Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTSO_LILarge-scale scRNA-seq analysis depicts the immune landscape of COVID-19 C_LIO_LILymphopenia and active T and B cell responses coexist and are shaped by age and sex C_LIO_LISARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses C_LIO_LICytokine storms with systemic S100A8/A9 are associated with COVID-19 severity C_LI

Isoflavone preventing ultraviolet radiation induced skin injuries of mice / 第二军医大学学报

Objective To explore the protective effect of external use of isoflavone cream on ultraviolet radiation induced skin injuries of mice and its mechanisms.Methods A total of 48 male ICR mice were randomly assigned to vehicle (control),ultraviolet radiation (UV),2％ isoflavone+UV and 3％ isoflavone+-UV groups,with 12 mice in each group,and the naked skin of mice in the four groups were treated with sesame oil (15 min),sesame oil (15 min) in combined UV (first radiation with 1.55 J/cm2 long-wave ultraviolet [UVA] for 18 min,and then with 0.95 J/cm2 middle-wave ultraviolet [UVB] for 11 min),2％ isoflavone (15 min) in combined UV and 3％ isoflavone (15 min) in combined UV,respectively.After radiation for 7 days,the UV-exposed skins were obtained to observe the morphological and histological changes using H-E staining.The contents of interleukin (IL)-1β,IL-6,tumor necrosis factor α (TNF-α),malondialdehyde (MDA),superoxide dismutase (SOD) and catalase (CAT) in the skins were determined using ELISA or corresponding kits.Results (1) UV irradiation caused erythema and crusting in skin,and inflammatory cell infiltration in the dermis and fractured elastic fiber were observed microscopically.Isoflavone pretreatment effectively ameliorated these damages in mice skin.(2) Compared with the control group,contents of IL-1β,IL-6 and TNF-α in the UV group were significantly increased (P＜0.05);however,the contents of IL-1β,IL-6 and TNF-α were significantly reversed by isoflavone pretreatment (P＜0.05,P＜0.01).(3) Compared with the control group,the skin MDA content in the UV group was significantly increased (P＜0.05),SOD and CAT contents were significantly decreased (P＜0.05);however,the isoflavone pretreatment significantly reversed the alterations of MDA,SOD and CAT (P＜0.05,P＜0.01).Conclusion Isoflavone exerts protective effects against the ultraviolet induced skin damage in mice through alleviating lipid peroxidation,oxidative stress and inflammatory response.