Decellularized Extracellular Matrix for Remodeling Bioengineering Organoid's Microenvironment.

Over the past decade, stem cell- and tumor-derived organoids are the most promising models in developmental biology and disease modeling, respectively. The matrix is one of three main elements in the construction of an organoid and the most important module of its extracellular microenvironment. However, the source of the currently available commercial matrix, Matrigel, limits the application of organoids in clinical medicine. It is worth investigating whether the original decellularized extracellular matrix (dECM) can be exploited as the matrix of organoids and improving organoid construction are very important. In this review, tissue decellularization protocols and the characteristics of decellularization methods, the mechanical support and biological cues of extraccellular matrix (ECM), methods for construction of multifunctional dECM and responsive dECM hydrogel, and the potential applications of functional dECM are summarized. In addition, some expectations are provided for dECM as the matrix of organoids in clinical applications.

Aptamer functionalized nucleic acid nano drug for targeted synergistic therapy for colon cancer.

Due to its complicated pathophysiology, propensity for metastasis, and poor prognosis, colon cancer is challenging to treat and must be managed with a combination of therapy. Using rolling circle transcription (RCT), this work created a nanosponge therapeutic medication system (AS1411@antimiR-21@Dox). Using the AS1411 aptamer, this approach accomplished targeted delivery to cancer cells. Furthermore, analysis of cell viability, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) content, and mitochondrial membrane potential (MMP) levels revealed that functional nucleic acid nanosponge drug (FND) can kill cancer cells. Moreover, transcriptomics uncovered a putative mechanism for the FND anti-tumor effect. These pathways, which included mitotic metaphase and anaphase as well as the SMAC-mediated dissociation of the IAP: caspase complexes, were principally linked to the cell cycle and cell death. In conclusion, by triggering cell cycle arrest and apoptosis, the nano-synergistic therapeutic system allowed for the intelligent and effective targeted administration of RNA and chemotherapeutic medicines for colon cancer treatment. The system allowed for payload efficiency while being customizable, targeted, reliable, stable, and affordable.

Current progress of miRNA-derivative nucleotide drugs: modifications, delivery systems, applications.

INTRODUCTION: miRNA-derivative clinical nucleotide drugs (mdCNDs) effectively treat several diseases, with numerous undergoing clinical trials. In early-stage trials in disease therapeutics, such as malignant pleural mesothelioma and hepatic virus C infection, mdCND's therapeutic potency is undeniably good for effectiveness and safety. AREAS COVERED: Fifteen mdCNDs undergoing clinical trials are introduced in this review. MiRNA modifications methods have been summarized, including phosphorothioate, cholesterol, locked nucleic acid, 2'-O-methyl, N,N-diethyl-4-(4-nitronaphthalen1-ylazo)-phenylamine modifications, and many more. Moreover, delivery systems, including self-assembled, inorganic ions nanoparticles, exosomes, and lipid-based nanosystems for mdCNDs targeted delivery, are presented. Among that, EnGeneIC, N-Acetylgalactosamine, liposomal nanoparticles, and cholesterol-conjugated for mdCNDs delivery are currently undergoing clinical trials. The pH, light, temperature, redox-responsive, enzyme, and specific-substance modes to trigger the release of miRNAs to target sites on-demand and the prospects of mdCNDs are discussed in this review. EXPERT OPINION: mdNCDs are one type of promising clinical drugs, however, it is still in the infancy. During the development process, it is imperative to advance in modifying miRNAs, especially at the 5'-end, to enhance targetability and stability against nucleases, develop a stimuli-responsive mode to control the release of mdCNDs to tissue cell-type-specific sites.

Cell-specific aptamers as potential drugs in therapeutic applications: A review of current progress.

Cell-specific aptamers are a promising emerging player in the field of disease therapy. This paper reviews the multidimensional research progress made in terms of their classification, modification, and application. Based on the target location of cell-specific aptamers, it is defined and classified cell-specific aptamers into three groups including aptamers for cell surface markers, aptamers for intracellular components, and aptamers for extracellular components. Moreover, the modification methods of aptamers to achieve improved stability and affinity are concluded. In addition, recent advances in the application of cell-specific aptamers are discussed, mainly focusing on the increasing research attraction of cell state improving helpers and cell recruitment mediators in the improvement of cellular microenvironments to achieve successful disease therapy. This review also highlights 11 types of clinical aptamer drugs. Finally, the challenges and future directions of potential clinical applications are presented. In summary, we believe that cell-specific aptamers are promising drugs in disease therapy.

Multidimensional analysis of the epigenetic alterations in toxicities induced by mycotoxins.

Mycotoxins contaminate all types of food and feed, threatening human and animal health through food chain accumulation, producing various toxic effects. Increasing attention is being focused on the molecular mechanism of mycotoxin-induced toxicity in all kinds of in vivo and in vitro models. Epigenetic alterations, including DNA methylation, non-coding RNAs (ncRNAs), and protein post-translational modifications (PTMs), were identified as being involved in various types of mycotoxin-induced toxicity. In this review, the emphasis was on summarizing the epigenetic alterations induced by mycotoxin, including aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEA), fumonisin B1 (FB1), and deoxynivalenol (DON). This review summarized and analyzed the roles of DNA methylation, ncRNAs, and protein PTMs after mycotoxin exposure based on recently published papers. Moreover, the main research methods and their deficiencies were determined, while some remedial suggestions are proposed. In summary, this review helps to understand better the epigenetic alterations induced by the non-genotoxic effects of mycotoxin.

Exosomes mediated the delivery of ochratoxin A-induced cytotoxicity in HEK293 cells.

Ochratoxin A (OTA) is one of the mycotoxins, which widely pollutes food systems and seriously threatens human health. OTA's target organ is the kidney. Exosome, as one of the extracellular vesicles, could be secreted by all kinds of cells. It contains different proteins, nucleic acid, and lipid, which are decided by their donor cells and could be uptake by the recipient cells, release their contents, and affect the recipient cell's life activity. In this study, a 24 h-treatment with 5 µM OTA was found to significantly reduce the cell viability of HEK293 cells and meanwhile to provide a sufficient quantity of exosomes, thus this concentration and time were selected for subsequent experiments. In addition, exosomes extracted by ultracentrifugation had higher purity, fewer impurities, and uniform morphology than that by the ExoQuick-TC kit. Furthermore, these exosomes increased ROS levels and decreased mitochondrial membrane potential in HEK293 cells. By RNA-seq, the cytotoxicity mechanisms induced by OTA-treated HEK293 cell-derived exosomes (EXO-OTA) and OTA were mainly the metabolism of proteins and the cell cycle respectively. Also, it proved that exosomes deliver partial OTA-induced cytotoxicity.