Morphological findings in the liver of diabetic rats after intraportal transplantation of neonatal isologous pancreatic islets

Morphological (light microscopical, immunohistological and electron microscopical) findings in the recipient liver of rats with streptozotocin-induced diabetes, obtained 9 months after intraportal injection of neonatal isologous pancreatic islets, are described and their significance discussed. - The results support the assumption of active ingrowth of nonmyelinated nerve fibers into the islet isografts. - The hepatocytes surrounding the islet isografts contain-obviously owing to the influence of unusually high and locally variable concentrations of insulin-a focally increased number of enlarged mitochondria, abundant glycogen and a smaller amount of neutral fat droplets. Furthermore, hepatocytes and cells looking like hepatocytes (hepato-cyte-like cells) with typically structured cytoplasmic beta(insulin)granules were found bordering the islet isografts. These results could be interpreted as an expression of arteficial or nonarteficial fusion of beta cells with hepatocytes, i.e. formation of hybrid cells (“in vivo hybridization”). Alternatively, they might reflect insulin uptake and storage in the hepatocytes. In addition, these findings suggest that contact between neonatal islet tissue and liver tissue could be a trigger for the in vivo transformation (modulation) of differentiated cells of similar embryonic development in the adult organism.     

Significant hepatic expression of IL-2 and IL-8 in biliary atresia compared with other neonatal cholestatic disorders

ObjectivesAlthough the exact etiology of biliary atresia (BA) is still elusive, inflammation plays a key role. Release of proinflammatory cytokines from activated immune cells perpetuates the injury and causes biliary destruction. We aimed to study interleukin (IL)-2 and IL-8 expression in liver tissue of BA patients compared with other neonatal cholestatic disorders.MethodsThe study included 59 infants with neonatal cholestasis in two groups; BA group (n = 31) and non-BA group (n = 28) with cholestatic disorders other than BA as controls. Demographic, clinical, laboratory, and histopathological parameters were collected. IL-2 and IL-8 immunostaining was performed. Immunostaining in portal cellular infiltrate was scored as positive or negative and expressed as the mean cell count in three portal tracts.ResultsThe mean value of IL-2 and IL-8 positive inflammatory cells was significantly higher in BA than in non-BA group (P-values of 0.004 and 0.002 respectively). IL-2 correlated significantly with IL-8 immunostaining in both BA and non-BA group (P < 0.0001 for both). Furthermore, both cytokines in both groups correlated significantly with inflammatory activity in liver biopsy while there was no significant correlation with the other studied parameters. Yet, there was a trend of increased expression of IL-2 and IL-8 with increasing stage of fibrosis in BA group. This trend was not observed in non-BA group.ConclusionThe significantly higher expression of IL-2 and IL-8 in patients with BA compared to non-BA suggests a potential role for these cytokines in the pathogenesis in therapy of this devastating neonatal hepatic disorder.     

遗传性胆红素代谢障碍与胆汁淤积NGS方法的建立及应用

为快速准确、低成本、高通量地检测我国人群常见的遗传性胆红素代谢障碍及胆汁淤积综合征，选择了10个易感基因的全部外显子及内含子剪切区的SNP/CNV，建立了基于二代测序技术（next generation sequencing, NGS）的靶向捕获测序方法。通过6例已知突变位点的样本对该方法的准确性进行验证，准确率为100%。收集首都医科大学附属北京友谊医院遗传性胆红素代谢障碍及胆汁淤积综合征患者39例进行检测，共检测到58种突变。检测结果与HGMD、ClinVar、OMIM突变数据库比较，未报道的突变通过千人基因组数据集对比并按照哈温平衡检验（HWE_P＞0.05）和χ^２ 检验确定新突变19种。检测到的不同突变类型有效地揭示了该类疾病的遗传多样性。NGS方法的建立及应用为临床诊断提供了新的技术手段。     

Nervous system and primary liver cancer

Recent advances have found irregular activities of the nervous system-associated factors in the development and progression of primary liver cancer. These factors contributed in the regulation of migration, proliferation, and apoptosis of cancer cells, and took a role in modulating invasion, metastasis, and recurrence after curative treatment. In clinical researches, neural-related factors were found to be significant prognostic factors, suggesting that the interactions between nervous system and primary liver cancer are indispensable in understanding underlying biological mechanisms. Herein, we reviewed up-to-date achievements in this area and the future perspectives of the interactions between the nervous system and primary liver cancer.