Ag85b/ESAT6-CFP10 adjuvanted with aluminum/poly-IC effectively protects guinea pigs from latent mycobacterium tuberculosis infection.

The high global burden of tuberculosis (TB) underscores the urgent need for an effective TB vaccine since the only licensed Bacillus Calmette-Guérin (BCG) vaccine is ineffective in preventing adult pulmonary TB and affords no protection against latent TB infection (LTBI). Herein we investigated the potential of Mycobacterium tuberculosis (Mtb) antigen proteins AEC comprised of Ag85b and ESAT6-CFP10 proteins in conjunction with aluminum (Al) and polyriboinosinic-polyribocytidylic acid (poly-IC) as a novel subunit vaccine against TB. The immunogenicity and protection induced by the adjuvanted vaccine were evaluated in two animal models. Mice vaccinated with AEC/Al/poly-IC exhibited significant antigen-specific humoral immune responses and cell-mediated immunity as determined by immunoassay and multicolor flow cytometric assay, and the protective effect of the vaccine was demonstrated in a guinea pig model of latent Mtb infection. Compared to the control group, the mean pathological scores and bacterial loads in lungs and spleens of AEC/Al/poly-IC-immunized guinea pigs were significantly reduced. These data indicate that the AEC/Al/poly-IC is highly immunogenic in mice and can effectively protect guinea pigs against latent Mtb infection; it may represent a promising candidate vaccine for the control of latent TB.

Multifunctional Silicon-Carbon Nanohybrids Simultaneously Featuring Bright Fluorescence, High Antibacterial and Wound Healing Activity.

In this work, a class of multifunctional silicon-carbon nanohybrids (designated as SiCNs), which simultaneously possess aqueous dispersibility, bright fluorescence (photoluminescence quantum yield [PLQY]: ≈28%), as well as high antibacterial and wound healing activity, is presented. Taking advantage of these unique merits, cell distribution and pharmacological behavior of the SiCNs is first investigated through tracking their strong and stable fluorescence. The high bacteria inhibition ability (≈82.9% killing rate toward S. aureus) and hemostatic effects (shorten the bleeding time from ≈60 to ≈15 s) of the resultant SiCNs are then demonstrated. Moreover, the wound closure promotion activity (10% lead in wound contraction) is systematically demonstrated in vivo, which is especially suitable for wound healing applications. The results suggest the SiCNs as a new kind of high-performance multifunctional nanoagents suitable for various biological and biomedical utilizations.

Fluorescein sodium ligand-modified silicon nanoparticles produce ultrahigh fluorescence with robust pH- and photo-stability.

Water-dispersed silicon nanoparticles (SiNPs) are facilely prepared in an aqueous phase via microwave-assisted synthesis. The whole synthetic procedure is accomplished in a one-pot microwave reaction, without the requirement of additional surface modification. Remarkably, the resultant SiNPs feature ultrahigh fluorescence (photoluminescent quantum yield (PLQY): ∼90%), robust pH- and photo-stability, and favourable biocompatibility.

Excitation-wavelength-dependent photoluminescence of silicon nanoparticles enabled by adjustment of surface ligands.

We herein present pioneering studies to reveal that excitation-wavelength-dependent photoluminescence properties of fluorescent silicon nanoparticles (SiNPs) can be realized by rationally designing surface ligands, i.e., several kinds of oxidized indole derivatives. The resultant ligand-decorated SiNPs exhibit strong fluorescence, with significant excitation-wavelength-dependent emissive shifting from ∼420 nm to ∼550 nm. Taking advantage of their unique optical merits, we further exploit the resultant ligand-decorated SiNPs as novel fluorescent labels for anti-counterfeiting and cell imaging.

Recombinant tuberculosis vaccine AEC/BC02 induces antigen-specific cellular responses in mice and protects guinea pigs in a model of latent infection.

PURPOSE: To preliminarily evaluate the immunogenicity and efficacy of the recombinant tuberculosis vaccine AEC/BC02 in which Ag85b and fusion protein ESAT6-CFP10 were combined with bacillus Calmette-Guérin CpG and an aluminum salt-based adjuvant system. METHODS: Groups of BALB/c mice were immunized intramuscularly three times at 10-day intervals with AEC/BC02 or the adjuvant alone and the vaccine-induced cell-mediated immune responses were evaluated. The efficacy of AEC/BC02 was evaluated in two guinea pig models, one a model of prevention and the other a model of latent infection. RESULTS: The AEC/BC02 vaccine induced strong cellular immune responses characterized by a high frequency of antigen-specific interferon-γ-secreting T cells in mice at different time points after the last vaccination. In the preventive model of guinea pig, AEC/BC02 did not protect against Mycobacterium tuberculosis as a pre-exposure vaccine. However, in a latent infection model of guinea pig, it effectively controlled the reactivation of M. tuberculosis and lowered the bacterial load in the lung and spleen. CONCLUSION: These results indicate AEC/BC02 can protect against reactivation of latent infection and may function as a therapeutic vaccine.

Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor.

CONTEXT: Clinical prediction of preterm delivery is largely ineffective, and the mechanism mediating progesterone (P) withdrawal and estrogen activation at the onset of human labor is unclear. OBJECTIVES: Our objectives were to determine associations of rates of change of circulating maternal CRH in midpregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy, and predelivery changes in the ratios of E3, estradiol (E2), and P. DESIGN AND SETTING: A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000-2004 at John Hunter Hospital, New South Wales, Australia, a tertiary care obstetric hospital. PATIENTS: Unselected subjects were recruited (including women with multiple gestations) and serial blood samples obtained. MAIN OUTCOME MEASURES: CRH daily percentage change in term and preterm singletons at 26 wk, ratios E3/E2, P/E3, and P/E2 and the association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset) were assessed. RESULTS: CRH percentage daily change was significantly higher in preterm than term singletons at 26 wk (medians 3.09 and 2.73; P = 0.003). In late pregnancy, CRH and E3 concentrations were significantly positively associated (P = 0.003). E3/E2 increased, P/E3 decreased, and P/E2 was unchanged in the month before delivery (medians: E3/E2, 7.04 and 10.59, P < 0.001; P/E3, 1.55 and 0.98, P < 0.001; P/E2, 11.78 and 10.79, P = 0.07). CONCLUSIONS: The very rapid rise of CRH in late pregnancy is associated with an E3 surge and critically altered P/E3 and E3/E2 ratios that create an estrogenic environment at the onset of labor. Our evidence provides a rationale for the use of CRH in predicting preterm birth and informs approaches to delaying labor using P supplementation.