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author:("Liu, xinping")
1.  Evidence of the presence of amyloid substance in the blood of familial amyloidotic polyneuropathy patients with ATTR Val30Met mutation 
Transthyretin (TTR) is a major amyloid fibril protein found in patients with familial amyloidotic polynuropathy (FAP) and senile systemic amyloidosis (SSA). Mainly synthesized in the live, TTR is transferred in the form of tetramer bound with thyroxine, retinol-binding protein (RBP) and lipoprotein in the blood. The aim of this study was to demonstrate the presence of amyloid substances in the blood by investigated the hemocoelom amyloid in different tissue sections from autopsies such as brain, kidney, heart and aorta arch tissue. Congo red staining was employed following by application of polarized light examination, to verify the presence of amyloid deposition in the tissues. Immunohistochemical staining was then performed to identify the specific type of amyloid deposition. Matrix-assisted laser desorption-ionization/time of flight mass spectrometry (MALDI-TOF/MS) was also used to analyze TTR mutation in FAP patients. All subjects were FAP ATTR Val30Met patients. In FAP patients, TTR amyloid deposition was found mainly in the tunica intima of the aortic arch. Interestingly, amyloid substance was found in the blood of FAP patient. Our results suggest that amyloid substance was present in the blood of FAP ATTR Val30Met patients.
PMCID: PMC4270544  PMID: 25550818
Amyloid; transthyretin; familial amyloidtic polynuropathy; immunohistochemistry; Congo red staining
2.  Tetherin has negligible activity in restricting hepatitis C virus in hepatocytes 
Innate immunity  2011;18(3):398-405.
We investigated the ability of tetherin, a recently identified antiviral factor, in restricting hepatitis C virus (HCV) in the Japanese fulminant hepatitis-1 (JFH-1) infectious cell culture system. Human hepatocytes (Huh7, Huh7.5.1) expressed low levels of endogenous tetherin, which could be induced by IFN-α. However, tetherin contributes little to IFN-α-mediated anti-HCV JFH-1 activity. Although tetherin could inhibit Vpu-deleted HIV-1 release, it had negligible activity in restricting HCV JFH-1 release from hepatocytes, which was evidenced by unaffected levels of intracellular/extracellular HCV RNA and infectious virus. The failure of tetherin’s anti-HCV activity could not be related to the counteraction of HCV, as HCV infection of hepatocytes affected neither tetherin expression nor anti-HIV function of tetherin. These observations imply that tetherin has negligible activity in the restriction of HCV JFH-1 in human hepatocytes.
doi:10.1177/1753425911412984
PMCID: PMC3937259  PMID: 21940748
Hepatitis C virus; innate immunity; interferon; tetherin; virus release
3.  Metabolic modulation of chromatin: implications for DNA repair and genomic integrity 
Frontiers in Genetics  2013;4:182.
The maintenance of genomic integrity in response to DNA damage is tightly linked to controlled changes in the damage-proximal chromatin environment. Many of the chromatin modifying enzymes involved in DNA repair depend on metabolic intermediates as cofactors, suggesting that changes in cellular metabolism can have direct consequences for repair efficiency and ultimately, genome stability. Here, we discuss how metabolites may contribute to DNA double-strand break repair, and how alterations in cellular metabolism associated with both aging and tumorigenesis may affect the integrity of our genomes.
doi:10.3389/fgene.2013.00182
PMCID: PMC3779809  PMID: 24065984
chromatin; DNA repair; metabolism; aging; cancer
4.  Mycophenolate Mofetil Inhibits Hepatitis C Virus Replication in Human Hepatic Cells 
Virus research  2012;168(1-2):33-40.
Hepatitis C virus (HCV) infection is the most common indication for liver transplantation and the major cause of graft failure. A widely used immunosuppressant, cyclosporine A (CsA), for people who receive organ transplantation, has been recognized to have the ability to inhibit HCV replication both in vivo and in vitro. In this study, we investigated the effects of several other immunosuppressants, including mycophenolate mofetil (MMF), rapamycin and FK506, on HCV replication in human hepatic cells. MMF treatment of hepatic cells before or during HCV infection significantly suppressed full cycle viral replication, as evidenced by decreased expression of HCV RNA, protein and production of infectious virus. In contrast, rapamycin and FK506 had little effect on HCV replication. Investigation of the mechanism(s) disclosed that the inhibition of HCV replication by MMF was mainly due to its depletion of guanosine, a purine nucleoside crucial for synthesis of guanosine triphosphate, which is required for HCV RNA replication. The supplement of exogenous guanosine could reverse most of anti-HCV effect of mycophenolate mofetil. These data indicate that MMF, through the depletion of guanosine, inhibits full cycle HCV JFH-1 replication in human hepatic cells. It is of interest to further determine whether MMF is indeed beneficial for HCV-infected transplant recipients in future clinical studies.
doi:10.1016/j.virusres.2012.06.009
PMCID: PMC3505383  PMID: 22728816
HCV recurrence; liver transplantation; immunosuppressant; mycophenolate mofetil
5.  (−)-Epigallocatechin gallate inhibits endotoxin-induced expression of inflammatory cytokines in human cerebral microvascular endothelial cells 
Background
(−)-Epigallocatechin gallate (EGCG) is a major polyphenol component of green tea that has antioxidant activities. Lipopolysaccharide (LPS) induces inflammatory cytokine production and impairs blood–brain barrier (BBB) integrity. We examined the effect of EGCG on LPS-induced expression of the inflammatory cytokines in human cerebral microvascular endothelial cells (hCMECs) and BBB permeability.
Methods
The expression of TNF-α, IL-1β and monocyte chemotactic protein-1 (MCP-1/CCL2) was determined by quantitative real time PCR (qRT-PCR) and ELISA. Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule (VCAM) in hCMECs were examined by qRT-PCR and Western blotting. Monocytes that adhered to LPS-stimulated endothelial cells were measured by monocyte adhesion assay. Tight junctional factors were detected by qRT-PCR (Claudin 5 and Occludin) and immunofluorescence staining (Claudin 5 and ZO-1). The permeability of the hCMEC monolayer was determined by fluorescence spectrophotometry of transmembrane fluorescin and transendothelial electrical resistance (TEER). NF-kB activation was measured by luciferase assay.
Results
EGCG significantly suppressed the LPS-induced expression of IL-1β and TNF-α in hCMECs. EGCG also inhibited the expression of MCP-1/CCL2, VCAM-1 and ICAM-1. Functional analysis showed that EGCG induced the expression of tight junction proteins (Occludin and Claudin-5) in hCMECs. Investigation of the mechanism showed that EGCG had the ability to inhibit LPS-mediated NF-κB activation. In addition, 67-kD laminin receptor was involved in the anti-inflammatory effect of EGCG.
Conclusions
Our results demonstrated that LPS induced inflammatory cytokine production in hCMECs, which could be attenuated by EGCG. These data indicate that EGCG has a therapeutic potential for endotoxin-mediated endothelial inflammation.
doi:10.1186/1742-2094-9-161
PMCID: PMC3408337  PMID: 22768975
67LR; endothelial; (−)-epigallocatechin gallate; LPS; NF-κB
6.  Protein phosphatase PP6 is required for homology-directed repair of DNA double-strand breaks 
Cell Cycle  2011;10(9):1411-1419.
DNA double-strand breaks (DSBs) are among the most lethal lesions associated with genome stability, which, when destabilized, predisposes organs to cancers. DSBs are primarily fixed either with little fidelity by non-homologous end joining (NHEJ) repair or with high fidelity by homology-directed repair (HDR). The phosphorylated form of H2AX on serine 139 (γ-H2AX) is a marker of DSBs. In this study, we explored if the protein phosphatase PP6 is involved in DSB repair by depletion of its expression in human cancer cell lines, and determined PP6 expression in human breast cancer tissues by immunohistochemistry staining. We found that bacterially produced PP6c (the catalytic subunit of PP6)-containing heterotrimeric combinations exhibit phosphatase activity against γ-H2AX in the in vitro phosphatase assays. Depletion of PP6c or PP6R2 led to persistent high levels of γ-H2AX after DNA damage and a defective HDR. Chromatin immunoprecipitation assays demonstrated that PP6c was recruited to the region adjacent to the DSB sites. Expression of PP6c, PP6R2 and PP6R3 in human breast tumors was significantly lower than those in benign breast diseases. Taken together, our results suggest that γ-H2AX is a physiological substrate of PP6 and PP6 is required for HDR and its expression may harbor a protective role during the development of breast cancer.
doi:10.4161/cc.10.9.15479
PMCID: PMC3117043  PMID: 21451261
protein phosphatase; PP6; γ-H2AX; DNA double-strand break; homology-directed repair
7.  Structural mechanism of the phosphorylation-dependent dimerization of the MDC1 forkhead-associated domain 
Nucleic Acids Research  2012;40(9):3898-3912.
MDC1 is a key mediator of the DNA-damage response in mammals with several phosphorylation-dependent protein interaction domains. The function of its N-terminal forkhead-associated (FHA) domain remains elusive. Here, we show with structural, biochemical and cellular data that the FHA domain mediates phosphorylation-dependent dimerization of MDC1 in response to DNA damage. Crystal structures of the FHA domain reveal a face-to-face dimer with pseudo-dyad symmetry. We found that the FHA domain recognizes phosphothreonine 4 (pT4) at the N-terminus of MDC1 and determined its crystal structure in complex with a pT4 peptide. Biochemical analysis further revealed that in the dimer, the FHA domain binds in trans to pT4 from the other subunit, which greatly stabilizes the otherwise unstable dimer. We show that T4 is phosphorylated primarily by ATM upon DNA damage. MDC1 mutants with the FHA domain deleted or impaired in its ability to dimerize formed fewer foci at DNA-damage sites, but the localization defect was largely rescued by an artificial dimerization module, suggesting that dimerization is the primary function of the MDC1 FHA domain. Our results suggest a novel mechanism for the regulation of MDC1 function through T4 phosphorylation and FHA-mediated dimerization.
doi:10.1093/nar/gkr1296
PMCID: PMC3351156  PMID: 22234877
8.  Soybean-derived Bowman-Birk inhibitor inhibits neurotoxicity of LPS-activated macrophages 
Background
Lipopolysaccharide (LPS), the major component of the outer membrane of gram-negative bacteria, can activate immune cells including macrophages. Activation of macrophages in the central nervous system (CNS) contributes to neuronal injury. Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, has anti-inflammatory properties. In this study, we examined whether BBI has the ability to inhibit LPS-mediated macrophage activation, reducing the release of pro-inflammatory cytokines and subsequent neurotoxicity in primary cortical neural cultures.
Methods
Mixed cortical neural cultures from rat were used as target cells for testing neurotoxicity induced by LPS-treated macrophage supernatant. Neuronal survival was measured using a cell-based ELISA method for expression of the neuronal marker MAP-2. Intracellular reactive oxygen species (ROS) production in macrophages was measured via 2', 7'-dichlorofluorescin diacetate (DCFH2DA) oxidation. Cytokine expression was determined by quantitative real-time PCR.
Results
LPS treatment of macrophages induced expression of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and of ROS. In contrast, BBI pretreatment (1-100 μg/ml) of macrophages significantly inhibited LPS-mediated induction of these cytokines and ROS. Further, supernatant from BBI-pretreated and LPS-activated macrophage cultures was found to be less cytotoxic to neurons than that from non-BBI-pretreated and LPS-activated macrophage cultures. BBI, when directly added to the neuronal cultures (1-100 μg/ml), had no protective effect on neurons with or without LPS-activated macrophage supernatant treatment. In addition, BBI (100 μg/ml) had no effect on N-methyl-D-aspartic acid (NMDA)-mediated neurotoxicity.
Conclusions
These findings demonstrate that BBI, through its anti-inflammatory properties, protects neurons from neurotoxicity mediated by activated macrophages.
doi:10.1186/1742-2094-8-15
PMCID: PMC3046894  PMID: 21324129
9.  Two novel hierarchical homogeneous nanoarchitectures of TiO2 nanorods branched and P25-coated TiO2 nanotube arrays and their photocurrent performances 
We report here for the first time the synthesis of two novel hierarchical homogeneous nanoarchitectures of TiO2 nanorods branched TiO2 nanotube arrays (BTs) and P25-coated TiO2 nanotube arrays (PCTs) using two-step method including electrochemical anodization and hydrothermal modification process. Then the photocurrent densities versus applied potentials of BTs, PCTs, and pure TiO2 nanotube arrays (TNTAs) were investigated as well. Interestingly, at -0.11 V and under the same illumination condition, the photocurrent densities of BTs and PCTs show more than 1.5 and 1 times higher than that of pure TNTAs, respectively, which can be mainly attributed to significant improvement of the light-absorbing and charge-harvesting efficiency resulting from both larger and rougher surface areas of BTs and PCTs. Furthermore, these dramatic improvements suggest that BTs and PCTs will achieve better photoelectric conversion efficiency and become the promising candidates for applications in DSSCs, sensors, and photocatalysis.
doi:10.1186/1556-276X-6-91
PMCID: PMC3212241  PMID: 21711607
10.  Tin Oxide Nanorod Array-Based Electrochemical Hydrogen Peroxide Biosensor 
Nanoscale Research Letters  2010;5(7):1177-1181.
SnO2 nanorod array grown directly on alloy substrate has been employed as the working electrode of H2O2 biosensor. Single-crystalline SnO2 nanorods provide not only low isoelectric point and enough void spaces for facile horseradish peroxidase (HRP) immobilization but also numerous conductive channels for electron transport to and from current collector; thus, leading to direct electrochemistry of HRP. The nanorod array-based biosensor demonstrates high H2O2 sensing performance in terms of excellent sensitivity (379 μA mM−1 cm−2), low detection limit (0.2 μM) and high selectivity with the apparent Michaelis–Menten constant estimated to be as small as 33.9 μM. Our work further demonstrates the advantages of ordered array architecture in electrochemical device application and sheds light on the construction of other high-performance enzymatic biosensors.
doi:10.1007/s11671-010-9622-1
PMCID: PMC2894215  PMID: 20596358
Nanostructure; SnO2; Nanorod array; Biosensor
11.  Tin Oxide Nanorod Array-Based Electrochemical Hydrogen Peroxide Biosensor 
Nanoscale Research Letters  2010;5(7):1177-1181.
SnO2 nanorod array grown directly on alloy substrate has been employed as the working electrode of H2O2 biosensor. Single-crystalline SnO2 nanorods provide not only low isoelectric point and enough void spaces for facile horseradish peroxidase (HRP) immobilization but also numerous conductive channels for electron transport to and from current collector; thus, leading to direct electrochemistry of HRP. The nanorod array-based biosensor demonstrates high H2O2 sensing performance in terms of excellent sensitivity (379 μA mM−1 cm−2), low detection limit (0.2 μM) and high selectivity with the apparent Michaelis–Menten constant estimated to be as small as 33.9 μM. Our work further demonstrates the advantages of ordered array architecture in electrochemical device application and sheds light on the construction of other high-performance enzymatic biosensors.
doi:10.1007/s11671-010-9622-1
PMCID: PMC2894215  PMID: 20596358
Nanostructure; SnO2; Nanorod array; Biosensor
12.  Carbon-Coated SnO2 Nanorod Array for Lithium-Ion Battery Anode Material 
Nanoscale Research Letters  2010;5(3):649-653.
Carbon-coated SnO2 nanorod array directly grown on the substrate has been prepared by a two-step hydrothermal method for anode material of lithium-ion batteries (LIBs). The structural, morphological and electrochemical properties were investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electrochemical measurement. When used as anodes for LIBs with high current density, as-obtained array reveals excellent cycling stability and rate capability. This straightforward approach can be extended to the synthesis of other carbon-coated metal oxides for application of LIBs.
doi:10.1007/s11671-010-9529-x
PMCID: PMC2894033  PMID: 20672094
Carbon-coated SnO2 nanorod array; Hydrothermal method; LIBs; Anode material; Array architecture
13.  Carbon-Coated SnO2 Nanorod Array for Lithium-Ion Battery Anode Material 
Nanoscale Research Letters  2010;5(3):649-653.
Carbon-coated SnO2 nanorod array directly grown on the substrate has been prepared by a two-step hydrothermal method for anode material of lithium-ion batteries (LIBs). The structural, morphological and electrochemical properties were investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electrochemical measurement. When used as anodes for LIBs with high current density, as-obtained array reveals excellent cycling stability and rate capability. This straightforward approach can be extended to the synthesis of other carbon-coated metal oxides for application of LIBs.
doi:10.1007/s11671-010-9529-x
PMCID: PMC2894033  PMID: 20672094
Carbon-coated SnO2 nanorod array; Hydrothermal method; LIBs; Anode material; Array architecture
14.  A novel and stable "two-hit" acute lung injury model induced by oleic acid in piglets 
Background
Children are susceptible to pulmonary injury, and acute lung injury (ALI) often results in a high mortality and financial cost in pediatric patients. Evidence has showed that oleic acid (OA) plays an important role in ALI. Therefore, it has special significance to study ALI in pediatric patients by using OA-induced animal models. Unfortunately, the animal model hs a high mortality due to hemodynamic instability. The aim of this study was to establish a novel hemodynamically stable OA-induced ALI model in piglets with two hits.
Methods
18 Chinese mini-piglets were randomized into three groups: group C (received saline-ethanol solution), group T (received OA-ethanol solution in routine administration manner) and group H (received OA-ethanol solution in two-hit manner). Hemodynamic and pulmonary function data were measured. Histopathological assessments were performed.
Results
Two piglets in group T died of radical decline of systemic blood pressure. Group T showed more drastic hemodynamic changes than group H especially during the period of 5 to 30 minutes after OA administration. Both Group T and group H all produced severe lung injury, while group C had no significant pathologic changes. OA-induced hypotension might be caused by pulmonary hypertension rather than comprised left ventricular function.
Conclusion
OA leads to severe pulmonary hypertension which results in hemodynamic fluctuation in OA-induced ALI model. It is the first report on hemodynamic stable ALI animal model in piglets using two-hit method. The two-hit ALI animal model fulfils the ALI criteria and has the following characteristics: hemodynamic stability, stable damage to gas exchange and comparability with pediatric patients in body weight and corresponding age. The two-hit ALI animal model can be used to study the basic mechanism and the therapeutic strategies for pediatric ALI.
doi:10.1186/1751-0147-51-17
PMCID: PMC2673213  PMID: 19331663
15.  Synthesis and Visible-Light Photocatalytic Property of Bi2WO6Hierarchical Octahedron-Like Structures 
Nanoscale Research Letters  2008;3(10):365-371.
A novel octahedron-like hierarchical structure of Bi2WO6has been fabricated by a facile hydrothermal method in high quantity. XRD, SEM, TEM, and HRTEM were used to characterize the product. The results indicated that this kind of Bi2WO6crystals had an average size of ~4 μm, constructed by quasi-square single-crystal nanosheets assembled in a special fashion. The formation of octahedron-like hierarchical structure of Bi2WO6depended crucially on the pH value of the precursor suspensions. The photocatalytic activity of the hierarchical Bi2WO6structures toward RhB degradation under visible light was investigated, and it was found to be significantly better than that of the sample fabricated by SSR. The better photocatalytic property should be strongly associated with the high specific surface area and the abundant pore structure of the hierarchical octahedron-like Bi2WO6.
doi:10.1007/s11671-008-9168-7
PMCID: PMC3244900
Nanostructure; Photodegradation; Optical absorption

Results 1-15 (15)