Borneol-modified docetaxel plus tetrandrine micelles for treatment of drug-resistant brain glioma.

OBJECTIVE: Glioma is the most common and deadly primary malignant tumor in adults. Treatment outcomes are ungratified due to the presence of blood-brain barrier (BBB), glioma stem cells (GSCs) and multidrug resistance (MDR). Docetaxel (DTX) is considered as a potential drug for the treatment of brain tumor, but its effectiveness is limited by its low bioavailability and drug resistance. Tetrandrine (TET) reverses the resistance of tumor cells to chemotherapy drugs. Borneol (BO) modified in micelles has been shown to promote DTX plus TET to cross the BBB, allowing the drug to better act on tumors. Therefore, we constructed BO-modified DTX plus TET micelles to inhibit chemotherapeutic drug resistance. SIGNIFICANCE: Provide a new treatment method for drug-resistant brain gliomas. METHODS: In this study, BO-modified DTX plus TET micelles were prepared by thin film dispersion method, their physicochemical properties were characterized. Its targeting ability was investigated. The therapeutic effect on GSCs was investigated by in vivo and in vitro experiments. RESULTS: The BO-modified DTX plus TET micelles were successfully constructed by thin film dispersion method, and the micelles showed good stability. The results showed that targeting micelles increased bEnd.3 uptake and helped drugs cross the BBB in vitro. And we also found that targeting micelles could inhibit cell proliferation, promote cell apoptosis and inhibit the expression of drug-resistant protein, thus provide a new treatment method for GSCs in vitro and in vivo. CONCLUSIONS: BO-modified DTX plus TET micelles may provide a new treatment method for drug-resistant brain gliomas.

Critical window for the association between early electronic screen exposure and hyperactive behaviors in preschool children.

Electronic screens have become an integral part of modern life, accompanied with growing concerns for children's neuropsychological development. This study aimed to evaluate the associations between measures of early life screen exposure and hyperactive behaviors among preschool children. The study also aimed to investigate their cumulative effects and the critical window for these associations. A cross-sectional survey was conducted among 52 625 mother-child dyads at preschools in LongHua District of Shenzhen, China. A self-administered structured questionnaire was used to assess socio-demographic characteristics, duration of children's electronic screen exposure in each of the first 3 years following birth and the presence of current hyperactive behaviors. A series of logistic regression models were used to examine the relationship between previous screen time and current hyperactive behaviors. A crossover analysis was used to explore the critical window for a significant relationship between screen time and hyperactive behaviors. We found that exposure to electronic screens in the first 3 years of life was associated with hyperactive behaviors in preschool children. A cumulative effect was shown in children with an average daily screen time less than 60 min, with adjusted ORs increasing from 1.262 to 1.989 as screen exposure years increased from 1 to 3 years. A critical window was identified in that children in the first 2 years after birth were vulnerable to electronic screen exposure. Exposure to televisions, mobile phones, and computers were all related to elevated risks for hyperactive behaviors. In conclusion, early screen exposure appears to increase the risk for hyperactive behaviors in preschool children with the presence of a cumulative effect, a critical window and different electronic screens having similar effects.

SENP1 has an important role in lung development and influences the differentiation of alveolar type 2 cells.

Post­translational modification via small ubiquitin­like modifier (SUMO) is involved in the regulation of various important cellular processes. SUMO modification can be regulated at the level of conjugation, and can also be reversed by the SUMO­specific proteases (SENPs). However, current studies of the regulation and function of SENP in lung development remain limited. In this study, the expression levels of SENP1 and SUMO1 were assessed during lung development in rats. SUMO1 modification occurred during lung development and changes in SENP1 expression were consistent with the changes in the presence of free SUMO1. In order to investigate the function of SENP1, alveolar type (AT) 2 cells were transfected with SENP1­targeting small interfering RNA, and the proliferation, apoptosis and differentiation function of AT2 cells was subsequently evaluated. Marked upregulation of conjugated SUMO1 was observed following SENP1 inhibition. Furthermore, depletion of SENP1 resulted in increased apoptosis, decreased proliferation and impaired differentiation status of AT2 cells. Thus, the results support that SENP1 is an essential regulator of the balance between SUMOylation and deSUMOylation during lung development, specifically affecting the proliferation and differentiation status of AT2 cells.