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Lapatinib, an oral tyrosine kinase inhibitor used as a first-line treatment for HER2-positive breast cancer, has been reported to be associated with hepatotoxicity; however, the underlying mechanisms remain unclear. In this study, we report that lapatinib causes cytotoxicity in multiple types of hepatic cells, including primary human hepatocytes, HepaRG cells, and HepG2 cells. A 24-h treatment with lapatinib induced cell cycle disturbances, apoptosis, and DNA damage, and decreased the protein levels of topoisomerase in HepG2 cells. We investigated the role of cytochrome P450 (CYP)-mediated metabolism in lapatinib-induced cytotoxicity using our previously established HepG2 cell lines, which express each of 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). We demonstrate that lapatinib is metabolized by CYP1A1, 3A4, 3A5, and 3A7. Among these, lapatinib-induced cytotoxicity and DNA damage were attenuated in cells overexpressing CYP3A5 or 3A7. Additionally, we measured the production of three primary metabolites of lapatinib (O -dealkylated lapatinib, N -dealkylated lapatinib, and N -hydroxy lapatinib) in CYP1A1-, 3A4-, 3A5-, and 3A7-overexpressing HepG2 cells. We compared the cytotoxicity of lapatinib and its 3 metabolites in primary human hepatocytes, HepaRG cells, and HepG2 cells and demonstrated that N -dealkylated lapatinib is more toxic than the parent drug and the other metabolites. Taken together, our results indicate that lapatinib-induced cytotoxicity involves multiple mechanisms, such as apoptosis and DNA damage; that N -dealkylated lapatinib is a toxic metabolite contributing to the toxic effect of lapatinib; and that CYP3A5- and 3A7-mediated metabolism plays a role in attenuating the cytotoxicity of lapatinib. [ABSTRACT FROM AUTHOR]

Herein, the effect of Cr2O3 on the crystallization and flow behavior of CaO–SiO2–Al2O3–Na2O–CaF2 continuous casting mold slags is investigated. The viscosity in the slag at 1200–1500 °C is measured by the rotating cylinder method and a quantitative relationship between the viscosity and the Raman structure Q3/Q2 is constructed. The time–temperature–transformation and continuous cooling transformation diagrams for various slags are obtained using a single hot‐thermocouple technique. The results show that with the crystallization temperature decreases, it can be observed that the crystal growth mode gradually changes from 3D spherical and 2D massive to 1D needle‐like. The study finds the transition from network modifier to network forming agent in the slag for Cr2O3 content from 0 to 3 wt%. The Cr2O3 added to 1–2 wt% decreases the viscosity and promotes crystallization. The viscosity increases and the crystallization is inhibited when the content of Cr2O3 increases to 3 wt%. Meanwhile, when Cr2O3 is added to 3 wt%, the Cr2O3 crystalline phase precipitates except for the main crystalline phase 2CaO·SiO2. [ABSTRACT FROM AUTHOR]

Numerous investigations proposed that the dissolution of chromite ore is the rate‐controlling step for the smelting reduction of chromite ore. The mechanism of chromite ore dissolution in the binary CaO‐SiO2 system is presented. The effect of basicity, temperature, and reducing conditions on chromite ore dissolution is elaborated. The solubility of chromite ore increases considerably when the basicity increases from 0.56 to 0.65. However, the solubility of chromite ore decreases when the basicity further increases from 0.65 to 0.74. The positive effect of reducing conditions on the solubility of chromite ore is evident. The maximum dissolved Cr2O3 in slag under reducing conditions by using a graphite crucible reaches 2.6 wt% after 15 min of dissolution. The element diffusion behavior at the chromite/slag interface is elaborated through SEM‐EDS technology. The analysis suggests that the rate‐controlling step in the early stage is the interface dissolution reaction. After a certain time, the rate‐controlling step becomes the mass transfer of Cr2O3 from the chromite ore to the chromite/slag interface. The activation energy of the dissolution reaction is Er$E_{\text{r}}$ = 285.29 kJ mol−1. [ABSTRACT FROM AUTHOR]

Baicalein is a plant‐derived compound, it has widespread attention among biomedical researchers due to its biocompatibility and efficient biological activities. But it has non‐solubility in physiological conditions and short bioavailability in the clinical process. The Discovery of a stimuli‐based drug delivery system (DDS) is a perfect strategy to improve the bioactivity of baicalin in post‐caesarean section wound care. We prepared a baicalein‐encapsulated pH‐responsive DDS with a zeolite imidazole framework‐8 (ZIF‐8) as a carrier. We investigated the material characteristics of DDS in terms of crystal structure, surface area morphology, particle size, FTIR, UV–vis, Powder XRD, and BET analysis techniques. The in vitro cytotoxicity, biocompatibility, and cell proliferation properties of BA@ZIF‐8 were assessed against human fibroblast L929 cells. In vitro studies showed that BA@ZIF‐8 nanocomposite significantly enhanced the biocompatibility against L929 cells after 72 h post‐exposure. The pH‐responsive drug release kinetics shows excellent baicalein release under acidic conditions and without unwanted drug release in physiological conditions. Wound scratch assay results revealed, that BA@ZIF‐8 nanocomposite‐treated cells exhibit the fastest cell proliferation and migration process in a very short period. In the antibacterial activity study, nanocomposite exposed dose depended on inhibition against wound infectious pathogens. The overall study signifies that BA@ZIF‐8 nano‐DDSs are effective and suitable DDS for stimuli‐based post‐caesarean section wound care. [ABSTRACT FROM AUTHOR]