Long non-coding RNAs in Sus scrofa ileum under starvation stress.

OBJECTIVE: In this study, we aimed to identify long non-coding RNAs (lncRNAs) that play important roles in starvation stress, analyze their functions, and discover potential molecular targets to alleviate starvation stress to provide a theoretical reference for subsequent in-depth research. METHODS: We generated a piglet starvation stress animal model. Nine Yorkshire weaned piglets were randomly divided into a long-term starvation stress group (starved for 72 h), short-term starvation stress group (starved for 48 h), and the control group. LncRNA libraries were constructed using high-throughput sequencing of piglet ileums. RESULTS: We obtained 11,792 lncRNAs, among which, 2,500 lncRNAs were novel. In total, 509 differentially expressed (DE)lncRNAs were identified in this study. Target genes of DElncRNAs were predicted via cis and trans interactions, and functional and pathway analyses were performed. Gene ontology functions and Kyoto encyclopedia of genes and genomes analysis revealed that lncRNA-targeted genes mainly participated in metabolic pathways, cellular processes, immune system processes, digestive systems, and transport activities. To reveal the mechanism underlying starvation stress, the interaction network between lncRNAs and their targets was constructed based on 26 DElncRNAs and 72 DEmRNAs. We performed an interaction network analysis of 121 DElncRNA-DEmRNA pairs with a Pearson correlation coefficient greater than 0.99. CONCLUSION: We found that MSTRG.19894.13, MSTRG.16726.3, and MSTRG.12176.1 might play important roles in starvation stress. This study not only generated a library of enriched lncRNAs in piglets, but its outcomes also provide a strong foundation to screen key lncRNAs involved in starvation stress and a reference for subsequent in-depth research.

Icaritin alleviates docetaxel-induced skin injury by suppressing reactive oxygen species via estrogen receptors.

BACKGROUND: Docetaxel (DTX) exhibits antitumor effects against breast cancer by stabilizing microtubules and increasing the accumulation of reactive oxygen species (ROS). DTX extravasation during infusion often causes skin injury. The present study aimed to investigate the effects and mechanisms of icaritin (ICT) on DTX-induced skin injury. METHODS: The effects of ICT on the viability and apoptosis of HaCaT cells were measured by SRB assay and flow cytometry, respectively. Endogenous LC3 puncta and microtubules were determined by immunofluorescence. The number of mitochondria was measured by MitoTracker orange staining. ROS were determined by dihydroethidium staining. The expression of markers of ROS and autophagy were measured by western blotting. Chloroquine, compound D, and tamoxifen were employed as the inhibitor for autophagy and AMPK, estrogen receptors (ERs) modulator, respectively. RESULTS: DTX inhibited the viability and decreased apoptosis of HaCaT cells, which can be rescued by ICT. ICT decreased microtubule bundles, increased the number of mitochondria, and attenuated ROS of HaCaT cells induced by DTX. ICT blocks autophagy and the autophagic flux. Compound C or tamoxifen diminished the protection effects of ICT on DTX-treated HaCaT cells. CONCLUSION: ICT alleviates DTX-induced skin injury by suppressing ROS, reducing microtubule bundles, and blocking autophagy via ERs. Our study indicated that ICT may be a potential candidate for DTX-induced skin injury.

A double-edged sword: The Kelch-like ECH-associated protein 1-nuclear factor erythroid-derived 2-related factor 2-antioxidant response element pathway targeted pharmacological modulation in nonalcoholic fatty liver disease.

Nutraceuticals activating the Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway are widely used for nonalcoholic fatty liver disease (NAFLD) because no specific drugs are approved yet. The pathology of NAFLD is summarized as the 'two-hit' hypothesis. The 'first hit' includes insulin resistance and lipid accumulation. Oxidative stress, lipid peroxidation, and inflammation are regarded as the 'second hit'. Now there is controversial evidence about the roles of the Keap1-Nrf2-ARE pathway and its activators in NAFLD. When the 'first hit' occurs, the hepatocyte-specific Nrf2 deficiency reduces insulin resistance and significantly attenuates lipid accumulation. However, when the 'second hit' occurs, Nrf2 activation reduces oxidative stress and combats inflammation. We reviewed the roles of the Keap1-Nrf2-ARE pathway as a double-edged sword in the development of NAFLD, its inhibitors as a novel therapeutic approach for early NAFLD, and the nutraceutical character of its activators.