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Objectives: Circular RNAs (circRNAs), with their multilevel and versatile regulation, have emerged as promising targets for treating complex and heterogeneous malignancies such as oral squamous cell carcinoma (OSCC). It is crucial to explore the function of key circRNAs and elucidate the underlying mechanisms to establish an effective in vivo delivery system to better utilize circRNAs as cancer treatment strategies. Materials and Methods: circRNA (circ‐OCAC) was identified as significantly downregulated in tumor samples compared to paracancerous tissues by RNA‐seq analysis of eight pairs of OSCC tissues. Functional experiments of circ‐OCAC were performed both in vitro and in vivo. The interactions between circ‐OCAC and miR‐411‐5p were clarified by RNA pull down and RNA immunoprecipitation (RIP) assays. Results: We observed that circ‐OCAC inhibits OSCC growth and metastasis by blocking the PI3K/Akt signaling pathway. To translate this observation in vivo, a pH‐responsive nanoparticle (pNP) was developed to target circ‐OCAC. Our results confirmed the advantages of the pNP‐circ‐OCAC system: high tumor enrichment capacity and good biosafety, which resulted in a significantly enhanced antitumor effect. Conclusions: This study demonstrated that targeting circ‐OCAC serves as a promising potential therapeutic strategy for OSCC. [ABSTRACT FROM AUTHOR]

Introduction: Rhynchophylline, as a traditional Chinese medicine, was used for the treatment of drug addiction. Objective: To investigate miRNAs expression profile in the rat hearts of methamphetamine dependence and the intervention mechanisms of rhynchophylline. Materials and Methods: This study detected the expression profile of miRNAs in the methamphetamine-induced rat hearts by microarray and verified the expression of miR-133a-5P and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) protein. Results: After conditioned place preference training, methamphetamine significantly increased the time spent in the drug-paired compartment, while rhynchophylline and MK-801 could reduce the time. Cluster analysis results of miRNAs showed that compared with the control group, the expression of miR-133a-5p in methamphetamine-induced rat hearts was decreased significantly; rhynchophylline could significantly increase the expression of miR-133a-5p. The result was verified by real-time polymerase chain reaction. The results of target gene predictive software and related research showed that ROCK2 protein may be the target gene of miR-133a-5p. The immunohistochemistry results of heart tissues showed that the expression of ROCK2 protein was significantly upregulated in the methamphetamine group and downregulate in the rhynchophylline group; the difference between the MK-801 group and the methamphetamine group was not significant. The result of western blot was consistent with the immunohistochemistry. Conclusion: The active ingredient of Chinese herbal medicine rhynchophylline can effectively inhibit the formation of methamphetamine-dependent conditional place preference (CPP) effect in rats to some extent. MiR-133a-5p may participate in the cardioprotective effects of CPP rats by targeting ROCK2. [ABSTRACT FROM AUTHOR]

Background: Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC., Methods: We performed combined single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell (TIL) subtype, CD103 + CD8 + TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103 + CD8 + TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC images., Results: We established intratumoral CD103 + CD8 + TILs density as a determinant of NACI efficacy in cancers. Our scRNA-seq results indicated that the population of CD103 + CD8 + TILs was dramatically increased in the responders of NACI-treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103 + CD8 + TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103 + CD8 + TILs were tumor-reactive T cells, while programmed cell death protein-1 (PD-1) blockade enhanced CD103 + CD8 + TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2-positive (TREM2 + ) macrophages might enhance the population of CD103 + CD8 + TILs and facilitate antitumor immunity during NACI treatment., Conclusions: Our study highlights the impact of intratumoral CD103 + CD8 + TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)