Biomedical subjects
Publications and source records attributed to Wei Li.
Four novel triterpenoid saponins, silenorubicosides A-D (1-4), together with four known saponins were isolated from the roots of Silene rubicunda. Their structures were established on the basis of spectroscopic analysis, including extensive 1D and 2D NMR (DQF-COSY, TOCSY, HETCOR, HMBC, and phase-sensitive NOESY) studies and chemical degradation.
Eight new phenolic glycosides, cucurbitosides F-M (1-8), were isolated from the seeds of Cucurbita pepo. Their structures were elucidated as 4-(2-hydroxyethyl)phenyl 5-O-(2-S-2-methylbutyryl)-beta-d-apiofuranosyl(l-->2)-beta-d-glucopyranoside (1), 4-(2-hydroxyethyl)phenyl 5-O-(3-methylbutyryl)-beta-d-apiofuranosyl(l-->2)-beta-d-glucopyranoside (2), 4-(2-hydroxyethyl)phenyl 5-O-nicotinyl-beta-d-apiofuranosyl(l-->2)-beta-d-glucopyranoside (3), 4-(2-hydroxyethyl)phenyl 5-O-(4-aminobenzoyl)-beta-d-apiofuranosyl(l-->2)-beta-d-glucopyranoside (4), 4-(2-hydroxyethyl)-2-methoxyphenyl 5-O-(2-S-2-methylbutyryl)-beta-d-apiofuranosyl(l-->2)-beta-d-glucopyranoside (5), 4-(hydroxymethyl)phenyl 5-O-(2-S-2-methylbutyryl)-beta-d-apiofuranosyl(l-->2)-beta-d-glucopyranoside (6), 4-(hydroxymethyl)phenyl 5-O-nicotinyl-beta-d-apiofuranosyl(l-->2)-beta-d-glucopyranoside (7), and 4-(hydroxymethyl)phenyl 5-O-(4-aminobenzoyl)-beta-d-apiofuranosyl(l-->2)-beta-d-glucopyranoside (8) on the basis of various spectroscopic analyses and analyses of hydrolysis products.
A new phytosterone named achyranthesterone A (1), along with the three known compounds stachysterone D (2), beta-ecdysone (3) and polypodine B (4) have been isolated from the roots of Achyranthes bidentata Bl. The structure of the new compound was determined as 2beta,3beta,14alpha,20S,21,22R,25-heptahydroxycholest-7-en-6-one on the basis of physico-chemical properties and spectral methods.
Small nucleolar RNAs (snoRNAs) are a kind of noncoding RNAs, and the vast majority of snoRNAs are involved in site-specific modifications of rRNAs. A novel box C/D snoRNA called snoR124 was found inOryza sativa, and it can direct 2'-O-ribose methylation of spliceosomal small nuclear RNAs (snRNAs). The snoRNA has two antisense elements, and the results of primer extensions at different dNTP concentrations provide evidence that snoR124 guide 2'-O-methylations of the C76 residue in the U4 snRNA and the T91 residue in the U5 snRNA. In addition, this snoRNA is located in a snoRNA gene cluster with another 7 snoRNAs which are identified to direct ribose methylations in rRNAs. This is consistent with the opinion that the snoRNA gene organization in plant is mainly gene cluster. The snoR124 is the first example of a snoRNA that directs modifications of RNAs other than rRNAs in plant; it will avail to get more insights into the function of snoRNAs in plant.
MOTIVATION: Transcription factors (TFs) regulate gene expression by recognizing and binding to specific regulatory regions on the genome, which in higher eukaryotes can occur far away from the regulated genes. Recently, Affymetrix developed the high-density oligonucleotide arrays that tile all the non-repetitive sequences of the human genome at 35 bp resolution. This new array platform allows for the unbiased mapping of in vivo TF binding sequences (TFBSs) using Chromatin ImmunoPrecipitation followed by microarray experiments (ChIP-chip). The massive dataset generated from these experiments pose great challenges for data analysis. RESULTS: We developed a fast, scalable and sensitive method to extract TFBSs from ChIP-chip experiments on genome tiling arrays. Our method takes advantage of tiling array data from many experiments to normalize and model the behavior of each individual probe, and identifies TFBSs using a hidden Markov model (HMM). When applied to the data of p53 ChIP-chip experiments from an earlier study, our method discovered many new high confidence p53 targets including all the regions verified by quantitative PCR. Using a de novo motif finding algorithm MDscan, we also recovered the p53 motif from our HMM identified p53 target regions. Furthermore, we found substantial p53 motif enrichment in these regions comparing with both genomic background and the TFBSs identified earlier. Several of the newly identified p53 TFBSs are in the promoter region of known genes or associated with previously characterized p53-responsive genes. SUPPLEMENTARY INFORMATION: Available at the following URL http://genome.dfci.harvard.edu/~xsliu/HMMTiling/index.html.
OBJECTIVE: Female sex hormones appear to be neuroprotective after traumatic brain injury by attenuating multiple mechanisms of secondary insult, including excitotoxicity and ischemia. The purpose of this study was to evaluate associations between gender and cerebrospinal fluid glutamate and lactate/pyruvate production and the role of hypothermia with gender in attenuating these markers. DESIGN: Prospectively collected data were analyzed for adult patients with severe traumatic brain injury. Gender comparisons for cerebrospinal fluid glutamate and lactate/pyruvate production were determined using ventricular samples obtained over the first 48 hrs postinjury. SETTING: University-based level I trauma center. PATIENTS: There were 123 patients, male n = 93 and female n = 30 (n = 686 cerebrospinal fluid samples), with severe traumatic brain injury (Glasgow Coma Scale score < or =8). INTERVENTIONS: A portion of these patients were part of a randomized controlled trial evaluating the effect of (48 hrs) therapeutic hypothermia after severe traumatic brain injury. The remainder received hypothermia (24 hrs) if they met clinical care criteria. Patients were cooled to 32-33 degrees C (within approximately 8 hrs) for either 24 or 48 hrs and then were rewarmed or remained normothermic. MEASUREMENTS AND MAIN RESULTS: Regression analyses using generalized estimating equations for repeated measures showed significant increases in cerebrospinal fluid glutamate production for males compared with females (p = .0023) and a significant interaction between glutamate concentration, gender, and time (p = .0035) by 24 hrs postinjury. Females had lower lactate/pyruvate ratios than males (p = .0006), and there was a significant interaction between lactate/pyruvate, gender, and time (p = .0045) throughout the first 48 hrs postinjury. Hypothermia attenuated glutamate levels, particularly for males, over the time course studied. CONCLUSIONS: These data suggest significant gender differences with glutamate and lactate/pyruvate production after severe traumatic brain injury. Gender- and hormone-mediated differences in central nervous system pathophysiology should be considered with clinical trials in traumatic brain injury.
OBJECTIVE: To examine the relationship between hypertension and health-related quality of life in patients attending hospital clinics in China. DESIGN AND METHODS: A cross-sectional survey. Patients over the age of 35 years attending outpatient clinics in 18 hospitals of eight major cities of northern and southern China were interviewed between June and July, 1999. Trained fieldworkers completed questionnaires regarding demographics, hypertension knowledge and awareness, treatment history and quality of life issues. Qualified physicians performed blood pressure assessments. RESULTS: A total of 9703 volunteers were enrolled; 4510 (46.5%) had hypertension. The results showed that hypertensive subjects scored lower in the multiple linear regression analyses in most questions on the quality of life questionnaire than those without hypertension after controlling for age, sex, sociodemographic factors, and co-morbidity. There was a strikingly high prevalence of physical complaints or symptoms. Among the variables considered, age, sex, hypertension, body mass index, educational level, smoking, history of cholesterol, family history of cardiovascular diseases and history of diabetes were statistically significantly correlated with health-related quality of life. Subjects aware of having high blood pressure had a lower health-related quality of life score than subjects with high blood pressure but unaware of the diagnosis. Among treated subjects, those with controlled hypertension had higher health-related quality of life scores than those with poorly controlled hypertension. CONCLUSIONS: Hypertensive individuals represent a vulnerable population that merits special attention from healthcare providers and systems. This is especially important given that low health-related quality of life can be a risk factor for subsequent cardiovascular events or complications.
OBJECTIVE: To compare the incidence of stroke and other cardiovascular events in hypertensive patients receiving a low-dose diuretic and low-dose calcium antagonist combination with those receiving low-dose diuretic monotherapy, and assess the effects of a small blood pressure difference at achieved levels lower than those achieved in previous placebo-controlled trials. METHODS: The Felodipine Event Reduction (FEVER) trial was an investigator-designed, prospective, multicentre, double-blind, randomized, placebo-controlled, parallel group trial. It enrolled 9800 Chinese patients, of either sex, aged 50-79 years, with one or two additional cardiovascular risk factors or disease, whose blood pressure, 6 weeks after switching from previous antihypertensive therapy to low-dose (12.5 mg a day) hydrochlorothiazide, was in the range 140-180 mmHg (systolic) or 90-100 mmHg (diastolic). These patients were randomly assigned either to low-dose felodipine extended release or placebo, and followed at 3-month intervals for an average of 40 months. RESULTS: The intention-to-treat analysis included 9711 randomly selected patients with only 30 (0.3%) lost to follow-up. A total of 31 842 patient-years of follow-up were accumulated, with 85.9% of patients remaining on blinded randomized treatment. Add-on therapy was given to 33.9% of the hydrochlorothiazide-felodipine patients and to 42.3% of the hydrochlorothiazide-placebo patients. In the felodipine group, systolic blood pressure (SBP)/diastolic blood pressure (DBP) decreased (from randomization to study end) from 154.2/91.0 to 137.3/82.5 mmHg, and in the placebo group from 154.4/91.3 to 142.5/85.0 mmHg, with an average difference throughout the trial of 4.2/2.1 mmHg. In the felodipine group, the primary endpoint (fatal and non-fatal stroke) was reduced by 27% (P = 0.001). Among secondary endpoints, all cardiovascular events were reduced by 27% (P < 0.001), all cardiac events by 35% (P = 0.012), death by any cause by 31% (P = 0.006), coronary events by 32% (P = 0.024), heart failure by 30% (P = 0.239), cardiovascular death by 33% (P = 0.019), cancer by 36% (P = 0.017) in the felodipine group. No significant differences were found in new-onset diabetes. Both treatments were very well tolerated. CONCLUSIONS: In moderately complicated hypertensive patients from China even a difference in SBP/DBP as small as 4/2 mmHg, such as that induced by adding low-dose felodipine to low-dose hydrochlorothiazide, is associated with very substantial reductions in the incidence of most types of cardiovascular events. As the SBP achieved in the felodipine group was below the recommended goal of less than 140 mmHg, and SBP in the placebo group was slightly above that level, FEVER provides the required evidence in support of the guidelines recommended goal, even for a hypertensive population not entirely consisting of patients with diabetes or previous cardiovascular events.
An actinomycete, strain FXJ46(T), was isolated from cypress forest soil in northern China and shown to have chemotaxonomic and morphological properties consistent with streptomycetes. It developed greyish aerial mycelium and pinkish-brown substrate mycelium on oatmeal agar. Phylogenetic analyses based on an almost complete 16S rRNA gene sequence of the strain and on the 120 nucleotide variable gamma-region of this molecule showed that it formed a distinct (but closely associated) line with Streptomyces griseoaurantiacus DSM 40430(T) in Streptomyces trees. However, the DNA-DNA relatedness between the two strains was only 48.8%. A number of phenotypic properties also readily distinguished the isolate from S. griseoaurantiacus and related Streptomyces species with validly published names. It is proposed, therefore, that this organism be classified as a novel species of the genus Streptomyces, for which the name Streptomyces jietaisiensis sp. nov. is proposed. The type strain is FXJ46(T) (=AS 4.1859(T)=JCM 12279(T)).
A soil actinomycete, strain 80-133(T), with the non-validly published name 'Microstreptospora cinerea', was the subject of a polyphasic study designed to clarify its taxonomic status. Comparative 16S rRNA gene sequence studies indicated that the organism belonged to the genus Streptomyces, a result in line with previous chemotaxonomic and morphological data. The strain belonged to the Streptomyces griseus clade, but could be distinguished from representatives of species assigned to this taxon by using DNA-DNA relatedness and phenotypic data. In light of these findings, it is proposed that the organism should be recognized as a novel species of the genus Streptomyces. The name proposed for this taxon is Streptomyces yanii sp. nov., with isolate 80-133(T) (=AS 4.1146(T)=JCM 3331(T)) as the type strain. It was also shown that representative strains of Streptomyces argenteolus, Streptomyces caviscabies, S. griseus and Streptomyces setonii belong to the same genomic species and have key phenotypic properties in common. It is proposed that S. caviscabies and S. setonii should be considered as later heterotypic synonyms of S. griseus and that S. argenteolus AS 4.1693(T) should also be assigned to this taxon.
Full scale B-cell activation requires not only B-cell receptor (BCR) engagement with antigen, but also costimulatory signals provided by T helper cells through the CD40-CD40 ligand (CD40L) interaction. It is hypothesized that a fusion protein of an antigen and soluble CD40L (CD40LT) would selectively target the costimulation to antigen-specific B cells, leading to synergy in the antibody response. This hypothesis was investigated by fusing green fluorescence protein (GFP), a generic antigen, with mouse CD40LT. Studies revealed that immunization in mice with the plasmid encoding GFP-CD40LT fusion protein led to synergistic induction of GFP-specific antibodies, while control plasmid(s) for GFP, CD40LT, or GFP plus CD40LT did not. Immunization with a single dose of the fusion protein also provoked a vigorous GFP-specific immunoglobulin G1 antibody response, but not other antibody isotypes. These results suggest that GFP-CD40LT fusion protein induces a GFP-specific B-cell activation and antibody response in an antigen-guided fashion. The potential application of this novel strategy in vaccine development is discussed.
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BACKGROUND: Brain activation differences between 12 control and 12 attention deficit hyperactivity disorder (ADHD) children (9- to 12-year-olds) were examined on two cognitive tasks during functional magnetic resonance imaging (fMRI). METHOD: Visual selective attention was measured with the visual search of a conjunction target (red triangle) in a field of distracters and response inhibition was measured with a go/no-go task. RESULTS: There were limited group differences in the selective attention task, with control children showing significantly greater intensity of activation in a small area of the superior parietal lobule region of interest. There were large group differences in the response inhibition task, with control children showing significantly greater intensity of activation in fronto-striatal regions of interest including the inferior, middle, superior and medial frontal gyri as well as the caudate nucleus and globus pallidus. CONCLUSION: The widespread hypoactivity for the ADHD children on the go/no-go task is consistent with the hypothesis that response inhibition is a specific deficit in attention deficit hyperactivity disorder.
BACKGROUND: The D antigen includes category D, partial D, and weak D types, which are important because anti-D alloimmunization can occur in some but not all persons that express a variant RHD allele. At present, there is little prospective information on the prevalence of D variants among obstetric patients and potential transfusion recipients. STUDY DESIGN AND METHODS: The RHD alleles were prospectively examined in a large patient population identified on the basis of a difference in anti-D reactivity between two reagents. RESULTS: Fifty-five discrepancies (0.96% of D-) were noted among 33,864 ethnically diverse patients over 18 months, of which 54 represented mutated RHD alleles. Seven obstetric patients were assigned D- status based on serology; only 1 patient had a partial RHD allele. Ten of 25 (36%) obstetric patients and 4 of 6 (67%) female potential transfusion recipients of childbearing age or younger were assigned D+ status, and they expressed a D variant known to permit anti-D alloimmunization. In total 20 RHD alleles were identified including category, DVa or DVa-like alleles (n = 7), DAR (n = 8), and four novel RHD alleles including two new DAU alleles. CONCLUSION: Given the complexity of D antigen expression, it is concluded that some clinically important D variants identified by standard serologic analysis phenotype as D+ and are potentially at risk for the development of anti-D.
Liver transplantation in mice is accepted spontaneously in all strain combinations. The mechanisms remain largely undefined. We hypothesize that signaling via the B7-CTLA4 receptor pathway is required for induction of liver transplant tolerance. Liver transplantation was performed from B10 (H2(b)) to C3H (H2(k)) mice. The recipients received anti-mouse CTLA4 mAb 0.25 mg i.p. every other day post-operatively. Liver grafts in anti-CTLA4 mAb treated recipients were acutely rejected. The allo-specific proliferative responses, anti-donor CTL and NK cell activities of GIC and SC and the serum levels of IFN-gamma and IL-2 from anti-CTLA4 mAb treated recipients were elevated significantly in comparison to the control mice. The frequency of IFN-gamma and IL-2 producing cells were markedly increased also in the anti-CTLA4 treated recipients. The immunohistology of liver grafts from anti-CTLA4 mAb treated mice showed extensively increased lymphocyte infiltration in the portal and general parenchymal areas, and expanded T-cell area in the spleen, with a reduction in the frequency of apoptotic cells observed by TUNEL staining compared with control mice. Thus CTLA4 signaling is critical for murine liver transplant tolerance induction. CTLA4 blockade promotes donor specific T-cell activation, cytotoxicity and Th1 polarization; protects alloreactive T cells from apoptotic death and induces liver allograft acute rejection.
We show that cytochrome P450scc (CYP11A1) in either a reconstituted system or in isolated adrenal mitochondria can metabolize vitamin D3. The major products of the reaction with reconstituted enzyme were 20-hydroxycholecalciferol and 20,22-dihydroxycholecalciferol, with yields of 16 and 4%, respectively, of the original vitamin D3 substrate. Trihydroxycholecalciferol was a minor product, likely arising from further metabolism of dihydroxycholecalciferol. Based on NMR analysis and known properties of P450scc we propose that hydroxylation of vitamin D3 by P450scc occurs sequentially and stereospecifically with initial formation of 20(S)-hydroxyvitamin D3. P450scc did not metabolize 25-hydroxyvitamin D3, indicating that modification of C25 protected it against P450scc action. Adrenal mitochondria also metabolized vitamin D3 yielding 10 hydroxyderivatives, with UV spectra typical of vitamin D triene chromophores. Aminogluthimide inhibition showed that the three major metabolites, but not the others, resulted from P450scc action. It therefore appears that non-P450scc enzymes present in the adrenal cortex to some extent contribute to metabolism of vitamin D3. We conclude that purified P450scc in a reconstituted system or P450scc in adrenal mitochondria can add one hydroxyl group to vitamin D3 with subsequent hydroxylation being observed for reconstituted enzyme but not for adrenal mitochondria. Additional vitamin D3 metabolites arise from the action of other enzymes in adrenal mitochondria. These findings appear to define novel metabolic pathways involving vitamin D3 that remain to be characterized.
AIM: To investigate the mechanism of action of a potent analgesic, (+/-)-meptazinol. METHODS: The structures of meptazinol enantiomers were compared with opioid pharmacophore and tramadol. RESULTS: Neither enantiomer of meptazinol fitted any patterns among the opioid pharmacophore and tramadol, although they did share some structural and pharmacological similarities. However, the structure superpositions implied that both enantiomers of meptazinol might share some similar analgesic mechanisms with typical opiate analgesics. CONCLUSION: Meptazinol should have a different mechanism of action to known analgesics, which would be helpful in further investigations of meptazinol in the search for non-addictive analgesics.
Tunicamycin-inducible gene A polypeptide (TIGA) is a member of the protein disulfide isomerase (PDI) family and is suggested to facilitate the folding of nascent polypeptides. The functional properties of TIGA were investigated here. TIGA acted as an isomerase, catalyzing the refolding of denatured and reduced ribonuclease A. TIGA also exhibited chaperone activity in the refolding of denatured prochymosin but not in the refolding of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), indicating that it had substrate specificity with respect to chaperone activity. Detailed study with a series of thioredoxin-motif (trx-motif) mutants revealed that the 2 trx-motifs of TIGA were not equal in activity. The N-terminal trx-motif was more active than the C-terminal trx-motif, and the first cysteine in each trx-motif was necessary for isomerase activity.