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Background: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of JuB on acetaminophen (APAP) overdose-induced hepatotoxicity have not been determined yet. Methods: C57BL/6 J mice were pre-treated with JuB (20 or 40 mg/kg) for seven days before APAP (400 mg/kg) injection. After 24 h of APAP treatment, serum, and liver tissues were collected to evaluate the therapeutic effects. To investigate whether the Nrf2-STING signaling pathway is involved in the protective effects of JuB against APAP-induced hepatotoxicity, the mice received the DMXAA (the specific STING agonist) or ML385 (the specific Nrf2 inhibitor) during the administration of JuB, and Hematoxylin-eosin staining, Real-time PCR, immunohistochemical, and western blot were performed. Results: JuB pretreatment reversed APAP-induced CYP2E1 accumulations and alleviated APAP-induced acute liver injury. Furthermore, JuB treatment significantly inhibited oxidative stress and the pro-inflammatory cytokines, as well as alleviated hepatocyte apoptosis induced by APAP. Besides, our result also demonstrated that JuB treatment upregulated the levels of total Nrf2, facilitated its nuclear translocation, upregulated the expression of HO-1 and NQO-1, and inhibited the APAP-induced STING pathway activation. Finally, we verified that the beneficial effects of JuB were weakened by DMXAA and ML385. Conclusion: Our study suggested that JuB could ameliorate APAP-induced hepatic damage and verified a previously unrecognized mechanism by which JuB prevented APAP-induced hepatotoxicity through adjusting the Nrf2-STING pathway.

Abstract Background Hepatocellular carcinoma (HCC) is a long-term malignancy that causes high morbidities and mortalities worldwide. Notably, long non-coding RNAs (LncRNAs) have been identified as candidate targets for malignancy treatments. Methods LncRNA LINC01116 and its Pearson-correlated genes (PCGs) were identified and analyzed in HCC patients. The diagnostic and prognostic value of the lncRNA was evaluated using data from The Cancer Genome Atlas (TCGA). Further, we explored the target drugs of LINC01116 for clinical application. Relationships between immune infiltration and PCGs, methylation and PCGs were explored. The diagnostic potentials were then validated by Oncomine cohorts. Results LINC01116 and the PCG OLFML2B are differentially and highly expressed in tumor tissues (both P ≤ 0.050). We found that LINC01116, TMSB15A, PLAU, OLFML2B, and MRC2 have diagnostic potentials (all AUC ≥ 0.700, all P ≤ 0.050) while LINC01116 and TMSB15A have prognostic significance (both adjusted P ≤ 0.050). LINC01116 was enriched in the vascular endothelial growth factor (VEGF) receptor signaling pathway, mesenchyme morphogenesis, etc. After that, candidate target drugs with potential clinical significance were identified: Thiamine, Cromolyn, Rilmenidine, Chlorhexidine, Sulindac_sulfone, Chloropyrazine, and Meprylcaine. Analysis of immune infiltration revealed that MRC2, OLFML2B, PLAU, and TMSB15A are negatively associated with the purity but positively associated with the specific cell types (all P 0.700). Conclusions Differentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressed OLFML2B could be a diagnostic signature involved in HCC via immune infiltrates.

Rill erosion is affected by the sand particle content in soil, especially in the wind and water erosion transition region of the Loess Plateau. The sediment transport capacity (STC) is a key parameter in rill erosion research, assessing the impact of aeolian sand intrusion on the STC of rill flow is of importance for a better understanding of rill erosion. This study aimed to assess the effect of aeolian sand intrusion on the STC on sandified loess slopes, with typical slopes and flow discharges, using a flume system which consisting of a sediment-feeding and a sediment-supply/settlement flume. The sediment feeding flume was jointed by 10° higher than that of the sediment measurement flume section. Three flow discharges (2, 4, and 8 L min−1) and four slope gradients (5°, 10°, 15°, and 25°) were used to represent the natural hydrological conditions under three intrusion rates (SIR) of aeolian sands (10%, 20%, and 50%). The results show that STC increased with slope gradient and flow discharge, and the relationship between the STC and the SIR was significantly affected by the slope gradient; the STCs decreased with the SIR on a slope of 5° but increased with the SIR on steep slopes of 15°–25°, implying a significant impact of slope gradient on the relationship between SIR and STC. The SIR of 50% resulted in the highest sediment concentration nearly 1200 kg m−3 on slopes of 25°. On sandified loess slopes of 10%, 20%, and 50% SIR, the STC were about 30%, 46%, and 57% higher than on loess slopes, indicating an increased erosion rate by sand particle intrusion into loess soil. These results highlight the impact of sand intrusion on STC of rill flow and provide deeper insights into the soil loss process on the sandified loess slope.

Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body’s primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.

Studies have shown that phosphatase and tensin homolog deleted on chromosome ten (PTEN) participates in the regulation of cochlear hair cell survival. Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression. However, whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear. In this study, we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours. We found that PTEN expression was increased in the organ of Corti, including outer hair cells, inner hair cells, and lateral wall tissues. Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons. In addition, noise exposure decreased p-PI3K and p-Akt levels. Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt. Bisperoxovanadium also prevented H2O2-induced hair cell death by reducing mitochondrial reactive oxygen species generation in cochlear explants. These findings suggest that bisperoxovanadium reduces noise-induced hearing injury and reduces cochlear hair cell loss.