The effect of Lycium Barbarum on spinal cord injury, particularly its relationship with M1 and M2 macrophage in rats

BACKGROUND: Our past researches suggested that L. barbarum exhibits direct neuroprotective and immune regulatory effects on the central nervous system, which are highly related to the events involved in the spinal cord injury, but not yet been investigated. Immune responses play an important role in the development of the pathology after secondary injury, particularly the M1 and M2 types of macrophage, on which special emphasis was laid in this study. METHODS: In our previous studies L. barbarum was administrated orally from 7 days before the injury to ensure a stabilized concentration in the blood. For clinical application, L. barbarum can only be administered after the injury. Therefore, both pre-injury and post-injury administration protocols were compared. In vivo and in vitro studies were conducted and analyzed immunohistochemically, including Western blotting. RESULTS: The lesion size in the pre-treated group was much larger than that in the post-treated group. To explain this difference, we first studied the effect of L. barbarum on astrocytes, which forms the glial scar encircling the lesion. L. barbarum did not significantly affect the astrocytes. Then we studied the effect of L. barbarum on microglia/macrophages, particularly the M1 and M2 polarization. After spinal cord injury, the deleterious M1 cells dominant the early period, whereas the beneficial M2 cells dominate later. We found that in the pre-treated group L. barbarum significantly enhanced the expression of M1 cells and suppressed that of M2 cells, while in the post-treated group LBP markedly promoted the activity of M2 cells. This explained the difference between the pre- and post-treated groups. CONCLUSIONS: Lycium barbarum has been wildly accepted to have beneficial effects in various central nervous system diseases. Our finding of deleterious effect of LBP administered at early period of spinal cord injury, indicates that its application should be avoided. The substantial beneficial effect of LBP when administered at later stage has an important impact for clinical application

Photoconductivity of biased graphene

Graphene is a promising candidate for optoelectronic applications such as photodetectors, terahertz imagers, and plasmonic devices. The origin of photoresponse in graphene junctions has been studied extensively and is attributed to either thermoelectric or photovoltaic effects. In addition, hot carrier transport and carrier multiplication are thought to play an important role. Here we report the intrinsic photoresponse in biased but otherwise homogeneous graphene. In this classic photoconductivity experiment, the thermoelectric effects are insignificant. Instead, the photovoltaic and a photo-induced bolometric effect dominate the photoresponse due to hot photocarrier generation and subsequent lattice heating through electron-phonon cooling channels respectively. The measured photocurrent displays polarity reversal as it alternates between these two mechanisms in a backgate voltage sweep. Our analysis yields elevated electron and phonon temperatures, with the former an order higher than the latter, confirming that hot electrons drive the photovoltaic response of homogeneous graphene near the Dirac point

Mechanism of action of the new anti-ischemia drug ranolazine

Myocardial ischemia is associated with reduced ATP fluxes and decreased energy supply resulting in disturbances of intracellular ion homeostasis in cardiac myocytes. In the recent years, increased persistent (late) sodium current was suggested to contribute to disturbed ion homeostasis by elevating intracellular sodium concentration with subsequent elevation of intracellular calcium. The new anti-ischemia drug ranolazine, a specific inhibitor of late sodium current, reduces sodium overload and hence ameliorates disturbed ion homeostasis. This is associated with symptomatic improvement of angina in patients. Moreover, ranolazine was shown to exhibit anti-arrhythmic effects. In the present article, we review the relevant pathophysiological concepts for the role of late sodium inhibition and summarize the most recent data from basic as well as clinical studies

Thermal Properties of Graphene, Carbon Nanotubes and Nanostructured Carbon Materials

Recent years witnessed a rapid growth of interest of scientific and engineering communities to thermal properties of materials. Carbon allotropes and derivatives occupy a unique place in terms of their ability to conduct heat. The room-temperature thermal conductivity of carbon materials span an extraordinary large range - of over five orders of magnitude - from the lowest in amorphous carbons to the highest in graphene and carbon nanotubes. I review thermal and thermoelectric properties of carbon materials focusing on recent results for graphene, carbon nanotubes and nanostructured carbon materials with different degrees of disorder. A special attention is given to the unusual size dependence of heat conduction in two-dimensional crystals and, specifically, in graphene. I also describe prospects of applications of graphene and carbon materials for thermal management of electronics.Comment: Review Paper; 37 manuscript pages; 4 figures and 2 boxe

Analysis of EGFR, HER2, and TOP2A gene status and chromosomal polysomy in gastric adenocarcinoma from Chinese patients

<p>Abstract</p> <p>Background</p> <p>The EGFR and HER2 genes are located on chromosomes 7 and 17, respectively. They are therapeutic targets in some tumors. The TOP2A gene, which is located near HER2 on chromosome 17, is the target of many chemotherapeutic agents, and co-amplification of HER2 and TOP2A has been described in several tumor types. Herein, we investigated the gene status of EGFR, HER2, and TOP2A in Chinese gastric carcinoma patients. We determined the rate of polysomy for chromosomes 7 and 17, and we attempted to clarify the relationship between EGFR, HER2, and TOP2A gene copy number and increased expression of their encoded proteins. Furthermore, we tried to address the relationship between alterations in EGFR, HER2, and TOP2A and chromosome polysomy.</p> <p>Methods</p> <p>One hundred cases of formalin fixed and paraffin embedded tumor tissues from Chinese gastric carcinoma patients were investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) methods.</p> <p>Results</p> <p>Forty-two percent of the cases showed EGFR overexpression; 16% showed EGFR FISH positive; 6% showed HER2 overexpression; and 11% showed HER2 gene amplification, including all six HER2 overexpression cases. TOP2A nuclear staining (nuclear index, NI) was determined in all 100 tumors: NI values ranged from 0.5 – 90%. Three percent of the tumors showed TOP2A gene amplification, which were all accompanied by HER2 gene amplification. Nineteen percent of the tumors showed chromosome 7 polysomy, and 16% showed chromosome 17 polysomy. Chromosome 7 polysomy correlated significantly with EGFR FISH-positivity, but was not associated with EGFR overexpression. HER2 overexpression associated significantly with HER2 gene amplification. TOP2A gene amplification was significantly associated with HER2 gene amplification. No relationship was found between alterations in the <it>EGFR</it>, <it>HER2</it>, and <it>TOP2A </it>genes and clinicopathologic variables of gastric carcinoma.</p> <p>Conclusion</p> <p>The data from our study suggest that chromosome 7 polysomy may be responsible for increased EGFR gene copy number in gastric carcinomas, and that HER2 gene amplification may be the major reason for HER2 protein overexpression. A combined investigation of the gene status of EGFR, HER2, and TOP2A should facilitate the identification of a target therapeutic regimen for gastric carcinoma patients.</p

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

<p>Abstract</p> <p>Background</p> <p>Neuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairments. In the present study, we investigated the possible preventive effects of 4-<it>O</it>-methylhonokiol, a constituent of <it>Magnolia officinalis</it>, on memory deficiency caused by LPS, along with the underlying mechanisms.</p> <p>Methods</p> <p>We investigated whether 4-<it>O</it>-methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 μg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4-<it>O</it>-methylhonkiol (0.5, 1 and 2 μM).</p> <p>Results</p> <p>Oral administration of 4-<it>O</it>-methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4-<it>O</it>-methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In <it>in vitro </it>study, we also found that 4-<it>O</it>-methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E₂, tumor necrosis factor-α, and interleukin-1β in the LPS-stimulated cultured astrocytes. 4-<it>O</it>-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effect on neuroinflammation, 4-<it>O</it>-methylhonokiol inhibited LPS-induced Aβ_1-42generation, β- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells.</p> <p>Conclusion</p> <p>These results suggest that 4-<it>O</it>-methylhonokiol inhibits LPS-induced amyloidogenesis via anti-inflammatory mechanisms. Thus, 4-<it>O</it>-methylhonokiol can be a useful agent against neuroinflammation-associated development or the progression of AD.</p

AAV2-Mediated Subretinal Gene Transfer of hIFN-α Attenuates Experimental Autoimmune Uveoretinitis in Mice

BACKGROUND: Recent reports show that gene therapy may provide a long-term, safe and effective intervention for human diseases. In this study, we investigated the effectiveness of adeno-associated virus 2 (AAV2) based human interferon-alpha (hIFN-α) gene therapy in experimental autoimmune uveoretinitis (EAU), a classic model for human uveitis. METHODOLOGY/PRINCIPAL FINDINGS: An AAV2 vector harboring the hIFN-α gene (AAV2.hIFN-α) was subretinally injected into B10RIII mice at two doses (1.5×10(6) vg, 1.5×10(8) vg). AAV2 vector encoding green fluorescent protein (AAV2.GFP) was used as a control (5×10(8) vg). The expression of hIFN-α in homogenized eyes and serum was detected by ELISA three weeks after injection. The biodistribution of vector DNA in the injected eyes, contralateral eyes and distant organs was determined by PCR. EAU was induced by immunization with IRBP(161-180) three weeks following vector injections, and evaluated clinically and pathologically. IRBP-specific proliferation and IL-17 expression of lymphocytes from the spleen and lymph nodes were assayed to test the influence of the subretinal delivery of AAV2.hIFN-α on the systemic immune response. hIFN-α was effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2.hIFN-α vector. DNA of AAV2.GFP was observed only in the injected eyes, but not in the distant organs or contralateral eyes. Subretinal injection of both doses significantly attenuated EAU activity clinically and histologically. For the lower dose, there was no difference concerning lymphocyte proliferation and IL-17 production among the AAV2.hIFN-α, AAV2.GFP and PBS injected mice. However, the higher dose of AAV2.hIFN-α significantly suppressed lymphocyte proliferation and IL-17 production. CONCLUSIONS/SIGNIFICANCE: Subretinal delivery of AAV2.hIFN-α lead to an effective expression within the eye for at least three months and significantly attenuated EAU activity. AAV2.hIFN-α was shown to inhibit the systemic IRBP-specific immune response