Novel biomimetic mesoporous silica nanoparticle system possessing targetability and immune synergy facilitates effective solid tumor immuno-chemotherapy.

New strategies that enhance both the targetability of chemotherapy drugs and the synergistic effects of chemotherapy and immunotherapy are urgently needed for efficacious solid tumor therapy. In this study, a novel biomimetic nanoparticle system possessing the properties of tumor targeting and immune synergy was designed to meet these requirements. Mesoporous silica nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX) were coated with cell membranes modified by glycosylphosphatidylinositol (GPI)-anchored anti-HER2 single chain variable fragment (scFv) and the GPI-anchored co-stimulatory molecule CD80 (to promote solid tumor-targeted chemotherapy and cooperated immunotherapy, respectively). The impact of the nanotherapeutic system on both tumor-targeted chemotherapy and cellular immune response was investigated through in vitro and in vivo experiments. The results show that the novel biomimetic therapeutic system effectively promoted antitumor efficiency in vitro and in vivo. In addition, this therapeutic system further enhanced antitumor capacity by increasing CD8+ T cell activation and cytokine production and reducing myeloid-derived suppressor cell (MDSC) levels in tumors.

Serum concentrations of neonicotinoids and their characteristic metabolites in elderly population from South China: Association with osteoporosis.

Neonicotinoids (NEOs) are extensively applied in global agricultural production for pest control but have adverse effects on human health. In this study, the concentrations of six NEOs and three characteristic metabolites were investigated by collecting 200 serum samples from an elderly population in China. Results showed that the NEOs and their metabolites were widely detected (89%-98 %) in the serum samples from the osteoporosis (OP) (n = 120) and non-OP (n = 80) population, and their median concentrations ranged from 0.04 ng/mL to 5.99 ng/mL and 0.01 ng/mL to 2.02 ng/mL, respectively. N-desmethyl-acetamiprid (ACE-dm) was the most abundant NEOs in the serum samples. Gender-related differences were found in concentrations of most NEOs and their metabolites in serum, with males having higher target analytes than females. Significantly (p < 0.05) positive correlations were observed among most NEO concentrations, suggesting that exposure source of these substances is common or related. However, associations between the concentrations of characteristic metabolites and their corresponding NEOs were insignificant, probably because the exogenous intake are the primary sources of metabolites of NEOs instead of the internal biotransformation. The associations between NEO concentrations (i.e., ACE-dm, dinotefuran, and olefin-imidacloprid) and OP (OR = 2.33-6.92, 95 % CI = 0.37-16.9, p-trend < 0.05) indicate that NEO exposure is correlated with increased odds of prevalent OP. This study is the first to document the profiles of NEOs and their metabolites in serum samples collected from an elderly population in South China and examine the relationships between NEO exposure and OP.

Neonicotinoid insecticide and their metabolite residues in fruit juices: Implications for dietary intake in China.

Neonicotinoid insecticides (NEOs) have become the most widely used insecticides worldwide, and they are ubiquitous in food (i.e., fruit juices). In the present study, occurrence of seven NEOs and four metabolites (m-NEOs) in 400 fruit juice samples were investigated. NEOs and m-NEOs were frequently detected (65%-86%) in fruit juice samples. The median residues of NEOs and m-NEOs were ranged from 0.06 ng/mL to 0.94 ng/mL. Seasonal variations in NEOs and m-NEOs in fruit juices were found, indicating that the target analyte residues during the dry season were remarkably higher than those of residues during wet season. The relative potency factor (RPF) method was used to integrate individual NEOs into a single metric [imidacloprid (IMIRPF)] representing the intakes of IMI equivalent to total NEOs for each fruit juice sample. The estimated daily intake (EDI) of total NEOs for the general Chinese population was obtained. The median IMIRPF for total fruit juices was 13.4 ng/g, and the median EDI of NEOs was 18.2 ng/kg bw/day for the general population. Although the EDIs in this study were considerably lower than the acceptable daily intake (60 µg/kg bw/day, ADI), the dietary exposure risks for total NEOs should not be ignored because of the increasing usage of NEOs and their ubiquitous presence in fruit juices in China. To the best of our knowledge, this report was the first time to document residues of NEO and m-NEO in fruit juice samples collected from China.

Occurrence of parabens and their metabolites in the paired urine and blood samples from Chinese university students: Implications on human exposure.

Parabens, a group of p-hydroxybenzoic acid esters, are extensively used in cosmetics, personal care products, pharmaceuticals, and foodstuff. In the present study, the total forms (free plus conjugated) of four parent parabens, such as methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), and four metabolites, namely methyl protocatechuate (OH-MeP), ethyl protocatechuate (OH-EtP), p-hydroxy benzoic acid (4-HB), and 3,4-dihydroxy benzoic acid (3,4-DHB), were detected in paired urine and blood samples collected from 196 Chinese university students. The median urinary and blood parabens and their metabolites concentrations ranged from 0.24 to 167 ng/mL and from <0.02 to 2.88 ng/mL, respectively. MeP was the predominant parent parabens, accounting for 68% and 52% of urine and blood samples, respectively. Furthermore, 4-HB predominantly contributed to the parabens and their metabolites in urine (54%) and blood (41%). Significant positive correlations were observed between the urinary levels and blood levels. Moreover, relatively high levels of parabens and their metabolites were detected in urine samples. Our results imply that urinary concentrations are good predictors of human exposure to parabens and metabolites. Gender-related difference in urinary concentrations of parabens and their metabolites were found. The median urinary levels of the tested compounds in females were significantly higher than those in males (Mann Whitney U test, p < 0.05 or 0.01). The estimated daily intakes (EDIs) of MeP, EtP, and PrP were also evaluated. The median values of EDIMeP, EDIEtP, and EDIPrP for all of the university students were estimated to be 25.9, 1.61, and 3.82 µg/kg bw/day, respectively. The median values (µg/kg bw/day) of EDIMeP, EDIEtP, and EDIPrP were higher in females (53.7, 8.65, and 5.22) than in males (8.41, 0.85, and 2.57). This study is the first study to report the occurrence of parabens and their metabolites in paired urine and blood samples in China.

SOCS-1 ameliorates smoke inhalation-induced acute lung injury through inhibition of ASK-1 activity and DISC formation.

Smoke inhalation leads to acute lung injury (ALI), a devastating clinical problem associated with high mortality. Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of apoptosis and pro-inflammatory cytokine signaling, two major contributors to the pathogenesis of ALI. We have found that SOCS-1 protects lung epithelial cells from smoke-induced apoptosis through two mechanisms. One is that SOCS-1 enhances degradation of ASK-1 and diminishes cleavage of pro-caspase-3 to repress smoke-triggered apoptosis in lung epithelial cells. The other is that SOCS-1 represses smoke-triggered DISC formation through altering TRADD-caspase-8 interaction rather than TNFR-1-TRADD interaction or TNFR-1-TRAF-2 interaction. In conclusion, SOCS-1 relieves smoke inhalation-induced lung injury by repressing ASK-1 and DISC-mediated epithelium apoptosis.