Biomedical subjects

Kui Wang

Publications and source records attributed to Kui Wang.

At least 37 records · Page 2Linked to original sources

PubMed2005

Hydrogen-bonding-driven preorganized zinc porphyrin receptors for efficient complexation of C60, C70, and C60 derivatives.

This paper describes the self-assembly of a new class of foldamer-based molecular tweezers, whose rigid folded conformations are stabilized by intramolecular hydrogen bonding. Two zinc porphyrin units are introduced to the ends of molecular tweezers Zn(2)1 and Zn(2)2, while three zinc porphyrin units are incorporated to the S-shaped bi-tweezers Zn(3)3, which may be regarded as a combination of two Zn(2)1 molecules. Due to the preorganized U-shaped feature, Zn(2)1 and Zn(2)2 are able to strongly complex C60, C70, and C60 derivative 25 in chloroform or toluene in a 1:1 binding stoichiometry, whereas Zn(3)3, which possesses two tweezer units, complexes the guests in a 1:2 stoichiometry. More stable complex Zn(3)3.24 is formed between Zn(3)3 and 24, a linear molecule bearing two C60 moieties at the ends, as a result of the cooperative interaction of two binding sites. Chiral induction is observed for all the three receptors upon complexation with C60-incoporated chiral phenylalanine derivative 29, although the complexation of 29 by the folding receptors is pronouncedly weaker than that of C60 and 25 due to increased steric hindrance. The driving force for the formation of the complexes is the well established pi-pi stacking between the zinc porphyrin and fullerene units. The 1H and 13C NMR, UV-vis, fluorescent, and circular dichroism spectroscopy have been used to investigate the complexing behavior of the folding receptors and the fullerene guests. The association constants of the corresponding complexes in toluene and chloroform (if possible) have been evaluated with the UV-vis and fluorescent titration experiments.

Journal Article↗

PubMed2005

La3+ stimulate the activity of calcineurin in two different ways.

It is well known that the activity of calcineurin (CaN) could be modulated by several transitional metal ions. In the present work, the effects of a calcium analog, lanthanum ion (La(3+)), on the activity of CaN were studied. It was found that La(3+) exerted multiple effects on CaN activity. La(3+) could stimulate CaN in the absence of calmodulin (CaM); whereas at low concentrations of La(3+), there was a slight inhibition of activation of CaN in the presence of CaM. Competitive experiments and limited trypsin proteolysis confirmed that La(3+) did not act on the catalytic core of CaN, but exerted its effect through direct action on the CaN regulatory domain similar to Mg(2+). In activity titration and spot blotting studies, La(3+)-containing CaM complexes were less effective in stimulating CaN than Ca(2+) or Mn(2+)-containing CaM; however, the binding affinity of these metal-CaM complexes to CaN was similar. These effects of La(3+) on CaN activity are unique among metal ions and may provide clues to understand the biological effects of La(3+).

Calcineurin↗

PubMed2005

Cholestane-3beta,5alpha,6beta-triol inhibits osteoblastic differentiation and promotes apoptosis of rat bone marrow stromal cells.

Converging lines of evidence suggest that oxidized lipids, long recognized as a risk factor in atherogenesis, also contribute to osteoporosis, but the underlying mechanism is not understood in detail. The effect of atherogenesis related factors including oxysterols on the differentiation and survival of marrow stromal cells (MSCs) would be very important in understanding the link between atherosclerosis and osteoporosis. In the present study, the effect of oxysterol cholestane-3beta,5alpha,6beta-triol (Triol) on osteoblastic differentiation and apoptosis of primary rat bone MSCs as well as the related mechanisms were studied. Triol inhibited MSCs osteoblastic differentiation as demonstrated by inhibition of alkaline phosphatase activity, osteocalcin secretion, and matrix mineralization. In the other aspect, Triol promoted MSCs apoptosis, as characterized by condensed or fragmented nuclei as well as active externalization of phosphatidyl serine to the cell surface. In addition, Triol was found to induce increases of intracellular Ca2+ and Ca2+-dependent reactive oxygen species generation in MSCs. These effects were involved in the action of Triol on apoptosis, but not on osteoblastic differentiation of MSCs. These results suggested that Triol might contribute to the decreased bone formation by inhibition of osteoblastic differentiation and promotion of apoptosis of MSCs, providing insights about common factors underlying the pathogenesis of atherosclerosis and osteoporosis.

Animals↗

PubMed2005

Inhibitory effect of Epimedium extract on S-adenosyl-L-homocysteine hydrolase and biomethylation.

In the present paper, the inhibitory effect of Epimedium extract on the activity of S-adenosyl-L-homocysteine (AdoHcy) Hydrolase was studied. The results showed that Epimedium extract inhibited the activity of recombinant human AdoHcy hydrolase in a dose-dependent manner. This inhibitory effect was also observed in hepatic cell line 7701 and hepatoma HepG2, however, the effect in 7701 cells was more potent than in HepG2 cells. The extract could significantly reduce AdoMet/AdoHcy ratio in 7701 cells in a dose-dependent manner, suggesting reduced biomethylation level in 7701 cells. In contrast, it resulted in elevated AdoMet/AdoHcy ratio in the HepG2 cells. The result of MALDI-MS assay indicated that epimedin A and ikarisoside F from the extract could bind to AdoHcy hydrolase. The present data suggested that Epimedium extract could inhibit the activity of AdoHcy hydrolase, thus regulating the cellular biomethylation as well as reducing cellular Hcy level. These results will provide new clues to the mechanisms of Epimedium in curing of cardiovascular disease and regulating tumor cell growth.

Adenosylhomocysteinase↗

PubMed2005

Metaproteomic analysis of Chesapeake Bay microbial communities.

BACKGROUND: Natural microbial communities are extremely complex and dynamic systems in terms of their population structure and functions. However, little is known about the in situ functions of the microbial communities. RESULTS: This study describes the application of proteomic approaches (metaproteomics) to observe expressed protein profiles of natural microbial communities (metaproteomes). The technique was validated using a constructed community and subsequently used to analyze Chesapeake Bay microbial community (0.2 to 3.0 microm) metaproteomes. Chesapeake Bay metaproteomes contained proteins from pI 4-8 with apparent molecular masses between 10-80 kDa. Replicated middle Bay metaproteomes shared approximately 92% of all detected spots, but only shared 30% and 70% of common protein spots with upper and lower Bay metaproteomes. MALDI-TOF analysis of highly expressed proteins produced no significant matches to known proteins. Three Chesapeake Bay proteins were tentatively identified by LC-MS/MS sequencing coupled with MS-BLAST searching. The proteins identified were of marine microbial origin and correlated with abundant Chesapeake Bay microbial lineages, Bacteroides and alpha-proteobacteria. CONCLUSION: Our results represent the first metaproteomic study of aquatic microbial assemblages and demonstrate the potential of metaproteomic approaches to link metagenomic data, taxonomic diversity, functional diversity and biological processes in natural environments.

Journal Article↗

PubMed2005

La3+-promoted proliferation is interconnected with apoptosis in NIH 3T3 cells.

Lanthanum ion (La(3+)) has been reported to affect proliferation or apoptosis of different cells. In the present study, La(3+) was confirmed to promote both proliferation and apoptosis of NIH 3T3 cells at the same concentrations. La(3+) was shown to promote proliferation by helping the cells to pass through the G1/S restriction point and enter S phase, however, the proliferating cells induced by incubation with La(3+) eventually underwent apoptosis. The proliferation and apoptosis of NIH 3T3 cells induced by La(3+) were well correlated with cell cycle alterations. La(3+) caused the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2; while inhibition of ERK phosphorylation by 2'-amino-3'-methoxyflavone (PD98059) suppressed both proliferation and apoptosis induced by La(3+). Based on the above experimental results, we postulated that La(3+)-promoted proliferation of NIH 3T3 cells could be interconnected with the cell apoptosis, possibly through cell cycle machinery. Our results thus support the recent hypothesis that proliferation and apoptosis of cell are intrinsically coordinated.

3T3 Cells↗

PubMed2005

Effects of development and iron status on ceruloplasmin expression in rat brain.

The increased iron content in the brain of subjects with aceruloplasminemia has implicated ceruloplasmin (CP) as a major factor in the regulation of regional brain iron content. In this study, we investigated the effects of age and iron on CP expression in rat brain. In all four regions, the iron concentrations increased with developmental age. There is a similar trend in age-induced changes in CP mRNA and protein. The CP mRNA and protein levels were both lowest at postnatal day (PND) 7. The expression increased gradually with age, reaching the highest at PND196 in the striatum and substantia nigra, and at PND21 and PND63 in the cortex and hippocampus, respectively. This suggests the existence of an age-dependent pre-transcriptional regulation and a regionally specific effect of age on CP expression in the brain. Although total iron in all four regions was significantly lower in the rats fed with a low-iron diet for 6 weeks and higher in the rats with a high-iron diet than those in the control animals, no significant between-group differences in CP mRNA and protein were found in these animals, except in the substantia nigra where a significant increase in CP protein in high-iron rats was observed, and the reverse in low-iron rats. These findings suggested that the effects of iron on CP expression in the brain may be region-specific, and that regulation of CP expression by iron in the substantia nigra was at the post-transcriptional level.

Aging↗

PubMed2005

A robustified modeling approach to analyze pediatric length of stay.

PURPOSE: Length of stay (LOS) is an important measure of the cost of pediatric hospitalizations, but the guidelines developed so far are not rigorously evidence-based. This study demonstrates a robust gamma mixed regression approach to analyze the positively skewed LOS variable, which has implications for future studies of pediatric health care management. METHODS: The robustified approach is applied to analyze hospital discharge data on childhood gastroenteritis in Western Australia (n=514). The model accounts for demographic characteristics and co-morbidities of the patients, as well as the dependency of LOS outcomes nested within the 58 hospitals in the State. The method is compared with the standard linear mixed regression with trimming of extreme observations. RESULTS: For the empirical application, the linear mixed regression results are sensitive to the magnitude of trimming. The identified significant factors from the robust regression model, namely infection, failure to thrive, and iron deficiency anemia are resistant to high-LOS outliers. CONCLUSIONS: Robust gamma mixed regression appears to be a suitable alternative to analyze the clustered and positively skewed pediatric LOS, without transforming and trimming the data arbitrarily.

Child, Hospitalized↗

PubMed2005

DNA interaction of dioxycyclobutenedione-(1,2-cyclohexanediamine) platinum(II) complex with potential anticancer activity.

Dioxycyclobutenedione-(1,2-cyclohexanediamine)platinum(II), (R,R-DC-Pt) was found to have stronger cytotoxicity against six cancer cell lines than cisplatin and its DNA interactions was studied by calorimetric measurements, (13)C NMR. The binding specificity study of DNA base with R,R-DC-Pt was conducted by HPLC. To understand the molecular mechanism of R,R-DC-Pt with stronger cytotoxicity than that of cisplatin, we studied R,R-DC-Pt interaction with an oligonucleotide, d(ACCACGTGGT)(2), which contained c-H-ras gene encoding GGT by NMR spectroscopy. The oligomer DNA double helix was destroyed almost completely upon the R,R-DC-Pt binding. However under the same condition, the cisplatin binding with DNA was not so affected, and instead another conformation was formed, which suggests that larger damage to DNA can be induced by R,R-DC-Pt complex than that by cisplatin.

Animals↗

PubMed2005

Modelling bivariate count series with excess zeros.

Bivariate time series of counts with excess zeros relative to the Poisson process are common in many bioscience applications. Failure to account for the extra zeros in the analysis may result in biased parameter estimates and misleading inferences. A class of bivariate zero-inflated Poisson autoregression models is presented to accommodate the zero-inflation and the inherent serial dependency between successive observations. An autoregressive correlation structure is assumed in the random component of the compound regression model. Parameter estimation is achieved via an EM algorithm, by maximizing an appropriate log-likelihood function to obtain residual maximum likelihood estimates. The proposed method is applied to analyze a bivariate series from an occupational health study, in which the zero-inflated injury count events are classified as either musculoskeletal or non-musculoskeletal in nature. The approach enables the evaluation of the effectiveness of a participatory ergonomics intervention at the population level, in terms of reducing the overall incidence of lost-time injury and a simultaneous decline in the two mean injury rates.

Accidents, Occupational↗

PubMed2005

Age-dependent and iron-independent expression of two mRNA isoforms of divalent metal transporter 1 in rat brain.

The DMT1(Nramp2/DCT1) is a newly discovered proton-coupled metal-ion transport protein. The cellular localization and functional characterization of DMT1 suggest that it might play a role in physiological iron transport in the brain. In the study, we evaluated effects of dietary iron and age on iron content and DMT1 expression in four brain regions: cortex, hippocampus, striatum, substantia nigra. Total iron content in all regions was significantly lower in the low-iron diet rats and higher in the high-iron diet rats than that in the control animals, showing that dietary iron treatment for 6-weeks can alter brain iron levels. Contrary to our expectation, there was no significant alternation in DMT1(+IRE) and (-IRE) mRNA expression and protein content in all brain regions examined in spite of the existence of the altered iron levels in these regions after 6-weeks' diet treatment although TfR mRNA expression and protein level were affected significantly, as was expected. The data demonstrates that expression of DMT1(+IRE) and (-IRE) was not regulated by iron in these regions of adult rats. The lack of response of DMT1 to iron status in the brain suggests that the IRE of brain DMT1 mRNA might be not really iron-responsive and that DMT1-mediated iron transport might be not the rate-limiting step in brain iron uptake in adult rats. Our findings also showed that development can significantly affect brain iron and DMT1(+IRE) and (-IRE) expression but the effect varies in different brain regions, indicating a regionally specific regulation in the brain.

Age Factors↗

PubMed2005

[Realgar nano-particles induce apoptosis and necrosis in leukemia cell lines K562 and HL-60].

OBJECTIVE: To examine the growth-inhibitory, apoptosis- and necrosis-inducing effects of realgar nano-particles (RNP) in human chronic myelogenous leukemia cell line K562 and acute myeloid leukemia cell line HL-60, and to find out the chemical species with efficacy. METHOD: A "solvent-relay" strategy was used for the preparation of RNP suspension. Cell viability was determined by MTT assay. Cell apoptosis and necrosis were characterized with Annexin V-PI double staining in association with flow cytometry and with morphological examination with Hoechst 33258 staining. Parallel experiments with arsenous acid (H3AsO3), the dominant form of arsenic trioxide in the solution, were conducted for comparison. RESULT: The mean diameter of RNP was 159.0 nm. RNP showed growth-inhibitory effect on both cell lines. The double staining test indicated that RNP induced both apoptosis and necrosis, and this was further confirmed by morphological examination. CONCLUSION: RNP induced both apoptosis and necrosis in leukemia cell lines K562 and HL-60. Thioarsenite species with both As-O and As-S bonds may be the active intermediates in the RNP.

Antineoplastic Agents↗

PubMed2005

[Comments on Nigel Wiseman's "A Practical Sictionary of Chinese Medicine"--on Wiseman' s literal translation].

Comments were made on the word-for-word literal translation method used by Mr. Nigel Wiseman in A Practical Dictionary of Chinese Medicine. He believes that only literal translation can reflect Chinese medical concepts accurately. The so-called "word-for-word" translation is actually "English-word-for-Chinese-character" translation. First, he made a list of Single Characters with English Equivalents, and then he replaced each character of Chinese medical terms with the assigned English equivalent. Many English terms thus produced are confusing. The defect of the word-for-word literal translation stems from the erroneous idea that the single character constitutes the basic element of meaning corresponding to the notion of "word" in English, and the meaning of a disyllabic or polysyllabic Chinese word is simply the addition of the meanings of the two or more characters. Another big mistake is the negligence of the polysemy of Chinese characters. One or two English equivalents can by no means cover all the various meanings of a polysemous character as a monosyllabic word. Various examples were cited from this dictionary to illustrate the mistakes.

Medicine, Chinese Traditional↗

PubMed2004

Cholestane-3beta, 5alpha, 6beta-triol promotes vascular smooth muscle cells calcification.

Oxysterols found in atherosclerotic plaque may be associated with vascular calcification. We investigated the effect of oxysterol cholestane-3beta, 5alpha, 6beta-triol (Triol) on in vitro calcification of rat vascular smooth muscle cells (VSMCs). In vitro calcification was induced by incubation of VSMCs with beta-glycerophosphate. Calcifying nodule formation, calcium deposition in extracellular matrix, and alkaline phosphatase (ALP) activity were measured as indices of calcification. Because apoptotic bodies can serve as nucleation sites for calcification, apoptosis of calcifying VSMCs was determined by Hoechst 33258 staining, TUNEL, and FITC-labeled annexin V/PI double staining. The calcium deposition and ALP activity in calcifying VSMCs were much higher than those in non-calcifying VSMCs. Triol increased calcifying nodule formation, calcium deposition, ALP activity, and apoptosis of nodular cells in calcifying VSMCs. As determined by 2,7-dichlorofluorescein fluorescence, Triol induced the generation of reactive oxygen species (ROS) in calcifying VSMCs dose- and time-dependently. Triol-induced increases in calcium deposition, ALP activity, apoptosis, and ROS generation were all attenuated by antioxidant vitamin C plus vitamin E (VC + VE). The results demonstrated that Triol promoted VSMCs calcification through direct increase of ALP activity and apoptosis, probably by ROS-related mechanism.

Alkaline Phosphatase↗

PubMed2004

Binding of La3+ to calmodulin and its effects on the interaction between calmodulin and calmodulin binding peptide, polistes mastoparan.

Binding of La(3+) to calmodulin (CaM) and its effects on the complexes of CaM and CaM-binding peptide, polistes mastoparan (Mas), were investigated by nuclear magnetic resonance (NMR) spectroscopy, fluorescence and circular dichroism spectroscopy, and by the fluorescence stopped-flow method. The four binding sites of La(3+) on CaM were identified as the same as the binding sites of Ca(2+) on CaM through NMR titration of La(3+) to uniformly (15)N-labeled CaM. La(3+) showed a slightly higher affinity to the binding sites on the N-terminal domain of CaM than that to the C-terminal. Large differences between the (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra of Ca(4)CaM and La(4)CaM suggest conformational differences between the two complexes. Fluorescence and CD spectra also exhibited structural differences. In the presence of Ca(2+) and La(3+), a hybrid complex, Ca(2)La(2)CaM, was formed, and the binding of La(3+) to the N-terminal domain of CaM seemed preferable over binding to the C-terminal domain. Through fluorescence titration, it was shown that La(4)CaM and Ca(2)La(2)CaM had similar affinities to Mas as Ca(4)CaM. Fluorescence stopped-flow experiments showed that the dissociation rate of La(3+) from the C-terminal domain of CaM was higher than that from the N-terminal. However, in the presence of Mas, the dissociation rate of La(3+) decreased and the dissociation processes from both global domains were indistinguishable. In addition, compared with the case of Ca(4)CaM-Mas, the slower dissociations of Mas from La(4)CaM-Mas and Ca(2)La(2)CaM-Mas complexes indicate that in the presence of La(3+), the CaM-Mas complex became kinetically inert. A possible role of La(3+) in the Ca(2+)-CaM-dependent pathway is discussed.

Apoproteins↗

PubMed2004

Recurrent ischaemic stroke hospitalisations: a retrospective cohort study using Western Australia linked patient records.

A retrospective cohort study was undertaken to determine factors that affect the frequency of recurrent ischaemic stroke hospitalisations. Linked hospitalisation records of all Western Australian patients admitted for ischaemic stroke for the first time during July-December 1995 were retrieved until December 2000 to derive the number of readmissions for recurrent strokes, patient medical conditions and co-morbidities at the index episode. A negative binomial regression model adjusting for inter-hospital variations was used to determine the prognostic factors influencing recurrent stroke hospitalisations. Of the 678 patients in the cohort, 124 (18.3%) experienced repeated episodes of ischaemic stroke. Rural residence and carotid endarterectomy procedure were positively associated with the recurrence frequency, the adjusted incidence rate ratio being 1.66 (95% CI: 1.17-2.36) and 3.96 (95% CI: 2.30-6.82), respectively. Rural patients contributed to 18% of the patients in the cohort yet they accounted for 27% of those sustaining repeated episodes of stroke. Readmissions were also related to the presence of diabetes at the index episode. The effect of diabetes, with adjusted incidence rate ratio 1.35 (95% CI: 1.01-1.79), was only evident after accounting for within hospital correlations. These findings have implications on hospital resource planning and secondary preventive strategies to reduce the burden of stroke.

Aged↗

PubMed2004

Binding of Cu2+ to S-adenosyl-L-homocysteine hydrolase.

S-Adenosylhomocysteine (AdoHcy) hydrolase regulates biomethylation and homocysteine metabolism. It has been proposed to be a copper binding protein playing an important role in copper transport and distribution. In the present work, the kinetics of binding and releasing of copper ions was studied using fluorescence method. The dissociation constant for copper ions with AdoHcy hydrolase was determined by fluorescence quenching titration and activity titration methods using ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), and glycine as competitive chelators. The experimental results showed that copper ions bind to AdoHcy hydrolase with a K(d) of approximately 10(-11) M. The association rate constant was determined to be 7 x 10(6) M(-1)s(-1). The releasing of copper ions from the enzyme was found to be biphasic with a k(1) of 2.8 x 10(-3) s(-1) and k(2) of 1.7x10(-5) s(-1). It is suggested that copper ions do not bind to the substrate binding sites because the addition of adenine substrate did not compete with the binding of copper to AdoHcy hydrolase. Interestingly, it was observed that EDTA could bind to AdoHcy hydrolase with a dissociation constant of K(1) = 8.0 x 10(-5) M and result in an increased affinity (K(d) = approximately 10(-17) M) of binding of copper ions to the enzyme.

Adenosylhomocysteinase↗

PubMed2004

Recurrent gastroenteritis among infants in Western Australia: a seven-year hospital-based cohort study.

PURPOSE: To investigate factors that affect the frequency of recurrent gastroenteritis among infants in Western Australia (WA). METHODS: A 7-year retrospective cohort study was undertaken on all infants born in 1995 who were admitted for gastroenteritis during their first year of life (n=514). Linked hospitalization records of the cohort were retrieved to derive the number of readmissions, microbiologic diagnoses, patient demographics, and co-morbidities at the index episode. A negative binomial regression model adjusting for inter-hospital variations was used to determine the prognostic factors influencing recurrent gastroenteritis. RESULTS: Diarrhea with no specific etiology accounted for 54.7% of the cases presented at index admission and 55.8% of the total 676 admissions for the cohort. Of the 514 infants, 119 (23%) experienced repeated episodes of gastroenteritis. The lowest proportion of recurrences was 15.4% for patients initially admitted for bacterial or viral diarrhea. Over 85% of the recurrences from either bacterial and viral diarrhea or etiology unspecified were readmitted under the same category. Aboriginality and dehydration were significantly associated with the recurrence frequency, the adjusted incidence rate ratio being 2.86 (95% CI, 1.92-4.26) and 0.66 (95% CI, 0.49-0.88), respectively. Aboriginal infants contributed to 58% of those patients in the cohort who sustained repeated episodes of gastroenteritis. The proportion of patients with the recurrent disease was also significantly higher for Aboriginals (39%) than for non-Aboriginals (15%). The effect of dehydration was evident after accounting for within hospital correlations. CONCLUSIONS: Hospitalizations for recurrent gastroenteritis were more frequent among Aboriginal children than non-Aboriginal children in WA. Readmissions were also related to the presence of dehydration at the index episode. These findings have implications for preventive strategies to reduce the burden of gastroenteritis.

Cohort Studies↗