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Kui Wang

Publications and source records attributed to Kui Wang.

52 records · Page 3Linked to original sources

Lanthanide ions promote the hydrolysis of 2,3-bisphosphoglycerate.

The 31P NMR studies showed that lanthanide ions promote the site-specific hydrolysis of 2,3-Bisphosphoglycerate (BPG) at pH 7.4 by cleaving the 2' phosphomonoester bond. The effect of fourteen trivalent lanthanide ions and Sc3+, and Y3+ were compared by the percentage of hydrolysis obtained by determining the inorganic phosphate produced. All the trivalent lanthanide ions promote the hydrolysis, but Sc3+ not. Among them, Ce3+ affects the reaction mostly. This was mainly attributed to the autooxidation of Ce3+ to Ce4+, since the promoting effect of Ce3+ is related to the increasing Ce4+ amount in the solution and depressed by adding sulphite. Ce4+ promotes the hydrolysis more efficiently than Ce3+ do. The pseudo first-order rate constant for the hydrolysis of BPG by Ce(SO4)2 (18.7 mM) at pH 1 and pH 2, 37 degrees C is 3.1 h(-1) and 0.65 h(-1) respectively. A mechanism with a hydroxo species as reactive intermediate was proposed for the trivalent lanthanide ions. The site-specificity was explainable by this mechanism.

2,3-Diphosphoglycerate↗

The permeability and cytotoxicity of insulin-mimetic vanadium compounds.

PURPOSE: The aim of this study was to investigate the mechanism of permeation and cytotoxicity of vanadium compounds, [VO(acac)2], [VO(ma)2], and vanadate. METHODS: Absorptive transport were carried out in Caco-2 monolayers grown on transwell inserts. Vanadium was quantified using inductively coupled plasma atomic emission spectrometry (ICP-AES). The change of Caco-2 cells in the microvilli morphology and F-actin structure was visualized by transmission electron microscopy and confocal laser scanning microscopy. RESULTS: The three vanadium compounds were taken up by Caco-2 cells via simple passive diffusion. [VO(acac)2] were mainly transcellularly transported and exhibited the highest apparent permeabilty coefficients (8.2 x 10(-6) cm(-1)). The cell accumulation of [VO(acac)2] was found to be greater than that of [VO(ma)2], and vanadate caused much less accumulation than the other two compounds. Vanadium compounds induced intracellular reactive oxygen species, reduced the transepithelial electric resistance, caused morphological change in microvilli, and led to different perturbation of F-actin structure. CONCLUSIONS: The three compounds exhibited different permeability due to different diffusion process and cellular uptake. The toxicity of vanadium complexes on Caco-2 monolayer involved F-actin-related change of tight junction and impairment of microvilli. The toxicity was also related to elevated intracellular reactive oxygen species (ROS) and their cellular accumulation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

[Effects of hydroxyl radicals low density lipoprotein and cholesterol on the calcium responding behavior of vascular endothelial cells].

OBJECTIVE: To investigate the effects of hydroxyl radicals, low density lipoprotein and cholesterol on the response of vascular endothelial cells to the change in extracellular calcium ion concentration. METHODS: After treatment with the above mentioned atherogenic factors respectively, the cells were loaded with Fluo-3 and then the response of the cells to the increase in extracellular [Ca(2+)] was observed under a confocal laser scanning microscope. RESULTS: Normal vascular endothelial cells were sensitive to the increase in extracellular [Ca(2+)]. The free calcium ions in cytosol increased pulsively until a maximum was reached, and then was reduced to the initial level rapidly. Treatment with hydroxyl radicals produced by Fe(2+)-EDTA made the cells rather slow to the change in extracellular [Ca(2+)]. A morphological examination showed that some damage to the cells was caused. After cultivation with low density lipoprotein (0.10 g x L(-1)), the cells lost most of their capability to modulate intracellular calcium ion and thus the calcium level remained high at the end of the experiment. If a hydroxyl radical treatment preceded the incubation with low density lipoprotein, a more serious damage was observed. Some of the cells were caused to death while the extracellular [Ca(2+)] increased. Upon exposing to a higher level of extracellular calcium ion, the cytosol [Ca(2+)] did not increase; contrarily, it decreased gradually. The hydroxyl radical oxidation followed by cholesterol treatment made the cells respond disorderly to the increase in extracellular [Ca(2+)], indicating that rather serious damage had been caused to the cells. CONCLUSION: These findings indicate that hydroxyl radicals, low density lipoprotein and cholesterol interfere with the response of vascular endothelial cells to extracellular calcium ions. This may be one of the ways these factors contribute to the initiation and development of atherosclerosis.

Arteriosclerosis↗

[La accumulation and microstructure change of leg bones of rats fed with La(NO(3))(3) in low dosage for a long term].

OBJECTIVE: To study La accumulation and microstructure change of leg bones of rats fed with La(NO(3))(3) in low dosage for a long term. METHODS: After the rats were fed by La(NO(3))(3) in dosage of 2 mg x (kg(-1) x d(-1)) for 6 months, the contents of La and Ca,P in the leg bones were determined by ICP MS and spectrophotometry; the microstructure changes of the leg bones were investigated by electron microscopy and X-ray powder diffraction. RESULTS: In the leg bones of tested rats, the contents of La and P increased greatly, and those of Ca did not change obviously, so that Ca/P ratio values decreased in comparison with the control group. CONCLUSION: La was accumulatied in the rat leg bones and the change of bone microstructure induced after the rats were fed with La(NO(3))(3) in low dosage for a long term.

Animals↗

La(3+), Gd(3+) and Yb(3+) induced changes in mitochondrial structure, membrane permeability, cytochrome c release and intracellular ROS level.

Lanthanides (Ln) were known to induce cell apoptosis, which might be the results of their effects on mitochondria (MT). This study was trying to clarify the role of MT and reactive oxygen species (ROS) in Ln-induced apoptosis. We found that micromolar or lower concentration of La(3+), Gd(3+) and Yb(3+) bound to MT and induced swelling of isolated MT; EGTA treatment can inhibit the process. In addition, La(3+), Gd(3+) and Yb(3+) increased the MT membrane fluidity and decreased the MT membrane potential (DeltaPsi(m)). All these were inferred to the results of MT permeability transition pore opening. Release of cytochrome c (Cyt-c) from the MT upon incubation with Ln ions was monitored by immunocytochemistry, however, Cyt-c release was observed only in the cytosol of cells. In parallel with these events, there was a higher level of ROS found in the cells exposed to Ln. It was proposed that Ln-induced apoptosis via the MT pathways and it was highly possible that ROS were involved in the mechanism.

Animals↗

[Effects of lanthanum on alkaline phosphatase].

OBJECTIVE: To investigate the effects of lanthanum on the activities of two kinds of alkaline phosphatase (AP)-rat liver AP and bovine intestine AP, and the preliminary mechanism involved. METHODS: A traditional colorimetric method was used to measure the activity of AP. The influence of La3+ on the intrinsic fluorescence of protein was studied by the method of fluorescence titration into the AP solution by LaCl3. The quenching equation was fitted based on the fluorescence spectrum, and then the binding number and the binding constants were calculated. RESULTS: Lanthanum increased the activity of rat liver AP, whereas it decreased that of bovine intestine AP. It was observed that the binding of La3+ quenched the fluorescence of bovine intestine AP, which indicated that La3+ could change the conformation of AP in solution. The number of binding sites and the binding constants that were calculated based on the fitted quenching equation were 78 and 2.1 x 10(4) respectively. CONCLUSION: La3+ has different effects on the activities of rat liver AP and bovine intestine AP; the binding of La3+ can induce the changes of conformation of bovine intestine AP, and inhibit its activity.

Alkaline Phosphatase↗

Post-transcriptional expression of DMT1 in the heart of rat.

Non-transferrin-bound iron (NTBI) overtaken by heart cells might be a key cause leading to iron-mediated injury in heart disorders. NTBI uptake by heart cells might be mediated by divalent metal transporter 1 (DMT1). The understanding of the role of DMT1 in heart iron metabolism is fundamental for elucidating the cause resulting in excessive iron in the heart. The study was to evaluate effects of age and dietary iron on DMT1 mRNA expression and protein synthesis in rat heart. DMT1 mRNA expression was determined by RT-PCR and sequence analysis, and DMT1 protein by Western blot analysis. DMT1 mRNAs with or without iron-responsive element (IRE) both were found in rat heart. Expression of two forms of DMT1 mRNAs was the lowest at the age of post-natal day (PND) 7, and then increased with the age, reaching the highest at PND196 (non-IRE form) and PND63 (IRE form), respectively. During different ages, the levels of DMT1 (IRE) mRNA were higher than those of DMT1 (non-IRE) mRNA and were significantly correlated with the non-heme iron contents in the heart. After fed a high iron for 6 weeks, the rats had a sixfold elevation in heart iron and 22% (non-IRE from) and 40% (IRE from) reduction in DMT1 protein compared to the controls. A low iron diet for 6-weeks caused cardiac hypertrophy and heart iron deficiency and also an increase in levels of two forms of DMT1 proteins. However, iron status had no significant effect on DMT1 (IRE) and DMT1 (non-IRE) mRNAs expression in the heart, although it can significantly influence heart transferrin receptor (TfR) mRNA expression. The results demonstrated that DMT1 mRNAs expression in the heart is age-dependent and that two forms of DMT1 mRNAs both are regulated by iron on the post-transcriptional level only.

Aging↗

A bivariate zero-inflated Poisson regression model to analyze occupational injuries.

The aim of many occupational safety interventions is to reduce the incidence of injury. However, when measuring intervention effectiveness within a period, population-based accident count data typically contain a large proportion of zero observations (no injury). This situation is compounded where injuries are categorized in a binary manner according to an outcome of interest. The distribution thus comprises a point mass at zero mixed with a non-degenerate parametric component, such as the bivariate Poisson. In this paper, a bivariate zero-inflated Poisson (BZIP) regression model is proposed to evaluate a participatory ergonomics team intervention conducted within the cleaning services department of a public teaching hospital. The findings highlight that the BZIP distribution provided a satisfactory fit to the data, and that the intervention was associated with a significant reduction in overall injury incidence and the mean number of musculoskeletal (MLTI) injuries, while the decline in injuries of a non-musculoskeletal (NMLTI) nature was marginal. In general, the method can be applied to assess the effectiveness of intervention trials on other populations at high risk of occupational injury.

Accidents, Occupational↗

Effects of LDL, cholesterol, and their oxidized forms on the precipitation kinetics of calcium phosphates.

BACKGROUND: LDL, cholesterol, and their oxidized forms are known cardiovascular risk factors and are often found in atherosclerotic lesions of various stages. Little is known, however, about whether they are directly involved in the formation of calcium phosphate compounds. METHODS: We used the pH-stat technique to follow the kinetics of calcium phosphate precipitation at pH 7.4, 37 degrees C, and ionic strength 0.150 mol/L, in the presence or absence of LDL, oxidized LDL, cholesterol, cholestane-3beta,5alpha,6beta-triol, and cholesteryl linoleate. The precipitates were characterized by x-ray diffraction, scanning and transmission electronic microscopy coupled with energy-dispersion x-ray analysis, and inductively coupled plasma atomic emission spectroscopy. RESULTS: Under the experimental conditions, LDL (14.8 and 43.1 mg/L protein) had no significant effect on the precipitation kinetics. Oxidized LDL (14.8 and 43.1 mg/L protein) prolonged the nucleation phase and diminished the amount of total precipitate, and both the extent of oxidation and the concentration of the protein affected the kinetics. Cholesterol microcrystals (71.4 and 143 mg/L) made the nucleation phase shorter (300 min vs 390 min for the control), and the precipitated particles had an organic core and a shell composed of calcium phosphates. L-alpha-Phosphatidylcholine vesicles (143 mg/L), cholesterol (71.4 mg/L)/phospholipid (143 mg/L) mixed vesicles, cholesteryl linoleate (143 mg/L), and cholestane-3beta,5alpha,6beta-triol (71.4 mg/L) prolonged the nucleation phase. CONCLUSIONS: LDL is not involved directly in the precipitation of calcium phosphates. Oxidized LDL inhibits both nucleation and crystal growth, possibly by attracting calcium ions in the solution and thus reducing supersaturation. Cholesterol microcrystals serve as seeds for the precipitation of hydroxyapatite, whereas L-alpha-phosphatidylcholine, cholesteryl linoleate, and cholestane-3beta,5alpha,6beta-triol exhibit inhibitive effects on the nucleation of calcium phosphates.

Calcium Phosphates↗

Modeling young driver motor vehicle crashes: data with extra zeros.

Much of the data collected on motor vehicle crashes is count data. The standard Poisson regression approach used to model this type of data does not take into account the fact there are few crash events and hence, many observed zeros. In this paper, we applied the zero-inflated Poisson (ZIP) model (which adjusts for the many observed zeros) and the negative binomial (NB) model to analyze young driver motor vehicle crashes. The results of the ZIP regression model are comparable to those from fitting a NB regression model for general over-dispersion. The findings highlight that driver confidence/adventurousness and the frequency of driving prior to licensing are significant predictors of crash outcome in the first 12 months of driving. We encourage researchers, when analyzing motor vehicle crash data, to consider the empirical frequency distribution first and to apply the ZIP and NB models in the presence of extra zeros due, for example, to under-reporting.

Accidents, Traffic↗

Complexation of ytterbium to human transferrin and its uptake by K562 cells.

There is an increasing interest in the use of lanthanides in medicine. However, the mechanism of their accumulation in cells is not well understood. Lanthanide cations are similar to ferric ions with regard to transferrin binding, suggesting transferrin-receptor mediated transport is possible; however, this has not yet been confirmed. In order to clarify this mechanism, we investigated the binding of Yb3+ to apotransferrin by UV-Vis spectroscopy and stopped-flow spectrophotometry, and found that Yb3+ binds to apotransferrin at the specific iron sites in the presence of bicarbonate. The apparent binding constants of these sites showed that the affinity of Yb3+ is lower than that of Fe3+and binding of Yb3+ in the N-lobe is kinetically favored while the C-lobe is thermodynamically favored. The first Yb3+ bound to the C-lobe quantitatively with a Yb/apotransferrin molar ratio of < 1, whereas the binding to the other site is weaker and approaches completeness by a higher molar ratio only. As demonstrated by 1H NMR spectra, Yb3+ binding disturbed the conformation of apotransferrin in a manner similar to Fe3+. Flow cytometric studies on the uptake of fluorescein isothiocyanate labeled Yb3+-bound transferrin species by K562 cells showed that they bind to the cell receptors. Laser scanning confocal microscopic studies with fluorescein isothiocyanate labeled Yb3+-bound transferrin and propidium iodide labeled DNA and RNA in cells indicated that the Yb3+ entered the cells. The Yb3+-transferrin complex inhibited the uptake of the fluorescein labeled ferric-saturated transferrin (Fe2-transferrin) complex into K562 cells. The results demonstrate that the complex of Yb3+-transferrin complex was recognized by the transferrin receptor and that the transferrin-receptor-mediated mechanism is a possible pathway for Yb3+ accumulation in cells.

Binding, Competitive↗

Antitumor activity of Z-ajoene, a natural compound purified from garlic: antimitotic and microtubule-interaction properties.

Ajoene, a garlic stable oil-soluble sulfur rich compound was generally isolated as a mixture of two isomers [(E, Z)-4,5,9-trithiadodeca-1,6,11-triene-9-oxide]. It has been described essentially as a potent inhibitor of platelet aggregation in vitro and in vivo. The antiproliferative effects of ajoene and experiments using a single isomer had received little attention. The present study aims at defining the antitumor activities of cis-Z-ajoene in vitro and in vivo. Antiproliferative activity of Z-ajoene was demonstrated against a panel of human tumor cell lines with IC(50) values varying from 5.2 mM to 26.1 mM and at a lower extent in normal marsupial kidney cells (PtK2). Meanwhile, Z-ajoene arrested HL60 cells in G(2)/M phase of cell cycle in a dose and time-dependent way. In PtK2 cells, exposure to 20 microM Z-ajoene for 6 h induced a complete disassembly of the microtubule network, that was associated with an increased number of cells blocked in early mitotic stages. An IC(50) for microtubule disassembly of 1 microM was determined by a fully automated microplate-based multi-detection reader. In vitro, a reversible inhibition of the microtubule protein assembly was observed with an IC(50) of 25 microM Z-ajoene. In vivo, Z-ajoene inhibited tumor growth by 38% and 42% in mice grafted with sarcoma 180 and hepatocarcinoma 22, respectively. For the first time, Z-ajoene was shown to be a potent inhibitor of tumor cell growth both in vitro and in vivo. The microtubule cytoskeleton appeared to be one of the Z-ajoene targets, but the mechanisms by which Z-ajoene interacted with microtubule appeared different from those of other microtubule poisons such as those of the Vinca alkaloids family. The ability of Z-ajoene to preferentially suppress the growth of neoplastic cells could provide a new approach in tumor therapy.

Animals↗

Z-ajoene induces apoptosis of HL-60 cells: involvement of Bcl-2 cleavage.

Garlic organosulfur components exhibit antitumor activity, but the molecular mechanisms underlying these effects have not been well characterized. We showed that Z-ajoene, a sulfur-rich compound purified from garlic, induced time- and dose-dependent apoptosis in HL-60 cells. This process implied the activation of caspase-3 and the cleavage of the antiapoptotic protein Bcl-2. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-[OMe]-fluoromethylketone inhibited Bcl-2 cleavage and apoptosis induced by Z-ajoene. This effect was partially prevented by treatment of HL-60 cells with the antioxidant N-acetylcysteine. Hence, the transmission of apoptotic signal induced by Z-ajoene involved a reactive oxygen species-dependent pathway leading to caspase-dependent Bcl-2 cleavage.

Antineoplastic Agents↗

Patients with advanced primary hepatocellular carcinoma treated by melatonin and transcatheter arterial chemoembolization: a prospective study.

OBJECTIVE: To observe the clinical efficacy of transcatheter arterial chemoembolization (TACE) and TACE+MLT (melatonin) on inoperable advanced primary hepatocellular carcinoma. METHODS: From January 1997 to January 1998, one hundred patients with inoperable advanced primary hepatocellular carcinoma were treated separately by TACE (50) and TACE+MLT (20 mg/d at 8:00 PM orally, 7 days before TACE)(50). RESULTS: The effective rates (WHO standards) of TACE and TACE+MLT were 16% and 28% respectively (P<0.05). After TACE or TACE+MLT, the resection rate at two-stage of TACE was 4% or 14% (P<0.01). The 0.5-, 1- and 2-year survival rates in the TACE group were 82%, 54% and 26% respectively; in the TACE+MLT group 100%, 68% and 40% respectively. The results were significantly better in the TACE+MLT group than in the TACE group. MLT could protect liver function from the damage caused by TACE. The IL-2 levels of all patients significantly increased, whereas sIL-2R expressions decreased after TACE+MLT as compared with the TACE group (P<0.01). CONCLUSIONS: With definite protection and treatment effect on the liver function damage caused by TACE, MLT can enhance the immunological activities of patients. It also can improve the effect of TACE by increasing the survival and resection rate after two-stage operation.

Adjuvants, Immunologic↗

Highly accurate and consistent method for prediction of helix and strand content from primary protein sequences.

OBJECTIVE: One of interesting computational topics in bioinformatics is prediction of secondary structure of proteins. Over 30 years of research has been devoted to the topic but we are still far away from having reliable prediction methods. A critical piece of information for accurate prediction of secondary structure is the helix and strand content of a given protein sequence. Ability to accurately predict content of those two secondary structures has a good potential to improve accuracy of prediction of the secondary structure. Most of the existing methods use composition vector to predict the content. Their underlying assumption is that the vector can be used to provide functional mapping between primary sequence and helix/strand content. While this is true for small sets of proteins we show that for larger protein sets such mapping are inconsistent, i.e. the same composition vectors correspond to different contents. To this end, we propose a method for prediction of helix/strand content from primary protein sequences that is fundamentally different from currently available methods. METHODS AND MATERIAL: Our method is accurate and uses a novel approach to obtain information from primary sequence based on a composition moment vector, which is a measure that includes information about both composition of a given primary sequence and the position of amino acids in the sequence. In contrast to the composition vector, we show that it provides functional mapping between primary sequence and the helix/strand content. RESULTS: A set of benchmarks involving a large protein dataset consisting of over 11,000 protein sequences from Protein Data Bank was performed to validate the method. Prediction done by a neural network had average accuracy of 91.5% for the helix and 94.5% for the strand contents. We also show that using the new measure results in about 40% reduction of error rates when compared with the composition vector results. CONCLUSIONS: The developed method has much better accuracy when compared with other existing methods, as shown on a large body of proteins, in contrast to other reported results that often target small sets of specific protein types, such as globular proteins.

Amino Acid Sequence↗