MiR-494-3p mediates oxaliplatin resistance of colorectal cancer cells via PTEN/AKT pathway

Purpose: To unravel the influence of miR-494-3p on the insensitivity of colorectal cancer (CRC) cells to oxaliplatin.Methods: The mRNA level of miR-494-3p in oxaliplatin-resistant HT-29 cells was evaluated with reverse transcript-polymerase chain reaction (RT-PCR). The cells were treated with miR-494-3p suppressor or mimic, and then apoptotic changes were determined flow cytometrically. Resistancerelated gene expressions were measured using RT-PCR and western blotting. In addition, in vivo mouse experiments were conducted.Results: MiR-494-3p expression in oxaliplatin-resistant HT-29 cells was much higher than that in parental HT-29 cells, accompanied by increased levels of MRP, P-gp, and AKT phosphorylation (p-AKT), and decreased phosphatase and tensin homolog (PTEN) (p < 0.001). The miR-494-3p mimic suppressed oxaliplatin-induced parental HT-29 cell apoptosis, while miR-494-3p inhibitor promoted oxaliplatin-resistant HT-29 cell apoptosis and decreased the levels of p-AKT, MRP and P-gp, while upregulating PTEN (p < 0.001). Furthermore, AKT inhibitor had similar effects as miR-494-3p inhibitor (p < 0.001). Experiments using nude mice demonstrated that inhibition of miR-494-3p accentuated the sensitivity of oxaliplatin-resistant HT-29 cells to oxaliplatin (p < 0.05).Conclusion: Suppression of miR-494-3p attenuates oxaliplatin insensitivity to CRC cells via a mechanism which may involve PTEN/AKT pathway. Therefore, miR-494-3p may be an effective target for overcoming drug resistance of CRC

Long-term whole blood DNA preservation by cost-efficient cryosilicification

This work was supported by the National Natural Science Foundation of China (21972047 to W.Z., 52003086 to Q.L.), Guangdong Provincial Pearl River Talents Program (2019QN01Y314 to Q.L.), the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2019ZT08Y318 to W.Z.), Natural Science Foundation of Guangdong Province, China (2021A1515010724 to Q.L.), China Postdoctoral Science Foundation (2020M672625, 2021T140213 to Q.L.), Science and Technology Project of Guangzhou, China (202102020352 to W.Z., 202102020259 to Q.L.), the Fundamental Research Funds for the Central Universities of China. The authors thank the support from the Guangzhou Women and Children’s Medical Center and Laboratory Animal Research Center of the South China University of Technology. S.W. acknowledges funding from the Basque Government Industry Department under the ELKARTEK and HAZITEK programs.Deoxyribonucleic acid (DNA) is the blueprint of life, and cost-effective methods for its long-term storage could have many potential benefits to society. Here we present the method of in situ cryosilicification of whole blood cells, which allows long-term preservation of DNA. Importantly, our straightforward approach is inexpensive, reliable, and yields cryosilicified samples that fulfill the essential criteria for safe, long-term DNA preservation, namely robustness against external stressors, such as radical oxygen species or ultraviolet radiation, and long-term stability in humid conditions at elevated temperatures. Our approach could enable the room temperature storage of genomic information in book-size format for more than one thousand years (thermally equivalent), costing only 0.5 $/person. Additionally, our demonstration of 3D-printed DNA banking artefacts, could potentially allow 'artificial fossilization'.Publisher PDFPeer reviewe

Synthetic Biohybrids of Red Blood Cells and Cascaded‐Enzymes@ Metal–Organic Frameworks for Hyperuricemia Treatment

Abstract Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast‐acting and long‐lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded‐enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF‐8 framework‐based nanoparticles, have been fabricated based on a super‐assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF‐8 nanoparticles‐based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF‐8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by‐product H2O2. In vivo results demonstrate that the biohybrids can effectively normalize the UA level of an acute hyperuricemia mouse model within 2 h and possess a longer elimination half‐life (49.7 ± 4.9 h). They anticipate that their simple and general method that combines functional nanomaterials with living cell carriers will be a starting point for the development of innovative drug delivery systems