Biomedical subjects

Yong Mao

Publications and source records attributed to Yong Mao.

13 recordsLinked to original sources

PubMed2007

Continuous requirement for pp60-Src and phospho-paxillin during fibronectin matrix assembly by transformed cells.

Fibronectin (FN) matrix assembly is an integrin-mediated process that is regulated by both the extracellular environment and intracellular signaling pathways. The activity of Src-family kinases is important for initiation of FN assembly by normal fibroblasts. Here we report that in HT1080 fibrosarcoma cells, Src kinase activity is required not only for the assembly of FN matrix but also for the maintenance of FN matrix fibrils at the cell surface. Dexamethasone-induced FN fibril formation by these cells was completely blocked for at least 24 h when Src-family kinase activity was inhibited by either PP1 or SU6656. Inhibition of Src after significant matrix had already been assembled, resulted in an increased rate of loss of detergent-insoluble FN. Binding of activation-dependent integrin antibodies reveals a role for Src in maintaining integrin activity. The requirement for Src kinase activity appears to depend, in part, on phosphorylation of paxillin at tyrosine 118 (Y118). Phospho-paxillin co-localized with FN fibrils, and overexpression of GFP-paxillin but not of GFP-paxillinY118F enhanced cell-mediated assembly of FN. Our results indicate that Src maintains FN matrix at the cell surface through its effect on integrin activity and paxillin phosphorylation.

Antineoplastic Agents, Hormonal↗

PubMed2006

Three-dimensional finite element analysis of weakened roots restored with different cements in combination with titanium alloy posts.

BACKGROUND: It is very difficult and relatively unpredictable to preserve and restore severely weakened pulpless roots. To provide much needed benefit basis for clinical practice, this study was carried out to analyze the stress distribution in weakened roots restored with different cements in combination with titanium alloy posts. Finite element analysis (FEA) was employed in the study. METHODS: A pseudo three-dimensional model of a maxillary central incisor with flared root canal, theoretically restored with titanium alloy posts in combination with different cements, was established. The analysis was performed by use of ANSYS software. The tooth was assumed to be isotropic, homogenous and elastic. A load of 100 N at an angle of 45 degrees to the longitudinal axis was applied at the palatal surface of the crown. The distributions of stresses in weakened roots filled with cements of different elastic modulus were analyzed by the three-dimensional FEA model. RESULTS: Several stress trends were observed when the stress cloud atlas obtained in the study was analyzed. With the increase of the elastic modulus of cements from 1.8 GPa to 22.4 GPa, the stress values in dentin decreased from 39.58 MPa to 31.43 MPa and from 24.51 MPa to 20.76 MPa (respectively, for maximum principle stress values and Von Mises stress values). When Panavia F and zinc phosphate cement were used, the stress peak values in dentin were very small with no significant difference observed, and the Von Mises stress values were 20.87 MPa and 20.76 MPa respectively. On the other hand, maximum principle stress value and Von Mises stress value in cement layer increased with the increase of the elastic modulus of cements. CONCLUSIONS: The result of this study demonstrated that elastic modulus was indeed one of the important parameters to evaluate property of the cements. Our three-dimensional FEA model study also found that the cement with elastic modulus similar to that of dentin could reinforce weakened root and reduce the stress in dentin. Thus, it may be a better choice for the restoration of weakened roots in clinical practice.

Adult↗

PubMed2006

Effects of insulin-like growth factor I on the development of osteoblasts in hyperglycemia.

The delayed wound healing of tooth extraction, the activation of alveolar absorption and the being hindered bone formation around the implants in diabetes are difficult to be solved for dentists. So, the aim of the study was to investigate the influences of hyperglycemia and insulin-like growth factor I (IGF-I) on osteoblasts. Osteoblasts were cultured in different conditions: normal glucose, mimic hyperglycemia, hyperglycemia with IGF-I, hyperglycemia with insulin. The proliferation and mineralization of osteoblasts were observed. As abnormal transport of glucose involved in the development of chronic complications in diabetes. The expression of glucose transporter 1 (GLUT1) was further evaluated by RT-PCR, immunofluorescence and Western blot in different groups. These results showed that hyperglycemia increased the proliferation and inhibited the mineralization of osteoblasts, while IGF-I seemed to reverse these effects. The levels of GLUT1 mRNA and protein in hyperglycemia were elevated by 51% and 35%, respectively, compared with that in normal glucose, while the levels in hyperglycemia with IGF-I were almost the same as that in normal glucose. In conclusion, the increased expression of GLUT1 may contribute to the delayed mineralization of osteoblasts in hyperglycemia. Also IGF-I may be a new drug for diabetic bone disease through normalizing the expression of GLUT1.

Animals↗

PubMed2006

Modulation of cell-fibronectin matrix interactions during tissue repair.

Environmental signals from the extracellular matrix (ECM) are transmitted by cell surface receptors that connect to the actin cytoskeleton and to multiple intracellular signaling pathways. To dissect how the ECM regulates cell functions, we are using a three-dimensional (3D) fibrin-fibronectin matrix, resembling the wound provisional matrix. Fibroblasts adhere to fibronectin in this matrix via concomitant engagement of alpha 5 beta 1 integrin receptors and syndecan-4, a transmembrane proteoglycan. An adhesive phenotype is developed with actin stress fibers and activation of focal adhesion kinase (FAK) and Rho GTPase. Lack of syndecan-4 engagement, as occurs in the presence of the ECM protein tenascin-C, promotes a motile phenotype; FAK and Rho signaling are downregulated and filopodia are extended. Fibronectin matrices have distinct effects on two other receptors: alpha 4 beta 1 and beta v beta 3 integrins. Although alpha 4 beta 1 does not naturally support strong cell interactions with a fibrin-fibronectin matrix, binding is dramatically enhanced by proteolytic cleavage of fibronectin. Conversely, activity of alpha v beta 3 is stimulated by multimeric fibronectin fibrils showing that the organization of fibronectin differentially affects integrin functions. Thus, deposition of additional ECM components, expression of co-receptors for ECM, cleavage of adhesive proteins, and the architecture of the ECM microenvironment are different mechanisms for modulating cell responses to fibronectin matrix.

Animals↗

PubMed2005

Stimulatory effects of a three-dimensional microenvironment on cell-mediated fibronectin fibrillogenesis.

The assembly of fibronectin into a fibrillar matrix is a regulated step-wise process that involves binding to integrin receptors and interactions between fibronectin molecules. This process has been studied extensively using cells in two-dimensional (2D) monolayer culture. In most situations in vivo, however, matrix assembly occurs within existing three-dimensional (3D) extracellular matrix networks. In an attempt to mimic this environment, we analyzed matrix assembly by fibroblasts cultured on a pre-assembled 3D fibronectin matrix and found significant stimulation of fibronectin fibril assembly compared to cells in 2D culture. Lower amounts of fibronectin were needed to initiate the assembly process, fibrils accumulated to higher density, and the 3D fibril organization played a key role in the stimulatory effect. Moreover, cells expressing activation-dependent integrins were able to assemble fibronectin matrix without exogenous stimulation, suggesting regulatory effects of the 3D fibronectin matrix on integrin activity. These results provide evidence for an additional level of control of fibronectin deposition through cell interactions with the local microenvironment.

Animals↗

PubMed2005

Multiclass cancer classification by using fuzzy support vector machine and binary decision tree with gene selection.

We investigate the problems of multiclass cancer classification with gene selection from gene expression data. Two different constructed multiclass classifiers with gene selection are proposed, which are fuzzy support vector machine (FSVM) with gene selection and binary classification tree based on SVM with gene selection. Using F test and recursive feature elimination based on SVM as gene selection methods, binary classification tree based on SVM with F test, binary classification tree based on SVM with recursive feature elimination based on SVM, and FSVM with recursive feature elimination based on SVM are tested in our experiments. To accelerate computation, preselecting the strongest genes is also used. The proposed techniques are applied to analyze breast cancer data, small round blue-cell tumors, and acute leukemia data. Compared to existing multiclass cancer classifiers and binary classification tree based on SVM with F test or binary classification tree based on SVM with recursive feature elimination based on SVM mentioned in this paper, FSVM based on recursive feature elimination based on SVM can find most important genes that affect certain types of cancer with high recognition accuracy.

Journal Article↗

PubMed2005

Fibronectin fibrillogenesis, a cell-mediated matrix assembly process.

The extracellular matrix provides a framework for cell adhesion, supports cell movement, and serves to compartmentalize tissues into functional units. Fibronectin is a core component of many extracellular matrices where it regulates a variety of cell activities through direct interactions with cell surface integrin receptors. Fibronectin is synthesized by many adherent cells which then assemble it into a fibrillar network. The assembly process is integrin-dependent and fibronectin-integrin interactions initiate a step-wise process involving conformational activation of fibronectin outside and organization of the actin cytoskeleton inside. During assembly, fibronectin undergoes conformational changes that expose fibronectin-binding sites and promote intermolecular interactions needed for fibril formation. In this review, the main steps of fibronectin assembly are described and recent studies on fibronectin conformational changes are discussed.

Actins↗

PubMed2005

Constructing support vector machine ensembles for cancer classification based on proteomic profiling.

In this study, we present a constructive algorithm for training cooperative support vector machine ensembles (CSVMEs). CSVME combines ensemble architecture design with cooperative training for individual SVMs in ensembles. Unlike most previous studies on training ensembles, CSVME puts emphasis on both accuracy and collaboration among individual SVMs in an ensemble. A group of SVMs selected on the basis of recursive classifier elimination is used in CSVME, and the number of the individual SVMs selected to construct CSVME is determined by 10-fold cross-validation. This kind of SVME has been tested on two ovarian cancer datasets previously obtained by proteomic mass spectrometry. By combining several individual SVMs, the proposed method achieves better performance than the SVME of all base SVMs.

Algorithms↗

PubMed2005

Parameters selection in gene selection using Gaussian kernel support vector machines by genetic algorithm.

In microarray-based cancer classification, gene selection is an important issue owing to the large number of variables and small number of samples as well as its non-linearity. It is difficult to get satisfying results by using conventional linear statistical methods. Recursive feature elimination based on support vector machine (SVM RFE) is an effective algorithm for gene selection and cancer classification, which are integrated into a consistent framework. In this paper, we propose a new method to select parameters of the aforementioned algorithm implemented with Gaussian kernel SVMs as better alternatives to the common practice of selecting the apparently best parameters by using a genetic algorithm to search for a couple of optimal parameter. Fast implementation issues for this method are also discussed for pragmatic reasons. The proposed method was tested on two representative hereditary breast cancer and acute leukaemia datasets. The experimental results indicate that the proposed method performs well in selecting genes and achieves high classification accuracies with these genes.

Algorithms↗

PubMed2005

[A hydrostatic compression device capable of generating both intermittent compressive forces and continuous compressive forces].

A hydrostatic compression device has been designed to study the effects of intermittent or continuous compressive forces on cells by trying to mimic in vivo forces. The model system is composed of two pistons that deliver and release compressed air under control of a motor to form an enclosed tissue culture chamber housing numerous tissues culture dishes. The continuous compressive forces and intermittent compressive forces are within 100-300 KPa and 0-30 KPa respectively. The compressive force is uniform in the system and can also result in the generation of shear forces along the interface between the cells and culture substratum, so the hydrostatic compression device can be used to study the characteristics of in vitro cells loading models.

Biomechanical Phenomena↗

PubMed2004

Spatial and temporal variability in schistosome cercarial density detected by mouse bioassays in village irrigation ditches in Sichuan, China.

A mouse bioassay was used monthly over the infection season of 2001 to determine the temporal and spatial variability of schistosome cercarial density in irrigation ditches in five villages in southwestern Sichuan Province in the People's Republic of China. Analysis of variance showed that approximately half of the variability was due to the village and site within the village, with little contribution from air temperature, weekly average rainfall, or the month within the infection season in which the bioassay was performed. The location-specific variability in these data suggest that epidemiologic studies will generally have low power to detect the influence of water-contact intensity on human parasite burden without taking account of variations in cercarial density at sites of water contact.

Animals↗

PubMed2003

The topoisomerase IIbeta circular clamp arrests transcription and signals a 26S proteasome pathway.

It has been proposed that the topoisomerase II (TOP2)beta-DNA covalent complex arrests transcription and triggers 26S proteasome-mediated degradation of TOP2beta. It is unclear whether the initial trigger for proteasomal degradation is due to DNA damage or transcriptional arrest. In the current study we show that the TOP2 catalytic inhibitor 4,4-(2,3-butanediyl)-bis(2,6-piperazinedione) (ICRF-193), which traps TOP2 into a circular clamp rather than the TOP2-DNA covalent complex, can also arrest transcription. Arrest of transcription, which is TOP2beta-dependent, is accompanied by proteasomal degradation of TOP2beta. Different from TOP2 poisons and other DNA-damaging agents, ICRF-193 did not induce proteasomal degradation of the large subunit of RNA polymerase II. These results suggest that proteasomal degradation of TOP2beta induced by the TOP2-DNA covalent complex or the TOP2 circular clamp is due to transcriptional arrest but not DNA damage. By contrast, degradation of the large subunit of RNA polymerase II is due to a DNA-damage signal.

Animals↗

PubMedDate not supplied

Accessibility to the fibronectin synergy site in a 3D matrix regulates engagement of alpha5beta1 versus alphavbeta3 integrin receptors.

Cell adhesion and migration on fibronectin (FN) extracellular matrix are mediated by integrin receptors. Integrins alpha5beta1 and alphavbeta3 require the RGD cell-binding sequence in FN, but alpha5beta1 also requires the nearby synergy site for maximal binding. In this study, we investigated how differences in the numbers of RGD or synergy sites within a three-dimensional (3D) FN-rich matrix influence cell adhesion and migration. CHO cell adhesion, spreading, and migration were reduced on 3D chimeric matrix containing FN lacking RGD (FN(RGD-)). Incorporation of FN with mutation of the synergy site (FN(syn-)), however, resulted in selective usage of integrins. CHO cells expressing alpha5beta1 showed decreased interactions with FN(syn-) chimeric matrix. In contrast, the presence of FN(syn-) had no effect on CHOalphavbeta3 cell migration. Interestingly, CHOalpha5/alphavbeta3 cells expressing both integrins selectively used alpha5beta1 for migration on wild type FN matrix but preferred alphavbeta3 for migration on FN(syn-) chimeric matrix. Thus sequestration or exposure of the FN synergy site within a 3D matrix may represent a novel mechanism for regulating cell functions through differential usage of integrin receptors. [Supplementary materials are available for this article. Go to the publisher's online edition of Cell Communication and Adhesion for the following free supplemental resource: a video recording shows migration of HT1080 cells on 3D matrix. HT1080 cells were allowed to attach to the matrix in serum-free DMEM for 2 h. FBS was then added to the medium to a final concentration of 10% and video recording was started. Images were taken every 5 min for 2 h. The video plays at 6 frames/s.].

Animals↗