Development of a MD-LC-MS/MS Method to Analyze 3 Bioactive Compounds in Huoxuezhitong Rubber Patch and Application to a Pharmacokinetic Study in Rats

Huoxuezhitong rubber patch, a well-known traditional Chinese medicine (TCM) prescription, is utilized to treat pain and inflammation. In this study, a microdialysis-ultra-high-performance liquid chromatography-tandem mass spectrometry (MD-LC-MS/MS) method was designed for the simultaneous determination of active constituents in the rubber patch, such as paeonol (Pae), eugenol (Eug), and piperine (Pip). A microdialysis probe was implanted in the subcutaneous tissue of a rat, which is intended to detect the subcutaneous concentrations of target components. Saline containing 30% ethanol acted as perfusion fluid. Analytes in the microdialysate were completely separated over an ACQITY UPLC RBEH C18 column (2.1mm×100mm, 1.7μm). The mobile phase was composed of 0.01% ammonia aqueous and acetonitrile-0.01% ammonia with gradient elution. The single-run analysis time was 10.0 minutes. The linear regression displayed good linear relationships in the ranges of 0.25–100 ng/mL for paeonol and eugenol and 0.001–5 ng/mL for piperine. The interday and intraday precision of the quality control samples exhibited relative standard deviations (RSD) Pip > Eug. The rank order of AUC0-720 and Cmax was both Eug > Pae > Pip. MRT0-∞ of Pip was higher than that of Pae and Eug. Eugenol showed a faster elimination and a shorter half-life. Paeonol showed a stronger drug reservoir function after removing the drug source

Correction to: M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway

An amendment to this paper has been published and can be accessed via the original article

Radiosensitization of clioquinol and zinc in human cancer cell lines

Abstract Background We previously reported that clioquinol acts as a zinc ionophore and inhibits the NF-κB signalling pathway. Other research has demonstrated that zinc deficiency plays a vital role in the occurrence and development of some solid tumours, and intracellular zinc supplementation may reverse this process and enhance the tumour sensitivity to anticancer treatment. Thus, we investigated the radiosensitization effects of clioquinol combined with zinc on HeLa and MCF-7 cells in vitro. Methods The dose effect of growth inhibition of clioquinol combined with zinc on cell viability was determined by a cell counting kit 8 (CCK-8) assay. The radiosensitization effect of clioquinol combined with zinc and/or MG132 in HeLa and MCF-7 cells was detected by the clonogenic assay. The cell cycle distribution and apoptosis of clioquinol combined with zinc on HeLa cells were analyzed by flow cytometry. A luciferase reporter construct was used to study the effect of clioquinol combined with zinc on NF-κB activity in HeLa cells. DNA double-strand breaks were detected by immunofluorescence. The mRNA and protein levels of ATM were analyzed by quantitative real-time PCR and Western blotting, respectively. Results Our research showed that clioquinol combined with zinc markedly increased the radiosensitivity of HeLa and MCF-7 cells in low toxic concentrations and resulted in a post-irradiation decrease in G2 phase arrest and an increase in apoptosis. Clioquinol combined with zinc also inhibited NF-κB activation, decreased ATM expression and increased DNA double-strand breaks (DSBs) induced by ionizing radiation. Conclusions These findings indicated that clioquinol combined with zinc enhanced the radiosensitivity of HeLa and MCF-7 cells by the down-regulation of ATM through the NF-κB signalling pathway

Simulation model of a non-contact triboelectric nanogenerator based on electrostatic induction

Based on the coupling effects of contact electrification and electrostatic induction, a triboelectric nanogenerator (TENG) can convert mechanical energy into electric power, which is at the cutting edge of alternative energy technology. Although a considerable number of TENGs with different configurations have been designed, some of them however, which only depend on the electrostatic induction effect have not received enough attention. Here, a non-contact TENG model consists of copper rings and charged dielectric sphere is presented, which is aimed at exploring the working process of TENGs caused by electrostatic induction. Two classical models, including vertical and horizontal double copper rings models are also proposed. Relevant advanced and accurate models of TENGs have been established through the finite element method. We anticipate that the constructed model and theoretical analysis are helpful for the design of non-contact model TENGs with complicated geometric construction, and expand their applications in various fields. (Figure presented.)

Anti-tumour activity of zinc ionophore pyrithione in human ovarian cancer cells through inhibition of proliferation and migration and promotion of lysosome-mitochondrial apoptosis

AbstractZinc pyrithione (ZPT) is widely used as an antimicrobial. Zinc is a necessary trace element of the human whose homeostasis associated with several cancers. However, the anticancer effect of increased Zinc in ovarian cancer is still unclear. This study focussed on the anti-tumour effects of ZPT combined with Zinc in SKOV3 and SKOV3/DDP cells. The cell viability, apoptosis, migration, and invasion assays were detected by CCK-8, flow cytometry, wound healing and transwell assay, respectively. The distribution of Zinc in cells was monitored by staining of Zinc fluorescent dye and lysosome tracker. The changes in lysosomal membrane stability were reflected by acridine orange fluorescence and cathepsin D reposition. Expression of the proteins about invasion and apoptosis was evaluated by western blot. The results indicated that ZPT combined with Zinc could notably reduce cell viability, inhibit migration and invasion in SKOV3 and SKOV3/DDP cells. Besides, ZPT performed as a Zinc carrier targeted lysosomes, caused the increase of its membrane permeability and the release of cathepsin D accompanied by mitochondrial apoptosis in SKOV3/DDP cells. In conclusion, our work suggests that ZPT combined with Zinc could inhibit proliferation, migration, invasion, and promote apoptosis by trigger the lysosome-mitochondrial apoptosis pathway in ovarian carcinoma

Feasibility of a novel dose fractionation strategy in TMI/TMLI

Abstract Background To report our experience in planning and delivering total marrow irradiation (TMI) and total marrow and lymphatic irradiation (TMLI) in patients with hematologic malignancies. Methods Twenty-seven patients undergoing bone marrow transplantation were treated with TMI/TMLI using Helical Tomotherapy (HT). All skeletal bones exclusion of the mandible comprised the treatment target volume and, for TMLI, lymph node chains, liver, spleen and/or brain were also included according to the clinical indication. Planned dose of 8Gy in 2 fractions was delivered over 1 day for TMI while 10Gy in 2 fractions BID was used for TMLI. Organs at risk (OAR) contoured included the brain, brainstem, lens, eyes, optic nerves, parotids, oral cavity, lungs, heart, liver, kidneys, stomach, small bowel, bladder and rectum. In particular, a simple method to avoid hot or cold doses in the overlapping region was implemented and the plan sum was adopted to evaluate dose inhomogeneity. Furthermore, setup errors from 54 treatments were summarized to gauge the effectiveness of immobilization. Results During the TMI/TMLI treatment, no acute adverse effects occurred during the radiation treatment. Two patients suffered nausea or vomiting right after radiation course. For the 9 patients treated with TMI, the median dose reduction of major organs varied 30–65% of the prescribed dose, substantially lower than the traditional total body irradiation (TBI). Meanwhile, average biological equivalent doses to OARs with 8Gy/2F TMI approach were not different from the conventional 12Gy/6F TMI approach. In the dose junction region, the 93% of PTV was covered by the prescribed dose without obvious hotspots. For the 27 patients, the overall setup corrections were lower than 3 mm except those in the SI direction for abdomen-pelvis region, demonstrating excellent immobilization. Conclusion The present study confirmed the technical feasibility of HT-based TMI/TMLI delivering 8-10Gy in 2 fractions over 1 day. For patients undergoing hematopoietic cell transplantation the proposed 8Gy/2F TMI (or 10Gy/2F TMLI) strategy may be a novel approach to improve delivery efficiency, increase effective radiation dose to target while maintaining low risk of severe organ toxicities

Oral pH value predicts the incidence of radiotherapy related caries in nasopharyngeal carcinoma patients

Abstract Radiotherapy-related caries is a complication of radiotherapy for nasopharyngeal carcinoma; however, factors influencing the occurrence, accurate prediction of onset, and protective factors of radiotherapy-related caries remain unclear. This study analyzed risk factors, disease predictors, and protective factors for radiotherapy-related caries in nasopharyngeal carcinoma. This prospective study included 138 nasopharyngeal carcinoma patients receiving radical radiotherapy at our hospital during June 2012–December 2016 and were followed up for dental caries. Patients’ clinical data on radiotherapy were collected, dynamic monitoring was performed to assess changes in oral pH values, and a questionnaire survey was administered to collect patients’ lifestyle habits. Time-dependent cox regression trees, event-free Kaplan–Meier curve, Mann–Whitely U test were used to analysis the results. The median follow-up time was 30 (12–60) months. Radiotherapy-related caries occurred in 28 cases (20.3%). Univariate analyses showed that radiotherapy-related caries was associated with patient’s age, oral saliva pH value, green tea consumption, and radiation dose to sublingual glands, but not with the radiation dose to the parotid and submandibular glands. Multivariate analysis showed that oral saliva pH value [hazard ratio (HR) = 0.390, 95% confidence interval = 0.204–0.746] was an independent prognostic factor for radiotherapy-related caries. Patients with oral saliva pH values ≤ 5.3 in the 9th month after radiotherapy represented a significantly higher risks for radiotherapy-related caries (p < 0.001). Green tea consumption was associated with the occurrence of radiotherapy-related caries, and oral saliva pH values could predict the occurrence of radiotherapy-related caries. Limiting radiation doses to sublingual glands can reduce the occurrence of radiotherapy-related caries