Effect of freeze‒thaw cycles on root-Soil composite mechanical properties and slope stability.

Natural disasters such as landslides often occur on soil slopes in seasonally frozen areas that undergo freeze‒thaw cycling. Ecological slope protection is an effective way to prevent such disasters. To explore the change in the mechanical properties of soil under the influence of both root reinforcement and freeze‒thaw cycles and its influence on slope stability, the Baijiabao landslide in the Three Gorges Reservoir area was taken as an example. The mechanical properties of soil under different confining pressures, vegetation coverages (VCs) and numbers of freeze‒thaw cycles were studied via mechanical tests, such as triaxial compression tests, wave velocity tests and FLAC3D simulations. The results show that the shear strength of a root-soil composite increases with increasing confining pressure and VC and decreases with increasing number of freeze‒thaw cycles. Bermuda grass roots and confining pressure jointly improve the durability of soil under freeze‒thaw conditions. However, with an increase in the number of freeze‒thaw cycles, the resistance of root reinforcement to freeze‒thaw action gradually decreases. The observed effect of freeze‒thaw cycles on soil degradation was divided into three stages: a significant decrease in strength, a slight decrease in strength and strength stability. Freeze‒thaw cycles and VC mainly affect the cohesion of the soil and have little effect on the internal friction angle. Compared with that of a bare soil slope, the safety factor of a slope covered with plants is larger, the maximum displacement of a landslide is smaller, and it is less affected by freezing and thawing. These findings can provide a reference for research on ecological slope protection technology.

Small intestinal angiosarcoma on clinical presentation, diagnosis, management and prognosis: A case report and review of the literature.

BACKGROUND: Angiosarcoma is a highly malignant soft-tissue sarcoma derived from vascular endothelial cells that mainly occurs in the skin and subcutaneous tissues. Small-intestinal angiosarcomas are rare, and the prognosis is poor. CASE SUMMARY: We reported a case of primary multifocal ileal angiosarcoma and analyze previously reported cases to improve our understanding of small intestinal angiosarcoma. Small intestinal angiosarcoma is more common in elderly and male patients. Gastrointestinal bleeding, anemia, abdominal pain, weakness, and weight loss were the common symptoms. CD31, CD34, factor VIII-related antigen, ETS-related gene, friend leukemia integration 1, and von Willebrand factor are valuable immunohistochemical markers for the diagnosis of small-intestinal angiosarcoma. Small-intestinal angiosarcoma most commonly occurs in the jejunum, followed by the ileum and duodenum. Radiation and toxicant exposure are risk factors for angiosarcoma. After a definite diagnosis, the mean and median survival time was 8 mo and 3 mo, respectively. Kaplan-Meier survival analysis showed that age, infiltration depth, chemotherapy, and the number of small intestinal segments invaded by tumor lesions were prognostic factors for small intestinal angiosarcoma. Multivariate Cox regression analysis showed that chemotherapy and surgery significantly improved patient prognosis. CONCLUSION: Angiosarcoma should be considered for unexplained melena and abdominal pain, especially in older men and patients with a history of radiation exposure. Prompt treatment, including surgery and adjuvant chemotherapy, is essential to prolonging patient survival.

[Mechanism of Xianglian Pills in improving dyslipidemia in obese mice induced by high-fat diet based on network pharmacology and intestinal flora].

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.

FGF2/FGFR signaling promotes cumulus-oocyte complex maturation in vitro.

Fibroblast growth factor 2 (FGF2), a member of FGF family, binds with FGF receptors (FGFR) to initiate biological functions in various somatic cells. However, little is known regarding the role of FGF2/FGFR on oocyte meiosis. In this study, we investigated expression patterns and functions of FGF2/FGFR during in vitro maturation (IVM) of mouse cumulus-oocyte complexes (COCs). Among four FGFRs, Ffgr1 was the most abundant in COCs. The transcripts for Fgf2 and Ffgr1 in COCs increased during IVM. Ffgr1 was present in oocytes and cumulus cells, while Fgf2 was present in only cumulus cells. Treatment of COCs with the selective FGFR inhibitor SU5402 blocked oocyte meiotic progression and downregulated expression of Bmp15 and Gdf9. In contrast, supplement of FGF2 promoted oocyte meiotic progression and upregulated Bmp15 and Gdf9 expression. Inhibition of FGFR with SU5402 reduced cumulus expansion and expressions of Ptx3, Has2 and Tnfaip6. Treatment with FGF2 increased Ptx3 and Has2 expression. Inhibition of FGFR had no effect on meiotic progression of denuded oocytes (DOs). However, co-culture of DOs with COCs or supplementation with FGF2 promoted meiotic progression of DOs. Inhibition of FGF2/FGFR signaling also downregulated Ffgr1 expression, while supplemental FGF2 upregulated Fgfr1 expression. Furthermore, inhibition of FGFR in COCs interrupted the c-Mos/MAPK pathway and maturation-promoting factor (MPF), as indicated by downregulation of oocyte c-mos and Ccnb1 transcripts, respectively. Overall, this study suggests that FGF2 produced by cumulus cells, activates a FGF2/FGFR autocrine/paracrine loop within COCs to regulate cumulus expansion and oocyte meiosis. These findings reveal a novel role for FGF2/FGFR signaling during in vitro maturation of COCs.

Ginsenoside Rb1 Ameliorates Age-Related Myocardial Dysfunction by Regulating the NF-[Formula: see text]B Signaling Pathway.

Age-related myocardial dysfunction is a very large healthcare burden. Here, we aimed to investigate whether ginsenoside Rb1 (Rb1) improves age-related myocardial dysfunction and to identify the relevant molecular mechanism. Young mice and aged mice were injected with Rb1 or vehicle for 3 months. Then, their cardiac function was inspected by transthoracic echocardiography. Serum and myocardium tissue were collected from all mice for histological or molecular expression analyses, including aging-related proteins, markers relevant to fibrosis and inflammation, and markers indicating the activation of the nuclear factor-kappa B (NF-[Formula: see text]B) pathway. Compared with the control condition, Rb1 treatment significantly increased the ejection fraction percentage and significantly decreased the internal diameter and volume of the left ventricle at the end-systolic and end-diastolic phases in aged mice. Rb1 treatment reduced collagen deposition and collagen I, collagen III, and transforming growth factor-[Formula: see text]1 protein expression levels in aged hearts. Rb1 also decreased the aging-induced myocardial inflammatory response, as measured by serum or myocardial interleukin-6 and tumor necrosis factor-[Formula: see text] levels. Furthermore, Rb1 treatment in aged mice increased cytoplasmic NF-[Formula: see text]B but decreased nuclear NF-[Formula: see text]B, which indicated the suppression of the NF-[Formula: see text]B signaling pathway by regulating the translocation of NF-[Formula: see text]B. Rb1 could alleviate aging-related myocardial dysfunction by suppressing fibrosis and inflammation, which is potentially associated with regulation of the NF-[Formula: see text]B signaling pathway.

Self-catalyzed metal organic chemical vapor deposition growth of vertical ß-Ga2O3 nanowire arrays.

Self-catalyzed metal organic chemical vapor deposition (MOCVD) growth of Ga2O3 nanowires on GaN layers prepared on a sapphire substrate has been studied. Nanowire orientations are found to be growth temperature dominated. The vertical yields over total (VOT) curve shows a maximum peak beyond 70% around 480 °C, based on scanning electron microscope observations. X-ray diffraction patterns revealed a primary ß-(-201) normal orientation of as grown nanowires all over the studied temperature interval. Further transmission electron microscopy characterization had confirmed ß-(-201) normal axial orientation of these vertical nanowires, which have well crystallinity. The ß-(010)//GaN(110) in-plane epitaxial relationship is consistent with reported Ga2O3 film/nanowire growth. Nanowires crystallized in ß-[001] axial orientation were considered to be the inclined ones. Based on contrast experiments, the temperature dominated growth behavior is considered a thermodynamic process. The two observed crystalline orientation might have distinguishable but similar system energy, which results in coexistence of multi orientation nanowires over a large temperature span and an optimum temperature window for vertical ß-(-201) normal orientation. The presented optimized ß-Ga2O3 nanowire arrays with highest VOT close to 90% should effectively promote development of reliable high performance devices based on Ga2O3 nanowires.

Oxyresveratrol prevents lipopolysaccharide/d-galactosamine-induced acute liver injury in mice.

Oxyresveratrol (Oxy) is a natural polyhydroxystilbene abundant in mulberry that has anti-inflammation and anti-oxidant activities. We evaluated the protective effect of Oxy in the context of the lipopolysaccharide and d-galactosamine (LPS/d-GalN) induced acute liver injury. Oxy restricted the development of histopathological changes, markedly reduced the activity of alanine transaminase (ALT) and aspartate transaminase (AST), which are indicators of impaired liver function. Oxy significantly regulated the contents of oxidative stress related enzymes and products, and inhibited expressions of inflammatory mediators and cytokines. Oxy treatment diminished the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway in liver, activated the Kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, and increased expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1(NQO1). Pretreatment with Oxy decreased LPS/d-GalN stimulated hepatocyte apoptosis by efficaciously raising the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) ratio, inhibiting the expression and activation of caspases, and activating the phosphoinoside-3-kinase (PI3K)-Akt pathway. Our results demonstrate the hepatoprotective efficacy of Oxy. The protection is mainly due to the prevention of TLR4/NF-κB pathway activation, induced activation of Keap1-Nrf2 signaling pathway, and decreased hepatocyte apoptosis. Oxy warrants further study as a potential therapeutic agent candidate for the management of acute liver injury.

Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice.

To investigate the effects and mechanism of diosmetin on acute hepatic failure (AHF), an AHF murine model was established through administration of lipopolysaccharides/D-galactosamine (LPS/D-GalN). In vitro, diosmetin scavenged free radicals. In vivo, diosmetin decreased mortality among mice, blocked the development of histopathological changes and hepatic damage, and suppressed levels of inflammatory mediators and cytokines. In addition, diosmetin prevented the expression of phosphorylated IKK, IκBα, and NF-κB p65 in the NF-κB signaling pathway, and JNK and p38 in the MAPK signaling pathway. Diosmetin also inhibited hepatocyte apoptosis. Thus, diosmetin exerts protective effects against endotoxin-induced acute hepatic failure in mice. The underlying mechanisms are antioxidation, NF-κB signaling inhibition, inflammatory mediator/cytokine attenuation, and hepatocyte apoptosis suppression. Diosmetin is thus a potential drug candidate for use in the treatment of acute hepatic failure.

Integrase-deficient lentivirus: opportunities and challenges for human gene therapy.

Lentiviruses are powerful tools for gene delivery and have been widely used for the dissection of gene functions in both replicating and quiescent cells. Recently, lentiviruses have also been used for delivering target sequences in gene therapy. Although the lentiviral system provides sustained exogenous gene expression, serious concerns have been raised due to its unfavorable insertion-mediated mutagenesis effect, thereby resulting in the silencing or activation of some unexpected genes. Thus, an array of modifications of the original vectors may reduce risks. Here, we briefly review the structure of the integrase protein, which is an essential protein for viral insertion and integration; the mechanisms of integrase-mediated integration; and the effects of the modifications of integrase. Moreover, we discuss the advantages resulting from integrase modifications and their future applications. Taken together, the generation of integrase-deficient lentivirus (IDLV) not only provides us with an opportunity to reduce the risk of virus-mediated insertions, which would improve the safety of gene therapy, but also favors gene correction and vaccine development.

Study on interaction between plasmid DNA and berberine derivatives with aliphatic chain by fluorescence analysis.

In this study, the fluorescence analysis was used to reveal the interaction between berberine derivatives and plasmid DNA. The results showed that berberine (C0) and its 8-alkyl derivatives can enhance the fluorescent intensity of plasmid DNA. Compared with 8-dodecyl- (C12) and 8-hexadecyl- (C16) berberine, 8-alkylberberine with shorter alkyl group, such as 8-ethyl (C2), 8-butyl (C4), 8-hexyl (C6), and 8-octyl (C8) berberine derivatives showed higher fluorescence increasing effect. Among all compounds, C4 showed highest fluorescence increasing effect. All compounds tested obviously enhanced fluorescent intensity at the concentration of 6.25 × 10(-5) mol/L. These results suggested that berberine and its derivatives can be selectively inserted to the grooves running down the plasmid DNA helix, thus, lead to the increase of fluorescence intensity of the reaction system. Also, adding proper length of aliphatic chain to berberine could promote the interaction between DNA and berberine derivatives. The results of this study may lay some useful foundation for the development of berberine-based medicine agents.

Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury.

OBJECTIVE: To explore the expression of Nrf2/ARE pathway in hindbrain tissue after the traumatic brain injury (TBI) and its anti-oxidative stress effect in the secondary nerve injury. METHODS: The mice with Nrf2 gene knockout were used for the establishment of brain injury model. The experimental animals were divided into four groups: (Nrf2(+)/(+)) sham-operation group, (Nrf2(+)/(+)) brain injury group, (Nrf2(-)/(-)) sham-operation group and (Nrf2(-)/(-)) brain injury group. The specimen 24 h after cerebral trauma was selected. Then RT-PCR method was adopted to detect the expression of Nrf2 mRNA in brain; Western blotting method was adopted to detect the levels of Nrf2, HO-1 and NQO1 proteins in brain; ELISA method was adopted to detect the oxidative stress indicators: protein carbonyls, 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: The Nrf2 mRNA and protein of Nrf2(-)/(-) mice were not expressed, and the difference of the relative amount of Nrf2 mRNA between Nrf2(+)/(+) TBI group and Nrf2(+)/(+) sham-operation group was not statistically significant (P>0.05); the level of Nrf2 protein in Nrf2(+)/(+) TBI group increased significantly compared with the Nrf2(+)/(+) sham-operation group (P<0.01); in the sham-operation groups, the levels of HO-1 and NQO1 proteins of Nrf2(-)/(-) mice decreased obviously compared with the Nrf2(+)/(+) mice (P<0.01); after brain injury, the levels of HO-1 and NQO1 proteins of Nrf2(+)/(+) mice increased obviously compared with the corresponding sham-operation group (P<0.01); the levels of HO-1 and NQO1 proteins of Nrf2(-)/(-) mice in TBI group had no obvious change compared with the corresponding sham-operation group (P>0.05); there was only a little amount of expression of protein carbonyls, 4-HNE and 8-OHdG proteins in brain tissues in the Nrf2(+)/(+) and Nrf2(-)/(-) sham-operation groups, and the difference was not statistically significant (P>0.05); after brain injury, the three oxidative stress indicators were significantly up-regulated in the Nrf2(+)/(+) and Nrf2(-)/(-) groups, and the up-regulation of the latter group was more significant (P<0.01). CONCLUSIONS: After TBI the Nrf2/ARE pathway is activated and the activity of Nrf2 transcription regulation increases. However, the regulation dose not occur in the gene transcription level and only could increase the Nrf2 protein level, while the mRNA expression level has no obvious change. The nerve cell protective effect of Nrf2/ARE pathway in TBI achieves through inhibiting the oxidative stress injuries.

Cutl1: a potential target for cancer therapy.

CDP, a key transcription regulator encoded by Cutl1 gene, has been demonstrated to be involved in repressing or promoting expression of target genes through its specific DNA-binding, meanwhile, the activity of CDP was influenced by some types of modifications including transcriptional, posttranscriptional, translational and posttranslational modifications. In this review, we systematically analyzed the role of CDP in normal development and tumor progression, and then emphasized its interactors and downstream molecules. Eventually, we concluded that Cut1 could promote cancer progression and its down-regulating expression will be a promising strategy for cancer therapy.

Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury

OBJECTIVE@#To explore the expression of Nrf2/ARE pathway in hindbrain tissue after the traumatic brain injury (TBI) and its anti-oxidative stress effect in the secondary nerve injury.@*METHODS@#The mice with Nrf2 gene knockout were used for the establishment of brain injury model. The experimental animals were divided into four groups: (Nrf2(+)/(+)) sham-operation group, (Nrf2(+)/(+)) brain injury group, (Nrf2(-)/(-)) sham-operation group and (Nrf2(-)/(-)) brain injury group. The specimen 24 h after cerebral trauma was selected. Then RT-PCR method was adopted to detect the expression of Nrf2 mRNA in brain; Western blotting method was adopted to detect the levels of Nrf2, HO-1 and NQO1 proteins in brain; ELISA method was adopted to detect the oxidative stress indicators: protein carbonyls, 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG).@*RESULTS@#The Nrf2 mRNA and protein of Nrf2(-)/(-) mice were not expressed, and the difference of the relative amount of Nrf2 mRNA between Nrf2(+)/(+) TBI group and Nrf2(+)/(+) sham-operation group was not statistically significant (P>0.05); the level of Nrf2 protein in Nrf2(+)/(+) TBI group increased significantly compared with the Nrf2(+)/(+) sham-operation group (P0.05); there was only a little amount of expression of protein carbonyls, 4-HNE and 8-OHdG proteins in brain tissues in the Nrf2(+)/(+) and Nrf2(-)/(-) sham-operation groups, and the difference was not statistically significant (P>0.05); after brain injury, the three oxidative stress indicators were significantly up-regulated in the Nrf2(+)/(+) and Nrf2(-)/(-) groups, and the up-regulation of the latter group was more significant (P<0.01).@*CONCLUSIONS@#After TBI the Nrf2/ARE pathway is activated and the activity of Nrf2 transcription regulation increases. However, the regulation dose not occur in the gene transcription level and only could increase the Nrf2 protein level, while the mRNA expression level has no obvious change. The nerve cell protective effect of Nrf2/ARE pathway in TBI achieves through inhibiting the oxidative stress injuries.

[The antiviral role of Toll-like receptor 3 in human lung epithelial cells infected with respiratory syncytial virus].

OBJECTIVE: In order to understand the production mechanism of interferon and provide a scientific basis for preventionand clinical therapy, the expression changes of Toll-like receptor (TLR3) mRNA and the role of TLR3 in human lung epithelial cells (A549 cells) infected with respiratory syncytial virus (RSV) were investigated in this study. METHODS: RSV infected A549 cells were treated with or without specific antibodies of TLR3 and collected at the selected timepoints after RSV infection (4, 8, 12, 16 and 24h). The expressions of TLR3, IFN-alpha, IFN-beta and RSV F mRNA were evaluated by RT-PCR. RESULT: It was found that RSV infection could markedly up-regulate the mRNA expression of TLR3, IFN-alpha, IFN-beta and RSV F protein in a time-dependent manner as the 24h mRNA expressions of them were 4 times, 3 times, 3 times and 0.7 times more than the basic expression, respectively. Treatment of TLR3 specific antibodies, whereas, significantly down-regulated the activation of TLR3. The mRNA expression of IFN-alpha and IFN-1beta also decreased accordingly and that of IFN-beta reduced more obviously than IFN-alpha, but that of RSV F protein rose significantly. CONCLUSION: Above data indicate that RSV infection could induce an apparent increase of antiviral genes of IFN-alpha and IFN-beta by activating TLR3 in human lung epithelial cells and the activated cells mediated Type I interferon is antiviral, which suggesting that TLR3 might play an important role in antiviral activity of RSV-infected human lung epithelial cells.

[The application of extracorporeal membrane oxygenation in critically ill patient].

OBJECTIVE: To evaluate the supportive effects on cardiopulmonary failure in critically ill patients treated with extracorporeal membrane oxygenation (ECMO). METHODS: A retrospective observational study of 9 patients treated in intensive care unit (ICU) of Peking University Third Hospital and Beijing Ditan Hospital from October 1, 2007 to December 26, 2009 with ECMO for various diseases was conducted. Clinical data was analyzed. RESULTS: Of 9 patients [mean age (26.8 ± 7.0) years, body mass index (28.3 ± 9.1) kg/m(2)] were enrolled, 3 were male and 6 were female. Two patients were treated with veno-arterial(V-A) ECMO for severe heart failure, and 7 with veno-venous(V-V) ECMO due to refractory acute respiratory distress syndrome ARDS caused by 2009 novel H1N1 virus infection. The doses of vasoactive agents and cardiac parameters changed greatly after the V-A mode. The setting of ventilator support were significantly decreased, and arterial oxygen saturation [SaO(2)], arterial blood carbon dioxide partial pressure [PaCO(2)] and blood pH value were improved significantly after the V-V mode ECMO. Acute renal insufficiency occurred in 5 patients, hyperbilirubinemia in 6 patients, and catheter related blood stream infection in 4 patients. Five patients were weaned from ECMO successfully and 4 of them rehabilitated, the treatment was withdrawn in 2 patients, and the other 2 patients died during the procedure. The mean amount of red blood cell suspension administered per patients was (15.1 ± 9.9) U, and length of ICU stay was (18.9 ± 15.7) days. CONCLUSIONS: ECMO has a rapid effect to temporarily support heart or lung function (partially or totally) during cardiopulmonary failure, leading to organ recovery. Attempts to reduce the incidence of complications might improve the prognosis of critically ill patients.

Ginsenoside Rb1 reverses H2O2-induced senescence in human umbilical endothelial cells: involvement of eNOS pathway.

OBJECTIVE: Senescence of endothelial cells has been implicated in endothelial dysfunction and atherogenesis. This study investigated the effects of Rb1, a major ginsenoside in ginseng, on H2O2-induced senescence in primary human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: Real-time PCR and Western blot were used to detect the mRNA and protein expression, respectively. H2O2 (40∼100 µmol/L) effectively increased SA-ß-gal activity and PAI-1 mRNA levels, two important senescence related biomarkers, in HUVECs, which were dramatically inhibited by Rb1 pre-incubation. Furthermore, Rb1 administration reversed the H2O2-decreased protein and mRNA levels of eNOS and its phosphorylation at Ser-1177, and the increased eNOS phosphorylation at Thr-495. As a result, Rb1 pretreatment restored the NO generation, as assayed by nitrate reductase method. However, pretreatment with L-NAME, a NOS inhibitor, abolished all the inhibitory effects of Rb1 on senescence. Importantly, Rb1 modulated the H2O2-altered caveolin-1 and pAkt, two most important regulators of eNOS expression and activity, in HUVECs. CONCLUSIONS: We showed that Rb1 effectively protects HUVECs from senescence through eNOS modulation.

The antiviral role of Toll-like receptor 3 in human lung epithelial cells infected with respiratory syncytial virus / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>In order to understand the production mechanism of interferon and provide a scientific basis for preventionand clinical therapy, the expression changes of Toll-like receptor (TLR3) mRNA and the role of TLR3 in human lung epithelial cells (A549 cells) infected with respiratory syncytial virus (RSV) were investigated in this study.</p><p><b>METHODS</b>RSV infected A549 cells were treated with or without specific antibodies of TLR3 and collected at the selected timepoints after RSV infection (4, 8, 12, 16 and 24h). The expressions of TLR3, IFN-alpha, IFN-beta and RSV F mRNA were evaluated by RT-PCR.</p><p><b>RESULT</b>It was found that RSV infection could markedly up-regulate the mRNA expression of TLR3, IFN-alpha, IFN-beta and RSV F protein in a time-dependent manner as the 24h mRNA expressions of them were 4 times, 3 times, 3 times and 0.7 times more than the basic expression, respectively. Treatment of TLR3 specific antibodies, whereas, significantly down-regulated the activation of TLR3. The mRNA expression of IFN-alpha and IFN-1beta also decreased accordingly and that of IFN-beta reduced more obviously than IFN-alpha, but that of RSV F protein rose significantly.</p><p><b>CONCLUSION</b>Above data indicate that RSV infection could induce an apparent increase of antiviral genes of IFN-alpha and IFN-beta by activating TLR3 in human lung epithelial cells and the activated cells mediated Type I interferon is antiviral, which suggesting that TLR3 might play an important role in antiviral activity of RSV-infected human lung epithelial cells.</p>

[Synthesis and anti-inflammatory activities of methylhesperetin-7-alkyl ether analogues].

To investigate the relationship between the structures of methylhesperetin-7-alkyl ether analogues and their anti-inflammatory activities, nine new compounds, methyl-hesperetin (2), methylhesperetin-7-ethyl ether (3), 7-n-butyl ether (4), 7-n-hexyl ether (5), 7-n-octyl ether (6), 7-n-decyl ether (7), 7-n-dodecyl ether (8), 7-n-tetradecyl ether (9) and 7-n-hexadecyl ether (10), were synthesized with the lead compound of methylhesperidin (1). Their structures were confirmed by UV, 1H NMR, MS and HR-MS spectral data. The in vivo antiinflammatory activities of these compounds were tested on mouse paw edema induced by Freund's complete adjuvant (FCA) and mouse capillary permeability induced by acetic acid with po dose of 300 mg x kg(-1) x d(-1). The result indicated that the anti-inflammatory activities of the synthetic compounds increased firstly and then decreased with the elongating of the length of alkyl chain. After 25-day oral administration of compounds 6, 7 and 8, the inhibitory rates on mouse paw edema of adjuvant arthritis (AA) were 31.9%, 38.5%, 39.1%, respectively. They showed the concentrations of COX-2 in serum of AA mice respectively were 79.3, 75.4, 73.9 ng x L(-1) and the concentrations of PGE2 were in correspondence with 275.4, 258.9, 242.6 ng x L(-1). The inhibitory rates of compounds 6 and 7 on mouse capillary permeability induced by acetic acid were, respectively, 42.4% and 41.5% after 5-day oral administration. Compared with the lead compound of methylhesperidin, the anti-inflammatory activities of compounds 6, 7 and 8 were increased and showed an effective inhibition on the symptom of adjuvant arthritis and capillary permeability in mice.

Rb1 protects endothelial cells from hydrogen peroxide-induced cell senescence by modulating redox status.

Senescence of endothelial cells has been proposed to play an important role in endothelial dysfunction and atherogenesis. In the present study we aimed to investigate whether ginsenoside Rb1, a major constituent of ginseng, protects endothelial cells from H(2)O(2)-induced endothelial senescence. While H(2)O(2) induced premature senescent-like phenotype of human umbilical vein endothelial cells (HUVECs), as judged by increased senescence-associated ß-galactosidase (SA-ß-gal) activity, enlarged, flattened cell morphology and sustained growth arrest, our results demonstrated that Rb1 protected endothelial cells from oxidative stress induced senescence. Mechanistically, we found that Rb1 could markedly increase intracellular superoxide dismutase (Cu/Zn SOD/SOD1) activity and decrease the malondialdehyde (MDA) level in H(2)O(2)-treated HUVECs, and suppress the generation of intracellular reactive oxygen species (ROS). Consistent with these findings, Rb1 could effectively restore the protein expression of Cu/Zn SOD, which was down-regulated in H(2)O(2) treated cells. Taken together, our data demonstrate that Rb1 exhibits antioxidant effects and antagonizes H(2)O(2)-induced cellular senescence.