Tamoxifen resistance remains to be a huge obstacle in the treatment of hormone-dependent breast cancer, and this therefore highlights the dire need to explore the underlying mechanisms. The epithelial-mesenchymal transition (EMT) is a molecular process through which an epithelial cell transfers into a mesenchymal phenotype. Roles of EMT in embryo development, cancer invasion and metastasis have been extensively reported. Herein, we established tamoxifen-resistant MCF-7/TR breast cancer cells and showed that MCF-7/TR cells underwent EMT driven by enhanced endogenous TGF-β/Smad signaling. Ectopic supplement of TGF-β promoted in MCF-7 cells a mesenchymal and resistant phenotype. In parallel, we demonstrated that resveratrol was capable of synergizing with tamoxifen and triggering apoptosis in MCF-7/TR cells. Further Western blot analysis indicated that the chemosensitizing effects of resveratrol were conferred with its modulation on endogenous TGF-β production and Smad phosphorylation. In particular, 50 μM resveratrol had minor effects on MCF-7/TR cell proliferation, but could significantly attenuate endogenous TGF-β production and the Smad pathway, ultimately leading to reversion of EMT. Collectively, our study highlighted distinct roles of EMT in tamoxifen resistance and resveratrol as a potential agent to overcome acquired tamoxifen resistance. The molecular mechanism of resveratrol chemosensitizing effects is, at least in part, TGF-β/Smad-dependent.

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against both Gram-positive and Gram-negative bacteria. Because of its clinical efficacy, meropenem is an excellent choice for the treatment of serious infections in both adults and children. The knowledge of tissue concentrations of antibiotic in an infection site is valuable for the prediction of treatment outcome. The aim of the present study is to investigate the effect of borneol on the concentration of meropenem in rat brain and blood and to find the potential relationships of the combined use of medicine and traditional Chinese medicine. Analysis of meropenem in the dialysates was achieved using the microdialysis technique and HPLC. At 40 min after the administration of an intraperitoneal injection of meropenem, the concentration of meropenem in brain in borneol+meropenem group was 2.25 (0.35) μg ml(-1), which was significantly higher than that in meropenem group [1.20 (0.12) μg ml(-1); P< 0.01]. Within 80 min of drug administration, the AUCbrain/AUCblood (area under the curve, AUC) in the borneol+meropenem group was 1.2 times that of the meropenem group. Borneol can increase the concentration of meropenem in the cerebrospinal fluid, but has no influence on its blood concentration. This study represents a successful application of the microdialysis technique, which is an effective method for the study of pharmacokinetics of meropenem.

Background Vacuum sealing drainage (VSD) and epidermal growth factor (EGF) both play an important role in the treatment of wounds. This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF. Methods We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations (0, 1, 5, 10, and 100 ng/ml) and different EGF action times (2, 10, and 30 min). A full-thickness skin defect model was established using male, 30-week-old Bama pigs. The experiment included groups as follows: routine dressing change after covering with sterile auxiliary material (Control), continuous negative pressure drainage of the wound (VSD), continuous negative pressure drainage of the wound and injection of EGF 10 min followed by removal by continuous lavage (V + E 10 min), and continuous negative pressure drainage of the wound and injection of EGF 30 min followed by removal by continuous lavage (V + E 30 min). The wound healing rate, histological repair effect and collagen deposition were compared among the four groups. Results An EGF concentration of 10 ng/ml and an action time of 10 min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells. The drug dispersion effect was better than drug infusion after bolus injection effect, and the contact surface was wider. Compared with other groups, the V + E 10 min group promoted wound healing to the greatest extent and obtained the best histological score. Conclusions A recombinant human epidermal growth factor (rhEGF) concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro. VSD combined with rhEGF kept in place for 10 min and then washed, can promote wound healing better than the other treatments in vivo.

Background Given its narrow treatment window, high toxicity, adverse effects, and individual differences in its use, we collected and sorted data on tacrolimus use by real patients with kidney diseases. We then used machine learning technology to predict tacrolimus blood concentration in order to provide a basis for tacrolimus dose adjustment and ensure patient safety. Methods This study involved 913 hospitalized patients with nephrotic syndrome and membranous nephropathy treated with tacrolimus. We evaluated data related to patient demographics, laboratory tests, and combined medication. After data cleaning and feature engineering, six machine learning models were constructed, and the predictive performance of each model was evaluated via external verification. Results The XGBoost model outperformed other investigated models, with a prediction accuracy of 73.33%, F-beta of 91.24%, and AUC of 0.5531. Conclusions Through this exploratory study, we could determine the ability of machine learning to predict TAC blood concentration. Although the results prove the predictive potential of machine learning to some extent, in-depth research is still needed to resolve the XGBoost model’s bias towards positive class and thereby facilitate its use in real-world settings.

Twelve new steroidal saponins, including eleven furostanol saponins, terrestrinin J-T (1-11), and one spirostanol saponin, terrestrinin U (12), together with seven known steroidal saponins 13-19 were isolated from T. terrestris. The structures of the new compounds were established on the basis of spectroscopic data, including 1D and 2D NMR and HRESIMS, and comparisons with published data.