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Biomedical subjects

B Hao

Publications and source records attributed to B Hao.

17 recordsLinked to original sources
PubMed2006

Bicyclol for chronic hepatitis B.

BACKGROUND: Bicyclol is a novel synthetic 'anti-hepatitis' drug, used in China for chronic hepatitis B. Until now, systematic reviews of bicyclol therapy have not been performed. OBJECTIVES: To study the benefits and harms of bicyclol for patients with chronic hepatitis B. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (July 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to July 2005), EMBASE (1980 to July 2005), Science Citation Index Expanded (1945 to July 2005), The Chinese Biomedical Database (1994 to August 2005), VIP Chinese Science and Technique Journals Database (1994 to August 2005), and China National Infrastructure (CNKI)(1994 to August 2005). We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Randomised clinical trials with bicyclol versus no intervention, placebo, or other interventions were included, irrespective of blinding, publication status, or language. DATA COLLECTION AND ANALYSIS: The primary outcome measures were mortality (total and liver-related) and liver-related morbidity (eg, cirrhosis and carcinoma). Secondary outcome measures were viral response and liver histology. MAIN RESULTS: The search identified one randomised clinical trial comparing bicyclol with bifendate (biphenyldicarboxylate) for patients with hepatitis B. The follow-up was three months. There was no evidence that bicyclol was superior to bifendate for loss of HBeAg (RR 1.38, 95% CI 0.95 to 2.00), seroconversion of HBeAg to HBeAb (RR 1.44, 95% CI 0.90 to 2.29), loss of HBV DNA (RR 1.19, 95%CI 0.93 to 1.53), or number of patients with normalised alanine aminotransferase and aspartate aminotransferase activity (RR 0.88, 95% CI 0.70 to 1.11 and RR 0.97, 95% CI 0.79 to 1.20, respectively). AUTHORS' CONCLUSIONS: Only one randomised clinical trial has examined the potential benefit of bicyclol for patients with chronic hepatitis B. This small, short-term trial found no evidence to support or refute its use. Large, randomised double-blind clinical trials with long-term follow-up are needed to examine the possible benefits and harms associated with bicyclol. Bicyclol can only be recommended for use in randomised trials.

Biphenyl Compounds↗
PubMed2006

A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer.

X-ray repair cross-complementing 1 (XRCC1) plays a key role in DNA base excision repair and cells lacking its activity are hypersensitive to DNA damage. Recently, we reported a SNP (rs3213245, -77T>C) in the XRCC1 gene 5' untranslated region (UTR) was significantly associated with the risk of developing esophageal squamous-cell carcinoma. Computer analysis predicted that this SNP was in the core of Sp1-binding motif, which suggested its functional significance. Gel shift and super shift assays confirmed that -77T>C polymorphic site in the XRCC1 promoter was within the Sp1-binding motif and the T>C substitution greatly enhanced the binding affinity of Sp1 to this region. Luciferase assays indicated that the Sp1-high-affinity C-allelic XRCC1 promoter was associated with a reduced transcriptional activity. The association between -77T>C and three other amino-acid substitution-causing polymorphisms in XRCC1 and risk of lung cancer was examined in 1024 patients and 1118 controls and the results showed that only the -77T>C polymorphism was significantly associated with an increased risk of developing lung cancer. Multivariate logistic regression analysis found that an increased risk of lung cancer was associated with the variant XRCC1 -77 genotypes (TC and CC) compared with the TT genotype (OR=1.46, 95% CI=1.18-1.82; P=0.001) and the increased risk was more pronounced in smokers (OR=1.63, 95% CI=1.20-2.21) than in non-smokers (OR=1.28, 95% CI=0.94-1.76). Taken together, these results showed that the functional SNP -77T>C in XRCC1 5'UTR was associated with cancer development owing to the decreased transcriptional activity of C-allele-containing promoter with higher affinity to Sp1 binding.

Adult↗
PubMed2006

Osteopontin regulation by protein kinase B (Akt) in HepG2 cells.

AIM: The mechanism responsible for osteopontin regulation is not understood in HepG2 cells. The aim of this study was to investigate the relationship between protein kinase B (Akt), a key gene in PI3K signal transduction pathway, and osteopontin expression. METHODS: HepG2 cells were transfected with constitutively active Akt and dominant negative Akt using lipofectin. The Akt transfection was confirmed by Western blot analysis. Osteopontin expression was detected by both Northern blot and Western blot. RESULTS: Overexpression of exogenous Akt was detected in HepG2 cells by Western blot, indicating that HepG2 cells were successfully transfected with the Akt genes. In serum-free condition, the expression of osteopontin was either low or undetectable in HepG2 cells transfected with vector only, however, the expression increased after transfection of cells with constitutively active Akt. Osteopontin expression decreased when HepG2 cells were transfected with dominant negative Akt. CONCLUSION: Protein kinase B (Akt) gene regulated osteopontin expression in RNA level and protein level, suggesting that osteopontin synthesis can be blocked by inactivation of the Akt gene. This leads to a potential means of intervention for the inhibition of metastases in liver cancer.

Base Sequence↗
PubMed2004

Linkage disequilibrium and haplotype architecture for two ABC transporter genes (ABCC1 and ABCG2) in Chinese population: implications for pharmacogenomic association studies.

Information about linkage disequilibrium (LD) patterns and haplotype structures for candidate genes is instructive for the design and analysis of genetic association studies for complex diseases and drug response. ABCC1 and ABCG2 are genes coding for two multidrug resistance (MDR) associated transporters; they are also related to some pathophysiological traits. To pinpoint the LD profiles of these MDR genes in Chinese, we systemically screened 27 unrelated individuals for single nucleotide polymorphisms (SNPs) in the coding and regulatory regions of these genes, and thereby characterized their haplotype structures. Despite marked variations in haplotype diversity, LD pattern and intragenic recombination intensity between the two genes, both loci could be partitioned into several LD blocks, in which a modest number of haplotypes accounted for a high fraction of the sampled chromosomes. We concluded that each locus has its own genomic LD profile, but that they still share a common segmental LD architecture with low haplotype diversity. Our data will benefit genetic association studies of complex traits and drug response possibly related to these genes.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2001

[Genetic polymorphism of eight STR loci in the Han population in Henan province].

OBJECTIVE: To investigate the allele frequencies of eight short tandem repeats(STR) loci: TH01, FES, D19S400, D7S820, D16S539, D20S161, D3S1545 and D5S818 in Han population in Henan province. METHODS: DNA was extracted with phenol-chloroform from EDTA-blood samples of the unrelated individuals in Henan province and amplified with PCR technique. The PCR product was analyzed with the undenatured PAGE vertical electrophoresis and silver-stain. RESULTS: The authors got the frequencies of the eight loci. The heterozygosities of the eight loci are 0.66, 0.67, 0.80, 0.76, 0.79, 0.79, 0.78 and 0.78; the discrimination powers are 0.83, 0.83, 0.94, 0.91, 0.93, 0.93, 0.92 and 0.92. CONCLUSION: The heterozygosities of the eight loci are high and the frequencies are in good agreement with Hardy-Weinberg equilibrium, so the eight loci can be used in individual identification testing.

Alleles↗
PubMed2000

New mechanistic insights from structural studies of the oxygen-sensing domain of Bradyrhizobium japonicum FixL.

The FixL heme domain serves as the dioxygen switch in the FixL/FixJ two-component system of Rhizobia. Recent structural studies of the Bradyrhizobium japonicum FixL heme domain (BjFixLH) have suggested an allosteric mechanism that is distinct from the classical hemoglobin model. To gain further insight into the FixL sensing mechanism, structures of BjFixLH bound to dioxygen, imidazole, and nitric oxide have been determined. These structures, particularly the structure of BjFixLH bound to its physiological ligand, dioxygen, have helped to address a number of important issues relevant to the BjFixLH sensing mechanism. On the basis of the oxy-BjFixLH structure, a conserved arginine is found to stabilize the dioxygen ligand in a mode reminiscent of the distal histidine in classical myoglobins and hemoglobins. The structure of BjFixLH bound to imidazole elucidates the structural requirements for accommodating sterically bulky ligands. Finally, the structure of BjFixLH bound to nitric oxide provides evidence for a structural intermediate in the heme-driven conformational change.

Animals↗
PubMed2000

[Relationship between interleukin-2, interleukin-2 receptor and the non-and hypo-responsiveness to hepatitis B vaccine].

OBJECTIVE: To study the relationship between interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R) and the non-and-hypo-responsiveness to hepatitis B vaccine. METHODS: Peripheral blood mononuclear cells (PBMC) isolated from 21 non-and -hypo-responders, 22 hyperresponders and 21 chronic HBsAg carriers were incubated in the presence of HBsAg and phytohaemagglutinin (PHA). The levels of IL-2 and sIL-2R in the supernatants of activated cells were measured by an enzyme-linked immunosorbent assay. RESULTS: The average level of IL-2 in the non-and-hypo-responders was significantly lower than that in the hyperresponders (t=8.80, P<0.001), but was comparable to that in chronic HBsAg carriers (q=0.06, P>0.5). Between the hyperresponders and the non-and-hypo-responders, the average sIL-2R levels showed no noticeable difference. CONCLUSION: The results suggest that low level of IL-2 may be one of the causes and mechanisms of non-and-hypo-responsiveness to hepatitis B vaccine.

Carrier State↗
PubMed2000

[Study on statistical method of distribution for erythrocyte morphological features by computerized image processing].

This study sought to develop a new statistic method for the semiautomatic analysis and classification of erythrocyte morphology based on the morphological features and shape analysis of erythrocytes by computer image processing. Shape factor as the description of the erythrocyte morphological features was used for the shape classification of erythrocytes. And the models and algorithms of erythrocytes image segmentation, cell body shape recognition and measure can be implemented through the VC++. The present method can efficiently and semi-automatically provide the statistical analysis of erythrocyte morphology, and can give the distribution of erythrocyte morphological features. The result showed that there was a significant difference between the distribution curves of the normal erythrocyte morphology (one apex) and hemolytic anemia's (two apices). By this way, it can be obtained the proportion data of different cell bodies' shapes. This method could provide some information for the study and diagnosis of the diseases (e.g. hemolytic anemia, pre-leukemia) related to erythrocyte morphology.

Algorithms↗
PubMed2000

[The influence of conception of time - space - orientation in pre - Qin society on traditional Chinese medicine theories].

The article discusses the views of the time - space - orientation of Wuxing (Five - Evolutive Phase), Yin - yang and Sifeng (Four - Wind), and its influence on traditional Chinese medical theories. It is shown that traditional Chinese medical theories are developed and established on the basis of the science and technology and social thought of the pre - Qin period, with some contents to be further discussed, and bias would be resulted if the issue is interpreted by concepts of post - Qin period.

China↗
PubMed1999

Structural basis for the design of antibiotics targeting peptide deformylase.

While protein synthesis in bacteria begins with a formylated methionine, the formyl group of the nascent polypeptide is removed by peptide deformylase. Since eukaryotic protein synthesis does not involve formylation and deformylation at the N-terminus, there has been increasing interest in peptide deformylase as a potential target for antibacterial chemotherapy. Toward this end and to aid in the design of effective antibiotics targeting peptide deformylase, the structures of the protein-inhibitor complexes of both the cobalt and the zinc containing Escherichia coli peptide deformylase bound to the transition-state analogue, (S)-2-O-(H-phosphonoxy)-L-caproyl-L-leucyl-p-nitroanilide (PCLNA), have been determined. The proteins for both deformylase-inhibitor complexes show basically the same fold as for the native enzyme. The PCLNA inhibitor adopts an extended conformation and fits nicely into a hydrophobic cavity located near the metal site. On the basis of these structures, guidelines for the design of high-affinity deformylase inhibitors are suggested. As our results show that the protein residues which interact with the PCLNA inhibitor are conserved over a wide variety of species, we suggest that antibiotics targeting deformylase could have wide applicability.

Amidohydrolases↗
PubMed1998

Structure of a biological oxygen sensor: a new mechanism for heme-driven signal transduction.

The FixL proteins are biological oxygen sensors that restrict the expression of specific genes to hypoxic conditions. FixL's oxygen-detecting domain is a heme binding region that controls the activity of an attached histidine kinase. The FixL switch is regulated by binding of oxygen and other strong-field ligands. In the absence of bound ligand, the heme domain permits kinase activity. In the presence of bound ligand, this domain turns off kinase activity. Comparison of the structures of two forms of the Bradyrhizobium japonicum FixL heme domain, one in the "on" state without bound ligand and one in the "off" state with bound cyanide, reveals a mechanism of regulation by a heme that is distinct from the classical hemoglobin models. The close structural resemblance of the FixL heme domain to the photoactive yellow protein confirms the existence of a PAS structural motif but reveals the presence of an alternative regulatory gateway.

Amino Acid Sequence↗
PubMed1997

Crystal structure of the Escherichia coli peptide deformylase.

Protein synthesis in bacteria involves the formylation and deformylation of the N-terminal methionine. As eukaryotic organisms differ in their protein biosynthetic mechanisms, peptide deformylase, the bacterial enzyme responsible for deformylation, represents a potential target for antibiotic studies. Here we report the crystallization and 2.9 A X-ray structure solution of the zinc containing Escherichia coli peptide deformylase. While the primary sequence, tertiary structure, and use of coordinated cysteine suggest that E. coli deformylase belongs to a new subfamily of metalloproteases, the environment around the metal appears to have strong geometric similarity to the active sites of the thermolysin family. This suggests a possible similarity in their hydrolytic mechanisms. Another important issue is the origin of the enzyme's specificity for N-formylated over N-acetylated substrates. Based on the structure, the specificity appears to result from hydrogen-bonding interactions which orient the substrate for cleavage, and steric factors which physically limit the size of the N-terminal carbonyl group.

Amidohydrolases↗
PubMed1997

[Isolation and determination of the seeds of Pachyrrhizus errosus protein by high performance gel filtration chromatography (GFC)].

From the seeds of Pachyrrhizus errosus, three protein constituents, namel PE1, PE2 and PE3, have been isolated and purified by extraction with 5mmol/L phosphate saline (0.9% NaCl) buffer (PB) at pH 7.2, and S-Sepharose Fast Flow Column (2.6cm x 15cm) chromatography which eluted with 5mmol/L phosphate buffer (pH 7.0) containing 1mmol/L NaCl. Three proteins were burther separated on two connected Protein-Pak 60+Protein-Pak 125 [7.5mm x 39cm, 10microm] columns with mobile phase of 0.2mol/L phosphate buffer (pH 6.5). The flow rate was kept constant at 0.8mL/min by YSB-2 type high press pump. The effluent was monitored at a wavelength of 280nm on photodiode array detector. These three proteins are proved to be homogeneous by SDS-PAGE, IEF and HPGFC experiments, and all present the typical absorption spectra in ultraviolet region. The moleculer weights of the three proteins are approxiamtely 33000D, 14500D and 14000D respectively by SDS-PAGE. But as using HPGFC analysis, the MW value of PE2 is 28000D. This indicates PE2 may be composed of two chains joined by disulfide bond, which is further proved from the latter amino acid composition analysis. The isoelectric points of three proteins are 4.5, 6.5 and 7.5 respectively by using IEF. The amion acids compositions of the three proteins were determined with OPA post-column derivatization/fluorescence detection.

Amino Acids↗
PubMed1996

Preliminary crystallographic studies of a protein from Pachyrrhizus erosus.

Crystals of a protein extracted from the seeds of Pachyrrhizus erosus have been obtained by vapor-phase diffusion. The crystal belongs to the space group P4(1)2(1)2 or P4(3)2(1)2 with cell parameters a = b = 62.52, c = 147.42 A. There is one protein molecule of 33 kDa in an asymmetric unit. A data set at 3.1 A has been collected on an area detector.

Journal Article↗