RESUMO
Cancer-associated fibroblasts (CAFs) are the most abundant stromal cells within the tumor microenvironment (TME). They extensively communicate with the other cells. Exosome-packed bioactive molecules derived from CAFs can reshape the TME by interacting with other cells and the extracellular matrix, which adds a new perspective for their clinical application in tumor targeted therapy. An in-depth understanding of the biological characteristics of CAF-derived exosomes (CDEs) is critical for depicting the detailed landscape of the TME and developing tailored therapeutic strategies for cancer treatment. In this review, we have summarized the functional roles of CAFs in the TME, particularly focusing on the extensive communication mediated by CDEs that contain biological molecules such as miRNAs, proteins, metabolites, and other components. In addition, we have also highlighted the prospects for diagnostic and therapeutic applications based on CDEs, which could guide the future development of exosome-targeted anti-tumor drugs.
Assuntos
Fibroblastos Associados a Câncer , Exossomos , MicroRNAs , Neoplasias , Humanos , Exossomos/metabolismo , Microambiente Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/metabolismo , Linhagem Celular Tumoral , Fibroblastos/metabolismoRESUMO
BACKGROUND: The therapeutic targeting of the tumor microenvironment (TME) in colorectal cancer (CRC) has not yet been fully developed and utilized because of the complexity of the cell-cell interactions within the TME. The further exploration of these interactions among tumor-specific clusters would provide more detailed information about these communication networks with potential curative value. METHODS: Single-cell RNA sequencing, spatial transcriptomics, and bulk RNA sequencing datasets were integrated in this study to explore the biological properties of MFAP5 + fibroblasts and their interactions with tumor-infiltrating myeloid cells in colorectal cancer. Immunohistochemistry and multiplex immunohistochemistry were performed to confirm the results of these analyses. RESULTS: We profiled heterogeneous single-cell landscapes across 27,414 cells obtained from tumors and adjacent tissues. We mainly focused on the pro-tumorigenic functions of the identified MFAP5 + fibroblasts. We demonstrated that tumor-resident MFAP5 + fibroblasts and myeloid cells (particularly C1QC + macrophages) were positively correlated in both spatial transcriptomics and bulk RNA-seq public cohorts. These cells and their interactions might shape the malignant behavior of CRC. Intercellular interaction analysis suggested that MFAP5 + fibroblasts could reciprocally communicate with C1QC + macrophages and other myeloid cells to remodel unfavorable conditions via MIF/CD74, IL34/CSF1R, and other tumor-promoting signaling pathways. CONCLUSION: Our study has elucidated the underlying pro-tumor mechanisms of tumor-resident MFAP5 + fibroblasts and provided valuable targets for the disruption of their properties.
Assuntos
Neoplasias Colorretais , Peptídeos e Proteínas de Sinalização Intercelular , Humanos , Transdução de Sinais , Células Mieloides/patologia , Fibroblastos/patologia , Neoplasias Colorretais/genética , Microambiente Tumoral/genéticaRESUMO
The efficient intermolecular alkoxylation reactions of various enol acetates and different alcohols are developed in the electrochemical process for the first time. Enol acetates derived from either aromatic, alkyl, or alicyclic ketones, and abundant free alcohols directly used in this synthetic strategy, make this transformation very valuable in synthesis and application in the future.
Assuntos
Álcoois , Cetonas , Álcoois/química , Estereoisomerismo , Cetonas/química , Acetatos/químicaRESUMO
In recent years, with the continuous in-depth exploration of the molecular mechanisms of tumorigenesis, numerous potential new targets for cancer treatment have been identified, some of which have been further developed in clinical practice and have produced positive outcomes. Notably, researchers' initial motivation for studying copper metabolism in cancer stems from the fact that copper is a necessary trace element for organisms and is closely connected to body growth and metabolism. Moreover, over the past few decades, considerable progress has been made in understanding the molecular processes and correlations between copper and cancer. Certain achievements have been made in the development and use of relevant clinical medications. The concept of "cuproptosis," a novel concept that differs from previous forms of cell death, was first proposed by a group of scientists last year, offering fresh perspectives on the targeting capabilities of copper in the treatment of cancer. In this review, we introduced the fundamental physiological functions of copper, the key components of copper metabolism, and a summary of the current research contributions on the connection between copper and cancer. In addition, the development of new copper-based nanomaterials and their associated mechanisms of action are discussed. Finally, we described how the susceptibility of cancer cells to this metallic nutrition could be leveraged to further improve the existing cancer treatment paradigm in the new setting.
Assuntos
Cobre , Neoplasias , Humanos , Cobre/metabolismo , Cobre/uso terapêutico , Neoplasias/tratamento farmacológico , CarcinogêneseRESUMO
BACKGROUND: Gastric cancer (GC) is a common cancer worldwide; however, its molecular and pathogenic mechanisms remain unclear. MicroRNAs (miRNAs), which target key genes in GC, are associated with tumor promotion or suppression. Therefore, identifying new miRNA mechanisms could improve the novel diagnostic and therapeutic strategies for patients with GC. METHODS: To explore the biological functions of miR-135b-5p in GC, bioinformatic analysis and in vitro functional assays, including colony formation, wound healing, Transwell, and EdU assays, were used to assess the proliferative, invasive, and migratory capacities of GC cells. Target genes were predicted using RNA-seq and online databases. Dual-luciferase reporter assay, fluorescence in situ hybridization and western blotting were used to confirm the regulatory relationship between miR-135b-5p and CLIP4. The role of CLIP4 in tumor progression was assessed using clinical samples and both in vitro and in vivo assays. The tumor-suppressive mechanism of CLIP4 in GC was elucidated using rescue assays. RESULTS: Our study identified that miR-135b-5p as one of the top three over-expressed miRNAs in GC tissues, with RT-qPCR confirming its upregulation. Functional analysis showed that upregulated miR-135b-5p promoted malignant phenotypes in GC cells. Mechanistic research indicated that miR-135b-5p acts as a cancer promoter by targeting CLIP4. Moreover, our study suggested that CLIP4 exerts its tumor-suppressive function by inhibiting the JAK2/STAT3 signaling pathway. CONCLUSION: This study reveals a novel mechanism by which miR-135b-5p exerts its tumor-promoting functions by targeting CLIP4. The tumor-suppressive function of CLIP4 by inactivating the JAK2/STAT3 pathway is also elucidated. Regulatory mechanism of CLIP4 by miR-135b-5p provides a promising novel therapeutic strategy for GC patients.
RESUMO
Intelligent labels provide customers with food freshness information. However, the existing label response is limited and can only detect a single kind of food. Here, an intelligent cellulose-based label with highly antibacterial activity for a multi-range sensing freshness was developed to overcome the limitation. Cellulose fibers were modified using oxalic acid to graft -COO- followed by binding chitosan quaternary ammonium salt (CQAS), the remaining charges of which attached methylene red and bromothymol blue to form response fibers and to further self-assemble into the intelligent label. CQAS electrostatically gathered the dispersed fibers, resulting in an increase in TS and EB of 282 % and 16.2 %, respectively. After that, the rest positive charges fixed the anionic dyes to broaden pH response range of 3-9 effectively. More significantly, the intelligent label exhibited highly antimicrobial activity, killing 100 % of staphylococcus aureus. The rapid acid-base response revealed the potential for practical application in which the label color from green to orange represented the milk or spinach from fresh to close to spoiled, and from green to yellow, and to light green indicated the pork fresh, acceptable, and close to spoiled. This study paves a way for the preparation of intelligent labels in large-scale and promote the commercial application to improve food safety.