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Biomedical subjects

Li Zeng

Publications and source records attributed to Li Zeng.

65 records · Page 4Linked to original sources

Bioreactors mediate the effectiveness of tissue engineering scaffolds.

We hypothesized that the mechanically active environment present in rotating bioreactors mediates the effectiveness of three-dimensional (3D) scaffolds for cartilage tissue engineering. Cartilaginous constructs were engineered by using bovine calf chondrocytes in conjunction with two scaffold materials (SM) (benzylated hyaluronan and polyglycolic acid); three scaffold structures (SS) (sponge, non-woven mesh, and composite woven/non-woven mesh); and two culture systems (CS) (a bioreactor system and petri dishes). Construct size, composition [cells, glycosaminoglycans (GAG), total collagen, and type-specific collagen mRNA expression and protein levels], and mechanical function (compressive modulus) were assessed, and individual and interactive effects of model system parameters (SM, SS, CS, SM*CS and SS*CS) were demonstrated. The CS affected cell seeding (higher yields of more spatially uniform cells were obtained in bioreactor-grown than dish-grown 3-day constructs) and subsequently affected chondrogenesis (higher cell numbers, wet weights, wet weight GAG fractions, and collagen type II levels were obtained in bioreactor-grown than dish-grown 1-month constructs). In bioreactors, mesh-based scaffolds yielded 1-month constructs with lower type I collagen levels and four-fold higher compressive moduli than corresponding sponge-based scaffolds. The data imply that interactions between bioreactors and 3D tissue engineering scaffolds can be utilized to improve the structure, function, and molecular properties of in vitro-generated cartilage.

Animals↗

Shh establishes an Nkx3.2/Sox9 autoregulatory loop that is maintained by BMP signals to induce somitic chondrogenesis.

Prior work has established that transient Shh signals from the notochord and floor plate confer a competence in somitic tissue for subsequent BMP signals to induce chondrogenesis. We have therefore proposed that Shh induces a factor(s) that renders somitic cells competent to chondrify in response to subsequent BMP signals. Recently, we have shown that forced expression of Nkx3.2, a transcriptional repressor induced by Shh, is able to confer chondrogenic competence in somites. In this work, we show that administration of Shh or forced Nkx3.2 expression induces the expression of the transcription factor Sox9 in the somitic tissue. Forced expression of Sox9 can, in turn, induce robust chondrogenesis in somitic mesoderm, provided that BMP signals are present. We have found that in the presence of BMP signals, Sox9 and Nkx3.2 induce each other's expression. Thus, Nkx3.2 may promote axial chondrogenesis by derepressing the expression of Sox9 in somitic mesoderm. Furthermore, forced expression of either Sox9 or Nkx3.2 not only activates expression of cartilage-specific genes in somitic mesoderm, but also promotes the proliferation and survival of the induced chondrocytes in the presence of BMP signals. However, unlike Nkx3.2, Sox9 is able to induce de novo cartilage formation in non-cartilage-forming tissues. Our findings suggest that Shh and BMP signals work in sequence to establish a positive regulatory loop between Sox9 and Nkx3.2, and that Sox9 can subsequently initiate the chondrocyte differentiation program in a variety of cellular environments.

Animals↗

A novel splice variant of the cell adhesion molecule contactin 4 ( CNTN4) is mainly expressed in human brain.

Axon-associated cell adhesion molecules (AxCAMs) of the immunoglobulin superfamily play important roles in the formation, maintenance, and plasticity of functional neuronal networks. Contactin4 ( CNTN4, BIG-2) is a member of the TAG-1/F3 subgroup of AxCAMs. We have cloned a novel splice variant of CNTN4, and term it CNTN4A. The complete nucleotide sequence of CNTN4 is also obtained by combining the insert sequences of two clones, which were isolated when screening the human fetal brain cDNA library with CNTN4A as a probe. CNTN4A protein has an N-terminal cleavable signal peptide, two FNIII-like domains, and a glycosyl phosphatidylinositol-anchoring domain. According to the search of the human genome database, CNTN4 was mapped to 3p25-26, a region very close to the breakpoints of the 3p syndrome. Expression analysis of CNTN4A shows that CNTN4A is mainly expressed in brain.

Alternative Splicing↗

Identification of a novel human DDX40gene, a new member of the DEAH-box protein family.

The DExH/D-box superfamily of RNA helicases seems to play key roles during RNA metabolism, such as pre-mRNA splicing, ribosome biogenesis, and others. We have cloned a new gene of the DEAH-box protein subgroup, designated DDX40 (DEAD/H-box polypeptide 40 gene). DDX40 contains 3656 nucleotides and codes for a putative 779-amino-acid protein. Sequence analysis of the cDNA product revealed that it contained a DEAH (Asp-Glu-Ala-His) sequence motif and other conserved motifs. The DDX40 protein shared 53% and 43% amino acid identity with human DDX8 and yeast Drh1, respectively, in the conserved region. Northern blot analysis showed that DDX40 was expressed ubiquitously in the eight tissues examined, implying a general physiological function of the protein. We speculate that, like other members of the DExH/D-box superfamily, DDX40 may play roles in pre-mRNA splicing, ribosome biogenesis and other RNA processing functions.

Amino Acid Sequence↗

Identification and characterization of AGTRAP, a human homolog of murine Angiotensin II Receptor-Associated Protein (Agtrap).

Several classes of cytoplasmic proteins have been found to interact specifically with the carboxyl-terminal cytoplasmic region of the angiotensin II type 1 (AT(1)) receptor to regulate different aspects of AT(1) receptor physiology. The murine Angiotensin II Receptor-Associated Protein (Agtrap) is a new member of them. We have recently cloned a new human gene cDNA that codes for a homolog of the murine Agtrap protein from a human fetal brain cDNA library. The deduced polypeptide product of the cDNA is 22 kDa in size, and its DNA and amino acid sequences are 85 and 77% identical to those of the mouse Agtrap gene, respectively. Hence we have named it the human Angiotensin II Receptor-Associated Protein (AGTRAP) gene. The mRNA of AGTRAP was most abundantly expressed in kidney, heart, pancreas and thyroid. Using the yeast two-hybrid screening of a human fetal brain cDNA library, we have identified a new interaction partner of the human AGTRAP protein, RACK1 (Receptor of Activated Protein C Kinase). The AGTRAP-RACK1 interaction was confirmed by GST fusion protein pull-down assays, co-immunoprecipitation and surface plasmon resonance. We suggest that the AGTRAP-RACK1 interaction may help to recruit signaling complex to the AT(1) receptor to affect AT(1) receptor signaling.

Adaptor Proteins, Signal Transducing↗

Cloning and characterization of a novel human transcription factor AP-2 beta like gene (TFAP2BL1).

The AP-2 transcription factor has been shown to play an important role in development, morphogenesis, apoptosis, cell-cycle control and has also been implicated in mammary oncogenesis. Here we report the cloning and characterization of a novel human transcription factor AP-2 like gene (TFAP2BL1), which is located on human chromosome 6p12.1-21.1. The TFAP2BL1 cDNA is 2076 base pairs in length, encoding a 452-amino acid polypeptide related to human Ap-2protein. TFAP2BL1 gene has significantly high homology to transcription factor AP-2 gene of human, mouse, chicken, sheep, fruit fly, and C. elegans at amino acid level. RT-PCR analysis shows its relatively high expression level in adult thymus, prostate, small intestine, skeletal muscle, placenta, brain, and testis tissues.

Amino Acid Sequence↗

Cloning, expression and characterization of a novel human VMP gene.

We report here cloning and characterization of a novel human gene, termed VMP, which is a vesicular membrane protein. RT-PCR analysis shows that VMP is expressed exclusively in brain of the 16 tissues examined, suggesting that it is a neuron-specific membrane protein. The cDNA encodes 195 amino acid with a putative molecular weight of about 24 KDa. VMP contains two putative membrane spanning domains and a hydrophilic tail homologous to the microtubule-binding domain of MAPs. So it is speculated that VMP may associated with microtubules through its C-terminal and plays an important role in vesicular organelles transport and nerve signals.

Base Sequence↗

Cloning and characterization of a novel human STAR domain containing cDNA KHDRBS2.

KHDRBS2, KH domain containing, RNA binding, signal transduction associated 2, is an RNA-binding protein that is tyrosine phosphorylated by Src during mitosis. It contains a KH domain,which is embedded in a larger conserved domain called the STAR domain. This protein has a 99% sequence identity with rat SLM-1 (the Sam68-like mammalian protein 1) and 98% sequence identity with mouse SLM-1 in its STAR domain. KHDRBS2 has the characteristic Sam68 SH2 and SH3 domain binding sites. RT-PCR analysis showed its transcript is ubiquitously expressed. The characterization of KHDRBS2 indicates it may link tyrosine kinase signaling cascades with some aspect of RNA metabolism.

Amino Acid Sequence↗

Four-dimensional wavelet compression of arbitrarily sized echocardiographic data.

Wavelet-based methods have become most popular for the compression of two-dimensional medical images and sequences. The standard implementations consider data sizes that are powers of two. There is also a large body of literature treating issues such as the choice of the "optimal" wavelets and the performance comparison of competing algorithms. With the advent of telemedicine, there is a strong incentive to extend these techniques to higher dimensional data such as dynamic three-dimensional (3-D) echocardiography [four-dimensional (4-D) datasets]. One of the practical difficulties is that the size of this data is often not a multiple of a power of two, which can lead to increased computational complexity and impaired compression power. Our contribution in this paper is to present a genuine 4-D extension of the well-known zerotree algorithm for arbitrarily sized data. The key component of our method is a one-dimensional wavelet algorithm that can handle arbitrarily sized input signals. The method uses a pair of symmetric/antisymmetric wavelets (10/6) together with some appropriate midpoint symmetry boundary conditions that reduce border artifacts. The zerotree structure is also adapted so that it can accommodate noneven data splitting. We have applied our method to the compression of real 3-D dynamic sequences from clinical cardiac ultrasound examinations. Our new algorithm compares very favorably with other more ad hoc adaptations (image extension and tiling) of the standard powers-of-two methods, in terms of both compression performance and computational cost. It is vastly superior to slice-by-slice wavelet encoding. This was seen not only in numerical image quality parameters but also in expert ratings, where significant improvement using the new approach could be documented. Our validation experiments show that one can safely compress 4-D data sets at ratios of 128:1 without compromising the diagnostic value of the images. We also display some more extreme compression results at ratios of 2000:1 where some key diagnostically relevant key features are preserved.

Algorithms↗

[Correlation and significance of E-cadherin and N-cadherin expression in prostate cancer].

BACKGROUND & OBJECTIVE: Decreased expression of E-Cadherin correlated with many kinds of cancer, but inappropriate expression of N-cadherin has been reported in breast cancer recently, which has a more distinct and direct role in promoting cancer cell motility than E-cadherin. The aim of this study was to investigate the correlation between E-Cadherin and N-Cadherin expression with the grade and stage of prostate cancer and their relationship with prostate specific antigen (PSA). METHODS: E-Cadherin and N-Cadherin expression in 56 prostate cancer samples were determined by immunohistochemical staining. RESULTS: Twenty-four patients (43%) were positive and 32 patients (57%) were negative in E-Cadherin expression. Eighteen patients (32%) were negative and 38 patients (68%) were positive in N-Cadherin expression. E-Cadherin and N-Cadherin were significantly related to the grade and stage of cancer and the change of F/T ratio (free prostate specific antigen/total prostate specific antigen ratio). There was no significant relationship between Cadherin expression and total prostate specific antigen (tPSA) or free prostate specific antigen (fPSA). CONCLUSION: E-Cadherin and N-Cadherin abnormal expressions may serve as the indicators to malignant degree and prognosis of the prostate cancer.

Aged↗

[Tumor relevance analysis of a highly conserved gene by using gene microarray hybridization].

Preliminary function research of a highly conserved human gene,which was cloned from human fetal cDNA library during large-scale cDNA sequencing,is illustrated in this article. Bioinformatics analysis indicates that this gene is highly conserved in human, mouse, fruit fly, thaliana and fission yeast. Other bioinformatics analysis implies its relevance with tumors. RT-PCR analysis shows its wide-ranging expression patterns. Its expression in 16 cancer cases (including 7 liver cancer cases, 5 pancreas cancer cases, 2 larynx cancer cases and 2 lung cancer cases) is studied by using gene microarray analysis. The result shows its relevance with tumors and implies it may have different status in different classification of tumors.

English Abstract↗