RESUMEN

Drug-Induced Liver Injury (DILI) and herb Induced Liver Injury (HILI) continues to pose a substantial challenge in both clinical practice and drug development, representing a grave threat to patient well-being. This comprehensive review introduces a novel perspective on DILI and HILI by thoroughly exploring the intricate microenvironment of the liver. The dynamic interplay among hepatocytes, sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, cholangiocytes, and the intricate vascular network assumes a central role in drug metabolism and detoxification. Significantly, this microenvironment is emerging as a critical determinant of susceptibility to DILI and HILI. The review delves into the multifaceted interactions within the liver microenvironment, providing valuable insights into the complex mechanisms that underlie DILI and HILI. Furthermore, we discuss potential strategies for mitigating drug-induced liver injury by targeting these influential factors, emphasizing their clinical relevance. By highlighting recent advances and future prospects, our aim is to shed light on the promising avenue of leveraging the liver microenvironment for the prevention and mitigation of DILI and HILI. This deeper understanding is crucial for advancing clinical practices and ensuring patient safety in the realm of DILI and HILI.

Asunto(s)

Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado , Humanos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Animales , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Microambiente Celular/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hepatocitos/metabolismo

RESUMEN

BACKGROUND: The efficacy of flavonoid supplementation in animal models of pulmonary fibrosis has been demonstrated. PURPOSE: We conducted a systematic review and meta-analysis to evaluate the efficacy and underlying mechanisms of flavonoids in animal models of bleomycin-induced pulmonary fibrosis. STUDY DESIGN: Relevant studies (n = 45) were identified from English- and Chinese-language databases from the inception of the database until October 2023. METHODS: Methodological quality was evaluated using the SYRCLE risk of bias tool. Statistical analyses were conducted using RevMan 5.3 and Stata 17.0. Lung inflammation and fibrosis score were the primary outcome indicators. RESULTS: Flavonoids can alleviate pathological changes in the lungs. The beneficial effects of flavonoids on pulmonary fibrosis likely relate to their inhibition of inflammatory responses, restoration of oxidative and antioxidant homeostasis, and regulation of fibroblast proliferation, migration, and activation by transforming growth factor ß1/mothers against the decapentaplegic homologue/AMP-activated protein kinase (TGF-ß1/Smad3/AMPK), inhibitor kappa B alpha/nuclear factor-kappa B (IκBα/NF-κB), phosphatidylinositol 3-kinase (PI3K)/AKT, interleukin 6/signal transducer/activator of transcription 3 (IL6/STAT3), and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathways. CONCLUSION: Flavonoids are potential candidate compounds for the prevention and treatment of pulmonary fibrosis. However, extensive preclinical research is necessary to confirm the antifibrotic properties of natural flavonoids.

Asunto(s)

Flavonoides , Fibrosis Pulmonar , Flavonoides/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Animales , Bleomicina , Modelos Animales de Enfermedad , Pulmón/efectos de los fármacos , Pulmón/patología , Antioxidantes/farmacología , Transducción de Señal/efectos de los fármacos

RESUMEN

Background: Acute liver injury (ALI) is an important global health concern, primarily caused by widespread hepatocyte cell death, coupled with a complex immune response and a lack of effective remedies. This study explores the underlying mechanisms, immune infiltration patterns, and potential targets for intervention and treatment ALI. Methods: The datasets of acetaminophen (APAP), carbon tetrachloride (CCl4), and lipopolysaccharide (LPS)-induced ALI were obtained from the GEO database. Differentially expressed genes (DEGs) were individually identified using the limma packages. Functional enrichment analysis was performed using KEGG, GO, and GSEA methods. The overlapping genes were extracted from the three datasets, and hub genes were identified using MCODE and CytoHubba algorithms. Additionally, PPI networks were constructed based on the String database. Immune cell infiltration analysis was conducted using ImmuCellAI, and the correlation between hub genes and immune cells was determined using the Spearman method. The relationship between hub genes, immune cells, and biochemical indicators of liver function (ALT, AST) was validated using APAP and triptolide (TP) -induced ALI mouse models. Results: Functional enrichment analysis indicated that all three ALI models were enriched in pathways linked to fatty acid metabolism, drug metabolism, inflammatory response, and immune regulation. Immune analysis revealed a significant rise in macrophage infiltration. A total of 79 overlapping genes were obtained, and 10 hub genes were identified that were consistent with the results of the biological information analysis after screening and validation. Among them, Clec4n, Ms4a6d, and Lilrb4 exhibited strong associations with macrophage infiltration and ALI.

Asunto(s)

Acetaminofén , Hígado , Animales , Ratones , Acetaminofén/efectos adversos , Hepatocitos , Genes Sobrepuestos , Biología Computacional

RESUMEN

Gracilaria lemaneiformis polysaccharide (GLP) has varieties of antioxidation, however, the therapeutic effects of GLP on ulcerative colitis (UC) and the potential mechanisms involved are still incomplete. In the study, the analysis of the ζ-potential, thermal, and morphology properties demonstrated that GLP was a negatively charged polymer, and had great thermostability and irregular network. Moreover, the GLP treatment has the effects of reducing the severity of colitis caused by dextran sulfate sodium by alleviating the colon damage of mice, and increasing the amount of short-chain fatty acids in the intestines, alleviating histopathological inflammation. The sequencing results and α-diversity analysis showed that GLP could improve biodiversity, restore the abundance of Bacteroidetes, and decrease the proportion of Firmicutes. The level of CCL-25 and CCR-9 were inhibited, CD40 and TGF-ß1 were increased. In summary, GLP has potentiality to be utilized as a hopeful functional food to the UC patients.