Abstract Purpose Microvascular invasion (MVI) is a risk factor for the recurrence and poor prognosis of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying MVI-mediated progression of HCC remain unclear. This study aimed to discuss the background of MVI-positive HCC through multiple approaches. Patients and methods: The cancer genome atlas (TCGA) database analysis, next-generation sequencing (NGS), time-of-flight mass-cytometry (CyTOF), imaging mass cytometry (IMC) and lipidomics were used to analyze the molecular characteristics of MVI-positive HCC. Results Pathway enrichment analysis of TCGA database and NGS showed that the enriched pathways in MVI-positive HCC were significantly involved in the tumor microenvironment (TME) remodeling; moreover, single-sample gene set enrichment (ssGSEA) and xCell analysis indicated that the TME of MVI-positive HCC might be in low immune state. In-depth interrogation of the immune landscapes using CyTOF showed that the ratio of Tregs to CD4 + T cells in MVI-positive HCC was higher than that in MVI-negative HCC. CD4 + T cells, CD8 + T cells, Tregs and tumor-associated macrophages (TAMs) express higher levels of immune exhaustion-related markers in MVI-positive HCC. IMC further showed that in MVI-positive HCC the distance between T cells and CAFs was significantly shortened, and the expression of PD-L1 in T cells was higher. The lipidomics results showed the cholesterol which may cause T cells to be in immune exhaustion was significantly elevated in MVI-positive HCC. Conclusion Through high-dimensional analysis, we found that there was immunosuppression of TME in MVI-positive HCC, which may be the cause of worse prognosis.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Abstract Introduction The main active components in hawthorn leaves possess various biological activities such as anti‐inflammatory, antioxidant, and hypolipidemic effects. Therefore, it is necessary to develop an effective and reliable extraction method to extract these active compounds from hawthorn leaves. Objective To establish a simple, rapid, and sensitive method for extraction and determination of polyphenolic compounds from hawthorn leaves. Methods In this study, a microwave‐assisted reaction and extraction (MARE) combined with ultra‐high‐performance liquid chromatography with ultraviolet detector method was established to extract and determine the polyphenolic compounds in hawthorn leaves. The solid reagent aqueous solutions were applied as extraction solvents, preventing the use of organic solvents. The target analytes were identified by quadrupole time‐of‐flight tandem mass spectrometry. Several experimental parameters that can significantly affect the extraction efficiency were evaluated and optimised. Results The optimal conditions were as follows: 0.1 g of sodium carbonate was used as solid reagent, the amount of sodium borate was set at 0.01 g, extraction time was 10 min, extraction temperature was set at 50°C, pH value was adjusted to 7. The validation experiments demonstrated that the method had high sensitivity with the limits of detection in the range 26.5–37.7 ng/mL. The average recoveries ranged from 80.22% to 93.27%. Conclusion In this work, the proposed MARE method was successfully applied to extract and determine polyphenolic compounds in hawthorn leaf samples. Compared with other reported methods, the present method was faster, greener, and more sensitive.
Abstract Background Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. Methods COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. Results The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV 20,50 /FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1β attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1β/STAT1 signaling via MTs. Conclusions These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1β/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD. Graphical Abstract Schematic mechanisms underlying the regulatory effects of melatonin on macrophage polarization and apoptosis in IAV infection plus cigarette stimulation-induced AECOPD model.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
