Integrated network toxicology, molecular docking, and in vivo experiments to elucidate molecular mechanism of aflatoxin B1 hepatotoxicity.

Due to the rise in temperature and sea level caused by climate change, the detection rate of aflatoxin B1 (AFB1) in food crops has increased dramatically, and the frequency and severity of aflatoxicosis in humans and animals are also increasing. AFB1 has strong hepatotoxicity, causing severe liver damage and even cancer. However, the mechanism of AFB1 hepatotoxicity remains unclear. By integrating network toxicology, molecular docking and in vivo experiments, this research was designed to explore the potential hepatotoxicity mechanisms of AFB1. Thirty-three intersection targets for AFB1-induced liver damage were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, and apoptosis were significantly enriched. In addition, the proteins of ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, and IGF1 exhibited good affinity with AFB1. In vivo experiments, significant pathological changes occurred in the liver of mice. AFB1 induction increased the expression levels of EGFR, ERK, and FOXO1, and decreased the expression levsls of PI3K and AKT1. Moreover, AFB1 treatment caused an increase in Caspase3 expression, and a decrease in Bcl2/Bax ratio. By combining network toxicology with in vivo experiments, this study confirms for the first time that AFB1 promotes the FOXO1 signaling pathway by inactivating PI3K/AKT1 and activating EGFR/ERK signaling pathways, hence aggravating hepatocyte apoptosis. This research provides new strategies for studying the toxicity of environmental pollutants and new possible targets for the development of hepatoprotective drugs.

Protection of taraxasterol against acetaminophen-induced liver injury elucidated through network pharmacology and in vitro and in vivo experiments.

BACKGROUND: Drug-induced liver injury (DILI) is primarily caused by drugs or their metabolites. Acetaminophen (APAP) is an over-the-counter antipyretic analgesic that exhibits high hepatotoxicity when used for long-term or in overdoses. Taraxasterol is a five-ring triterpenoid compound extracted from traditional Chinese medicinal herb Taraxacum officinale. Our previous studies have demonstrated that taraxasterol exerts protective effects on alcoholic and immune liver injuries. However, the effect of taraxasterol on DILI remains unclear. HYPOTHESIS/PURPOSE: This study aimed to elucidate the effects and mechanisms of action of taraxasterol on APAP-induced liver injury using network pharmacology and in vitro and in vivo experiments. METHODS: Online databases of drug and disease targets were used to screen the targets of taraxasterol and DILI, and a protein-protein interaction network (PPI) was constructed. Core target genes were identified using the tool of Analyze of Cytoscape, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed. Oxidation, inflammation and apoptosis were evaluated to determine the effect of taraxasterol on APAP-stimulated liver damage in AML12 cells and mice. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to explore the potential mechanisms of taraxasterol against DILI. RESULTS: Twenty-four intersection targets for taraxasterol and DILI were identified. Among them, 9 core targets were identified. GO and KEGG analysis showed that core targets are closely related to oxidative stress, apoptosis, and inflammatory response. The in vitro findings showed that taraxasterol alleviated mitochondrial damage in AML12 cells treated with APAP. The in vivo results revealed that taraxasterol alleviated pathological changes in the livers of mice treated with APAP and inhibited the activity of serum transaminases. Taraxasterol increased the activity of antioxidants, inhibited the production of peroxides, and reduced inflammatory response and apoptosis in vitro and in vivo. Taraxasterol promoted Nrf2 and HO-1 expression, suppressed JNK phosphorylation, and decreased the Bax/Bcl-2 ratio and caspase-3 expression in AML12 cells and mice. CONCLUSION: By integrating network pharmacology with in vitro and in vivo experiments, this study indicated that taraxasterol inhibits APAP-stimulated oxidative stress, inflammatory response and apoptosis in AML12 cells and mice by regulating the Nrf2/HO-1 pathway, JNK phosphorylation, and apoptosis-related protein expression. This study provides a new evidence for the use of taraxasterol as a hepatoprotective drug.

Emission spectral non-Markovianity in qubit-cavity systems in the ultrastrong coupling regime.

We study the emission spectra of the dissipative Rabi and Jaynes-Cummings models in the non-Markovian and ultrastrong coupling regimes. We have derived a polaron-transformed Nakajima-Zwanzig master equation (PTNZE) to calculate the emission spectra, which eliminates the well-known limitations of the Markovian approximation and the standard second-order perturbation. Using the time-dependent variational approach with the multiple Davydov ansatz as a benchmark, the PTNZE is found to yield accurate emission spectra in certain ultrastrong coupling regimes where the standard second-order Nakajima-Zwanzig master equation breaks down. It is shown that the emission spectra of the dissipative Rabi and Jaynes-Cummings models are, in general, asymmetric under various initial conditions. Direct comparisons of spectra for the two models illustrate the essential role of the qubit-cavity counter-rotating term and the spectral features under different qubit-cavity coupling strengths and system initial conditions.

Effect of recombinant human basic fibroblast growth factor combined with local application of insulin on pain and healing in diabetic patients with deep II degree burns.

OBJECTIVE: To investigate the efficacy of recombinant human basic fibroblast growth factor (rh-bFGF) combined with local application of insulin (INS) in diabetic patients with deep II degree burns, and to analyze the changes in pain and healing. METHODS: Seventy-eight diabetic patients with deep II degree burns treated in our hospital were divided into the observation group (n=39) for combination therapy of rh-bFGF and local INS, and the control group (n=39) for rh-bFGF alone. The two groups were compared regarding treatment effect, wound healing time, pain degree (Visual Analogue Scale, VAS), wound exudate rate, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α), as well as adverse reactions. RESULTS: Compared with the control group, the total clinical effective rate was evidently higher in the observation group (P<0.05). The wound healing time was shorter and the VAS score was lower in the observation group as compared to the control group (both P<0.05). The observation group showed significantly lower wound exudate rate and higher HIF-1α and VEGF protein levels in wound tissue than the control group (all P<0.05). No adverse reactions such as abnormalities in blood routine and hepatorenal function were observed in the two groups during treatment. CONCLUSIONS: rh-bFGF combined with local application of INS is markedly effective in diabetic patients with deep II degree burns. It can relieve pain and shorten healing time, with low wound exudate rate and high safety profile.

Five-in-one nursing management promotes rapid recovery of patients after thoracic surgery.

OBJECTIVE: To explore the application effect of five-in-one nursing management in the rapid recovery of patients undergoing thoracic surgery. METHODS: This prospective study included 45 patients admitted to thoracic surgery before the implementation of five-in-one nursing as the control group and 40 patients admitted during the implementation as the test group. The patients in the control group were nursed by conventional nursing plan, whole those in the test group received the five-in-one nursing management. The perioperative indicators, mental state, postoperative rehabilitation, surgical complications, and nursing satisfaction were compared between the two groups. RESULTS: Compared with the control group, the time of extubation, the time of getting out of bed for the first time, the recovery time of bowel sounds, the time of the first defecation, and the length of hospital stay in the experimental group were significantly shortened (P<0.05). At 24 h after surgery, MTL and GAS levels of patients in the test group were significantly higher than those of the control group (P<0.001). Moreover, the test group had lower visual analogue score (VAS) at different times after the operation, as well as lower the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores after nursing than the control group (P<0.001). The total incidence of postoperative complications in the experimental group was significantly reduced, while nursing satisfaction was significantly increased (P<0.001) when compared with the control group. CONCLUSION: The five-in-one nursing management effectively promoted the rapid recovery of patients after thoracic surgery, shortened the length of hospital stay, and improved nursing satisfaction.

Protective effects of astragaloside IV against ovalbumin-induced lung inflammation are regulated/mediated by T-bet/GATA-3.

Bronchial asthma is characterized by chronic lung inflammation, airway hyperresponsiveness, and airway remodelling. Astragaloside IV (3-O-ß-D-xylopyranosyl-6-O-ß-D-glucopyranosyl-cycloastragenol, AST), the primary pure saponin isolated from the root of Astragalus membranaceus, is an effective compound with distinct pharmacological effects including anti-inflammation, immunoregulation, and antifibrosis. However, the effect of AST on asthma remains unclear. In the present study, in the murine model of asthma, the airway hyperresponsiveness was relieved after treatment with AST, accompanied by a reduction of inflammatory cells. In addition, the levels of IL-4 and IL-5 decreased, while the IFN-γ level increased, in bronchoalveolar lavage fluid. The compound also significantly inhibited the synthesis of GATA-3-encoding mRNA and protein in addition to increasing the synthesis of T-bet-encoding mRNA and protein in both lung tissues and CD4+ T cells. Our findings indicate that AST treatment inhibits ovalbumin-induced airway inflammation by modulating the key master switches GATA-3 and T-bet, which results in committing T helper cells to a Th1 phenotype.