Liver fibrosis-derived exosomal miR-106a-5p facilitates the malignancy by targeting SAMD12 and CADM2 in hepatocellular carcinoma.

The mechanism of hepatocellular carcinoma (HCC) development induced by liver fibrosis is obscure. The objective of this study is to establish miRNAs from exosomes associated with liver fibrosis, and to identify potential biomarkers for the prediction of personalized clinical management effectiveness in HCC. Our research focused on miRNAs from exosomes and mRNA from liver fibrosis, which we found in the gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) evaluated miRNAs from exosomes associated with liver fibrosis, and Wilcoxon analysis assessed differentially expressed mRNAs (DEGs) across liver fibrosis/normal tissues. Following that, DEGs were assessed through gene set enrichment analysis (GSEA), gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, based on the screened targeted genes, including SAMD12 and CADM2, we further elucidated their correlation in HCC patients from the BEST database. The Kaplan-Meier Plotter platform was applied to evaluate the prognostic values of miRNA in HCC. In vitro and vivo experiments validated our findings. Six miRNAs associated with liver fibrosis were evaluated in our investigation. In-depth research presented exosome-derived miR-106a-5p, SAMD12 and CADM2 could exert valuable predictive implications for HCC treatment and illness assessment. Serum miR-106a-5p derived from liver fibrosis was decreased compared with healthy individuals. SAMD12 and CADM2 were diminished in liver cancer cell lines, and their knockdown of them exacerbated the proliferation capacities of liver cells in vitro. Exosome-derived miRNA of liver fibrosis modulated tumorigenesis by targeting SAMD12 and CADM2 in HCC.

Thallium exposure at low concentration leads to early damage on multiple organs in children: A case study followed-up for four years.

Thallium (TI) is one of the most toxic heavy metals and priority pollutant metals. The emerging TI environmental pollution worldwide has posed a great threat to human health. However, based on the World Health Organization (WHO), the risk and severity of adverse health effects of TI in the range of 5-500 µg/L are uncertain. Moreover, evidence regarding the adverse impacts of TI on children's health is still insufficient. Herein, we aim to investigate the early adverse effects of TI on children's health and provide references for the WHO to establish stricter safety limits of TI. From 2015 to 2019, urinary TI and many clinical laboratory parameters related to blood routine, hepatic, renal, myocardial, coagulation function and serum electrolyte were measured in six children aged 1-9 years. The urinary TI concentration ranged from 13.4 µg/L to 60.1 µg/L with a mean of 36.1 µg/L and a median of 34.8 µg/L in six children in 2015. Although only four children felt a little poor appetite, several laboratory abnormalities indicated early damage in liver, renal, and myocardial functions in all children in 2015. After treatment and following up for four years, although the children's TI concentration decreased below 5 µg/L, their liver and renal functions did not completely recover, and their myocardial function worsened. Results indicated that impaired liver, renal, and myocardial functions were closely associated with elevated urinary TI concentration in children. Considering the increasing use of TI in high-technology industries and emerging TI environmental-contamination zones worldwide, establishing stricter safety limits of TI and paying more attention to the adverse health effects of TI on children are urgently required. SUMMARY: We found that a relatively low concentration of thallium (13.4 µg/L to 60.1 µg/L) impaired liver, renal, and myocardial function in six children. After treatment and following up these children for four years, although their urinary TI concentration decreased below 5 µg/L, their liver and renal functions did not completely recover, and their myocardial function worsened.