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.

Research has implicated endocannabinoids (eCBs) as significant regulators of neuroinflammation that may contribute to autism spectrum disorder (ASD). This study investigated the effect of the main eCBs, namely N-acylethanolamine (NAE) and 2-arachidonoylglycerol (2-AG), on ASD and their underlying mechanisms through in vivo and in vitro experiments. Results showed that elevating NAE or 2-AG ameliorated social deficits and restricted and repetitive behaviors and corrected neuropathological damage. Additionally, enhancing 2-AG protected valproic acid (VPA)-exposed rats against nerve damage by modulating abnormal neuroinflammation, as evidenced by the fact that 2-AG decreased microglial reactivity with reduced pro-inflammatory responses and increased anti-inflammatory responses. While, NAE only had a subtle effect on regulating neuroinflammation. Collectively, these findings suggested that elevating both NAE and 2-AG could improve ASD symptoms. Elevating 2-AG may play a neuroprotective role by generating a reparative milieu reactive to abnormal neuroinflammation, but NAE does not. Therefore, eCBs may be a promising therapeutic target for ASD.