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Biomedical subjects

Ying Li

Publications and source records attributed to Ying Li.

At least 199 records · Page 11Linked to original sources
PubMed2005

In vitro bioactivation of dihydrobenzoxathiin selective estrogen receptor modulators by cytochrome P450 3A4 in human liver microsomes: formation of reactive iminium and quinone type metabolites.

Estrogens and selective estrogen receptor modulators (SERMs) are prescribed widely in the clinic to alleviate symptoms in postmenopausal women, and they are metabolized to reactive intermediates, which may elicit adverse effects. As part of our efforts to develop safer SERMs, in vitro covalent protein binding of (2S,3R)-(+)-3-(4-hydroxyphenyl)-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol (I) was evaluated. Radioactivity from [3H]I became covalently bound to proteins in a fashion that was both time- and NADPH-dependent in human liver microsomes and reached a value of 1106 pmol equiv/mg protein following a 45 min incubation. At least three pathways are involved in the bioactivation of I, namely, oxidative cleavage of the dihydrobenzoxathiin moiety to give a hydroquinone/para-benzoquinone redox couple, hydroxylation at position 5 or 7 of the benzoxathiin moiety leading to an o-quinone intermediate, and metabolism of the piperidine ring to give an iminium ion. The latter reactive intermediate was identified as its bis-cyano adduct when human liver microsomal incubations were performed in the presence of sodium cyanide. Structural modification of I, including a replacement of the piperidine with a pyrrolidine group, led to (2S,3R)-(+)-3-(3-hydroxyphenyl)-2-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-2,3-dihydro-1,4-benzoxathiin-6-ol (II), which did not form a reactive iminium ion. Following the incubation of II with human liver microsomes, covalent binding to proteins was reduced (461 pmol equiv/mg protein), the residual level of binding apparently due to the formation of a rearranged biphenyl quinone type metabolite. Studies with inhibitory antibodies and chemical inhibitors showed that P450 3A4 was the primary enzyme responsible for oxidative bioactivation of I and II in human liver microsomes. These studies thus demonstrated that gaining an understanding of bioactivation mechanisms may be exploited in terms of guiding structural modifications of drug candidates to minimize covalent protein binding and, hopefully, to lower the potential for drug-mediated adverse effects.

Benzoquinones↗
PubMed2005

A model order selection criterion with applications to cardio-respiratory-renal systems.

We introduce a model order selection criterion called signal prediction error (SPE) for the identification of a linear regression model, which can be an adequate representation of a resting physiologic system. SPE is an estimate of the prediction error variance due only to model estimation error and not unobserved noise, which distinguishes it from the widely used final prediction error (FPE). We then present a theoretical analysis of SPE, which predicts that its ability to select correctly the model order is more dependent on the signal-to-noise ratio (SNR) and less dependent on the number of data samples available for analysis. We next propose a heuristic procedure based on SPE (called SPE(D)) to improve its robustness to SNR levels. We then demonstrate, through simulated physiologic data at high SNR levels, that SPE will be equivalent to consistent model order selection criteria for long data records but will become superior to FPE and other model order selection criteria as the size of the data record decreases. The simulated data results also show that SPE(D) is indeed a significant improvement over SPE in terms of robustness to SNR. Finally, we demonstrate the applicability of SPE and SPE(D) to actual cardio-respiratory-renal data.

Algorithms↗
PubMed2005

A novel artemisinin derivative, 3-(12-beta-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo.

AIM: To study the immunosuppressive activity of SM735 {[3-(12-beta-artemisininoxy)] phenoxyl succinic acid}, a synthetic artemisinin derivative with nonsteroidal anti-inflammatory drug structure, with the aim of finding potential immunosuppressive agents. METHODS: Concanavalin A (ConA), lipopolysaccharide (LPS), and mixed lymphocyte reaction (MLR), were used to induce the proliferation of splenocytes, and [3H]-thymidine incorporation was used to evaluate the proliferation of splenocytes. Cytokine production was promoted with ConA, LPS, or PMA plus ionomycin, and was detected with the enzyme-linked immunosorbent assay. Dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC) were used to induce delayed-type hypersensitivity and quantitative hemolysis of SRBC (QHS) mouse models, as criteria for the evaluation of in vivo immune activity. RESULTS: SM735 strongly inhibited the proliferation of splenocytes induced by ConA, LPS, or MLR, with IC(50) values of 0.33 micromol/L, 0.27 micromol/L, and 0.51 micromol/L, respectively. When compared with a CC(50) value of 53.1 micromol/L, SM735 had a favorable safety range. SM735 dose-dependently inhibited proinflammatory cytokine production [including interleukins (IL)-12, interferon (IFN)-gamma and IL-6] induced by LPS or PMA plus ionomycin. Upon ConA stimulation, SM735 suppressed IFN-gamma in a dose-dependent manner, but did not affect IL-2 secretion. SM735 also strongly suppressed both T-cell-mediated delayed-type hypersensitivity (DTH) and B-cell-mediated QHS reactions. CONCLUSION: SM735 had strong immunosuppressive activity in vitro and in vivo, suggesting a potential role for SM735 as an immunosuppressive agent, and established the groundwork for further research on SM735.

Animals↗
PubMed2005

Inhibition of hepatitis B virus gene expression and replication by helioxanthin and its derivative.

Chronic hepatitis B virus (HBV) infection continues to be an important worldwide cause of morbidity and mortality. All the currently approved therapeutic drugs have their limitations: interferon-alpha (IFN-alpha) has limited efficacy and a high incidence of adverse effects; nucleoside analogues are very efficient HBV DNA inhibitors, but resistance occurs eventually. Therefore, it is important to develop new non-nucleoside/nucleotide agents with different modes of action that can be used for antiviral combination therapy. Here, we report on a novel class of compounds, helioxanthin and its derivative 5-4-2, which had potent anti-HBV activities in HepG2.2.15 cells, with the EC50s of 1 and 0.08 microM, respectively. The lamivudine-resistant HBV, L526M/M550V double mutant strain, was also sensitive to helioxanthin and 5-4-2. This class of compounds not only inhibited HBV DNA, but also decreased HBV mRNA and HBV protein expression. The EC50 of HBV DNA inhibition was consistent with the EC50 of HBV 3.5 Kb transcript inhibition, which was 1 and 0.09 microM for helioxanthin and 5-4-2 respectively. Western blot analysis of cell lysate from HepG2.2.15 cells showed that the core protein expression decreased in a dose-dependent manner after drug treatment. In conclusion, helioxanthin and 5-4-2 are potentially unique new anti-HBV agents, which possess a different mechanism of action from existing therapeutic drugs. Both compounds inhibited HBV RNA and protein expression in addition to inhibiting HBV DNA.

Antiviral Agents↗
PubMed2005

Four-color flow cytometry shows strong concordance with bone marrow morphology and cytogenetics in the evaluation for myelodysplasia.

The ability of 4-color flow cytometry (FC) to help identify myelodysplastic syndromes (MDSs) was evaluated in 124 bone marrow aspirates from unselected patients with unexplained cytopenias and/or monocytosis. The morphologic features of bone marrow aspirate smears were correlated with FC and cytogenetic findings blindly, and patterns of antigen expression were compared with patterns seen in nonneoplastic and normal marrow specimens. Of 124 cases, 58 (46.7%) had definitive FC abnormalities ("flow-abnormal"), 19 cases (15.3%) had mild FC abnormalities of indeterminate significance, and 47 cases (37.9%) had essentially normal FC. Highly significant differences were identified between the flow-abnormal group and other groups in mean myeloid blast percentages and numbers of abnormal antigens expressed, even when the analysis was limited to cases with fewer than 5% myeloid blasts. Strikingly, flow-abnormal cases constituted 50 (89%) of the 56 morphologically abnormal cases and 31 (94%) of the 33 cytogenetically abnormal cases, demonstrating the strong concordance of FC-identified antigenic abnormalities with morphologic features and cytogenetics in the evaluation of patients with unexplained cytopenias.

Antigens, CD↗
PubMed2005

Cloning and functional analysis of the sequences flanking mini-Tn5 in the magnetosomes deleted mutant NM4 of Magnetospirillum gryphiswaldense MSR-1.

A magnetosome deleted mutant NM4 of Magnetospirillum gryphiswaldense MSR-1 was generated by mini-Tn5 transposon mutagenesis, and a 5045-bp fragment flanking mini-Tn5 in NM4 was cloned by Anchored PCR. Sequencing analysis showed that this fragment involved six putative open reading frames (ORFs); the mini-Tn5 was inserted into ORF4. Functional complementary test indicated that the 5045-bp fragment was required for biosynthesis of magnetosomes in M. gryphiswaldense MSR-1. The protein encoded by ORF4 had 25% of identity with the chemotaxis protein CheYIII of Caulobacter crescentus CB15, and the protein encoded by ORF4 contained a conserved signal receiver domain that can receive the signal from the sensor partner of the bacterial two-component systems. It was suggested that the protein encoded by ORF4 may take part in the signal transduction relating to biosynthesis of magnetosomes.

Amino Acid Sequence↗
PubMed2005

Baseline pulmonary function and quality of life 9 years later in a middle-aged Chinese population.

STUDY OBJECTIVE: This research examined the association of baseline pulmonary function with future quality of life (QOL). METHODS: We collected baseline pulmonary function data in 1993 and 1994, and assessed QOL using the Chinese 35-Item Quality of Life Instrument in 2002 in a cohort of 1,356 participants. We used Pearson correlation analysis, multivariate analysis of variance, and multivariate linear regression analysis to assess the relationship between pulmonary function and QOL. RESULTS: The baseline percentage of age- and height-predicted FEV1 (FEV1%) was significantly correlated with the resurvey total QOL score (r = 0.126, p < 0.001) and with QOL scores for the general (r = 0.074, p = 0.006), physical (r = 0.085, p = 0.002), independence (r = 0.178, p < 0.001), and psychological (r = 0.064, p = 0.018) domains but not with the social and environmental domains after adjusting for age and sex. These associations were weaker for the percentage of age- and height-predicted FVC. Multiple linear regression showed that the above associations were independent of baseline and resurvey smoking status. Inclusion of respiratory symptoms in the model reduced the regression coefficients from 0.82 to 0.41 for the total QOL score and from 1.43 to 0.94 for the independence domain score, for a 10% change in FEV1%. The age- and sex-adjusted mean total QOL scores were 78, 76, 76, and 69, respectively (p < 0.001), for the groups of normal, symptomatic only, impaired pulmonary function only, and both symptomatic and impaired pulmonary function. This trend was also significant for the general, physical, independence, and psychological domain scores. CONCLUSION: Impaired baseline pulmonary function has a significant negative impact on QOL in later life that is independent of age, sex, height, and smoking status and is largely mediated through the development of chronic respiratory symptoms.

China↗
PubMed2005

Uncoupled metabolism stimulated by chemical uncoupler and oxic-settling-anaerobic combined process to reduce excess sludge production.

The effects of three uncoupled metabolic systems (conventional activated sludge process with the addition of 3,3', 4',5-tetrachlorosalicylanilide [TCS], oxic-settling-anaerobic [OSA] process modified by insertion of a sludge-holding tank in the sludge return line, and TCS and OSA combined process) on reducing excess sludge production were studied. Compared with the control conventional activated sludge process, the most effective system was the combined process, which could reduce excess sludge production by 46.90%. The 180-d operation results confirmed that TCS is an effective chemical uncoupler in reducing the sludge yield but that it had an adverse effect on substrate removal capability, effluent nitrogen concentration, and sludge settleability. The OSA process decreased excess sludge production by only 26% but had less adverse effect on effluent quality and could improve sludge settleability. The effluent total phosphorous concentration of the three systems was slightly lower than of the control unit. Microbial populations were monitored by both microscopic and molecular biologic analysis method (polymerase chain reaction [PCR]-denaturing gradient gel electrophoresis [DGGE]). The presence of TCS caused metazoans to disappear and decreased the number and activity of protozoa. PCR amplification of 16S rRNA and sequent DGGE analysis found a shift in the diversity of the predominant species. The results imply that OSA combined with the chemical uncoupler process may effectively reduce excess sludge yield and not affect process performance significantly.

Aerobiosis↗
PubMed2005

Independent origin of the growth hormone gene family in New World monkeys and Old World monkeys/hominoids.

The growth hormone (GH) gene family represents an erratic and complex evolutionary pattern, involving many evolutionary events, such as multiple gene duplications, positive selection, the birth-and-death process and gene conversions. In the present study, we cloned and sequenced GH-like genes from three species of New World monkeys (NWM). Phylogenetic analysis strongly suggest monophyly for NWM GH-like genes with respect to those of Old World monkeys (OWM) and hominoids, indicating that independent gene duplications have occurred in NWM GH-like genes. There are three main clusters of genes in putatively functional NWM GH-like genes, according to our gene tree. Comparison of the ratios of nonsynonymous and synonymous substitutions revealed that these three clusters of genes evolved under different kinds of selective pressures. Detailed analysis of the evolution of pseudogenes showed that the evolutionary pattern of this gene family in platyrrhines is in agreement with the so-called birth-and-death process.

Animals↗
PubMed2005

Episodic evolution of prolactin receptor gene in mammals: coevolution with its ligand.

Divergence of proteins in signaling pathways requires ligand and receptor coevolution to maintain or improve binding affinity and/or specificity. In this paper we show a clear case of coevolution between the prolactin (PRL) gene and its receptor (prolactin receptor, PRLR) in mammals. First we observed episodic evolution of the extracellular and intracellular domains of the PRLR, which is closely consistent with that seen in PRL. Correlated evolution was demonstrated both between PRL and its receptor and between the two domains of the PRLR using Pearson's correlation coefficient. On comparing the ratio of the nonsynonymous substitution rate to synonymous substitution rate (omega = d(N)/d(S)) for each branch of the star phylogeny of mammalian PRLRs, separately for the extracellular domain (ECD) and the transmembrane domain/intracellular domain (TMD/ICD), we observed a lower omega ratio for ECD than TMD/ICD along those branches leading to pig, dog and rabbit but a higher ratio for ECD than TMD/ICD on the branches leading to primates, rodents and ruminants, on which bursts of rapid evolution were observed. These observations can be best explained by coevolution between PRL and its receptor and between the two domains of the PRLR.

Amino Acid Sequence↗
PubMed2005

Structural and photocatalytic properties of TiO2 films fabricated on silicon substrates by MOCVD method.

Silicon ( 111) and Silicon(100) were employed for fabrication of TiO2 films by metal organic chemical vapor deposition( MOCVD). Titanium(IV) isopropoxide(Ti[O(C3H7)4] ) was used as a precursor. The as-deposited TiO2 films were characterized with FE-SEM, XRD and AFM. The photocatalytic properties were investigated by decomposition of aqueous Orange II . And UV-VIS photospectrometer was used for checking the absorption characteristics and photocatalytic degradation activity. The crystalline and structural properties of TiO2 film had crucial influences on the photodegradation efficiency. For MOCVD in-situ deposited films on Si substrates, the photoactivities varied following a shape of "M": at lower(350 degrees C ), middle(500 degrees C ) and higher(800 degrees C ) temperature of deposition, relative lower photodegradation activities were observed. At 400 degrees C and 700 degrees C of deposition, relative higher efficiencies of degradation were obtained, because one predominant crystallite orientation could be obtained as deposition at the temperature of two levels, especially a single anatase crystalline TiO2 film could be obtained at 700 degrees C.

Azo Compounds↗
PubMed2005

[Analysis of clinical characteristics and risk factors of corneal melting after laser in situ keratomileusis].

OBJECTIVE: To study the characteristics of corneal melting after laser in situ keratomileusis and to investigate the risk factors for corneal melting. METHODS: Twelve eyes of 11 patients with corneal melting after LASIK were studied. The patients consisted of 6 men and 5 women, ranging in age from 26 to 41 years. Each eye was routinely examined with slit lamp microscope and confocal microscope. All patients were conducted with systemic examination, especially immunologic index such as rheumatoid factor, anti-SSA and anti-SSB antibodies. The patients with systemic diseases were treated for the systemic diseases as well as for the ocular disorders. RESULTS: Corneal melting occurred unilaterally in all cases; 8 in the left eye and 4 in the right eye. The intervals between onset of corneal melting and LASIK ranged from 2 to 5 weeks. Corneal melting tended to begin from the rim of corneal flaps, especially in the inferior and nasal rims. Eight cases (67%) either had corneal epithelium denudation or thinner corneal flaps during operation or had corneal epithelium edema or epithelium implantation post operatively. 6 cases (55%) were combined with systemic diseases, 1 with thyroiditis, 2 with systemic lupus erythematous, 2 with Sjogren syndrome and 1 with rheumatoid arthritis. One patient once had superficial scleritis, one patient was combined with eczema and erythema of the skin; one patient had foreign body beneath the corneal flap; other patients had no accompanying disorders (3 eyes). All of the cases were cured with treatment by cyclosporine A, topical steroids and protective agents for the cornea. The course of corneal melting ranged from 23 days to 45 days (mean 30.3 days). Corneal nebula or macula of different degrees remained. Four cases had astigmatism with sphere changes above 1.0 diopters. The actual corrected visual acuity of 5 eyes was 2 lines lower than the expected corrected visual acuity, 2 eyes 1 line lower, 5 eyes unchanged. CONCLUSION: Corneal melting is a non-infectious corneal disorder and may accompany with systemic diseases. LASIK may be an inductive factor for corneal melting. A thorough inquiry and examination for systemic diseases are of great importance for the prevention of corneal melting. The treatment for corneal melting should be combined with diagnosis and treatment for the accompanying systemic diseases.

Adult↗
PubMed2005

[The cut-off point of waist circumference for identifying metabolic syndrome in Chinese adults].

OBJECTIVE: Metabolic syndrome has attracted more attention from scientists of related areas due to its association with increased risk of cardiovascular disease and diabetes. The clinical identification criteria for metabolic syndrome issued by ATP III of NECP indicate the enlarged waist as the first component using the cut-offs derived from Caucasians. The purpose of this study is to investigate the appropriate cut-offs of waist circumference for Chinese adults as a component of metabolic syndrome. METHODS: Database of 13732 Chinese adults with 35 - 59 years from the risk factor survey in 1998 (the 9(th) Five Year National Project on trends and prediction of cardiovascular disease) was used to analyze the ORs of clustering of risk components by different strata of waist circumference. The sensitivity, specificity and distance in ROC curve by different cut-offs of waist circumference for identifying two or more risk components of metabolic syndrome were estimated to find the cut-off point for men and women with the shortest distance in ROC curve. RESULTS: The ORs of clustering of risk components increased significantly with the size of waist circumference. The waist circumference (>/= 85 cm for men, >/= 80 cm for women) corresponded to the shortest distance in ROC curve, namely, at these cut-offs, the rates of false positive and false negative for identifying clustering of two or more risk components were the minimum. CONCLUSIONS: If a person had three or more of the following components, metabolic syndrome could be defined: waist circumference >/= 85 cm in men or >/= 80 cm in women, SBP >/= 130 mm Hg or DBP >/= 85 mm Hg, TG >/= 1.69 mmol/L, HDL-C < 1.03 mmol/L and fasting blood glucose >/= 6.1 mmol/L. The prevalence of metabolic syndrome was 19.3% and 13.9% in middle-aged men and women respectively. In these patients the combination of enlarged waist, high blood pressure and high TG was the most frequent. This recommendation need further confirmed in representative sample of Chinese population.

Adult↗
PubMed2005

[Relationship Between Molecular Marker of Western Main Pig H-FABP Gene and IMF Content.].

By using 265 pigs from eight breeds including Duroc,Landrace,Large White,Neijiang,Rongchang,Hanjiang Black,Hanzhong White,Bamei and wild ones, the genetic variations of 5'-upstream region from and the second intron in porcine H-FABP gene were checked by PCR-RFLP molecular marker with HinfI, Hae III and MspI,and effect of H-FABP gene on IMF content was then analyzed by least square analysis.The results showed as follows:(1) 8 pig breeds and wild pig had polymorphism at Hinf I-RFLP site. In above detected breeds,large white,Bamei pig, Hanjiang Black,Hanzhong White pig breeds and wild pig presented low polymorphism while other breeds have mediate polymorphism;(2)Among the tested breeds only 4 Chinese local pig breeds had no polymorphism at the Hae III-RFLP and Msp I-RFLP sites,but Duroc,Landrace,Largewhite, Hanzhong White pig breeds and wild pig had polymorphism. Wild pig at the Hae III-RFLP , Landrace,Largewhite and wild pig at the Hae III-RFLP and Msp I-RFLP sites were low polymorphism,others were mediate polymorphism;(3) H-FABP gene increased IMF content significantly(p0.05). Genetic effect of H-FABP gene on IMF content were HH>Hh>hh,DD.

Animals↗