Irregularly shaped microplastics (MPs) released from infant feeding bottles (PP-IFBs) may exhibit increased cytotoxicity, in contrast to the commonly studied spherical MPs. This study presents an initial analysis of the thermal-oxidative aging process of plastic shedding from feeding bottles, and investigates the inflammatory response induced by these atypical MPs in human intestinal cells (Caco-2). The PP-IFBs' surface displayed non-uniform white patches and increased roughness, revealing substantial structural alteration and shedding, especially during actions such as shaking, boiling water disinfection, and microwave heating. FT-IR and 2D-COS analyses revealed that oxygen targeted the C-H and C-C bonds of polypropylene molecular chain, producing RO· and ·OH, thereby hastening polypropylene degradation. When human intestinal cells were exposed to MPs from PP-IFBs, oxidative stress was triggered, resulting in lowered glutathione levels, augmented reactive oxygen species (ROS), and heightened lipid peroxidation. Elevated levels of pro-inflammatory cytokines (IL-6 and TNFα) signified an active inflammatory process. The inflammatory response was notably more intense when exposed to MPs released through boiling water disinfection and microwave heating treatments, primarily due to the larger quantity of MPs released and their higher proportion of smaller particles. Furthermore, the NLRP3 inflammasome was identified as critical in initiating this inflammatory chain reaction due to the mitochondrial ROS surge caused by MPs exposure. This was further validated by inhibitor studies, emphasizing the role of the ROS/NLRP3/Caspase-1/IL-1β signaling pathway in in promoting intestinal inflammation. Therefore, swift actions are recommended to protect infants against the potential health effects of MPs exposure.

Difenoconazole (DIF), a common broad-spectrum triazole fungicide, is associated with an increased risk of cardiovascular diseases. Unfortunately, little attention has been paid to the mechanisms underlying this association. In this study, zebrafish embryos were exposed to DIF (0, 0.3, 0.6 and 1.2 mg/L) from 4 to 96 h post fertilization (hpf) and cardiovascular toxicity was evaluated. Our results showed that DIF decreased hatching rate, survival rate and heart rate, with increased malformation rate. Cardiovascular deformities are the most prominent, including pericardial edema, abnormal cardiac structure and disrupted vascular pattern in two transgenic zebrafish models (myl7:egfp and fli1:egfp). DIF exacerbated oxidative stress by via accumulation of reactive oxygen species (ROS) and inhibition of antioxidant enzyme. Cardiovascular apoptosis was triggered through increased expression of p53, bcl-2, bax and caspase 9, while DIF suppressed the transcription of key genes involved in calcium signaling and cardiac muscle contraction. These adverse outcomes were restored by the antioxidant N-acetyl-L-cysteine (NAC), indicating that oxidative stress played a crucial role in DIF-induced cardiovascular toxicity caused by apoptosis and inhibition of cardiac muscle contraction. Taken together, this study revealed the key role of oxidative stress in DIF-induced cardiovascular toxicity and provided novel insights into strategies to mitigate its toxicity.

Gastrointestinal cancers are the most common type of cancer affecting humans. High expression of HOX transcript antisense intergenic RNA (HOTAIR), a long noncoding RNA (lncRNA), in various types of different tumors may be associated with poor prognosis. In the present study, we performed a meta-analysis of the relationship between HOTAIR expression and gastrointestinal cancers. Five databases were comprehensively searched for all literature until January 2023. Moreover, the target genes of HOTAIR were predicted by coexpression analysis based on The Cancer Genome Atlas (TCGA) gene expression matrix for six gastrointestinal cancer types. Finally, the mechanism through which HOTAIR affects tumors of the digestive system was systematically reviewed. Our results showed that the high HOTAIR expression group had worse outcomes with a pooled hazard ratio (HR) of 1.56 (95% confidence interval [CI] = 1.38–1.75, P<0.001). Furthermore, HOTAIR was identified as an unfavorable prognostic factor for overall survival (OS) in the esophageal carcinoma (ESCA) and gastric cancer (GC), as the HR were 1.94 and 1.58, respectively. The high correlation between the expression of homeobox C (HOXC) family genes and HOTAIR, with correlation coefficients of 0.863 (HOXC11), 0.664 (HOXC10), 0.645 (HOXC8), and 0.581 (HOXC12). The ‘cell cycle’ pathway and pathways relating to infections, namely ‘herpes simplex virus 1 infection’ and ‘complement and coagulation cascades’ were significantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Also, we perform a systematic review to summarize the related oncogenic mechanism of HOTAIR. In conclusion, the HOTAIR has been identified as a potential prognostic factor in patients with gastrointestinal cancers.

Background: Globally, gastrointestinal (GI) cancer is one of the most prevalent malignant tumors. However, studies have not established glycolysis-related gene signatures that can be used to construct accurate prognostic models for GI cancers in the Asian population. Herein, we aimed at establishing a novel glycolysis-related gene expression signature to predict the prognosis of GI cancers. Methods: First, we evaluated the mRNA expression profiles and the corresponding clinical data of 296 Asian GI cancer patients in The Cancer Genome Atlas (TCGA) database (TCGA-LIHC, TCGA-STAD, TCGA-ESCA, TCGA-PAAD, TCGA-COAD, TCGA-CHOL and TCGA-READ). Differentially expressed mRNAs between GI tumors and normal tissues were investigated. Gene Set Enrichment Analysis (GSEA) was performed to identify glycolysis-related genes. Then, univariate, LASSO regression and multivariate Cox regression analyses were performed to establish a key prognostic glycolysis-related gene expression signature. The Kaplan-Meier and receiver operating characteristic (ROC) curves were used to evaluate the efficiency and accuracy of survival prediction. Finally, a risk score to predict the prognosis of GI cancers was calculated and validated using the TCGA data sets. Furthermore, this risk score was verified in two Gene Expression Omnibus (GEO) data sets (GSE116174 and GSE84433) and in 28 pairs of tissue samples. Results: Prognosis-related genes (NUP85, HAX1, GNPDA1, HDLBP and GPD1) among the differentially expressed glycolysis-related genes were screened and identified. The five-gene expression signature was used to assign patients into high- and low-risk groups (p < 0.05) and it showed a satisfactory prognostic value for overall survival (OS, p = 6.383 × 10^–6). The ROC curve analysis revealed that this model has a high sensitivity and specificity (0.757 at 5 years). Besides, stratification analysis showed that the prognostic value of the five-gene signature was independent of other clinical characteristics, and it could markedly discriminate between GI tumor tissues and normal tissues. Finally, the expression levels of the five prognosis-related genes in the clinical tissue samples were consistent with the results from the TCGA data sets. Conclusions: Based on the five glycolysis-related genes (NUP85, HAX1, GNPDA1, HDLBP and GPD1), and in combination with clinical characteristics, this model can independently predict the OS of GI cancers in Asian patients.

Objective: Cyclin-dependent kinase 1 (CDK1) regulates the cell cycle and is highly expressed in most tumors. CDK1 expression has been associated with poor disease prognosis. This study aimed to identify the prognostic value of CDK1 in pan-cancer and investigate the association between CDK1 expression and immune cell infiltration. Methods: CDK1 expression and its correlation with prognosis in pan-cancer were analyzed using online databases. Immune infiltration was assessed by ESTIMATE and CIBERSORT algorithms. We then evaluated the relationship between CDK1 expression and tumor mutational burden (TMB), microsatellite instability (MSI), or tumor-infiltrating immune cells. In addition, we performed the co-expression analysis of immune-related genes and GO analysis with CDK1 expression in pan-cancer. Finally, we compared the CDK1 expression profile with the immune-related genes in 30 pairs of clinical gastrointestinal tumor samples. Results: Our analysis demonstrated overexpression of CDK1 in most tumor tissues, especially in gastrointestinal tumors. The high expression of CDK1 was associated with poor overall survival, disease-specific survival, disease-free interval, and progression-free interval in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), and sarcoma (SARC). Besides, CDK1 expression was significantly associated with TMB in 22 cancer types and MSI in 8 cancer types as well as greater frequencies of MSI-high (MSI-H) status and high tumor mutational burden (TMB-H) in uterine corpus endometrial carcinoma (UCEC), stomach adenocarcinoma (STAD), sarcoma (SARC), rectum adenocarcinoma (READ), mesothelioma (MESO), head and neck squamous cell carcinoma (HNSC), and colon adenocarcinoma (COAD). In addition, CDK1 expression correlated with immune cell infiltrating levels, such as M0, M1, or M2 macrophages, memory CD4 T cells, T follicular helper cells, and naive B cells. Our data showed that CDK1 was remarkably correlated with 47 immune-related and immune checkpoint genes in many cancer types. Furthermore, CDK1 was up-regulated in gastrointestinal tumor samples, especially in gastric cancer and intestinal cancer. CDK1 was positively correlated with IDO1 in gastric cancer and PD-1 in intestinal cancer. Conclusion: Taken together, our data demonstrated the roles of CDK1 in oncogenesis and metastasis in pan-cancer. Thus, CDK1 is a potential prognostic biomarker and a target for tumor immunotherapy.