Li Wang

Fudan University, Shanghai, Shanghai Shi, China

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Publications (28)104.13 Total impact

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    ABSTRACT: The purpose of this study is to evaluate the MRI features of mucinous borderline ovarian tumors (MBOT). MRI morphology of 30 MBOT proven MBOT by surgery and pathology was retrospectively studied and correlated with the histopathological findings. On MRI, tumors were classified into three morphological categories: (i) unilocular cyst in five (17%) tumors. (ii) multilocular cyst in 23 (76%) tumors. (iii) solid mass in 2 (7%) tumors. MRI features of tumors were identified including the multilocularity (23/30, 77%), honeycomb loculi (15/30, 50%), signal discrepancy (different signal intensity on T1WI and T2WI) (19/30, 63%), thickened wall or septa (>3 mm) (16/30, 53%). Intestinal type and endocervical type of MBOT, two distinctly histologic subtypes, were found in 20 (67%) and 10 (33%) tumors respectively. There were a higher prevalence of multilocularity (P = 0.026), honeycomb loculi (P = 0.025), and signal discrepancy (P = 0.024) in intestinal type than endocervical type of MBOT. Typical MRI features of MBOT are large multilocular tumors with honeycomb loculi, heterogeneous signal intensity of the loculi, and thickened wall or septa.J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 09/2014; 40(3). DOI:10.1002/jmri.24408 · 2.79 Impact Factor
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    ABSTRACT: PurposeTo investigate the spectrum of MRI appearances of ovarian serous borderline tumor (SBT). Materials and Methods Following ethics approval, 31 patients with 51 histologically proven ovarian SBTs underwent preoperative MRI. Images were evaluated, by two observers for the location, shape, size, internal architecture, signal intensity, and extent or stage of the tumors. The MRI findings were correlated with pathological findings. ResultsTwenty of 31 patients (65%) demonstrated bilateral ovarian SBTs on MRI. Three MRI morphological patterns of ovarian SBT were identified: (i) Mainly cystic mass with multiple intracystic papillary projections from the wall and septations was observed in 24 (47%) tumors. (ii) Solid mass with hierarchical branching papillary and fibrous stalk architecture was observed in 8 (16%) tumors. The branching papillary projections were hyperintensity on T2WI, intermediate intense on DWI, and enhanced intensely after the administration of Gd-DTPA. The internal branching fibrous stalks were hypointensity on T2WI and enhanced slightly. (iii) Mixed cystic-solid mass was observed in 19 (37%) tumors. The cystic and solid components had the architecture and signal intensity similar to those of cystic and solid SBTs. Papillary projections were the common architecture of all three types of tumors. Conclusion On MRI, the ovarian SBT has some morphological distinguishing features. The solid papillary architecture with internal branching fibrous stalk is a somewhat more characteristic MRI appearance. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 07/2014; 40(1). DOI:10.1002/jmri.24339 · 2.79 Impact Factor
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    ABSTRACT: To investigate diffusion-weighted (DW) magnetic resonance (MR) imaging for differentiating borderline from malignant epithelial tumours of the ovary. This retrospective study included 60 borderline epithelial ovarian tumours (BEOTs) in 48 patients and 65 malignant epithelial ovarian tumours (MEOTs) in 54 patients. DW imaging as well as conventional MR imaging was performed. Signal intensity on DW imaging was assessed and apparent diffusion coefficient (ADC) value was measured. The results were correlated with histopathology and cell density. The majority of MEOTs showed high signal intensity on DW imaging, whereas most BEOTs showed low or moderate signal intensity (P = 0.000). The mean ADC value of the solid components in BEOTs (1.562 +/- 0.346 x 10(-3) mm(2)/s) was significantly higher than in MEOTs (0.841 +/- 0.209 x 10(-3) mm(2)/s). A threshold value of 1.039 x 10(-3) mm(2)/s permitted the distinction with a sensitivity of 97.0 %, a specificity of 92.2 % and an accuracy of 96.4 %. There was an inverse correlation between ADC value and cell density (r = -0.609; P = 0.0000) which was significantly lower in BEOTs than in MEOTs. DW imaging is useful for differentiating borderline from malignant epithelial tumours of the ovary. aEuro cent DW MR imaging is useful for differentiating BEOTs from MEOTs. aEuro cent Patients with BEOTs are treated differently from patients with MEOTs. aEuro cent Conservative fertility-sparing laparoscopic surgery can be performed in patients with BEOTs. aEuro cent BEOTs often affect young women of childbearing age.
    European Radiology 05/2014; 24(9). DOI:10.1007/s00330-014-3236-4 · 4.34 Impact Factor
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    ABSTRACT: To investigate MRI in differentiating borderline mucinous cystadenoma (MC) from benign MC of the ovary. We studied MR images of 26 benign MCs and 24 borderline MCs of the ovary. The following MRI features of tumors were evaluated and compared between two groups: laterality, shape, size, loculation, signal intensity of the fluid, thickness of the septation and the wall, and vegetations. The results of the MRI were then compared with the pathological findings. Honeycomb loculi, high signal intensity on T1WI, and low signal intensity on T2WI of the intracystic content, thickened septation or wall (≥5 mm), and vegetations (≥5 mm) were significantly more common in borderline MC than in benign MC with the sensitivity and specificity of identifying borderline MC of 50.0% and 80.8%, 41.7% and 96.2%, 45.8% and 96.2%, and 62.5% and 96.2%, respectively. The presence of any one of the following features-honeycomb loculi with a low signal intensity on T2WI, thickened septation or wall (≥5 mm), and vegetations (≥5 mm)-yielded the sensitivity, specificity, and accuracy of identifying borderline MC of 91.7%, 92.3%, and 92.0%, respectively. MRI has the ability to accurately demonstrate the morphological characteristics of ovarian MC and reliably differentiate borderline MC from benign MC. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 01/2014; 39(1). DOI:10.1002/jmri.24083 · 2.79 Impact Factor
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    ABSTRACT: To investigate the magnetic resonance imaging (MRI) characteristics of ovarian Sertoli-Leydig cell tumors (SLCT). The clinical, MRI and pathological findings of five cases of SLCT were reviewed retrospectively. MRI appearances of tumors including laterality, shape and size, architecture, wall, septa and vegetation, signal intensity and contrast-enhancement pattern were evaluated and correlated with pathological findings. Two tumors were solid which appeared as low signal intensity on T1-weighted imaging (T1WI) and moderate on T2-weighted imaging (T2WI) with multiple small cysts in one of them. The remaining three SLCT were multilocular cystic with the irregularly thickened wall and septa, and with solid area and mural nodules in one of them. The cystic components had the same signal intensity as urine. All the solid components were intensely enhanced after administration of contrast medium. All five tumors were pathologically intermediate differentiation and at FIGO stage I. SLCT demonstrate variable MRI morphological appearances. However, the irregularly thickened wall and septa, the moderate T2WI signal intensity and obvious enhancement in the solid components are three MRI features.
    Journal of Ovarian Research 10/2013; 6(1):73. DOI:10.1186/1757-2215-6-73 · 2.03 Impact Factor
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    ABSTRACT: Angiogenesis is essential for tumor growth, progression and metastasis. Studies indicate that expression and activity of ecto-5'-nucleotidase (CD73) are elevated in metastatic carcinomas. Our previous studies found that angiogenesis of tumor xenografts was decreased when the activity of CD73 in cancer cells was inhibited, implying that this enzyme is involved in tumor angiogenesis. To elucidate the mechanism, we investigated CD73 influence on tumor angiogenesis in both in vitro assays and in tumor bearing mice. We found that capillary-like structures were formed more in CD73(+/+) pulmonary microvascular endothelial cells (PMECs) than CD73(-/-) PMECs, and this was more pronounced when the cells were cultured in cancer-conditioned medium. Meanwhile, CD73 decreased endothelial cells adhesion to collagen IV and promoted migration. Additionally, the extent of tumor angiogenesis and the size of tumors were greater in CD73(+/+) mice than in CD73(-/-) mice. Thus, we concluded that CD73 can promote endothelial cells forming new vessels in cancer condition, facilitating tumor growth and hematogenous metastasis.
    Clinical and Experimental Metastasis 03/2013; 30(5). DOI:10.1007/s10585-013-9571-z · 3.73 Impact Factor
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    ABSTRACT: The objective of this study was to evaluate the role of magnetic resonance diffusion-weighted imaging (DWI) in differentiating malignant from benign thyroid nodules. The prospective study included 111 consecutive patients with solitary thyroid nodules (23 malignant and 88 benign nodules) who underwent DWI. The DWI signal and apparent diffusion coefficient (ADC) values of the nodules were determined and correlated with the histopathologic findings. The majority (65%) of malignant thyroid nodules showed slightly hyperintense, and the majority (69%) of benign nodules were hyperintense on DWI (P < 0.01). The ADC values were lower in the thyroid cancer than in the adenoma and nodular goiter (P < 0.05). When the b factor was 500 s/mm, an ADC value of 1.704 × 10 mm/s can be threshold differentiating malignant from benign nodules, with 92% sensitivity, 88% specificity, and 87% accuracy. The higher cell density and more severe desmoplastic response were the causes of the lower ADC value of thyroid cancer. Diffusion-weighted imaging can be a promising noninvasive imaging to discriminate malignant from benign nodules.
    Journal of computer assisted tomography 01/2013; 37(4):505-10. DOI:10.1097/RCT.0b013e31828d28f0 · 1.60 Impact Factor
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    ABSTRACT: Epithelial ovarian cancer is one of the most malignant cancers in women and resistant to chemotherapy is the major obstacle for the five-year survival rate. Cisplatin is one of the effective anticancer drug used in the ovarian cancer. To find a good strategy to cure the tumors which is resistant to cisplatin, the cisplatin-resistant 3SKOV3 cells were selected from SKOV-3 ovarian cancer cells. Furthermore, the isolated mesenchymal stem cells were infused systemically to try to cure the transplanted tumor induced by 3SKOV3 cells in nude mice. The morphology and cell membrane CD44 expression were investigated by microscope and flow cytometry. The biological behaviors of resistant 3SKOV3 and its parental SKOV3 cells, including proliferation, adhesion, and cell cycle were determined by CCK8, absorbance assay and FCM methods. The transplanted tumors were set up in nude mice with 3SKOV3 cells injection. The growth rate of transplanted tumors was detected following with MSCs injection. The 3SKOV3 cells have different morphologic manifestation and expressed high level of CD44 molecule. At the same time, 3SKOV3 cells have less adhesion ability and less S-phase ratio. The isolated MSCs from bone marrow could inhibit the growth of transplanted tumor via systemic injection. The cisplatin-resistant 3SKOV3 cells have the different biological behaviors as its parental SKOV3 cells. The present study indicated that systemic MSCs have the therapeutic role on ovarian cancer. However, further investigations are in progress to elucidate the underlying mechanism.
    International journal of clinical and experimental pathology 01/2013; 6(11):2506-14. · 1.78 Impact Factor
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    ABSTRACT: Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer's disease (AD). In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Aβ peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2×Tg models. Herein, we test the efficacy and safety of this vaccine in halting and reversing Alzheimer's pathology in 9-month-old APP+PS1 mice. The results showed that administration of this vaccine elicits a long-lasting antibody titer, which correlated well with a reduction of Aβ burden upon histological analysis. Cognitive function in transgenic responders to the vaccine was rescued to levels similar to those found in non-transgenic mice, indicating that the vaccine is capable of providing therapeutic benefit in APP+PS1 mice when administered after the onset of AD pathology. The vaccine also shows indications of circumventing past safety problems observed in AD immunotherapy, as Th1 pro-inflammatory cytokines were not elevated after long-term vaccine administration. Moreover, microhemorrhaging and T-cell infiltration into the brain are not observed in any of the treated subjects. All in all, this vaccine has many advantages over contemporary vaccines against Alzheimer's disease, and may lead to a viable treatment for the disease in the future.
    PLoS ONE 12/2012; 7(12):e49468. DOI:10.1371/journal.pone.0049468 · 3.53 Impact Factor
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    ABSTRACT: Caffeine and melatonin have been shown to protect the Swedish mutant amyloid precursor protein (APP(sw)) transgenic mouse model of Alzheimer's disease from cognitive dysfunction. But their mechanisms of action remain incompletely understood. These Alzheimer's mice have extensive mitochondrial dysfunction, which likely contributes to their cognitive decline. To further explore the mechanism through which caffeine and melatonin protect cognitive function in these mice, we monitored the function of isolated mitochondria from APP(sw) mice treated with caffeine, melatonin, or both in their drinking water for one month. Melatonin treatment yielded a near complete restoration of mitochondrial function in assays of respiratory rate, membrane potential, reactive oxygen species production, and ATP levels. Caffeine treatment by itself yielded a small increase in mitochondrial function. However, caffeine largely blocked the large enhancement of mitochondrial function provided by melatonin. Studies with N2a neuroblastoma cells stably expressing APP(sw) showed that specific inhibition of cAMP-dependent phosphodiesterase (PDE) 4 or cGMP-dependent PDE5 also blocked melatonin protection of mitochondrial function, but A(2a) and A(1) adenosine receptor antagonists were without effect. Melatonin or caffeine at the concentrations used to modulate mitochondrial function in the cells had no effect on cAMP-dependent PDE activity or cellular cAMP or cGMP levels. Therefore, caffeine and increased cyclic nucleotide levels likely block melatonin signaling to mitochondria by independent mechanisms that do not involve adenosine receptor antagonism. The results of this study indicate that melatonin restores mitochondrial function much more potently than caffeine in APP(sw) transgenic mouse and cell models of Alzheimer's disease.
    Neuropharmacology 09/2012; 63(8):1368-79. DOI:10.1016/j.neuropharm.2012.08.018 · 4.82 Impact Factor
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    ABSTRACT: Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities and play a critical role in skin allergic reactions, which are manifested with rapid edema and increases of vascular permeability. The exact mechanisms of mast cell tryptase promoting vascular permeability, however, are unclear and, therefore, we investigated the effect and mechanism of tryptase or human mast cells (HMC-1) supernatant on the permeability of human dermal microvascular endothelial cells (HDMECs). Both tryptase and HMC-1 supernatant increased permeability of HDMECs significantly, which was resisted by tryptase inhibitor APC366 and partially reversed by anti-VEGF antibody and SU5614 (catalytic inhibitor of VEGFR). Furthermore, addition of tryptase to HDMECs caused a significant increase of mRNA and protein levels of VEGF and its receptors (Flt-1 and Flk-1) by Real-time RT-PCR and Western blot, respectively. These results strongly suggest an important role of VEGF on the permeability enhancement induced by tryptase, which may lead to novel means of controlling allergic reaction in skin.
    05/2012; 2012:941465. DOI:10.5402/2012/941465
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    ABSTRACT: Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer's disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65-88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2-4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (-51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 μM) in MCI subjects were associated with no conversion to dementia during the ensuing 2-4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI.
    Journal of Alzheimer's disease: JAD 03/2012; 30(3):559-72. DOI:10.3233/JAD-2012-111781 · 3.61 Impact Factor
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    ABSTRACT: Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer's disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine's established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD.
    Journal of Alzheimer's disease: JAD 03/2011; 25(2):323-35. DOI:10.3233/JAD-2011-110110 · 3.61 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) affects millions of people world-wide and new effective and safe therapies are needed. Cotinine, the main metabolite of nicotine, has a long half-life and does not have cardiovascular or addictive side effects in humans. We studied the effect of cotinine on amyloid-β (Aβ) aggregation as well as addressed its impact on working and reference memories. Cotinine reduced Aβ deposition, improved working and reference memories, and inhibited Aβ oligomerization in the brains of transgenic (Tg) 6799 AD mice. In vitro studies confirmed the inhibitory effect of cotinine on Aβ1-42 aggregation. Cotinine stimulated Akt signaling, including the inhibition of glycogen synthase kinase 3β (GSK3β), which promotes neuronal survival and the synaptic plasticity processes underlying learning and memory in the hippocampus and cortex of wild type and Tg6799 AD mice. Simulation of the cotinine-Aβ1-42 complex using molecular dynamics showed that cotinine may interact with key histidine residues of Aβ1-42, altering its structure and inhibiting its aggregation. The good safety profile in humans and its beneficial effects suggest that cotinine may be an excellent therapeutic candidate for the treatment of AD.
    Journal of Alzheimer's disease: JAD 02/2011; 24(4):817-35. DOI:10.3233/JAD-2011-102136 · 3.61 Impact Factor
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    ABSTRACT: A number of mutations in GATA4 and NKX2.5 have been identified to be causative for a subset of familial congenital heart defects (CHDs) and a small number of sporadic CHDs. In this study, we evaluated common GATA4 and NKX2.5 mutations in 135 Chinese pediatric patients with non-familial congenital heart defects. Two novel mutations in the coding region of GATA4 were identified, namely, 487C >T (Pro163Ser) in exon 1 in a child with tetralogy of Fallot and 1220C >A (Pro407Gln) in exon 6 in a pediatric patient with outlet membranous ventricular septal defect. We also found 848C >A (Pro283Gln) in exon 2 of the NKX2.5 gene in a pediatric patient with ventricular septal defect, patent ductus arteriosus and aortic isthmus stenosis. None of the mutations was detected in healthy control subjects (n = 114). This study suggests that GATA4 and NKX2.5 missense mutations may be associated with congenital heart defects in pediatric Chinese patients. Further clinical studies with large samples are warranted.
    Genetica 12/2010; 138(11-12):1231-40. DOI:10.1007/s10709-010-9522-4 · 1.75 Impact Factor
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    ABSTRACT: In this study, we modified distally based posterior tibial artery perforator flaps for repair of soft-tissue defects close to the distal perforating artery in the distal lower leg. The flap was designed along the axial network around the saphenous nerve. Flap transfer was performed in 45 cases. The size of the defects after debridement ranged from 4 × 3 cm to 20 × 8 cm (mean, 13 × 5.5 cm). Flap size ranged from 9 × 3 cm to 25 × 10 cm (mean, 16 × 7 cm). In this series, 41 flaps survived completely. Venous congestion was not observed. At a mean follow-up of 16.5 months, all flaps matched the recipient sites in color, texture, and thickness. Donor site morbidity was minimal. The modified distally based posterior tibial artery perforator flap is a reliable and useful option for coverage of the soft-tissue defect close to the distal perforating artery in the distal lower leg.
    Journal of Reconstructive Microsurgery 11/2010; 27(3):145-50. DOI:10.1055/s-0030-1268853 · 1.01 Impact Factor
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    ABSTRACT: To investigate the effect of Pinellia extract (PE) on HeLa cell line and to study its associated mechanisms, in order to provide theoretical foundations for its applying in clinical prevention and treatment of cervical disease. HeLa cell line was incubated in media containing different concentrations of PE. Growth of cells was observed and photo-generated with inverted phase microscope; cell activity was detected by MTT assay; cell apoptosis detected by flow cytometry, protein expression of proliferating cell nuclear antigen proliferating cell nuclear antigen (PCNA) was detected by immuno-cytochemistry, and protein expression of Bcl-2 was determined by immunofluorescence. PE showed obvious inhibition on the proliferation of HeLa cells, cell apoptosis appeared after PE treatment in a time and dose dependent manner; PCNA and Bcl-2 protein expressions reduced significantly after being effected by PE for 24 h. PE can obviously inhibit the growth and induce the apoptosis of HeLa cells, and its mechanism is possibly realized through down-regulating the expressions of PCNA and Bcl-2. The study set a primary experimental base for further studying the action mechanism of PE and developing new anti-tumor agents.
    Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 03/2010; 30(3):303-7.
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    ABSTRACT: Despite numerous studies, there is no definitive evidence that high-frequency electromagnetic field (EMF) exposure is a risk to human health. To the contrary, this report presents the first evidence that long-term EMF exposure directly associated with cell phone use (918 MHz; 0.25 w/kg) provides cognitive benefits. Both cognitive-protective and cognitive-enhancing effects of EMF exposure were discovered for both normal mice and transgenic mice destined to develop Alzheimer's-like cognitive impairment. The cognitive interference task utilized in this study was designed from, and measure-for-measure analogous to, a human cognitive interference task. In Alzheimer's disease mice, long-term EMF exposure reduced brain amyloid-beta (Abeta) deposition through Abeta anti-aggregation actions and increased brain temperature during exposure periods. Several inter-related mechanisms of EMF action are proposed, including increased Abeta clearance from the brains of Alzheimer's disease mice, increased neuronal activity, and increased cerebral blood flow. Although caution should be taken in extrapolating these mouse studies to humans, we conclude that EMF exposure may represent a non-invasive, non-pharmacologic therapeutic against Alzheimer's disease and an effective memory-enhancing approach in general.
    Journal of Alzheimer's disease: JAD 01/2010; 19(1):191-210. DOI:10.3233/JAD-2010-1228 · 3.61 Impact Factor
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    ABSTRACT: Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer's disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain amyloid-beta (Abeta) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Abeta levels in both brain interstitial fluid and plasma without affecting Abeta elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Abeta, but also decreases in both soluble and deposited Abeta in hippocampus and cortex. Irrespective of caffeine treatment, plasma Abeta levels did not correlate with brain Abeta levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Abeta1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated, both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first, that both plasma and brain Abeta levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD; and second, that plasma Abeta levels are not an accurate index of brain Abeta levels/deposition or cognitive performance in aged AD mice.
    Journal of Alzheimer's disease: JAD 08/2009; 17(3):681-97. DOI:10.3233/JAD-2009-1071 · 3.61 Impact Factor
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    ABSTRACT: The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of Alzheimer disease.
    Journal of Pineal Research 07/2009; 47(1):82-96. DOI:10.1111/j.1600-079X.2009.00692.x · 7.81 Impact Factor

Publication Stats

438 Citations
104.13 Total Impact Points

Institutions

  • 2006–2014
    • Fudan University
      • • Department of Pathology
      • • Department of Physiology and Pathophysiology
      • • Department of Integrated Traditional Chinese Medicine and Western Medicine
      • • Hospital of Obstetrics and Gynecology
      Shanghai, Shanghai Shi, China
  • 2010–2012
    • USF Health Byrd Alzheimer's Institute
      Tampa, Florida, United States
    • Hebei Medical University
      Chentow, Hebei, China
  • 2009–2012
    • University of South Florida
      • Department of Cell Biology, Microbiology and Molecular Biology
      Tampa, Florida, United States