Glycyrrhizin alleviates radiation-induced lung injury by regulating the NLRP3 inflammasome through endoplasmic reticulum stress.

Objective: Radiation pneumonitis (RP) is the major adverse response of radiation therapy for thoracic malignant tumors, and there is a lack of effective interventions. The aim of this study was to investigate the radioprotective effect of Glycyrrhizin (GL) on RP and its potential mechanism. Method: The body weight and lung weight of mice were monitored. HE staining was used to observe lung injury, and the expression of endoplasmic reticulum (ER) stress biomarkers and the activation of NLRP3 inflammasome were determined by Western blotting and immunohistochemistry. Flow cytometry was performed to check MLE-12 apoptosis. ER stress activator, Tunicamycin (Tuni), was used to verify the potential mechanism of GL. A systemic pharmacology explored the potential targets and pathways of GL. Results: In this study, the lungs of irradiated mice showed significant pneumonic changes. In vivo and in vitro assay, NLRP3 inflammasome was significantly activated, the expression of ER stress biomarkers was elevated, flow cytometry confirms increased apoptosis in irradiated MLE-12 cells. GL inhibits the activation of NLRP3 inflammasome and ER stress pathways. Furthermore, systemic pharmacology revealed that the radioprotective effect of GL may be related to the MAPK signaling pathway. Conclusion: In the present study, the results indicated that GL may regulate NLRP3 inflammasome through ER stress, thus exerting irradiation-protective effects on RP, and the ER stress pathway may be a potential target for RP treatment.

Thioridazine combined with carboplatin results in synergistic inhibition of triple negative breast cancer by targeting cancer stem cells.

Cancer stem cells (CSCs) in triple-negative breast cancer (TNBC) are closely related to tumorigenesis and metastasis. Thioridazine (THZ) is a usual phenothiazine antipsychotic drug that can destroy CSCs. We aimed to explore whether THZ could sensitize metastatic TNBC cells, especially the CSCs, to carboplatin (CBP) treatment. Metastatic TNBC cells, 4T1 cells, and tumor-bearing mice were treated with THZ and CBP as monotherapy or combination therapy. MTT, flow cytometry, electron microscopy, immunohistochemistry and western blotting were applied to assess the cell viability, apoptosis, mitochondrial morphology and the relevant protein levels, respectively. Tumor size and lung metastasis under different treatments as well as tumorigenesis of residual tumor cells from each group were monitored. THZ combined with CBP inhibited 4T1 tumor cell proliferation and induced apoptosis by inhibiting the PI3K-AKT-mTOR pathway and activating estrogen receptor stress. THZ also showed strong activity against breast CSCs, THZ combined with CBP significantly destroyed cancer cells, inhibited lung metastasis and relieved the tumor burden; Our data demonstrated that THZ can sensitize TNBC cells to CBP treatment and this combination therapy may provide a bright strategy for TNBC treatment by targeting both cancer cells and CSCs.

Coordination environment evolution of Eu3+ during the dehydration and re-crystallization processes of Sm(1-x)Eu(x)[B9O13(OH)4]·H2O by photoluminescent characteristics.

There are limited photoluminescence (PL) studies for rare earth borates with crystalline water molecules, which are usually supposed to have low PL efficiency because the vibrations of H2O or -OH may lead to emission quenching. We investigated the PL properties of Sm(1-x)Eu(x)[B9O13(OH)4]·H2O (x = 0-1.00) and their dehydrated products α-Sm(1-x)Eu(x)B5O9. There is no quenching effect in those studied polyborates because the large borate ionic groups isolate the Eu(3+) activators very well. Sm(3+) and Eu(3+) are basically separated luminescent activators. Comparatively, Sm(3+) shows a very small emission intensity, which can be almost ignored, therefore our interest is focused on the Eu(3+) luminescence. By TG-DSC and powder XRD experiments, we defined three weight-loss steps for Eu[B9O13(OH)4]·H2O and a re-crystallization process to α-EuB5O9, during which luminescent spectra of Eu(3+) are recorded. It shows an interesting variety and therefore is a good medium to understand the coordination environment evolution of Eu(3+), even for the intermediate amorphous phase. In fact, the coordination symmetry of Eu(3+) in the amorphous state is the lowest. The high efficiency of the f-f transitions and large R/O value (3.8) imply this amorphous phase is potentially a good red-emitting UV-LED phosphor. Anhydrous α-EuB5O9 shows the highest luminescent efficiency excited by Eu(3+) CT transition. In addition, α-Sm(1-x)Eu(x)B5O9 was synthesized by a sol-gel method directly for the first time, and α-EuB5O9 shows superior PL properties due to its better crystallinity. A lot of hydrated polyborates with crystalline water molecules remain unexplored and our study shows their potential as good phosphors.