Near-Infrared-II Light Induced Mild Hyperthermia Activate Cisplatin-Artemisinin Nanoparticle for Enhanced Chemo/Chemodynamic Therapy and Immunotherapy.

Chemodynamic therapy (CDT) is an effective cancer treatment that uses Fenton reaction to induce cancer cell death. Current clinical applications of CDT are limited by the dependency of external supply of metal ions as well as low catalytic efficiency. Here, a highly efficient metal-free CDT by using endoperoxide bridge-containing artesunate as free radical-generating substance is developed. A Pt(IV) prodrug (A-Pt) containing two artesunate molecules in the axial direction is synthesized, which can be decomposed into cisplatin and artesunate under reducing intracellular environment in tumor cells. To improve the catalytic efficiency for Fenton reaction, a near-infrared-II (NIR-II) photothermal agent IR1048 is incorporated to achieve a mild hyperthermia effect. By encapsulating the A-Pt and IR1048 with human serum albumin, A-Pt-IR NP are formulated for efficient drug delivery in 4T1 tumor-bearing mice. NIR-II light irradiation of A-Pt-IR NP treated mice show accelerated Fenton reaction. In addition, A-Pt-IR NP could also induce strong immunogenic cell death, which effectively reverses the immunosuppressive tumor microenvironment, and augments antitumor immunity. This study demonstrates that A-Pt-IR NP are potent biodegradable NIR-II active chemotherapy/CDT nanomedicine for clinical translation.

Xiao-Yao-San reduces blood-brain barrier injury induced by chronic stress in vitro and vivo via glucocorticoid receptor-mediated upregulation of Occludin.

Blood-brain barrier (BBB) is a barrier which maintains the material exchange balance of brain microenvironment and could be destroyed by chronic stress (CS). Glucocorticoids (GCs) can mimic the chronic stress induced damage to BBB. GCs induced BBB trauma models in vitro and in vivo to explore the effects of the traditional medicine Xiao-Yao-San (XYS). In this research, we found CS could injure the BBB to change the biochemical index, which could be reversed by XYS in vitro. The abilities of cell proliferation, invasion, and the expression of tight junction related genes (Occludin, Claudin, JAM-1 and ZO-1) were suppressed by CS and the trauma could be reversed by XYS partly. It was showed that GRs interacted with Occludin directly and inhibited Occluding expression. In rats BBB trauma model, the GC content was deceased and BBB permeability was repaired by XYS. The expression of Occludin, Claudin, JAM-1 and ZO-1 were increased in the treatment of XYS. In our research, it shown that XYS affect the content of the GC and GR which interacted with Occludin directly for the first time. In addition, we also found that XYS could reduce BBB injury induced by CS via GR in BBB model in vitro. Therefore, it proves that XYS is a potential BBB repair medicine and may help to elucidate mechanism of brain pathology.

miR-221-5p acts as an oncogene and predicts worse survival in patients of renal cell cancer.

BACKGROUND: Renal cell carcinoma(RCC) is one of the most common malignancies in kidney, and usually leads to poor prognosis. Therefore, identifying novel biomarkers for predicting the progression and prognosis of RCC is essential. The purpose of this study is aimed to evaluate the function of miR-221-5p in RCC and the clinical value of miR-221-5p in RCC prognosis after surgery. MATERIALS AND METHODS: In our study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay, and flow cytometry assay were performed to explore miR-221-5p expression level and its proliferation, migration and apoptosis in clear cell RCC(ccRCC). Besides, we collected 196 formalin-fixed and paraffin-embedded (FFPE) tissue samples of patients who received partial or radical nephrectomy from May 2006 to October 2016 at Shenzhen Traditional Chinese Medicine Hospital and People's Liberation Army 303 Hospital. The relative levels of miR-221-5p from the FFPE tissue samples was detected by RT-qPCR. The Kaplan-Meier method, Cox regression analyses, and ROC curve analysis were performed to approve the effect of the miR-221-5p expression on patient survival. RESULTS: In our study, we found that miR-221-5p is significantly upregulated in ccRCC tissues and ccRCC cell lines. Moreover, miR-221-5p promotes cell proliferation, mobility, and inhibits cell apoptosis in 786-O and ACHN cell lines. The Kaplan-Meier analysis indicated that patients with high expression of miR-221-5p had a significantly poor prognosis (P = 0.013). The Cox regression analyses showed that patients with high expression of miR-221-5p remained to have a shorter overall survival (P = 0.025). The ROC curve of miR-221-5p expression combined with tumor stage showed an area under the curve of 0.658 (P < 0.001). CONCLUSION: Our results indicated that miR-221-5p might not only be an oncogene in ccRCC cells but also might be an independent prognosis factor of ccRCC.