Biomedical subjects

Qiang Tan

Publications and source records attributed to Qiang Tan.

9 recordsLinked to original sources

PubMed2006

Tissue-engineered trachea: History, problems and the future.

This review tries to summarize the efforts over the past 20 years to construct a tissue-engineered trachea. After illustrating the main technical bottlenecks faced nowadays, we discuss what might be the solutions to these bottlenecks. You may find out why the focus in this research field shifts dramatically from the construction of a tubular cartilage tissue to reepithelialization and revascularization of the prosthesis. In the end we propose a novel concept of 'in vivo bioreactor', defined as the design of a perfusion system inside the scaffold, and explain its potential application in the construction of a tissue-engineered trachea.

Animals↗

PubMed2006

Sildenafil extends survival and graft function in a large animal lung transplantation model.

OBJECTIVE: Restoring intracellular cGMP and inducing NO-synthesis attenuates ischemia-associated early pulmonary allograft dysfunction. Phosphodiesterase-5 (PDE), predominantly expressed in lung tissue, plays a pivotal role in modulating the cGMP/NO-synthase pathway in endothelial and epithelial cells. In this study, we evaluate the effect of employing sildenafil (Viagra), a specific inhibitor of PDE-5, to counteract ischemia/reperfusion (I/R) injury in a single lung transplantation model of extended ischemia. METHODS: Donor animals (weight matched outbred pigs, 28-35 kg) in the treatment group (I) (n=5) were injected with 0.7 mg sildenafil/kg into the pulmonary artery (PA) prior to inflow occlusion. For perfusion, Perfadex, containing 0.7 mg sildenafil/l was used, and the graft stored at 1 degrees C in the perfusion solution. After 24h ischemia, unilateral left lung transplantation was performed. Starting at reperfusion, group I received continuous sildenafil (0.7 mg sildenafil/kg), over 6h. Except for the sildenafil application, the control group (II) (n=4) was treated identically (PGE1 was injected into the PA). One hour after reperfusion, the right main bronchus (MB) and right PA were occluded. Over the next 5h, cardiopulmonary parameters (systemic atrial, PA, central venous, left atrial pressure, pCO(2), pO(2)) were measured, including extravascular lung water (EVLW). Thiobarbituric acid-reactive substance assay (TBARS) and myeloperoxidase (MPO) analysis from lung tissue were run. RESULTS: All recipients of group I survived the 6-h reperfusion period; in contrast, all control animals died within 1-2h after occlusion of the right side. In comparison to a marked rise in pulmonary vascular resistance (PVR) in group II (>1000 dynescm(-5)), PVR in group I remained stable, moderately elevated from baseline (baseline: 150-180 dynescm(-5) vs endpoint: 1000 dynescm(-5)). EVLW in group I did not increase during reperfusion (baseline: 6.75+/-1.4 mg/kg vs endpoint: 6.7+/-1.0mg/kg), in contrast to group II, where pulmonary edema at 2-h reperfusion preceded terminal graft failure (group I: 9.7+/-0.1mg/kg vs group II: 6.48+/-1.8 mg/kg). Tissue reactive free radicals at endpoint measurement in group I did not differ significantly from native tissue. Yet, when compared to specimen taken from group II at time of terminal graft failure, a significant increase in free radicals was noted (group I: 13.8+/-1.6 pmol/g vs group II: 18.5+/-3.0 pmol/g, p<0.05). CONCLUSION: Sildenafil treatment prevents terminal early graft failure, allowing lung transplantation after 24-h ischemia time. Reperfusion edema was strikingly diminished, preserving pulmonary structural and functional integrity while prolonging graft ischemia time. Employing the established PDE-5 inhibitor sildenafil during lung perfusion, storage, and implantation, ischemic tolerance may be extended and early graft function improved.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2005

Antagonist-induced, activation function-2-independent estrogen receptor alpha phosphorylation.

Estrogen receptor alpha (ERalpha) serine 118 (Ser118) phosphorylation modulates activation function-1 (AF1) function. Correct positioning of helix 12 promotes agonist-dependent recruitment of cyclin-dependent kinase-7 to catalyze this event. In this study we show robust cyclin-dependent kinase-7-independent, AF2 antagonist-induced Ser118 phosphorylation. Estradiol (E2) and ICI-182,780 (ICI-780) induce Ser118 phosphorylation of wild-type ERalpha and either of two helix 12 mutants, suggesting AF2-independent action, probably via shedding of 90-kDa heat shock protein. With E2 treatment, the predominantly nuclear, phosphorylated ERalpha in COS-1 cells is detergent soluble. Although levels of ICI-780-induced phosphorylation are profound, Ser118-phosphorylated ERalpha is aggregated over the nucleus or in the cytoplasm, fractionating with the cell debris and making detection in cleared lysates improbable. Selective ER modulators (SERMs) elicit a mixed response with phosphorylated ERalpha in both detergent-soluble and -insoluble compartments. Apparent ligand-induced loss of ERalpha protein from cleared lysates is thus due to ligand-induced redistribution into the pellet, not degradation. The COS-1 response to ICI-780 can be mimicked in MCF-7 cells treated with a proteasome inhibitor to block authentic ligand-induced degradation. With SERMs and antagonists, the magnitude of Ser118-phosphorylated receptor redistribution into the insoluble fraction of COS-1 cells correlates with the magnitude of authentic ERalpha degradation in MCF-7 cells. A strong inverse correlation with ligand-induced uterotropism in vivo (P < 0.0001) and direct correlation with AF2-independent transrepression of the matrix metalloprotease-1 promoter in endometrial cells in vitro are seen. These data suggest that ligand-induced Ser118 phosphorylation of ERalpha can be AF2 independent. Furthermore, they identify translocation of Ser118-phosphorylated ERalpha out of the nucleus, leading to cytoplasmic aggregation, as an antagonist pathway that may precede receptor degradation.

Animals↗

PubMed2005

Estrogen receptor ligands. Part 10: Chromanes: old scaffolds for new SERAMs.

The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm, and lowered serum cholesterol levels in ovx'd adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs).

Animals↗

PubMed2005

Analysis of closed abdominal injury in pregnant women.

OBJECTIVE: To explore the characteristics of closed abdominal injury in pregnancy women and its treatment. METHODS: The clinical data of 37 pregnancy patients with closed abdominal injury treated in our hospital from June 1993 to June 2003 were collected and analyzed. RESULTS: All the 37 patients were treated with operation. Among them 2 early pregnancy patients with intestinal rupture and 1 patient with retroperitoneal hematoma were treated under laparoscope; in other 34 pregnancy patients laparotomy was performed. Of the 34 patients 8 used cesarean section because premature separation of placenta and enlarged womb interrupted the management of intra-abdominal organ injury. In the 37 patients 33 (89.1%) were cured, 4 (10.8%) die, postoperative complication rate was 16.2% (6/37). Two patients (5.4%) suffered from abdominal cavity infection, 3 (8.1%) from pulmonary infection, and 1 (2.7%) had multi-organ failure. CONCLUSIONS: For pregnancy patients with closed abdominal injury, besides obsteric diseases intra-abdominal injury should be given much attention. Accurate diagnosis and timely treatment can gain the time to save the life of both mother and fetus.

Abdominal Injuries↗

PubMed2004

Estrogen receptor ligands. Part 5: The SAR of dihydrobenzoxathiins containing modified basic side chains.

Dihydrobenzoxathiin analogs (1-11) with modifications on the basic side chain region were prepared and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. The compounds generally maintained a high degree of selectivity for ERalpha over ERbeta, similar to the original lead compound I. Many of the compounds also maintained high potency in the inhibition of human carcinoma MCF-7 cell growth. However, all were less potent in the inhibition of estradiol-triggered uterine growth. This work demonstrates the sensitive nature of modification to the antagonist basic side chain region.

Binding Sites↗

PubMed2004

Estrogen receptor ligands. Part 6: Synthesis and binding affinity of dihydrobenzodithiins.

Dihydrobenzodithiin compounds (1-6) were prepared to explore the expansion of the dihydrobenzoxathiin lead compounds I-III as SERAMs (Selective Estrogen Receptor Alpha Modulators). The dihydrobenzodithiin compounds generally maintained a high degree of selectivity for ERalpha over ERbeta, however, they lacked the in vivo antagonism/agonism activity exhibited by the lead class in an immature rat uterine growth model.

Animals↗

PubMed2001

The Synthesis of CP-263,114 and CP-225,917: Striking Long-Range Stereocontrol in the Fashioning of C7 Financial support was provided by the National Institutes of Health (Grant nos. CA-28824 and HL-25848 for S.J.D., CA-08748 for the Sloan-Kettering Institute Core Facility). Q.T. gratefully acknowledges the US Department of Defense for a postdoctoral fellowship (U.S. Army grant no. DAMD-17-99-1-9373). We thank the Pfizer Corporation, particularly Dr. T. Kaneko and Dr. T. T. Dabrah for discussions and for providing valuable CP samples from fermentation broth. We are grateful to Dr. Dongfang Meng for his major contributions to this work. We also thank George Sukenick of the Sloan-Kettering Institute Core Facility for mass spectral analyses and assistance in NMR spectroscopic and HPLC analyses, and Sylvi Rusli for mass spectral analyses.

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Journal Article↗

PubMed2000

The Synthesis of CP-263,114 and CP-225,917: Striking Long-Range Stereocontrol in the Fashioning of C7 Financial support was provided by the National Institutes of Health (Grant nos. CA-28824 and HL-25848 for S.J.D., CA-08748 for the Sloan-Kettering Institute Core Facility). Q.T. gratefully acknowledges the US Department of Defense for a postdoctoral fellowship (U.S. Army grant no. DAMD-17-99-1-9373). We thank the Pfizer Corporation, particularly Dr. T. Kaneko and Dr. T. T. Dabrah for discussions and for providing valuable CP samples from fermentation broth. We are grateful to Dr. Dongfang Meng for his major contributions to this work. We also thank George Sukenick of the Sloan-Kettering Institute Core Facility for mass spectral analyses and assistance in NMR spectroscopic and HPLC analyses, and Sylvi Rusli for mass spectral analyses.

Explore the source record for details and available documents.

Journal Article↗