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Biomedical subjects

Qiang Liu

Publications and source records attributed to Qiang Liu.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Clinical significance of neuro-reactive autoantibodies in neuro-psychiatric systemic lupus erythematosus].

OBJECTIVE: To investigate the clinical significance of specific/non-specific neuro-reactive autoantibodies in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Samples of serum and cerebrospinal fluid (CSF) were collected from 25 NPSLE patients, 11 patients with SLE complicated with central nervous system (CNS) infection (control group 1), and 10 SLE patients without CNS infection (non-NPSLE, control group 2)) were detected, Indirect immunofluorescence technique was used to detect the anti-nuclear antibody (ANA) based on the slides with human epithelium cell of laryngocarcinoma of the line Hep-2 or on the slides with cerebellum and peripheral nerve of monkey, he type of immunofluorescence were assayed. RESULTS: The percentages of ANA positive serum of the NPSLE, SLE control 1, and SLE control 2 groups were 92% (23/25), 100% (11/11), and 100% (10/10) respectively without significant differences between any 2 groups (all P > 0.05). The percentage of ANA positive CSF of the NPSLE was 60% (15/25), significantly higher than that of the SLE control group 1 (27%, 3/11, P < 0.01). There was no significant correlation between the titer of serum ANA and the titer of CSF ANA (P > 0.05). The positive rate of neuro-reactive autoantibodies was 40% (10/25), significantly higher than those of the 2 control groups (both 0, both P > 0.001). CONCLUSION: (1) The ANA positivity in the CSF of the NPSLE group is associated with the disease activity and CNS involvement, the higher the titer of autoantibodies the severe the clinical manifestations. (2) The neuro-reactive autoantibodies in the serum may associate with NPSLE with still unknown mechanism.

Adolescent↗
PubMed2006

Iptakalim modulates ATP-sensitive K(+) channels in dopamine neurons from rat substantia nigra pars compacta.

Iptakalim, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, exerts neuroprotective effects on dopaminergic (DA) neurons against metabolic stress-induced neurotoxicity, but the mechanisms are largely unknown. Here, we examined the effects of iptakalim on functional K(ATP) channels in the plasma membrane (pm) and mitochondrial membrane using patch-clamp and fluorescence-imaging techniques. In identified DA neurons acutely dissociated from rat substantia nigra pars compacta (SNc), both the mitochondrial metabolic inhibitor rotenone and the sulfonylurea receptor subtype (SUR) 1-selective K(ATP) channel opener (KCO) diazoxide induced neuronal hyperpolarization and abolished action potential firing, but the SUR2B-selective KCO cromakalim exerted little effect, suggesting that functional K(ATP) channels in rat SNc DA neurons are mainly composed of SUR1. Immunocytochemical staining showed a SUR1-rather than a SUR2B-positive reaction in most dissociated DA neurons. At concentrations between 3 and 300 microM, iptakalim failed to hyperpolarize DA neurons; however, 300 microM iptakalim increased neuronal firing. In addition, iptakalim restored DA neuronal firing during rotenone-induced hyperpolarization and suppressed rotenone-induced outward current, suggesting that high concentrations of iptakalim close neuronal K(ATP) channels. Furthermore, in human embryonic kidney 293 cells, iptakalim (300-500 microM) closed diazoxide-induced Kir6.2/SUR1 K(ATP) channels, which were heterologously expressed. In rhodamine-123-preloaded DA neurons, iptakalim neither depolarized mitochondrial membrane nor prevented rotenone-induced mitochondrial depolarization. These data indicate that iptakalim is not a K(ATP) channel opener in rat SNc DA neurons; instead, iptakalim is a pm-K(ATP) channel closer at high concentrations. These effects of iptakalim stimulate further pharmacological investigation and the development of possible therapeutic applications.

ATP-Binding Cassette Transporters↗
PubMed2006

Roles of nicotinic acetylcholine receptor beta subunits in function of human alpha4-containing nicotinic receptors.

Naturally expressed nicotinic acetylcholine receptors (nAChR) containing alpha4 subunits (alpha4*-nAChR) in combination with beta2 subunits (alpha4beta2-nAChR) are among the most abundant, high-affinity nicotine binding sites in the mammalian brain. beta4 subunits are also richly expressed and colocalize with alpha4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, alpha4beta4-nAChR also may exist and play important functional roles. In this study, properties were determined of human alpha4beta2- and alpha4beta4-nAChR heterologously expressed de novo in human SH-EP1 epithelial cells. Whole-cell currents mediated via human alpha4beta4-nAChR have approximately 4-fold higher amplitude than those mediated via human alpha4beta2-nAChR and exhibit much slower acute desensitization and functional rundown. Nicotinic agonists induce peak whole-cell current responses typically with higher functional potency at alpha4beta4-nAChR than at alpha4beta2-nAChR. Cytisine and lobeline serve as full agonists at alpha4beta4-nAChR but are only partial agonists at alpha4beta2-nAChR. However, nicotinic antagonists, except hexamethonium, have comparable affinities for functional alpha4beta2- and alpha4beta4-nAChR. Whole-cell current responses show stronger inward rectification for alpha4beta2-nAChR than for alpha4beta4-nAChR at a positive holding potential. Collectively, these findings demonstrate that human nAChR beta2 or beta4 subunits can combine with alpha4 subunits to generate two forms of alpha4*-nAChR with distinctive physiological and pharmacological features. Diversity in alpha4*-nAChR is of potential relevance to nervous system function, disease, and nicotine dependence.

Acetylcholine↗
PubMed2006

RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer.

A tumor suppressor function has been attributed to RUNX3, a member of the RUNX family of transcription factors. Here, we examined alterations in the expression of three members, RUNX1, RUNX2, and RUNX3, and their interacting partner, CBF-beta, in breast cancer. Among them, RUNX3 was consistently underexpressed in breast cancer cell lines and primary tumors. Fifty percent of the breast cancer cell lines (n = 19) showed hypermethylation at the promoter region and displayed significantly lower levels of RUNX3 mRNA expression (P < 0.0001) and protein (P < 0.001). In primary Singaporean breast cancers, 9 of 44 specimens showed undetectable levels of RUNX3 by immunohistochemistry. In 35 of 44 tumors, however, low levels of RUNX3 protein were present. Remarkably, in each case, protein was mislocalized to the cytoplasm. In primary tumors, hypermethylation of RUNX3 was observed in 23 of 44 cases (52%) and was undetectable in matched adjacent normal breast epithelium. Mislocalization of the protein, with or without methylation, seems to account for RUNX3 inactivation in the vast majority of the tumors. In in vitro and in vivo assays, RUNX3 behaved as a growth suppressor in breast cancer cells. Stable expression of RUNX3 in MDA-MB-231 breast cancer cells led to a more cuboidal phenotype, significantly reduced invasiveness in Matrigel invasion assays, and suppressed tumor formation in immunodeficient mice. This study provides biological and mechanistic insights into RUNX3 as the key member of the family that plays a role in breast cancer. Frequent protein mislocalization and methylation could render RUNX3 a valuable marker for early detection and risk assessment.

Antimetabolites, Antineoplastic↗
PubMed2006

Expression of mRNA for multiple serotonin (5-HT) receptor types/subtypes by the peripheral blood mononuclear cells of rhesus macaques.

To find out whether rhesus macaque peripheral blood mononuclear cells (PBMCs) express mRNA for 5-HT receptors, blood samples from normal healthy rhesus monkeys were used to isolate PBMCs by Ficoll-paque density gradient centrifugation. Total RNA was extracted from MT-2 cells, Hut-78 cells, naive or phytohemagglutinin (PHA) stimulated human and monkey PBMCs. One tube RT-PCR was performed using primers specific for human 5-HT1A, 5-HT1B, 5-HT1E, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors. Amplicons of expected sizes were obtained from human cell lines as well as both human and monkey PBMCs. Both PHA stimulated human and monkey PBMCs express mRNAs for 5-HT1A, 5-HT1B, 5-HT1E, 5-HT2A, 5-HT3, 5-HT4, 5-HT6 receptor types/subtypes. However, mRNAs for 5-HT1B, 5-HT1E and 5-HT2A cannot be confidently detected in some of the PBMC samples without PHA stimulation. 5-HT2B and 5-HT7 receptor mRNA was not detected in most of the samples and 5-HT2C receptor mNRA was not detected at all. FACS analysis revealed that CD3+ lymphocyte increased more than 20% among lymphocytes in the PHA stimulated PBMCs. These data indicate that similar to human PBMC, rhesus macaque PBMC may express multiple types of 5-HT receptors and the expression profile could change after PHA stimulation due to either the changes in cell composition or changes in gene transcription level. This provided a basis for further studies on the neuroimmunomodulatory interactions of 5-HT in rhesus macaques.

Animals↗
PubMed2006

Aquaporin-4 knockout regulated cocaine-induced behavior and neurochemical changes in mice.

Aquaporin-4 (AQP4) is the predominant water channel of brain, which mediates transmembrane water movement at the blood-brain barrier and at the brain-cerebrospinal fluid interface. It has been reported that AQP4 deletion results in an increase of amino acid and monoamine levels in some brain regions of mice, suggesting that AQP4 may participate in region-specific alterations in brain amino acid and monoamine metabolism. In the present study, we examined whether AQP4 affects neurotransmission in acute and chronic cocaine exposure mice. For this purpose, both wild-type and AQP4 knockout mice were used with locomotor activity evaluation and microdialysis methods. The results reveal that AQP4 deletion attenuated locomotor activity in acute and repeated cocaine exposure mice, and induced a decrease of extracellular dopamine and glutamate levels in the nucleus accumbens (NAc), a brain region known to be critically involved in the addictive properties of cocaine. Therefore, AQP4 may play a role in regulating extracellular cocaine-induced dopamine and glutamate release in the brain reward center, and in turn AQP4 deletion may attenuate cocaine reinforcement and dependence.

Animals↗
PubMed2006

Efficient corner-pumped Yb:YAG/YAG composite slab laser.

A high efficiency Yb:YAG/YAG composite slab laser is presented, in which the corner-pumped scheme is adopted. The slab is a composite crystal of Yb:YAG bonded thermally with undoped YAG at both edges. The pump light from diode arrays is coupled into the slab through four chamfers at the four corners independently. The pump absorption efficiency is studied, and an analysis method has been developed as a guide to optimize the geometric parameters of the composite slab, to obtain higher pump absorption efficiency and uniformity. The influence of the internal thermal lens on the laser resonator is analyzed. A 1016 W continuous-wave output has been obtained with the slope efficiency and optical-to-optical efficiency of 42.8% and 34.4%, respectively.

Journal Article↗
PubMed2006

Platform technologies to support brain-computer interfaces.

There is a lack of adequate and cost-effective treatment options for many neurodegenerative diseases. The number of affected patients is in the millions, and this number will only increase as the population ages. The developing areas of neuromimetics and stimulative implants provide hope for treatment, as evidenced by the currently available, but limited, implants. New technologies are emerging that are leading to the development of highly intelligent, implantable sensors, activators, and mobile robots that will provide in vivo diagnosis, therapeutic interventions, and functional replacement. Two key platform technologies that are required to facilitate the development of these neuromimetic and stimulative implants are data communication channels and the devices' power supplies. In the research reported in this paper, investigators have examined the use of novel concepts that address these two needs. These concepts are based on ionic volume conduction (VC) to provide a natural communication channel to support the functioning of these devices, and on biofuel cells to provide a continuously rechargeable power supply that obtains electrons from the natural metabolic pathways. The fundamental principles of the VC communication channels, including novel antenna design, are demonstrated. These principles include the basic mechanisms, device sensitivity, bidirectionality of communication, and signal recovery. The demonstrations are conducted using mathematical and finite element analysis, physical experiments, and animal experiments. The fundamental concepts of the biofuel cells are presented, and three versions of the cells that have been studied are discussed, including bacteria-based cells and two white cell-based experiments. In this paper the authors summarize the proof or principal experiments for both a biomimetic data channel communication method and a biofuel cell approach, which promise to provide innovative platform technologies to support complex devices that will be ready for implantation in the human nervous system in the next decade.

Animals↗
PubMed2006

Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and glutamate levels in the nucleus accumbens of rats.

Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been reported that Ipt inhibited cocaine-induced dopamine and glutamate release, suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a heterologously expressed SH-EP1 cell line and in native midbrain dopamine neurons. In the present study, we examined whether Ipt prevents nicotine-induced neurotransmitter release in the nucleus accumbens (NAc) using in vivo microdialysis methods in awake, freely moving rats. Ipt was administered through a microdialysis probe, following systemic administration of nicotine (0.5 mg/kg, s.c.). The results show that acute nicotine treatment induced an increase of both dopamine and glutamate levels in the rat NAc, and that Ipt significantly attenuated nicotine's effects in a concentration-dependent manner. Therefore, Ipt may serve as a novel compound to block nicotine-induced dopamine and glutamate release in the brain reward center, in turn decreasing nicotine reinforcement and dependence.

Analysis of Variance↗
PubMed2006

Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis.

Nicotine reduces beta-amyloidosis and has a beneficial effect against Alzheimer's disease (AD), but the underlying mechanism is not clear. The abnormal interactions of beta-amyloid (Abeta) with metal ions such as copper and zinc are implicated in the process of Abeta deposition in AD brains. In the present study, we investigated the effect of nicotine on metal homeostasis in the hippocampus and cortex of APP(V717I) (London mutant form of APP) transgenic mice. A significant reduction in the metal contents of copper and zinc in senile plaques and neuropil is observed after nicotine treatment. The densities of copper and zinc distributions in a subfield of the hippocampus CA1 region are also reduced after nicotine treatment. We further studied the mechanism of nicotine-mediated effect on metal homeostasis by using SH-SY5Y cells overexpressing the Swedish mutant form of human APP (APPsw). Nicotine treatment decreases the intracellular copper concentration and attenuates Abeta-mediated neurotoxicity facilitated by the addition of copper, and these effects are independent of the activation of nicotinic acetylcholine-receptor. These data suggest that the effect of nicotine on reducing beta-amyloidosis is partly mediated by regulating metal homeostasis.

Amyloid beta-Peptides↗
PubMed2006

Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans.

Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB-3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized that AEX-3 may regulate a second Rab that regulates these processes with RAB-3. We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C. elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also expressed in intestinal cells. We identify aex-6 alleles as containing mutations in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1 (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3 regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic transmission, and that RAB-27 potentially acts through its effector RBF-1 to promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function.

Animals↗
PubMed2006

Regulating the drought-responsive element (DRE)-mediated signaling pathway by synergic functions of trans-active and trans-inactive DRE binding factors in Brassica napus.

DREB1/C-repeat binding factor (CBF) is a plant-specific family of transcription factors and plays a crucial role in freeze tolerance. In the present work, two groups of drought-responsive element binding factor (DREB)-like genes were isolated from Brassica napus, named Group I and Group II. The two groups of genes were both induced by low temperature, but the expression of Group I preceded that of Group II. The Group I DREBs could specifically bind with the DRE cis-acting element and activate the expression of downstream genes, but Group II factors were trans-inactive although they still had the ability to bind with DRE, which was confirmed by electrophoretic mobility shift assay. Fluorescence quenching assays indicated that the DRE binding ability of the two groups was similar. Co-expression of Group II could depress the trans-activation activity of Group I DREB in a concentration-dependent manner. These results strongly suggested that the trans-active Group I DREBs were expressed at the early stage of cold stress to open the DRE-mediated signaling pathway in cold stress, whereas the trans-inactive Group II DREBs were expressed at the later stage to close the signal pathway in a competitive manner. The results herein provide a new insight into the regulation mechanisms of the DRE-mediated signaling pathway in response to cold stress.

Amino Acid Sequence↗
PubMed2006

The conserved Ala37 in the ERF/AP2 domain is essential for binding with the DRE element and the GCC box.

Four AP2/EREBP genes encoding putative ethylene-responsive element binding factor (ERF)/AP2 domains were cloned from Brassica napus, and these genes could be induced by low temperature, ethylene, drought, high salinity, abscisic acid and jasmonate treatments. These four genes, named BnDREBIII-1 to BnDREBIII-4, were highly homologous and the 37th amino acid was the only difference among their ERF/AP2 domains. BnDREBIII-1 was demonstrated to be able to bind to both dehydration-responsive element and the GCC box and transactivate the expression of downstream genes, while BnDREBIII-4 could bind neither. Further results suggested that Ala37 might play a crucial role in the DNA binding or the stability of the ERF/AP2 domain.

Abscisic Acid↗
PubMed2006

Low conductance gap junctions mediate specific electrical coupling in body-wall muscle cells of Caenorhabditis elegans.

Invertebrate innexins and their mammalian homologues, the pannexins, are gap junction proteins. Although a large number of such proteins have been identified, few of the gap junctions that they form have been characterized to provide combined information of biophysical properties, coupling pattern, and molecular compositions. We adapted the dual whole cell voltage clamp technique to in situ analysis of electrical coupling in Caenorhabditis elegans body-wall muscle. We found that body-wall muscle cells were electrically coupled in a highly organized and specific pattern. The coupling was characterized by small (350 pS or less) junctional conductance (G(j)), which showed a bell-shaped relationship with junctional potential (V(j)) but was independent of membrane potential (V(m)). Injection of currents comparable to the junctional current (I(j)) into body-wall muscle cells caused significant depolarization, suggesting important functional relevance. The innexin UNC-9 appeared to be a key component of the gap junctions. Both Myc- and green fluorescent protein-tagged UNC-9 was localized to muscle intercellular junctions. G(j) was greatly inhibited in unc-9(fc16), a putative null mutant. Specific inhibition of UNC-9 function in muscle cells reduced locomotion velocity. Despite UNC-9 expression in both motor neurons and body-wall muscle cells, analyses of miniature and evoked postsynaptic currents in the unc-9 mutant showed normal neuromuscular transmission. These analyses provide a relatively detailed description of innexin-based gap junctions in a native tissue and suggest that innexin-based small conductance gap junctions can play an important role in processes such as locomotion.

Animals↗
PubMed2006

Genome-wide profiling of segmental-regulated transcriptomes in human epididymis using oligo microarray.

Sperm maturation during passage through the epididymis depends on regionalized gene expression which maintains the progressively changing environment within the epididymal tubule. Towards defining the genes that drive the sequential maturation of spermatozoa, we profiled regionally regulated gene expression pattern in the epididymis of a fertile young male donor using Affymetrix human genome U133 plus 2.0 microarray representing approximately the whole human genome. Over 15000 transcripts, almost one-third of the total on the array were identified in whole epididymis. Among them, 65% were detected in all three regions of the epididymis, 410 or 2.6% were present only in one region and the remaining 32.4% were distributed in two regions. Region-specific transcripts observed in caput (264), corpus (61) and cauda (81) epididymides were further classified as empirically determined reported genes or ESTs. This study revealed for the first time, the expression in human epididymis of a number of region-specific genes. The original data will be made publicly available on the Shanghai Science and Technology Database (http://www.scbit.org/human_epididymis_transcriptomes).

Adult↗
PubMed2006

Neuronal nicotinic acetylcholine receptors serve as sensitive targets that mediate beta-amyloid neurotoxicity.

Alzheimer's disease (AD) is the most common form of brain dementia characterized by the accumulation of beta-amyloid peptides (Abeta) and loss of forebrain cholinergic neurons. Abeta accumulation and aggregation are thought to contribute to cholinergic neuronal degeneration, in turn causing learning and memory deficits, but the specific targets that mediate Abeta neurotoxicity remain elusive. Recently, accumulating lines of evidence have demonstrated that Abeta directly modulates the function of neuronal nicotinic acetylcholine receptors (nAChRs), which leads to the new hypothesis that neuronal nAChRs may serve as important targets that mediate Abeta neurotoxicity. In this review, we summarize current studies performed in our laboratory and in others to address the question of how Abeta modulates neuronal nAChRs, especially nAChR subunit function.

Alzheimer Disease↗
PubMed2006

Efficient site-specific integration of large transgenes by an enhanced herpes simplex virus/adeno-associated virus hybrid amplicon vector.

We previously demonstrated that a herpes simplex virus type 1 (HSV-1)/adeno-associated virus (AAV) hybrid amplicon vector constructed by inserting the sequences of regulatory protein (rep) and inverted terminal repeats of AAV into an HSV amplicon vector resulted in the enhanced stability of transgene expression compared to the original HSV-1 amplicon vector. However, problems related to the expression of Rep compromised its therapeutic applications. We report here a new HSV/AAV hybrid amplicon vector system that not only solved problems associated with Rep expression but also markedly improved the stable transduction efficiency of this vector. This new HSV/AAV vector is designed in a way that little or no Rep would be expressed in packaging cells, but it can be expressed in transduced cells if Cre recombinase is provided. Furthermore, Rep expression will be automatically suppressed as a consequence of Rep-mediated integration. Our results showed that the new hybrid amplicon vector yielded titers comparable to those of standard amplicon vectors. When Cre-expressing 293 cells were transduced, a low level of Rep expression was detected, and stable transduction was achieved in approximately 22% of transduced cells; of those cells, approximately 70% transduction was achieved by Rep-mediated site-specific integration. In the majority of the stably transduced cells, Rep expression was no longer observed. Our results also proved that this vector system is capable of efficiently accommodating and site-specifically integrating large transgenes, such as the full-length dystrophin expression cassette. Thus, the new HSV/AAV vector demonstrated unique advantages in safe and effective delivery of long-lasting transgene expression into human cells.

Blotting, Southern↗