures, an effect which could be partially reversed by treatment with cystatin C. Moreover, in vivo DA neurons survival study showed that administration of cystatin C in rats with 6-OHDA-induced lesion partially rescued the nigral DA neurons. The results indicate that the 6-OHDA lesioning induced a relatively slow but sustained up-regulation of cystatin C expression and suggest that the inhibitor may exert a neuroprotective action on DA neurons. The findings raise the possibility that cysteine proteinase inhibitors may be new candidates for neuroprotective treatment of Parkinson's disease. Cystatin C may be useful therapeutically in limiting neuropathy in Parkinson's disease.

Animals↗
PubMed2005

Feature generation using genetic programming with application to fault classification.

One of the major challenges in pattern recognition problems is the feature extraction process which derives new features from existing features, or directly from raw data in order to reduce the cost of computation during the classification process, while improving classifier efficiency. Most current feature extraction techniques transform the original pattern vector into a new vector with increased discrimination capability but lower dimensionality. This is conducted within a predefined feature space, and thus, has limited searching power. Genetic programming (GP) can generate new features from the original dataset without prior knowledge of the probabilistic distribution. In this paper, a GP-based approach is developed for feature extraction from raw vibration data recorded from a rotating machine with six different conditions. The created features are then used as the inputs to a neural classifier for the identification of six bearing conditions. Experimental results demonstrate the ability of GP to discover autimatically the different bearing conditions using features expressed in the form of nonlinear functions. Furthermore, four sets of results--using GP extracted features with artificial neural networks (ANN) and support vector machines (SVM), as well as traditional features with ANN and SVM--have been obtained. This GP-based approach is used for bearing fault classification for the first time and exhibits superior searching power over other techniques. Additionaly, it significantly reduces the time for computation compared with genetic algorithm (GA), therefore, makes a more practical realization of the solution.

Algorithms↗
PubMed2005

Development of pontine noradrenergic A5 neurons requires brain-derived neurotrophic factor.

Pontine noradrenergic A5 neurons play a pivotal role in maturation and regulation of the brainstem respiratory rhythm-generating network. Analysis of newborn brain-derived neurotrophic factor (BDNF)-null mice revealed a marked loss of tyrosine hydroxylase-positive A5 neurons compared to wildtype controls that was rescued by null mutation of the proapoptotic gene Bax. In cultures of the A5 region from E12.5 rat embryos, BDNF significantly increased the number and branching of tyrosine hydroxylase-positive neurons. Immunoneutralization of endogenous glial cell line-derived neurotrophic factor partially inhibited the BDNF-dependent increase in the number of tyrosine hydroxylase-positive cells without affecting neurite number. The A5 nucleus is the first brainstem cell group identified at which BDNF is required in vivo for development of neurons critical for cardiorespiratory control.

Analysis of Variance↗
PubMed2005

Novel DNA sequences from natural strains of the nitrogen-fixing symbiotic bacterium Sinorhizobium meliloti.

Variation in genome size and content is common among bacterial strains. Identifying these naturally occurring differences can accelerate our understanding of bacterial attributes, such as ecological specialization and genome evolution. In this study, we used representational difference analysis to identify potentially novel sequences not present in the sequenced laboratory strain Rm1021 of the nitrogen-fixing bacterium Sinorhizobium meliloti. Using strain Rm1021 as the driver and the type strain of S. meliloti ATCC 9930, which has a genome size approximately 370 kilobases bigger than that of strain Rm1021, as the tester, we identified several groups of sequences in the ATCC 9930 genome not present in strain Rm1021. Among the 85 novel DNA fragments examined, 55 showed no obvious homologs anywhere in the public databases. Of the remaining 30 sequences, 24 contained homologs to the Rm1021 genome as well as unique segments not found in Rm1021, 3 contained sequences homologous to those published for another S. meliloti strain but absent in Rm1021, 2 contained sequences homologous to other symbiotic nitrogen-fixing bacteria (Rhizobium etli and Bradyrhizobium japonicum), and 1 contained a sequence homologous to a gene in a non-nitrogen-fixing species, Pseudomonas sp. NK87. Using PCR, we assayed the distribution of 12 of the above 85 novel sequences in a collection of 59 natural S. meliloti strains. The distribution varied widely among the 12 novel DNA fragments, from 1.7% to 72.9%. No apparent correlation was found between the distribution of these novel DNA sequences and their genotypes obtained using multilocus enzyme electrophoresis. Our results suggest potentially high rates of gene gain and loss in S. meliloti genomes.

Base Sequence↗