RUNX2 Reverses p53-Induced Chemotherapy Resistance in Gastric Cancer.

Objective: Gastric cancer is one of the most common malignancies worldwide; however, its overall mortality has not improved significantly over the last decade. Chemoresistance plays a critical role in this issue. This study aimed to clarify the role and mechanism of runt-related transcription factor 2 (RUNX2) in platinum-based chemotherapy resistance. Methods: First, a drug-resistant model of gastric cancer cells was established to evaluate the relative expression level of the RUNX2 as a potential biomarker of chemotherapy resistance. Next, exogenous silencing was conducted to study whether RUNX2 could reverse drug resistance and understand the underlying mechanisms. Simultaneously, the correlation between the clinical outcomes of 40 patients after chemotherapy and the RUNX2 expression levels in tumor samples was analyzed. Results: We discovered that RUNX2 was significantly expressed in drug-resistant gastric cancer cells and tissues; it was also reversibly resistant to transformation treatment by exogenous RUNX2 silencing. It is confirmed that RUNX2 negatively regulates the apoptosis pathway of the p53 to reduce the chemotherapeutic effects of gastric cancer. Conclusion: RUNX2 is a possible target for platinum-based chemotherapy resistance.

Effects of linalool on Botrytis cinerea growth and control of tomato gray mold.

We examined the antifungal characteristics of linalool against Botrytis cinerea using plate inhibition assay and spore germination assay, and assessed the capacity of linalool in controlling tomato gray mold disease via tomato pot inoculation assay. The results showed that linalool exhibited strong inhibitive effects on mycelial growth of B. cinerea, with an EC50 value of 0.581 mL·L-1. In the spore germination test, linalool treatment inhibited spore germination in a dose-dependent manner. The electric conductivity and the malondialdehyde (MDA) contents were significantly increased in linalool-treated B. cinerea than that of the control, indicating that linalool induced oxidative damage and destroyed the cell membrane integrity in B. cinerea. The activities of the superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in the linalool-treated B. cinerea were decreased significantly by 27.4%, 68.9% and 26.0%, respectively, suggesting that linalool inhibited the antioxidant activity of B. cinerea. In the pot experiment, the diameter of lesions in linalool-treated tomatoes was significantly smaller than that of the control. The activities of SOD, POD, CAT, polyphenol oxidase, and phenylalnine ammonialyase in the linalool-treated tomatoes increased, while the MDA content decreased, suggesting that linalool could alleviate the oxidative damage caused by B. cinerea and promote plant disease resistance. In summary, linalool had inhibitory effect on the growth of B. cinerea and could control gray mold disease in tomatoes. These findings could lay the foundation for developing bota-nical antifungal agents for management of tomato gray mold disease.

Metabolic responses to Lactobacillus plantarum contamination or bacteriophage treatment in Saccharomyces cerevisiae using a GC-MS-based metabolomics approach.

Bacteriophage can be used as a potential alternative agent for controlling Lactobacillus plantarum contamination during bioethanol production. However, how Saccharomyces cerevisiae respond against contaminative L. plantarum or added bacteriophage remains to be fully understood. In this study, gas chromatography-mass spectrometry and a multivariate analysis were employed to investigate the intracellular biochemical changes in S. cerevisiae cells that were elicited by L. plantarum contamination or bacteriophage treatment. The intracellular metabolite profiles originating from different groups were unique and could be distinguished with the aid of principal component analysis. Moreover, partial least-squares-discriminant analysis revealed a group classification and pairwise discrimination, and 13 differential metabolites with variable importance in the projection value greater than 1 were identified. The metabolic relevance of these compounds in the response of S. cerevisiae to L. plantarum contamination or bacteriophage treatment was discussed. Besides generating lactic acid and competing for nutrients or living space, L. plantarum contamination might also inhibit the growth of S. cerevisiae through regulating the glycolysis in S. cerevisiae. Moreover, increased concentrations of monounsaturated fatty acids secondary to bacteriophage treatment might lead to more membrane fluidity and promote the cell viability of S. cerevisiae.

Club drug use and associated high-risk sexual behaviour in six provinces in China.

AIM: To investigate the characteristics of the different club drugs and associated high-risk sexual behaviours in China. DESIGN: Multicentre cross-sectional study. SETTING: Drug Detoxification and Rehabilitation Centres in six provinces, China. PARTICIPANTS: A total of 1434 eligible club drug users were included. MEASUREMENTS: Participants were investigated by trained interviewers using a self-designed structured questionnaire to collect information on club drug use and associated behaviours. FINDINGS: Methamphetamine was the most commonly abused drug in participants (73.92%), who used it in their or their friends' homes by non-injection for the purpose of feeling euphoria. Among participants with sexual behaviours after club drug use, 75.21% reported having engaged in sex with multiple partners after club drug use during the past year and 79.84% had unprotected sex after using club drug during the past year. A two-level logistic model showed that male gender [adjusted odds ratio (AOR)=7.14; 95% confidence interval (CI)=4.17-12.5], unmarried (AOR=1.71, 95% CI=1.04-2.79), long duration of club drug use during their life-time (AOR=1.76, 95% CI=1.28-2.42) and severe acute intoxication after using club drugs during the past year (AOR=2.11, 95% CI=1.07-4.15) were independent risk factors of multiple sex partners during the past year. Another two-level model showed that the club drug users who were female (AOR=1.79, 95% CI=1.03-3.11) and had polydrug use during their lifetime (AOR=1.55, 95% CI=1.01-2.34) had more risk for unprotected sex during the past year than without these characteristics. CONCLUSION: High-risk sexual behaviours are common among club drug users in China. The prevention and intervention of club drug use could decrease the risk of sexual behaviours which further prevent HIV transmission and other sexually transmitted infections in China.

Prevalence and correlates of HIV and HCV infection among amphetamine-type stimulant users in 6 provinces in China.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Metabolic responses to ethanol in Saccharomyces cerevisiae using a gas chromatography tandem mass spectrometry-based metabolomics approach.

During the fermentation process, Saccharomyces cerevisiae cells are often inhibited by the accumulated ethanol, and the mechanism of the S. cerevisiae response to ethanol is not fully understood. In the current study, a systematic analytical approach was used to investigate the changes in the S. cerevisiae cell metabolome that were elicited by treatment with various concentrations of ethanol. Gas chromatography-mass spectrometry and a multivariate analysis were employed to investigate the ethanol-associated intracellular biochemical changes in S. cerevisiae. The intracellular metabolite profiles that were found upon treatment of the cells with different concentrations of ethanol were unique and could be distinguished with the aid of principal component analysis. Furthermore, partial least-squares-discriminant analysis revealed a group classification and pairwise discrimination between the control without ethanol and ethanol treated groups, and 29 differential metabolites with variable importance in the projection value greater than 1 were identified, which was also confirmed by the subsequent hierarchical cluster analysis. The metabolic relevance of these compounds in the response of S. cerevisiae to ethanol stress was investigated. Under ethanol stress, the glycolysis was inhibited and the use of carbon sources for fermentation was diminished, which might account for the growth inhibition of S. cerevisiae cells. It was suggested that S. cerevisiae cells change the levels of fatty acids, e.g., hexadecanoic, octadecanoic and palmitelaidic acids, to maintain the integrity of their plasma membrane through decreasing membrane fluidity in the medium containing ethanol. Moreover, the increased levels of some amino acids idemtified in the cells of ethanol-treated experimental group might also confer ethanol tolerance to S. cerevisiae. These results reveal that the metabolomics strategy is a powerful tool to gain insight into the molecular mechanism of a microorganism's cellular response to environmental stress factors.

[Risk factors which were associated with heroin use during the methadone maintenance treatment among 1301 patients in 9 cities of China.].

OBJECTIVE: To determine the proportion of heroin use among patients who were involved in community-based methadone maintenance treatment (MMT) program and to identify the risk factors associated with heroin use. METHODS: This study was conducted in 9 MMT clinics within 3 provinces. Thirteen hundred and one patients who met the study criteria were selected from each of the five groups with different dosages of methadone users. An administrative questionnaire was applied to explore the demographics, drug abuse-related behaviors and MMT services received by the clients, etc. The prevalence of depression and anxiety among the clients were also collected by SAS and SDS. Urine samples were collected as a biological marker to indicate if heroin had been used. RESULTS: Of the 1301 patients, 76.2% were males. The mean age was (34.6 +/- 6.5) years while 71.7% had an education level of primary school or below. The average daily dosage of methadone was (48.1 +/- 29.4) mg and self-satisfied evaluation score on treatment was 8.6. On average, 27.7% urine samples showed positive opiate evidence. Marital status, employment status, treatment retention, self-satisfied evaluation score on dosage and dropout history were found to be significantly associated with heroin use, while gender, education level and dosage had no significant association with heroin use. It seemed that risk factors that associated with heroin use were different from areas to areas. CONCLUSION: High quality MMT clinic services, high self-satisfied score, longer treatment retention and low dropout rate seemed to have the effects of reducing the risk of ongoing heroin abuse under the methadone maintenance treatment program.