-
[show abstract]
[hide abstract]
ABSTRACT: In recent years, amphetamine-type stimulants (ATS) have increased dramatically in East-south Asia, especially in China. Most ATS users suffered from psychosis comorbidity, and depression is the main syndrome in ATS users.
A cross-sectional study of depressive symptoms and associated factors among ATS users was conducted in compulsory and voluntary drug detoxification and rehabilitation centers of Beijing and Guangdong Province from March, 2010 to August, 2010. Total 402 eligible participants were recruited and investigated by trained interviewers using a structured questionnaire, the depression was measured by the short 13-item Beck Depression Inventory (BDI-13). Multiple logistic regression was used to determine the impact of associated risk factors of depressive symptoms (%≥8). PRINCIPLE FINDING: The mean score of BDI-13 is 8.11, and 169 participants (42.04%) have depressive symptoms, including 106 (26.37%) with moderate and 63 (15.67%) with severe depressive symptoms. Higher dose of ATS use, history of ATS relapse were associated with moderate and severe depressive symptoms, the adjusted odds ratios (OR) was 2.62, (95% CI: 1.45-4.74) and 2.01 (95% CI: 1.18-3.42) respectively. The cessation of 12 months or more had less risk of depressive symptoms than the current users, the OR was 0.46 (95% CI: 0.24-0.91), and the ATS users reporting nicotine dependence and alcohol drinking had significantly more risk of depressive symptoms for 3.11 (1.83-5.28) and 2.22 (1.35-3.65) times than those without these behaviors.
Depressive symptoms co-occurred frequently among ATS users in China. The efforts that facilitate drug users' attempts to stop using ATS use and relapse, quit cigarette smoking and stop alcohol drinking during the ATS treatment and management process should be supported as they may contribute to improving the mental health among this population.
PLoS ONE 01/2013; 8(4):e60544. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The unfavorable pharmacokinetics and low tumor specificity hampered the potential clinical utility of Onconase, a promising modality in anticancer treatment with unique targets and novel mechanism of action. In this study, a modular and multi-stage drug delivery system (DDS) that can break down organ (renal accumulation), cellular (cancer cell specific uptake) and sub-cellular (endosomal escape) level barriers encountered by Onconase during its long journey from injection site to the cytoplasm of cancer cell was designed. Human serum albumin fusion extended the half-life of Onconase and significantly decreased its kidney accumulation. Epithelial cell adhesion molecular (EpCAM) specific antibody fragment appending enhanced binding and internalization of Onconase toward EpCAM positive cancer cell and increased its tumor accumulation and retention. Tethering Onconase to its carrier by cleavable disulfide linker prompted endosomal escape and restored its cytotoxicity. In vivo antitumor efficacy assay in human tumor xenograft model revealed that only when the entire organ, cellular and sub-cellular level barriers had been broken down, will Onconase turn into a potent antitumor agent.
Journal of Controlled Release 05/2012; 159(3):346-52. · 5.73 Impact Factor
-
Yan-Ping Bao, Zhi-Min Liu,
Zhi Lian,
Jian-Hua Li,
Rui-Min Zhang,
Cong-Bin Zhang,
Wei Hao,
Xu-Yi Wang,
Min Zhao,
Hai-Feng Jiang,
Shi-Yan Yan,
Qing-Liang Wang,
Zhi Qu,
Hao-Ran Zhang,
Ping Wu,
Jie Shi,
Lin Lu
[show abstract]
[hide abstract]
ABSTRACT: China has experienced an epidemic of amphetamine-type stimulant (ATS) use in recent years. The present study explored the status and correlates of HIV and hepatitis C virus (HCV) infection among ATS users in China.
A multicenter cross-sectional study of HIV and HCV status and associated behaviors among ATS users was conducted in 6 provinces from September 2009 to December 2010. Socioeconomic/behavioral risk factors were measured. Blood samples were collected to test for HIV and HCV antibodies.
Of the 1327 ATS users, the prevalence of HIV and exposure to HCV were 4.5% and 43.5%, respectively, with large geographic variations (0%-20.3% and 8.6%-67.1%, respectively). HIV infection was independently associated with living in Yunnan province [adjusted odds ratio = 15.8; 95% confidence interval (CI): 2.0 to 125.1), polydrug use (adjusted odds ratio = 2.6; 95% CI: 1.3 to 5.4), increased frequency of sexual behavior (adjusted odds ratio = 2.0; 95% CI: 1.1 to 4.1), history of sex with sexually transmitted infection-positive persons (adjusted odds ratio = 11.4; 95% CI: 1.3 to 98.9), and HCV infection (adjusted odds ratio = 2.8; 95% CI: 1.2 to 6.7). HCV was associated with study site, marital status, unemployment (adjusted odds ratio = 1.8; 95% CI: 1.3 to 2.4), a longer duration of ATS use, and history of injection use of ATS (adjusted odds ratio = 13.3; 95% CI: 1.5 to 116.1).
The prevalence of HIV was high among ATS users in Yunnan province but quite rare elsewhere, and the prevalence of exposure to HCV was high in 6 provinces. Risk factors emphasize the need for new prevention strategies toward this population at risk in China.
JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2012; 60(4):438-46. · 4.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Human serum albumin (HSA) fusion (Albufusion) technology has evolved to be a general strategy to increase the in vivo half-lives of therapeutic proteins. However, because of the steric hindrance effect of HSA, conventional Albufusion technology improves the pharmacokinetics (PK) at the cost of pharmacodynamics (PD). To achieve balanced PK and PD of interferon-α2b (IFN-α2b) and HSA fusion protein, protease cleavage sites or disulfide linkage that enabled releasing of intact IFN-α2b with full activity was introduced between these two moieties. Nonreleasable and releasable fusion proteins showed similar cell surface receptor binding affinities; however, releasable fusion proteins exhibited release efficiency proportional increase of in vitro antiviral and antiproliferative activities. The release rate also had a profound impact on the in vivo pharmaceutical properties of fusion proteins. Releasable fusion proteins with intermediate release rate had the most balanced PK and PD, which translated into improved therapeutic efficacy in the HT29 human colon cancer xenograft model. Releasable Albufusion (rAlbufusion) allows tailored design of the PK/PD profile and greatly extends the utility of conventional Albufusion technology.
Molecular Pharmaceutics 03/2012; 9(3):664-70. · 4.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore the prevalence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and the risk factors among opiate drug users in Beijing.
The opiate drug users enrolled in methadone maintenance treatment clinics of Beijing from 30 November 2004 to 31 March 2008 were investigated. The blood samples were collected and tested for HIV and HCV infection and questionnaires were used for all subjects admitted.
Among 1211 eligible subjects, 12 HIV and 713 HCV-positive subjects were observed; the HIV and HCV prevalences were .99% and 58.88%, respectively. Young age, unemployment, injection drug use, and more frequent and longer drug use were the independent risk factors for HCV infection using the multiple logistic regression analysis. The younger drug users are more likely to be infected than the older ones, and the adjusted odds ratios (OR) of 18-30 and 30-40 versus 40-54 years were 1.81 (95% confidence interval (95% CI): 1.13-1.92) and 1.51 (95% CI: 1.08-2.10). The drug users who were unemployed (OR = 1.70, 95% CI: 1.23-2.37), with injection drug use (OR = 10.99, 95% CI: 7.26-16.65), with more frequent drug use (OR = 2.42, 95% CI: 1.31-2.46), and with longer heroin abuse history (OR = 8.06, 95% CI: 1.19-57.54) were more likely to be infected with HCV.
The HCV infection was popular among opiate drug users in Beijing. The findings indicated the need for educating the users taking into account their low literacy levels and the necessity for job training and decreasing the injection drug use and the frequency of drug use administrated as the prevention and intervention methods for controlling the HIV/HCV infection in this population.
The American Journal of Drug and Alcohol Abuse 12/2011; 38(2):140-5. · 1.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Drug abuse has resulted in a huge public health and economic burden in China, especially the rapid spread of HIV/AIDS and hepatitis C virus (HCV) infection. Multiple HIV and HCV subtypes were detected among drug users in China, this study reviews the molecular distribution of HIV and HCV among injection drug users (IDUs) and explores new epidemiologic trends of HIV and HCV among drug users in China.
The 2009 National Narcotic Control Commission report showed that the percentage of users of 'new-type drugs', including amphetamine-type stimulants (ATS: methamphetamine and MDMA/ecstasy) and ketamine, was about 27% of total drug users. The pooled data from published papers showed that CRF07BC was the predominant HIV-1 subtype, which accounted for 38.8%, and it was followed by AE, which accounted for 22.7% among HIV-positive IDUs. Following these, the CRF08BC, B' and C subtypes accounted for about 10.8%, 9.9% and 9.2%, respectively. Subtype 6a was the predominant HCV subtype, accounting for 36.7%, and subtypes 3b, 1a, 3a and 1b were the next most predominant subtypes.
With the increase of 'new-type drugs' use and AE HIV-1 subtype infection among IDUs, the situation regarding HIV/AIDS and HCV infection has become complicated. More comprehensive prevention and intervention strategies should be instigated for the extensive high-risk populations in China.
Current opinion in psychiatry 03/2010; 23(3):187-94. · 3.57 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Interferon-alpha2b (IFN-alpha2b) and human serum albumin (HSA) fusion protein (IFN-alpha2b-HSA) is a promising long acting formulation of IFN-alpha2b for the treatment of hepatitis C. However, accelerated mechanical and thermal stress tests revealed that IFN-alpha2b-HSA was prone to disulfide-linked aggregation. The formation of aggregates was associated with an increase in immunogenicity in mice. The addition of non-ionic surfactant Tween 80 increased the stability of IFN-alpha2b-HSA against agitation, but its thermal stability was not improved. Moreover, Tween 80 prompted the aggregation of IFN-alpha2b-HSA during quiescent storage. To increase the stability of IFN-alpha2b-HSA, the unpaired cysteine residue in this fusion protein was substituted with serine by site-directed mutagenesis. The resultant fusion protein was designated as IFN-alpha2b-HSA(C34S). IFN-alpha2b-HSA(C34S) had significant higher stability over IFN-alpha2b-HSA, which was evidenced by the facts that after agitation for 72 h or incubation at 60 degrees C for 2 h, more than 90% of IFN-alpha2b-HSA(C34S) remained monomeric. Consistent with its improved stability, the immunogenicity of IFN-alpha2b-HSA(C34S) increased less significantly after agitation. Pharmacokinetics studies in rats revealed that both fusion proteins had similar pharmacokinetic behavior, both with a half-life of about 50 h.
European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2009; 72(2):405-11. · 3.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore the characteristics of nicotine dependence among Chinese opiate addicts, a survey was conducted among 357 opiate addicts in Drug Detoxification and Rehabilitation Center from 4 different provinces by using a self-designed questionnaire and Fagerström Test for Nicotine Dependence (FTND). Among the 357 opiate addicts, 355 (99.4%) had the history of cigarette smoking and the mean cigarette smoked per day were 19.1, 34.9, 21.5 and 21.5 sticks during the time of before drug taking, addiction phase, abstinence period and after abstinence respectively. Among 347 smokers with FTND score, 67.2% were severe nicotine dependence (FTND score > or =7.0). The lower education degree, injection, poly-drug use and 3 or more relapse were dependently associated with the severe nicotine dependence, and the adjusted odds ratio (OR) were 3.8 (1.5-10.0), 2.3 (1.3-4.0), 3.7 (2.1-6.5) and 1.9 (1.1-3.4) respectively. This study exhibited high rate of cigarette smoking in Chinese opiate addicts and the majority had severe nicotine dependence and suggested that a comprehensive intervention of cigarette smoking should be paid attention to during substance abuse treatment in China.
Addictive behaviors 06/2009; 34(11):955-8. · 2.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The harm associated with high-risk injected opiate use and the threat of the HIV epidemic among injecting drug users has become a worldwide problem. Twenty years ago, in the face of a rapid increase in mortality rates among injecting drug users and the upcoming threat of HIV, the first harm-reduction programs were implemented in the Western world. This paper is a literature review describing four forms of harm reduction currently in use in Europe, North America, and Australia. Each represents a reasonable counterapproach to the threat of increased prevalence of HIV among injecting drug users in transitional and developing countries. The paper attempts to explain the concepts behind the most commonly used types of harm reduction and provides a brief overview of the advantages and disadvantages of each and the reasons for their implementation. The main focus of the review is on the definition and the practical aspects of harm reduction; it includes a brief introduction of Chinese harm-reduction efforts and their implications.
Acta Pharmacologica Sinica 05/2009; 30(5):513-21. · 1.95 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Onconase, an RNAse extracted from embryos of the Northern leopard frog (Rana pipiens), is in a confirmatory phase IIIb clinical trial for the treatment of unresectable malignant mesothelioma. Because the current purification process for onconase is cumbersome and laborious, the development of more efficient and cost-effective alternative sources is imperative. In this study, we assessed the potential of Pichia pastoris as an expression host for the large-scale production of onconase. Because of its specific N-terminal structure, active onconase with a correct N-terminus could not be secreted by an alpha-mating factor (alpha-MF)-prepro secretion signal, and an alpha-MF-pre secretion signal should be used instead. Onconase accumulated to a high concentration (about 300 and 150 mg L(-1) for glycosylated onconase and aglycosylated mutein, respectively) in high cell density fermentation, and was purified to homogeneity with high yields (56% for glycosylated onconase and 67% for aglycosylated mutein) by a simple purification process consisting of cation exchange chromatography and size exclusion chromatography. In vitro activity assays revealed that glycosylation decreased both the RNAse activity and the cytotoxic activity of onconase. The high expression level and subsequent facile purification process make P. pastoris an efficient and cost-effective host for the large-scale production of onconase.
FEMS Yeast Research 04/2009; 9(4):591-9. · 2.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To estimate, via meta-analysis, the influence of different methadone dose ranges and dosing strategies on retention rates in methadone maintenance treatment (MMT).
A systematic literature search identified 18 randomized controlled trials (RCTs) evaluating methadone dose and retention. Retention was defined as the percentage of patients remaining in treatment at a specified time point. After initial univariate analyses of retention by Pearson chi-squares, we used multilevel logistic regression to calculate summary odds ratios (ORs) and 95% confidence intervals for the effects of methadone dose (above or below 60 mg/day), flexible vs. fixed dosing strategy, and duration of follow-up.
The total number of opioid-dependent participants in the 18 studies was 2831, with 1797 in MMT and 1034 receiving alternative mediations or placebo. Each variable significantly predicted retention with the other variables controlled for. Retention was greater with methadone doses > or = 60 than with doses < 60 (OR: 1.74, 95% CI: 1.43-2.11). Similarly, retention was greater with flexible-dose strategies than with fixed-dose strategies (OR: 1.72, 95% CI: 1.41-2.11).
Higher doses of methadone and individualization of doses are each independently associated with better retention in MMT.
The American Journal of Drug and Alcohol Abuse 01/2009; 35(1):28-33. · 1.55 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Expression of recombinant protein HSA-AX15(R13K) in Pichia pastoris GS115 strain produced both the intact protein and its two degradation products with molecular weights of around 43kDa and 66.2kDa, respectively. To reduce or avoid the degradation, a modified P. pastoris GS115 stain, in which YPS1 gene was disrupted, was constructed via homologous recombination and used as a host strain for the HSA-AX15(R13K) expression. After 60h of induction during culture, it was found that the degradation product of around 66.2kDa was reduced significantly in the supernatant of yps1-disrupted strain compared with that in the supernatant of wild-type strain. By the Western blot analysis of culture supernatants from wild-type and yps1-disrupted strains expressing HSA-AX15(R13K), the significant improvement was also seen in the degradation product of around 43kDa. Comparison of cell growth between the two strains demonstrated a similar growth tendency, thereby indicating that the disruption of YPS1 gene has no effect on the normal physiology of GS115 strain. Following induction for 60h, the yield of intact HSA-AX15(R13K) in the yps1 disruptant was three-fold higher than that in the wild-type strain. Therefore, such a P. pastoris mutant deficient in YPS1 activity is suitable for the high-level expression of recombinant protein HSA-AX15(R13K).
Journal of Biotechnology 11/2008; 139(2):131-6. · 3.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previous studies in our laboratory have shown that when the N-terminus of interferon-alpha2b (IFN-alpha2b) was directly fused of to the C-terminus of human serum albumin (HSA), the resultant fusion protein (HSA-IFN-alpha2b) was heterogeneous (migrated as doublets on non-reducing SDS-PAGE) and unstable (prone to form covalent aggregates). The heterogeneity and instability of HSA-IFN-alpha2b was ascribed to the structural disturbance between HSA and IFN-alpha2b. To alleviate such structural disturbance, linkers with different lengths (1, 2, 5, 10 amino acid residues) or different conformation (flexible linker (FL, GGGGS), rigid linker (RL, PAPAP) or helix-forming linker (HL, AEAAAKEAAAKA)) were inserted between HSA and IFN-alpha2b. It was demonstrated that linker with 5 amino acid residues was sufficient to separated HSA and IFN-alpha2b effectively, as fusion protein with this linker migrated as single band on non-reducing SDS-PAGE. The fusion proteins with FL, RL and HL linkers were purified to homogeneity with yields of 20%, while the recovery rate of HSA-IFN-alpha2b was only 10%. Accelerated thermal stress tests showed that in contrast to HSA-IFN-alpha2b, fusion proteins with FL, RL and HL linkers were free of aggregates after stored at 37 degrees C for 10 days. Stability tests also revealed that fusion proteins with FL, RL and HL linkers had different susceptibility to hydrolysis, with HSA-RL-IFN-alpha2b being the least susceptible to hydrolysis at pH 6 and 7. Activity assay revealed that the insertion of FL, RL and HL linkers increased the anti-viral activity of fusion protein by 39%, 68% and 115%, respectively.
Protein Expression and Purification 06/2008; 61(1):73-7. · 1.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In an attempt to increase the secretion capacity of Pichia pastoris (Pp), PpPMR1 gene was disrupted with GS115 as parent strain, and the resultant mutant was designated as Pppmr1. Pppmr1 displayed a Ca2+-dependent growth defect, which was consistent with the PMR1 mutation in other yeasts. HSA-L5-IFNalpha2b, a human serum albumin (HSA) and inferferon-alpha2b (IFNalpha2b) fusion protein with a flexible linker of 5 amino acid residues, was employed as a reporter to study the effects of PpPMR1 disruption on the secretion of heterologous protein. Because of its decreased viability after induction, Pppmr1 secreted more HSA-L5-IFNalpha2b only during the early phase (the first 15 hours) of induction. Although HSA-L5-IFNalpha2b secreted from GS115 and Pppmr1 had similar antiviral activity, the latter was heterogeneous (migrated as doublets on non-reducing SDS-PAGE) and unstable (prone to aggregation at neutral to mild alkaline pH). Site-directed mutagenesis revealed that the heterogeneity of HSA-L5-IFNalpha2b secreted from Pppmr1 was originated from the incomplete disulphide bridge pairing between Cys1 and Cys98 of IFNalpha2b. To be secreted homogeneously from Pppmr1 and to be stable in aqueous solution, the linker of the fusion protein should be extended to 10 amino acid residues.
Yeast 05/2008; 25(4):279-86. · 1.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Albuferon is a novel long-acting interferon resulted from the direct genetic fusion of human albumin and interferon-alpha2b (HSA-IFN-alpha2b). Albuferon, co-developed by Human Genome Sciences Inc. and Novartis, is currently in late stage development for the treatment of hepatitis C. It was unexpected that HSA-IFN-alpha2b secreted from Pichia pastoris migrated as doublets on non-reducing SDS-PAGE and was prone to form covalent aggregates in aqueous solution. The heterogeneity and instability of HSA-IFN-alpha2b lowered its recovery rate to about 10% and necessitated lyophilized formulation. Site-directed mutagenesis revealed that the heterogeneity and instability of HSA-IFN-alpha2b was caused by the incomplete disulfide bridge formation between Cys1 and Cys98 of IFN-alpha2b. To alleviate the structural perturbation of IFN-alpha2b by HSA, IFN-alpha2b-HSA fusion protein, in which IFN-alpha2b was located at the N-terminus, was created. IFN-alpha2b-HSA was shown to be homogeneous and stable at 37 degrees C for at least 10 days. The improved homogeneity and stability of IFN-alpha2b-HSA increased the recovery rate by 2.5-fold and made the development of stable solution formulation possible. In vitro antiviral assays showed that both fusion proteins retained the activity of IFN-alpha2b, and the EC(50) of HSA-IFN-alpha2b, and IFN-alpha2b-HSA was calculated to be 120+/-12.5, and 160+/-1 1.3ng/ml, respectively. The increased recovery rate and the possibility of solution formulation of IFN-alpha2b-HSA may compensate for its slightly decreased in vitro activity, and makes it to be a promising therapeutic agent that deserves further evaluation.
Journal of Biotechnology 10/2007; 131(3):245-52. · 3.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Many studies have provided evidence that heat shock protein 65 (Hsp65) can elicit potent specific cellular adaptive immune responses (e.g. CD8(+) cytotoxic T-cell effectors or classic CTLs) based on their ability to chaperone antigenic peptides. Hsp65 is thus an effective carrier for heterologous peptide epitopes for therapeutic vaccines against cancer or chronic infectious diseases. The core antigen of hepatitis B virus (HBcAg) is extremely immunogenic, and functions as both a T-cell-dependent and a T-cell-independent antigen. Therefore, HBcAg may be a promising candidate target for therapeutic vaccine control of chronic HBV infection. Here, a chimeric protein, Hsp65Bc, was created by fusing the HBcAg sequence to the carboxyl terminus of the Hsp65 sequence in E. coli. Analysis of its antigenicity and immunogenicity revealed that HBc epitopes are surface accessible. Hsp65Bc induced moderate anti-HBc immune responses as well as a strong specific T-cell response in BALB/c mice. These results indicate that Hsp65Bc may have potential as a vaccine for treatment of HBV chronic infection.
Vaccine 06/2007; 25(22):4478-86. · 3.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To construct two kinds of anti-gastrin immunogen based on P64K protein from Neisseria meningitids and to compare their immunogenic effect.
G17P64K gene was cloned and ligated into pET28a plasmid, then transformed into BL21(DE3). After inoculation of LB medium and IPTG induction, the recombinant protein was solubly expressed at a high level. The purification of G17P64K fusion protein was similar to that of P64K. An initial step of purification consisting of 30% saturated ammonium sulfate precipitation was done. Additional fine optimizations included phenyl-sepharose, G200 Sephadex gel filtration and Q-sepharose anion exchanger chromatography. Highly purified protein was obtained and sequenced at the N-terminal amino acid residues. Polypeptide was synthesized by Fmoc solid phase chemical method and cross-linked to carrier protein P64K and DT mutant by MBS method and then the rabbit anti-gastrin 17 antibody was prepared by immunizing rabbit with cross-linked and fused protein. The titer and the activity in vitro of antibody were assessed.
G17P64K gene and the recombinant bacteria were obtained. After four steps purification, protein sample that has the purity above 90% was achieved. At the 84(th) day after the first immunization, the titer of antibody against cross-linked protein reached 51,200. Evaluation of the antibody in vitro manifested that it had a high inhibitory activity on the growth of tumor cell SW480.
The P64K-polypeptide cross-linked immunogen immunized rabbit and achieved a higher titer antibody against gastrin 17 than the G17P64K fusion protein immunogen, which could inhibit the growth of the tumor cell SW480.
World Journal of Gastroenterology 05/2006; 12(13):2040-6. · 2.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Drug abuse has spread quickly since reemerging as a national problem in China in the late 1980s. The number of registered drug abusers increased from 70,000 in 1990 to more than one million by the end of 2004. In addition to opioids, abuse of 'new' types of drugs including 3,4-methylenedioxymethamphetamine (MDMA) and ketamine has spread since 1997. Illicit drug trafficking and production have swept most of southern China, and throughout the country drug abuse has caused many problems for both abusers and the community. One major drug-related problem is the spread of HIV, which has caused major social and economic damage in China. In response, the Chinese government has begun an anti-drug campaign, including legislative measures to control drug abuse. However, changing the public's attitudes toward drug abusers and breaking the link between drug use and HIV spread are equally important.
Acta Pharmacologica Sinica 03/2006; 27(2):140-4. · 1.95 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Drug abuse has spread quickly since reemerging as a national problem in China in the late 1980s. The number of registered drug abusers increased from 70 000 in 1990 to more than one million by the end of 2004. In addition to opioids, abuse of “new” types of drugs including 3,4-methylenedioxymethamphetamine (MDMA) and ketamine has spread since 1997. Illicit drug trafficking and production have swept most of southern China, and throughout the country drug abuse has caused many problems for both abusers and the community. One major drug-related problem is the spread of HIV, which has caused major social and economic damage in China. In response, the Chinese government has begun an anti-drug campaign, including legislative measures to control drug abuse. However, changing the public's attitudes toward drug abusers and breaking the link between drug use and HIV spread are equally important.
Acta Pharmacologica Sinica 01/2006; 27(2):140 - 144. · 1.95 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To study the secretory expression of human hepatocyte growth factor (hdHGF) gene in Pichia pastoris.
The full-length gene of human cDNA encoding the deleted variant of hdHGF was cloned by RT-PCR and overlapping-fragment PCR technique using mRNA of human placenta as a template. The cloned hdHGF cDNA was inserted into the Escherichia coli-yeast shuttle vector of pPIC9. The constructed plasmid, pPIC9-hdHGF, was transformed into the GS115 cells of the methylotrophic yeast, P pastoris, using a chemical method. The Mut(+ ) transformants were screened to obtain high-expression strains by the test and analysis of expressed products of shake-flask culture. A secretory form of rhdHGF was made with the aid of the leader peptide sequence of Saccharomyces cerevisiae alpha-factor.
The expressed products, which showed a band of molecular mass of about 80 ku, were observed on 15% SDS-PAGE and identified by Western blotting and N-terminal amino acid sequencing. In the high cell density culture of 5 L fermentor by fed-batch culture protocol, the cell biomass was reached at approximately 135 g (DCW)/L. The productivity of secreted total supernant protein concentration attained a high-level expression of more than 8.0 g/L and the ratio of rhdHGF band area was about 12.3% of the total band area scanned by SDS-PAGE analysis, which estimated that the product of rhdHGF was 500-900 mg/L.
The P pastoris system represents an attractive tool of generating large quantities of hdHGF for both research and industrial purposes.
World Journal of Gastroenterology 01/2006; 11(45):7097-103. · 2.47 Impact Factor
