Hepatitis B virus (HBV) infection is a major driver of hepatocarcinogenesis. Ferroptosis is a type of iron-mediated cell death that can suppress liver transformation. Previous studies have linked HBV to ferroptosis in liver fibrosis and acute liver failure. However, whether ferroptosis is involved in HBV-mediated liver cancer is poorly understood. Here, we identified heat shock protein family A member 8 (HSPA8) as a crucial host factor that modulates HBV replication and ferroptosis in liver cancer. Hepatitis B X protein (HBx) upregulated HSPA8 by coactivating the transcription factor heat shock factor 1 (HSF1) in cells. HSPA8 enhanced HBV replication by recruiting hepatitis B core protein (HBc) to the HBV covalently closed circular DNA (cccDNA) minichromosome, forming a positive feedback loop. Moreover, HSPA8 suppressed ferroptosis in liver cancer cells by upregulating expression of SLC7A11/GPX4 and decreasing erastin-mediated ROS and Fe2+ accumulation in cells in vitro and in vivo. Inhibition of HSPA8 reduced the growth of HBV-positive liver tumors and increased sensitivity to erastin. In conclusion, HBx-elevated HSPA8 regulates both HBV replication and ferroptosis in liver cancer. Targeting HSPA8 could be a promising strategy for controlling HBV and hepatocarcinogenesis.
Objective: To explore the effects of single-session transcranial direct current stimulation (tDCS) on aerobic performance and explosive force in the one-arm pull-down of long-term trained rock climbers.Method: Twenty athletes (twelve male and eight female) from the Rock Climbing Team of Hunan province (Hunan, China) were selected for a randomized double-blind crossover study. After baseline tests, All subjects visited laboratories twice to randomly receive either sham or a-tDCS at a current intensity of 2 mA for 20 min. The two visits were more than 72 h apart. Immediately after each stimulation, subjects completed a 9-min 3-level-load aerobic test and a one-arm pull-down test.Results: Differences in the heart rate immediately after 9-min incremental aerobic exercises revealed no statistical significance between each group (p > 0.05). However, the decrease in heart rate per unit time after exercise after real stimulation was significantly better than before stimulation (p < 0.05), and no statistical significance was observed between after sham stimulation and before stimulation (p > 0.05). One-arm pull-down explosive force on both sides after real stimulation was improved by a-tDCS compared with before stimulation, but with no significant difference (p > 0.05). Real stimulation was significantly improved, compared with sham stimulation on the right side (p < 0.05).Conclusion: Single-session tDCS could potentially benefit sports performance in professional athletes.
Lipid metabolism disorders may considerably contribute to the formation and development of atherosclerosis (AS). Traditional Chinese medicine has received considerable attention in recent years owing to its ability to treat lipid metabolism disorders using multiple components and targets. Verbena officinalis (VO), a Chinese herbal medicine, exhibits anti-inflammatory, analgesic, immunomodulatory, and neuroprotective effects. Evidence suggests that VO regulates lipid metabolism; however, its role in AS remains unclear. In the present study, an integrated network pharmacology approach, molecular docking, and molecular dynamics simulation (MDS) were applied to examine the mechanism of VO against AS. Analysis revealed 209 potential targets for the 11 main ingredients in VO. Further, 2698 mechanistic targets for AS were identified, including 147 intersection targets between VO and AS. Quercetin, luteolin, and kaempferol were considered key ingredients for the treatment of AS based on a potential ingredient target–AS target network. GO analysis revealed that biological processes were primarily associated with responses to xenobiotic stimuli, cellular responses to lipids, and responses to hormones. Cell components were predominantly focused on the membrane microdomain, membrane raft, and caveola nucleus. Molecular functions were mainly focused on DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and transcription factor binding. KEGG pathway enrichment analysis identified pathways in cancer, fluid shear stress, and atherosclerosis, with lipid and atherosclerosis being the most significantly enriched pathways. Molecular docking revealed that three key ingredients in VO (i.e., quercetin, luteolin, and kaempferol) strongly interacted with three potential targets (i.e., AKT1, IL-6, and TNF-α). Further, MDS revealed that quercetin had a stronger binding affinity for AKT1. These findings suggest that VO has beneficial effects on AS via these potential targets that are closely related to the lipid and atherosclerosis pathways. Our study utilized a new computer-aided drug design to identify key ingredients, potential targets, various biological processes, and multiple pathways associated with the clinical roles of VO in AS, which provides a comprehensive and systemic pharmacological explanation for the anti-atherosclerotic activity of VO.
Fungicides are often used to extend the storage time of postharvest satsuma mandarin fruit. In recent years, fungicide residue has become an issue of food safety. This study aimed to investigate the distribution and migration of three typical fungicides (imazalil, prochloraz, thiophanate-methyl) in postharvest satsuma mandarins using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three fungicides could quickly penetrate satsuma mandarins and their gradient concentrations of residues in the fruit were: carpopodium > mesocarp > epicarp > pulp. However, the residues of three fungicides in the edible pulp were obviously lower than the maximum residue limit (MRL = 5.0 mg kg−1 in China). Residues of the three fungicides decreased in epicarp and carpopodium but increased in mesocarp and pulp during storage. Fungicides could quickly penetrate the fruit, settling primarily in the carpopodium but little in the pulp. Both epicarp and carpopodium were the breakthrough pathways for the fungicides entering the fruit, while epicarp was the main route for the penetration of fungicides. These findings shed new information on the behavior of fungicides and the safety issue of satsuma mandarins.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.