Multifunctional titanium phosphate carriers for enhancing drug delivery and evaluating real-time therapeutic efficacy of a hydrophobic drug component in Euphorbia kansui.

Nanoparticles are often used to serve as drug delivery systems to improve the therapeutic efficacy of some hydrophobic drugs. In this work, PEG and peptide-modified titanium phosphate nanoparticles (TiP-PEG/peptide) were synthesized to enhance the drug delivery efficacy of tirucalla-8,24-diene-3ß,11ß-diol-7-one (KS-01), a major bioactive and hydrophobic component extracted from Euphorbia kansui. This drug delivery system with a loading efficiency of about 29.8 mg KS-01/1 g TiP-PEG/peptide exerted a significantly lower cell viability rate of MCF-7 than free KS-01, indicating that these carriers can effectively increase the therapeutic efficacy by improving its water solubility. Moreover, according to the fluorescence intensity of FAM which can be generated by caspase-3 cleaving DEVD-embedded peptide, the caspase-3 level could be determined and the therapeutic efficacy could be visualized in real time.

Clinical characteristics of 68 children with atypical hand, foot, and mouth disease caused by coxsackievirus A6: a single-center retrospective analysis.

Background: Hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CV-A6) has become prevalent in many parts of the world. It is commonly referred to as atypical HFMD which more likely to present as bullous lesions. Compared with traditional HFMD, its misdiagnosis rate is relatively high, which brings difficulties to clinical diagnosis. We retrospectively analyze the clinical characteristics of children with HFMD with bullous lesions caused by CV-A6. Methods: The study included 68 children with atypical HFMD caused by CV-A6 who were hospitalized from 2018 to 2020. Data of the children including age, sex, month of HFMD onset, the morphologies and distribution of rashes, the details of fever, the presence or absence of onychomadesis, and laboratory test results were analyzed and compared between an infant group (<1 year), a toddler group (1-<3 years), and a preschool group (3-<6 years). Results: Of the 68 children, 67 were younger than 5 years old, with a male to female ratio of 1.62:1. The disease peaked in the period from June to September. With 75.0% of the infant group had more than three kinds of rashes; 95.0% of the preschool group had rashes in more than five locations. These differences were statistically significant (P<0.05). All children had fever. The peak fever in the toddler group was lower (P=0.033). No critical cases were observed in any of the groups. Of the 61 children who were successfully followed up, 68.9% developed onychomadesis within 2-3 weeks. The proportion of cases with abnormal liver function was 83.3%, 41.7%, and 10.0% in the infant, toddler, and preschool groups (P<0.001). The proportion of cases with increased serum creatine kinase MB isoenzyme (CK-MB) were significantly higher in the toddler group (P<0.05). Conclusions: Atypical HFMD caused by CV-A6 infection usually occurred in children under 5 years old. The morphologies of the rashes in the infant group changed more, while the rashes in the preschool group was more widely distributed. The incidence of critical cases was low. More than half of the cases can develop onychomadesis in the recovery period. Organ damage was relatively mild in the preschool group.

[Variations and Influencing Factors of Oral Bioaccessibility of Polybrominated Diphenyl Ethers in Soils Using an In-vitro Gastrointestinal Model].

Intake of contaminated soils is considered as an important exposure pathway of polybrominated diphenyl ethers (PBDEs) to humans, especially for children during their outdoor hand-to-mouth activities. Oral bioaccessibility is an essential tool to quantitatively assess the exposure risk of pollutants. In this study, we employed an in vitro digestion model to mimic the gastrointestinal digestion of typical PBDEs (BDE-28, BDE-47, BDE-99 and BDE-153 at a series of initial concentrations) in three natural soil samples with different TOC contents and to verify a previous hypothesis that the sorption of PBDE fraction mobilized from soil into digestive fluid on the surface of residual solid phase may lead to an underestimation of bioaccessibility of PBDEs. In addition, a method with multiple fluid-to-solid ratios was applied to calibrate the underestimation. The results indicated that the calibrated digestibility values were commonly higher than those without correction. For the different soil samples, the averaged increasing rates of PBDE digestibility at different initial concentrations ranged from 14.3% to 42.3%, from 11.1% to 32.1%, from 4.9% to 12.3% and from 0.0% to 7.7% for BDE-28, BDE-47, BDE-99 and BDE-153, respectively. Therefore, the bioaccessibility of PBDEs in gastrointestinal gut would be significantly underestimated without calibration, especially for tri- and tetra-BDEs and soil samples with low TOC contents or high PBDEs concentrations. The corrected digestibility values of BDE-28, BDE-47, BDE-99 and BDE-153 were 21.9%-54.7%, 18.8%-43.1%, 13.4%-27.2% and 9.3%-19.9%, respectively. The results indicated that the PBDEs digestibility was negatively correlated with lgK(ow); whereas there was no significant correlation of PBDE bioaccessibility with TOC contents in soils or with initial concentrations of PBDEs, particularly for the highly brominated components.

pH-sensitive polydopamine nanocapsules for cell imaging and drug delivery based on folate receptor targeting.

A pH-triggered drug delivery system that can specially target to folate-receptors-overexpressing cancer cells was designed based on newly developed polydopamine capsules and folic acid. The polycapsules bioconjugates possess capabilities of high drug loading, enhanced folate-receptor-mediated cell uptake, and sustained drug release by intracellular pH changes. It was also found that the sustained release of drugs significantly increased reactive oxygen species (ROS) level in targeted cells. The efficient cell-specific endocytosis and intracellular pH-responsive controlled drug delivery of the capsules is promising for future in vivo therapeutic applications.