PubMed Health⌕ Search

Biomedical subjects

Q Ding

Publications and source records attributed to Q Ding.

At least 19 recordsLinked to original sources
PubMed2006

Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function.

The ability of exercise to benefit neuronal and cognitive plasticity is well recognized. This study reveals that the effects of exercise on brain neuronal and cognitive plasticity are in part modulated by a central source of insulin-like growth factor-I. Exercise selectively increased insulin-like growth factor-I expression without affecting insulin-like growth factor-II expression in the rat hippocampus. To determine the role that insulin-like growth factor-I holds in mediating exercise-induced neuronal and cognitive enhancement, a specific antibody against the insulin-like growth factor-I receptor was used to block the action of insulin-like growth factor-I in the hippocampus during a 5-day voluntary exercise period. A two-trial-per-day Morris water maze was performed for five consecutive days, succeeded by a probe trial 2 days later. Blocking hippocampal insulin-like growth factor-I receptors did not significantly attenuate the ability of exercise to enhance learning acquisition, but abolished the effect of exercise on augmenting recall. Blocking the insulin-like growth factor-I receptor significantly reversed the exercise-induced increase in the levels of brain-derived neurotrophic factor mRNA and protein and pro-brain-derived neurotrophic factor protein, suggesting that the effects of insulin-like growth factor-I may be partially accomplished by modulating the precursor to the mature brain-derived neurotrophic factor. A molecular analysis revealed that exercise significantly elevated proteins downstream to brain-derived neurotrophic factor activation important for synaptic function, i.e. synapsin I, and signal transduction cascades associated with memory processes, i.e. phosphorylated calcium/calmodulin protein kinase II and phosphorylated mitogen-activated protein kinase II. Blocking the insulin-like growth factor-I receptor abolished these exercise-induced increases. Our results illustrate a possible mechanism by which insulin-like growth factor-I interfaces with the brain-derived neurotrophic factor system to mediate exercise-induced synaptic and cognitive plasticity.

Animals↗
PubMed2005

Evidence of increased oxidative damage in subjects with mild cognitive impairment.

OBJECTIVE: To determine if increased levels of oxidative damage are present in the brains of persons with mild cognitive impairment (MCI), a condition that often precedes Alzheimer disease (AD). METHODS: The authors assessed the amount of protein carbonyls, thiobarbituric acid-reactive substances (TBARS), and malondialdehyde in the superior and middle temporal gyri (SMTG) and cerebellum of short postmortem interval and longitudinally evaluated normal subjects and those with MCI and early AD. RESULTS: Elevated levels of protein carbonyls (approximately 25%), malondialdehyde (approximately 60%), and TBARS (approximately 210%) were observed in the SMTG of individuals with MCI and early AD vs normal control subjects. The elevation in TBARS was associated with the numbers of neuritic but not diffuse plaques. Levels of protein carbonyls increased as delayed verbal memory performance declined. CONCLUSION: Oxidative damage occurs in the brain of subjects with mild cognitive impairment, suggesting that oxidative damage may be one of the earliest events in the onset and progression of Alzheimer disease.

Aged↗
PubMed2004

Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by Gly.

Prothrombin deficiency is a rare bleeding disorder inherited as an autosomal recessive trait. In this study, we reported a Chinese family with hereditary prothrombin deficiency. The proposita had a prolonged activated partial thromboplastin time (APTT, 71.6 s) and prothrombin time (PT, 28.0 s). The coagulation factors activities were normal except that prothrombin coagulation activity was markedly reduced, and the prothrombin antigen level was moderately decreased. Nucleotide sequencing of amplified DNA revealed a novel mutation, Glu (GAG) to Gly (GGG) at residue 29, which normally undergoes gamma-carboxylation within the Gla domain of prothrombin. The proposita was identified as homozygous, while her father, mother and maternal grandmother were heterozygous for the mutation. Gla29 has been demonstrated as one of the key residue for Ca2+-binding, membrane interaction and biological activity of prothrombin.

Amino Acid Substitution↗
PubMed2003

Type I coagulation factor V deficiency caused by compound heterozygous mutation of F5 gene.

A 16-year-old Chinese female with prolonged bleeding after surgery has been studied. Routine clotting tests revealed a prolonged activated partial thromboplastin time (APTT; 126.6 s) and prothrombin time (PT; 42.8 s). The coagulation factors activities were normal except for factor V, which was only 0.3% of normal. DNA analysis of the FV gene revealed five nucleotide substitutions in exons, including two silent mutations (G327A and A5112G), one polymorphism (G1628A), a G1348T missense mutation and 4887 approximately 8delG. These abnormalities were associated with her FV deficiency, perhaps by causing a Gly392Cys substitution in FV amino acid sequence or by introducing a premature stop codon at amino acid position 1390. This is the third case in which FV deficiency is caused by compound heterozygous mutation of F5 gene, and is the first report from a Chinese family.

Adolescent↗
PubMed2002

The complete nucleotide sequence of Beet black scorch virus (BBSV), a new member of the genus Necrovirus.

The complete nucleotide sequence of Beet black scorch virus (BBSV) was determined. The BBSV genome is composed of 3641 nucleotides and has similar organization with Tobacco necrosis virus D of 61% nucleotide identity. The 5'-proximal open reading frame (ORF) encodes a putative 23 kDa protein and a 82 kDa protein by reading-through of an amber termination codon. Three small ORFs located in the center of the genome may encode for a 4.2 kDa protein and two 7 kDa proteins. The 3'-proximal ORF encodes a 24.5 kDa protein equivalent in mass to the viral coat protein. Considering biological and molecular similarities with TNV, it is concluded that BBSV is a new member of the genus Necrovirus.

Base Sequence↗
PubMed2001

TGF-beta1 up-regulates paxillin protein expression in malignant astrocytoma cells: requirement for a fibronectin substrate.

Cytokines can influence the interactions between members of the integrin cell adhesion receptor family and the extracellular matrix thereby potentially affecting cell function and promoting cell adhesion, growth and migration of malignant astrocytoma tumor cells. As malignant astrocytoma cells synthesize TGF-beta1 in vivo, we analysed the effects of TGF-beta1 on signaling events associated with integrin receptor ligation, focusing on the effects on paxillin, a phosphorylated adaptor protein, that acts as a scaffold for signaling molecules recruited to focal adhesions. TGF-beta1-stimulation of primary astrocytes and serum-starved U-251MG malignant astrocytoma cells attached to fibronectin induced a substantial increase in the levels of paxillin protein (fivefold increase at 2.0 ng/ml) in a dose- and time-dependent manner compared to the levels observed on plating onto fibronectin in the absence of stimulation. In the astrocytoma cells, this resulted in an increase in the pool of tyrosine-phosphorylated paxillin, although it did not appear to alter the extent of phosphorylation of the paxillin molecules. In contrast, in primary astrocytes the protein levels were upregulated in the absence of a parallel increase in phosphorylation. The TGF-beta1-stimulated increase in paxillin levels required ligation of the fibronectin receptor, as it was not induced when the cells were plated onto vitronectin, collagen or laminin. The increase in the pool of paxillin on TGF-beta1 stimulation of the fibronectin-plated astrocytoma cells was associated with an increase in translation, but was not associated with an increase in the steady-state levels of paxillin mRNA. Stimulation with TGF-beta1 on a fibronectin substrate increased subsequent attachment and spreading of U-251MG cells onto fibronectin and, to a lesser extent, vitronectin, but not collagen. Our results indicate that physiologic levels of TGF-beta1 stimulate the expression of paxillin protein at the level of translation through a process that requires engagement of the fibronectin receptor, and promotes attachment and spreading of malignant astrocytoma cells on fibronectin.

Animals↗
PubMed2001

Phosphorylation of the CCAAT displacement protein (CDP)/Cux transcription factor by cyclin A-Cdk1 modulates its DNA binding activity in G(2).

Stable DNA binding by the mammalian CCAAT displacement protein (CDP)/Cux transcription factor was previously found to be up-regulated at the G(1)/S transition as the result of two events, dephosphorylation by the Cdc25A phosphatase and proteolytic processing, to generate an amino-truncated isoform of 110 kDa. In S phase, CDP/Cux was shown to interact with and repress the core promoter of the p21(WAF1) gene. Here we demonstrate that DNA binding by p110 CDP/Cux is down-modulated as cells progress into G(2). Accordingly, cyclin A-Cdk1 was found to bind to CDP/Cux and modulate its DNA binding activity in vitro and in vivo. Interaction with CDP/Cux required the presence of both cyclin A and a cyclin-dependent kinase (Cdk)-activating kinase-activated Cdk1 and involved the Cut homeodomain and a downstream Cy motif. Phosphorylation of serines 1237 and 1270 caused inhibition of DNA binding in vitro. In cotransfection studies, cyclin A-Cdk1 inhibited CDP/Cux stable DNA binding and prevented repression of the p21(WAF1) reporter. In contrast, mutant CDP/Cux proteins in which serines 1237 and 1270 were replaced with alanines were not affected by cyclin A-Cdk1. In summary, our results suggest that the phosphorylation of CDP/Cux by cyclin A-Cdk1 contributes to down-modulate CDP/Cux activity as cells progress into the G(2) phase of the cell cycle.

Animals↗
PubMed2001

Proteasomes and proteasome inhibition in the central nervous system.

Although the proteasome is responsible for the majority of intracellular protein degradation, and has been demonstrated to play a pivotal role in a diverse array of cellular activities, the role of the proteasome in the central nervous system is only beginning to be elucidated. Recent studies have demonstrated that proteasome inhibition occurs in numerous neurodegenerative conditions, and that proteasome inhibition is sufficient to induce neuron death, elevate intracellular levels of protein oxidation, and increase neural vulnerability to subsequent injury. The focus of this review is to describe what is currently known about proteasome biology in the central nervous system and to discuss the possible role of proteasome inhibition in the neurodegenerative process.

Animals↗
PubMed2001

Suppressor of fused negatively regulates beta-catenin signaling.

Suppressor of fused (Su(fu)) is a negative regulator of the Hedgehog signaling pathway that controls the nuclear-cytoplasmic distribution of Gli/Ci transcription factors through direct protein-protein interactions. We show here that Su(fu) is present in a complex with the oncogenic transcriptional activator beta-catenin and functions as a negative regulator of T-cell factor (Tcf)-dependent transcription. Overexpression of Su(fu) in SW480 (APC(mut)) colon cancer cells in which beta-catenin protein is stabilized leads to a reduction in nuclear beta-catenin levels and in Tcf-dependent transcription. This effect of Su(fu) overexpression can be blocked by treatment of these cells with leptomycin B, a specific inhibitor of CRM1-mediated nuclear export. Overexpression of Su(fu) suppresses growth of SW480 (APC(mut)) tumor cells in nude mice. These observations indicate that Su(fu) negatively regulates beta-catenin signaling and that CRM-1-mediated nuclear export plays a role in this regulation. Our results also suggest that Su(fu) acts as a tumor suppressor.

Active Transport, Cell Nucleus↗
PubMed2001

Alterations of MAPK activities associated with intestinal cell differentiation.

Three distinct groups of mitogen-activated protein kinases (MAPKs) have been identified in mammalian cells (i.e., ERK, JNK, and p38) which play an important role in the differentiation and apoptosis of various cells. The purpose of our present study was to determine MAPK activity and levels associated with sodium butyrate (NaBT)-mediated differentiation and apoptosis in the human colon cancer cell lines Caco-2 and HT29. Intestinal alkaline phosphatase (IAP) activity, a marker of intestinal differentiation, was increased at 48 h after NaBT treatment followed by cell death at 72 h. ERK activity was decreased in differentiated Caco-2 cells either induced with NaBT or allowed to differentiate spontaneously and in HT29 cells treated with NaBT. The combination of the MEK inhibitor, PD98059, with NaBT further increased IAP activity and cell death compared with NaBT alone. In contrast to ERK, JNK1 activity and c-Jun phosphorylation was increased 8 h after NaBT treatment suggesting a role for the JNK pathway in intestinal cell differentiation and apoptosis. p38 activity was increased at 24 and 48 h after NaBT treatment. Taken together, our results suggest that alterations in MAPKs (i.e., ERK inhibition and JNK induction) contribute to the differentiation and apoptotic pathways in intestinal cells.

Alkaline Phosphatase↗
PubMed2001

Gene therapy of HSV-TK transferred by the EBV based expression vector on experimental hepatocellular carcinoma.

To study the therapeutic effects of herpes simplex virus thymidine kinase (HSV-TK) gene transferred by the EBV-based expression vector (pDR2) on experimental hepatocellular carcinoma, pDR2-TK gene was delivered into human hepatocellular carcinoma cell line SMMC-7721 by using liposome-mediated transfection technique, and then gene expression was detected by RT-PCR, and the killing effects were examined through MTT method. In the nude mice hepatoma model, the antitumor effects of pDR2-TK/GCV system was evaluated in terms of tumor growth. MTT results showed that the pDR2-TK/GCV had cytotoxic effect and about 70% SMMC-7721 cells were killed when GCV was at 1000 mumol/L. In vivo experiment showed that the tumor size in nude mice with transferred pDR2-TK gene was significantly smaller than that in control group (P < 0.01). On the 10th day the tumor in 3 mice (60%) disappeared completely after GCV treatment. It is concluded that the pDR2-TK/GCV system has marked killing effects on the experimental hepatocellular carcinoma.

Animals↗
PubMed2001

Proteasome inhibition in oxidative stress neurotoxicity: implications for heat shock proteins.

Recent studies have demonstrated that inhibition of the proteasome, an enzyme responsible for the majority of intracellular proteolysis, may contribute to the toxicity associated with oxidative stress. In the present study we demonstrate that exposure to oxidative injury (paraquat, H(2)O(2), FeSO(4)) induces a rapid increase in reactive oxygen species (ROS), loss of mitochondrial membrane potential, inhibition of proteasome activity, and induction of cell death in neural SH-SY5Y cells. Application of proteasome inhibitors (MG115, epoxomycin) mimicked the effects of oxidative stressors on mitochondrial membrane potential and cell viability, and increased vulnerability to oxidative injury. Neural SH-SY5Y cells stably transfected with human HDJ-1, a member of the heat shock protein family, were more resistant to the cytotoxicity associated with oxidative stressors. Cells expressing increased levels of HDJ-1 displayed similar degrees of ROS formation following oxidative stressors, but demonstrated a greater preservation of mitochondrial function and proteasomal activity following oxidative injury. Cells transfected with HDJ-1 were also more resistant to the toxicity associated with proteasome inhibitor application. These data support a possible role for proteasome inhibition in the toxicity of oxidative stress, and suggest heat shock proteins may confer resistance to oxidative stress, by preserving proteasome function and attenuating the toxicity of proteasome inhibition.

Animals↗
PubMed2001

[Analysis on the surveillanca data of newborn death from 1990 to 1999 in Rugao City, Jiangsu province].

A surveillance and data analysis on the cause and death rate of newborn death in Rugao city, Jiangsu Provinces was conducted from 1990 to 1999. There were 1300 cases died in these 10 years. The mortality rate was 0.92% and the proportion of male to female was 1.53:1. More cases (75%) were died in the early stage after birth. The causes of the newborn death were in the order of premature, asphyxia, pneumonia, congenital anomaly and accidental asphyxia. More babies (75.62%) were died in hospitals. The emphasis on newborn health care was pointed out and had discussions. Taking comprehensive measures would be the key point to reduce newborn mortality rate.

Asphyxia Neonatorum↗
PubMed2000

[Relationship between hot spot mutation in hepatitis B virus basic core promotor and HBeAg status].

OBJECTIVE: This paper was to study the influence of hot spot mutation in hepatitis B virus (HBV) basic core promotor (BCP) (nt1762 and nt1764) on HBeAg status of asymptomatic HBV carriers. METHODS: Mismatched PCR was used to amplify the fragment of HBVBCP and the fragments were analysed by restrict enzyme assay. Ninety cases of HBV infection were tested for hot spot mutations in HBVBCP. RESULTS: Twenty-six (43.3%) of 60 asymptomatic HBV carriers with HBeAg negative were found to have hot spot mutations in HBVBCP, among which 20 cases were accompanied by the mutation of nt 1896 in HBV Pre-C region. Hot-spot mutation in HBVBCP, however, occurred only in 3(10%) of 30 asymptomatic HBV carriers with HBeAg positive. For further investigation the HBVBCP hot spot mutations in asymptomatic HBV carriers without mutation of HBV Pre-C region were studied. Six(31.6%) of 19 asymptomatic HBV carriers with HBeAg negative were found to have hot spot mutation in HBVBCP. Two(7.1%) of 28 asymptomatic HBV carriers with HBeAg positive had hot spot mutations in HBVBCP, and there was a statistically significant difference between two groups. CONCLUSIONS: Hot spot mutations in HBVBCP is common in the HBV carriers with HBeAg negative and usually accompanies with nt1896 mutation of HBV Pre-C region. It is possible that Hot spot mutation in HBVBCP is a new reason of HBeAg negative HBV infection.

Adult↗
PubMed2000

Identification and molecular characterization of the Choristoneura fumiferana multicapsid nucleopolyhedrovirus genomic region encoding the regulatory genes pkip, p47, lef-12, and gta.

Choristoneura fumiferana multicapsid nucleopolyhedrovirus (CfMNPV) is a baculovirus pathogenic to spruce budworm, the most damaging insect pest in Canadian forestry. CfMNPV is less virulent to its host insect and its replication cycle is slower than the baculovirus type species Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) but the basis of these characteristics is not known. We have now identified, localized, and determined the sequence of the region of CfMNPV carrying potentially important regulatory genes including p47, lef-12, gta, and pkip. DNA database searches revealed that this region of CfMNPV is most closely related to the homologous OpMNPV genes. Transcription analysis demonstrated that CfMNPV P47 is encoded by a 1.6-kb transcript, LEF-12 is encoded by a 2.6-kb transcript, and GTA is encoded by a 2.1-kb transcript. Transcripts for these genes were detectable at 6 h postinfection but all of them showed a burst in expression levels between 12 and 24 h postinfection corresponding to the time of initiation of CfMNPV DNA replication. A polyclonal antibody, raised against CfMNPV P47, detected a nuclear 43-kDa polypeptide from 12 to 72 h postinfection, demonstrating that the CfMNPV p47 gene product is first expressed at a time corresponding to the burst of transcriptional activity between the early and the late phases. Both AcMNPV and CfMNPV P47 translocate to the nucleus of infected cells.

Amino Acid Sequence↗
PubMed2000

Characterization and regulation of E2F activity during Caco-2 cell differentiation.

The specific mechanisms controlling intestinal cell differentiation remain largely undefined. The retinoblastoma (Rb) proteins (pRb, p130, and p107) appear crucial to the terminal differentiation process of certain cells through their association and repression of E2F transcription factors. We have examined the expression of pRb-related proteins p130 and p107 as well as the regulation of E2F during spontaneous differentiation of the Caco-2 intestinal cell line. Nuclear protein levels of p130 and p107 were increased with Caco-2 differentiation. Induction of a slower-migrating E2F complex was noted in postconfluent (i.e., differentiated) Caco-2 cells; p130 protein was the predominant component of this E2F complex with a minor contribution from cyclin-dependent kinase-2. A small component of p107 binding was identified by deoxycholate release gel shift assays. In contrast, no pRb binding to E2F was noted in Caco-2 cells. In addition to increased association with p130, E2F-4 phosphorylation was markedly decreased in differentiated Caco-2 cells, whereas E2F protein levels remained unchanged. Taken together, our findings suggest that the regulation of E2F function may be an important contributing factor in the cell cycle block and spontaneous differentiation of Caco-2 cells. This regulation of E2F occurs most likely through its increased association with p130 as well as decreased phosphorylation.

Blotting, Western↗
PubMed2000

p125 focal adhesion kinase promotes malignant astrocytoma cell proliferation in vivo.

p125 focal adhesion kinase (p125FAK) is a cytoplasmic tyrosine kinase that is activated upon engagement of integrin cell adhesion receptors, and initiates several signaling events that modulate cell function in vitro. To determine the biologic role of p125FAK in malignant astrocytic tumor cells, U-251MG human malignant astrocytoma cells were stably transfected with p125FAK cDNA using the TET-ON system, and stable clones isolated that exhibited an estimated 5- or 20-fold increase in p125FAK expression on administration of 0.1 or 2.0 microg/ml doxycycline, respectively. In vitro studies demonstrated that induction of p125FAK resulted in a 2- to 3-fold increase in cell migration, increased p130CAS phosphorylation, localization of exogenous p125FAK to focal adhesions, and a 2-fold increase in soft agar growth. To determine the role of p125FAK in vivo, clones were injected stereotactically into the brains of scid mice. A 4.5-fold estimated increase in p125FAK expression was induced by administration of doxycycline in the drinking water. Analysis of xenograft brains demonstrated that, upon induction of p125FAK, there was a 1.6- to 2.8-fold increase in tumor cell number, and an increase in mAb PCNA-labeling of tumor cells in the absence of a change in the apoptotic index. Compared to normal brain, the expression of p125FAK was elevated in malignant astrocytic tumor biopsies from patient samples. These data demonstrate for the first time that p125FAK promotes tumor cell proliferation in vivo, and that the underlying mechanism is not associated with a reduction in apoptosis.

Agar↗