Liver injury changes the biological characters of serum small extracellular vesicles and reprograms hepatic macrophages in mice

BACKGROUND Serum small extracellular vesicles(sEVs)and their small RNA(sRNA)cargoes could be promising biomarkers for the diagnosis of liver injury.However,the dynamic changes in serum sEVs and their sRNA components during liver injury have not been well characterized.Given that hepatic macrophages can quickly clear intravenously injected sEVs,the effect of liver injury-related serum sEVs on hepatic macrophages deserves to be explored.AIM To identify the characteristics of serum sEVs and the sRNAs during liver injury and explore their effects on hepatic macrophages.METHODS To identify serum sEV biomarkers for liver injury,we established a CCL4-induced mouse liver injury model in C57BL/6 mice to simulate acute liver injury(ALI),chronic liver injury(CLI)and recovery.Serum sEVs were obtained and characterized by transmission electron microscopy and nanoparticle tracking analysis.Serum sEV sRNAs were profiled by sRNA sequencing.Differentially expressed microRNAs(miRNAs)were compared to mouse liver-enriched miRNAs and previously reported circulating miRNAs related to human liver diseases.The biological significance was evaluated by Ingenuity Pathway Analysis of altered sEV miRNAs and conditioned cultures of ALI serum sEVs with primary hepatic macrophages.RESULTS We found that both ALI and CLI changed the concentration and morphology of serum sEVs.The proportion of serum sEV miRNAs increased upon liver injury,with the liver as the primary contributor.The altered serum sEV miRNAs based on mouse studies were consistent with human liver disease-related circulating miRNAs.We established serum sEV miRNA signatures for ALI and CLI and a panel of miRNAs(miR-122-5p,miR-192-5p,and miR-22-3p)as a common marker for liver injury.The differential serum sEV miRNAs in ALI contributed mainly to liver steatosis and inflammation,while those in CLI contributed primarily to hepatocellular carcinoma and hyperplasia.ALI serum sEVs decreased both CD86 and CD206 expression in monocyte-derived macrophages but increased CD206 expression in resident macrophages in vitro.CONCLUSION Serum sEVs acquired different concentrations,sizes,morphologies and sRNA contents upon liver injury and could change the phenotype of liver macrophages.Serum sEVs therefore have good diagnostic and therapeutic potential for liver injury.

Sturge-Weber syndrome： a case report and review of literatures

Sturge-Weber syndrome （SWS）, or encephalo- trigeminal angiomatosis, is a rare, congenitalneurocutaneous syndrome characterized by unilateral facial cutaneous vascular malformation （nevus flammeus or port-wine stain） in association with ipsilateral leptomeningeal angiomatosis. Prevalence is approximately one per 50 000 live births. Males and females are equally affected and there is no racial bias. 1,2 The common clinical manifestations of SWS include progressive seizures, unilateral cutaneous vascular nevus following the ophthalmic divisions of the trigeminal nerve, ipsilateral glaucoma, contralateral hemiparesis, hemiatrophy, hemianopia and mental retardation. The radiographic hallmark of SWS is ＂tram-line＂ or gyriform calcifications usually involving the occipital and parietal lobes. Histologic studies have revealed that intracranial lesions of SWS display as leptomeningeal angiomatosis, and gyriform calcifications, neuronal loss, astrogliosis in underlying brain tissue.

The pathogenesis of Chlamydia pneumoniae-type pneumonitis in mice

Objective To evaluate mice as experimental animals for Chlamydia pneumoniae (C.pneumoniae) infection and investigate the pathogenesis of C.pneumoniae derived pneumonitis.Methods Icr mice were inoculated with the C.pneumoniae strain, CWL-029, either intranasally or intravenously. After a single dose inoculation, mice were killed on the 1st, 3rd, 7th, 14th, 21st, 28th and 60th days. The pathological changes in lung tissue were analyzed.Results The Icr mice were shown to be susceptible to C.pneumoniae. Inoculation into mice with C.pneumoniae induced a prolonged course of lung infection, as demonstrated by persistence of lung pathology (up to 60 days). Via intranasal inoculation of mice, lung pathology was characterized by patchy interstitial pneumonitis with predominately neutrophil leukocyte infiltration early (within the first 7 days) and lymphocyte infiltration in the later stages (14 days later) of infection. After intravenous inoculation, a similarly developed interstitial pneumonitis was observed, but it was milder and patchier, especially in early stages. C.pneumoniae DNA was detected by polymerase chain reaction (PCR) intermittently in the lung tissue. Inoculated mice developed serum IgG antibody responses.Conclusion The Icr mice were susceptible to C.pneumoniae, resulting in a pulmonary infection characterized by interstitial pneumonitis, occurring most strongly via intranasal inoculation.