Biomedical subjects

Li Liu

Publications and source records attributed to Li Liu.

At least 163 records · Page 9Linked to original sources

PubMed2005

The second subunit of the replication factor C complex (RFC40) and the regulatory subunit (RIalpha) of protein kinase A form a protein complex promoting cell survival.

Replication Factor C (RFC) is required for the loading of Proliferating Cell Nuclear Antigen (PCNA) onto DNA during DNA replication, repair and recombination. RFC40, the second subunit of the RFC complex, and PCNA have been shown to be overexpressed in gestational trophoblastic diseases. Using RFC40 as the bait in a yeast two-hybrid screening, we have identified a novel interaction between RFC40 and the regulatory subunit (RIalpha) of cAMP-dependent Protein kinase A (PKA). The interaction sites between these two proteins were investigated and mapped to the N-terminus of RIalpha and the C-terminus of RFC40. Moreover, it was demonstrated that the C-subunit of PKA was not associated with the RFC40-RIalpha complex. Furthermore, RFC37, the third subunit of the RFC complex, competes with RIalpha and displaces it from the RFC40-RIalpha complex. Interestingly, downregulation of endogenous RIalpha by 8-chloro cAMP, in MCF7 breast cancer cells led to reduction in the amount of RFC40-RIalpha complex, together with decrease in cell survival.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2005

Tiam1 gene expression and its significance in colorectal carcinoma.

AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis. METHODS: Expressions of Tiam1 gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptase-polymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiam1 expression with the invasive ability was also analyzed. RESULTS: Tiam1 gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116, LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiam1 gene was highly related to the metastatic potential of colorectal carcinoma cells. CONCLUSION: Tiam1 gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.

Cell Line, Tumor↗

PubMed2005

Fabrication of a novel Li(x)MoOy film modified electrode and its application as an electrochemical sensor of iodate.

A novel organic gel film modified electrode was simply and conveniently fabricated by casting Li(x)MoOy and polypropylene carbonate (PPC) onto the surface of a gold electrode. The cyclic voltammetry and amperometry studies demonstrated that the Li(x)MoOy film modified electrode has a high stability and a good electrocatalytic activity for the reduction of iodate. In amperometry, a good linear relationship between the steady current and the concentration of iodate was obtained in the range from 3x10(-7) to 1x10(-4) mol L-1 with a correlation coefficient of 0.9997 and a detection limit of 1x10(-7) mol L-1.

Journal Article↗

PubMed2005

Immortalization of human small airway epithelial cells by ectopic expression of telomerase.

Two immortalized human airway epithelial cell lines were established by the ectopic expression of human telomerase reverse transcriptase (hTERT). These cell lines have been continuously cultured for >200 population doublings (PDs). They are characterized by an overexpression of hTERT mRNA, elongated telomere length and higher telomerase activity. Early passage of these cells (<20 PDs) expressed the p16 protein at a level comparable to their parental cells. In later passages (>150 PDs), p16 protein was decreased but recovered to the early passage level upon treatment with a methylation inhibitor, 5-Aza-CdR. Chromosome analysis showed a near-diploid karyotype albeit with a gain or loss of certain chromosomes and a few stable translocations in both cell lines. No p53 gene alterations were found in these cell lines. They remained anchorage dependent in growth and were non-tumorigenic in nude mice. These two cell lines are the first reported immortalized human airway epithelial cell lines by hTERT expression without incorporation of virus or other genes, which may serve as a useful model system for studies on bronchial carcinogenesis.

Animals↗

PubMed2005

Preparation of chitosan-g-polycaprolactone copolymers through ring-opening polymerization of epsilon-caprolactone onto phthaloyl-protected chitosan.

The new biodegradable chitosan graft copolymer, chitosan-g-polycaprolactone, was synthesized by the ring-opening graft copolymerization of epsilon-caprolactone onto phthaloyl-protected chitosan (PHCS) at the hydroxyl group in the presence of tin(II) 2-ethylhexanoate catalyst via a protection-graft-deprotection procedure. Toluene acted as a swelling agent in this heterogeneous system. The grafting reactions were conducted with various PHCS/monomer/toluene feed ratios to obtain chitosan-g-polycaprolactone copolymers with various polycaprolactone contents. The chemical structure of the chitosan-g-polycaprolactone was characterized by Fourier transform infrared and one- and two-dimensional NMR spectroscopy. After deprotection, the phthaloyl group was removed and the amino group was regenerated. Thus the obtained chitosan-g-polycaprolactone was an amphoteric hybrid with a large amount of free amino groups and hydrophobic polycaprolactone side chains. Some properties of the final product were also investigated, such as crystallinity, thermal property, and solubility.

Amino Acids↗

PubMed2005

Differential display of proteins involved in the neural differentiation of mouse embryonic carcinoma P19 cells by comparative proteomic analysis.

Mouse embryonic carcinoma P19 cell has been used extensively as a model to study molecular mechanisms of neural differentiation in vitro. After retinoic acid (RA) treatment and aggregation, P19 cells can differentiate into neural cells including neurons and glial cells. In this study, comparative proteomic analysis is utilized to approach the protein profiles associated with the RA-induced neural differentiation of P19 cells. Image analysis of silver stained two-dimensional gels indicated that 28 protein spots had significantly differential expression patterns in both quantity and quality. With mass spectrometry analysis and protein functional exploration, many proteins demonstrated an association with distinct aspects of neural differentiation. These proteins were gag polyprotein, rod cGMP-specific 3',5'-cyclic phosphodiesterase, 53 kDa BRG1-associated factor A, N-myc downstream regulated 1, Vitamin D receptor associated factor 1, stromal cell derived factor receptor 1, phosphoglycerate mutase, Ran-specific GTPase-activating protein, and retinoic acid (RA)-binding protein. While some cytoskeleton-related proteins such as beta cytoskeletal actin, gamma-actin, actin-related protein 1, tropomyosin 1, and cofilin 1 are related to cell migration and aggregation, other proteins have shown a relationship with distinct aspects of neural differentiation including energy production and utilization, protein synthesis and folding, cell signaling transduction, and self-protection. The differential expression patterns of these 28 proteins indicate their different roles during the neural differentiation of P19 cells. As an initial step toward unveiling the regulations involved in the commitment of pluripotent cells to a neural fate, information from this study may be helpful to uncover the molecular mechanisms of neural differentiation.

Animals↗

PubMed2005

Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma.

Malignant astrocytoma, the most prevalent primary brain tumor, is resistant to all known therapies and frequently harbors mutations that inactivate p53 and activate Ras signaling. We have generated mouse strains that lack p53 and harbor a conditional allele of the NF1 tumor suppressor that negatively regulates Ras signaling. The mice develop malignant astrocytomas with complete penetrance. The majority of tumors display characteristics of glioblastoma multiforme with concomitant alteration of signaling pathways previously described in the human counterparts of this neoplasm. We find that the sequence of tumor suppressor inactivation influences tumorigenicity and that earliest evidence of tumor formation localizes to regions of the brain that contain a multipotent stem cell population capable of in vivo differentiation into neurons and glia.

Animals↗

PubMed2005

Tubal ligation does not affect hormonal changes during the early menopausal transition.

BACKGROUND: To determine if women with a bilateral tubal ligation (BTL) were more likely to experience hormonal changes indicative of the transition to menopause or an increase in menopausal symptoms compared to women without a BTL. METHODS: Menopausal symptoms and hormone profiles of 134 women reporting a BTL were compared throughout the course of a 4-year follow-up study to 172 women without a BTL. Generalized linear regression models for repeated measures were used to estimate the independent effect of BTL on menopausal symptoms and hormonal levels adjusted for covariates. RESULTS: Forty-four percent of women reported a BTL and over one-half of women with a BTL experienced hot flashes. Women with a BTL had similar hormonal levels over the study period compared to women without a BTL. In addition, no relationship was found between BTL and any of the menopausal symptoms, including hot flashes, decreased libido or increased anxiety adjusting for age, race, body mass index (BMI), education, menopausal status and parity. CONCLUSION: These findings document that women with a BTL have similar changes in sex hormone levels over the perimenopausal period compared to women without a BTL independent of other covariates. In addition, the reporting of menopausal symptoms was similar between the groups.

Adult↗

PubMed2005

Successful treatment of experimental autoimmune myocarditis by adenovirus-mediated gene transfer of antisense CIITA.

Experimental autoimmune myocarditis (EAM) has been used as a model for human myocarditis in relation to the autoimmune mechanism and proved as a T cell-mediated autoimmune disease. Interaction of T cell receptors (TCR) with its ligand peptide-MHC complex on APCs is critical for antigen-specific T cell activation under physiological and pathological conditions. CIITA is a transcriptional coactivator that functions as a key regulatory factor for MHC-II expression. To achieve effective inhibition of interaction of TCR and peptide-MHC-II complex, adenovirus vectors containing antisense CIITA were constructed and their effects in preventing EAM were examined. Ad-CIITA was injected intravenously into mice on days 0-2 or 14-16 after myosin immunization to study the preventive effects on EAM in the T cell activation phase or inflammatory phase. Disease severity was determined by the microscopic grade of heart check, concentration of plasma cTnI, and cellular and humoral immune responses on day 21. Results show that onset of EAM after Ad-CIITA treatment on days 0-2 was almost completely inhibited and antigen-specific lymphocyte proliferation was significantly reduced in adenovirus treatment group, which demonstrate that this adenovirus vector inhibit auto-responsive T cells activation and proliferation. Moreover, compared with EAM mice, even administered on days 14-16, the Ad-CIITA treated mice achieved significant reduction in disease severity. It indicates the therapeutic potential of blocking T cells activation by gene-transfer in myocarditis.

Adenoviridae↗

PubMed2005

Phthalide Lactones from Ligusticum chuanxiong inhibit lipopolysaccharide-induced TNF-alpha production and TNF-alpha-mediated NF-kappaB Activation.

The dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae) is a traditional Chinese medicine (TCM) herb for the prevention and treatment of inflammatory and cardiovascular diseases. However, the role of phthalide lactones from Ligusticum chuanxiong in the therapeutic actions is not yet fully understood. In the present study, two phthalide lactones from the herb, Z-ligustilide and senkyunolide A, were identified and characterized as inhibitors of lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes. The results of gene expression studies showed that the observed TNF-alpha suppression was related to their inhibitory activity on TNF-alpha mRNA transcription. Furthermore, the two phthalides exhibited significant suppressive effects on TNF-alpha-mediated nuclear factor-kappaB (NF-kappaB) activation in reporter gene assays. Taken together, the results suggest that Z-ligustilide and senkyunolide A may have potential applications in the treatment of inflammation and related diseases based on their inhibitory activity on TNF-alpha production and TNF-alpha bioactivity. New insights into the therapeutic basis of the TCM herb, Ligusticum chuanxiong, are presented.

Benzofurans↗

PubMed2005

Provisional stenting for multivessel PCI.

BACKGROUND: Bare stents reduce acute complications and repeat revascularization following percutaneous coronary intervention (PCI), but are costly and may lead to in-stent restenosis. It remains unclear whether stents should be universally implanted or whether provisional stenting mainly to suboptimal balloon dilatation results is an acceptable approach for multivessel PCI. OBJECTIVE: To compare the long-term clinical restenosis and target lesion revascularization (TLR) of stented and non-stented coronary artery lesions in patients who had multivessel PCI. METHODS: We performed retrospective analysis of matched data from 129 consecutive patients who underwent multivessel PCI (at least optimal balloon angioplasty to one coronary artery segment and balloon angioplasty plus stenting to another coronary artery in the same patient, all lesions are de novo native coronary artery lesions with vessel diameter >/=2.5 mm). The study endpoint was restenosis and repeat revascularization at one-year follow-up. RESULTS: Baseline characteristics were similar in both groups. Low in-hospital MACE (3.1%). Acute myocardial infarction, emergency revascularization via either PCI or CABG was detected and angiographic success was achieved in 99.3% of lesions in both groups. The rate of clinically driven angiographic restenosis and TLR at one-year (follow-up 100%) was similar (17.1% versus 18.6%, P=0.871, and 13.9% versus 16.3%, P=0.728, for optimal balloon angioplasty versus provisional stenting. CONCLUSIONS: The main findings from this study are that long-term angiographic restenosis and TLR was comparable for optimal balloon angioplasty and provisional stenting, suggesting that provisional stenting is an acceptable approach for multivessel PCI.

Age Distribution↗

PubMed2005

Inhibition of neuronal apoptosis by the cyclin-dependent kinase inhibitor GW8510: identification of 3' substituted indolones as a scaffold for the development of neuroprotective drugs.

Increasing evidence suggests that neuronal apoptosis is triggered by the inappropriate activation of cyclin-dependent kinases leading to an abortive re-entry of neurons into the cell cycle. Pharmacological inhibitors of cell-cycle progression may therefore have value in the treatment of neurodegenerative diseases in humans. GW8510 is a 3' substituted indolone that was developed recently as an inhibitor of cyclin-dependent kinase 2 (CDK2). We found that GW8510 inhibits the death of cerebellar granule neurons caused by switching them from high potassium (HK) medium to low potassium (LK) medium. Although GW8510 inhibits CDK2 and other CDKs when tested in in vitro biochemical assays, when used on cultured neurons it only inhibits CDK5, a cytoplasmic CDK that is not associated with cell-cycle progression. Treatment of cultured HEK293T cells with GW8510 does not inhibit cell-cycle progression, consistent with its inability to inhibit mitotic CDKs in intact cells. Neuroprotection by GW8510 is independent of Akt and MEK-ERK signaling. Furthermore, GW8510 does not block the LK-induced activation of Gsk3beta and, while inhibiting c-jun phosphorylation, does not inhibit the increase in c-jun expression observed in apoptotic neurons. We also examined the effectiveness of other 3' substituted indolone compounds to protect against neuronal apoptosis. We found that like GW8510, the VEGF Receptor 2 Kinase Inhibitors [3-(1H-pyrrol-2-ylmethylene)-1,3-dihydroindol-2-one], {(Z)-3-[2,4-Dimethyl-3-(ethoxycarbonyl)pyrrol-5-yl)methylidenyl]indol-2-one} and [(Z)-5-Bromo-3-(4,5,6,6-tetrahydro-1H-indol-2-ylmethylene)-1,3-dihydroindol-2-one], the Src family kinase inhibitor SU6656 and a commercially available inactive structural analog of an RNA-dependent protein kinase inhibitor 5-Chloro-3-(3,5-dichloro-4-hydroxybenzylidene)-1,3-dihydro-indol-2-one, are all neuroprotective when tested on LK-treated neurons. Along with our recent identification of the c-Raf inhibitor GW5074 (also a 3' substituted indolone) as a neuroprotective compound, our findings identify the 3' substituted indolone as a core structure for the designing of neuroprotective drugs that may be used to treat neurodegenerative diseases in humans.

Animals↗

PubMed2005

Attitudes and predictive factors for live kidney donation: a comparison of live kidney donors versus nondonors.

BACKGROUND: Live donor kidney transplantation (LDKT), although far from risk free, is a reasonably safe procedure for medically suitable donors. We hypothesized that both potential recipients and donors have identifiable and modifiable factors that contribute to the likelihood of LDKT. The objectives of this study were to describe and quantify these factors using anonymous, confidential questionnaires. METHODS: Specifically designed questionnaires addressing personal characteristics, knowledge, and beliefs about LDKT were mailed to 127 previous donors and 387 relatives of patients newly listed on the cadaver transplant wait-list. Ninety-eight (77%) and 243 (63%) responses were returned by donors and nondonors, respectively. RESULTS: There were significant differences between groups in gender, ethnicity, hours worked per week, and annual income. Significant differences were seen in both knowledge and beliefs about LDKT. Most donors indicated they made their decisions without lengthy deliberation or research about kidney donation. Only 20% of nondonors feel they are well informed about LDKT. CONCLUSION: It is likely possible to improve knowledge about LDKT among friends and relations of patients with renal failure, but it is not certain that this will lead to increased donation because most donors don't appear to deliberate or research organ donation before making a commitment to donate. Strategies to educate potential donors should initially focus on the recipient.

Adult↗

PubMed2005

Establishment and utilization of a tetracycline-controlled inducible RNA interfering system to repress gene expression in chronic myelogenous leukemia cells.

RNA interference (RNAi), a posttranscriptional gene silencing process mediated by small double-stranded RNA specifically complementary to the targeted transcript, has been used extensively in the development of novel therapeutic approaches against various human diseases including chronic myelogenous leukemia (CML). Here, we report the successful construction of a tetracycline-controlled siRNA in CML cell line K562. A K562 cell line stably expressing the reverse tetracycline-controlled transactivator (rtTA) was constructed. A tetracycline responsive element (TRE) was integrated into the RNA polymerase III promoter region of pBS/U6 that was used to drive specific siRNA to target the novel cytokine receptor-like factor 3 (CRLF3) gene. The results show that rtTA was able to recognize the TRE to prevent siRNA-mediated exogenous and endogenous CRLF3 gene repressions. Moreover, CRLF3-siRNA mediated gene repression could be induced in a dose-dependent manner in the presence of doxycycline. Thus, the inducible siRNAi system in K562 cells might be useful for the study of RNAi-mediated therapeutic approaches against CML.

Base Sequence↗

PubMed2005

The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication.

The role and functional domain of hepatitis B virus (HBV) X protein (HBx) in regulating HBV transcription and replication were investigated with a transient transfection system in the human hepatoma cell line HepG2 using wild-type or HBx-minus HBV genome constructs and a series of deletion or mutation HBx expression plasmids. We show here that HBx has augmentation effects on HBV transcription and replication as a HBV mutant genome with defective X gene led to decreased levels of 3.5-kb HBV RNA and HBV replication intermediates and that these decreases can be restored by either transient ectopic expression of HBx or a stable HBx expression cell line. The C-terminal two-thirds (amino acids [aa] 51 to 154), which contain the transactivation domain, is required for this function of HBx; the N-terminal one-third (aa 1 to 50) is not required. Using the alanine scanning mutagenesis strategy, we demonstrated that the regions between aa 52 to 65 and 88 to 154 are important for the augmentation function of HBx in HBV replication. By the luciferase reporter gene analysis, we found that the transactivation and coactivation activities of HBx coincide well with its augmentation function in HBV transcription and replication. These results suggest that HBx has an important role in stimulating HBV transcription and replication and that the transcriptional transactivation function of HBx may be critical for its augmentation effect on HBV replication.

Amino Acid Sequence↗

PubMed2005

Inactivation of NF1 in CNS causes increased glial progenitor proliferation and optic glioma formation.

The gene responsible for neurofibromatosis type 1 (NF1) encodes a tumor suppressor that functions as a negative regulator of the Ras proto-oncogene. Individuals with germline mutations in NF1 are predisposed to the development of benign and malignant tumors of the peripheral and central nervous system (CNS). Children with this disease suffer a high incidence of optic gliomas, a benign but potentially debilitating tumor of the optic nerve; and an increased incidence of malignant astrocytoma, reactive astrogliosis and intellectual deficits. In the present study, we have sought insight into the molecular and cellular basis of NF1-associated CNS pathologies. We show that mice genetically engineered to lack NF1 in CNS exhibit a variety of defects in glial cells. Primary among these is a developmental defect resulting in global reactive astrogliosis in the adult brain and increased proliferation of glial progenitor cells leading to enlarged optic nerves. As a consequence, all of the mutant optic nerves develop hyperplastic lesions, some of which progress to optic pathway gliomas. These data point to hyperproliferative glial progenitors as the source of the optic tumors and provide a genetic model for NF1-associated astrogliosis and optic glioma.

Animals↗

PubMed2005

Spatial processing in color reproduction.

We consider the reproduction of color subject to material and neighborhood constraints. By "material constraints," we mean any constraints that are applied to the amount of ink, lights, voltages, and currents that are used in the generation of color. In the first instance we consider the problem of reproducing a target color constrained by maximum additive color signals, such as in the phosphorescence process in a cathode ray tube. In the second instance we consider the more difficult problem of reproducing color subject to constraints on the maximum primary color variations in a (spatial) neighborhood. We introduce the idea of adjacent color variance (ACV) and then attempt to reproduce colors subject to an upper bound on the ACV. An algorithm that is suitable for this task is the method of vector space projections (VSP). In order to use VSP for constrained color reproduction, we use a novel approach to linearize nonlinear CIE-Lab space constraints. Experimental results are furnished that demonstrate that using the ACV as a bound helps to reduce reproduction artifacts in a color image.

Algorithms↗

PubMed2005

Synthesis and evaluation of a novel gene reporter molecule: detection of beta-galactosidase activity using 19F NMR of a fluorinated vitamin B6 conjugate+.

Gene therapy has emerged as a promising strategy for treatment of various diseases. However, widespread implementation is hampered by difficulties in assessing the success of transfection, in particular, the spatial extent of expression in the target tissue and the longevity of expression. Thus, the development of non-invasive reporter techniques based on appropriate molecules and imaging modalities may help to assay gene expression. We now report the design, synthesis and evaluation of a novel in vivo gene transfection reporter molecule 3-O-(beta-D-galactopyranosyl)-6-fluoropyridoxol (GFPOL) using fluorinated vitamin B(6) as the (19)F NMR sensitive aglycone. GFPOL exhibits the following strengths as an in vivo (19)F NMR gene expression reporter: (a) large chemical shift response to enzyme cleavage (Deltadelta=8.00 ppm); (b) minimal toxicity for substrate or aglycone; (c) good water solubility; (d) good blood stability; (e) pH responsiveness of aglycone.

Fluorine↗