Phloretin-induced STAT3 inhibition suppresses pancreatic cancer growth and progression via enhancing Nrf2 activity.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a malignant pancreatic tumor charactered by a rapid progression and high lethal rate. Hyperactivation of STAT3 signaling exerts a vital effect on the growth and progression of PDAC. While dietary flavonoid phloretin has anti-inflammatory and antioxidant activities, it remains unclear whether phloretin has anti-tumor effects on PDAC. PURPOSE: The focus of the present study is to elucidate the effects of phloretin on PDAC and investigate its underlying molecular mechanisms. STUDY DESIGN AND METHODS: Effect of phloretin were assessed in the pancreatic cancer cells (PCCs) by colony formation assay, real-time cell analysis, flow cytometry, Immunofluorescence staining, and cell migration assay. The expressions of mRNA and protein were respectively analyzed by quantitative PCR and Western blotting. A xenograft model was used to appraise the antitumor efficacy of phloretin. RESULTS: Phloretin treatment significantly restrained cell viability and metastasis, induced DNA injury and ROS accumulation, and triggered mitochondrial-dependent apoptosis in PCCs. Mechanistically, phloretin exhibits anti-tumor potential via inactivating STAT3 signaling and enhancing Nrf2 activity. STAT3 overexpression and Nrf2 silencing partially relieved phloretin-induced inhibition on cell growth and metastasis in PCCs. Phloretin remarkably blocked pancreatic tumor growth and metastasis in vivo. CONCLUSIONS: Phloretin suppresses pancreatic cancer growth and progression through inhibition of STAT3 mediated by enhancing Nrf2 activity. Phloretin may serve as a promising therapeutic agent for PDAC.

Amino Acid Metabolism-Related lncRNA Signature Predicts the Prognosis of Breast Cancer.

Background and Purpose: Breast cancer (BRCA) is the most frequent female malignancy and is potentially life threatening. The amino acid metabolism (AAM) has been shown to be strongly associated with the development and progression of human malignancies. In turn, long noncoding RNAs (lncRNAs) exert an important influence on the regulation of metabolism. Therefore, we attempted to build an AAM-related lncRNA prognostic model for BRCA and illustrate its immune characteristics and molecular mechanism. Experimental Design: The RNA-seq data for BRCA from the TCGA-BRCA datasets were stochastically split into training and validation cohorts at a 3:1 ratio, to construct and validate the model, respectively. The amino acid metabolism-related genes were obtained from the Molecular Signature Database. A univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression, and a multivariate Cox analysis were applied to create a predictive risk signature. Subsequently, the immune and molecular characteristics and the benefits of chemotherapeutic drugs in the high-risk and low-risk subgroups were examined. Results: The prognostic model was developed based on the lncRNA group including LIPE-AS1, AC124067.4, LINC01655, AP005131.3, AC015802.3, USP30-AS1, SNHG26, and AL589765.4. Low-risk patients had a more favorable overall survival than did high-risk patients, in accordance with the results obtained for the validation cohort and the complete TCGA cohort. The elaborate results illustrated that a low-risk index was correlated with DNA-repair-associated pathways; a low TP53 and PIK3CA mutation rate; high infiltration of CD4+ T cells, CD8+ T cells, and M1 macrophages; active immunity; and less-aggressive phenotypes. In contrast, a high-risk index was correlated with cancer and metastasis-related pathways; a high PIK3CA and TP53 mutation rate; high infiltration of M0 macrophages, fibroblasts, and M2 macrophages; inhibition of the immune response; and more invasive phenotypes. Conclusion: In conclusion, we attempted to shed light on the importance of AAM-associated lncRNAs in BRCA. The prognostic model built here might be acknowledged as an indispensable reference for predicting the outcome of patients with BRCA and help identify immune and molecular characteristics.

Controllable synthesis of CsPbI3 nanorods with tunable photoluminescence emission.

So far the controllable synthesis of one-dimensional (1D) CsPbI3 nanocrystals still remains a challenge due to the fast reaction kinetics of the iodine system as compared with other halide perovskites. Here we report the direct synthesis of high-quality 1D CsPbI3 nanorods by a facile solvothermal method. The as-prepared CsPbI3 nanorods show high purity and uniform morphology with ultrafine diameters down to ∼5 nm. By simply changing the solvothermal reaction conditions, fine-tuning of the sizes of the CsPbI3 nanorods can be well achieved, which leads to the successful modulation of their photoluminescence (PL) emission. The solvothermal reaction offers relatively low crystal growth rate, which is of great importance for the size control of the CsPbI3 nanocrystals. PL quantum yields (PLQYs) and lifetime results indicate that the obtained nanorods maintain a good surface state over long reaction time. Our work not only provides a reliable means for the synthesis of 1D iodine-related perovskites, but also expands the study of size-related PL properties on perovskites nanocrystals.

Solvothermal synthesis of Mn-doped CsPbCl3 perovskite nanocrystals with tunable morphology and their size-dependent optical properties.

Doping metal ions in inorganic halide perovskite (CsPbX3, X = Cl, Br, I) nanocrystals (NCs) endows the NCs with unique optical characteristics, and has thus attracted immense attention. However, controllable synthesis of high-quality doped perovskite NCs with tunable morphology still remains challenging. Here, we report a facile, effective and unified strategy for the controllable synthesis of Mn-doped CsPbCl3 quantum dots (QDs) and nanoplatelets (NPLs) via a single-step solvothermal method. The incorporation of Mn2+ into CsPbCl3 NCs introduces new broad photoluminescence (PL) emission from Mn2+ while maintaining the structure of host CsPbCl3 NCs nearly intact. The PL intensity, emission peak position and size of the NCs can be accurately adjusted by altering the experimental parameters such as Mn-to-Pb feed ratio and reaction time. Especially, by changing the amount of ligands, Mn-doped CsPbCl3 QDs, NPLs or their mixtures can be obtained. Both of the Mn-doped QDs and NPLs exhibit a size-dependent quantum confinement effect, which is confirmed by the relationship between the size of NCs and the exciton emission peaks. The solvothermal reaction condition plays an important role for the precise control of the structure, morphology and PL properties of the Mn-doped NCs. The as-prepared Mn-doped CsPbCl3 NPLs with thickness down to ∼2 nm exhibit a PL quantum yield (PLQY) of more than 22%. This work introduces a new strategy for the controllable synthesis of Mn-doped perovskite NCs, which provides ideas for the in-depth study of the dope-and-grow process and can be extended to approaches of doping other metal ions.

Solvothermal synthesis of cesium lead halide perovskite nanowires with ultra-high aspect ratios for high-performance photodetectors.

One-dimensional (1D) inorganic perovskite nanowires (NWs) have attracted promising attention for application in the fields of photodetection, lasers and lighting due to their outstanding optoelectronic properties. However the direct synthesis of highly pure all-inorganic perovskite NWs with well-defined morphologies and compositions still remains challenging. Here we report the controllable synthesis of brightly emitting cesium lead halide CsPbX3 (X = Cl, Br) NWs and their assembly into high-performance photodetector nanodevices. High quality CsPbX3 NWs have been directly synthesized via a solvothermal method without using post-synthetic anion-exchange reactions. The NWs are single-crystalline, with uniform diameters of ∼10 nm and lengths of up to tens of microns, showing ultra-high aspect ratios. Both CsPbCl3 and CsPbBr3 NWs show excellent photoluminescence (PL) characteristics with narrow emission spectra and high PL quantum yields (PLQYs). The photodetectors constructed on the CsPbX3 NWs and interdigital electrodes (with interdigitation widths up to 100 µm) exhibit promising photoelectric properties, achieving high switching ratios (5.8 × 103 for CsPbCl3 NW devices and 1.1 × 103 for CsPbBr3 NW devices) and fast response time. The present solvothermal approach is controllable, convenient, and is easily realized for quantifiable preparation, and can further promote the application of the all-inorganic perovskite NWs in the optoelectronic field.