Pulmonary lymphomatoid granulomatosis in a 4-year-old girl: A case report.

BACKGROUND: Pulmonary lymphomatoid granulomatosis (PLG) is a lymphoproliferative disease associated with Epstein-Barr viral infection occurring mainly in adults and rarely in children. It is characterized by multiple pulmonary nodules. Its diagnosis depends on lung biopsy findings. Most patients are immunodeficient, and it commonly presents in children undergoing chemotherapy for leukemia. We report the case of a child with PLG caused by a mutation in the macrophage-expressed gene 1 (MPEG1), suggesting possible PLG occurrence in children undergoing treatment for pulmonary nodular lesions. CASE SUMMARY: This study reports a case of PLG without apparent immunodeficiency, suggesting the possibility of this disease occurrence during the treatment of pulmonary nodular lesions in children. Initially, the cause was assumed to be an atypical pathogen. Following conventional anti-infective treatment, chest computed tomography findings revealed that there were still multiple nodules in the lungs. Additionally, the patient was found to be infected with the Epstein-Barr virus. Histopathological examination of the resected lung revealed lymphoproliferative lesions with necrosis. Small lymphocytes, plasma cells, and histiocytes were observed in the background, although Reed-Sternberg cells were absent. Immunohistochemical staining [CD20(+), CD30(+), and CD3(+)] and EBV-encoded small RNA1/2 in situ hybridization of small lymphocytes revealed approximately 200 cells/high-power field. Whole exon sequencing of the patient revealed a mutation in the MPEG1. The patient was eventually diagnosed with PLG and transferred to the Department of Pediatric Oncology for bone marrow transplantation. CONCLUSION: As PLG is rare and fatal, it should be suspected in clinical settings when treatment of initial diagnosis is ineffective.

Induction of activation of the antioxidant response element and stabilization of Nrf2 by 3-(3-pyridylmethylidene)-2-indolinone (PMID) confers protection against oxidative stress-induced cell death.

The antioxidant response elements (ARE) are a cis-acting enhancer sequence located in regulatory regions of antioxidant and detoxifying genes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a member of the Cap 'n' Collar family of transcription factors that binds to the ARE and regulates the transcription of specific ARE-containing genes. Under oxidative stress, Nrf2/ARE induction is fundamental to defense against reactive oxygen species (ROS) and serves as a key factor in the protection against toxic xenobiotics. 3-(3-Pyridylmethylidene)-2-Indolinone (PMID) is a derivative of 2-indolinone compounds which act as protein kinase inhibitors and show anti-tumor activity. However, the role of PMID in the oxidative stress remains unknown. In the present study, we showed that PMID induced the activation of ARE-mediated transcription, increased the DNA-binding activity of Nrf2 and then up-regulated the expression of antioxidant genes such as HO-1, SOD, and NQO1. The level of Nrf2 protein was increased in cells treated with PMID by a post-transcriptional mechanism. Under CHX treatment, the stability of Nrf2 protein was enhanced by PMID with decreased turnover rate. We showed that PMID reduced the ubiquitination of Nrf2 and disrupted the Cullin3 (Cul3)-Keap1 interaction. Furthermore, cells treated with PMID showed resistance to cytotoxicity by H(2)O(2) and pro-oxidant 6-OHDA. PMID also up-regulated the antioxidant level in BALB/c mice. Taken together, the compound PMID induces the ARE-mediated gene expression through stabilization of Nrf2 protein and activation of Nrf2/ARE pathway and protects against oxidative stress-mediated cell death.

Hepassocin regulates cell proliferation of the human hepatic cells L02 and hepatocarcinoma cells through different mechanisms.

Hepassocin (HPS) is a specific mitogenic active factor for hepatocytes, and inhibits growth by overexpression in hepatocellular carcinoma (HCC) cells. However, the mechanism of HPS regulation on growth of liver-derived cells still remains largely unknown. In this study, we found that HPS was expressed and secreted into the extracellular medium in cultured L02 human hepatic cells; conditional medium of L02 cells promoted proliferation of L02 cells and this activity could be blocked by anti-HPS antibody. Moreover, we identified the presence of receptor for HPS on L02 cells and HepG2 human hepatoma cells. Overproduction of truncated HPS, which signal peptide was deleted, significantly inhibited the proliferation of HCC cells and induced cell cycle arrest. These findings suggest that HPS promotes hepatic cell line L02 cells proliferation via an autocrine mechanism and inhibits HCC cells proliferation by an intracrine pathway.