The accumulation of deoxyribonucleic acid (DNA) oxidative damage mediated by reactive oxygen species (ROS) is closely associated with liver diseases. 8-Oxoguanine (8-OxoG), a prevalent DNA oxidation product, plays a significant role in liver disease progression. The base excision repair (BER) pathway, comprising over 30 proteins including 8-OxoG DNA glycosylase1 (OGG1), MutY homolog (MUTYH), and MutT homolog protein 1 (MTH1), is responsible for the clearance and mismatch repair of 8-OxoG. Abnormally high levels of 8-OxoG and dysregulated expression and function of 8-OxoG repair enzymes contribute to the onset and development of liver diseases. Consequently, targeting the 8-OxoG production and repair system with agonists or inhibitors may offer a promising approach to liver disease treatment. This review summarizes the impact of 8-OxoG accumulation and dysregulated repair enzymes on various liver diseases, including viral liver disease, alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), cholestatic liver disease (CLD), liver fibrosis, cirrhosis, and liver cancer. Additionally, we review natural constituents as potential therapeutic agents that regulate 8-OxoG production, repair enzymes, and repair system-related signal pathways in oxidative damage-induced liver diseases.
Humans ; Liver Diseases/genetics* ; Biological Products/pharmacology* ; DNA Repair/drug effects* ; Guanine/metabolism* ; Animals ; Disease Progression ; DNA Damage ; Oxidative Stress

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanism by which Hypericum japonicum Thunb-Prunella vulgaris treat liver injury.Mice were randomly divided into four groups:a control group(CON),a model group(CCl4),a high-dose drug group(TXD-H),and a low-dose drug group(TXD-L).A mouse liver in-jury model was established using CCl4 induction.The pathological morphology of liver tissue was observed,and the serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Active ingredients of traditional Chinese medicine and targets related to these medicines and diseases were obtained from databases such as TCMSP,PubChem,Swiss Tar-get Prediction,GeneCards,and DisGeNET.The intersection of these targets was used to identify potential drug targets.A network diagram illustrating the relationships between"drug-active com-ponent-intersection target"was constructed using Cytoscape.Potential targets were analyzed using the STRING database for protein-protein interaction(PPI)analysis and the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Tools software.Subsequently,key target genes,including those related to the NLRP3 inflammasome and pyroptosis,were detected to validate the molecular docking results.Animal experimental results showed that compared to the CON group,serum AST and ALT activities in the CCl4 group mice were significantly increased(P＜0.01),while in the TXD-L group,serum AST and ALT activities were significantly decreased(P＜0.05)compared to the CCl4 group,and in the TXD-H group,AST and ALT activities were significantly decreased(P＜0.01).Through network pharmacology,135 potential targets were i-dentified,with key components found to be tetramethoxyluteolin,quercetin,kaempferol,luteolin and morin based on degree values,and key targets including TNF,SRC,AKT1,EGFR and ESR1.GO enrichment analysis yielded 304 entries,while KEGG enrichment analysis identified 91 biologi-cal pathways.Molecular docking results demonstrated strong binding between the main compo-nents of Hypericum japonicurn Thunb-Prunella vulgaris and key targets.qPCR results showed that compared to the CON group,the CCl4 group exhibited upregulated relative expression levels of SRC,EGFR,TNF-α,AKT1,and IL-18 mRNA,with significant increases in MyD88,NF-κB,IL-1β,NLRP3,Caspase-1,and ASC mRNA(P＜0.05),and significant upregulation of TLR4 and GS-DMD mRNA(P＜0.01).Compared to the CCl4 group,the TXD-H group displayed significant downregulation of EGFR,AKT1,TLR4,IL-1β,and GSDMD mRNA(P＜0.01),significant decrea-ses in TNF-α,MyD88,NF-κB,NLRP3,and ASC mRNA(P＜0.05),while SRC,IL-18,and Caspase-1 mRNA showed a downward trend.In conclusion,Hypericum japonicum Thunb-Prunel-la vulgaris exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the NF-κB-NLRP3 pathway to reduce hepatocyte pyroptosis may be one of the important pathways for its protective effects.

Objective To analyze the cunent situation and latent profiles of nurses'perceived organizational support,and explore the influencing factors of different types.Methods Through convenience sampling,a total of 1,860 nurses from the Pearl River Delta,Northern Guangdong,Eastern Guangdong and Western Guangdong regions of Guangdong Province were selected for the survey between October and December 2023.The demographic questionnaire,the Perceived Organizational Support Scale,and the Psychological Resilience Scale were used for investigation.The latent profiles of the nurses'perceived organizational support,the influencing factors of latent profiles were identified by single-factor analysis and multivariate Logistic regression.Results The score of the items of the perceived organizational support in l,819 nurses is(3.47±0.88)scores.Nurses perceived organizational support is divided into 3 latent classes,namely"poor group"(10.1％),"balanced group"(44.4％),and"rich group"(45.5％).The influencing factors include recruitment type,hospital level,and psychological resilience(all P＜0.05).Conclusion The perceived organizational support among nurses is moderately high and heterogeneous,which could be divided into 3 latent profiles.Nursing managers should focus on nurses from the poor group and balanced group and intervene with nurses according to the influencing factors of the different latent profiles to improve the level of nurses perceived organizational support.

Objective To analyze the cunent situation and latent profiles of nurses'perceived organizational support,and explore the influencing factors of different types.Methods Through convenience sampling,a total of 1,860 nurses from the Pearl River Delta,Northern Guangdong,Eastern Guangdong and Western Guangdong regions of Guangdong Province were selected for the survey between October and December 2023.The demographic questionnaire,the Perceived Organizational Support Scale,and the Psychological Resilience Scale were used for investigation.The latent profiles of the nurses'perceived organizational support,the influencing factors of latent profiles were identified by single-factor analysis and multivariate Logistic regression.Results The score of the items of the perceived organizational support in l,819 nurses is(3.47±0.88)scores.Nurses perceived organizational support is divided into 3 latent classes,namely"poor group"(10.1％),"balanced group"(44.4％),and"rich group"(45.5％).The influencing factors include recruitment type,hospital level,and psychological resilience(all P＜0.05).Conclusion The perceived organizational support among nurses is moderately high and heterogeneous,which could be divided into 3 latent profiles.Nursing managers should focus on nurses from the poor group and balanced group and intervene with nurses according to the influencing factors of the different latent profiles to improve the level of nurses perceived organizational support.

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanism by which Hypericum japonicum Thunb-Prunella vulgaris treat liver injury.Mice were randomly divided into four groups:a control group(CON),a model group(CCl4),a high-dose drug group(TXD-H),and a low-dose drug group(TXD-L).A mouse liver in-jury model was established using CCl4 induction.The pathological morphology of liver tissue was observed,and the serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Active ingredients of traditional Chinese medicine and targets related to these medicines and diseases were obtained from databases such as TCMSP,PubChem,Swiss Tar-get Prediction,GeneCards,and DisGeNET.The intersection of these targets was used to identify potential drug targets.A network diagram illustrating the relationships between"drug-active com-ponent-intersection target"was constructed using Cytoscape.Potential targets were analyzed using the STRING database for protein-protein interaction(PPI)analysis and the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Tools software.Subsequently,key target genes,including those related to the NLRP3 inflammasome and pyroptosis,were detected to validate the molecular docking results.Animal experimental results showed that compared to the CON group,serum AST and ALT activities in the CCl4 group mice were significantly increased(P＜0.01),while in the TXD-L group,serum AST and ALT activities were significantly decreased(P＜0.05)compared to the CCl4 group,and in the TXD-H group,AST and ALT activities were significantly decreased(P＜0.01).Through network pharmacology,135 potential targets were i-dentified,with key components found to be tetramethoxyluteolin,quercetin,kaempferol,luteolin and morin based on degree values,and key targets including TNF,SRC,AKT1,EGFR and ESR1.GO enrichment analysis yielded 304 entries,while KEGG enrichment analysis identified 91 biologi-cal pathways.Molecular docking results demonstrated strong binding between the main compo-nents of Hypericum japonicurn Thunb-Prunella vulgaris and key targets.qPCR results showed that compared to the CON group,the CCl4 group exhibited upregulated relative expression levels of SRC,EGFR,TNF-α,AKT1,and IL-18 mRNA,with significant increases in MyD88,NF-κB,IL-1β,NLRP3,Caspase-1,and ASC mRNA(P＜0.05),and significant upregulation of TLR4 and GS-DMD mRNA(P＜0.01).Compared to the CCl4 group,the TXD-H group displayed significant downregulation of EGFR,AKT1,TLR4,IL-1β,and GSDMD mRNA(P＜0.01),significant decrea-ses in TNF-α,MyD88,NF-κB,NLRP3,and ASC mRNA(P＜0.05),while SRC,IL-18,and Caspase-1 mRNA showed a downward trend.In conclusion,Hypericum japonicum Thunb-Prunel-la vulgaris exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the NF-κB-NLRP3 pathway to reduce hepatocyte pyroptosis may be one of the important pathways for its protective effects.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.

Purpose: The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells. Materials and Methods: nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro. Results: A high-affinity peptide (nABPD1, KD=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (KD=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells. Conclusion nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.