Isoorientin Ameliorates APAP-Induced Hepatotoxicity via Activation Nrf2 Antioxidative Pathway: The Involvement of AMPK/Akt/GSK3β

Oxidative stress has been highlighted as therapeutic targets for acetaminophen (APAP)-induced hepatotoxicity. Isoorientin (Iso), a well-known flavonoid-like compound, has been shown to have antioxidant potential. However, the effect of Iso on APAP-induced liver injury has not yet been elucidated. The present study investigated the hepatoprotective effect of Iso and its underlying mechanism. C57BL/6J mice were used to evaluate the hepatoprotective effect of Iso in vivo and HepG2 cells were utilized to further decipher the mechanisms of Iso -induced Nrf2 activation. We found that Iso treatment significantly reduced APAP-induced hepatotoxicity by reducing the lethality, histopathological liver changes, and alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum. These effects were accompanied by decreased malondialdehyde (MDA) formation and myeloperoxidase level (MPO), and by decreased superoxide dismutase (SOD) and glutathione (GSH) depletion. Moreover, Iso induced Nrf2 activation and translocation as well as upstream AMPK/Akt/GSK3β activation. Furthermore, Iso effectively alleviated mitochondrial dysfunction by reducing c-jun N-terminal kinase phosphorylation and translocation, Bax mitochondrial translocation, and apoptosis-inducing factor and cytochrome c release. Further mechanistic investigations revealed that the activation of Nrf2 by Iso via the AMPK/Akt/GSK3β pathway contributed to the hepatoprotective activity of Iso in vitro. In addition, the Iso-mediated inhibition of APAP-induced the lethality, histopathological changes and mitochondrial dysfunction observed in WT mice was nearly absent in Nrf2-/- mice. In summary, Iso ameliorated APAP-induced hepatotoxicity by activating Nrf2 via the AMPK/Akt/GSK3β pathway

Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure

Inflammation and oxidative stress are essential for the pathogenesis of fulminant hepatic failure (FHF). Asiatic acid (AA), which is a pentacyclic triterpene that widely occurs in various vegetables and fruits, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of AA against lipopolysaccharide (LPS) and d-galactosamine (GalN)-induced FHF and the underlying molecular mechanisms. Our findings suggested that AA treatment effectively protected against LPS/d-GalN-induced FHF by lessening the lethality; decreasing the alanine transaminase and aspartate aminotransferase levels, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α production, malondialdehyde formation, myeloperoxidase level and reactive oxygen species generation (i.e., H2O2, NO, and O2−), and increasing the glutathione and superoxide dismutase contents. Moreover, AA treatment significantly inhibited mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway activation via the partial induction of programmed cell death 4 (PDCD4) protein expressions, which are involved in inflammatory responses. Furthermore, AA treatment dramatically induced the expression of the glutamate-cysteine ligase modifier subunit, the glutamate-cysteine ligase catalytic subunit, heme oxygenase-1, and NAD (P) H: quinoneoxidoreductase 1 (NQO1), which are largely dependent on activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) through the induction of AMP-activated protein kinase (AMPK) and glycogen synthase kinase-3β (GSK3β) phosphorylation. Accordingly, AA exhibited protective roles against LPS/d-GalN-induced FHF by inhibiting oxidative stress and inflammation. The underlying mechanism may be associated with the inhibition of MAPK and NF-κB activation via the partial induction of PDCD4 and upregulation of Nrf2 in an AMPK/GSK3β pathway activation-dependent manner

Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways

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Identification of porcine PARP11 as a restricted factor for pseudorabies virus

IntroductionPRV infection in swine can cause devastating disease and pose a potential threat to humans. Advancing the interplay between PRV and host is essential to elucidate the pathogenic mechanism of PRV and identify novel anti-PRV targets.MethodsPARP11-KO PK-15 cells were firstly constructed by CRISPR/Cas9 technology. Next, the effect of PARP11-KO on PRV infection was determined by RT-qPCR, TCID50 assay, RNA-seq, and western blot.Results and discussionIn this study, we identified PARP11 as a host factor that can significantly affect PRV infection. Inhibition of PARP11 and knockout of PARP11 can significantly promoted PRV infection. Subsequently, we further found that PARP11 knockout upregulated the transcription of NXF1 and CRM1, resulting in enhanced transcription of viral genes. Furthermore, we also found that PARP11 knockout could activate the autophagy pathway and suppress the mTOR pathway during PRV infection. These findings could provide insight into the mechanism in which PARP11 participated during PRV infection and offer a potential target to develop anti-PRV therapies

LGG/LAC-MMT combination mitigates AFB1-induced liver and intestinal injury in mice based on intestinal microbiota modulation

AFB1 induces hepatotoxicity and enterotoxicity. Lactobacillus acidophilus (LAC) and Lactobacillus rhamnosus (LGG), both belonging to LAB, have strong binding affinity for AFB1. Montmorillonite (MMT) not only adsorbs AFB1 but also serves as a carrier for LAB, thereby enhancing their colonization ability and prolonging their survival. Despite the unclear effects of LGG/LAC-MMT combination on AFB1-induced tissue injury and intestinal microbiota disruption, this study aimed to determine whether it could effectively alleviate tissue damage from AFB1 exposure and enhance LAB colonization capacity in mouse intestines. Separately, LGG (2 × 109 cfu/mL) and LAC (2 × 109 cfu/mL) were combined with MMT (0.5 mg/kg), and the AFB1-intoxicated mice were gavaged with the mixtures for 4 weeks. Findings suggested that LGG, LAC, and MMT supplementation restored oxidative stress and inflammatory caused by AFB1 to some degree. Furthermore, they altered the intestinal microbiota structure, enhancing the colonization ability of LABs, thereby alleviating liver and intestinal injury. The combination of LGG/LAC-MMT was more effective, especially LAC-MMT. Overall, LGG/LAC-MMT exhibits a synergistic effect and can effectively ameliorate AFB1-induced tissue injury and intestinal microbiota disorder

Guidelines for burn rehabilitation in China

Abstract Quality of life and functional recovery after burn injury is the final goal of burn care, especially as most of burn patients survive the injury due to advanced medical science. However, dysfunction, disfigurement, contractures, psychological problems and other discomforts due to burns and the consequent scars are common, and physical therapy and occupational therapy provide alternative treatments for these problems of burn patients. This guideline, organized by the Chinese Burn Association and Chinese Association of Burn Surgeons aims to emphasize the importance of team work in burn care and provide a brief introduction of the outlines of physical and occupational therapies during burn treatment, which is suitable for the current medical circumstances of China. It can be used as the start of the tools for burn rehabilitation.</jats:p