Equipment Safety ; Nanostructures ; adverse effects

Environmental Monitoring ; Humans ; Occupational Health

Antitumor effects of erythromycin and the related mechanism were investigated in the present study. Neuroblastoma cells (SH-SY5Y) were exposed to erythromycin at different concentrations for different durations. Cell proliferation was measured by cell counting, and cell viability was examined by MTT assay. Cell cycle phase distribution and the cytosolic calcium level were detected by flow cytometry. Mitochondrial membrane potential was measured by the JC-1 probe staining and fluorescent microscopy. The expression of an oncogene (c-Myc) and a tumor suppressor [p21 (WAF1/Cip1)] proteins was analyzed by using Western blotting. Erythromycin could inhibit the proliferation of SH-SY5Y cells in a concentration- and time-dependent manner. The cell cycle was arrested at S phase. Mitochondrial membrane potential collapsed and the cytosolic calcium was overloaded in SH-SY5Y cells when treated with erythromycin. The expression of c-Myc protein was down-regulated, while that of p21 (WAF1/Cip1) protein was up-regulated. It was concluded that erythromycin could restrain the proliferation of SH-SY5Y cells. The antitumor mechanism of erythromycin might involve regulating the expression of c-Myc and p21 (WAF1/Cip1) proteins.

Objective To evaluate the in vitro antiviral activity of HB-13,a compound derivant from berberine and its prodrug berberine,against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Methods Vero cells were cultured in vitro and infected with HSV.Then,various concentrations of HB-13, berberine,and aciclovir were used to treat these infected cells.The cytopathic effect was observed to deter- mine the antiviral effects and cytotoxicity of HB-13 and berberine.Results For HB-13,berberine and acy- clovir,the half toxicity concentration (TC_(50)) to Vero cells was 31.99,380 and more than 800?g/mL, respectively;the average half inhibitory concentration (IC_(50)) against HSV-1 was 1.328,more than 100,and 0.443?g/mL,respectively,the treatment index (TI) against HSV-1 was 24.09,less than 3.80,and more than 1805.87,respectively;the IC_(50) against HSV-2 was 1.344,more than 100,and 0.679?g/mL,respectively,the TI against HSV-2 was 23.80,less than 3.80 and more than 1178.20,respectively.Conclusion HB-13 possesses marked antiviral activity against HSV-1 and HSV-2 in vitro,while berberine does not.

The purpose of this study is to prepare galactosyl modified lipid bilayer-coated mesoporous silica nanoparticles (GPEM) to enhance the antitumor efficacy against hepatocellular carcinoma cells. The irinotecan (CPT-11) loaded mesoporous silica nanoparticles (MSNs) was coated with the Gal-P123 modified functional lipid bilayer by thin-film dispersion method. Nanoparticles were characterized with particle size, zeta potential, morphology and drug release in vitro. Afterwards, the cell uptake, intracellular concentration of CPT-11, cell apoptosis rate and cytotoxicity were evaluated on human hepatocellular carcinoma cell line Huh-7. The results showed that MSNs were coated with intact lipid bilayers and the nanoparticles had clear core-shell structure. GPEM is stable with the mean particle size of (78.01 +/- 2.04) nm. The low leakage rate in normal physiological conditions in vitro is contributed to the protection of stable lipid bilayer, and the fast drug release in acid environment due to the destruction of the lipid bilayer. On the cell level, the vector could improve the intracellular CPT-11 concentration by 4 times because of the functional lipid bilayer. The high CPT-11 concentration led to the increasement of apoptosis rate by 48.6%, and the reduction of half maximal inhibitory concentration (IC50) values of CPT-11 by 2 times, indicating stronger cell cytotoxicity.
Antineoplastic Agents ; chemistry ; pharmacokinetics ; Apoptosis ; Camptothecin ; analogs & derivatives ; chemistry ; pharmacokinetics ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Humans ; Lipid Bilayers ; chemistry ; Liver Neoplasms ; drug therapy ; pathology ; Nanoparticles ; chemistry ; Particle Size ; Silicon Dioxide ; chemistry

Objective:To investigate the heterogeneity of epitopes recognized by anti-GBM autoantibodies in sera from a large cohort of Chinese patients with anti-GBM disease and its clinical significance.Methods: The present study included 108 patients with anti-GBM disease who were diagnosed in our hospital, between Jan 1991 and May 2009, with complete clinical and renal pathological data. Sera or plasma exchange of the patients were used to incubate with cryostat section of normal human renal tissue for indirect immunofluorescence (IIF) assay. The cryostat sections of normal renal tissue were pre-treated by 6 mol/L urea to unmask cryptic epitopes, and untreated cryostat sections were used to detect natural exposed epitopes. The sera were diluted from 1:2 to 1:512 to determine titers of anti-GBM autoantibodies Patients with anti-GBM autoantibodies against cryptic or exposed epitopes were further stratified;their clinical and pathological associations were analyzed. Results: Sera from all the 108 patients could recognize cryptic epitopes on normal renal tissue ( urea treated section). IIF showed IgG linear staining along GBM. However, sera from 56/108 patients (group A) could also recognize exposed epitopes on normal renal tissue (untreated section) ; sera from the rest 52/108 patients (group B) could not recognize exposed epitopes. In urea treated condition, the average titer of anti-GBM autoantibodies from sera of patients in group A was significantly higher than that in group B (P＜0.01) , ANCA-positive patients in group A were significant less than that in group B (P＜0.01) . There was no significant difference between the two groups in regard to other clinical data (including serum creatinine) and renal histopathologic data. Conclusion: Anti-GBM autoantibodies from some patients with anti-GBM disease could recognize natural exposed epitopes, however, their anti-GBM titer for cryptic epitopes was higher than that of those recognizing cryptic epitopes only and the prevalence of serum ANCA was significantly less.

OBJECTIVETo explore the action mechanism of the immune active components of sappon wood (SWE) for antagonizing reject reaction by observing the influence of its ethyl acetate extract on mRNA expression of myocardial GrB in rat model of allogenic ectopic cardiac transplantation.

METHODSAnimal model of abdominal cardiac ectopic transplantation was established taking Wistar rat as the donor and SD rat as the receptor. The successfully modeled rats were randomly divided into the model group, the SWE group and the CsA group. GrB mRNA expression was detected by RT-PCR method and myocardial pathomorphologic picture was observed in routine.

RESULTSThe pathologic changes in the SWE group (23 scores) and the CsA group (14 scores) were milder than in the model group (31 scores), the former two could markedly alleviate the myocardial pathologic injury (P<0.05, P<0.01). The GrB mRNA expression in the model group was 1.3000 +/- 0.1207, the SWE group 0. 7070 +/- 0.1215, and the CsA group 0.6700 +/- 0.0997, respectively; compared with the model group, the latter two could obviously down-regulate the expression of GrB mRNA (P<0.01) and no significant difference was found between the latter two groups (P>0.05).

CONCLUSIONSWE could alleviate the pathologic change, down-regulate the mRNA expression of myocardial GrB in allogenic ectopic transplanted myocardium of rats, it is possibly one of the factors for its antagonizing effect against reject reaction.

Acetates ; chemistry ; Animals ; Caesalpinia ; chemistry ; Gene Expression Regulation, Enzymologic ; drug effects ; Graft Rejection ; drug therapy ; Granzymes ; genetics ; Heart ; drug effects ; Heart Transplantation ; immunology ; Male ; Models, Animal ; Myocardium ; metabolism ; pathology ; Plant Extracts ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Rats ; Transplantation, Homologous

Recently traditional Chinese medicine (TCM)-induced liver injury has been an unresolved critical issue which impacts TCM clinical safety. The premise and key step to reduce or avoid drug-induced liver injury (DILI) is to identify the drug source of liver injury in early stage. Then the timely withdrawal of drug and treatment can be done. However, the current diagnosis of DILI is primarily governed by exclusive method relying on administering history supplied by patients and experience judgment from doctors, which lacks objective and reliable diagnostic indices. It is obvious that diagnosis of TCM-induced liver injury is especially difficult due to the complicated composition of TCM medication, as well the frequent combination of Chinese and Western drugs in clinic. In this paper, we proposed construction of research pattern and method for objective identification of TCM-related DILI based on translational toxicology, which utilizes clinical specimen to find specific biomarkers and characteristic blood-entering constituents, as well the clinical biochemistry and liver biopsy. With integration of diagnosis marker database, bibliographic database, medical record database and clinical specimen database, an integrative diagnosis database for TCM-related DILI can be established, which would make a transformation of clinical identification pattern for TCM-induced liver injury from subjective and exclusive to objective and index-supporting mode. This would be helpful to improve rational uses of TCM and promote sustainable development of TCM industry.
Animals ; Biomarkers, Pharmacological ; metabolism ; Biopsy ; methods ; Chemical and Drug Induced Liver Injury ; diagnosis ; metabolism ; pathology ; Early Diagnosis ; Humans ; Liver ; drug effects ; pathology ; Medicine, Chinese Traditional ; adverse effects ; Rats

Adenoids ; diagnostic imaging ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Hypertrophy ; Magnetic Resonance Imaging ; Male ; Radiographic Image Enhancement ; methods ; Tomography, Spiral Computed ; methods

This study aims to explore the efficacy of interferon-α (IFN-α) combined with either entecavir (ETV) or adefovir (ADV) therapy versus IFN-α mono-therapy for chronic hepatitis B (CHB) patients,and to identify the factors associated with treatment outcomes.Totally,159 CHB patients receiving interferon-based treatment for 48 weeks were enrolled in this retrospective study,including IFN-α mono-therapy group (group A,n=44),IFN-α plus ADV group (group B,n=53) and IFN-α plus ETV group (group C,n=62).The primary measures of efficacy assessments were the changes in HBsAg.Cox regression analysis was used to identify the predictors of treatment outcomes.The predictive values of the factors were assessed by ROC analysis.For patients with baseline hepatitis B surface antigen (HBsAg) level ＜1000 IU/mL,the reductions in mean HBsAg levels at week 48 were greater in group C than that in group A (P＜0.05).Higher rate of HBeAg seroconversion was achieved in the combined therapy group than in IFN-α mono-therapy group at week 48 (P＜0.05).Two factors were independently associated with HBeAg seroconversion:baseline HBeAg level ＜2.215 log10 index/mL and △HBeAg (.decline in HBeAg from baseline) ＞0.175 log10 at week 12.In conclusion,interferon-α plus ETV therapy can accelerate HBsAg decline as compared with interferon-α mono-therapy in CHB patients with lower baseline HBsAg levels,and the combination therapy was superior to IFN-α mono-therapy in increasing the rate of HBeAg seroconversion.Baseline HBeAg and △HBeAg at week 12 can independently predict HBeAg seroconversion in patients subject to interferon-based therapy for 48 weeks.