Unravelling the heterogeneity of oral squamous cell carcinoma by integrative analysis of single-cell and bulk transcriptome data.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy of the head and neck with rising global incidence. Despite advances in treatment modalities, OSCC prognosis remains diverse due to the complex molecular and cellular heterogeneity within tumours, as well as the heterogeneity in tumour microenvironment (TME). In this study, we utilized single-cell RNA sequencing (scRNA-seq) analysis to explore distinct subpopulations of tumour cells in OSCC tissues and their interaction with components in TME. We identified four major tumour cell subpopulations (C0, C1, C2 and C3) with unique molecular characteristics and functional features. Pathway enrichment analysis revealed that C0 primarily expressed genes involved in extracellular matrix interactions and C1 showed higher proliferation levels, suggesting that the two cell subpopulations exhibited tumour aggressiveness. Conversely, C2 and C3 displayed features associated with keratinization and cornified envelope formation. Accordingly, C0 and C1 subpopulations were associated with shorter overall and disease-free survival times, while C2 and C3 were weakly correlated with longer survival. Genomic analysis showed that C1 demonstrated a positive correlation with tumour mutation burden. Furthermore, C0 exhibited resistant to cisplatin treatment, while C1 showed more sensitive to cisplatin treatment, indicating that C0 might exhibit more aggressive compared to C1. Additionally, C0 had a higher level of communication with fibroblasts and endothelial cells in TME via integrin-MAPK signalling, suggesting that the function of C0 was maintained by that pathway. In summary, this study provided critical insights into the molecular and cellular heterogeneity of OSCC, with potential implications for prognosis prediction and personalized therapeutic approaches.

Exploring NK-Cell molecules that impact the immune response and microenvironment in head and neck squamous cell carcinoma.

NK cells play a role in various cancers, but their role in head and neck squamous cell carcinoma (HNSCC) still needs to be explored. All public data are obtained from the Cancer Genome Atlas Program (TCGA) database. All analysis was performed using specific packages in R software. In our study, we quantified the immune microenvironment of HNSCC through multiple algorithms. Next, we identified NK cell-associated genes by quantifying NK cells, including SSNA1, TRIR, PAXX, DPP7, WDR34, EZR, PHLDA1 and ELOVL1. Then, we explored the single-cell expression pattern of these genes in the HNSCC microenvironment. Univariate Cox regression analysis indicated that the EZR, PHLDA1 and ELOVL1 were related to the prognosis of HNSCC patients. Following this, we selected EZR for further analysis. Our results showed that the patients with high EZR expression might have a poor prognosis and worse clinical features. Biological enrichment analysis showed that EZR is associated with many oncogenic pathways and a higher tumour stemness index. Meanwhile, we found that EZR can remodel the immune microenvironment of HNSCC. Moreover, we noticed that EZR could affect the immunotherapy and specific drug sensitivity, making it an underlying clinical target. In summary, our results can improve the understanding of NK cell in HNSCC. Meanwhile, we identified EZR as the underlying clinical target of HNSCC.

hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region. Circular RNA (circRNA), as one kind of noncoding RNA, involves in biological processes in diverse cancers. circRNA functions mainly as the microRNA (miRNA) sponge, competitively binding to miRNAs to regulate target gene expressions. However, the expression profiles and roles of circRNAs in OSCC are still unexplored. circRNA microarrays and quantitative real-time polymerase chain reaction was used to identify the hsa_circRNA_100533 downregulated in OSCC tissues and cell lines. Bioinformatics methods were used to predict the interactions among circRNAs, miRNA, and target genes. Based on the luciferase reporter assay and AGO2 RIP assay, we found that hsa_circRNA_100533 binds to miRNAs as a miRNA sponge. hsa_circRNA_100533 inhibited cell proliferation, migration, and promoted cell apoptosis in OSCC cell lines, which could be blocked by hsa-miR-933 overexpression. hsa_circRNA_100533 binds to hsa-miR-933 as a miRNA sponge to regulate GNAS expression, and to modulate cell proliferation, migration, and apoptosis. In summary, the hsa_circRNA_100533-miR-933-GNAS axis affect the proliferation and apoptosis of OSCC cells through the mechanism of competing endogenous RNAs. hsa_circRNA_100533 may function as promising diagnostic biomarkers and effective therapeutic targets for OSCC.

Effects of X-ray on the metacestodes of Echinococcus granulosus in vitro.

BACKGROUND: Radiotherapy may represent an alternative treatment modality for cystic echinococcosis (CE), but there is no adequate evidence for it up to now. In this study, we aim to investigate the parasiticidal effects of X-ray on the metacestodes of Echinococcus granulosus in vitro. METHODS: Protoscoleces obtained from sheep naturally infected with CE were cultivated in RPMI 1640 medium containing 10% fetal bovine serum (FBS) at 37 °C in 5% CO2. Upon encystation on day 14, the metacestodes were subjected to various intensities of X-ray. Metacestode structures were observed using light microscope and transmission electron microscopy (TEM), and Real-Time PCR was carried out to determine the expression of EgTPX, EgHSP70, EgEPC1 and Caspase-3. RESULTS: On day 14, encystation was noticed in the majority of protoscoleces in the control group. In the X-ray groups, the encystation rate showed significant decrease compared with that of the control group (P < 0.05), especially the groups subjected to a dose of ≥40 Gy (P < 0.01). Light microscope findings indicated the hooklets on the rostellum were deranged in the irradiation group, and malformation was noticed in the suckers in a dose dependent manner. For the TEM findings, the cellular structure of the germinal layer of the cysts was completely interrupted by X-ray on day 7. The expression of EgTPX, EgHSP70, EgEPC1 and Caspase-3 was up-regulated after irradiation, especially at a dose of ≥45Gy (P < 0.05). CONCLUSIONS: X-ray showed parasiticidal effects on the metacestodes of E. granulosus. Irradiation triggered increased expression of EgTPX, EgHSP70, EgEPC1 and Caspase-3.

Modeling of cancer photothermal therapy using near-infrared radiation and functionalized graphene nanosheets.

Photothermal therapy using near-infrared radiation and local heating agents can induce selective tumor ablation with limited harm to the surrounding normal tissue. Graphene sheets are promising local heating agents because of their strong absorbance of near-infrared radiation. Experimental studies have been conducted to study the heating effect of graphene in photothermal therapy, yet few efforts have been devoted to the quantitative understanding of energy conversion and transport in such systems. Herein, a computational study of cancer photothermal therapy using near-infrared radiation and graphene is presented using a Monte Carlo approach. A three-dimensional model was built with a cancer cell inside a cube of healthy tissue. Functionalized graphene nanosheets were randomly distributed on the surface of the cancer cell. The effects of the concentration and morphology of the graphene nanosheets on the thermal behavior of the system were quantitatively investigated. The interfacial thermal resistance around the graphene sheets, which affects the transfer of heat in the nanoscale, was also varied to probe its effect on the temperature increase of the cancer cell and the healthy tissue. The results of this study could guide researchers to optimize photothermal therapy with graphene, while the modeling approach has the potential to be applied for investigating alternative treatment plans.

[Application of adipose-derived mesenchymal stem cells in craniomaxillofacial restoration and reconstruction].

Craniomaxillofacial hard and soft tissue defects are clinically common and frequently encountered diseases that seriously affect the appearance and function of patients. Restoration and reconstruction of craniomaxillofacial hard and soft tissues are comprehensive clinical problems that require a multi-disciplinary approach and are faced with many unresolved issues. Development of tissue engineering has introduced new concepts to craniomaxillofacial restoration and reconstruction. Tissue engineering primarily aims to determine suitable seed cells. Recently, adipose-derived mesenchymal stem cells (AdSCs) were found to be relatively ideal seed cells because they are easy to obtain from numerous sources and have multiple potencies under certain inducing circumstances and high augmenting ability. This review provides an overview of the application of AdSCs in craniomaxillofacial restoration and reconstruction.