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Biomedical subjects

Jie Liu

Publications and source records attributed to Jie Liu.

At least 145 records · Page 8Linked to original sources
PubMed2005

Lamina propria and olfactory bulb ensheathing cells exhibit differential integration and migration and promote differential axon sprouting in the lesioned spinal cord.

Olfactory bulb-derived (central) ensheathing cell (OB OEC) transplants have shown significant promise in rat models of spinal cord injury, prompting the use of lamina propria-derived (peripheral) olfactory ensheathing cells (LP OECs) in both experimental and clinical trials. Although derived from a common embryonic precursor, both sources of OECs reside in different nervous system compartments postnatally, and their ability to promote regeneration and efficacy after transplantation may differ depending on both their source and mode of transplantation. Here, we have purified green fluorescent protein-expressing LP and OB OECs, assayed their biological differences in vitro, and transplanted them acutely either directly into or rostral and caudal to a dorsolateral funiculus crush. LP and OB OECs exhibit multiple morphological and antigenic similarities in vitro, and, after transplantation, they both attenuate lesion and cavity formation and promote angiogenesis, endogenous Schwann cell infiltration, and axonal sprouting. However, an increased mitotic rate and migratory ability of LP OECs in vitro was reflected in vivo by their superior ability to migrate within the spinal cord, reduce cavity formation and lesion size, and differentially stimulate outgrowth of axonal subpopulations compared with OB OECs. An undesired behavior (autotomy) was also significantly enhanced by LP OEC, over OB OEC, transplantation. These results suggest that LP and OB OECs exhibit intrinsic biological differences that, after transplantation into the lesioned CNS, result in differences in postlesion spinal cord neuropathology and anatomical and behavioral regeneration outcomes that also vary depending on direct versus rostrocaudal transplantation.

Animals↗
PubMed2005

Acquired cadmium resistance in metallothionein-I/II(-/-) knockout cells: role of the T-type calcium channel Cacnalpha1G in cadmium uptake.

Metallothioneins (MTs) are cytoplasmic proteins that sequester certain divalent cations and are considered a primary cellular defense against the toxic transition metal cadmium (Cd(2+)). MT-I/II(-/-) knockout [MT(-/-)] cells are available and serve as an excellent tool to study non-MT-related mechanisms in metal tolerance. In the current study, Cd(2+)-resistant MT(-/-) (CdR) and CdR revertant (CdR-rev) cell lines were developed and characterized to investigate non-MT-mediated cellular protection mechanisms. Resistance to Cd(2+) was approximately 70-fold higher in CdR than the parental MT(-/-) cell line (IC(50) = 20 versus 0.3 microM, respectively) and was stable in the absence of Cd(2+) for 35 days. Accumulation of Cd(2+) by the CdR cell line was reduced by approximately 95% compared with parental cells, primarily because of a decreased Cd(2+) uptake. Cd(2+) uptake by the MT(-/-) parental cell line was independent of sodium, energy, and electrogenic potential. Uptake was saturable (K(m) = 65 nM; V(max) = 4.9 pmol/mg/min) and pH-dependent (maximal at pH 6.5-7). Potent inhibitors of Cd(2+) uptake included Zn(2+) (IC(50) = 7 microM), Mn(2+) (IC(50) = 0.4 microM), and the T-type Ca(2+) channel antagonist mibefradil (IC(50) = 5 microM), whereas other metals (including Fe(2+)) and L-type Ca(2+) channel antagonists had little effect. Immunoblot and real-time reverse transcription-polymerase chain reaction analysis indicated that the Cacnalpha(1G) T-type Ca(2+) channel was expressed at a reduced level in CdR compared with the parental MT(-/-) cell line, suggesting it is important for Cd(2+) uptake. The CdR1-rev cell line was found to have a Cd(2+) uptake and sensitivity level in between that of the CdR1 and MT(-/-) cell lines. Consistent with this was an intermediate expression of Cacnalpha(1G) in the CdR-rev cell line. These data suggest that decreased expression of Cacnalpha(1G) protects cells from Cd(2+) exposure by limiting Cd(2+) uptake.

Animals↗
PubMed2005

Anti-androgenic activities of Ganoderma lucidum.

The inhibitory effects of methanol extracts of 19 edible and medicinal mushrooms on 5alpha-reductase activity were examined. The extract of Ganoderma lucidum Fr. Krast (Ganodermataceae) showed the strongest 5alpha-reductase inhibitory activity. The treatment of the fruit body of Ganoderma lucidum or the extract prepared from it significantly inhibited the testosterone-induced growth of the ventral prostate in castrated rats. These results showed that Ganoderma lucidum might be a useful ingredient for the treatment of benign prostatic hyperplasia (BPH).

Androgen Antagonists↗
PubMed2005

Endothelial-monocyte activating polypeptide II alters fibronectin based endothelial cell adhesion and matrix assembly via alpha5 beta1 integrin.

Mature Endothelial-Monocyte Activating Polypeptide (mEMAP) II functions as a potent antiangiogenic peptide. Although the anti-tumor effect of mEMAP II has been described, little is known regarding its mechanism of action. Observations that mEMAP II induced apoptosis only in a subset of migrating and proliferating endothelial cells (EC) suggests a targeted effect on cells engaged in angiogenic activities which are known to rely upon cell adhesion and migration. Indeed, we demonstrate that mEMAP II inhibited fibronectin (FN) dependent microvascular EC (MEC) adhesion and spreading and we show that this depends upon the alpha5 beta1 integrin. Immunofluorescence analysis demonstrated that mEMAP II-dependent blockade of FN-alpha5 beta1 interactions was associated with disassembly of both actin stress fiber networks and FN matrix. These findings suggest that mEMAP II blocks MEC adhesion and spreading on fibronectin, via a direct interaction with the integrin alpha5 beta1, thus implicating that alpha5 integrin may be a mediator of mEMAP II's antiangiogenic function.

Angiogenesis Inhibitors↗
PubMed2005

Biliverdin reductase, a major physiologic cytoprotectant, suppresses experimental autoimmune encephalomyelitis.

Oxidative stress plays an important role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Bilirubin is regarded today as a potent antioxidant. Recent studies show that the potent antioxidant actions of bilirubin reflect an amplification mechanism whereby biliverdin reductase (BVR) physiologically regenerates bilirubin in a catalytic cycle. We hypothesized that BVR might prove to be a new effective target for the treatment of free radical-mediated diseases. In this study, we demonstrated that treatment with BVR ameliorated both clinical and pathological signs of EAE more efficiently than treatments with traditional antioxidant enzymes. In vitro, interference with cellular BVR activity by siRNA elicited greater increases in reactive oxygen species and cell death than interference with the activities of other antioxidant enzymes. Further studies showed that BVR surpasses other enzymes by the multifactorial functions of its only end product, bilirubin, including anti-complement activity, and an activity that inhibits antibody-dependent cell-mediated cytotoxicity of lymphocytes. Since BVR regenerates bilirubin in a redox cycle without significantly increasing the concentration of bilirubin, our results suggest that BVR may represent a novel strategy for the treatment of multiple sclerosis and other oxidative stress-mediated diseases.

Animals↗
PubMed2005

Toxic effects of fumonisin in mouse liver are independent of the peroxisome proliferator-activated receptor alpha.

Fumonisin mycotoxins occur worldwide in corn and corn-based foods. Fumonisin B1 (FB1) is a rodent liver carcinogen and suspected human carcinogen. It inhibits ceramide synthase and increases tissue sphinganine (Sa) and sphingosine (So) concentrations. Events linking disruption of sphingolipid metabolism and fumonisin toxicity are not fully understood; however, Sa and So were shown to bind mouse recombinant peroxisome proliferator-activated receptor alpha (PPARalpha) in vitro. To investigate the role of PPARalpha in fumonisin hepatotoxicity in vivo, wild-type (WT) and PPARalpha-null mice were fed control diets or diets containing 300 ppm FB1, Fusarium verticillioides culture material (CM) providing 300 ppm FB1, or 500 ppm of the peroxisome proliferator WY-14,643 (WY) for 1 week. WY-fed WT mice exhibited hepatomegaly, an effect not found in WY-fed PPARalpha-null mice, and WY did not change liver sphingoid base concentrations in either strain. Hepatotoxicity found in FB1- and CM-fed WT and PPARalpha-null mice was similar, qualitatively different from that found in WY-treated animals, and characterized by increased Sa concentration, apoptosis, and cell proliferation. Transcript profiling using oligonucleotide arrays showed that CM and FB1 elicited similar expression patterns of genes involved in cell proliferation, signal transduction, and glutathione metabolism that were different from that altered by WY. Real-time RT-PCR analysis of gene expression demonstrated PPARalpha-dependence of lipid metabolism gene expression in WY-treated mice, whereas PPARalpha-independent alterations of genes in lipid metabolism, and other categories, were found in CM- and FB1-fed mice. Together, these findings demonstrate that FB1- and CM-induced hepatotoxicity in mice does not require PPARalpha.

Administration, Oral↗
PubMed2005

The application of macroporous resins in the separation of licorice flavonoids and glycyrrhizic acid.

Glycyrrhizic acid (GA) and licorice flavonoids (LF) are the two classes of bioactive components in licorice with known pharmacological effects. But long-term excessive intake of GA may cause sodium retention and hypertension. In this study, the performance and adsorption characteristics of four widely used macroporous resins for the separation of deglycyrrhizinated, flavonoids enriched licorice has been critically evaluated. The sorption and desorption properties of LF and GA on macroporous resins including XDA-1, LSA-10, D101 and LSA-20 have been compared. The adsorption capacity was found to depend strongly on the pH of the feed solution. XDA-1 offers much higher adsorption capacity for GA and LF than other resins, and its adsorption data fit the best to the Freundlich isotherm. XDA-1 also shows much higher adsorption affinity towards LF than that of GA based on calculated results from the measured adsorption isotherms. Dynamic adsorption and desorption experiments have been carried out on a XDA-1 resin packed column to obtain optimal parameters for separating GA and LF. An enriched LF extract (about 21.9% purity) free of GA, and an enriched GA extract with 66% purity can be separated from crude licorice extract in one run.

Adsorption↗
PubMed2005

Band structure, phonon scattering, and the performance limit of single-walled carbon nanotube transistors.

Semiconducting single-walled carbon nanotubes are studied in the diffusive transport regime. The peak mobility is found to scale with the square of the nanotube diameter and inversely with temperature. The maximum conductance, corrected for the contacts, is linear in the diameter and inverse temperature. These results are in good agreement with theoretical predictions for acoustic phonon scattering in combination with the unusual band structure of nanotubes. These measurements set the upper bound for the performance of nanotube transistors operating in the diffusive regime.

Journal Article↗
PubMed2005

Crystal structures of the main peptidase from the SARS coronavirus inhibited by a substrate-like aza-peptide epoxide.

The main peptidase (M(pro)) from the coronavirus (CoV) causing severe acute respiratory syndrome (SARS) is one of the most attractive molecular targets for the development of anti-SARS agents. We report the irreversible inhibition of SARS-CoV M(pro) by an aza-peptide epoxide (APE; k(inact)/K(i) = 1900(+/-400) M(-1) s(-1)). The crystal structures of the M(pro):APE complex in the space groups C2 and P2(1)2(1)2(1) revealed the formation of a covalent bond between the catalytic Cys145 S(gamma) atom of the peptidase and the epoxide C3 atom of the inhibitor, substantiating the mode of action of this class of cysteine-peptidase inhibitors. The aza-peptide component of APE binds in the substrate-binding regions of M(pro) in a substrate-like manner, with excellent structural and chemical complementarity. In addition, the crystal structure of unbound M(pro) in the space group C2 revealed that the "N-fingers" (N-terminal residues 1 to 7) of both protomers of M(pro) are well defined and the substrate-binding regions of both protomers are in the catalytically competent conformation at the crystallization pH of 6.5, contrary to the previously determined crystal structures of unbound M(pro) in the space group P2(1).

Binding Sites↗
PubMed2005

Dose-dependent beneficial and detrimental effects of ROCK inhibitor Y27632 on axonal sprouting and functional recovery after rat spinal cord injury.

Axonal regeneration within the injured central nervous system (CNS) is hampered by multiple inhibitory molecules in the glial scar and the surrounding disrupted myelin. Many of these inhibitors stimulate, either directly or indirectly, the Rho intracellular signaling pathway, providing a strong rationale to target it following spinal cord injuries. In this study, we infused either control (PBS) or a ROCK inhibitor, Y27632 (2 mM or 20 mM, 12 microl/day for 14 days) into the intrathecal space of adult rats starting immediately after a cervical 4/5 dorsal column transection. Histological analysis revealed that high dose-treated animals displayed significantly more axon sprouts in the grey matter distal to injury compared to low dose-treated rats. Only the high dose regimen stimulated sprouting of the dorsal ascending axons along the walls of the lesion cavity. Footprint analysis revealed that the increased base of support normalized significantly faster in control and high dose-treated animals compared to low dose animals. Forepaw rotation angle, and the number of footslips on a horizontal ladder improved significantly more by 6 weeks in high dose animals compared to the other two groups. In a food pellet reaching test, high dose animals performed significantly better than low dose animals, which failed to recover. There was no evidence of mechanical allodynia in any treatment group; however, the slightly shortened heat withdrawal times normalized only with the high dose treatment. Collectively, our data support beneficial effects of high dose Y27632 treatment but indicate that low doses might be detrimental.

Actin Depolymerizing Factors↗
PubMed2005

A novel rat medial prefrontal cortical slice preparation to investigate synaptic transmission from amygdala to layer V prelimbic pyramidal neurons.

Electrophysiological recordings from identified synapses in CNS slice preparations in vitro provide important information regarding the connectivity of neuronal circuits and the underlying cellular mechanisms responsible for neuronal excitability and synaptic transmission. We present an anatomical, electrophysiological, and pharmacological characterization of a novel brain slice preparation (BLA-mPFC) to investigate basolateral amygdala synaptic input to rat layer V medial prefrontal cortex pyramidal neurons. A fluorescent tracer (DiI) unilaterally infused in vivo into the basolateral amygdala was used to detect amygdala efferent fibers innervating layer V of the prelimbic and infralimbic cortices within prefrontal cortex slices. In vitro, evoked synaptic responses elicited by stimulating identified basolateral amygdala pathway terminals within the acute BLA-mPFC slice preparation yielded monosynaptic excitatory postsynaptic responses in layer V pyramidal neurons from the prelimbic cortex as determined by extracellular and intracellular recordings. The BLA-mPFC preparation provides essential knowledge of amygdaloid input to the medial prefrontal cortex where information from various brain areas is integrated and returned to subcortical structures, such as the amygdala itself. In addition to investigating normal synaptic function, this preparation provides opportunities to investigate this synapse in animals which have received drugs chronically or have been manipulated genetically to model specific mental diseases known to involve prefrontal cortex and/or amygdala pathology (e.g., schizophrenia, addiction, anxiety, and depression).

Amygdala↗
PubMed2005

Dynamic conformational changes of extracellular S5-P linkers in the hERG channel.

The hERG channel has an unusually long 'S5-P linker' (residues 571-613) that lines the outer mouth of the pore. Previously, we have shown that residues along this S5-P linker are critical for the fast-inactivation process and K(+) selectivity of the hERG channel. Here we used several approaches to probe the structure of this S5-P linker and its interactions with other domains of the hERG channel. Circular dichroism and NMR analysis of a synthetic hERG S5-P linker peptide suggested that this linker is quite dynamic: its central region (positions 583-593) can be unstructured or helical, depending on whether it is immersed in an aqueous phase or in contact with a hydrophobic environment. Cysteine introduced into positions 583-597 of the S5-P linker can form intersubunit disulphide bonds, and at least four of them (at 584, 585, 588 and 589) can form disulphide bonds with counterparts from neighbouring subunits. We propose that the four S5-P linkers in a hERG channel can engage in dynamic conformational changes during channel gating, and interactions between S5-P linkers from neighbouring subunits contribute importantly to channel inactivation.

Amino Acid Sequence↗
PubMed2005

Controlled fabrication of a biological vascular substitute.

Autologous and synthetic vessel grafts have been used as a vascular substitute for cardiovascular bypass procedures. However, these materials are limited by the availability of appropriate caliber autologous vessels, increased susceptibility to thrombosis and intimal hyperplasia following surgery. Electrospinning technology offers the potential for controlling composition, structure and mechanical properties of biomaterials. Vascular graft scaffolds have been fabricated using electrospun polymer blends of Type I collagen, elastin from ligamentum nuchae, and poly (d,l-lactide-co-glycolide). This study demonstrates improved electrospinning characteristics versus previous studies by increasing polymer concentration and adding PLGA to the polymer blend. Additionally, new in vitro biocompatibility and mechanical testing data is presented. The scaffolds possess tissue composition and mechanical properties similar to native vessels. The electrospun vessel matrix is biocompatible and does not elicit local or systemic toxic effects when implanted in vivo. This study demonstrates the promise of electrospinning as a fabrication process for a functional vascular graft for clinical use.

Animals↗
PubMed2005

Oleanolic acid and ursolic acid: research perspectives.

Oleanolic acid and ursolic acid are ubiquitous triterpenoids in plant kingdom, medicinal herbs, and are integral part of the human diet. During the last decade over 700 research articles have been published on their research, reflecting tremendous interest and progress in our understanding of these triterpenoids. This included the isolation and purification of these tritepernoids from various plants and herbs, the chemical modifications to make more effective and water soluble derivatives, the pharmacological research on their beneficial effects, the toxicity studies, and the clinical use of these triterpenoids in various diseases including anticancer chemotherapies. A briefly commentary is attempted here for their research perspectives.

Animals↗
PubMed2005

A selective HPLC method for the determination of indapamide in human whole blood: application to a bioequivalence study in Chinese volunteers.

Indapamide was extracted from human whole blood with diethyl ether and was determined by a HPLC-UV method using an Inertsil ODS-3 column and an isocratic mobile phase consisting of 55% buffer solution (2 g KH(2)PO(4), 3 ml H(3)PO(4) and 3.5 ml triethylamine in 1l of H(2)O), 40% acetonitrile and 5% methanol for 12.5 min, and then a gradient flush from 100% isocratic to a mixture of 20% isocratic mobile phase and 80% methanol for 3 min. Indapamide and glipizide (internal standard) were eluted from the column at about 10.5 and 12.8 min, respectively. The method had within day precision values in the range +/- 1.2 to +/- 9.7% (n = 5) and between day precision in the range +/- 3.3 to +/- 9.7%. The method was linear over the range of 10-400 ng/ml of indapamide in blood (R = 0.999). The LOQ (s/n = 10) of the method was 10 ng/ml. The method was applied in a study of the pharmacokinetics and bioequivalence of generic indapamide capsules (2.5 mg) in comparison with reference indapamide tablets (2.5mg), in 20 healthy male Chinese volunteers. The mean values of major pharmacokinetic parameters of C(max), AUC(0-48), AUC(0-infinity), T(max), and t(1/2) of indapamide in healthy male Chinese volunteers after po a single 5 mg dose for the test product were 331.0 +/- 39.2 ng/ml, 6,193.7+/-873.5 ng h/ml, 7311.8+/-1,232.3 ng h/ml, 3.2+/-0.9h, and 17.3+/-2.8 h, respectively. There was no significant differences between the two formulations.

Area Under Curve↗
PubMed2005

Low level, long-term inorganic arsenite exposure causes generalized resistance to apoptosis in cultured human keratinocytes: potential role in skin co-carcinogenesis.

Inorganic arsenic is a human carcinogen that targets the skin. Carcinogenesis is a multistep process in which acquired apoptotic resistance is a common event and prior work in non-skin cells shows acquired resistance to apoptosis occurs with chronic arsenite exposure. In the present study, when HaCaT cells, an immortalized, non-tumorigenic human keratinocyte cell line, were continuously exposed to low-level inorganic arsenite (as sodium arsenite; 100 nM) for 28 weeks, the cells acquired a generalized resistance to apoptosis. This included resistance to apoptosis induced by acute high concentrations of arsenite, ultraviolet A (UVA) irradiation, and several chemotherapeutic compounds (cisplatin, etoposide and doxorubicin). These arsenite-tolerant (As-TL) cells showed similar levels of UVA-induced reactive oxygen species (ROS) and oxidative DNA damage when compared to passage match control cells. Because cellular apoptosis is dependent on the balance between proapoptotic and survival pathways, the roles of protein kinase B (PKB), a key antiapoptotic molecule, in this acquired apoptotic resistance were investigated. Stimulation of apoptosis markedly decreased nuclear phosphorylated PKB (P-PKB) levels in control cells, but As-TL cells showed greatly increased stability of nuclear P-PKB. Pretreatment of the As-TL cells with LY294002 or Wortmannin, which specifically inhibit PKB phosphorylation, completely blocked apoptotic resistance in As-TL cells, indicating acquired apoptotic resistance is associated with increased stability of nuclear P-PKB. Because arsenic and UV irradiation are co-carcinogenic in mouse skin, resistance to UV-induced apoptosis in As-TL cells may allow UV-damaged cells to escape normal cell population controls and initiate the carcinogenic cascade. The observation that As-TL cells show no lessening of UV-induced genotoxicity supports this possibility.

Apoptosis↗
PubMed2005

Integrated single-walled carbon nanotube/microfluidic devices for the study of the sensing mechanism of nanotube sensors.

A method to fabricate integrated single-walled carbon nanotube/microfluidic devices was developed. This simple process could be used to directly prepare nanotube thin film transistors within the microfluidic channel and to register SWNT devices with the microfludic channel without the need of an additional alignment step. The microfluidic device was designed to have several inlets that deliver multiple liquid flows to a single main channel. The location and width of each flow in the main channel could be controlled by the relative flow rates. This capability enabled us to study the effect of the location and the coverage area of the liquid flow that contained charged molecules on the conduction of the nanotube devices, providing important information on the sensing mechanism of carbon nanotube sensors. The results showed that in a sensor based on a nanotube thin film field effect transistor, the sensing signal came from target molecules absorbed on or around the nanotubes. The effect from adsorption on metal electrodes was weak.

Adsorption↗