Search

Accumulated evidence has shown that microRNAs (miRNAs) are closely related to the pathogenesis and progression of senile cataracts. Here we investigate the effect of miR-29a-3p in cataractogenesis and determined the potential molecular mechanism involved. In this study, we constructed a selenite cataract model in rats and obtained the miRNAs related to cataracts by whole transcriptome sequencing. To investigate the effect and mechanism of miR-29a-3p on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, luciferase reporter assay, Edu assay, and western blot analysis. Sequencing data showed downregulation of miR-29a-3p in rats with selenite cataracts. Down-regulation of miR-29a-3p could promote lens epithelial cells (SRA01/04) proliferation and inhibit cell apoptosis, and miR-29a-3p silence could inhibit the development of cataracts. Additionally, CAND1 was a direct target gene for miR-29a-3p. These data demonstrate that miR-29a-3p inhibits apoptosis of lens epithelial cells by regulating CAND1, which may be a potential target for senile cataracts. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Jiang-Xian HuGan (JXHG) formulated by five natural products including Freshwater clam (Corbicula fluminea) , Curcuma longa L., Ligustrum lucidum , Eclipta prostrata (L.) L. and Paeonia lactiflora Pall. , has exhibited a great hepatoprotective effect. Aim of this study We investigated the effect of JXHG on concanavalin A (ConA)-induced acute live injury in mice, and to elucidate its underlying molecular mechanisms. Materials and methods Jiangkanling Capsule (900 mg/kg), low-dose JXHG (LJXHG, 700 mg/kg), high-dose JXHG (HJXHG, 1400 mg/kg) were administered to mice by oral gavage daily for 20 days prior to a single intravenous injection of ConA (20 mg/kg). Liver injury was evaluated by measuring the serum levels of enzymes and cytokines as well as liver histological analysis. We also measured the hepatic expression of cytokines at mRNA levels and the proteins related to NF-κB and Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways. Result Our results showed that JXHG pretreatment significantly alleviated ConA-induced live injury as evidenced by decreased serum levels of glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST), and reduced hepatocyte apoptosis and mortality. Furthermore, JXHG was able to significantly reduce the serum levels of proinflammatory cytokines, down-regulate the mRNA expression of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and up-regulate IL-10 as well as superoxide-dimutase-1 (SOD1), glutathione reductase (GSR) and Glutathione peroxidase 2 (GPX2) mRNA in the liver tissues after Con A injection. In addition, JXHG pretreatment dramatically suppressed the phosphorylation of NF-κB p65 (p65), increased Nrf2 expression, and decreased the expression ratio of cleaved caspase-3/caspase-3 in liver tissues. Conclusion These results suggest that JXHG protects against ConA-induced acute live injury through inhibiting NF-κB mediated inflammatory pathway and promoting Nrf2 mediated anti-oxidative stress signaling pathway. [ABSTRACT FROM AUTHOR]

Cataract is the leading cause of blindness in the world, and there is a lack of effective treatment drugs. CircRNA plays an important part in a variety of diseases, however, the role of circRNA in cataracts remains largely unknown. In this study, we constructed a cataract model of rats and obtained the circRNAs related to cataracts by whole transcriptome sequencing and circRNA-mRNA co-expression network. To investigate the effect and mechanism of circRNA 06209 on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, dual luciferase reporter assay, RIP assay, actinomycin D assay, and Western blot analysis. We identify that a necroptosis-related circRNA, circRNA 06209, is down-regulated in cataracts. Vitro experiments showed that up-regulation of circRNA 06209 could promote cell proliferation and inhibit cell apoptosis. Vivo experiments revealed that circRNA 06209 overexpression could inhibit the development of cataracts. Mechanistically, circRNA 06209 acts as a miRNA sponge and competitively binds to miR-6848-5p to curb the inhibitory effect of miR-6848-5p on ALOX15, thereby affecting cell viability and apoptosis. This study found that circRNA 06209 plays a critical part in inhibiting cataracts through the miR-6848-5p/ALOX15 pathway, suggesting that circRNA 06209 may be a promising therapeutic target for cataracts. • In this manuscript, we constructed a cataract rat model and obtained the circRNAs related to cataracts by whole transcriptome sequencing and circRNA-mRNA co-expression network. We found that circRNA 06209 plays a critical part in inhibiting cataracts through the miR-6848-5p/ALOX15 pathway, suggesting that circRNA 06209 may be a promising therapeutic target for cataracts. [ABSTRACT FROM AUTHOR]

Although the causal relationship between Alzheimer's disease (AD) and iron overload remains unclear, iron dyshomeostasis or improper transport mechanisms are speculated to lead to the accumulation of this neurotoxic metal in the hippocampal formation and other cerebral areas related to neurodegenerative diseases, resulting in the formation of reactive oxygen species (ROS) and, ultimately, cell death. In this study, exposure to high dietary iron (HDI) revealed no significant difference in the number of iron-positive cells and iron content in the cortex and hippocampal region between wild-type (WT) and APP/PS1 mice; however, compared with the control mice, the HDI-treated mice exhibited upregulated divalent metal transporter 1 (DMT1) and ferroportin (Fpn) expression, and downregulated transferrin receptor (TFR) expression. Importantly, we confirmed that there were significantly fewer NeuN-positive neurons in both APP/PS1 and WT mice given HDI, than in the respective controls. Moreover, this iron-induced neuron loss may involve increased ROS and oxidative mitochondria dysfunction, decreased DNA repair, and exacerbated apoptosis and autophagy. Although HDI administration might trigger protective antioxidant, anti-apoptosis, and autophagy signaling, especially in pathological conditions, these data clearly indicate that chronic iron exposure results in neuronal loss due to apoptosis, autophagy, and ferroptosis, hence increasing the risk for developing AD. [ABSTRACT FROM AUTHOR]