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Biomedical subjects

Wei Tan

Publications and source records attributed to Wei Tan.

30 records · Page 2Linked to original sources
PubMed2004

IL-6 plays an obligatory role in late preconditioning via JAK-STAT signaling and upregulation of iNOS and COX-2.

OBJECTIVE: We sought to determine whether interleukin (IL)-6 modulates myocardial infarction or the late phase of preconditioning (PC). METHODS: Wild-type and IL-6(-/-) mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion with or without six cycles of coronary occlusion/reperfusion 24 h earlier. Myocardial IL-6 protein expression, activation of Janus kinase (JAK) 1 and JAK2, and signal transducers and activators of transcription (STAT) 1 and STAT3 after ischemic PC protocol were examined. The expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was determined 24 h after the PC ischemia. RESULTS: In preconditioned wild-type mice, infarct size was reduced from 60.5+/-2.6% of the risk region to 33.5+/-3.6%, indicating a late PC effect. In nonpreconditioned IL-6(-/-) mice, infarct size was similar to that observed in wild-type mice (59.9+/-3.8%), indicating that the deletion of IL-6 has no effect on infarct size. However, in preconditioned IL-6(-/-) mice, infarct size was not reduced (65.1+/-3.1%), indicating that the infarct-sparing effect was completely abrogated. Ischemic PC increased the expression of IL-6 in the cytoplasm of cardiomyocytes in the ischemic/reperfused zone. In IL-6(-/-) mice, the ischemic PC-induced activation of JAK1 and JAK2 and STAT1 and STAT3 was significantly reduced, and the increase in iNOS and COX-2 protein expression 24 h after the PC ischemia was markedly attenuated. CONCLUSION: IL-6 does not modulate myocardial infarct size in naïve myocardium. However, following a PC stimulus, IL-6 is obligatorily required for the activation of the JAK-STAT pathway, the ensuing upregulation of iNOS and COX-2 (co-mediators of late PC), and the development of a cardioprotective phenotype.

Animals↗
PubMed2004

Administration of a CO-releasing molecule at the time of reperfusion reduces infarct size in vivo.

Although carbon monoxide (CO) has traditionally been viewed as a toxic gas, increasing evidence suggests that it plays an important homeostatic and cytoprotective role. Its therapeutic use, however, is limited by the side effects associated with CO inhalation. Recently, transition metal carbonyls have been shown to be a safe and effective means of transporting and releasing CO groups in vivo. The goal of the present study was to test whether a water-soluble CO-releasing molecule, tricarbonylchloro(glycinato) ruthenium (II) (CORM-3), reduces infarct size in vivo when given in a clinically relevant manner, i.e., at the time of reperfusion. Mice were subjected to a 30-min coronary artery occlusion followed by 24 h of reperfusion and were given either CORM-3 (3.54 mg/kg as a 60-min intravenous infusion starting 5 min before reperfusion) or equivalent doses of inactive CORM-3, which does not release CO. CORM-3 had no effect on arterial blood pressure or heart rate. The region at risk did not differ in control and treated mice (44.5 +/- 3.5% vs. 36.5 +/- 1.6% of the left ventricle, respectively). However, infarct size was significantly smaller in treated mice [25.8 +/- 4.9% of the region at risk (n = 13) vs. 47.7 +/- 3.8% (n = 14), P < 0.05]. CORM-3 did not increase carboxyhemoglobin levels in the blood. These results suggest that a novel class of drugs, CO-releasing molecules, can be useful to limit myocardial ischemia-reperfusion injury in vivo.

Animals↗
PubMed2004

Tumor necrosis factor-alpha does not modulate ischemia/reperfusion injury in naïve myocardium but is essential for the development of late preconditioning.

The role of tumor necrosis factor (TNF)-alpha in myocardial ischemia/reperfusion injury remains controversial. We used homozygous TNF-alpha null mice (TNF-alpha(-/-)) to determine whether TNF-alpha modulates myocardial ischemia/reperfusion injury. Mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. When wild-type mice were preconditioned with six cycles of 4-min coronary occlusion/4-min reperfusion 24 h before the 30-min occlusion, infarct size was reduced from 58.6 +/- 1.9% of the risk region to 19.3 +/- 3.6%, indicating a late preconditioning (PC) effect. In non-preconditioned TNF-alpha(-/-) mice, infarct size was similar to that observed in wild-type mice (55.5 +/- 3.7%). However, in TNF-alpha(-/-) mice preconditioned with six occlusion/reperfusion cycles 24 h earlier, infarct size was not reduced (55.2 +/- 5.7%), indicating that the late PC protection against infarction was completely abolished. While minimal TNF-alpha immunoreactivity was detected in sham-operated hearts, extensive TNF-alpha expression was noted in the cytoplasm of cardiomyocytes in the ischemic/reperfused region 30 min after the PC ischemia. At 30 min after PC, wild-type mice exhibited increased DNA-binding activity of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) and nuclear translocation of p65, c-Jun and c-Fos; all of these changes were absent in TNF-alpha(-/-) mice. These data demonstrate that TNF-alpha does not modulate infarct size in the naïve (non-preconditioned) state but is essential for the development of the late phase of ischemic PC, possibly via the activation of NF-kappa B and AP-1 transcription factors.

Active Transport, Cell Nucleus↗
PubMed2004

[Prognostic value of expression of FASE, HER-2/neu, bcl-2 and p53 in stage I non-small cell lung cancer].

OBJECTIVE: To evaluate the prognostic value of expression of fatty acid synthase (FASE), HER-2/neu, bcl-2 and p53 in stage I non-small cell lung cancer (NSCLC). METHODS: Expression of FASE, HER-2/neu, bcl-2 and p53 protein was detected by immunohistochemical staining in 84 patients with stage I NSCLC who underwent surgery. Multiple clinical parameters and survival were analyzed. RESULTS: The expression of FASE, HER-2/neu, bcl-2 and p53 was 29.8%, 40.5%, 33.3% and 39.3%, respectively. The local recurrence and bone-metastasis rate were higher in FASE positive patients than in negative patients (28.0% vs 10.2%, P = 0.05; 61.5% vs 23.9%, P = 0.017, respectively). The 5-year survival rate was lower in HER-2/neu and FASE positive patients than in negative patients (37.7% vs 67.7%, P = 0.0083; 35.1% vs 66.1%, P = 0.0079, respectively), which showed that HER-2/neu and FASE expression were associated with significantly poor survival. Patients whose tumors were both HER-2/neu and FASE negative had better outcome, with a 5-year survival rate of 78.2%, compared with 36.3% in those whose tumors were positive for either one (P = 0.002). However, bcl-2 and p53 were not independent prognostic factors for survival. CONCLUSION: HER-2/neu and FASE are independent prognostic factor in stage I non-small cell lung cancer patients who expressed one or both markers.

Adult↗
PubMed2003

Functional dissection of transcription factor ZBRK1 reveals zinc fingers with dual roles in DNA-binding and BRCA1-dependent transcriptional repression.

The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in both activation and repression of gene transcription by virtue of its direct interaction with sequence-specific DNA-binding transcription factors. However, the mechanistic basis by which BRCA1 mediates the transcriptional activity of these regulatory proteins remains largely unknown. To clarify this issue, we have examined the functional interaction between BRCA1 and ZBRK1, a BRCA1-dependent KRAB eight zinc finger transcriptional repressor. We report here the identification and molecular characterization of a portable BRCA1-dependent transcriptional repression domain within ZBRK1 composed of zinc fingers 5-8 along with sequences in the unique ZBRK1 C terminus. This C-terminal repression domain functions in a BRCA1-, histone deacetylase-, and promoter-specific manner and is thus functionally distinguishable from the N-terminal KRAB repression domain in ZBRK1, which exhibits no BRCA1 dependence and broad promoter specificity. Significantly, we also find that the BRCA1-dependent transcriptional repression domain on ZBRK1 includes elements that modulate its sequence-specific DNA binding activity. These findings thus reveal the presence within ZBRK1 of functionally bipartite zinc fingers with dual roles in sequence-specific DNA-binding and BRCA1-dependent transcriptional repression. We discuss the implications of these findings for the role of BRCA1 as ZBRK1 co-repressor.

BRCA1 Protein↗
PubMed2003

Microfluidic patterning of cells in extracellular matrix biopolymers: effects of channel size, cell type, and matrix composition on pattern integrity.

The organization of cells within an extracellular matrix is critical to promote appropriate cellular interactions and tissue function in vivo. The ability to design and create biologically relevant cellular arrangements via microfluidic patterning on surfaces provides new capabilities for tissue engineering and biomimetics. The purpose of this article is to describe techniques using microfluidic patterning of three-dimensional biopolymer matrices to improve cellular pattern integrity and to provide microscale control over cellular microenvironments. Results demonstrated that the incorporation of extracellular matrix biopolymers in cell microfluidic patterning results in a more stable pattern of adherent human endothelial cells than patterning without matrix components after several days in vitro. This may be important for carrying out long-term biological experiments and tissue engineering in vitro. Moreover, chemical components in the patterned biopolymer matrices, such as collagen, chitosan, and fibronectin, influenced the ability of the matrices to control cell migration and pattern stability over time. Thus, microfluidic patterning of cells in extracellular matrix biopolymers was shown to be useful in patterning multiple cell types in well-defined three-dimensional geometries.

Biopolymers↗
PubMed2002

[Significance of fatty acid synthase expression in non-small cell lung cancer].

OBJECTIVE: To evaluate the expression of fatty acid synthase (FAS) in non-small cell lung cancer (NSCLC). METHODS: FAS was examined by immunohistochemical S-P technique in 175 specimens of NSCLC patients. Multiple clinical factors were analyzed according to their relation with expression of FAS. RESULTS: The overall FAS expression rate was 31.4% (55/175). The expression of FAS in the non-adenocarcinoma patients was significantly higher than that of adenocarcinoma patients (38.4% vs 22.4%, P = 0.036). Higher FAS expression was also detected in patients who had vascular invasion or bone metastasis than those without (75.0% vs 29.3%, P = 0.02 and 46.9% vs 28.0%, P = 0.037). But, there was no significant difference between FAS and other clinical factors such as age, sex, smoking index, tumor size, stage, degree of differentiation, lymphatic metastasis, local recurrence or distant metastasis. Although there was no significant difference in the survival rates of FAS positive and negative patients (P = 0.066), the survival rate of FAS positive stage I patients was lower than that of negative ones (P = 0.005). CONCLUSION: Fatty acid synthase in the specimens of non-small cell lung cancer patients has no correlation with most clinical factors, except that, in early lesions, it may signify poor prognosis.

Adult↗
PubMed2001

U2AF participates in the binding of TAP (NXF1) to mRNA.

TAP/NXF1 is a conserved mRNA export receptor serving as a link between messenger ribonucleoproteins (mRNPs) and the nuclear pore complex. The mechanism by which TAP recognizes its export substrate is unclear. We show here that TAP is added to spliced mRNP in human cells. We identified a distinct region of TAP that targets it to mRNP. Using yeast two-hybrid screens and in vitro binding studies, we found that this region coincides with a direct binding site for U2AF35, the small subunit of the splicing factor U2AF. This interaction is evolutionarily conserved across metazoa, indicating its significance. We further found in human cells that the exogenously expressed large U2AF subunit, U2AF65, accumulates in spliced mRNP, leading to the recruitment of U2AF35 and TAP. Similarly to TAP, U2AF65 stimulated directly the nuclear export and expression of an mRNA that is otherwise retained in the nucleus. Together with our finding that U2AF is continuously exported from the nucleus, these data suggest that U2AF participates in nuclear export, by facilitating TAP's addition to its mRNA substrates.

Binding Sites↗
PubMedDate not supplied

Layer-by-layer microfluidics for biomimetic three-dimensional structures.

Due to the complex structures of living systems, with size scales spanning from the micron to millimeter range, the use of microtechnology to recreate in vivo-like architecture has exciting potential applications. However, most microscale systems are two-dimensional, and few three-dimensional (3-D) systems are being explored. We have developed a versatile technique, combining surface engineering with layer-by-layer microfluidics technology, to create a 3-D microscale hierarchical tissue-like structure. The process involves immobilization of a cell-matrix assembly, cell-matrix contraction, and pressure-driven microfluidic delivery. An aminopropyltriethoxysilane-glutaraldehyde activated chip is used to effectively immobilize the cell-matrix assemblies while maintaining cell viability. Pressure-driven microfluidics is applied to transport cells-matrices with controlled flow rates, determined from dynamic flow imaging. By taking advantage of the contraction of the biopolymer matrices by cells, layer-by-layer microfluidics can be used to build multilayers of cell-matrix inside a microchannel and the thickness of each layer can be controlled down to microscale dimensions. Confocal and electron microscopy images of the final structure show a hierarchical layered cellular configuration composed of heterogeneous biomimetic materials. For a model system, a biomimetic arterial structure is formed using three types of vascular cells to mimic the 3-tunic structure found in vivo. This approach provides solutions to fabricate hierarchical "neotissues" with controlled microarchitectures and 3-D configurations of multiple cell types.

Biomimetic Materials↗
PubMedDate not supplied

Improving the integrity of three-dimensional vascular patterns by poly(ethylene glycol) conjugation.

Development of functional tissue-engineering constructs may require that multiple cell types be organized in controlled three-dimensional (3-D) microarchitectures with proper nutrient diffusion and vascularization. In the past few years, a variety of microscale techniques have demonstrated the ability to control protein and cell attachment in defined patterns. Nevertheless, maintenance of these patterns over time has been a significant challenge due to nonspecific protein adsorption and cell migration. To this end, we have investigated the effectiveness of poly(ethylene glycol) (PEG) thin films in maintaining the integrity of 3-D cellular patterns, using human umbilical vein endothelial cells (HUVEC) as a model system. These HUVEC constructs were created using extracellular matrix (ECM)-based microfluidic patterning. Our results indicated that PEG-conjugated substrates improve cell pattern integrity as compared to control silicon. The compliance multifactor (a measure of pattern integrity; higher value means lower pattern integrity) was about 3.66 +/- 0.29 on day 5 for PEG-conjugated surfaces, compared with 8.23 +/- 0.42 for control surfaces ECM-based microfluidic patterning coupled with stable PEG-conjugated surfaces may serve as a vital tool for vascularized tissue engineering.

Cells, Cultured↗
PubMedDate not supplied

Structural and functional optical imaging of three-dimensional engineered tissue development.

A significant amount of the data collected by cell biologists and tissue engineers relies on invasive imaging techniques to visualize dynamic structural and functional properties in engineered tissues. We report the use of optical coherence tomography and the comparative use of confocal microscopy to nondestructively and noninvasively monitor the structural and functional characteristics of three-dimensional engineered tissues over time. The engineered tissue model is composed of chitosan scaffolds and fibroblasts transfected with vinculin fused to green fluorescent protein. We image the developmental process of engineered tissues from changes of tissue microarchitecture to cell-matrix adhesions in three dimensions. These findings demonstrate the potential for optical coherence tomography in applications in cell and tissue biology, tissue engineering, and drug discovery.

Animals↗