Chinese Angelica Polysaccharide (CAP) Alleviates LPS-Induced Inflammation and Apoptosis by Down-Regulating COX-1 in PC12 Cells

Background/Aims: Chinese angelica polysaccharide (CAP) is the main effective ingredient of angelica sinensis and exerts anti-inflammatory and anti-apoptotic effects on many diseases. This study aimed to explore the pharmacological potential of CAP on spinal cord injury (SCI). Methods: PC12 cells were pretreated by CAP and were subjected to LPS. Transfection was performed to alter the expression of COX-1. Cell viability and apoptotic cell rate were measured by CCK-8 and flow cytometry respectively. qRT-PCR and western blot analysis were performed to assess the expression changes of pro-inflammatory cytokines, apoptosis-related factor and core kinases in PI3K/AKT pathway. Results: LPS stimulation induced significant cell damage in PC12 cells as cell viability was repressed, apoptosis was induced and the expression levels of IL-1β, IL-6, IL-8, and TNF-α were increased. CAP pretreatment protected PC12 cells against LPS-induced cell damage. Meanwhile CAP treatment reduced the expression of COX-1 even in LPS-stimulated PC12 cells. More importantly, COX-1 overexpression abolished the protective effects of CAP on LPS-injured PC12 cells. Finally, Western blot analytical results showed that CAP activated PI3K/AKT pathway also in a COX-1-dependent manner. Conclusion: CAP exerted anti-apoptotic and anti-inflammatory effects on LPS-injured PC12 cells via down-regulation of COX-1

PL - 038 Habitual swimming exercise induced partial resistance to rat Alzheimer's disease

Objective  In MSSE, we have divided male 2.5-month-old Sprague-Dawley rats into the following 4 groups: control (C), habitual swimming (SW), Alzheimer’s disease (AD) induction without swimming (AD), and habitual swimming and then AD induction (SA), and found the perfect resistance of habitual swimming to AD induction by using the P value statistics of the 5 behavior parameters of rats and the 23 physiological and biochemical parameters of their hippocampus. The topological difference  of four groups were further calculated in this paper by using quantitative difference (QD) and self-similar approach. Methods 1. The logarithm to base golden section τ (lt) is called golden logarithm. It was found that σ=ltσ ≈ 0.710439287156503. 2. For a process from x1 to x2, lx(1,2)=lt(x2/x1) and its absolute vale are called the process logarithm and its QD, QDx(1,2). There are QD threshold values (αx,βx,γx) of function x which can be calculated in terms of σ. The function x is kept to be constant if QDx(1,2) < αx. A function in/far from its function-specific homeostasis is called a normal/dysfunctional function. A normal function can resist a disturbance under its threshold so that QDx(1,2) < βx. A dysfunctional function is defined as the QD is significant if βx ≦QDx(1,2) < γx and extraordinarily significant if QDx(1,2) ≧ γx. 3. Self-similarity was studied in the fractal literature: a pattern is self-similar if it does not vary with spatial or temporal scale. First-order self-similarity condition leads to the power law between two data sets A = {xi} and B = {yi}; yi = ai xi if the QDi of ai and the average of {ai} is smaller than βmin=min{βi} and the average QD of {QDi} is smaller than αmin=min{αi}. 4. The σ algorithm for integrative biology was established based on high-order self-similarity. Those parameters that contribute to the topological difference were the biomarkers. Results The 28 dimension data set consisted of all the 28 parameters. The first-order self-similarity held true for the 28 dimension data sets between groups C and SW. The topological algorithm of other groups suggested three AD biomarkers, protein carbonyl, granules density of presynaptic synaptophysin in the hippocampal CA1 and malondialdehyde intensity. The first two biomarkers were completely reversed by exercise pretreatment, but the third biomarker was partially reversed. Conclusions  Exercise pretraining exerts partial benefits on AD that support its use as a promising new therapeutic option for prevention of neurodegeneration in the elderly and/or AD population.&nbsp

Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination

Background: The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model. Methodology/Principal Findings: Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 mg HA per dose) included rg-A/Vietnam/1203/ 2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 mg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60 % in single A/Anhui/1/2005 vaccine group. Conclusion/Significance: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination agains

Mink is a highly susceptible host species to circulating human and avian influenza viruses

Pandemic influenza, typically caused by reassortment of human and avian influenza viruses, can result in severe or fatal infections in humans. Timely identification of potential pandemic viruses must be a priority in influenza virus surveillance. However, the range of host species responsible for the generation of novel pandemic influenza viruses remain unclear. In this study, we conducted serological surveys for avian and human influenza virus infections in farmed mink and determined the susceptibility of mink to prevailing avian and human virus subtypes. The results showed that farmed mink were commonly infected with human (H3N2 and H1N1/pdm) and avian (H7N9, H5N6, and H9N2) influenza A viruses. Correlational analysis indicated that transmission of human influenza viruses occurred from humans to mink, and that feed source was a probable route of avian influenza virus transmission to farmed mink. Animal experiments showed that mink were susceptible and permissive to circulating avian and human influenza viruses, and that human influenza viruses (H3N2 and H1N1/pdm), but not avian viruses, were capable of aerosol transmission among mink. These results indicate that farmed mink could be highly permissive “mixing vessels” for the reassortment of circulating human and avian influenza viruses. Therefore, to reduce the risk of emergence of novel pandemic viruses, feeding mink with raw poultry by-products should not be permitted, and epidemiological surveillance of influenza viruses in mink farms should be urgently implemented

Phyllaemblicin B inhibits Coxsackie virus B3 induced apoptosis and myocarditis.

Coxsackie virus B3 (CVB3) is believed to be a major contributor to viral myocarditis since virus-associated apoptosis plays a role in the pathogenesis of experimental myocarditis. In this study, we investigated the in vitro and in vivo antiviral activities of Phyllaemblicin B, the main ellagitannin compound isolated from Phyllanthus emblica, a Chinese herb medicine, against CVB3. Herein we report that Phyllaemblicin B inhibited CVB3-mediated cytopathic effects on HeLa cells with an IC(50) value of 7.75+/-0.15microg/mL. In an in vivo assay, treatment with 12mgkg(-1)d(-1) Phyllaemblicin B reduced cardiac CVB3 titers, decreased the activities of LDH and CK in murine serum, and alleviated pathological damages of cardiac muscle in myocarditic mice. Moreover, Phyllaemblicin B clearly inhibited CVB3-associated apoptosis effects both in vitro and in vivo. These results show that Phyllaemblicin B exerts significant antiviral activities against CVB3. Therefore, Phyllaemblicin B may represent a potential therapeutic agent for viral myocarditis

OsLIC, a Novel CCCH-Type Zinc Finger Protein with Transcription Activation, Mediates Rice Architecture via Brassinosteroids Signaling

Rice architecture is an important agronomic trait and a major limiting factor for its high productivity. Here we describe a novel CCCH-type zinc finger gene, OsLIC (Oraza sativa leaf and tiller angle increased controller), which is involved in the regulation of rice plant architecture. OsLIC encoded an ancestral and unique CCCH type zinc finge protein. It has many orthologous in other organisms, ranging from yeast to humane. Suppression of endogenous OsLIC expression resulted in drastically increased leaf and tiller angles, shortened shoot height, and consequently reduced grain production in rice. OsLIC is predominantly expressed in rice collar and tiller bud. Genetic analysis suggested that OsLIC is epistatic to d2-1, whereas d61-1 is epistatic to OsLIC. Interestingly, sterols were significantly higher in level in transgenic shoots than in the wild type. Genome-wide expression analysis indicated that brassinosteroids (BRs) signal transduction was activated in transgenic lines. Moreover, transcription of OsLIC was induced by 24-epibrassinolide. OsLIC, with a single CCCH motif, displayed binding activity to double-stranded DNA and single-stranded polyrA, polyrU and polyrG but not polyrC. It contains a novel conserved EELR domain among eukaryotes and displays transcriptional activation activity in yeast. OsLIC may be a transcription activator to control rice plant architecture