Qiqihar Medical University

Glyphosate (GLP) is one of the most widely used herbicides in the world. However, its underlying effects on the liver remain unclear. This study aims to investigate the toxic effects and the gut microbiome– and serum metabolite–related mechanisms of GLP on the liver in mice.

16S rDNA sequencing and UPLC-Q-TOF-MS/MS were used to investigate the mechanisms of GLP toxicity in mice administered with 0, 50, 250 and 500 mg/kg/day GLP for 30 days.

GLP induced hepatocyte edema and ballooning as well as inflammatory cell infiltration. Exposure to GLP resulted in increased levels of serum ALT, TBIL, DBIL, and GLU. Microbiota analysis at the phylum level demonstrated that the proportions of Patescibacteria decreased in the GLP-treated group. The genus-level analysis identified 11 different genera, with eight decreased and three increased in the GLP-exposed group. Metabolomics analysis of serum showed 42 differential metabolites between the GLP and control groups. The metabolic pathway enrichment analysis revealed that the pentose phosphate pathway (PPP) and pyrimidine metabolism were significantly activated. Spearman analysis showed that the changes in the differential metabolites of the PPP and pyrimidine metabolism and gut microbiota were strongly associated with the biochemical index.

In conclusion, GLP exposure induces hepatic injury through alterations in the gut microbiome and metabolic pathways, particularly by activating the pentose phosphate pathway and pyrimidine metabolism.

Alcohol dependence (AD) is a global public health concern with strong genetic characteristics. The purpose of this study was to explore the underlying pathogenic genes and mechanisms associated with AD.

This study employed a multi-omics Mendelian randomization approach to identify potential disease-causing genes for AD. Specifically, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomization (SMR) to pinpoint candidate genes associated with AD. Additionally, mediating Mendelian randomization was utilized to investigate the mediating role of the gut microbiota in the relationship between immune cell phenotypes and AD.

Two susceptibility genes associated with AD, ADH1C and POLI, were identified a joint analysis of SMR and integrated cross-tissue and single tissue TWAS in European population. A new genetic locus associated with AD, rs62307318, was uncovered through cross-organism TWAS. This finding was further validated using Mendelian randomization and Phenome-wide association analysis. Additionally, Mendelian randomization identified Paceibacteria as a possible mediator between Myeloid DC AC and AD.

This study identified two genes closely related to AD and explored the possible pathogenesis of AD, which provides a new insight into the treatment and pathogenesis of AD.

Head and neck squamous cell carcinomas (HNSCC) is an aggressive malignancy, necessitating early diagnostic biomarkers. This study explores EFNA1's role in HNSCC and its potential for early screening.

Data from TCGA, CCLE, and Depmap databases were analyzed. Serum samples from HNSCC patients and controls were tested using ELISA. Cell proliferation, apoptosis assays, and KEGG pathway analysis were conducted. Western blotting assessed EphA2pS898, EphA2, and EFNA1's impact on the AKT/ERK1/2 pathway.

EFNA1 expression was significantly higher in HNSCC tissues compared to healthy tissues (P < 0.05). ROC analysis showed an AUC of 0.924 for EFNA1 in predicting HNSCC, indicating its diagnostic potential. Serum EFNA1 levels were elevated pre-surgery and decreased post-surgery (P < 0.05), correlating with poor prognosis (P = 0.021). EFNA1 knockdown in BICR78 and SNU46 cells induced apoptosis (P < 0.05). EFNA1 overexpression increased proliferation, which was reversed by EFNA1 antibody. EFNA1 downregulated AKT/ERK1/2 pathway activity, with its interference preventing full pathway activation.

EFNA1 is a promising biomarker for early HNSCC screening and a potential therapeutic target.