Adult ; Aortic Valve ; microbiology ; pathology ; Autopsy ; Brain ; microbiology ; pathology ; Endocarditis, Bacterial ; complications ; microbiology ; pathology ; Female ; Heart Ventricles ; microbiology ; pathology ; Humans ; Mitral Valve ; pathology ; Sepsis ; complications ; microbiology ; pathology ; Substance Abuse, Intravenous ; complications ; microbiology ; pathology ; Young Adult

Aim To explore the inhibitory effect of Euonymus alatus on hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice and its mechanism. Methods Eighty C57BL/6 male mice were randomly divided into eight groups: normal group, CCl4model group, Euonymus alatus(EA) ethanol extracts groups in early stage(EAE), EA ethanol extracts groups in later stage(EAL),two drug groups with low/medium/high dose(EAE-L/M/H, EAL-L/M/H), with 10 mice in each group. Fibrosis model was established by injecting CCl4in peritoneal cavity,and the study lasted for 30 days. Different doses of drugs were given from 1 st day to 15 th day in EAE while from 16 th day to 30 th day in EAL,then all mice were sacrificed to for the observation of the morphological changes and collage-nous fiber by HE and Masson staining. Liver index, ALT,AST and TNF-α were tested by ELISA. The ex-pressions of α-SMA and CollagenⅠwere measured by immunohistochemistry and Western blot. Results Compared to normal group, liver index, ALT, AST, TNF-α, α-SMA and CollagenⅠ in EA groups were lower than those in model group in a dose-dependent manner(P<0.01 or P<0.05). Liver morphology and collagenous fiber in EAE and EAL were better than those in model group in a dose-dependent manner. The effect of EAE were superior to that of the EAL in HE, Masson, α-SMA, Collagen Ⅰ indexes(P <0.05). Conclusions Euonymus alatus may inhibit the process of hepatic fibrosis in mice with dose-effect de-pendence, and drug treatment in early stage performs better,which may be related to the decrease of TNF-α that affects the expression of α-SMA and Collagen Ⅰ.

Objective To evaluate the application of non-bioartificial liver support system (ALSS) combined with liver transplantation(LT) in treating mid-or end-stage chronic severe hepati- tis.Methods ALSS plus liver transplantation were employed in treating 28 patients with mid-or end- stage chronic severe hepatitis.Clinical data from the patients before and after treatment were collect- ed.The survive rate of ALSS plus LT group were compared with that of medication group 99 cases and medication plus ALSS group 30 cases.The data were analyzed with t test and X~2 test.Results After 57 times ALSS treatment,the serum total bilirubin(TBil),prothromin time(PT),bile acid, blood urea nitrogen(BUN),creatnine(Cr) and ammonia of all the 28 patients got improved(P 0.05).The clinical symptoms and signs of the patients were ameliorated at median 3 d(1～153 d). All patients were bridged to liver transplantation successfully after median 20 d(1～153 d).The 3 and 6 months post-operation survival rate of ALSS plus LT group(71.4%,71.4%) were significantly higher than those in medication group(18.2%,11.1%) and medication plus ALSS group(36.7%, 26.6%)(P

Animals ; Dynorphins ; metabolism ; Parkinson Disease ; drug therapy ; metabolism ; Peptides ; pharmacology ; Rats ; Scorpion Venoms ; pharmacology

Scutellarin is a flavonoid extracted from a traditional Chinese herb, Erigeron breviscapus. The present study investigated the effect of scutellarin on MUC5AC mucin production and the possible mechanism. Human bronchial epithelial 16 (HBE16) cells were pretreated with scutellarin for 60 min, and then exposed to human neutrophil elastase (HNE) or interleukin (IL)-13 for 12 hr. RT-PCR and ELISA were performed to measure the amount of MUC5AC mucin production. The results showed that scutellarin inhibited MUC5AC expression both in mRNA and protein level induced by HNE in a concentration-dependent manner. However, scutellarin failed to inhibit MUC5AC mucin production induced by IL-13. To investigate the intracellular mechanisms associated with the effect of scutellarin on MUC5AC mucin production, western blotting was carried out to examine the phosphorylation of protein kinase C (PKC), signal transducer and activator of transcription 6 (STAT6) and extracellular signal-regulated kinase 1/2 (ERK1/2). The phosphorylation of PKC and ERK1/2 was attenuated after treatment with scutellarin, whereas STAT6 was not significantly affected. Therefore, it is suggested that scutellarin down-regulates MUC5AC mucin production on HBE16 cells via ERK-dependent and PKC-dependent pathways.
Apigenin/chemistry/*pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Down-Regulation ; Epithelial Cells/*drug effects/metabolism ; Erigeron/chemistry ; Glucuronic Acids/chemistry/*pharmacology ; Humans ; Interleukin-13/*pharmacology ; Leukocyte Elastase/*pharmacology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mucin 5AC/genetics/*metabolism ; Phosphorylation ; Protein Kinase C/metabolism ; Respiratory Mucosa/drug effects/*metabolism ; STAT6 Transcription Factor/metabolism ; Signal Transduction

OBJECTIVETo investigate the effect of interleukin-13 (IL-13) on mucus secretion in vivo and the possible mechanism.

METHODSThe SD rats were randomly divided into control group, IL-13 group and IL-13 plus SP600125 group. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2) and the level of MUC5AC in the lung tissues were examined using Western blotting. RT-PCR was performed to examine the mRNA level of STAT4 and STAT6, and electrophoretic mobility shift assays (EMSA) was used to detect the DNA-binding activities of Forkhead box a2 (FOXA2) and activator protein-1 (AP-1).

RESULTSIL-13 caused a significant increase in MUC5AC and p-JNK1/2 expression, but did not affect the phosphorylation of ERK1/2. The expression of MUC5AC was attenuated after treatment with SP600125. A significant increase in STAT6 was observed in IL-13 group compared with that in the control group, whereas the expression of STAT4 mRNA was not significantly affected. The DNA-binding activity of FOXA2 was down-regulated after IL-13 exposure, which did not affect the DNA-binding activity of AP-1.

CONCLUSIONIL-13 down-regulates mucus secretion via STAT6-FOXA2 pathway in vitro.

Animals ; Bronchi ; secretion ; Female ; Hepatocyte Nuclear Factor 3-beta ; genetics ; metabolism ; Interleukin-13 ; pharmacology ; Male ; Mucin 5AC ; metabolism ; Mucus ; secretion ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; STAT6 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; drug effects

Biliary Tract Diseases ; etiology ; surgery ; therapy ; Blood Loss, Surgical ; prevention & control ; Graft Rejection ; etiology ; therapy ; Humans ; Liver Transplantation ; adverse effects

This paper reports the surface morphology and I-V curves of porous silicon (PS) samples and related devices. The observed fabrics on the PS surface were found to affect the electrical property of PS devices. When the devices were operated under different external bias (10 V or 3 V) for 10 min, their observed obvious differences in electrical properties may be due to the different control mechanisms in the Al/PS interface and PS matrix morphology.
Electrochemistry ; instrumentation ; methods ; Electrodes ; Electromagnetic Fields ; Gold ; chemistry ; Materials Testing ; Molecular Conformation ; Porosity ; Silicon ; chemistry ; Surface Properties

OBJECTIVETo construct a multiple myeloma (MM)-specific APE1siRNA expression vector, and detect the specific knock-down effect of the siRNA on expression of APE1 protein.

METHODSAPE1siRNA cDNA sequence was designed, synthesized and inserted into pSilencer 2.0-U6 linear expression vector. pSilencer APE1siRNA was digested by enzyme EcoRI and BamHI, then linear vector and IgP fragments were conjugated by T4 DNA ligase. pSilencer IgP-APE1siRNA and pSilencer IE-IgP-APE1siRNA were digested by enzyme EcoRI or XhoI. Linear vector and IE or Kappa fragments were conjugated by T4 DNA ligase. Then a MM specific pSilencer K-IE-IgP-APE1siRNA was cloned. The recombinant products were identified by DNA sequencing and enzyme digestions at each step. pSilencer K-IE-IgP-APE1siRNA plasmid was transfected to KM3, HOS, MDA-231 cells by liposome. APE1 gene silence induced by RNAi was analysed by Western blot.

RESULTSAPE1 protein in KM3 cells could be knocked down effectively and specifically by pSilencer K-IE-IgP-APE1siRNA vector. After 2 days, the level of APE1 protein in KM3 cells transfected with siRNA was 0.118 +/- 0.047, while that transfected with plasmid only was 0.988 +/- 0.029. The efficiency of gene silence was 90%.

CONCLUSIONA MM specific APE1siRNA expression vector was successfully constructed.

Base Sequence ; Cell Line, Tumor ; Cloning, Molecular ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; genetics ; Genetic Vectors ; genetics ; Humans ; Molecular Sequence Data ; Multiple Myeloma ; genetics ; RNA Interference ; RNA, Small Interfering ; genetics ; Transfection

BACKGROUNDCurrently anti-inflammatory therapy with steroids for allergic rhinitis need long-term repeated administration, although it is effective. Gene therapy is being suggested to substitute it. The aim of this study was to investigate nonviral vector mediated exogenous gene expression in COS-7 cells in vitro and the effect of intranasal mouse interleukin (mIL)-12 transgene expression on allergen induced eosinophil infiltration of nasal mucosa in a murine model of allergic rhinitis.

METHODSIn vitro COS-7 cells were infected with Epstein-Barr virus (EBV)/lipoplex. The expression of IL-12 p70 in cell culture supernatant was examined by enzyme-linked immunosorbent assay (ELISA). In mice with ovalbumin (OVA) induced allergic rhinitis, EBV/lipoplex was administered by nasal drops before OVA challenge once a day from day 1 to day 10. The expression of IL-12 mRNA and protein, the change of eosinophil count in nasal mucosa and serum total IgE were measured 24 hours after the last challenge.

RESULTSEBV/lipoplex could effectively transfect COS-7 cells. The expression of IL-12 p70 in cell culture supernatant was significantly more than in blank control. IL-12 via EBV plasmid vector transduction could be overexpressed in vivo. In pGEG.mIL-12 treated models, the nasal mucosa revealed a high level of widespread mIL-12 transduction by immunohistochemistry and in situ hybridization. Histological evaluation revealed marked suppression of eosinophil infiltration in nasal mucosa. The eosinophil count in allergic rhinitis group [(26.5 +/- 9.8)/high-power field (HPF)] was significantly increased over control group [(0.40 +/- 0.52)/HPF] (F = 56.94, P < 0.01), while the count in IL-12 gene therapy group [(4.60 +/- 2.63)/HPF] was significantly less than that of allergic group (F = 56.9, P < 0.01). Serum total IgE between in gene therapy mice [(88.83 +/- 6.71) ng/ml] and allergic rhinitis mice [(103.1 +/- 5.7) ng/ml] showed a significant difference (F = 1216, P < 0.05).

CONCLUSIONSNonviral EBV plasmid vector, pGEG.mIL-12 was able to overexpress exogenous gene both in vitro and in murine nasal mucosa in vivo. IL-12 overexpression via EBV/lipoplex could stem allergen induced eosinophil infiltration in nasal mucosa in murine models of allergic rhinitis, which may suggest a new cytokine immunogenetic therapy for allergic rhinitis.

Administration, Intranasal ; Animals ; COS Cells ; Cercopithecus aethiops ; Eosinophilia ; therapy ; Genetic Therapy ; Herpesvirus 4, Human ; genetics ; Immunoglobulin E ; blood ; Interleukin-12 ; genetics ; Lipids ; administration & dosage ; Male ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa ; metabolism ; Rhinitis, Allergic, Perennial ; therapy ; Rhinitis, Allergic, Seasonal ; therapy