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Biomedical subjects

Hao Chen

Publications and source records attributed to Hao Chen.

At least 55 records · Page 3Linked to original sources
PubMed2006

[The protective effect of heat shock protein 72 by Doxorubicin in cold ischemia-reperfusion injury of the rat liver].

OBJECTIVE: To observe induction of heat shock reaction by pretreatment of Doxorubicin (DXR) in long-term cold preservation-reperfusion injury of the rat liver. METHODS: The rats were administered intravenously by DXR at a dose of 1 mg/kg body weight in DXR group and by saline in control group. After 48 hours, the rat liver was perfused by using cold University of Wisconsin (UW) solutions and was preserved in UW solution at 4 degrees C for 48 hours. Recipient liver was perfused for 1 and 3 hours after orthotopic liver transplantation. Tumor necrosis factor-alpha (TNF-alpha) mRNA, cytokine-induced neutrophil chemoattractant (CINC) mRNA, macrophage inflammatory protein (MIP-2) mRNA was measured by RT-PCR and heat shock protein 72 (HSP72), nuclear factor-kappaB (NF-kappaB) by Western blot. The serum levels of TNF-alpha, CINC, MIP-2 by ELISA and AST were measured. The survival rate of 7 days was observed. RESULTS: The expression of TNF-alpha mRNA, CINC mRNA and MIP-2 mRNA was stronger in control group than in DXR group. HSP72 was expressed in SA group but not in control group and oppositely NF-kappaB was expressed in control group but not in DXR group. Serum AST, TNF-alpha, CINC and MIP-2 concentrations were significantly lower in DXR group than in control group (P < 0.05). The survival rate of 7 days was significantly higher in DXR group than in control group (50% vs. 0%, P < 0.05). CONCLUSIONS: These data suggested that long-term cold ischemia-reperfusion injury was attenuated in liver graft with pretreatment of DXR. The induction of HSP72 may offer protection to hepatocytes by restraining the activation of NF-kappaB and inflammation.

Animals↗
PubMed2006

Upregulation of ionotropic glutamate receptor subunits within specific mesocorticolimbic regions during chronic nicotine self-administration.

Nicotine, an addictive substance, is the major psychoactive component in cigarette smoke. Both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate (NMDA) receptors are essential for the acute stimulative effects of nicotine on the mesocorticolimbic dopamine system, yet little is known about the effects of chronic nicotine treatment on glutamate receptors. Therefore, we used a model of chronic nicotine self-administration (SA), which emulates important aspects of nicotine intake by humans, to determine whether glutamate receptor subunits were affected. After 18 days of saline vs nicotine SA, ionotropic glutamate receptor subunit levels were determined in brain regions within the mesocorticolimbic system by Western blotting. In prefrontal cortex (PFC), the levels of NMDA receptor subunit 2A (NR2A) and NR2B were increased by 67% (p=0.04) and 83% (p=0.027), respectively. In the ventral tegmental area (VTA), glutamate receptor subunit 2/3 (GluR2/3) increased by 34% (p=0.011). Nicotine SA did not affect the expression of these subunits in dorsal striatum and nucleus accumbens. These findings suggest that chronic nicotine SA selectively increased the levels of ionotropic glutamate receptor subunits in a brain region-specific manner.

Animals↗
PubMed2006

Collision-induced dissociation studies of protonated ether--(H2O)n (n = 1-3) clusters.

We have studied the protonated ether-(H2O)n (n = 1-3) complexes containing tetrahydrofuran, dimethyl, diethyl, dibutyl, and butylmethyl ethers using a flowing afterglow triple-quadrupole mass spectrometer. Collision-induced dissociation, CID, of all clusters with n = 1, 2 shows sequential water loss. The n = 3 cluster of dimethyl ether shows sequential water loss, while all other ether clusters display selective product formation. The CID spectra are interpreted based on known energetics, and theoretical studies of the dimethyl and diethyl ether systems.

Journal Article↗
PubMed2006

Metabolism-dependent mutagenicity of a compound containing a piperazinyl indazole motif: Role of a novel p450-mediated metabolic reaction involving a putative oxaziridine intermediate.

Compound 1a (6-chloro-5-{3-[4-(1H-indazol-3-yl)-piperazin-1-yl]-propyl}-3,3-dimethyl-1,3-dihydro-indol-2-one) was mutagenic to Salmonella typhimurium TA98 in the presence of rat liver S9 subcellular fraction. The metabolism of 1a in rat liver S9 or microsomes demonstrated that it underwent a P450-mediated N-deindazolation (loss of indazole ring) as a predominant metabolic pathway. To investigate a possible link between metabolism and mutagenicity, a structural analogue 1b (6-chloro-5-{3-[4-(1H-indazol-3-yl)-piperidin-1-yl]-propyl}-3,3-dimethyl-1,3-dihydro-indol-2-one), the cleaved product 2a (6-chloro-3,3-dimethyl-5-(3-piperazin-1-yl-propyl)-1,3-dihydro-indol-2-one), and the core motif 3a (3-piperazinyl indazole) were evaluated in the Ames assay. It was found that 1b was not mutagenic to Salmonella typhimurium TA98 in the absence or presence of a metabolic activating system. In contrast to 1a, 1b did not undergo the metabolic cleavage (loss of indazole ring). Marginal mutagenicity of 2a to TA98 was observed with rat liver S9, whereas 3a was shown to be a promutagen. It was further demonstrated that 1a inactivated P450 3A, the principle enzyme catalyzing the N-deindazolation reaction, in an NADPH-, time-, and concentration-dependent manner. The kinetics of inactivation was characterized by a K(I) of 8.1 microM and k(inact) of 0.114 min(-1). The differences in mutagenicity between 1a and 1b suggest that a chemical bond extending from the 3-position of the indazole to a heteroatom (as part of another cyclic ring) is a prerequisite for the toxicity. The metabolic process leading to the elimination of the indazole from the rest of the molecule apparently plays a key role in causing mutagenicity. It is postulated that the N-deindazolation of 1a proceeds via an oxaziridine intermediate, the formation of which is indirectly inferred from the presence of benzoic acid in microsomal incubations. Benzoic acid is thought to be derived from the hydrolysis of 3-indazolone, an unstable product generated from the oxaziridine. Evidence suggests that the electrophilic oxaziridine intermediate may be responsible for the mutagenicity and inactivation of P450 3A.

Animals↗
PubMed2006

Prevalence of photodermatosis in four regions at different altitudes in Yunnan province, China.

Idiopathic photodermatoses are common diseases in dermatology clinics that are associated with ultraviolet (UV) irradiation. The group includes a few dermatoses such as polymorphous light eruption (PLE) and chronic actinic dermatitis (CAD). The prevalence of PLE and CAD in China has not been previously reported. To investigate the population-based prevalence of polymorphous light eruption (PLE) and chronic actinic dermatitis (CAD) in six minority groups living in four regions with significantly different altitudes in the Yunnan province, a questionnaire survey was administered to 4899 residents of random villages in Yuanjiang county (Dai and Hani minorities), Kunming city (Han people and Yi minority), Lijiang county (Naxi minority), and Shangri-La county (Zang minority). The altitudes of these counties are 380 m, 1870 m, 2410 m and 3280 m a.s.l., respectively. The results showed that, first, there were 2400 males (49.0%) and 2499 females (51.0%). The prevalence of PLE was 0.65% (32/4899), and the prevalence of CAD was 0.18% (9/4899). PLE was higher among females than males (3.8 vs 1, P < 0.01). The CAD prevalence was not significantly different between males and females (1.6 vs 1, P > 0.05). Second, the prevalence of PLE was increased in higher elevations regions compared to lower elevations (P < 0.01). However, the prevalence of CAD was not significantly different among the four regions (P > 0.05). Third, the mean times of sun exposure for PLE and CAD were 6.0 and 6.5 h/day, respectively. The mean durations of PLE and CAD were 5.8 years, and 6.6 years, respectively. The study demonstrated that the prevalence of PLE is higher than that of CAD in Yunnan, and that the prevalence of PLE is correlated with altitude.

Adult↗
PubMed2006

Mineral formation in joints caused by complete or joint-specific loss of ANK function.

UNLABELLED: To reveal the ANK complete loss of function phenotype in mice, we generated conditional and null alleles. Mice homozygous for the null allele exhibited widespread joint mineralization, similar in severity to animals harboring the original ank allele. A delayed yet similar phenotype was observed in mice with joint-specific loss of ANK function. INTRODUCTION: The ANK pyrophosphate regulator was originally identified and proposed to play a key role in articular cartilage maintenance based on a single spontaneous mouse mutation (ank) that causes severe generalized arthritis. A number of human mutations have subsequently been reported in the human ortholog (ANKH), some of which produce skull and long bone defects with no apparent defects in joints or articular cartilage. None of the currently known mouse or human mutations clearly eliminate the function of the endogenous gene. MATERIALS AND METHODS: Two new Ank alleles were generated using homologous recombination in mouse embryonic stem (ES) cells. Joint range of motion assays and muCT studies were used to quantitatively assess phenotypic severity in wildtype, heterozygous, and homozygous mice carrying either the null (Anknull) or original (Ankank) allele. A Gdf5-Cre expressing line was crossed to mice harboring the conditional (Ankfloxp) allele to eliminate ANK function specifically in the joints. Histological stains and beta-galactosidase (LACZ) activity were used to determine the correlation between local loss of ANK function and defective joint phenotypes. RESULTS: Anknull/Anknull mice develop severe ectopic postnatal crystal deposition in almost every joint of the body, leading to eventual joint fusion and loss of mobility. The severity of phenotype in these mice is indistinguishable from that of Ankank/Ankank mice. In addition, despite the widespread expression of Ank in many tissues, the specific deletion of Ank in joints also produces joint mineralization and ankylosis. CONCLUSIONS: These studies show that ANK function is required locally in joints to inhibit mineral formation and that the Ank gene plays a key role in postnatal maintenance of joint mobility and function.

Alleles↗
PubMed2006

Quaternary structure, substrate selectivity and inhibitor design for SARS 3C-like proteinase.

The SARS coronavirus 3C-like proteinase is recognized as a potential drug design target for the treatment of severe acute respiratory syndrome. In the past few years, much work has been done to understand the catalytic mechanism of this target protein and to design its selective inhibitors. The protein exists as a dimer/monomer mixture in solution and the dimer was confirmed to be the active species for the enzyme reaction. Quantitative dissociation constants have been reported for the dimer by using analytic ultracentrifuge, gel filtration and enzyme assays. Though the enzyme is a cysteine protease with a chymotrypsin fold, SARS 3C-like proteinase follows the general base catalytic mechanism similar to chymotrypsin. As the enzyme can cut eleven different sites on the viral polyprotein, the substrate specificity has been studied by synthesized peptides corresponding or similar to the cleavage sites on the polyprotein. Predictive model was built for substrate structure and activity relationships and can be applied in inhibitor design. Due to the lack of potential drugs for the treatment of SARS, the discovery of inhibitors against SARS 3C-like proteinase, which can potentially be optimized as drugs appears to be highly desirable. Various groups have been working on inhibitor discovery by virtual screening, compound library screening, modification of existing compounds or natural products. High-throughput in vitro assays, auto-cleavage assays and viral replication assays have been developed for inhibition activity tests. Inhibitors with IC50 values as low as 60 nM have been reported.

Animals↗
PubMed2006

Abdominal cluster transplantation and management of perioperative hemodynamic changes.

BACKGROUND: Multivisceral transplantation (MTX, or cluster transplantation) is defined as the transplantation of three or more abdominal organs en bloc, namely the liver together with the pancreatoduodenal complex, the stomach as well as the small bowel with/without the right hemicolon. Up to May 1999, only 72 cases were reported to the Intestinal Transplant Registry. Organ cluster transplantation may carry with complex hemodynamic alterations. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of multivisceral transplantation and the management of hemodynamic changes. METHODS: A Swan-Ganz catheter was placed to assist in monitoring the patients' hemodynamic status. After the transplantation, the 2 patients were closely observed in the intensive care unit in terms of vital signs;disseminated intravascular coagulation (DIC) including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg) and D-dimer, and arterial blood gas; and quantity and characteristics of drainage. Additionally, intra-abdominal hemorrhage was supervised by bedside B-ultrasonography or enhanced computed tomography (CT) examination. Whole blood viscosity was monitored 2 weeks after transplantation. The blood flow of the hepatic artery and portal vein and arterial resistant index were assessed routinely by Doppler ultrasonography. RESULTS: Hemodynamic changes were observed during perioperation. Liver and renal function recovered within one week after transplantation. Enteral feedings and oral intake were gradually increased with a reciprocal decrease in parenteral nutrition. Despite systemic antibiotics were given according to the results of frequent cultures, patient 1 died from cytomegalovirus (CMV) infection 4 months after transplantation and patient 2 died of a systemic sepsis 2 months after the operation. CONCLUSIONS: Many factors contribute to the success of multivisceral transplantation. In order to maintain hemodynamics stable during perioperation, preoperative coagulatory function should be corrected, and stable circulation, serum electrocyte balance, and normal body temperature should be kept during the operation in addition to the treatment of intra-abdominal hemorrhage and making up for the loss of body fluid. However, complications, infection and rejection are barriers for the improvement of graft survival.

Adenomatous Polyps↗
PubMed2006

[Auditory brainstem response in normal guinea pigs and those with gentamicin-induced hearing loss under awake and anesthetic conditions].

OBJECTIVE: To observe the alterations of auditory brainstem response (ABR) in guinea pigs with gentamicin-induced hearing loss under awake and anesthetic conditions. METHODS: We recorded the ABR in 20 normal guinea pigs and 20 with gentamicin-induced hearing loss before and after anesthesia for statistical analysis. RESULTS: No significant difference was observed in the waveform, response threshold (RT), I and III peak latencies (PL), I-III interpeak latencies (IPL) of ABR between awake and anesthetic conditions in normal guinea pigs (P>0.05), nor did gentamicin-induced hearing loss showed obvious impact on the ABR parameters (P>0.05). CONCLUSION: No significant ABR alterations occur under awake and anesthetic conditions in either normal guinea pigs or those with hearing loss, therefore ABR test can be performed without anesthesia to ensure the success and error minimization of the experiment.

Anesthesia↗
PubMed2005

Adenovirus-mediated small-interference RNA for in vivo silencing of angiotensin AT1a receptors in mouse brain.

Because of the lack of pharmacological approaches, molecular genetic methods have been required to differentiate between angiotensin type 1(AT1) receptor subtypes AT1a and AT1b. RNA interference is a new tool for the study of gene function, producing specific downregulation of protein expression. In this study, we used the small hairpin RNA (shRNA) cassette method to screen target sites for selectively silencing AT1a or AT1b receptor subtypes in cultured Neuro-2a cells using real-time RT-PCR. For in vivo functional studies, we used C57BL mice with arterial telemetric probes and computerized licking monitors to test the effect of adenovirus carrying the DNA sequence coding AT1a shRNA (Ad-AT1a-shRNA). Ad-AT1a-shRNA was injected into the lateral ventricle (intracerebroventricular) or the brain stem nucleus tractus solitaries/dorsal vagal nucleus (NTS/DVN) with measurement of water intake, blood pressure (BP), and heart rate (HR) for up to 20 days after injection. Tissue culture studies verified the specificity and the efficiency of the constructs. In animal studies, beta-galactosidase staining and Ang receptor binding assays showed expression of shRNA and downregulation of Ang AT1 receptors in the subfornical organ and NTS/DVN by >70%. Intracerebroventricular injection of Ad-AT1a-shRNA increased water intake with no effect on BP or HR. In contrast, microinjection of Ad-AT1a-shRNA into NTS/DVN caused a decrease in BP with no effect on HR or water intake. Results demonstrate the use of the RNA interference method in site-directed silencing of gene expression and provide a method for the in vivo study of Ang AT1 receptor function.

Adenoviridae↗
PubMed2005

Integrative genetic analysis of transcription modules: towards filling the gap between genetic loci and inherited traits.

Genetic loci that regulate inherited traits are routinely identified using quantitative trait locus (QTL) mapping methods. However, the genotype-phenotype associations do not provide information on the gene expression program through which the genetic loci regulate the traits. Transcription modules are 'self-consistent regulatory units' and are closely related to the modular components of gene regulatory network [Ihmels, J., Friedlander, G., Bergmann, S., Sarig, O., Ziv, Y. and Barkai, N. (2002) Revealing modular organization in the yeast transcriptional network. Nat. Genet., 31, 370-377; Segal, E., Shapira, M., Regev, A., Pe'er, D., Botstein, D., Koller, D. and Friedman, N. (2003) Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data. Nat. Genet., 34, 166-176]. We used genome-wide genotype and gene expression data of a genetic reference population that consists of mice of 32 recombinant inbred strains to identify the transcription modules and the genetic loci regulating them. Twenty-nine transcription modules defined by genetic variations were identified. Statistically significant associations between the transcription modules and 18 classical physiological and behavioral traits were found. Genome-wide interval mapping showed that major QTLs regulating the transcription modules are often co-localized with the QTLs regulating the associated classical traits. The association and the possible co-regulation of the classical trait and transcription module indicate that the transcription module may be involved in the gene pathways connecting the QTL and the classical trait. Our results show that a transcription module may associate with multiple seemingly unrelated classical traits and a classical trait may associate with different modules. Literature mining results provided strong independent evidences for the relations among genes of the transcription modules, genes in the regions of the QTLs regulating the transcription modules and the keywords representing the classical traits.

Animals↗
PubMed2005

[The study of treatment of osteoporotic thoracolumbar multi-vertebral compressive fractures by kyphoplasty with one balloon].

OBJECTIVE: To evaluate the effect of kyphoplasty in treating osteoporotic thoracolumbar multi-vertebral compressive fractures with one balloon. METHODS: thirteen cases (37 vertebral bodies) of osteoporotic thoracolumbar multi-vertebral compressive fractures were treated. The patients were women, range 65 to 79 years old, and all with well intact posterior wall of vertebral body. 37 thoracolumbar vertebral bodies were treated by Kyphoplasty with one balloon under "C" armed imaging guiding. RESULTS: All 13 patients tolerated well. The mean height of the anterior, media and posterior vertebral bodies was (1.9 +/- 0.5) cm, (1.5 +/- 0.5) cm, (2.6 +/- 0.5) cm preoperatively and (2.1 +/- 0.4) cm, (2.2 +/- 0.4) cm, (2.8 +/- 0.5) cm postoperatively (P < 0.001). The mean kyphosis was improved from (31.3 +/- 14.1) degrees to (24.8 +/- 11.3) degrees. There was not back pain and deformed correction was maintained well after 17.3 months' follow up, No complication occurred. CONCLUSION: The balloon was not damaged, because the pressure was lower than usual pressure, the cost of patients was saved. In this study, we fulfilled small amount of cement in vertebral body which reduced the leakage of cement. Fracture of close vertebral body was also reduced because of lower stiffness and modulus of elasticity of adjacent vertebral body.

Aged↗
PubMed2005

The N-terminal octapeptide acts as a dimerization inhibitor of SARS coronavirus 3C-like proteinase.

The 3C-like proteinase of severe acute respiratory syndrome (SARS) coronavirus has been proposed to be a key target for structural-based drug design against SARS. Accurate determination of the dimer dissociation constant and the role of the N-finger (residues 1-7) will provide more insights into the enzyme catalytic mechanism of SARS 3CL proteinase. The dimer dissociation constant of the wild-type protein was determined to be 14.0microM by analytical ultracentrifugation method. The N-finger fragment of the enzyme plays an important role in enzyme dimerization as shown in the crystal structure. Key residues in the N-finger have been studied by site-directed mutagenesis, enzyme assay, and analytical ultracentrifugation. A single mutation of M6A was found to be critical to maintain the dimer structure of the enzyme. The N-terminal octapeptide N8 and its mutants were also synthesized and tested for their potency as dimerization inhibitors. Peptide cleavage assay confirms that peptide N8 is a dimerization inhibitor with a K(i) of 2.20mM. The comparison of the inhibitory activities of N8 and its mutants indicates that the hydrophobic interaction of Met-6 and the electrostatic interaction of Arg-4 contribute most for inhibitor binding. This study describes the first example of inhibitors targeting the dimeric interface of SARS 3CL proteinase, providing a novel strategy for drug design against SARS and other coronaviruses.

Binding Sites↗