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Biomedical subjects

Ming Zhang

Publications and source records attributed to Ming Zhang.

At least 145 records · Page 8Linked to original sources

[Experimental study on apoptosis in leukemia cells induced by econazole].

To investigate apoptosis of mouse leukemia cell (WEHI-3) induced by econazole and its mechanism, apoptosis induced by econazole was examined by flow cytometry, while free calcium ([Ca(2+)]i) was determined by Fura-2 fluorescein load technique. The protein was isolated from endoplasmic reticulum of WEHI-3 cells, and then the expression of caspase-12 and caspase-7 was evaluated by Western blot. The results showed that WEHI-3 exhibited typical change of apoptosis when it was treated by econazole, [Ca(2+)]i was significantly higher in comparison with the control. The expression of caspase-12 and caspase-7 enhanced as the econazole concentration increased. In conclusion, econazole can induce WEHI-3 cell apoptosis and the caspase-12 plays a key role in this process.

Animals↗

[Cold stress causes early apoptosis in caudal fin cells of Colossoma brachypomum].

CBT cell line developed from a warm-water fish Colossoma Brachypomum,was used to evaluate the effects of cold stress on fish cells. Cell viability was measured by Thiazolyl blue (MTT) method and cellular ultrastructure was examined under transmission electron microscope. Externalization of phosphatidylserine(PS) and mitochondrial membrane potential(MMP) were monitored with confocal laser scanning microscope. Results showed that cell viability and MMP decreased in a time-dependent manner, and the early events of apoptosis such as chromatin condensation, margination and PS externalization occurred, when the cells were exposed to 10 degrees C. It suggested that low temperature (10 degrees C) could induce apoptosis in Colossoma Brachypomum CBT cells.

Animals↗

[Inertial effects on interface pressure between prosthetic socket and residual limb].

A quantitative understanding of interface pressure distribution between prosthetic socket and residual limb is fundamental for an optimal design of prosthesis. Most of traditional finite element (FE) models were static. In this paper a 3-D nonlinear finite element model was developed according to the data of one transtibial amputee. The interface pressures at residual limb were predicted, and the effect of inertial loads was investigated quantitatively. The results show that interface pressures were mainly distributed at patella tendon, lateral tibia, media tibia and popliteal depression regions. Interface pressure had the similar double-peaked waveform in stance phase. The average difference in interface pressure between the two cases with and without consideration of inertial loads was 8.4% in stance phase, while it was up to 20.1% in swing phase with considerably different change trend. It is found that inertial effects during walking can not be ignored.

Artificial Limbs↗

[Advances in the research of differentiation of embryonic stem cells into hepatocytes].

Orthotopic liver transplantation has proven to be effective in the treatment of a variety of life-threatening liver diseases, however, the limitations of donated organs available and long-term immunosuppression provided an impetus for developing alternative therapies. Cell replacement strategies have been one major effective approach for overcoming the obstacles of organ transplantation in recent years. The exogenous cells should be able to proliferate and differentiate into mature hepatic cells after grafting. Use of mature hepatocytes is also hampered by limited tissue source and inability to proliferate and maintain the function for a long term in vitro. Embryonic stem cells are immortal and pluripotent and may provide a novel cell source for potential cell therapy. This review summarizes the mechanisms of controlling early liver development and hepatic differentiation of visceral endoderm in embryoid bodies, and provides an overview of diverse differentiation systems in vitro and in vivo that were applied to hepatic research in recent years. Several studies have demonstrated that ES cell-derived hepatocytes can incorporate into liver tissue and function in vivo , but a few of them have shown complete restoration of liver function after transplantation into mice with liver diseases. Further studies should be made to exploit efficient methods and clinical applications of hepatocytes derived from ES cells in the future. In addition to clinical transplantation for treatment of liver diseases, ES cells can provide a valuable tool for drug discovery applications and study on of molecular basis of hepatic differentiation.

Animals↗

[The dose-effect relationship of water fluoride levels and renal damage in children].

OBJECTIVE: To explore the dose-effect relationship of water fluoride levels and renal damage in children and observe the difference of renal function between high-loaded fluoride people and dental fluorosis people in the same water fluoride level region. METHODS: 210 children were divided into seven groups in term of drinking water fluoride levels and whether they suffered from dental fluorosis. Fluoride concentrations in urine and serum and activities of urine NAG and gamma-GT were determined. RESULTS: The urine and serum fluoride of high-loaded fluoride people and dental fluorosis people increased compared with control, moreover fluoride contents in urine and serum increased gradually with the increase of fluoride level in drinking water. Urine NAG and gamma-GT activities significantly increased in dental fluorosis people from area of 2.58 mg/L fluoride in drinking water and in those two groups from area of 4.51 mg/L fluoride in drinking water. Moreover, there existed an obvious dose-effect relationship between the drinking water fluoride concentration and NAG and gamma-GT activity. CONCLUSION: Over 2.0 mg/L fluoride in drinking water can cause renal damage in children, and the damage degree increases with the drinking water fluoride content. Renal damage degree is not related to whether the children suffered from dental fluorosis and mainly due to water fluoride concentration.

Adolescent↗

[An experimental study on the influence of hypoxia induction factor-1alpha on the glycolysis of the rat myocardial cell under hypoxic condition].

OBJECTIVE: To investigate the influence of hypoxia induction factor-1alpha (HIF-1alpha) on glycosis of rat myocardial cell under hypoxic condition. METHODS: The myocardial cells of the rats were routinely isolated and cultured. The cells were divided into single hypoxia (H) and HIF-1alpha inhibiting (I) groups. The cells in H group were cultured in glucose-free medium with mixed low-oxygen gas [1% O2, 94% N2 and 5% CO2 (v/v)]. While the cells in I group were cultured with low-oxygen gas after the cell model of low expression of HIF-1alpha protein constructed by RNAi technique. The cells in both groups were all observed before hypoxia (routine culture) and at the time points of 1, 3, 6, 12 and 24 hours of hypoxia. The LA (lactate acid ) content in the supernatant of the culture and the activity of the key enzymes in glycolysis such as hexokinase (HK), phosphofructokinase (PFK) and lactate dehydrogenase (LDH) of both groups of cells were determined at all the time points. RESULTS: (1) After hypoxia, the HK and PFK activities of the rat myocardial cells in H and I groups were obviously increased at the beginning and decreased thereafter when compared with that before hypoxia. While the activities of HK and PFK in H group at 1, 3 and 6 hours after hypoxia were evidently higher than those in I group (P <0.05 or 0.01), and the peak activity of them in H and I groups was 159 +/- 13 U/g vs 133 +/- 55 U/g, and 298 +/- 44 U/g vs 188 +/- 55 U/g, respectively. (2) Compared with normal control (92 +/- 12 U/g), the LDH activity of the cells in H group after hypoxia increased significantly, reaching the peak at 6 hours after hypoxia (2 568 +/- 125 U/g, P < 0. 01), and it decreased thereafter, while that in I group peaked at 3 hours after hypoxia (2125 +/- 126 U/g, P <0.01). The LA content in the culture supernatant in H group increased significantly after hypoxia with the passage of time, while that in I group increased in smaller magnitude (P <0.01). CONCLUSION: High expression of HIF-1alpha in the rat myocardial cells after hypoxia could directly cause continuous enhancement of cell glycolysis, which was beneficial to the protection of myocardial cells under hypoxic condition.

Animals↗

[Clustered shoot induction and rapid propagation on Pinellia ternate].

OBJECT: To establish the rapid propagation system of Pinellia ternate. METHOD: The Clustered shoots were induced by the explant lamina and petiole from the terminal bud of Pinellia ternate tuber in test tube. RESULT: The plantlets could regenerate from the lamina and petiole directly without via the callus. The MS Medium with 2.0 mg/L 6-BA and 0.1 mg/L NAA was optimal for the induction of culstered shoots from explants of lamina; the MS with 2.0 mg/L 6-BA and 0.25 mg/L NAA was best for the explants of petiole; and the 1/2 MS with 1.0 mg/L KT and 2.0 mg/L NAA was the better medium for induction of roots. CONCLUSION: The regenerated rate of Pinellia ternata can improve by inducing the clustered shoots from the explants of lamina and petiole directly.

Culture Media↗

5-fluorouracil and hydroxyurea enhance adenovirus-mediated transgene expression in colon and hepatocellular carcinoma cells.

PURPOSE: To investigate the efficient transduction of tumor cells which remains a major limitation of cancer gene therapy. METHODS: In this study, we tested whether treatment with antimetabolic drugs 5-FU and hydroxyurea (HU) could improve adenovirus-mediated gene expression in tumor cells. RESULTS: We found that 5-FU and HU treatment significantly increased beta-gal activity in adenovirus (Ad.CMVBG)-infected human colon carcinoma (LoVo) and hepatocellular carcinoma (SMMC7721) cells in a dose- and time-dependent manner. These increases were maximized at 5.01+/-0.42-fold and 3.32+/-0.32-fold for 5-FU (50 microM), and at 6.60+/-0.50-fold and 4.82+/-0.43-fold for HU (5 mM) treatment, respectively, after 48 h infection. Transient increases in viral uptake, determined by real-time PCR for viral DNA content and by confocal microscopy for viral particles, were observed in 5-FU or HU-treated cells that partially contribute to the overall increases of beta-gal expression. Moreover, mRNA levels for the beta-gal gene in infected cells were significantly increased in both LoVo and SMMC7721 cells by 5-FU and HU treatment in contrast to the inhibition of viral DNA replication and the unchanged mRNA levels for alpha-actin gene. The induction appeared to be the result of enhanced transcription since beta-gal mRNA half-life was not affected by drug treatment. However, similar induction was not detected in CMV-beta-gal-expressing stable cells, suggesting that an adenovirus-associated mechanism might be involved in this induction. CONCLUSIONS: Our findings suggest that it may be possible to improve tumor cell transduction by adenovirus using chemotherapy.

Adenoviridae↗

A role for NF-kappa B subunits p50 and p65 in the inhibition of lipopolysaccharide-induced shock.

To evaluate the possibility that NF-kappaB subunits p50 and p65 have a role in limiting the systemic inflammatory response induced by endotoxin, we compared the susceptibility of wild-type (WT), p65+/-, p50-/-, and p50-/-p65+/- (3X) mice to LPS-induced shock. Interestingly, whereas p65+/- mice were no more sensitive than WT mice to LPS-induced shock, 3X mice were exquisitely sensitive to the toxic effects of LPS. Mice lacking p50 alone displayed an intermediate phenotype. Sensitivity to LPS was a property of the innate immune system and was characterized by elevated circulating levels of TNF in both p50-/- and 3X mice. The ability of LPS to induce shock depended upon TNF, and 3X mice were significantly more sensitive to the toxic effects of TNF than were p50-deficient mice. The expression of several LPS-inducible proinflammatory genes, including IFN-gamma, was significantly higher within the spleens of p50-/- mice than in the spleens of WT mice, and interestingly, the expression of IFN-gamma was augmented still further within the spleens of 3X mice. These results demonstrate that NF-kappaB subunits p50 and p65 have critical inhibitory functions during the systemic response to LPS and raise the possibility that these functions could be essential in preventing mortality associated with systemic inflammatory response syndromes.

Animals↗

Improving conformational searches by geometric screening.

MOTIVATION: Conformational searches in molecular docking are a time-consuming process with wide range of applications. Favorable conformations of the ligands that successfully bind with receptors are sought to form stable ligand-receptor complexes. Usually a large number of conformations are generated and their binding energies are examined. We propose adding a geometric screening phase before an energy minimization procedure so that only conformations that geometrically fit in the binding site will be prompted for energy calculation. RESULTS: Geometric screening can drastically reduce the number of conformations to be examined from millions (or higher) to thousands (or lower). The method can also handle cases when there are more variables than geometric constraints. An early-stage implementation is able to finish the geometric filtering of conformations for molecules with up to nine variables in 1 min. To the best of our knowledge, this is the first time such results are reported deterministically. CONTACT: mzhang@mdanderson.org.

Algorithms↗

Structural characterization of a 2-O-acetylglucomannan from Dendrobium officinale stem.

A heteropolysaccharide obtained from an aqueous extract of dried stem of Dendrobium officinale Kimura and Migo by anion-exchange chromatography and gel-permeation chromatography, was investigated by chemical techniques and NMR spectroscopy, and is demonstrated to be a 2-O-acetylglucomannan, composed of mannose, glucose, and arabinose in 40.2:8.4:1 molar ratios. It has a backbone of (1-->4)-linked beta-d-mannopyranosyl residues and beta-d-glucopyranosyl residues, with branches at O-6 consisting of terminal and (1-->3)-linked Manp, (1-->3)-linked Glcp, and a small proportion of arabinofuranosyl residues at the terminal position. The acetyl groups are substituted at O-2 of (1-->4)-linked Manp and Glcp. The main repeating unit of the polysaccharides is reported.

Carbohydrate Sequence↗

Multiple functions of maspin in tumor progression and mouse development.

Maspin is a unique serpin with diverse biological functions. Initially identified from human normal mammary epithelial cells, maspin expression is either reduced or completely silenced in breast cancers. Numerous studies have implicated maspin function in cancer progression and angiogenesis. Maspin has also been targeted for breast cancer gene therapy. Recently, transgenic and gene knockout mouse models have been used by our laboratory to identify the biological functions of maspin in vivo. In this review, we summarize the multiple functions of maspin in tumor progression and mouse development. These data demonstrate that maspin not only plays a role in tumor progression and metastasis but also is a key regulatory molecule for normal mammary gland and embryonic development.

Animals↗

Cluster models of dose-volume effects.

PURPOSE: Describe cluster models, normal-tissue complication probability models in which both the number and the spatial location of radiation-sterilized functional subunits play a role in defining complication probability. METHODS AND MATERIALS: Computer simulation was used to determine the maximum size cluster of sterilized subunits associated with a given dose distribution. Complications were associated with large clusters. RESULTS: Cluster models showed a volume effect, as increasing effect for constant dose when the volume increased or constant effect when the dose was reduced with increasing volume. Cluster models gave similar results to existing models when tissues were irradiated uniformly. With inhomogeneous dose distributions, on the other hand, different spatial distributions of "hot spots" may lead to different predictions of complication probability by cluster models. The result was that a higher complication probability resulted when hot spots were contiguous (clustered) than when they were dispersed, even if both situations are characterized by the same dose-volume histogram. A potential advantage of cluster models is to provide an easy, internally consistent way to predict complications arising from the inhomogeneous dose distributions that sometimes arise with intensity-modulated radiotherapy. CONCLUSION: Cluster models offer a new way to quantify complication probability in treatment situations in which a wide variety of hot-spot distributions occur.

Animals↗

Third-generation superoxide anion sensor based on superoxide dismutase directly immobilized by sol-gel thin film on gold electrode.

A third-generation biosensor for superoxide anion (O(2)*-) was developed based on superoxide dismutase (SOD) immobilized by thin silica-PVA sol-gel film on gold electrode surface. A rapid and direct electron transfer of SOD in the thin sol-gel film at the gold electrode was realized without any mediators or promoters. The characterization of the SOD electrodes showed a quasi-reversible electrochemical redox behavior with a formal potential of 80 + 5 mV (versus SCE) in 50 mmol l(-1) phosphate buffer solution (PBS), pH 7.0. The heterogeneous electron transfer rate constant was evaluated to be about 2.1s(-1). The anodic and cathodic transfer coefficients are 0.6 and 0.4, respectively. Based on biomolecular recognition for specific reactivity of SOD toward O(2)*- the SOD electrode was applied to a sensitive and selective measurement of O(2)*- with the low operation potential (-0.15 V versus SCE) in phosphate buffer solution, pH 7.0. The amperometric response was proportional to O(2)*- concentration in the range of 0.2-1.6 micromol l(-1) and the detection limit was 0.1 micromol l(-1) at a signal-to-noise ration of 3. The preparation of SOD electrode is easy and simple. The uniform porous structure of the silica-PVA sol-gel matrix results in a fast response rate of immobilized SOD and is very efficient for stabilizing the enzyme activity.

Biosensing Techniques↗

Tamoxifen induces the expression of maspin through estrogen receptor-alpha.

Maspin (mammary serine protease inhibitor) is a tumor suppressor gene that plays an important role in inhibiting tumor growth, invasion and metastasis. Maspin expression is down regulated at transcription level in primary and metastatic breast tumor cells. Previous studies on hormonal regulation of maspin prompt us to test whether an estrogen antagonist tamoxifen (TAM) can exert its anti-tumor function by up regulating maspin gene expression. For this purpose, we first tested whether maspin promoter could be activated in normal and several breast tumor cells. We then carried out a series of promoter analysis in which estrogen receptors and TAM were reconstituted in an in vitro cell culture system. Here we report our new finding that tumor suppresser gene maspin is one of the TAM target genes. TAM induces a maspin/luciferase reporter in cell culture and this induction requires the presence of (estrogen receptor alpha) ERalpha but not estrogen receptor-beta (ERbeta). Maspin promoter deletion and mutation analysis showed that the cis element(s) within a region between -90and+87 bp but not the HRE site (-272 bp) was involved in TAM induction of maspin expression. TAM bound ERalpha may directly control maspin gene expression through the interaction with cofactor (s). Analysis using several ERalpha mutants showed that the N-terminal A/B motif (AF-1) was critical for maspin basal level transcription activation. An ERalpha mutant with point mutations at DNA binding domain abolished estrogen induction of an ERE-luciferase reporter but was still active in activating maspin promoter by TAM. LBD-AF2 domain was required for ERalpha-dependent TAM induction. Deletion of LBD-AF2 or a point mutation in the ERalpha LBD-AF2 region (LBDmtL539A) completely abolished the activation of maspin promoter, suggesting that TAM induction of maspin involves the recruitment of cofactor(s) by ERalpha to the maspin promoter region. This finding indicates that one of the pathways for cancer prevention and tumor inhibition by TAM is mediated through the activation of tumor suppressor gene maspin in breast cancer.

Animals↗

Hormonal defect in maspin heterozygous mice reveals a role of progesterone in pubertal ductal development.

Progesterone and PR are mainly thought to affect tertiary ductal side branching and alveologenesis in late stage of mammary gland development. Here, we present evidence that they also play a role in early ductal development. This conclusion derived from our analysis of maspin heterozygous (Mp+/-) mice that showed defective ductal development at puberty. The defect was due to a reduced systemic level of progesterone. We show that treatment of Mp+/- mice with progesterone rescued the defect of ductal development. When both wild-type and Mp+/- mice were ovariectomized at 4 wk of age, treatment with progesterone alone can stimulate their ductal growth. In addition, treatment of wild-type mice with the progesterone inhibitor RU486 slowed ductal development in a dose-dependent manner. To confirm that progesterone receptor (PR) was required for progesterone action in ductal development at pubertal stage, we treated ovariectomized PR-deficient (PRKO) and wild-type mice with progesterone and examined ductal development at 7 wk of age. Whereas wild-type mammary glands displayed abundant ductal growth after progesterone treatment, there was a significant retardation of ductal growth in PRKO mice. Furthermore, we observed reduced ductal development in intact PRKO mice at 7 wk of age compared with that of wild-type mice. However, the defect was rescued at late stage of mammary development in PRKO mice. These data demonstrate that progesterone signaling, which is mediated by PR, plays an important role in early ductal development. In PRKO mice, a compensatory mechanism occurs that rescues the ductal defect at a late stage of mammary development.

Animals↗

Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin.

Human and simian immunodeficiency viruses (HIV and SIV), influenza virus, and hepatitis C virus (HCV) have heavily glycosylated, highly variable surface proteins. Here we explore N-linked glycosylation site (sequon) variation at the population level in these viruses, using a new Web-based program developed to facilitate the sequon tracking and to define patterns (www.hiv.lanl.gov). This tool allowed rapid visualization of the two distinctive patterns of sequon variation found in HIV-1, HIV-2, and SIV CPZ. The first pattern (fixed) describes readily aligned sites that are either simply present or absent. These sites tend to be occupied by high-mannose glycans. The second pattern (shifting) refers to sites embedded in regions of extreme local length variation and is characterized by shifts in terms of the relative position and local density of sequons; these sites tend to be populated by complex carbohydrates. HIV, with its extreme variation in number and precise location of sequons, does not have a net increase in the number of sites over time at the population level. Primate lentiviral lineages have host species-dependent levels of sequon shifting, with HIV-1 in humans the most extreme. HCV E1 and E2 proteins, despite evolving extremely rapidly through point mutation, show limited sequon variation, although two shifting sites were identified. Human influenza A hemagglutinin H3 HA1 is accumulating sequons over time, but this trend is not evident in any other avian or human influenza A serotypes.

Animals↗