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Biomedical subjects

Li Li

Publications and source records attributed to Li Li.

At least 235 records · Page 13Linked to original sources
PubMed2005

[A multicenter randomized clinical trial of weekly paclitaxel and carboplatin vs three weeks paclitaxel and carboplatin as first line chemotherapy in epithelial ovarian cancer].

OBJECTIVE: To compare the efficacy of combination regiments of taxol given weekly plus carboplatin and taxol given every three weeks plus carboplatin. To observe the toxicity of the two regiments. To observe the two-year survival rate in the two groups. METHODS: Total 125 eligible patients in 13 centers of CGOG were entered into the two arms of this randomized clinical trial, of whom 51 were entered into weekly taxol group and 74 entered into 3 weeks taxol group. RESULTS: 81.6% (102/125) of patients had satisfactory decreasing of CA125 level after optimal cytoreductive surgery and chemotherapy. 86.3% (44/51) of patients is in weekly group and 78.4% (58/74) of patients in three weeks group (P > 0.05). Relapse frequency is 29.7% in every three weeks group and 19.6% in weekly group (P > 0.05). Median interval to relapse is 15.7 months in every three weeks group and 13.6 months in weekly group (P > 0.05). One-year survival rate is 95.2% in every three weeks and 93.9% in weekly group (P > 0.05). Two-year survival rate is 78.7% in every three weeks and 85.3% in weekly group (P > 0.05). Grade III and IV myelosuooression is 45.9% in three weeks group and, 27.5% in weekly group (P < 0.05). CONCLUSION: (1) The two regiments had equal efficacy. (2) Myelosuppression was less frequency in the weekly group than in every three weeks group. (3) Weekly taxol therapy has mild toxicity and is more suitable for the old and feeble patients. Weekly taxol therapy can be conveniently administered in outpatients department.

Adult↗
PubMed2005

[Expression of dihydropyrimidine dehydrogenase in human colorectal carcinoma and its clinical implications].

OBJECTIVE: The study was to explore the dihydropyrimidine dehydrogenase (DPD) expression level in human colorectal carcinoma and its clinical implications. METHODS: Fifty-three patients with colorectal carcinoma were detected by immunohistochemical stain. These patients had undergone radical surgical treatment in the First Hospital of Xi'an Jiaotong University and had been followed up for 5 years after the operation. cases Twenty-two had received 5-fluorouracil-based adjuvant chemotherapy. RESULTS: DPD expression was predominantly observed in the cytoplasm of the tumor cells, and also partly in the nucleus. The positive rate of DPD expression was 73.58% (39/53). DPD expression in patients with different histopathology was obviously different (P < 0.05). There was no significant correlation between the expression of DPD and the efficacy of chemotherapy. By Kaplan-Meier methods, the survival patients with of negative DPD expression was longer than those with positive DPD expression, and then five-year survival rates were 12.97% and 42.86%, respectively (P < 0.05). The prognosis of patients with positive DPD expression was significantly poorer outcome than that of patients with negative DPD expression. CONCLUSION: These findings suggest that DPD expression might be one of the important prognostic parameters for colorectal cancer patients.

Adult↗
PubMed2005

A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation.

The inward rectifier K(+) channel Kir2.1 mediates the potassium I(K1) current in the heart. It is encoded by KCNJ2 gene that has been linked to Andersen's syndrome. Recently, strong evidences showed that Kir2.1 channels were associated with mouse atrial fibrillation (AF), therefore we hypothesized that KCNJ2 was associated with familial AF. Thirty Chinese AF kindreds were evaluated for mutations in KCNJ2 gene. A valine-to-isoleucine mutation at position 93 (V93I) of Kir2.1 was found in all affected members in one kindred. This valine and its flanking sequence is highly conserved in Kir2.1 proteins among different species. Functional analysis of the V93I mutant demonstrated a gain-of-function consequence on the Kir2.1 current. This effect is opposed to the loss-of-function effect of previously reported mutations in Andersen's syndrome. Kir2.1 V93I mutation may play a role in initiating and/or maintaining AF by increasing the activity of the inward rectifier K(+) channel.

Adult↗
PubMed2005

Functional identification of the non-specific nuclease from white spot syndrome virus.

The product encoded by the wsv191 gene from shrimp white spot syndrome virus (WSSV) is homologous with non-specific nucleases (NSN) of other organisms. To functionally identify the protein, the wsv191 gene was expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein with 6His-tag at C-terminal. The fusion protein (termed as rWSSV-NSN) was purified using Ni-NTA affinity chromatography under denatured conditions, renatured and characterized by three methods. The results showed that rWSSV-NSN could hydrolyze both DNA and RNA. 5'-RACE result revealed that the transcription initiation site of the wsv191 gene was located at nucleotide residue G of the predicted ATG triplet. Therefore, we concluded that the next ATG should be the genuine translation initiation codon of the wsv191 gene. Western blot analysis revealed that the molecular mass of natural WSSV-NSN was 37 kDa.

Amino Acid Sequence↗
PubMed2005

Differences between left and right ventricular chamber geometry affect cardiac vulnerability to electric shocks.

Although effects of shock strength and waveform on cardiac vulnerability to electric shocks have been extensively documented, the contribution of ventricular anatomy to shock-induced polarization and postshock propagation and thus, to shock outcome, has never been quantified; this is caused by lack of experimental methodology capable of mapping 3-D electrical activity. The goal of this study was to use optical imaging experiments and 3-D bidomain simulations to investigate the role of structural differences between left and right ventricles in vulnerability to electric shocks in rabbit hearts. The ventricles were paced apically, and uniform-field, truncated-exponential, monophasic shocks of reversed polarity were applied over a range of coupling intervals (CIs) in experiment and model. Experiments and simulations revealed that reversing the direction of externally-applied field (RV- or LV- shocks) alters the shape of the vulnerability area (VA), the 2-D grid encompassing episodes of arrhythmia induction. For RV- shocks, VA was nearly rectangular indicating little dependence of postshock arrhythmogenesis on CI. For LV- shocks, the probability of arrhythmia induction was higher for longer than for shorter CIs. The 3-D simulations demonstrated that these effects stem from the fact that reversal of field direction results in relocation of the main postshock excitable area from LV wall (RV- shocks) to septum (LV- shocks). Furthermore, the effect of septal (but not LV) excitable area in postshock propagation was found to strongly depend on preshock state. Knowledge regarding the location of the main postshock excitable area within the 3-D ventricular volume could be important for improving defibrillation efficacy.

Animals↗
PubMed2005

Up-regulation of uncoupling protein 2 by cyanide is linked with cytotoxicity in mesencephalic cells.

Uncoupling protein 2 (UCP-2) regulates mitochondrial function by increasing proton leak across the inner membrane to dissociate respiration from ATP synthesis and reduce reactive oxygen species generation. A number of studies have shown that UCP-2 expression protects cells from oxidative stress mediated injuries. In the current study, we show UCP-2-mediated reduction in mitochondrial function contributes to the mitochondrial dysfunction and the necrotic death of primary cultured mesencephalic cells (MCs) after exposure to cyanide, a complex IV inhibitor. The necrotic cell death was directly related to the level of mitochondrial dysfunction, as shown by reduction in ATP levels and decreased mitochondrial membrane potential. Treatment with cyanide for 6 h or longer upregulated UCP-2 expression. Blockade of up-regulation with a transcription or a translational inhibitor reduced the response to cyanide. Knockdown with RNAi or transfection with a UCP-2 dominant-negative interfering mutant reduced the cyanide-induced mitochondrial dysfunction and cell death, showing that constitutive expression of UCP-2 plays a role in the response to cyanide. Overexpression of UCP-2 by transfection with human full-length cDNA potentiated the cyanide toxicity. These findings indicate that UCP-2 can serve as a regulator of mitochondria-mediated necrotic cell death, in which enhanced expression can increase the vulnerability of primary MCs to injury due to complex IV-mediated inhibition by cyanide.

Adenosine Triphosphate↗
PubMed2005

Compact detector for proteins based on two-photon excitation of native fluorescence.

A compact, inexpensive detector for proteins has been constructed based on two-photon excitation of fluorescence from phenylalanine, tyrosine, and tryptophan. The fluorescence was excited by a solid-state microchip laser operating at 532 nm. Detection limits for phenylalanine, tyrosine, and tryptophan were 62 microM, 2.0 microM, and 470 nM, respectively, in a volume of 3 fL. The detection limit for a test protein, bovine serum albumin, was 130 nM.

Animals↗
PubMed2005

BAFF supports human B cell differentiation in the lymphoid follicles through distinct receptors.

B cell-activating factor of the tumor necrosis factor family (BAFF/BLys) plays a critical role in B cell survival and immune responses through its three receptors: BAFF receptor (BAFF-R/BR3), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA). Using specific antibodies, we have investigated the expression of BAFF-R on human tonsillar B cells and their functional roles in naive and germinal center (GC) B cell differentiation. Our studies show that BAFF-R is the dominant receptor on naive B cells. However, three receptors are differentially modulated during in vitro GC-B cell differentiation. BAFF-R expression increased initially and then decreased with a corresponding induction of TACI and BCMA expression during differentiation to plasma cells (PCs). Consistently, blocking of BAFF-R alone with specific mAb inhibited GC-B cell proliferation and PC generation in the early period of their differentiation, whereas depletion of BAFF with TACI-Ig exhibited consistent inhibition throughout the differentiation. Finally, histological and molecular analyses of human tonsil tissue revealed that follicular dendritic cells produce BAFF. In conclusion, BAFF in the GC plays an important role through more than one receptor, and the three known receptors are differentially modulated as GC-B cells differentiate to PCs.

Antibodies, Monoclonal↗
PubMed2005

Expression of TGF-beta1 in smooth muscle cells regulates endothelial progenitor cells migration and differentiation.

OBJECTIVE: Endothelial angiogenesis in the intima of the arterial wall is one of key events in the pathogenesis of arteriosclerosis. The molecular mechanisms by which transforming growth factor beta 1 (TGFbeta1) and endothelial progenitor cells may be responsible for angiogenesis of arteriosclerosis lesions are poorly understood. MATERIALS AND METHODS: Primary culture smooth muscle cells were transfected with pMAMneoTGFbeta1. ELISA checked VEGF expression in smooth muscle cells. Human EPCs (CD34+ cells) were cultured in pMAMneoTGFbeta1 or pMAMneo transfected smooth muscle cells conditional medium. After 21 days, differentiated endothelial colonies were confirmed by immunofluorescence for von Willebrand factor (vWF) and vascular-endothelial (VE)-cadherin. The VEGFR-1 expression in differentiated endothelial colonies was detected by ELISA. Cells migration and adhesion toward pMAMneoTGFbeta1 and pMAMneo transfected smooth muscle cells were also measured in parallel flow chamber. RESULTS: Abundant TGFbeta1 stable expressed in smooth muscle cells. TGFbeta1 transfected smooth muscle cells expressed significantly higher level VEGF than pMAMneo group. As judged by positive staining for endothelial markers vWF and VE-cadherin, the combination of TGFbeta1 transfected smooth muscle cells conditional medium produced significantly more endothelial colonies (P<0.05) than did pMAMneo group. The adhesion force between endothelial progenitor cells and smooth muscle cells in TGFbeta1 group was higher than control. CONCLUSION: TGFbeta1 expressed smooth muscle cells can be helpful for increasing endothelial progenitor cells adhesion and differentiation. It may be responsible for angiogenesis of arteriosclerosis lesions and useful for blood vessel tissue engineering.

Antigens, CD↗
PubMed2005

Role of Ras/PKCzeta/MEK/ERK1/2 signaling pathway in angiotensin II-induced vascular smooth muscle cell proliferation.

The role of protein kinase C (PKC) and its cross talk with extracellular signal-regulated kinase (ERK) cascade in angiotensin II (AngII)-elicited vascular smooth muscle cell (VSMC) proliferation are still unclear. In this study, the PKC pathway of AngII to activate ERK1/2 and induce cell proliferation was investigated in rat aortic smooth muscle cells. The proliferation of VSMCs was tested by [3H]-thymidine incorporation assay. Phosphorylated and non-phosphorylated PKCzeta, ERK1/2, Elk-1, and mitogen-activated ERK-activating kinase (MEK) were estimated by Western blot analysis. The interactions of signal molecules were examined by immunoprecipitation. AngII-induced VSMC proliferation and activation of ERK1/2 and nuclear transcription factor Elk-1 were all down-regulated by PKC non-specific inhibitor (staurosporine) and PKCzeta pseudosubstrate inhibitor (PS-PKCzeta). Dominant negative Ras transfection into VSMCs decreased AngII-induced PKCzeta and ERK1/2 phosphorylation. AngII stimulated the association of PKCzeta with Ras. AngII-induced MEK phosphorylation was inhibited by PKCzeta pseudosubstrate inhibitor and the PKCzeta-MEK complex was detected by immunoprecipitation. These results suggest that PKCzeta isoform is involved in VSMC proliferation and Elk-1 activation. AngII can activate ERK1/2 by Ras/PKCzeta/MEK pathway, which may be one of the important signal transduction pathways in AngII-induced VSMC proliferation.

Angiotensin II↗
PubMed2005

Pi class glutathione S-transferase genes are regulated by Nrf 2 through an evolutionarily conserved regulatory element in zebrafish.

Pi class GSTs (glutathione S-transferases) are a member of the vertebrate GST family of proteins that catalyse the conjugation of GSH to electrophilic compounds. The expression of Pi class GST genes can be induced by exposure to electrophiles. We demonstrated previously that the transcription factor Nrf 2 (NF-E2 p45-related factor 2) mediates this induction, not only in mammals, but also in fish. In the present study, we have isolated the genomic region of zebrafish containing the genes gstp1 and gstp2. The regulatory regions of zebrafish gstp1 and gstp2 have been examined by GFP (green fluorescent protein)-reporter gene analyses using microinjection into zebrafish embryos. Deletion and point-mutation analyses of the gstp1 promoter showed that an ARE (antioxidant-responsive element)-like sequence is located 50 bp upstream of the transcription initiation site which is essential for Nrf 2 transactivation. Using EMSA (electrophoretic mobility-shift assay) analysis we showed that zebrafish Nrf 2-MafK heterodimer specifically bound to this sequence. All the vertebrate Pi class GST genes harbour a similar ARE-like sequence in their promoter regions. We propose that this sequence is a conserved target site for Nrf 2 in the Pi class GST genes.

Amino Acid Sequence↗
PubMed2005

Generation of hematopoietic repopulating cells from human embryonic stem cells independent of ectopic HOXB4 expression.

Despite the need for alternative sources of human hematopoietic stem cells (HSCs), the functional capacity of hematopoietic cells generated from human embryonic stem cells (hESCs) has yet to be evaluated and compared with adult sources. Here, we report that somatic and hESC-derived hematopoietic cells have similar phenotype and in vitro clonogenic progenitor activity. However, in contrast with somatic cells, hESC-derived hematopoietic cells failed to reconstitute intravenously transplanted recipient mice because of cellular aggregation causing fatal emboli formation. Direct femoral injection allowed recipient survival and resulted in multilineage hematopoietic repopulation, providing direct evidence of HSC function. However, hESC-derived HSCs had limited proliferative and migratory capacity compared with somatic HSCs that correlated with a distinct gene expression pattern of hESC-derived hematopoietic cells that included homeobox (HOX) A and B gene clusters. Ectopic expression of HOXB4 had no effect on repopulating capacity of hESC-derived cells. We suggest that limitations in the ability of hESC-derived HSCs to activate a molecular program similar to somatic HSCs may contribute to their atypical in vivo behavior. Our study demonstrates that HSCs can be derived from hESCs and provides an in vivo system and molecular foundation to evaluate strategies for the generation of clinically transplantable HSC from hESC lines.

Animals↗
PubMed2005

Mechanisms of enhanced shock-induced arrhythmogenesis in the rabbit heart with healed myocardial infarction.

Shock-induced vulnerability and defibrillation have been mostly studied in structurally normal hearts. However, defibrillation therapy is normally applied to patients with diseased hearts, frequently those with prior myocardial infarction (MI). Shock-induced vulnerability and defibrillation have not been well studied under this condition. We sought to examine the mechanisms of shock-induced arrhythmogenesis and arrhythmia maintenance in a rabbit model of healed MI (4 wk or more postinfarction). Ligation of the lateral division or posterolateral division of the left coronary artery at a level of 40-70% from the apex was performed 53 +/- 21 days before acute experiments. Shock-induced vulnerability was assessed in infarcted (n = 8) and structurally normal (n = 8) hearts by delivering internal monophasic shocks at different shock strengths and delivery phases. Electrical activities from the anterior epicardium during shock application and during shock-induced arrhythmias were optically recorded and quantitatively analyzed. Ligation resulted in a transmural left ventricular free wall infarction mainly located at the apical region with a consistent endocardial border zone (BZ) as confirmed by histological studies. There were significant increases in the incidence, severity, and duration of shock-induced arrhythmias in the infarcted hearts versus controls due to 1) postshock break-excitation wavefronts that frequently originated near the infarction BZ and 2) the existence of an infarction BZ that created an anatomic reentry pathway and facilitated arrhythmia maintenance. In conclusion, the infarction BZ contributes to both increased shock-induced arrhythmogenesis and arrhythmia maintenance in the rabbit model of healed MI.

Animals↗
PubMed2005

Divergent folding pathways of two homologous proteins, BPTI and tick anticoagulant peptide: compartmentalization of folding intermediates and identification of kinetic traps.

Bovine pancreatic trypsin inhibitor (BPTI) and tick anticoagulant peptide (TAP) are two structurally homologous proteins, which have been shown to exhibit distinct mechanisms of oxidative folding. We demonstrate here differences of their folding properties using the technique of disulfide scrambling. Two extensively unfolded homologous isomers (beads-form) of BPTI (Cys5-Cys14, Cys30-Cys38, Cys51-Cys55) and TAP (Cys5-Cys15, Cys33-Cys39, Cys55-Cys59) were allowed to refold in parallel via disulfide shuffling of 13 potential isomers to form the native structure. Folding intermediates were trapped by acid quenching and analyzed by HPLC. The results reveal the following diversities: (a) there are two predominant folding intermediates of BPTI and seven well-populated folding intermediates of TAP. One of the two predominant BPTI intermediates (Cys5-Cys14, Cys30-Cys51, Cys38-Cys55) contains a native disulfide Cys30-Cys51 and constitutes about 34% of the total BPTI folding intermediates. In contrast, the TAP counterpart (Cys5-Cys15, Cys33-Cys55, Cys39-Cys59) represents only 5% of the total TAP intermediates; (b) three isomers of TAP sharing a stable non-native disulfide bond Cys15-Cys33 are shown to act as kinetic traps of TAP folding. Their counterparts are conspicuously absent in the BPTI folding; and (c) most significantly, folding intermediates of BPTI are found to be energetically compartmentalized, whereas most folding intermediates of TAP are inter-convertible and exist in dynamic equilibrium. Our studies further demonstrate optimal concentrations of denaturant required for destabilization of kinetic traps and acceleration of TAP folding.

Animals↗
PubMed2005

Molecular and biochemical characterization of the selenocysteine Se-methyltransferase gene and Se-methylselenocysteine synthesis in broccoli.

Selenium (Se) plays an indispensable role in human nutrition and has been implicated to have important health benefits, including being a cancer preventative agent. While different forms of Se vary in their anticarcinogenic efficacy, Se-methylselenocysteine (SeMSC) has been demonstrated to be one of the most effective chemopreventative compounds. Broccoli (Brassica oleracea var. italica) is known for its ability to accumulate high levels of Se with the majority of the selenoamino acids in the form of Se-methylselenocysteine. Therefore, it serves as a good model to study the regulation of SeMSC accumulation in plants. A cDNA encoding selenocysteine Se-methyltransferase, the key enzyme responsible for SeMSC formation, was cloned from broccoli using a homocysteine S-methyltransferase gene probe from Arabidopsis (Arabidopsis thaliana). This clone, designated as BoSMT, was functionally expressed in Escherichia coli, and its identity was confirmed by its substrate specificity in the methylation of selenocysteine. The BoSMT gene represents a single copy sequence in the broccoli genome. Examination of BoSMT gene expression and SeMSC accumulation in response to selenate, selenite, and sulfate treatments showed that the BoSMT transcript and SeMSC synthesis were significantly up-regulated in plants exposed to selenate but were low in plants supplied with selenite. Simultaneous treatment of selenate with selenite significantly reduced SeMSC production. In addition, high levels of sulfate suppressed selenate uptake, resulting in a dramatic reduction of BoSMT mRNA level and SeMSC accumulation. Our results reveal that SeMSC accumulation closely correlated with the BoSMT gene expression and the total Se status in tissues and provide important information for maximizing the SeMSC production in this beneficial vegetable plant.

Amino Acid Sequence↗
PubMed2005

Differential expression of domain III neutralizing epitopes on the envelope proteins of West Nile virus strains.

Neutralization of flaviviruses by antibody is primarily mediated via epitopes in the viral envelope (E) protein. Comparative studies using neutralizing monoclonal antibodies revealed differential expression of epitopes within the E protein domain III of ten naturally occurring West Nile virus strains representing major subtypes of genetic lineages 1 and 2. Residues that defined these subtype-specific determinants were identified by mutational studies and found to be surface exposed in the domain III structure. Mutations of residue 332 had the most significant effects on variation of domain III neutralizing epitopes among strains.

Amino Acid Sequence↗
PubMed2005

[Effect of tetramethylpyrazine on the responses of respiration and expression of nNOS in brainstem to hypoxia in rats].

The aim of the present study was to investigate the effect of tetramethylpyrazine (TMP) on the changes of respiration and expression of neuronal nitric oxide synthase (nNOS) in brainstem induced by hypoxia in the rats. Hypoxia was induced by inhalation of 8% O2-balanced N2.The electromyogram (EMG) of diaphragm was monitored to evaluate the respiratory response of the rats to hypoxia. The immunohistochemical staining technique was used to study the change of the expression of nNOS in the brainstem during hypoxia. In the rats of hypoxia group, a successive process of response, excitatory followed by inhibitory, was produced. Twenty min after hypoxia, a significant inhibition of respiration occurred, which was characterized with a marked decrease in the inspiratory duration, the respiratory frequency, and the amplitude of inspiration and a prolongation of expiratory duration (P<0.05). In the rats of pretreated with TMP, the respiratory activity was not obviously depressed (P>0.05). In the rats of hypoxia group, the level of nNOS immunoreactivity was enhanced remarkably in the lateral reticular nucleus, nucleus of trapezoid, hypoglossal nucleus and the facial nucleus compared with the control group (P<0.05). In the rats of pretreated with TMP, the nNOS level increased further in the nuclei mentioned above (P<0.05). The results obtained indicate that TMP can reverse the inhibitory effect of hypoxia on respiration in the rats and that nNOS may be involved in the respiratory protective action of TMP.

Animals↗