Biomedical subjects

Wenbin Chen

Publications and source records attributed to Wenbin Chen.

12 recordsLinked to original sources

PubMed2005

Regulation of FasL expression: a SH3 domain containing protein family involved in the lysosomal association of FasL.

As a death factor of T cells and Natural Killer (NK) cells, Fas Ligand (FasL) is stored in association with secretory lysosomes. Upon stimulation, these cytotoxic granules are transported to the cell membrane where FasL is exposed on the cell surface, shed or secreted. It has been noted before that the proline-rich domain within the cytosolic part of FasL is required for its vesicular association. However, the molecular interactions involved in targeting FasL to secretory lysosomes or to the plasma membrane have not been elucidated. We now identified a family of structurally related proteins that upon co-expression with FasL reallocate the death factor from a membrane to an intracellular localization. Members of this protein family are characterized by a similar domain structure and include FBP17, PACSIN1-3, CD2BP1, CIP4, Rho-GAP C1 and several hypothetical proteins. We show that all tested members of this "FCH/SH3-family" co-precipitate FasL from transfectants. The interactions strictly depend on functional SH3 domains within the FCH/SH3 proteins. Since co-expression of FasL with individual FCH/SH3 proteins dramatically alters the intracellular localization of FasL especially in non-hematopoietic cells, our data suggest that FCH/SH3 proteins might play an important role for the subcellular distribution and lysosomal association of FasL.

Animals↗

PubMed2005

Finding dominant sets in microarray data.

Clustering allows us to extract groups of genes that are tightly coexpressed from Microarray data. In this paper, a new method DSF_Clust is developed to find dominant sets (clusters). We have preformed DSF_Clust on several gene expression datasets and given the evaluation with some criteria. The results showed that this approach could cluster dominant sets of good quality compared to kmeans method. DSF_Clust deals with three issues that have bedeviled clustering, some dominant sets being statistically determined in a significance level, predefining cluster structure being not required, and the quality of a dominant set being ensured. We have also applied this approach to analyze published data of yeast cell cycle gene expression and found some biologically meaningful gene groups to be dug out. Furthermore, DSF_Clust is a potentially good tool to search for putative regulatory signals.

Algorithms↗

PubMed2005

System-level identification of transcriptional circuits underlying mammalian circadian clocks.

Mammalian circadian clocks consist of complexly integrated regulatory loops, making it difficult to elucidate them without both the accurate measurement of system dynamics and the comprehensive identification of network circuits. Toward a system-level understanding of this transcriptional circuitry, we identified clock-controlled elements on 16 clock and clock-controlled genes in a comprehensive surveillance of evolutionarily conserved cis elements and measurement of their transcriptional dynamics. Here we report the roles of E/E' boxes, DBP/E4BP4 binding elements and RevErbA/ROR binding elements in nine, seven and six genes, respectively. Our results indicate that circadian transcriptional circuits are governed by two design principles: regulation of E/E' boxes and RevErbA/ROR binding elements follows a repressor-precedes-activator pattern, resulting in delayed transcriptional activity, whereas regulation of DBP/E4BP4 binding elements follows a repressor-antiphasic-to-activator mechanism, which generates high-amplitude transcriptional activity. Our analysis further suggests that regulation of E/E' boxes is a topological vulnerability in mammalian circadian clocks, a concept that has been functionally verified using in vitro phenotype assay systems.

Animals↗

PubMed2005

[A study on the repair of bone defects with deproteinized bone surrounded by titanium mesh and osteoblasts].

To investigate the ability of composite graft of osteobalsts and deproteinized bone-titanium mesh (DPB-TM) scaffold to repair cranial bone defect. 30 rabbits were randomly divided into 3 groups. The passage 3 fetal rabbit osteoblasts were seeded into porous DPB-TM scaffolds at the density of 5 x 10(6) ml(-1) as the experimental group. The same defects were respectively reconstructed by DPB-TM or osteoblasts as the control groups. After 12 weeks, the result was evaluated by three-dimensional computed tomographic scanning, gross inspection, scanning electron microscopy, histological examination and mechanics test, respectively. In the experimental group, bone trabecula was observed to pass the defect and interface was mixed. No demarcation between the region of the bone defect and the normal bone was observed. There was plenty of new bone on the scaffold. Part of the scaffold was absorbed. In view of mechanics, the intensity of artificial bone (18.93+/-1.12 MPa) was higher than that of normal bone (16.96+/-1.60 MPa) (P<0.05). In the control groups, only fibrous tissue was observed in the defect region, there was no new bone formation. The tissue engineering bone constructed by osteoblasts and DPB-TM scaffold can be applied to the repair of bone defect.

Animals↗

PubMed2004

Molecular-timetable methods for detection of body time and rhythm disorders from single-time-point genome-wide expression profiles.

Detection of individual body time (BT) via a single-time-point assay has been a longstanding unfulfilled dream in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To achieve this dream, we created a "molecular timetable" composed of >100 "time-indicating genes," whose gene expression levels can represent internal BT. Here we describe a robust method called the "molecular-timetable method" for BT detection from a single-time-point expression profile. The power of this method is demonstrated by the sensitive and accurate detection of BT and the sensitive diagnosis of rhythm disorders. These results demonstrate the feasibility of BT detection based on single-time-point sampling, suggest the potential for expression-based diagnosis of rhythm disorders, and may translate functional genomics into chronotherapy and personalized medicine.

Animals↗

PubMed2003

[Effect of FGF-BP on angiogenesis in squamous cell carcinoma].

OBJECTIVE: To localize fibroblast growth factors binding protein (FGF-BP) mRNA in squamous cell carcinoma (SCC) and study the FGF-BP association with vascularity. METHODS: Thirty-five primary squamous cell carcinoma specimens, 8 metastatic squamous cell carcinoma specimens and 7 histologically adjacent tissues were studied. The localization of FGF-BP mRNA expression was performed using in situ hybridization with 35 S-labeled human FGF-BP. Microvessels in tumor specimens were identified by von Willebrand Factor-specific immunohistochemical staining for endothelial cells. RESULTS: In situ hybridization demonstrated that FGF-BP mRNA was overexpressed in SCC. But a specific hybridization signal for FGF-BP mRNA was not detected in normal adult muscle, larynx, tongue, and lymph node. The highest density of microvessels was observed at the invasive edge of the tumor. The mean microvessel count in FGF-BP positive SCC was significantly higher than that in FGF-BP negative tumors (P < 0.001). CONCLUSION: The results demonstrated that FGF-BP is present in SCC of the head and neck. The association of FGF-BP expression with angiogenesis suggests that FGF-BP may be an angiogenic factor in SCC.

Adult↗

PubMed2002

A transcription factor response element for gene expression during circadian night.

Mammalian circadian clocks consist of complex integrated feedback loops that cannot be elucidated without comprehensive measurement of system dynamics and determination of network structures. To dissect such a complicated system, we took a systems-biological approach based on genomic, molecular and cell biological techniques. We profiled suprachiasmatic nuclei and liver genome-wide expression patterns under light/dark cycles and constant darkness. We determined transcription start sites of human orthologues for newly identified cycling genes and then performed bioinformatical searches for relationships between time-of-day specific expression and transcription factor response elements around transcription start sites. Here we demonstrate the role of the Rev-ErbA/ROR response element in gene expression during circadian night, which is in phase with Bmal1 and in antiphase to Per2 oscillations. This role was verified using an in vitro validation system, in which cultured fibroblasts transiently transfected with clock-controlled reporter vectors exhibited robust circadian bioluminescence.

Animals↗

PubMed2002

Acute effect of tetrandrine pulmonary targeting microspheres on hypoxic pulmonary hypertension in rats.

OBJECTIVE: To assess the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and evaluate its selective action on pulmonary circulation. METHODS: Twenty rats were exposed to hypoxic conditions for 3 weeks. Ten rats were used as normoxic controls. We administered Tet pulmonary targeting microspheres to 10 hypoxic rats and Tet aqueous solution to 10 hypoxic rats and the 10 control rats. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization, and mean systemic blood pressure (mSBP) was measured by left femoral catheterization. RESULTS: Rats exposed to hypoxia developed pulmonary hypertension. The decrease in mPAP in rats treated with Tet pulmonary targeting microspheres was significantly greater than that in rats receiving Tet aqueous solution (P < 0.05), and the effects were longer with Tet pulmonary targeting microspheres. Moreover, Tet pulmonary targeting microspheres, unlike Tet aqueous solution, did not decrease mSBP. CONCLUSION: Tet pulmonary targeting microspheres were more effective than Tet aqueous solution treating hypoxic pulmonary hypertension and acted selectively on the pulmonary circulation.

Alkaloids↗

PubMed2002

[Effect of adrenomedullin on the regulation of pulmonary arterial pressure in hypoxic rats].

OBJECTIVE: To evaluate the effect of adrenomedullin (ADM) on pulmonary circulation and the change of ADM in plasma and lung tissue from rats with hypoxic pulmonary hypertension. METHODS: Fifty Wistar rats were divided into the control group (10 rats) and the hypoxic group (40 rats). The animal model of pulmonary hypertension was established by exposing the rats to normobaric hypoxic conditions for 3 weeks; Mean pulmonary arterial pressure (mPAP) was measured by right cardiac catheterization, and mean systemic blood pressure (mSBP) was measured by left femoral catheterization. The thickness of pulmonary arterioles was measured by a computerized image analyser. The level of ADM in plasma and lung tissue was measured by radioimmunoassay. We ADM was administered in doses of 0.5, 1.0, 2.0 nmol/kg respectively to 30 hypoxic rats and the changes in mPAP and mSBP to ADM was evaluated. RESULTS: Rats exposed to hypoxia developed pulmonary hypertension, the mPAP in the control group being (16 +/- 3) mm Hg and in hypoxic group being (30 +/- 4) mm Hg, and the difference was significant (P < 0.01). The hypoxic rats developed significantly thickened pulmonary arterioles. The plasma level of ADM was (288 +/- 24) pg/ml in the hypoxic rats and (168 +/- 25) pg/ml in the control group the difference being significant (P < 0.01). The level of ADM in the lung homogenates from the hypoxic group was (2 319 +/- 238) pg/g and that from the control group was (1 153 +/- 127) pg/g and the difference was significant (P < 0.01). The ADM levels had a positive correlation with the mPAP (gamma = 0.567 and 0.612 P < 0.01, respectively). Administration of exogenous ADM reduced the mPAP in a dose-dependent manner in hypoxic rats, and the effect lasted 5 approximately 15 minutes. CONCLUSION: ADM has a relaxing effect on pulmonary circulation. The change of ADM in plasma and lung tissue may serve as a compensatory mechanism in maintaining the stability of pulmonary circulation in hypoxic condition.

Adrenomedullin↗

PubMed2002

[The prophylactic effect of BCG polysaccharides nucleic acid on the acute attack of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the prophylactic effect of BCG polysaccharides nucleic acid (BCG-PSN) on patients with chronic obstructive pulmonary disease and inquire about the mechanism thereof. METHODS: Sixty patients with chronic obstructive pulmonary disease were divided into two groups. In the treatment group, 36 patients received BCG-PSN 0.5 mg intramuscular injection, quaque die alterna, for 18 times. All patients revisited the hospital every 2 weeks and were followed up for 6 months. The number and days of patients with acute attack in 3 and 6 months were assessed. In the treatment group, the blood samples were collected before treatment and 3 and 6 months after treatment for the measurement of the blood IgA, IgG, IgM, CD3, CD4 and CD8. RESULTS: The number and days of patients with acute attack in the treatment group were significantly lower than those in the control group. After the treatment by BCG-PSN, blood CD4 and CD4/CD8 were significantly increased. CONCLUSION: BCG-PSN increases the patient's cellular immunocompetence and thus serves as a good protection against the acute attack of chronic obstructive pulmonary disease.

Aged↗

PubMed2002

Expression of adrenomedullin and its receptor in lungs of rats with hypoxic pulmonary hypertension.

OBJECTIVE: To investigate the role of adrenomedullin (AM) in the development of hypoxic pulmonary hypertension (HPH), and to assess the expression of AM and adrenomedullin receptor (AMR) in the lungs of rats with HPH. METHODS: We exposed 10 rats to normobaric hypoxic conditions for 3 weeks to establish rat model of pulmonary hypertension; and 10 other rats were used as normoxic controls. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization. The thickness of pulmonary arterioles was measured by a computerized image analyzer. We used the reverse transcription-polymerase chain reaction (RT-PCR) to assess the change of expression of AM and AMR in lung of HPH rat model. RESULTS: Compared with the control group, hypoxic rats developed remarkable pulmonary hypertension, increment in the thickness of pulmonary arterioles and right ventricular hypertrophy (P < 0.01). Chronic hypoxia elicited a considerable increment in expression of AM and AMR in the lungs of rats, and the ratio of AM/beta-actin and AMR/beta-actin in lungs of rats treated with hypoxia were significantly higher (P < 0.01). CONCLUSIONS: The AM plays an important role in regulating pulmonary vascular tone and can ameliorate the development of hypoxic pulmonary hypertension in rats.

Adrenomedullin↗

PubMedDate not supplied

Segmentation of discrete vector fields.

In this paper, we propose an approach for 2D discrete vector field segmentation based on the Green function and normalized cut. The method is inspired by discrete Hodge Decomposition such that a discrete vector field can be broken down into three simpler components, namely, curl-free, divergence-free, and harmonic components. We show that the Green Function Method (GFM) can be used to approximate the curl-free and the divergence-free components to achieve our goal of the vector field segmentation. The final segmentation curves that represent the boundaries of the influence region of singularities are obtained from the optimal vector field segmentations. These curves are composed of piecewise smooth contours or streamlines. Our method is applicable to both linear and nonlinear discrete vector fields. Experiments show that the segmentations obtained using our approach essentially agree with human perceptual judgement.

Algorithms↗