RESUMEN
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that often develops unnoticed. Typically, these tumors are identified at advanced stages, resulting in a relatively low chance of successful treatment. Anoikis serves as a natural defense against the spread of tumor cells, meaning circumventing anoikis can effectively inhibit tumor metastasis. Nonetheless, studies focusing on anoikis in the context of HNSCC remain scarce. METHODS: Anoikis-related genes (ARGs) were identified by using the GeneCards and Harmonizome databases. Expression data of these genes and relevant clinical features were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A LASSO regression and a prognostic risk score model were developed to determine their prognostic significance. The analysis included the use of the CIBERSORT algorithm to quantify immune and stromal cell presence. Furthermore, in vitro and in vivo, we confirmed the expression and functional roles of proteins and mRNA of genes independently predictive of prognosis. RESULTS: The study identified eight genes linked to prognosis (ANXA5, BAK1, CDKN2A, PPARG, CCR7, MAPK11, CRYAB, CRYBA1) and developed a prognostic model that effectively forecasts the survival outcomes for patients with HNSCC. A higher survival likelihood is associated with lower risk scores. In addition, a significant relationship was found between immune and risk score, and ANXA5 deletion promoted the killing of HNSCC cells by activated CD8+ T cells. During the screening process, 65 different chemotherapeutic drugs were found to have significant differences in IC50 values when comparing high- and low-risk categories. ANXA5 emerged as a gene with independent prognostic significance, exhibiting notably elevated protein and mRNA levels in HNSCC tissue compared to non-tumorous tissue. The suppression of ANXA5 gene activity resulted in a substantial decrease in both the growth and mobility of HNSCC cells. Animal model experiments demonstrated that inhibiting ANXA5 suppressed HNSCC growth and migration in vivo. CONCLUSION: Through bioinformatics, a prognostic risk model of high precision was developed, offering valuable insights into the survival rates and immune responses in patients with HNSCC. ANXA5 is highlighted as a significant prognostic factor among the identified genes, indicating its promise as a potential therapeutic target for those with HNSCC.
Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Pronóstico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Proliferación Celular/genética , Ratones , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Anoicis/genética , Biomarcadores de Tumor/genética , Masculino , FemeninoRESUMEN
Nanoplastics (NPs) and polycyclic aromatic hydrocarbons (PAHs) are recognized as persistent organic pollutant (POPs) with demonstrated physiological toxicity. When present in aquatic environments, the two pollutants could combine with each other, resulting in cumulative toxicity to organisms. However, the combined impact of NPs and PAHs on microorganisms in seawater is not well understood. In this study, we conducted an exposure experiment to investigate the individual and synergistic effects of NPs and PAHs on the composition, biodiversity, co-occurrence networks of microbial communities in seawater. Exposure of individuals to PAHs led to a reduction in microbial community richness, but an increase in the relative abundance of species linked to PAHs degradation. These PAHs-degradation bacteria acting as keystone species, maintained a microbial network complexity similar to that of the control treatment. Exposure to individual NPs resulted in a reduction in the complexity of microbial networks. Furthermore, when PAHs and NPs were simultaneously present, the toxic effect of NPs hindered the presence of keystone species involved in PAHs degradation, subsequently limiting the degradation of PAHs by marine microorganisms, resulting in a decrease in community diversity and symbiotic network complexity. This situation potentially poses a heightened threat to the ecological stability of marine ecosystems. Our work strengthened the understanding of the combined impact of NPs and PAHs on microorganisms in seawater.
Asunto(s)
Microbiota , Hidrocarburos Policíclicos Aromáticos , Agua de Mar , Contaminantes Químicos del Agua , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Agua de Mar/química , Agua de Mar/microbiología , Contaminantes Químicos del Agua/toxicidad , Microbiota/efectos de los fármacos , Bacterias/efectos de los fármacos , Microbiología del Agua , Microplásticos/toxicidad , Biodiversidad , Monitoreo del AmbienteRESUMEN
BackgroundThe biased immune reactions of the adenotonsillar tissues are not always reflected by the serum immunoglobulin E (IgE); thus, we hypothesize that the systemic atopic status may not be changed after the adenotonsillectomy (AT) in children.MethodsTwenty-five children with AT and 23 age-matched healthy children were enrolled into this study, and followed up for ~4 years. Nasal Symptoms Scores (NSS), Quality of Life Scores (QOLS), specific IgE (sIgE), cytokines, and inflammatory cell were documented in all the subjects before and after study.ResultsFourteen patients and three healthy controls had positive serum sIgE levels (>0.35 kU/l) at the study-start that was not changed by the study-end. Two patients and two sIgE-negative healthy controls showed the Dermatophagoidespteronyssinus sensitization at the study-end. NSS and QOLS showed significant improvement after the surgery in the sIgE-positive patients (P<0.05), whereas no significant changes were found in the sIgE-negative patients (P=1.00). In addition, the serum sIgE-negative patients showed significant increases in interleukin (IL)-4, IL-5, and IL-10 levels in the serum (P<0.001), although no significant differences were found post surgery (P=0.667, 0.408, and 0.714, respectively).ConclusionsOur study showed that AT did not affect the pediatric atopic status. The systemic atopy may be independent of the tonsillar and adenoid tissues in children.