Study on the Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactone Derivatives.

With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. Mycobacterium marinum, as a model organism of Mycobacterium tuberculosis, can be used for the rapid and efficient screening of bioactive compounds. The 14-membered resorcylic acid lactones (RALs) have a wide range of bioactivities such as antibacterial, antifouling and antimalarial activity. In order to further study their bioactivities, we initially constructed a 14-membered RALs library, which contains 16 new derivatives. The anti-M. marinum activity was evaluated in vitro. Derivatives 12, 19, 20 and 22 exhibited promising activity with MIC90 values of 80, 90, 80 and 80 µM, respectively. The preliminary structure-activity relationships showed that the presence of a chlorine atom at C-5 was a key factor to improve activity. Further studies showed that 12 markedly inhibited the survival of M. marinum and significantly reduced the dosage of positive drugs isoniazid and rifampicin when combined with them. These results suggest that 12 is a bioactive compound capable of enhancing the potency of existing positive drugs, and its effective properties make it a very useful leads for future drug development in combating TB resistance.

Effect of VEGF-targeted antisense gene therapy on retinoblastoma cell line SO-RB50 in vitro and in vivo.

AIM: To evaluate the possibility of generation 4 polyamidoamine (G4PAMAM) dendrimers acting as the delivery system of vascular endothelial growth factor (VEGF) antisense oligodeoxynucleotides (VEGFASODN), and to investigate the anti-tumor effect of G4PAMAM/VEGFASODN complex on the cultured cells and the mouse tumor xenograft model. METHODS: The transfection efficiency was assessed by Flow cytometry (FCM). Thiazolyl tetrazolium (MTT) assay was performed to determine the relative growth rate (RGR) of the cells after transfection. Then a mouse tumor xenograft model of human retinoblastoma was established. Different interventions were given to the mice by intratumoral injection and the tumor growth was monitored. The expression of VEGF mRNA was detected by reverse transcription PCR (RT-PCR), the expression of VEGF protein was determined by western blot analysis, and the microvessel density (MVD) was measured by immunohistochemistry (IHC) staining. RESULTS: G4PAMAM/VEGFASODN exhibited a high transfection rate in vitro, and the transfection rates of different doses of G4PAMAM/VEGFASODN groups increased with higher doses. This effect was accompanied by a dose-depended reduction in cell viability. The tumor growth in the tumor-bearing athymic mice was significantly inhibited in the G4PAMAM/VEGFASODN group. The expressions of VEGF mRNA and protein were obviously inhibited in the G4PAMAM/VEGFASODN group (P<0.05), and the MVD of the G4PAMAM/VEGFASODN group was lower than that of the other groups (P<0.05). CONCLUSION: VEGFASODN can be delivered into the cultured and transplanted retinoblastoma cells efficiently by G4PAMAM, suppress the expressions of VEGF mRNA and protein, and reduce the MVD of tumor tissues. The G4PAMAM/VEGFASODN complex has antitumor properties in vitro and in vivo.

[A retrospective survey of childhood corporal punishment by school teachers in students].

OBJECTIVE: To ascertain the prevalence of childhood corporal punishment by teachers in students, to explore the influencing factors and associations between childhood corporal punishment and psychological problems. METHODS: Five hundred and twenty-eight students from a college and a technical secondary school in Hebei province were surveyed by self-administered questionnaire anonymously in Dec. 2004. The questionnaire used for this survey mainly included (1) general demographic information; (2) 5 forms of childhood corporal punishments, in this study, cases of teachers' corporal punishments were defined as those who answered positively one or more of the 5 questions relating to childhood corporal punishment by school teachers occurring before the age of 16 years; (3) Symptom Checklist-90 (SCL-90); (4) Youth Risk Behaviours. RESULTS: Overall, 57.6% of students reported having been corporally punished at least one time, one of four forms of corporal punishment by teachers before age of 16 years, the four forms corporal punishment were non-contact corporal punishment, e.g., running for punishment, repeat-doing homework many times for punishment, standing for punishment, kneel down for punishment, not allowing to eat, sending outside in winter, etc. (53.4%), hitting/kicking/pushing very hard with open hands/fist/feet/other part of body (16.1%), beating with an object (10.2%), and locking in a small compartment/tying with rope (0.2%). No students reported having been choked, or burned/scalded, or stabbed with a sharp object by the teachers. Males had a significantly higher overall prevalence rate than females (66.4% vs. 46.6%, chi(2) = 21.01, P = 0.000). There was no statistically significant association between a history of childhood corporal punishment and the three other demographic indicators, which included residence region (rural and non-rural area) prior to 16 years of age, parental education level, and whether the respondent lived in a single or multiple children family. Compared with their peers who had not experienced childhood corporal punishment by teachers, the students with two or more forms of corporal punishments by teachers showed significantly higher scores (punished group vs. unpunished group) of psychological symptoms of somatization (0.78 vs. 0.42), obsessiveness (1.22 vs. 0.98), interpersonal sensitivity (1.24 vs. 0.89), depression (1.06 vs. 0.76), anxiety (0.90 vs. 0.64), hostility (1.11 vs. 0.68), paranoid ideation (1.11 vs. 0.71) and psychoticism (0.84 vs. 0.56), and showed significantly higher rates in sadness (54.7% vs. 26.3%), drunk (37.2% vs. 20.1%), involving in physical fighting (15.1% vs. 3.6%) in the past year and current smoking (36.0% vs. 14.5%). CONCLUSIONS: The problem of corporal punishment by teachers is common in schools, and the problem has a significant correlation with youth mental health problems. The results highlighted urgent needs to increase public awareness on children rights, creating learning-friendly environment in school.