Search PubMed⌕ Search

Biomedical subjects

Meng Li

Publications and source records attributed to Meng Li.

36 records · Page 2Linked to original sources
PubMed2006

Drug-drug interactions involving membrane transporters in the human kidney.

The kidneys play a critical role in the elimination of xenobiotics. Factors affecting the ability of the kidney to eliminate drugs may result in marked changes in the pharmacokinetics of a given compound. Drug-drug interactions due to competitive inhibition of renal organic anion or cation secretion systems have been noticed clinically for a long time. However, our understanding of the physical sites of interactions, that is, the specific transport proteins that the interacting drugs act on, has just begun very recently. This review summarises the latest progress in molecular identification and functional characterisation of major drug transporters in the human kidney. In particular, the review focuses on relating cloned renal drug transporters to clinically observed drug-drug interactions. The authors' opinion on the current status and future directions of research in these areas is also offered.

Drug Interactions↗
PubMed2006

Edaravone protects PC12 cells from ischemic-like injury via attenuating the damage to mitochondria.

BACKGROUND: Edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein expression and recovering from damage to mitochondria after OGD (oxygen-glucose deprivation)-reperfusion. METHODS: Viability of PC12 cells which were injured at different time of OGD injury, was quantified by measuring MTT (2-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyltetrazolium bromide) staining. In addition, PC12 cells' viability was also quantified after their preincubation in different concentration of edaravone for 30 min followed by (OGD). Furthermore, apoptotic population of PC12 cells that reinsulted from OGD-reperfusion with or without preincubation with edaravone was determined by flow cytometer analysis, electron microscope and Hoechst/PI staining. Finally, change of Bcl-2/Bax protein expression was detected by Western blot. RESULTS: (1) The viability of PC12 cells decreased with time (1 - 12 h) after OGD. We regarded the model of OGD 2 h, then replacing DMEM (Dulbecco's Modified Eagle's Medium) for another 24 h as an OGD-reperfusion in this research. Furthermore, most PC12 cells were in the state of apoptosis after OGD-reperfusion. (2) The viability of PC12 cells preincubated with edaravone at high concentrations (1, 0.1, 0.01 micromol/L) increased significantly with edaravone protecting PC12 cells from apoptosis after OGD-reperfusion injury. (3) Furthermore, edaravone attenuates the damage of OGD-reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression after OGD-reperfusion. CONCLUSION: Neuroprotective effects of edaravone on ischemic or other brain injuries may be partly mediated through inhibition of Bcl-2/Bax apoptotic pathways by recovering from the damage of mitochondria.

Animals↗
PubMed2006

[Effects of conditioned medium derived from keratinocytes on fibroblasts].

OBJECTIVE: To observe the effects of keratinocytes on proliferation and collagen secretion of fibroblasts. METHODS: The conditioned medium, collected from cultured keratinocytes, was added to the cultured fibroblasts as the tested groups (12.5%, 25% and 50% groups) and DMEM as control group. The MTT, hydroxyproline colorimetric method and flow cytometer were employed to measure the fibroblast proliferation, the collagen secretion and the change of the cell cycle. RESULTS: In fibroblast proliferation, the absorbency(A) value of tested groups was significantly different from that of the control group (P<0.01). A value increased as increasing concentration, there was statistically significant difference between the concentrations of 25%, 50% and the concentration of 12.5% (P<0.01), but no statistically significant difference between the concentrations of 25% and 50% (P>0.01). In collagen secretion, there was no statistically significant difference between the tested groups and the control group(P>0. 01), and between the tested groups(P>0.01). In cell cycle, 50% of conditioned medium could make the fibroblast pass the limit of G1/S and S/G2 period, the cell rates of S,G2-M period increased. CONCLUSION: The conditioned medium from keratinocytes can increase fibroblasts proliferation, have little effect on general collagen secretion.

Cell Cycle↗
PubMed2005

Detection and quantification of mutations in the plasma of patients with colorectal tumors.

The early detection of cancers through analysis of circulating DNA could have a substantial impact on morbidity and mortality. To achieve this goal, it is essential to determine the number of mutant molecules present in the circulation of cancer patients and to develop methods that are sufficiently sensitive to detect these mutations. Using a modified version of a recently developed assay for this purpose, we found that patients with advanced colorectal cancers consistently contained mutant adenomatous polyposis coli (APC) DNA molecules in their plasma. The median number of APC DNA fragments in such patients was 47,800 per ml of plasma, of which 8% were mutant. Mutant APC molecules were also detected in >60% of patients with early, presumably curable colorectal cancers, at levels ranging from 0.01% to 1.7% of the total APC molecules. These results have implications for the mechanisms through which tumor DNA is released into the circulation and for diagnostic tests based on this phenomenon.

Adult↗
PubMed2005

Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development.

Recent studies of mouse mutant aphakia have implicated the homeobox gene Pitx3 in the survival of substantia nigra dopaminergic neurons, the degeneration of which causes Parkinson's disease. To directly investigate a role for Pitx3 in midbrain DA neuron development, we have analysed a line of Pitx3-null mice that also carry an eGFP reporter under the control of the endogenous Pitx3 promoter. We show that the lack of Pitx3 resulted in a loss of nascent substantia nigra dopaminergic neurons at the beginning of their final differentiation. Pitx3 deficiency also caused a loss of tyrosine hydroxylase (TH) expression specifically in the substantia nigra neurons. Therefore, our study provides the first direct evidence that the aphakia allele of Pitx3 is a hypomorph and that Pitx3 is required for the regulation of TH expression in midbrain dopaminergic neurons as well as the generation and/or maintenance of these cells. Furthermore, using the targeted GFP reporter as a midbrain dopaminergic lineage marker, we have identified previously unrecognised ontogenetically distinct subpopulations of dopaminergic cells within the ventral midbrain based on their temporal and topographical expression of Pitx3 and TH. Such an expression pattern may provide the molecular basis for the specific dependence of substantia nigra DA neurons on Pitx3.

Animals↗
PubMed2005

Midbrain dopaminergic development in vivo and in vitro from embryonic stem cells.

The midbrain dopaminergic (mDA) neurons play a key role in the function of a variety of brain systems, including motor control and reward pathways. This has led to much interest in these neurons as targets for intervention in human disorders such as Parkinson's disease and schizophrenia. A major area of interest is to direct embryonic stem (ES) cells to differentiate into mDA neurons in vitro, which can then be used for cell therapy or drug screening. At present, our understanding of mDA development in vivo is limited. However, recent studies have identified a number of regulatory factors that influence the development of mDA neurons in vivo. Such studies will not only increase our understanding of mDA development in vivo, they may also promote new paradigms for regulating mDA production from ES cells in vitro. Here we review the current knowledge on mDA development in vivo and mDA differentiation.

Animals↗
PubMed2004

SoxB transcription factors specify neuroectodermal lineage choice in ES cells.

Knowledge of lineage decision machinery in pluripotent embryonic stem (ES) cells may shed light on the process of germ layer segregation in the mammalian embryo and enable directed differentiation in vitro for biomedical applications. We have investigated the contribution of Class B1 Sox transcription factors to lineage choice during ES cell differentiation. We report that forced expression of Sox1 or Sox2 did not impair propagation of undifferentiated ES cells, but upon release from self-renewal promoted differentiation into neuroectoderm at the expense of mesoderm and endoderm. The efficient specification of a primary lineage by transcription factor manipulation provides a paradigm for instructing differentiation of ES cells for biopharmaceutical screening and cell therapy applications.

Animals↗
PubMed2004

Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neurons.

We have generated embryonic stem (ES) cells and transgenic mice with green fluorescent protein (GFP) inserted into the Pitx3 locus via homologous recombination. In the central nervous system, Pitx3-directed GFP was visualized in dopaminergic (DA) neurons in the substantia nigra and ventral tegmental area. Live primary DA neurons can be isolated by fluorescence-activated cell sorting from these transgenic mouse embryos. In culture, Pitx3-GFP is coexpressed in a proportion of ES-derived DA neurons. Furthermore, ES cell-derived Pitx3-GFP expressing DA neurons responded to neurotrophic factors and were sensitive to DA-specific neurotoxin N-4-methyl-1, 2, 3, 6-tetrahydropyridine. We anticipate that the Pitx3-GFP ES cells could be used as a powerful model system for functional identification of molecules governing mDA neuron differentiation and for preclinical research including pharmaceutical drug screening and transplantation. The Pitx3 knock-in mice, on the other hand, could be used for purifying primary neurons for molecular studies associated with the midbrain-specific DA phenotype at a level not previously feasible. These mice would also provide a useful tool to study DA fate determination from embryo- or adult-derived neural stem cells.

Animals↗
PubMed2003

Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knock-in mice.

The transcription factor Sox1 is the earliest and most specific known marker for mammalian neural progenitors. During fetal development, Sox1 is expressed by proliferating progenitor cells throughout the central nervous system and in no tissue but the lens. We generated a reporter mouse line in which egfp is inserted into the Sox1 locus. Sox1GFP animals faithfully recapitulate the expression of the endogenous gene. We have used the GFP reporter to purify neuroepithelial cells by fluorescence-activated cell sorting from embryonic day 10.5 embryos. RNAs prepared from Sox1GFP+ and Sox1GFP- embryo cells were then used to perform a pilot screen of subtracted cDNAs prepared from differentiating embryonic stem cells and arrayed on a glass chip. Fifteen unique differentially expressed genes were identified, all previously associated with fetal or adult neural tissue. Whole mount in situ hybridization against two genes of previously unknown embryonic expression, Lrrn1 and Musashi2, confirmed the selectivity of this screen for early neuroectodermal markers.

Animals↗
PubMed2003

Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture.

Mouse embryonic stem (ES) cells are competent for production of all fetal and adult cell types. However, the utility of ES cells as a developmental model or as a source of defined cell populations for pharmaceutical screening or transplantation is compromised because their differentiation in vitro is poorly controlled. Specification of primary lineages is not understood and consequently differentiation protocols are empirical, yielding variable and heterogeneous outcomes. Here we report that neither multicellular aggregation nor coculture is necessary for ES cells to commit efficiently to a neural fate. In adherent monoculture, elimination of inductive signals for alternative fates is sufficient for ES cells to develop into neural precursors. This process is not a simple default pathway, however, but requires autocrine fibroblast growth factor (FGF). Using flow cytometry quantitation and recording of individual colonies, we establish that the bulk of ES cells undergo neural conversion. The neural precursors can be purified to homogeneity by fluorescence activated cell sorting (FACS) or drug selection. This system provides a platform for defining the molecular machinery of neural commitment and optimizing the efficiency of neuronal and glial cell production from pluripotent mammalian stem cells.

Animals↗
PubMed2003

[Diagnosis and treatment of spinal dural arteriovenous fistulas: 110 cases report].

OBJECTIVE: To discuss the diagnosis, treatment and prognosis of spinal dural arteriovenous fistulas (SDAVF). METHODS: The clinical and following-up date from 110 patients with SDAVF diagnosed by spinal MRI and spinal angiography were analyzed retrospectively. RESULTS: Draining vein between fistula and spinal cord was interrupted by laminectomy approach as first choice in 61 patients, by hemi-laminectomy approach in 37, and by endovascular embolization in 12, and re-operation due to recurrence after embolization in 3. Anticoagulation, hydration and early rehabilitation were used postoperatively. Complete disappearance of SDAVF was confirmed in all 106 patients who received postoperative spinal angiography. The para-medullary tortuous flow voids fully disappeared in 74 patients and partly disappeared in 15 on postoperative T(2)-weighted MRI. Follow up of 98 patients showed complete recovery in 54 patients, improvement in 34, and no change in 10. Three of the 10 patients were reoperated on because of recurrence 1 to 5 years after embolization. CONCLUSIONS: SDAVF can produce good outcome after early diagnosis and treatment. Interruption of the draining vein between fistula and spinal cord by hemi-laminectomy approach is the first choice for the treatment of SDAVF.

Adult↗
PubMed2003

Initial comparison of intracranial aneurysm embolization with mechanical detachable spirals and with Guglielmi detachable coils.

OBJECTIVE: To compare the embolization effects of intracranial aneurysm with mechanical detachable spirals (MDS) and with Guglielmi detachable coils (GDC). METHODS: One hundred and twenty cases with 125 intracranial aneurysms were embolized in Beijing Hospital from March 1995 to July 1999. Sixty-six aneurysms in 64 cases were embolised with MDS, 51 in 48 with GDC, and 8 in 8 with both MDS and GDC. Clinical data including sex, age, subarachnoid hemorrhage (SAH), Hunt & Hess grading, diameter and neck width of aneurysms, number and length of coils used per aneurysm, occlusive ratio, and complications were compared between MDS and GDC groups. RESULTS: MDS and GDC group were comparable (t-test or chi2-test, all P value > 0.10) in terms of age, sex, diameter of aneurysms [(8.46 +/- 3.42) mm vs. (7.38 +/- 3.45) mm], neck width [(3.49 +/- 1.50) mm vs. (3.26 +/- 1.52) mm], coils number [(4.65 +/- 3.01) vs. (4.24 +/- 2.65)] and their length [(460.2 +/- 398.5) mm vs. (422.9 +/- 387.1) mm] used per aneurysm, occlusive ratio in aneurysms embolized > or = 80% [(95.00% +/- 6.32%) vs. (94.19% +/- 7.63%)], mortality and permanent complications (7.8% vs. 4.2%). CONCLUSIONS: MDS and GDC are all materials for embolization of intracranial aneurysms. MDS is less expensive, but more difficult to control and of propensity to complications while GDC is more compliant, easier to be used, safer, and have many alternative types for use as well a more extensive indications.

Adult↗
PubMed2003

[Effects of growing process and climatic conditions on grain quality of spring-sown wheat].

In the period of 1998-2000, 10 wheat varieties were used to study the effects of growth, development process and climatic conditions on the quality of wheat grains through spring sowing experiments in Beijing. The results showed that there were no significant variations on the quality traits among the varieties while there were significant variations among different years. The most significant negative correlation had been shown between the days from sowing to ripening and hardness of the grains and between the days from heading to ripening and the content of wet gluten of the grains. There was a significant negative correlation between day-night temperature difference during the period from heading to ripening and content of NIR protein. The results also showed that there was most significant negative correlation between total radiation, day-night temperature difference and the content of wet gluten of the grains. There was significant positive correlation between total sunlight and the content of wet gluten of the grains. The significant negative correlation was present between sedimentation value and total radiation, total sunlight, average temperature of daytime, day-night temperature difference.

Climate↗
PubMed2002

[Diagnosis and treatment of spinal cord cavernous angioma].

OBJECTIVE: To investigate the diagnosis and treatment of patients with spinal cord cavernous angioma. METHODS: Clinical data on 23 patients with intramedually cavernous angiomas were analyzed. The function of the spinal cord was evaluated before and after treatment using the Aminoff & Logue scale. RESULTS: All patients underwent resection of spinal cord cavernous angioma except two patients who refused surgical treatment. Complete removal was achieved in 18 patients, and subtotal removal in 3. Twenty-one patients with spinal cavernous angioma were confirmed pathologically. The postoperative neurological status was improved in 15 patients, remained unchanged in 4, and aggravated in 2. No deaths occurred. CONCLUSIONS: MRI is specific in diagnosis of intramedually cavernous angioma. The outcome of surgical treatment is better. Surgical treatment is suitable for patients with symptoms.

Adolescent↗
PubMed2002

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.

Animals↗
PubMed1999

Balloon occlusion test and therapeutic occlusion on traumatic carotid cavernous fistulas.

OBJECTIVE: To evaluate the safety of the balloon occlusion test(BOT) and therapeutic occlusion of the internal carotid artery(ICA). METHODS: The data of 43 patients hospitalized consecutively with traumatic intractable carotid cavernous fistulas (TICCF) were analyzed. Therapeutic occlusion of ICA was performed on 39 cases and BOT was only performed on the remaining 4 cases. Our assessment consisted of: (1) angiographic evaluation of collateral circulation with or without BOT of ICA, and (2) evaluation of clinical tolerance to therapeutic occlusion of ICA with hypotensive challenge for 30 minutes. Complications of BOT and therapeutic occlusion of ICA were also analyzed retrospectively. RESULTS: Complications related to BOT occurred in 1 case (2.3%) without causing permanent deficits. Complications related to therapeutic occlusion of ICA occurred in 4 cases (10%), including 1 technical (2.5%), 2 temporary (5%) and 1 permanent (2.5%) deficit. There was no fistula recurrence or mortality. CONCLUSIONS: BOT of ICA is safe and economical. The reliability of the results is almost the same compared with that of other more complicated methods of assessing therapeutic occlusion of ICA. And it is easy to treat TICCF with therapeutic occlusion of ICA.

Journal Article↗