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ABSTRACT: BACKGROUND: Radiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation-induced brain injury (RI). Treatment for RI remains a challenge. We conducted this study to investigate the indications of neurosurgery, operation time and prognosis of patients with RI after NPC radiotherapy who underwent neurosurgical management. METHODS: This was a follow-up study between January 2005 and July 2011. Fifteen NPC cases of RI who underwent neurosurgery were collected. Brain Magnetic resonance imaging (MRI), surgery and histology were studied. The outcome was assessed by LENT/SOMA scales and modified Rankin scale. RESULTS: Brain lesion resection (86.7%) was more common than decompressive craniotomy (13.3%). According to LENT/SOMA scale before and six months after surgery, 13 of 15, 12 of 15, 14 of 15, and 14 of 15 cases showed improvement at subjective, objective, management and analytic domains, respectively. 12 of 15 patients showed improvement of modified Rankin scale after surgery. Three patients who underwent emergency surgery showed significant improvement (average score increment of 2, 2.7, 2.7, 3 and 2 at LENT/SOMA scale subjective, objective, management, analytic, and modified Rankin scale, respectively), as compared with 12 cases underwent elective surgery (average score increment of 1, 1, 1.4, 1.8 and 1 at LENT SOMA scale subjective, objective, management, analytic, and modified Rankin scale, respectively). CONCLUSIONS: Neurosurgery, including brain necrotic tissue resection and decompressive craniotomy, improves the prognosis for RI patients, especially for those with indications of emergency surgery.
Radiation Oncology 04/2013; 8(1):88. · 2.32 Impact Factor
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ABSTRACT: Epilepsy is a cryptogenic neurological disorder characterized by recurrent seizures which may be precipitated by a variety of endogenous or exogenous factors, and usually occurs many months or years after a precipitating injury. Timely diagnosis and treatment at the early stage of epilepsy are very important for patients to prevent serious lesions and improve the quality of their life. In this study, the metabonomics approach based on the GC-MS technique, multivariate statistical analysis and the metabolism network analysis were applied to investigate metabolic changes in epileptic patients. The outcome of this study suggested that ten endogenous metabolites and five metabolism pathways were mainly involved and showed marked perturbations in epileptic patients. It not only enhances the understanding of the pathology of epilepsy, but also provides an experimental foundation for the therapeutic strategy of epilepsy. Furthermore, this work demonstrates the powerful predictive potential of the metabolic network analysis to neurological disease.
Molecular BioSystems 06/2012; 8(8):2197-204. · 3.53 Impact Factor
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ABSTRACT: hTERTC27, a 27-kDa hTERT C-terminal polypeptide has been demonstrated to cause hTERT-positive HeLa cell apoptosis and inhibits the growth of mouse melanoma. hTERTC27 has been associated with telomere dysfunction, regulation of gene-regulated apoptosis, the cell cycle and activation of natural killer (NK) cells, but its mechanism of action is not fully understood. Here, we report that dendritic cells (DCs) transduced with hTERTC27 can increase T-cell proliferation, and augment the concentration of interleukin-2 (IL-2) and interferon-γ (IFN-γ) in the supernatants of T cells. It can also induce antigen-specific cytotoxic T lymphocytes (CTL) against glioma cells in vitro. Moreover, hTERTC27 gene-transduced DCs exhibit a very potent cytotoxicity to glioma cells in vivo. It could prolong the survival time and inhibit the growth of glioma-bearing mice. These data suggest that hTERTC27 gene-transduced DCs can efficiently enhance immunity against gliomas in vitro and in vivo.
Oncology Reports 12/2011; 27(4):1163-9. · 1.84 Impact Factor
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ABSTRACT: Radiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation encephalopathy (RE). To investigate the characteristics of epilepsy in RE after NPC radiotherapy, we observed 101 RE patients after NPC radiotherapy during a 5-year study period. Seizure semiology, brain magnetic resonance imaging (MRI), electroencephalography (EEG) were studied. We found that epilepsy is a common symptom in these patients, with an incidence of 15.8%. In the variables of age, sex, post-radiotherapy interval, radiation dose, radiotherapy techniques, and radiation field, there were no significant differences between RE patients with and without epilepsy. Furthermore, we investigated seizure semiology and EEG records in RE patients with epilepsy, and found that generalized tonic-clonic seizure (GTCS) was the most common type. Cystic lesions in temporal lobes in MRI were more common in RE patients with epilepsy (18.74%), as compared with RE patients without epilepsy (9.41%).
Epilepsy research 05/2011; 96(1-2):24-8. · 2.48 Impact Factor
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ABSTRACT: Opioids are powerful pain relievers, but also potent inducers of dependence and tolerance. Chronic morphine administration (via subcutaneous pellet) induces morphine dependence in the nucleus accumbens, an important dependence region in the brain, yet the cellular mechanisms are mostly unknown. Toll-like receptor 2 (TLR2) plays an essential function in controlling innate and inflammatory responses. Using a knockout mouse lacking TLR2, we assessed the contribution of TLR2 to microglia activation and development of morphine dependence. We report here that mice deficient in TLR2 inhibit morphine-induced the levels of microglia activation and proinflammatory cytokines. Moreover, in TLR2 knockout mice the main symptoms of morphine withdrawal were significantly attenuated. Our data reveal that TLR2 plays a critical role in morphine-induced microglia activation and dependence.
Neuroscience Letters 02/2011; 489(1):43-7. · 2.11 Impact Factor
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ABSTRACT: Following cerebral infarction, hypoxic tissues remains in the ischemic cortex for long periods of time. Glial fibrillary acidic protein (GFAP) is a specific marker of astrocytes, which is thought to be essential for neuronal survival. We aimed to clarify the relationship between hypoxic tissue and astrocytes following cerebral infarction. Rats with middle cerebral artery occlusion were randomly divided into a 1.5-hour ischemia-reperfusion(1.5-hour IR) group and a permanent ischemia (PI) group. Hypoxic tissue and GFAP fluorescence intensity in the ischemic cortex were observed postoperatively on days 1, 3, 7, and 14. Results showed that hypoxic tissue was present from day 1 to 14 in the 1.5-hour IR group and on days 1 and 3 in the PI group. The GFAP fluorescence intensity in the 1.5-hour IR group was stronger than that in the PI group at the same time point of observation. Over time, GFAP expression increased and peaked at 7 days in each group, followed by a decrease in signal. In hypoxic tissue, the GFAP fluorescence intensity was stronger than that in the surrounding tissue at all observation time points. These data indicate that astrocytes were strongly activated in hypoxic tissue induced by temporary ischemia followed by reperfusion. The activation of astrocytes may partially contribute to the survival and repair of hypoxic tissue following brain ischemia.
The International journal of neuroscience 01/2011; 121(1):1-7. · 0.86 Impact Factor
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Lei He,
Hui Li,
Lin Chen,
Junying Miao,
Yulin Jiang,
Yi Zhang,
Zuoxiang Xiao,
Gregory Hanley, Yi Li,
Xiumei Zhang,
Gene LeSage,
Ying Peng,
Deling Yin
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ABSTRACT: Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6), the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or µ-opioid receptor (µOR) deficient primary microglia, suggesting an involvement of MAPK and µOR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require μOR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and µOR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of µOR is capable of preventing opioid-induced brain damage.
PLoS ONE 01/2011; 6(4):e18190. · 4.09 Impact Factor
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Ling Long, Yi Li,
Yi Dong Wang,
Qing Yu He,
Mei Li,
Xiao Dong Cai,
Kou Peng,
Xiang Pen Li,
Dan Xie,
Yan Ling Wen,
De Ling Yin,
Ying Peng
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ABSTRACT: Fetal alcohol spectrum disorder (FASD) is a challenging public health problem. Previous studies have found an association between FASD and oxidative stress. In the present study, we assessed the role of oxidative stress in ethanol-induced embryonic damage and the effect of (-)-epigallocatechin-3-gallate (EGCG), a powerful antioxidant extracted from green tea, on the development of FASD in a murine model.
Pregnant female mice were given intraperitoneal ethanol (25%, 0.005 to 0.02 ml/g) on gestational day 8 (G8) to establish the FASD model. On G10.25, mice were sacrificed and embryos were collected and photographed to determine head length (HL), head width (HW), and crown rump length (CRL). For mice given EGCG, administration was through a feeding tube on G7 and G8 (dose: 200, 300, or 400 mg/kg/d, the total amount for a day was divided into 2 equal portions). G10.25 embryos were evaluated morphologically. Brain tissues of G9.25 embryos were used for RT-PCR and western blotting of neural marker genes and proteins and detection of oxidative stress indicators.
Administration of ethanol to pregnant mice on G8 led to the retardation of embryonic growth and down-regulation of neural marker genes. In addition, administration of ethanol (0.02 ml/g) led to the elevation of oxidative stress indicators [hydrogen peroxide (H₂O₂) and malondialdehyde (MDA)]. Administration of EGCG on G7 and G8 along with ethanol on G8 ameliorated the ethanol-induced growth retardation. Mice given EGCG (400 mg/kg/d) along with ethanol had embryo sizes and neural marker genes expression similar to the normal controls. Furthermore, EGCG (400 mg/kg on G7 and G8) inhibited the increase in H₂O₂ and MDA.
In a murine model, oxidative stress appears to play an important role in ethanol-induced embryonic growth retardation. EGCG can prevent some of the embryonic injuries caused by ethanol.
Alcoholism Clinical and Experimental Research 11/2010; 34(11):1929-36. · 3.34 Impact Factor
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Kou Peng, Yi Li,
Ling Long,
Dong Li,
Qiuli Jia,
Yidong Wang,
Qingyu Shen,
Yamei Tang,
Lu Wen,
Hsiang-Fu Kung,
Ying Peng
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ABSTRACT: Neuronal apoptosis sculpts the developing brain, and nearly all identified classes of neurons seem to be produced "in excess" during development. FoxO transcription factors regulate apoptosis in vitro in deprived of neurotrophins. It is unknown if FoxO3a is involved in the development of neurons. Here, we report a role of FoxO3a during neuronal development in zebrafish. By using in situ hybridization, we revealed that FoxO3a transcripts in zebrafish were gradually confined to regions of the central nervous system during embryonic development, including the forebrain, midbrain, midbrain-hindbrain boundary and hindbrain. By using FoxO3a morpholino antisense oligonucleotides, we observed that FoxO3a loss-of-function led to neural developmental defects, including increased neural apoptosis as detected by acridine orange and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling. These defects could be partially rescued by the injection of FoxO3a mRNA. In this study, we found that FoxO3a loss-of-function resulted in the decreased expression of neuronal markers as determined by in situ hybridization and relative quantitative real-time PCR. Furthermore, the activation of FoxO3a was required for the maintenance of neuron survival but not necessary for the induction of neurogenesis. Our results indicated that FoxO3a might be essential for the maintenance of neural development in zebrafish. Therefore, this work provides novel evidence of FoxO3a in the embryonic neurodevelopment from zebrafish to other mammals.
Neuroscience Letters 10/2010; 484(2):98-103. · 2.11 Impact Factor
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ABSTRACT: Hypoxic tissue has been observed in the surrounding areas of the ischemic core following cerebral infarction. The underlying mechanisms for this potentially reversible ischemic region remain to be determined. In this study, we generated permanent brain ischemia (PI) and reperfusion after inducing ischemia for 1.5 h (ischemia-reperfusion or IR) in a rat model of middle cerebral artery occlusion. Using immunofluorescence, we observed hypoxic tissue in ischemic brains and assessed microvessel density in and surrounding the hypoxic tissue. We found that the hypoxic tissues were observed at 1 and 3 days in PI rats and at 1, 3, 7, and 14 days in IR rats. The hypoxic tissue gradually decreased over time. The microvessel density increased in a time-dependent manner in focal brain ischemic tissue in PI and IR rats. Furthermore, IR induced a significant increase in microvessel density when compared with PI rats (P < 0.05). Microvessel density surrounding hypoxic tissue was significantly higher when compared with within the hypoxic tissue (P < 0.05). These data demonstrate that hypoxic tissue may exist for a long period (14 days) following brain IR and indicate that hypoxic tissue usually existed with low microvessel density. Furthermore, the duration of hypoxic tissue was partially dependent on the degree of microvessel proliferation.
Neurological Sciences 10/2010; 31(6):765-71. · 1.32 Impact Factor
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ABSTRACT: Glioma derived from the neural ectoderm is the most common brain tumor and is of great damage to human health among all lethal tumors. Scientists have been trying their best to find new methods and develop new drugs to treat glioma in recent years. The animal glioma model is of great importance to the research. Researchers have developed many animal glioma models, like the rat and mouse model. Now we are trying to develop a new zebrafish glioma model, which has much more advantages and fewer disadvantages than the traditional models in regard to gene mutation, chemical induction, and xenografts. Establishing a glioma model in zebrafish is feasible and would be of great use to patients with this common brain tumor.
Chinese journal of cancer 06/2010; 29(6):621-5.
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ABSTRACT: Resveratrol is emerging as a novel anticancer agent. However, the mechanism(s) by which resveratrol exerts its effects on endometrial cancer (EC) are unknown. We previously reported that beta-arrestin 2 plays a critical role in cell apoptosis. The role of ß-arrestin 2 in resveratrol modulation of endometrial cancer cell apoptosis remains to be established.
EC cells HEC1B and Ishikawa were transfected with either ß-arrestin 2 RNA interfering (RNAi) plasmid or beta-arrestin 2 full-length plasmid and control vector. The cells were then exposed to differing concentrations of resveratrol. Apoptotic cells were detected by TUNEL assay. Expression of total and phosphorylated Akt (p-Akt), total and phosphorylated glycogen synthase kinase 3 beta (p-GSK3ß), and caspase-3 were determined by Western blot analysis. Our data demonstrate that inhibition of ß-arrestin 2 increases the number of apoptotic cells and caspase-3 activation. Additionally ß-arrestin 2 exerted an additive effect on resveratrol-reduced levels of p-Akt and p-GSK3ß. Overexpression of ß-arrestin 2 decreased the percentage of apoptosis and caspase-3 activation and attenuated resveratrol-reduced levels of p-Akt and p-GSK3ß. Taken together, our studies demonstrate for the first time that ß-arrestin 2 mediated signaling plays a critical role in resveratrol-induced apoptosis in EC cells.
Resveratrol primes EC cells to undergo apoptosis by modulating beta-arrestin 2 mediated Akt/GSK3ß signaling pathways.
These inspiring findings would provide a new molecular basis for further understanding of cell apoptotic mechanisms mediated by ß-arrestin 2 and may provide insights into a potential clinical relevance in EC.
Biochimica et Biophysica Acta 05/2010; 1800(9):912-8. · 4.66 Impact Factor
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Lin Chen,
Wanliang Shi,
Hui Li,
Xiuli Sun,
Xionglin Fan,
Gene Lesage,
Yi Li, Yi Zhang,
Xiumei Zhang,
Ying Zhang,
Deling Yin
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ABSTRACT: Although it is established that opioid and Mycobacterium tuberculosis are both public health problems, the mechanisms by which they affect lung functions remain elusive.
We report here that mice subjected to chronic morphine administration and M. tuberculosis infection exhibited significant apoptosis in the lung in wild type mice as demonstrated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. Morphine and M. tuberculosis significantly induced the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, deficiency in TLR9 significantly inhibited the morphine and M. tuberculosis induced apoptosis in the lung. In addition, chronic morphine treatment and M. tuberculosis infection enhanced the levels of cytokines (TNF-alpha, IL-1beta, and IL-6) in wild type mice, but not in TLR9 knockout (KO) mice. The bacterial load was much lower in TLR9 KO mice compared with that in wild type mice following morphine and M. tuberculosis treatment. Morphine alone did not alter the bacterial load in either wild type or TLR9 KO mice. Moreover, administration of morphine and M. tuberculosis decreased the levels of phosphorylation of Akt and GSK3beta in the wild type mice, but not in TLR9 KO mice, suggesting an involvement of Akt/GSK3beta in morphine and M. tuberculosis-mediated TLR9 signaling. Furthermore, administration of morphine and M. tuberculosis caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type mice, but not in TLR9 KO mice, indicating a role of Bcl-2 family in TLR9-mediated apoptosis in the lung following morphine and M. tuberculosis administration.
These data reveal a role for TLR9 in the immune response to opioids during M. tuberculosis infection.
PLoS ONE 01/2010; 5(2):e9205. · 4.09 Impact Factor
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ABSTRACT: Toll-like receptor 2 (TLR2), a key immune receptor in the TLR family, is widely expressed in various systems, including the immune and nervous systems and plays a critical role in controlling innate and adaptive immune responses. We previously reported that opioids inhibit cell growth and trigger apoptosis. However, the underlying mechanism by which TLR2 mediates apoptosis in response to opioids is not yet known. Here we show that chronic morphine treatment in primary neurons dramatically increased the expression of TLR2 at both the messenger RNA and protein levels. In addition, TLR2 deficiency significantly inhibited chronic morphine-induced apoptosis in primary neurons. Activation of caspase-3 after morphine treatment is impaired in TLR2 deficient primary neurons. Moreover, morphine treatment failed to induce an increased level of phosphorylated glycogen synthase kinase 3 beta (GSK3beta) in TLR2 deficient primary neurons, suggesting an involvement of GSK3beta in morphine-mediated TLR2 signaling. These results thus demonstrate that opioids prime neurons to undergo apoptosis by inducing TLR2 expression. Our data suggest that inhibition of TLR2 is capable of preventing opioids-induced damage to neurons.
Biochemical and Biophysical Research Communications 11/2009; 391(1):426-30. · 2.48 Impact Factor
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Bing Liang,
Ming-Liang He,
Chu-yan Chan,
Yang-chao Chen,
Xiang-Ping Li, Yi Li,
Dexian Zheng,
Marie C Lin,
Hsiang-Fu Kung,
Xin-Tao Shuai,
Ying Peng
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ABSTRACT: Combined treatment using nonviral agent-mediated enzyme/prodrug therapy and immunotherapy had been proposed as a powerful alternative method of cancer therapy. The present study was aimed to evaluate the cytotoxicity in vitro and the therapeutic efficacy in vivo when the cytosine deaminase/5-fluorocytosine (CD/5-FC) and TNF-related apoptosis-inducing ligand (TRAIL) genes were jointly used against rat C6 glioma cells. The potency of the FA-PEG-PEI used as a nonviral vector was tested in the FR-expressed C6 glioma cells and Wistar rats. The C6 glioma cells and animal model were treated by the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL. The antitumor effect was evaluated by survival assays and tumor volume. This study revealed a significant increase of cytotoxicity in vitro following the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL treatments in C6 glioma cells. Animal studies showed a significant growth inhibition of the C6 glioma xenografts using the combined treatment. These results demonstrated that the combined treatment generated additive cytotoxic effect in C6 glioma cells in both in vitro and in vivo conditions, and indicated that such treatment method using both enzyme/prodrug therapy and TRAIL immunotherapy might be a promising therapeutic strategy in treating glioma.
Biomaterials 06/2009; 30(23-24):4014-20. · 7.40 Impact Factor
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ABSTRACT: We have previously reported that morphine induces apoptosis. However, the underlying molecular mechanisms remain to be elucidated. Toll-like receptor 2 (TLR2), a key immune receptor in the TLR family, modulates cell survival and cell death in various systems. Evidence indicates that beta-arrestin 2 acts as a negative regulator of innate immune activation by TLRs. Here, we investigated the roles of TLR2, the downstreaming mediator MyD88, and beta-arrestin 2 in morphine-induced apoptosis. We showed that overexpression of TLR2 in HEK293 cells caused a significant increase in apoptosis after morphine treatment. Inhibition of MyD88 by transfecting dominant negative MyD88 or overexpression of beta-arrestin 2 by transfecting beta-arrestin 2 full length plasmid in TLR2 overexpressing HEK293 cells attenuated morphine-induced apoptosis. Our study thus demonstrates that TLR2 signaling mediates the morphine-induced apoptosis, and beta-arrestin 2 is a negative regulator in morphine-induced, TLR2-mediated apoptosis.
Biochemical and Biophysical Research Communications 01/2009; 378(4):857-61. · 2.48 Impact Factor
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ABSTRACT: Neural stem cells are capable of differentiating into three major neural cell types, but the underlying molecular mechanisms remain unclear. Here, we investigated the mechanism by which integrin beta4 modulates mouse neural stem cell differentiation in vitro. Inhibition of endogenous integrin beta4 by RNA interference inhibited the cell differentiation and the expression of fibroblast growth factor receptor 2 but not fibroblast growth factor receptor 1 or fibroblast growth factor receptor 3. Overexpression of integrin beta4 in neural stem cells promoted neural stem cell differentiation. Furthermore, integrin beta4-induced differentiation of neural stem cells was attenuated by SU5402, the inhibitor of fibroblast growth factor receptors. Finally, we investigated the role of integrin beta4 in neural stem cell survival: knockdown of integrin beta4 did not affect survival or apoptosis of neural stem cells. These data provide evidence that integrin beta4 promotes differentiation of mouse neural stem cells in vitro possibly through fibroblast growth factor receptor 2.
The international journal of biochemistry & cell biology 10/2008; 41(4):916-24. · 4.89 Impact Factor
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Yi Zhang,
Robert Foster,
Xiuli Sun,
Qiaoqiao Yin, Yi Li,
Gregory Hanley,
Charles Stuart,
Yili Gan,
Chuanfu Li,
Zhiyong Zhang,
Deling Yin
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ABSTRACT: Restraint stress, either physical or psychological, can modulate immune function. However, the mechanisms associated with stress-induced lymphocyte reduction remains to be elucidated. We have previously shown that chronic stress induces Fas-mediated lymphocyte reduction. Here, we investigated the mechanisms by which restraint stress modulates lymphocyte reduction. Our data have shown that inhibition of p53 by the p53 inhibitor PFT-alpha attenuates stress-induced reduction in lymphocyte numbers. These results were verified using p53 knockout mice, suggesting a pivotal role of p53 in this process. In addition our data have indicated that PI3K/nuclear factor kappa B (NF-kappaB) signaling pathway plays an important role in the stress-induced lymphocyte reduction. Our study thus demonstrates that restraint stress promotes lymphocyte reduction through p53 and PI3K/NF-kappaB pathways.
Journal of Neuroimmunology 08/2008; 200(1-2):71-6. · 2.96 Impact Factor
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ABSTRACT: A great challenge for gene therapy is to develop a high efficient gene delivery system with low toxicity. Nonviral vectors are still attractive although the current agents displayed some disadvantages (i.e., low transfection efficiency, high toxicity). To overcome the high toxicity of poly(ethylene imine) (PEI) and low transfection efficiency of PEGylated PEI (PEG-PEI), we linked a cell specific target molecule folate (FA) on poly(ethylene glycol) (PEG) and then grafted the FA-PEG onto hyperbranched PEI 25kDa. The FA-PEG- grafted-hyperbranched-PEI (FA-PEG-PEI) effectively condensed plasmid DNA (pDNA) into nanoparticles with positive surface charge under a suitable N/P ratio. Tested in deferent cell lines (i.e., HEK 293T, glioma C6 and hepatoma HepG2 cells), no significant cytotoxicity of FA-PEG-PEI was added to PEG-PEI. More importantly, significant transfection efficiency was exhibited in FA-targeted cells. Reporter assay showed that FA-PEG-PEI/pDNA complexes had significantly higher transgene activity than that of PEI/pDNA in folate-receptor (FR) positive (HEK 293T and C6) cells but not FR-negative (HepG2) cells. These results indicated that FA-PEG-PEI might be a promising candidate for gene delivery with the characteristics of good biocompatibility, potential biodegradability, and relatively high gene transfection efficiency.
Biochemical and Biophysical Research Communications 04/2008; 367(4):874-80. · 2.48 Impact Factor
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ABSTRACT: In this paper, a novel nano-scale conductive film which combines the advantages of both traditional anisotropic conductive adhesives/films (ACAs/ACFs) and nonconductive adhesives/films (NCAs/NCFs) is introduced and developed for next generation high performance ultra-fine pitch packaging applications. This novel interconnect film possesses the properties of electrical conduction along the z-direction with relatively low bonding pressure (ACF-like) and the ultra-fine pitch (< 100 nm) capability (NCF-like). Unlike typical ACF which requires 1-5 vol% of conductive fillers, the novel nano-scale conductive film only needs less than 0.1 vol% conductive fillers to achieve good electrical conductance in the z direction. The nano-scale conductive film also allows a lower bonding pressure than NCF to achieve a much lower joint resistance (over two orders of magnitude lower than typical ACF joints) and higher current carrying capability. With low temperature sintering of nano-silver fillers, the joint resistance of the nano-scale conductive film could be as low as 10<sup>-5</sup> Ohm, even lower than the NCF and lead-free solder joints. The insertion loss of nano-scale joints are almost the same as the standard ACF or NCF joints, suggesting that the nano-ACF joints are suitable for reliable high frequency adhesive joints in microelectronics packaging. The reliability of the nano-scale conductive film after high temperature and humidity test (85degC/85%RH) was also improved compared to the NCF joints. In order to reduce the silver migration and maintain a good insulation/dielectric property in the x-y plane for the nano-scale conductive film, self-assembled molecular wires (SAM) are used to passivate/protect the silver nano fillers. The protection of silver nano particles with molecular monolayers reduced the silver migration dramatically and no migration was observed upon application of high voltages (up to 500 V) due to the formation of surface chelating compounds between-
the SAM and nano silver fillers. The migration behavior of SAM passivated nano-Ag conductive adhesives was investigated by analyzing the results with the migration model.
Electronic Components and Technology Conference, 2007. ECTC '07. Proceedings. 57th; 07/2007
