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Biomedical subjects

W He

Publications and source records attributed to W He.

At least 37 records · Page 2Linked to original sources

A new murine oxidative stress model associated with senescence.

A murine oxidative stress model was established via ozone inhalation, which was identified by detection of the response of antioxidant defense system, levels of oxidative products and effects of natural antioxidants on this model. Male BALB/c mice were exposed to 1.2 mg/m(3) ozone for 10 h per day. The control group was exposed to flowing air. From inhaling ozone, mice were killed at day 5, 10, 15 and 20, respectively. Exposure to ozone made mice show the increase of malondialdehyde (MDA) contents in heart, kidney and liver, as well as 8-OHdG levels in urine, and resulted in cytological nuclear concentration in brain neurons or thymocytes. Ozone exposure also impaired antioxidative capacity such as the decrease of total antioxidation capacity (TAC) in sera, reduced glutathione (GSH) in sera or thymus and glutathione-S-transferase (GST) activity in spleen or thymus but not in liver. Correlation analysis showed the significant inverse correlation (r=-0.894, P<0.05) between thymus weight index and inhalation doses of ozone. Meanwhile, thymocyte in model mice proliferated more poorly than normal controls. Catechin and clove extract could reverse parts of changes above induced by ozone inhalation. These results suggest that exposure to ozone can result in an increased production of reactive oxygen species in vivo, which causes oxidative stress. The mice under oxidative stress showed senescence-related alterations in physiological parameters as well. Taken together, our data demonstrates that an oxidative stress model in mice has been successfully established by ozone inhalation, which would be helpful to probe the relationship between oxidative stress and senescence and evaluate effects of antioxidants.

8-Hydroxy-2'-Deoxyguanosine↗

Structural revision of isovalertatins M03, M13, and M23 isolated from the culture of Streptomyces luteogriseus.

Three aminooligosaccharides, isovalertatins M03 (1), M13 (2), and M23 (3) were isolated and purified from the culture filtrate of Streptomyces luteogriseus. Their physicochemical properties, liquid chromatographic behavior, and spectroscopic data were in full accordance with the reported compounds [Xu, Q.; Wang, Q.; Lu, D. CN Patent 1100756, 1995; Chem. Abstr. 1995, 123, 110278n], but their structures were reinvestigated and revised by spectroscopic methods, including ESI multistage mass spectrometry and 2-dimensional NMR techniques.

Amines↗

Structural determinants for regulation of phosphodiesterase by a G protein at 2.0 A.

A multitude of heptahelical receptors use heterotrimeric G proteins to transduce signals to specific effector target molecules. The G protein transducin, Gt, couples photon-activated rhodopsin with the effector cyclic GMP phosophodiesterase (PDE) in the vertebrate phototransduction cascade. The interactions of the Gt alpha-subunit (alpha(t)) with the inhibitory PDE gamma-subunit (PDEgamma) are central to effector activation, and also enhance visual recovery in cooperation with the GTPase-activating protein regulator of G-protein signalling (RGS)-9 (refs 1-3). Here we describe the crystal structure at 2.0 A of rod transducin alpha x GDP x AlF4- in complex with the effector molecule PDEgamma and the GTPase-activating protein RGS9. In addition, we present the independently solved crystal structures of the RGS9 RGS domain both alone and in complex with alpha(t/i1) x GDP x AlF4-. These structures reveal insights into effector activation, synergistic GTPase acceleration, RGS9 specificity and RGS activity. Effector binding to a nucleotide-dependent site on alpha(t) sequesters PDEgamma residues implicated in PDE inhibition, and potentiates recruitment of RGS9 for hydrolytic transition state stabilization and concomitant signal termination.

3',5'-Cyclic-GMP Phosphodiesterases↗

Smads mediate signaling of the TGFbeta superfamily in normal keratinocytes but are lost during skin chemical carcinogenesis.

The Smads are the signaling mediators of the TGFbeta superfamily. In the present study, we examined Smad expression in mouse epidermis and chemically-induced skin tumors. Mutations in Smad2 and -4 genes were also screened. Transcripts of Smad1 through -5 were constantly expressed in the epidermis regardless of changes in TGFbeta signaling, state of differentiation and stages of carcinogenesis. Smad7 transcripts were barely detectable in keratinocytes, but were induced by TGFbeta1 treatment and in chemically-induced skin tumors. At the protein level, Smad1 was detected throughout the epidermis, whereas Smad2 through -5 exhibited greater levels in suprabasal layers than basal keratinocytes. In cultured keratinocytes, Smad2, -3 and -4 underwent nuclear translocation upon TGFbeta1 treatment. Furthermore, nuclear translocation of Smads correlated with decreased BrdU labeling in proliferative keratinocytes. Although no mutations were detected in the Smad2 and -4 genes in tumors, proteins of Smad1 through -5 were partially or completely lost in carcinomas. These data document that Smads are expressed at high levels in the epidermis and mediate signaling of the TGFbeta superfamily. During skin carcinogenesis, loss of Smad1 through -5 and overexpression of Smad7 may contribute to the loss of growth inhibition mediated by TGFbeta superfamily members, thus resulting in tumor progression.

9,10-Dimethyl-1,2-benzanthracene↗

Purification, refolding of hybrid hIFNgamma-kringle 5 expressed in Escherichia coli.

The DNA sequence coding for plasminogen kringle 5 (pK5), an inhibitor of angiogenesis, was fused with that coding for interferon gamma and over-produced in the form of inactive inclusion bodies in E. coli. The amount of fusion protein was about 40% of total protein produced. The fusion protein contained in the inclusion bodies was solubilized in 8 M urea and purified by anion-exchange chromatography. We employed the orthogonal experimental design L16(4(5)) (5 factors, 4 levels, 16 experiments) procedure for researching the influence of denaturant, aggregation suppressor L-arginine, NaCl, pH, and glycine on the refolding procedure. Our results suggest that the presence of appropriate L-arginine, NaCl, and denaturant in the refolding buffer inhibits the aggregation of the fusion protein and increases the yield of renatured protein with biological activity. The refolded fusion protein, gammaIFN/pk5, has in vitro anti-endothelial cell proliferation activity.

Angiogenesis Inhibitors↗

RGS proteins: lessons from the RGS9 subfamily.

RGS proteins enhance the time resolution of G protein signaling cascades by accelerating GTP hydrolysis of G alpha subunits of heterotrimeric G proteins. RGS9-1, a photoreceptor-specific RGS protein, is the first vertebrate member of this sizeable family whose physiological function in a well-defined G protein pathway has been identified. It is essential for normal subsecond recovery kinetics of the light responses in retinal photoreceptors. Understanding this role allows RGS9-1 to serve as a useful model for understanding how specificity and regulation of RGS function are achieved. In addition to the catalytic RGS domain, shared among all members of this family, RGS9-1 contains several other domains, which are also found in a closely related subset of RGS proteins, the RGS9 subfamily. One of these domains, the G gamma-like (GGL) domain, has been identified as the attachment site for G beta 5 proteins, which act as obligate subunits for this subfamily. Results from RGS9-1 and other subfamily members suggest that specificity is achieved by cell type-specific transcription, RNA processing, and G beta 5-dependent protein stabilization. In addition, membrane localization via specific targeting domains likely plays an important role.

Animals↗

Copper(II) ion induced monolayer formation of p-tert-butylthiacalix[4]arene at the air-water interface.

The monolayer properties of p-tert-butylthiacalix[4]arene (TCA) at the air-water interface was investigated by the measurements of surface pressure-area isotherms. However, TCA only exists as a trimmer aggregate on the subphase of deionized water. Copper(II) ion in the subphase can induce the monolayer formation of TCA. The UV-Vis spectra and FTIR spectra of the transferred films suggested that the monolayer forrmation was fulfilled through the coordination of copper(II) ion to TCA at the air-water surface.

Air↗

Prediction and confirmation of a site critical for effector regulation of RGS domain activity.

A critical challenge of structural genomics is to extract functional information from protein structures. We present an example of how this may be accomplished using the Evolutionary Trace (ET) method in the context of the regulators of G protein signaling (RGS) family. We have previously applied ET to the RGS family and identified a novel, evolutionarily privileged site on the RGS domain as important for regulating RGS activity. Here we confirm through targeted mutagenesis of RGS7 that these ET-identified residues are critical for RGS domain regulation and are likely to function as global determinants of RGS function. We also discuss how the recent structure of the complex of RGS9, Gt/i1alpha-GDP-AlF4- and the effector subunit PDEgamma confirms their contact with the effector-G protein interface, forming a structural pathway that communicates from the effector-contacting surface of the G protein and RGS catalytic core domain to the catalytic interface between Galpha and RGS. These results demonstrate the effectiveness of ET for identifying binding sites and efficiently focusing mutational studies on their key residues, thereby linking raw sequence and structure data to functional information.

Amino Acid Sequence↗

The yeast cytoplasmic LsmI/Pat1p complex protects mRNA 3' termini from partial degradation.

A key aspect of understanding eukaryotic gene regulation will be the identification and analysis of proteins that bind mRNAs and control their function. Recently, a complex of seven Lsm proteins and the Pat1p have been shown to interact with yeast mRNAs and promote mRNA decapping. In this study we present several observations to indicate that the LsmI/Pat1 complex has a second distinct function in protecting the 3'-UTR of mRNAs from trimming. First, mutations in the LSM1 to LSM7, as well as PAT1, genes led to the accumulation of MFA2pG and PGK1pG transcripts that had been shortened by 10-20 nucleotides at their 3' ends (referred to as trimming). Second, the trimming of these mRNAs was more severe at the high temperature, correlating with the inability of these mutant strains to grow at high temperature. In contrast, trimming did not occur in a dcp1 Delta strain, wherein the decapping enzyme is lacking. This indicates that trimming is not simply a consequence of the inhibition of mRNA decapping. Third, the temperature-sensitive growth of lsm and pat1 mutants was suppressed by mutations in the exosome or the functionally related Ski proteins, which are required for efficient 3' to 5' mRNA degradation of mRNA. Moreover, in lsm ski double mutants, higher levels of the trimmed mRNAs accumulated, indicating that exosome function is not required for mRNA trimming but that the exosome does degrade the trimmed mRNAs. These results raise the possibility that the temperature-sensitive growth of the lsm1-7 and pat1 mutants is at least partially due to mRNA trimming, which either inactivates the function of the mRNAs or makes them available for premature 3' to 5' degradation by the exosome.

3' Untranslated Regions↗

Antitumor activity of expanded human tumor-infiltrating gammadelta T lymphocytes.

BACKGROUND: The objective of this study was to investigate the antitumor activity of selectively expanded gammadelta T cells in tumor-infiltrating lymphocytes (gammadeltaTILs) or tumor ascites lymphocytes (gammadeltaTALs) from patients with colorectal and ovarian epithelial carcinoma (OEC) in vitro and in vivo. METHODS: gammadeltaTILs/TALs were expanded by the solid-phase antibody method; their cytolytic and proliferative activities in vitro were detected by the MTT method and 3H-TdR incorporation and their effect in vivo was evaluated by the nude mice model. RESULTS: Expanded gammadeltaTILs from colorectal tumors demonstrated marked cytotoxicities to allogeneic human colon adenocarcinoma HR8348 and lymphoma Daudi cells, as well as xenogeneic murine thymoma EL-4 cell lines. Cytokines, including IL-2, IL-4, IL-12, IL-15, TNF-alpha and INF-gamma, could promote the cytotoxicities of gammadeltaTILs to tumor cells, whereas IL-10, GM-CSF and TFG-beta had no effect on such killing activities. Rested gammadeltaTILs could proliferate strongly in response to mitomycin C-treated Daudi and EL-4 tumor cells, but not to HR8348 tumor cells, suggesting that the latter might possess only cytotoxicity-related antigen recognized by gammadeltaTILs. Either alphabetaTILs or gammadeltaTILs from patients with OEC displayed cytotoxicities to allogeneic or autologous OEC cell lines at a similar strength in vitro. Transferring gammadeltaTILs into Daudi cell-bearing BALB/c nude mice with an injection of IL-2 was able to maintain a high survival rate of the mice for 30 days, when compared with mice treated with alphabetaTILs or without any treatment (p < 0.05). Without coinjection of IL-2, after 3 months of Daudi tumor inoculation, a high survival rate was observed in gammadeltaTIL-treated mice. Similarly, adoptive gammadeltaTALs from the ascites of patients with OEC transferred into nude mice displayed a stronger antitumor response to OEC SKOV3 cells than alphabetaTALs in vivo. Tumor volumes in gammadeltaTAL-treated mice were smaller than in alphabetaTAL-treated or non-TAL-treated mice within the period from day 23 to day 50 after tumor inoculation (p < 0.05). Fifty days after SKOV3 tumor inoculation, a decreasing trend of carcinogenic rate was observed in gammadeltaTAL-treated nude mice. CONCLUSION: Taken together, our results suggest that gammadeltaT cells could be a new candidate for adoptive immunotherapy in the future treatment of patients with cancer.

Adenocarcinoma↗

[Investigation of water sorption and solubility of three denture soft lining materials].

This assay was made to investigate the water sorption and solubility of autopolymerizing hydrogel, acrylic resin and silicone denture soft lining materials. The test discs with 50 mm in diameter and 1 mm in thickness were prepared according to powder and liquid ratio. The weight of sample was measured after 24 h drying (m1). The sample was put into artificial saliva and distilled water for 7 d and 28 d, the moisture weight was measured after soaking (m2). After drying again, the last data of weight (m3) was acquired till the constant mass was recorded. Finally the values of water sorption and water solubility were calculated respectively with statistical analysis. The results showed the means of percentage about absorption at 7 d and 28 d were 28.62% and 24.96% for hydrogel, 1.89% and 1.65% for acrylic resin, 0.25% and 0.29% for silicone in artificial saliva. The percentage solubility at two stages were 0.56% and 0.51% for hydrogel, 0.74% and 0.83% for acrylic resin, 0.10% and 0.12% for silicone. In distilled water, the means of percentage about absorption at 7 d and 28 d were 30.15% and 27.85% for hydrogel, 3.64% and 6.17% for acrylic resin, 0.83% and 0.98% for silicone. The percentage solubility at two stages were 0.79% and 1.16% for hydrogel, 0.86% and 1.01% for acrylic resin, 0.10% and 0.14% for silicone respectively. The conclusion is that the order of percentage about absorption for these three denture soft lining materials were hydrogel > acrylic resin > silicone. The percentage solubility of acrylic resin was higher than that of the other two materials because of the plasticizer existing in acrylic resin material. In some degree, the ionic component increased may affect water sorption and solubility. Further clinical demonstration is needed for this hydrogel with higher percentage absorption.

Absorption↗

Study of the distribution of non-point source pollution in the watershed of the Miyun Reservoir, Beijing, China.

Nitrogen and phosphorus are major nutrients to cause eutrophication to degrade the water quality of the Miyun Reservoir, a very important drinking water source of Beijing in China. These are mainly from non-point sources. The watershed in Miyun County is selected as the study region with a total area of 1400 km2. Four typical monitoring catchments and two experimental units were used to monitor the precipitation, runoff, sediment yield and pollutant loading related to various land uses in the meantime. The results show that the total nutrient loss amount of TN and TP is 898.07 t/a, and 40.70 t/a, respectively, in which nutrient N and P carried by runoff is 91.3% and 77.3%, respectively. There is relatively heavier soil erosion at the northern mountain area whereas the main nutrient loss occurs near the northeast rim of the reservoir. Different land uses influence the loss of non-point source pollutants. The amount of nutrient loss from agricultural land per unit is the highest, nutrient loss from forestry is the second highest and that from grassland is the lowest. However, due to the variability of land use areas, agricultural land contributes the greatest amount of TP and forestry lands the greatest amount of TN.

Agriculture↗

Aortic and mitral valve replacement with retrograde perfusion in the beating heart.

OBJECTIVE: To estimate the value of aortic valves and combined mitral valve replacement with retrograde perfusion in beating hearts. METHODS: Continuous retrograde coronary sinus perfusion with beating hearts was used in 83 patients undergoing aortic valve or aortic valve combined with mitral valve replacement, without application of cardioplegia. After aortic valve replacement, the retrograde perfusion was changed to antegrade perfusion for mitral valve replacement or correction of the other deformities (group A). Cold blood cardioplegia solution (15 degrees C) was infused at intervals in 20 cases (group B). The following parameters were tested: lactate, ET, CTn-T and MDA in blood; myocardial ultra-structure; and cardiac rhythm and cardiac output (CO). RESULTS: All biochemical values increased after cardiopulmonary bypass (P < 0.05-0.01). Empty and beating heart sinus rhythm was maintained in group A. Myocardial ultrastructure did not change significantly. The pump was stopped smoothly as the surgical procedure finished. No postoperative low cardiac output syndrome or arrhythmia was observed. Eight-one patients recovered smoothly, two died from renal failure or infective shock. When the pump stopped, all patients in group B were supported by 5-10 micrograms.kg-1.min-1 dopamine. Transient pacing was used in 9 patients. One patient died from low cardiac output syndrome. CONCLUSION: This method is a good myocardial protection which simulates physiologic status. It is applicable to aortic valve and combined mitral valve replacement of patients with large heart or heart failure and long time aortic cross-clamping. Ideal clinical effect can be achieved.

Adolescent↗

[Physiological and growth responses of Sabina vulgaris to disturbance of leaf removal].

To examine the physiological and growth responses to Sabina vulgaris to natural disturbance, a field experiment to simulate the grazing and pest disturbance was conducted in Maowusu sandy land through artificially removing leaves. The disturbance of leaf removal could modify the species' diurnal physiological dynamics through changing the timing of extreme values, and moreover, change the average daily values of physiological indexes significantly. Leaf removal could affect the growth traits, but not biomass allocation significantly. The consequences of the disturbance were confined by its means and intensity, and there existed significant differences in sensitivity of different physiological and growth characteristics e.g., net photosynthesis rate and transpiration rate to leaf removal. The disturbance of leaf removal, especially that of old leaf removal, had compensation effects. Therefore, moderately removing the leaves on the shoots with less than 2 years old could enhance the growth and the biomass accumulation of current-year shoots.

Trees↗

[Effects of nitric oxide (NO) on the cardiac function in severely scalded rats].

OBJECTIVE: To investigate the effects of NO on the cardiac function in severely scalded rats and to elucidate its mechanism. METHODS: Ninety Sprague-Dawley (SD) rats inflicted with 30% TBSA III degree scalding were employed as the model and divided randomly into five groups, i.e. burn (B), shamburn (SB), L-arginine (L-Arg), N-nitroso-L-argininemethylester (L-NAME) and L-Arg + L-NAME groups. Cardiac functional indices, myocardial content of malondialdehyde (MDA) and myocardial Ca (calcium) transport were examined in the rats of all the groups, respectively. RESULTS: Compared to those in B group, the mean arterial pressure (MAP), left ventricular summit pressure (LVSP), the +/- dp/dt max in left ventricle pressure and the cardiac Lo in L-NAME group increased obviously. While those in L-Arg group decreased significantly but those in L-Arg + L-NAME group exhibited no remarkable change. The MDA content in L-NAME group was evidently lower than that in B group, while the calcium transport index of sarcoplasmic reticulum in L-NAME group increased obviously. CONCLUSION: Nitric oxide, massively produced postburn, exerted inhibitory effects on cardiac function by means of the cytotoxicity of its owns and other free radicals, which might be closely related to the decrease of its calcium transport function of sarcoplasmic reticulum.

Animals↗

[Influence of heart position change on body surface potential distribution].

Based on a 3-D emulational body torso model, the influence of changes of heart position caused by deep inspiration etc. on body surface potential maps(BSPMs) was studied in forward electrocardiography. In this report, BSPMs and ECGs during QRS were provided while the heart was in the normal position, or rotated clockwise to the vertical or counterclockwise to the transverse.

Algorithms↗

[Comparative study on the characteristics of electrocardiac signals in time domain and frequency domain].

There are two methods (time domain and frequency domain) for the analysis of electrocardiac signals. In this paper is reported a study on them by way of comparison. With the use of filtering method in frequency domain, certain low frequency components were filtered, the time domain waveform was retrieved by IFFT, and the biphase T wave appeared in time domain. After some high frequency components were filtered, time domain wave was retrieved by IFFT, and amplified, the time domain representation of high frequency ECS could be shown obviously, i.e. there was no evident structure in time domain representation of high frequency components in P- and T-waves, but there was evident structure in high frequency components in QRS complex. The duration of QRS depended upon high frequency components, and it was prolonged by filtering certain high frequency components. The slurring of QRS complex was caused by increasing high frequency components, on ventricular depolarized QRS-complex, there were both triangular pulse-like and atriangular pulse-like waveforms, and their power spectrum had both types of feature, single peak and inversepower spectrum. There was no regularity in the spectrum of entire cycle, P- and T-waves, but these was some structure in QRS wave.

Adult↗

Analysis of the T cell receptor V delta region gene repertoire in bronchoalveolar lavage fluid (BALF) and peripheral blood of asthmatics.

OBJECTIVE: To explore the role of gamma delta T cells in the airway of asthmatics and to identify the forces which induce and maintain the inflammatory process. METHODS: Peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were obtained from 7 asthmatic subjects and 7 nonsmoker control subjects. The percentage of gamma delta T cells in the PB and BALF was measured by immunofluorescent staining and flow cytometry. The frequency of usage and the clonality of V delta subfamilies (V delta 1-V delta 3) were assessed by RT-PCR and gene scanning. RESULTS: A higher proportion of gamma delta T cell was detected in the BALF of asthmatic subjects (7.8% +/- 4.7%) than that from control subjects (3.3% +/- 3.0%, P = 0.04). No selective usage for a particular V delta subfamily was found, but the relative expression level of V delta 1 was significantly higher in the asthmatic airway (44% +/- 13%) than in the control (19% +/- 5%, P = 0.0002). In asthmatic subjects, the monoclonal or oligoclonal expansion of gamma delta T lymphocytes was predominant in the BALF, especially V delta 1+ T lymphocytes. CONCLUSIONS: Antigenic specific gamma delta T cells might play an important role in the inducement and maintenance of airway inflammation. Persistent antigenic stimulation may be the key factor that maintains chronic airway inflammation in asthma.

Adult↗