Methamphetamine inhibits Toll-like receptor 9-mediated anti-HIV activity in macrophages.

Toll-like receptor 9 (TLR9) is one of the key sensors that recognize viral infection/replication in the host cells. Studies have demonstrated that methamphetamine (METH) dysregulated host cell innate immunity and facilitated HIV infection of macrophages. In this study, we present new evidence that METH suppressed TLR9-mediated anti-HIV activity in macrophages. Activation of TLR9 by its agonist CpG-ODN 2216 inhibits HIV replication, which was demonstrated by increased expression of TLR9, interferon (IFN)-α, IFN regulatory factor-7 (IRF-7), myeloid differentiation factor 88 (MyD88), and myxovirus resistance gene A (MxA) in macrophages. However, METH treatment of macrophages greatly compromised the TLR9 signaling-mediated anti-HIV effect and inhibited the expression of TLR9 downstream signaling factors. Dopamine D1 receptor (D1R) antagonists (SCH23390) could block METH-mediated inhibition of anti-HIV activity of TLR9 signaling. Investigation of the underlying mechanisms of the METH action showed that METH treatment selectively down-regulated the expression of TLR9 on macrophages, whereas it had little effect on the expression of other TLRs. Collectively, our results provide further evidence that METH suppresses host cell innate immunity against HIV infection by down-regulating TLR9 expression and its signaling-mediated antiviral effect in macrophages.

[Acceptability and influencing factors on pre-exposure prophylaxis programs among female sex workers in Guangxi, China].

OBJECTIVE: To study the acceptability of pre-exposure prophylaxis (PrEP) program on prevention of human immunodeficiency virus (HIV) infection among female sex workers (FSWs) in Guangxi of China. METHODS: A cross-sectional survey using convenience sampling was administered among 405 FSWs in Nanning, Liuzhou and Beihai cities of Guangxi, China. Self-designed questionnaire, face to face interviews were used to collect HIV-related risk behaviors, knowledge and acceptability of PrEP. RESULTS: After an introduction on PrEP, presuming that it was effective, safe and free of charge, 85.9% of the 405 FSWs said they would use it. Data from logistic regression analysis showed that significant factors of intent to use PrEP would include the followings: workplace (OR = 2.256, P = 0.009), monthly income (OR = 0.257, P = 0.004), family closeness (OR = 0.338, P = 0.012), knowledge on HIV/AIDS (OR = 2.802, P = 0.028), HIV/AIDS risk was introduced from a strange client (OR = 0.363, P = 0.049), whether the gatekeeper ordering the use of condom (OR = 0.432, P = 0.010), whether consistent using condom with clients (OR = 3.010, P = 0.002), whether ever using drugs to prevent STD infection (OR = 3.570, P = 0.049) etc. CONCLUSION: Awareness on HIV/AIDS knowledge and self-protection seemed the main influential factors while health education might promote the acceptability of PrEP.

[The correlation analysis between environmental factors, bone morphogenetic protein-4 and transforming growth factor beta-3 polymorphisms in nonsyndromic cleft lip with or without cleft palate].

OBJECTIVE: To investigate the effects of interactions among environmental factors, bone morphogenetic protein-4 (BMP4) and transforming growth factor beta-3 (TGF-ß(3)) polymorphisms on nonsyndromic cleft lip and cleft palate (NSCLP). METHODS: The data of environmental exposures were collected with questionnaires. Genotypes were determined with techniques of polymerase chain reaction-restriction fragment length polymorphism. Interactions between genes, environmental factors and NSCLP were analyzed using multifactor dimensionality reduction (MDR) method. The interactions were validated by logistic regression analysis. RESULTS: There was no correlation between three single nucleotide polymorphism (SNP) associated with NSCLP. The developmental accident of NSCLP had higher risk in the interaction between BMP4 T538C, maternal passive smoking and infection in first trimester pregnancy, as well as in the interaction of six factors between TGF-ß(3) G15572-, maternal passive smoking, infections, multivitamin supplement in the first trimester pregnancy, paternal smoking and high risk drinking before realizing pregnancy than in other interactions of environmental factors. The results could be validated by logistic regression analysis. CONCLUSIONS: The NSCLP is induced by the interactions between genes and environmental risk factors.