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Biomedical subjects

Zhong Xie

Publications and source records attributed to Zhong Xie.

9 recordsLinked to original sources
PubMed2005

Activity-dependent dendritic spine structural plasticity is regulated by small GTPase Rap1 and its target AF-6.

Activity-dependent remodeling of dendritic spines is essential for neural circuit development and synaptic plasticity, but the mechanisms that coordinate synaptic structural and functional plasticity are not well understood. Here we investigate the signaling pathways that enable excitatory synapses to undergo activity-dependent structural modifications. We report that activation of NMDA receptors in cultured cortical neurons induces spine morphogenesis and activation of the small GTPase Rap1. Rap1 bimodally regulates spine morphology: activated Rap1 recruits the PDZ domain-containing protein AF-6 to the plasma membrane and induces spine neck elongation, while inactive Rap1 dissociates AF-6 from the membrane and induces spine enlargement. Rap1 also regulates spine content of AMPA receptors: thin spines induced by Rap1 activation have reduced GluR1-containing AMPA receptor content, while large spines induced by Rap1 inactivation are rich in AMPA receptors. These results identify a signaling pathway that regulates activity-dependent synaptic structural plasticity and coordinates it with functional plasticity.

2-Amino-5-phosphonovalerate↗
PubMed2005

[Efficacy of concurrent radio-chemotherapy and chemotherapy alone in the treatment of locally advanced non-small-cell lung cancer].

OBJECTIVE: To evaluate the effect and acute toxicity of concurrent radio-chemotherapy, by NVB and DDP, plus concurrent radiotherapy in comparison with chemotherapy alone in the treatment of inoperable locally advanced non-small-cell lung cancer (LANSCLC). METHODS: Sixty-four patients with inoperable LANSCLC were randomly divided by envelope method into two groups: concurrent radio-chemotherapy group (n = 33) and conventional chemotherapy group (n = 31). The patients in conventional chemotherapy group were treated by NP regimen (NVB + DDP): NVB 25 mg/m(2), d1, 8 and DDP 25-30 mg/m(2) d1-3. In the radio-chemotherapy group by NP regimen plus conventional radiotherapy by (60)Co: 64-68 Gy/2 Gy x 5/w x 6-7w. RESULTS: All patients completed the treatment schedule. The overall response rate (CR + PR) in the radio-chemotherapy group was significantly higher than that in the conventional chemotherapy group: 81.8% vs 45.2%, (P < 0.01) with 1- and 2-year survival rates of 69.7% vs 38.7% (P < 0.05) and 39.4% vs 16.1% (P < 0.05). without any significant difference in the acute toxicity between two groups (P > 0.05). CONCLUSION: Compared with conventional chemotherapy (NVP and DDP), concurrent radio-chemotherapy (NVP and DDP plus concurrent radiotherapy) is more effective and tolerable for the inoperable locally advanced non-small-cell lung cancer.

Adult↗
PubMed2005

Design a usable protocol screening database: the user-centered approach.

Patient eligibility screening is a very important component of clinical research. Data obtained from such a task can serve valuable purposes beyond the specific protocol they are generated for and therefore should be captured and stored. We applied a user-centered design framework to evaluate the existing screening process and database at the Neurosurgery Department, M. D. Anderson Cancer Center and to design and develop a usable protocol patient screening interface.

Clinical Trials as Topic↗
PubMed2004

Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and p38.

Chronic glial activation in neurodegenerative diseases contributes to neuronal dysfunction and neuron loss through production of neuroinflammatory molecules. However, the molecular mechanisms, particularly the signal transduction pathways involved in glia-dependent neuron death, are poorly understood. As a first step to address this question, we used a neuron-glia co-culture system that allows diffusion of soluble molecules between glia and neurons to test the potential importance of mitogen-activated protein kinase (MAPK) signaling pathways in the glia-induced neuron death. Activation of glia in co-culture by lipopolysaccharide (LPS) induced apoptotic-like neuron death. The MAPKs tested (p38, JNK, ERK1/2) were activated in both glia and neurons following LPS treatment, suggesting their involvement in both glial activation and neuronal response to diffusible, glia-derived neurotoxic molecules. Inhibitors of p38 and JNK partially blocked neuron death in the LPS-treated co-culture, whereas an ERK1/2 pathway inhibitor did not protect neurons. These results show that p38 and JNK MAPKs, but not ERK1/2 MAPK, are important signal transduction pathways contributing to glia-induced neuron death.

Animals↗
PubMed2004

Ubiquitinated or sumoylated retinoic acid receptor alpha determines its characteristic and interacting model with retinoid X receptor alpha in gastric and breast cancer cells.

Retinoic acid receptor alpha (RARalpha) plays an important role in mediating all-trans retinoic acid (ATRA) signals. In this study, we found that ATRA up-regulated RARalpha mRNA and protein expression in gastric cancer BGC-823 cells. However, in breast cancer MCF-7 cells it down-regulated RARalpha protein expression with no effect on its RARalpha mRNA. Immunoprecipitation/Western blot analysis showed that, although sumoylated and ubiquitinated RARalpha existed simultaneously in both cancer cell lines, ATRA exerted different regulatory effects on sumoylation and ubiquitination of RARalpha. In MCF-7 cells, ATRA treatment enhanced the ubiquitination of RARalpha and the subsequent degradation of RARalpha through the ubiquitin/proteasome pathway. This resulted in a reduction in the DNA binding activity of RARalpha/retinoid X receptor alpha (RXRalpha) heterodimer, the separation of RXRalpha from RARalpha and the translocation of RXRalpha from the nucleus to the cytoplasm. By contrast, in BGC-823 cells, ATRA augmented sumoylation, not ubiquitination, of RARalpha. The stability of sumoylated RARalpha was significantly stronger than in non-sumoylated RARalpha. These results also showed an increase in the DNA binding activity of the RARalpha/RXRalpha heterodimer and the stability of nuclear localization of this heterodimer, which normally facilitates the ATRA signal transduction. In conclusion, our results reveal a novel mechanism for the regulation of RARalpha-dependent signal transduction through the ubiquitin/proteasome pathway in breast cancer cells and the sumoylation pathway in gastric cancer cells.

Breast Neoplasms↗
PubMed2003

Aging and glial responses to lipopolysaccharide in vitro: greater induction of IL-1 and IL-6, but smaller induction of neurotoxicity.

Glial activation during aging was analyzed in primary glia cultured from brain regions sampled across the life span. An initial study showed that phenotypes of activated astrocytes and microglia from aging rat cerebral cortex persisted in primary cultures (Neurobiol. Aging 19 (1998), 97). We extend these findings by examining effects of age on the activation of glial cultures from adult rat brain in response to lipopolysaccharide (LPS), an inflammatory stimulus. Mixed glia from F344 male rats, aged 3 and 24 months, cultured from cerebral cortex (Cx), hippocampus (Hc), and striatum (St), were assayed for cytokines implicated in Alzheimer's disease: IL-1alpha, IL-1beta, IL-6, and TNF-alpha. Regional differences across all age groups included consistently lower expression of these cytokines in glia derived from Cx than Hc and St. Aging increased basal IL-6 mRNA and secretion by >or=3-fold in glia from Cx and Hc. Aging also increased LPS-induced IL-1 and IL-6 in Hc more than in Cx, whereas no significant effects of age were seen in St-derived glial cytokines. TNF-alpha secretion did not differ by donor age (basal or LPS-induced). Nitric oxide production by microglia from Cx of aging brains showed a smaller induction in response to LPS, with proportionately less neurotoxicity. Thus, glial activation during aging shows regional selectivity in cytokine expression, with opposite effects of aging on the increased inducibility of IL-1 and IL-6 vs the decreased production of nitric oxide.

Age Factors↗
PubMed2003

Task centered visualization of Electronic Medical Record flow sheet.

Usability problem of Electronic Medical Record (EMR) systems is a major hurdle for their acceptance. In this study we used the methodology of Human-Centered Distributed Information Design (HCDID) to compare and evaluate Flow Sheet module of two commercial EMR systems. After which we tried to develop usable interface of a flow sheet using visualization, focusing on task-representation mapping during design and development.

Attitude to Computers↗
PubMed2002

Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1-42- and lipopolysaccharide-activated microglia.

The amyloid beta-peptide (Abeta) activates microglia and promotes the generation of cytokines and oxygen species, including nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha), which can be either neurotoxic or neuroprotective. We show that neuron death in cocultures of rat cortical microglia and neurons activated by lipopolysaccharide (LPS) or Abeta1-42 plus interferon gamma (IFNgamma) is caused by short-lived diffusible molecules and follows the generation of superoxide and/or peroxynitrite as determined by electron paramagnetic spectroscopy. Neurotoxicity induced by LPS or Abeta1-42 plus IFNgamma is blocked by inhibitors of NO synthesis and by the peroxynitrite (ONOO-) decomposition catalysts FeTMPyP [5,10,15,20-tetrakis(n-methyl-4'-pyridyl)porphinato iron (III) chloride] and FeTPPS [5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride] but not by the TNF-alpha inhibitor pentoxifylline. The specificity of FeTMPyP for ONOO- was confirmed by its ability to block the toxicity of a peroxynitrite donor but not of NO donors or of high levels of superoxide in a yeast mutant lacking superoxide dismutase 1. These results implicate peroxynitrite as a mediator of the toxicity of activated microglia, which may play a major role in Abeta1-42 neurotoxicity and Alzheimer's disease.

Amyloid beta-Peptides↗