Risk factors for children s blood lead levels in one city of Jiangsu / 中国学校卫生

Objective@#To understand the level and risk factor of lead exposure among children in one city of Jiangsu.@*Methods@#In northern Jiangsu Province, 373 children from 2 primary schools were enrolled and were tested for blood lead and heavy metal exposure. Lead exposure was tested in household dust of 46 children. A multivariate Logistic regression was used for lead exposure risk analysis. Spatial distribution of lead contamination in household dust was conducted and compared with the location of industrial enterprises.@*Results@#The geometric mean of blood lead in 373 children was 25.80 mg/L,the blood lead of 3 children (0.8%) was more than 100 mg/L. Pencil biting ( OR=4.26, 95%CI=1.61-10.68, P <0.05) and lead contamination in surrounding environment ( OR=2.93, 95%CI=1.24-7.34, P =0.02) was positively related to high blood lead level in children. The geometric mean household dust lead concentrations in 46 children was 302.27 μg/mg, and household with high dust lead levels were mainly located around manufacturing enterprises.@*Conclusion@#Environmental factors correlate with blood lead level in children. Efficient strategies and public health policies are urgently needed to control and prevent environmental lead pollution. Families and schools should actively carry out health education to engourage children good hygiene habits, and effectively reduce lead exposure.

Development of Different Methods for Preparing Acinetobacter baumannii Outer Membrane Vesicles Vaccine: Impact of Preparation Method on Protective Efficacy.

Acinetobacter baumannii (A. baumannii) is becoming a common global concern due to the emergence of multi-drug or pan-drug resistant strains. Confronting the issue of antimicrobial resistance by developing vaccines against the resistant pathogen is becoming a common strategy. In this study, different methods for preparing A. baumannii outer membrane vesicles (AbOMVs) vaccines were developed. sOMV (spontaneously released AbOMV) was extracted from the culture supernatant, while SuOMV (sucrose-extracted AbOMV) and nOMV (native AbOMV) were prepared from the bacterial cells. Three AbOMVs exhibited significant differences in yield, particle size, protein composition, and LPS/DNA content. To compare the protective efficacy of the three AbOMVs, groups of mice were immunized either intramuscularly or intranasally with each AbOMV. Vaccination via both routes conferred significant protection against lethal and sub-lethal A. baumannii challenge. Moreover, intranasal vaccination provided more robust protection, which may be attributed to the induction of significant sIgA response in mucosal sites. Among the three AbOMVs, SuOMV elicited the highest level of protective immunity against A. baumannii infection, whether intramuscular or intranasal immunization, which was characterized by the expression of the most profound specific serum IgG or mucosal sIgA. Taken together, the preparation method had a significant effect on the yield, morphology, and composition of AbOMVs, that further influenced the protective effect against A. baumannii infection.

Toll-like receptors: Triggers of regulated cell death and promising targets for cancer therapy.

Toll-like receptors (TLRs) belong to a family of pattern recognition receptors (PRRs). It is well known that TLRs play an essential role in activating innate and adaptive immune responses. TLRs are involved in mediating inflammatory responses and maintaining epithelial barrier homeostasis, and they are highly likely to activate various signalling pathways during cancer chemotherapy. For a long time, much research focused on the immune modulating function of TLRs in cancer genesis, pathology and therapeutic strategies. However, recent reports have suggested that except for the innate and adaptive immune responses that they initiate, TLRs can signal to induce regulated cell death (RCD), which also plays an important role in the antitumor process. TLR agonists also have been investigated as cancer therapeutic agents under clinical evaluation. In this review, we focused on the mechanism of RCD induced by TLR signals and the important role that they play in anticancer therapy combined with recent experimental and clinical trial data to discuss the possibility of TLRs as promising targets for cancer therapy. TLRs represent triggers of regulated cell death and targets for cancer therapy. The molecular mechanisms of TLR-induced RCD and relationship between TLR-signalling pathways and cancer remain to be investigated by further studies.

Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori.

BACKGROUND: Helicobacter pylori (H. pylori) infection remains a global public health issue, especially in Asia. Due to the emergence of antibiotic-resistant strains and the complexity of H. pylori infection, conventional vaccination is the best way to control the disease. Our previous study found that the N-acetyl-neuroaminyllactose-binding hemagglutinin protein (HpaA) is an effective protective antigen for vaccination against H. pylori infection, and intranasal immunization with the immunodominant HpaA epitope peptide (HpaA 154-171, P22, MEGVLIPAGFIKVTILEP) in conjunction with a CpG adjuvant decreased bacterial colonization in H. pylori-infected mice. However, to confer more robust and effective protection against H. pylori infection, an optimized delivery system is needed to enhance the P22-specific memory T cell response. RESULTS: In this study, an intranasal nanoemulsion (NE) delivery system offering high vaccine efficacy without obvious cytotoxicity was designed and produced. We found that this highly stable system significantly prolonged the nasal residence time and enhanced the cellular uptake of the epitope peptide, which powerfully boosted the specific Th1 responses of the NE-P22 vaccine, thus reducing bacterial colonization without CpG. Furthermore, the protection efficacy was further enhanced by combining the NE-P22 vaccine with CpG. CONCLUSION: This epitope-loaded nanoemulsion delivery system was shown to extend antigen release and elicit potent Th1 response, it is an applicable delivery system for intranasal vaccine against H. pylori.

Intranasal immunization with immunodominant epitope peptides derived from HpaA conjugated with CpG adjuvant protected mice against Helicobacter pylori infection.

HpaA is considered to be an effective protective antigen for vaccination against Helicobacter pylori (H. pylori) infection. Oral immunization with HpaA significantly decreases bacterial colonization in H. pylori infected mice. In this study, we investigated whether subcutaneous or intranasal immunization with HpaA could protect against H. pylori infection. Mice immunized subcutaneously with HpaA in Complete Freund's adjuvant, but not mice intranasally immunized with HpaA in CpG adjuvant acquired protection against H. pylori infection. However, intranasal immunization with immunodominant epitope peptides in CpG adjuvant protected mice against H. pylori infection, and immunodominant epitope peptides stimulated stronger Th1 responses and mediated more robust protection against H. pylori infection than subdominant ones. Our results suggest that the length of a candidate antigen is critical for particular vaccination routes, and that immunodominant epitope peptides are promising candidates for protection against H. pylori infection through nasal vaccination.

An immunopotentiator, ophiopogonin D, encapsulated in a nanoemulsion as a robust adjuvant to improve vaccine efficacy.

As an ingredient of vaccines, adjuvants are indispensable for enhancing and directly inducing robust and extensive adaptive immune responses associated with vaccine antigens. In this study, we initially determined that a new molecular immunopotentiator, ophiopogonin D (OP-D), enhanced the antibody response to antigen. Because OP-D has certain disadvantages, including poor solubility, we next encapsulated OP-D in a nanoemulsion adjuvant (nanoemulsion-encapsulated OP-D, NOD) using low-energy emulsification methods. The NOD thus produced was small, with an average size of 76.45 nm, and exhibited good distribution (PdI value 0.16), significantly increasing the solubility of OP-D. Furthermore, NOD exhibited reduced cellular toxicity and acute toxicity. Our results showed that a fusion antigen of MRSA (HlaH35LIsdB348-465) formulated with NOD significantly improved humoral and cellular immune responses compared to those observed in the antigen/OP-D and antigen/AlPO4 groups. Compared with antigen/OP-D, the antigen formulated with NOD more effectively promoted antigen uptake by dendritic cells (DCs) and the activation of antigen-presenting cells (APCs). Moreover, the NOD-formulated antigen had ideal protective efficacy in a MRSA sepsis model by inducing more potent antibody responses and a Th1/Th17-biased CD4+ T cell immune response. Therefore, these results suggest that NOD is a promising and robust adjuvant platform for a MRSA vaccine. STATEMENT OF SIGNIFICANCE: We first identified a new powerful immunopotentiator, Ophiopogonin D, among dozens of natural products and then used nanotechnology to construct a highly efficient and low toxic adjuvant system (NOD). Our approach intersects natural medicinal chemistry, nanomaterials and immunology, revealing that a strong adjuvant activity of this adjuvant system was verified in vitro and in vivo, and the application of MRSA subunit vaccine model for survival experiments achieved a 100% protection rate. This research illustrate that NOD is a promising and robust adjuvant platform for subunit vaccines.

Immune response effects of diverse vaccine antigen attachment ways based on the self-made nanoemulsion adjuvant in systemic MRSA infection.

Nanoemulsion adjuvants-based vaccines have potent induced immune responses against methicillin-resistant Staphylococcus aureus (MRSA) infection. However, the efficacies and immune responses of different antigen-attaching ways on self-made nanoemulsion adjuvants remain unknown. In this study, we designed three formulations of nanoemulsion adjuvants (encapsulation, mixture, and combination) to explore their immune response-enhancing effects and their underlying mechanism in a systemic infection model of MRSA. Our results showed that the three nanoemulsion-attachment ways formulated with a fusion antigen of MRSA (HlaH35LIsdB348-465) all improved humoral and cellular immune responses. When compared with the mixture and combination formulations, the nanoemulsion-encapsulation group effectively promoted the antigen uptake of dendritic cells (DCs) in vitro, the activation of DC in draining lymph nodes and the delayed release of antigen at injection sites in vivo. Moreover, the encapsulation group induced a more ideal protective efficacy in a MRSA sepsis model by inducing more potent antibody responses and a Th1/Th17 biased CD4+ T cell response when compared with the other two attachment ways. Our findings suggested that the encapsulated formulation of vaccine with nanoemulsion adjuvant is an effective attachment way to provide protective immunity against MRSA infection.

Protective effects of a nanoemulsion adjuvant vaccine (2C-Staph/NE) administered intranasally against invasive Staphylococcus aureus pneumonia.

No licensed Staphylococcus aureus (S. aureus) vaccine is currently available. To develop an effective S. aureus vaccine, we selected the recombinant proteins staphylococcal enterotoxin B (rSEB) and manganese transport protein C (rMntC) as vaccine candidates and formulated a 2C-Staph vaccine. Based on the optimised formation of nanoemulsion (NE) technology, we constructed a novel NE adjuvant vaccine, 2C-Staph/NE. The 2C-Staph/NE particles showed a suitable diameter (24.9 ± 0.14 nm), a good protein structure of integrity and specificity, and high thermodynamic stability. 2C-Staph formulated with an NE adjuvant induced higher survival rates than a 2C-Staph/MF59 vaccine in sepsis and pneumonia models. Moreover, intramuscular vaccination with 2C-Staph/NE yielded protection efficacy in a sepsis model, and the intranasal vaccination route induced a potent protective effect in a pneumonia model. Intranasal vaccination with 2C-Staph/NE induced a strong mucosal response with high levels of IgA and IL-17A in bronchoalveolar lavage fluid (BALF), and the IgG levels in the BALF were comparable to those induced by the intramuscular vaccination route. Furthermore, the serum and BALF induced by intranasal administration showed potent opsonophagocytic activity against S. aureus. And, the IL-17A played a protective role in the pneumonia model demonstrated by a cytokine neutralization test. Taken together, our results showed that intranasal administration of 2C-Staph formulated with an NE adjuvant yielded ideal protection in a murine S. aureus pneumonia model.

Inhibited biofilm formation and improved antibacterial activity of a novel nanoemulsion against cariogenic Streptococcus mutans in vitro and in vivo.

The aim of this study was to prepare a novel nanoemulsion loaded with poorly water-soluble chlorhexidine acetate (CNE) to improve its solubility, and specifically enhance the antimicrobial activity against Streptococcus mutans in vitro and in vivo. In this study, a novel CNE nanoemulsion with an average size of 63.13 nm and zeta potential of -67.13 mV comprising 0.5% CNE, 19.2% Tween 80, 4.8% propylene glycol, and 6% isopropyl myristate was prepared by the phase inversion method. Important characteristics such as the content, size, zeta potential, and pH value of CNE did not change markedly, stored at room temperature for 1 year. Also, compared with chlorhexidine acetate water solution (CHX), the release profile results show that the CNE has visibly delayed releasing effect in both phosphate-buffered saline and artificial saliva solutions (P<0.005). The minimum inhibitory concentration and minimum bactericidal concentration of CHX for S. mutans (both 0.8 µg/mL) are both two times those of CNE (0.4 µg/mL). Besides, CNE of 0.8 µg/mL exhibited fast-acting bactericidal efficacy against S. mutans, causing 95.07% death within 5 minutes, compared to CHX (73.33%) (P<0.01). We observed that 5 mg/mL and 2 mg/mL CNE were both superior to CHX, significantly reducing oral S. mutans numbers and reducing the severity of carious lesions in Sprague Dawley rats (P<0.05), in an in vivo test. CNE treatment at a concentration of 0.2 µg/mL inhibited biofilm formation more effectively than CHX, as indicated by the crystal violet staining method, scanning electron microscopy, and atomic force microscopy. The cell membrane of S. mutans was also severely disrupted by 0.2 µg/mL CNE, as indicated by transmission electron microscopy. These results demonstrated that CNE greatly improved the solubility and antimicrobial activity of this agent against S. mutans both in vitro and in vivo. This novel nanoemulsion is a promising medicine for preventing and curing dental caries.