Traditional Chinese ancient prescriptions have been used for treatment of liver cancer for a long history and the scientific and rational compatibility is a great wealth for modern research and development (R&D) of new drugs. The research and development of new drugs are often accompanied with a large investment, a long cycle and a high risk, especially for the anti-tumor drugs R&D which are facing more risks and lower successful rate. In this research, the regularity of compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions by computer program. The results can offer help to the R&D of anti-hepatoma new drugs and reduce the risk of drug screening. In addition, we surveyed 22 companies in this field from six provinces such as Beijing, Shanghai, Tianjin and so on and obtained 240 risk assessment questionaires. Then we used qualitative analysis method to interpret the greatest impacts for the risks in the process of R&D, production and sales of anti-hepatoma new drugs. The study provides a basis for anti-liver cancer drugs R&D researchers, who can take effective measures to reduce the R&D risks and improve successful rate.
Carcinoma, Hepatocellular ; drug therapy ; history ; China ; Drug Discovery ; history ; Drug Incompatibility ; Drug Prescriptions ; history ; Drugs, Chinese Herbal ; history ; therapeutic use ; History, Ancient ; Humans ; Liver Neoplasms ; drug therapy ; history ; Research ; history

In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti-atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9 [hCD36] and CHO [hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC50 of 2.80 and 8.79 micromol x L(-1) in Sf9[hCD36] and CHO [hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce DiI-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.
Animals ; CD36 Antigens ; antagonists & inhibitors ; genetics ; metabolism ; CHO Cells ; Cells, Cultured ; Cricetulus ; Dose-Response Relationship, Drug ; Foam Cells ; cytology ; High-Throughput Screening Assays ; Humans ; Lipoproteins, LDL ; metabolism ; Macrophages ; cytology ; metabolism ; Mice ; Molecular Structure ; Plasmids ; Receptors, Scavenger ; antagonists & inhibitors ; Sf9 Cells ; Spodoptera ; Transfection

Rabies virus ; physiology

The epidemiological survey of prevalence of NIDDM (non-insulin dependent diabetes mellitus) and IGT(impaired glucose tolerance)was conducted among 9450 residents aged 25～70 in some areas of Hubei Province, China. The results show that NIDDM and IGT prevalences are 2.62% and 4.48%, respectively. There is no significant difference between male and female (P>0.05). The NIDDM prevalence in cities is slightly higher than that in countryside, but the difference is not significant (P>0.05). However, the IGT prevalence in city is significantly higher than that in countryside (P<0.01). The prevalence of both NIDDM and IGT is increasing along with the age of the population. It is also significantly related to the family history of NIDDM, hypertension, and high body mass index (BMI). By using stepwise logistic regression to analyse the risk factors of NIDDM, age (OR=1.86),BMI(OR=2.69), family history (OR=2.84) and hypertension (OR=2.23) entered the model (significance level is α=0.05).

Alveolar epithelial type II (AT II) cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells (fibroblasts). Progenitor cells are believed to possess capability of multi-potent transdifferentiation, which is closely related to the niche, suggesting the importance of establishment of a lung progenitor cell niche model. We hypothesized that pulmonary surfactant-associated protein A (SPA) suicide gene system would cause AT II cell to kill itself through apoptosis and leave its niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine kinase (rAAV-SPA-TK) system was established to get targeted apoptotic AT II cells. The apoptosis of AT II cells was detected by using MTT. The results showed that cloned SPA gene promoter had specific transcriptional activity in SPA high expression cells, and SPA high expression cells (H441) transfected with TK gene had higher sensitivity to ganciclovir (GCV) than SPA low expression cells (A549). In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system was observed by TUNEL. Finally, the successful packaging and application of rAAV-SPA-TK system provide experimental basis to get specific lung progenitor cell (AT II) niche in vitro and in vivo.

Objective To investigate the effect of resveratrol on the expression of peroxisome proliferator activated re-ceptor γ coactivator-1α(PGC-1α)in skeletal muscle of rats with chronic obstructive pulmonary disease(COPD). Methods A total of 45 male Sprague Dawley rats were randomly divided into control group,model group and resveratrol group,15 rats in each group. The rats in the model group and resveratrol group were made COPD model through the intratracheal instillation of lipopolysaccharide and repeated smoke exposure,except the rats in the control group. From the 29th day of smoke exposure,the rats in the control group and model group were given 2 mL saline by gavage,once a day for 30 days;and the rats in the resvera-trol group were given 2 mL resveratrol solution by gavage(100 mg·kg - 1 ·d - 1 ),once a day for 30 days. After 30 days of con-tinuous gavage,the rats were sacrificed,then arterial blood and skeletal muscles were harvested. The level of tumor necrosis factor-α(TNF-α)in serum and skeletal muscle of rats was detected by enzyme linked immunosorbent assay. The expression of PGC-1α,nuclear respiratory factor 1(NRF1),mitochondrial transcription factor A(Tfam)and cytochrome C oxidase Ⅳ(COXⅣ)mRNA in skeletal muscle tissues of rats was determined by quantitative real-time polymerase chain reaction. The expres-sion of PGC-1α,NRF1,Tfam and COX Ⅳ protein was detected by Western blot. Results The level of TNF-α in serum and skeletal muscle tissues of rats in the model group and resveratrol group was significantly higher than that in the control group (P < 0. 01). The level of TNF-α in serum and skeletal muscle tissues of rats in the resveratrol group was significantly lower than that in the model group(P < 0. 01). The expression of PGC-1α,NRF1,Tfam,COX Ⅳ protein and mRNA in skeletal mus-cle tissues of rats in the resveratrol group and model group was significantly lower than that in the control group(P < 0. 01). The expression of PGC-1α,NRF1,Tfam,COX Ⅳ protein and mRNA in skeletal muscle tissues of rats in the resveratrol group was significantly higher than that in the model group(P < 0. 01,P < 0. 05). Conclusion Resveratrol can reduce the level of TNF-α in serum and skeletal muscle tissues of COPD rats,increase the expression of PGC-1α,thereby improving the mitochon-drial biosynthesis function.

AIMTo investigate whether NR2B-pERK1/2-pElk-1 signaling contributes to the Y-maze learning and memory of rat brain.

METHODS45 adult male SD rats were divided into 4 groups: (1) Ifenprodil peritoneal injection group (Ifenprodil ip, n = 14); (2) DMSO peritoneal injection group(DMSO ip, n = 15); (3) Ifenprodil cerebral ventricle injection group (Ifenprodil ic, n = 8); (4) DMSO cerebral ventricle injection group(DMSO ic, n = 8). Y-maze training and test were used as an learning and memory enhancing stimulus. Immunohistochemical and Western blotting methods were used for detecting pERK1/2 and pElk-1 expression intensity of different brain regions.

RESULTSCompared with the DMSO ip group, the ifenprodil ip group showed no change on the Y-maze learning score (P > 0.05), but its Y-maze memory score tested 24 after learning decreased (P < 0.05). Ifenprodil peritoneal injection made brain pERK1/2 and pElk-1 expression decreased generally. In hippocampus, marginal division of striatum(MrD), amygdala,these changes were more significant (P < 0.05). Compared with the DMSO ic group, the reconsolidation of Y-maze memory tested 6 hours after ifenprodil injection was impaired in ifenprodil ic group (P < 0.05). The OD value of pERK1/2 and pElk-1 positive bands in ifenprodil ic group attenuated generally. The pElk-1 positive bands of caudate putamen and MrD almost disappeared in ifenprodil ic group.

CONCLUSIONNR2B is essential for the formation of long-term memory, reconsolidation of Y-maze memory. The deactivation of NR2B by ifenprodil will impair these courses. Meanwhile, the deactivation of NR2B attenuates pERK1/2 and pElk-1 expression of learning and memory related regions after Y-maze learning and memory reconsolidation test. In MrD and caudate putamen, the pElk-1 expression are completely blocked by ifenprodil after memory reconsolidation test.

Animals ; Avoidance Learning ; physiology ; Dimethyl Sulfoxide ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Male ; Maze Learning ; physiology ; Memory ; physiology ; Piperidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism ; ets-Domain Protein Elk-1 ; metabolism

OBJECTIVETo establish the biological exposure limit values of urinary S-phenylmercapturic acid (SPMA) for assessing occupational exposure to benzene.

METHODSStudy participants were selected from 55 workers of benzene exposures below 32.5 mg/m(3). The concentration of personal exposure to benzene was measured by gas chromatography and sampled with personal sampler. The urine samples were collected at the end of work shift and individual internal exposure level was evaluated by determination of SPMA in urine by HPLC/MS method. Comparison of external and internal exposure was assessed by the relative internal exposure (RIE) index.

RESULTSThe benzene exposure level ranged from 0.71 to 32.17 mg/m(3) (geometric mean 6.98 mg/m(3), median 7.50 mg/m(3)). The urinary SPMA at the end of the work shift were significantly correlated with benzene exposure, (microg/g Cr) = -8.625 + 18.367X (mg/m(3)), r = 0.8035, (P < 0.01). According to the occupational exposure limit for benzene in China and calculation of regression equation, the expected value of urinary SPMA was 101.58 microg/g Cr. Mean level of biotransformation of per mg/m(3) benzene to urinary SPMA was 18.23 microg/g Cr and the metabolic efficiencies of benzene transformation to urinary SPMA decreased with benzene exposure increased.

CONCLUSIONBased on abroad documents and data, biological limit value for occupational exposure to benzene in China is recommended as follows: 100 microg/g Cr (47 micromol/mol Cr) for SPMA in the urine at the end of shift.

Acetylcysteine ; analogs & derivatives ; urine ; Adult ; Benzene ; adverse effects ; analysis ; Benzene Derivatives ; urine ; China ; Humans ; Middle Aged ; Occupational Exposure ; adverse effects ; analysis ; Threshold Limit Values ; Young Adult

Objective To observe the status of occuh hepatitis B virus infection in chronic viral hepatitis patients with non-A to E hepatitis virus infection and explore the diagnostic value of fluorescence quantitative polymerase chain reaction (FQ-PCR) technique for occult hepatitis B virus infection. Methods The amount of HBV-DNA in serum and liver tissue from 57 patients with non-A to E hepatitis virus infection who were diagnosed as chronic viral hepatitis by Menghini method liver biopsy were detected by using FQ-PCR technique,then the relation between the viral load of HBV DNA in liver tissue and hepatic inflammatory activity were analyzed.Results Thirteen (22.81% ),22 (38.60%) patients were positive for HBV DNA in serum and liver tissue,respectively.The positive rate and the level of HBV DNA quantity in liver tissue were significantly higher than those in serum;HBV DNA was found positive in both serum and liver tissue in 13 cases,negative in both serum and liver tissue in 35,positive in liver tissue but negative in serum in 9,and in none of the cases HBV DNA was positive in serum but negative in liver tissue ( P<0.01 ).The logarithmic value of HBV DNA from 13 patients in liver tissue and in serum was respectively:(6.62±1.21 ) copies/g vs.(4.03±1.06) copies/ml,P < 0.01.The hepatic lesions of all HBV DNA positive patients were active pathologic changes,but the level of HBV DNA in liver tissue was not significantly correlated with the grade of hepatic inflammation activity ( P0.05 ).Conclusion Occult HBV infection is the etiology of part of the chronic viral hepatitis patients with non-A-E hepatitis virus infection.Missed diagnosis will occur if diagnosis of hepatitis B is only hased on detection of serum HBV markers. It is useful for improvement of the diagnostic level of HBV infection via detection of HBV DNA quantitatively in serum especially in liver tissue of chronic viral hepatitis with non-A-E hepatitis virus infection by using FQ-PCR technique The chronic viral hepatitis patients occult HBV infection should be also given effective anti-viral therapy.

BACKGROUNDExpression of murine calcium-activated chloride channel family member 3 (mCLCA3) has been reported to be increased in the airway epithelium of asthmatic mice challenged with ovalbumin (OVA). However, its role in asthmatic airway inflammation under no OVA exposure has not yet been clarified.

METHODSmCLCA3 plasmids were transfected into the airways of normal BALB/c mice. mCLCA3 expression and airway inflammation in mouse lung tissue were evaluated. Cell differentials and cytokines in bronchoalveolar lavage fluid (BALF) were analyzed. The expression of mCLCA3 protein and mucus protein mucin-5 subtype AC (MUC5AC) were analyzed by Western blotting. The mRNA levels of mCLCA3, MUC5AC and interleukin-13 (IL-13) were determined quantitatively.

RESULTSmCLCA3 expression was not detected in the control group while strong immunoreactivity was detected in the OVA and mCLCA3 plasmid groups, and was strictly localized to the airway epithelium. The numbers of inflammatory cells in lung tissue and BALF were increased in both mCLCA3 plasmid and OVA groups. The protein and mRNA levels of mCLCA3 and MUC5AC in the lung tissue were significantly increased in the mCLCA3 plasmid and OVA groups compared to the control group. The level of IL-13, but not IL-4, IL-5, IFN-γ, CCL2, CCL5 or CCL11, was significantly increased compared with control group in BALF in the mCLCA3 plasmid and OVA groups. The level of IL-13 in the BALF in the mCLCA3 plasmid group was much higher than that in the OVA group (P < 0.05). The level of mCLCA3 mRNA in lung tissue was positively correlated with the levels of MUC5AC mRNA in lung tissue, IL-13 mRNA in lung tissue, the number of eosinophils in BALF, and the content of IL-13 protein in BALF. The level of IL-13 mRNA in lung tissue was positively correlated with the number of eosinophils in BALF and the level of MUC5AC mRNA in lung tissue.

CONCLUSIONThese findings suggest that increased expression of a single-gene, mCLCA3, could simulate an asthma attack, and its mechanism may involve mCLCA3 overexpression up-regulating IL-13 expression.

Allergens ; Animals ; Asthma ; Chloride Channels ; Female ; Inflammation ; chemically induced ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; genetics ; metabolism ; Interleukin-5 ; genetics ; metabolism ; Mice ; Mice, Inbred BALB C ; Mucin 5AC ; genetics ; metabolism ; Ovalbumin ; pharmacology