Celastrol alleviated acute kidney injury by inhibition of ferroptosis through Nrf2/GPX4 pathway.

Ferroptosis is an important pathological process in acute kidney injury (AKI) which could lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). As an active ingredient of Chinese medicine Tripterygium wilfordii, celastrol has been reported to alleviate inflammation and preclinical studies have confirmed its anticancer effect. In the present study, we investigated the renal protective effects of celastrol against cisplatin induced AKI. Mice were administrated cisplatin by intraperitoneal injection and we found that celastrol reduced serum levels of BUN and creatinine, inhibited renal dysfunction, inflammation and oxidative stress. In addition, renal iron accumulation and ferroptosis were significantly reduced by celastrol treatment. Further mechanistic analyses suggested that Nrf2 is essential for celastrol upregulated GPX4 to alleviate ferroptosis and reduction of LDH release, intracellular iron accumulation and lipid peroxidation. These findings expand the potential uses of celastrol for treatment of various kinds of AKI associated with ferroptosis.

Apatinib enhances chemosensitivity of acute myeloid leukemia hl60 cells to cytarabine by inducing apoptosis.

PURPOSE: To investigate the effect of apatinib combined with cytarabine on acute myeloid leukemia (AML) HL60 cells and its relevant mechanisms. METHODS: HL60 cells were treated with control, apatinib alone, cytarabine alone and apatinib combined with cytarabine. Cell proliferation in each group was detected via methy thiazolyl tetrazolium (MTT) assay, changes in the cell cycle and mitochondrial transmembrane potential in each group after treatment were detected via flow cytometry, and apoptosis was detected via Annexin V-PI double labeling. Moreover, changes in cell cycle-related proteins and apoptosis-associated proteins in each group after treatment were detected via Western blotting. RESULTS: MTT assay revealed that the sub-lethal dose of apatinib combined with cytarabine had a higher inhibitory rate on tumor cells than cytarabine alone. Cell cycle assay showed that apatinib combined with cytarabine could effectively arrest HL60 cells in G0/G1 phase in the combination group. In combination group, the expression level of the positive regulator cyclin D1 was decreased, while the expression levels of the negative regulators p21 and p27 were significantly up-regulated compared with those in single application groups. Results of apoptosis assay manifested that in the combination group, the mitochondrial transmembrane potential of HL60 cells could be synergistically destroyed, and the proportion of apoptotic cells was also obviously increased. Results of Western blotting demonstrated that the levels of apoptosis-associated proteins cleaved caspase-9, cleaved caspase-3, cleaved PARP and Bax in the combination group after treatment were remarkably up-regulated, while the Bcl-2 protein level was significantly down-regulated. CONCLUSION: Apatinib combined with cytarabine resists acute myeloid leukemia through synergistically regulating cell cycle and promoting apoptosis.

MiR-223 promotes oral squamous cell carcinoma proliferation and migration by regulating FBXW7.

Abnormally expressed microRNAs (miRNAs) contribute widely to human cancer, including oral squamous cell carcinoma (OSCC), by regulating their downstream targets. MiR-223 has been proved to be up-regulated in both gastric cancer and ovarian cancer. However, the effect of miR-223 on OSCC is still unclear. Here, we showed that miR-223 was over-expressed in OSCC tissues using qRT-PCR. Next, we investigated the biological mechanism of miR-223 in OSCC. The results demonstrated that miR-223 facilitated the cell proliferation and migration of OSCC using MTT assay and Transwell assay. Furthermore, we stated that the FBXW7 expression was decreased in OSCC and re-expression of FBXW7 inhibited the proliferation and migration of OSCC. In addition, FBXW7 mimic inversed the promotion effect of miR-223 in regulating of OSCC cells. In short, miR-223 promoted OSCC cell proliferation and migration by downregulating FBXW7, which provided a novel therapeutic strategy for OSCC.