Organoids are powerful systems to facilitate the study of individuals' disorders and personalized treatments because they mimic the structural and functional characteristics of organs. However, the full potential of organoids in research has remained unrealized and the clinical applications have been limited. One of the reasons is organoids are most efficient grown in reconstituted extracellular matrix hydrogels from mouse-derived, whose poorly defined, batch-to-batch variability and immunogenicity. Another reason is that organoids lack host conditions. As a component of the tumor microenvironment, microbiota and metabolites can regulate the development and treatment in several human malignancies. Here, we introduce several engineering matrix materials and review recent advances in the coculture of organoids with microbiota and their metabolites. Finally, we discuss current trends and future possibilities to build more complex cocultures.
Statement of Problem MicroRNAs are small non-coding RNAs that regulate an array of functions by targeting crucial genes. A significant dysregulation in the TP53 profile has been observed in the head and neck squamous cell carcinoma (HNSCC) patients. Hence, the present in silico study was designed to identify those microRNAs which target TP53 gene and demonstrate their differential expression in HNSCC cases.
Materials and Methods The study was extended further to explore their exosomal location using database such as EVmiRNA and ExoCarta. The study follows an observational in silico design. Computational tool miRDB was used identify the microRNA targets of TP53 gene. The UALCAN server was used to ascertain the expression of microRNA in HNSCC cases derived from the Cancer Gene Atlas dataset. The survival of HNSCC patients based on the differential expression microRNA markers were recorded. Further, each of the microRNA was queried for their exosomal presence using EVmiRNA.
Results About 102 microRNA targets of TP53 gene with a target score in the range of 95-50 were identified. The differential expression data for 52 microRNAs was retrieved from the UALCAN database. The microRNAs hsa-miR-421, hsa-miR-548f-5p, and hsa-let-7c-5p were found to be differentially expressed with marked influence over the survival of HNSCC patients. Furthermore, hsa-miR-421 and hsa-let-7c-5p were found to have an exosomal origin especially in body fluids such as blood and saliva.
Conclusion The results accumulated from the present study identified three microRNAs which can affect the functions of TP53 gene and bring about serious outcomes in HNSCC patients. The microRNAs of exosomal origin targeting TP53 gene in HNSCC patients can be a promising prognostic marker, which can be further used as a therapeutic lead by designing inhibitors.
Dendritic cells (DCs) play a key role in initiating and regulating immune responses, and in addition to their roles in vivo, DCs are used as natural adjuvants for various tumor vaccines. In vitro, monocytes can be used to induce DCs, but in tumor patients, due to insufficient bone marrow hematopoiesis, extramedullary hematopoiesis and tumor-associated myeloid cells expand, and monocytes mainly exist in the form of myeloid-derived suppressor cells (MDSCs). The purpose of this experiment was to explore the differences in the differentiation and immune function of DCs induced by MDSCs in tumor patients. In a mouse model, we used normal mouse bone marrow cell-derived DCs as control cells, and in a tumor-bearing model, we induced MDSCs in the spleen to generate DCs (MDSC-DCs). Through flow cytometry, we found that the production of MDSC-DCs was significantly higher than that of control mice, and the secretion of interferon-γ of MDSC-DCs was significantly reduced. Through OVA antigen presentation experiments, we found that the antigen presentation ability of MDSC-DCs was significantly decreased. Through adoptive treatment of tumor-bearing mice cells, we found that the antitumor immune function of MDSC-DCs was significantly reduced. After that, we explored the mechanism of the decrease of immune function activity of MDSC-DCs. We determined that the surface markers of MDSC-DCs were changed by flow cytometry. Through flow sorting and RNA sequencing, we found that some pathways and key gene expression in MDSC-DCs were changed. In conclusion, this study found that the immune function of MDSC-DCs decreased and explored the mechanism of the decreased immune function activity.