Proteomic and biochemical analyses reveal the activation of unfolded protein response, ERK-1/2 and ribosomal protein S6 signaling in experimental autoimmune myocarditis rat model

<p>Abstract</p> <p>Background</p> <p>To investigate the molecular and cellular pathogenesis underlying myocarditis, we used an experimental autoimmune myocarditis (EAM)-induced heart failure rat model that represents T cell mediated postinflammatory heart disorders.</p> <p>Results</p> <p>By performing unbiased 2-dimensional electrophoresis of protein extracts from control rat heart tissues and EAM rat heart tissues, followed by nano-HPLC-ESI-QIT-MS, 67 proteins were identified from 71 spots that exhibited significantly altered expression levels. The majority of up-regulated proteins were confidently associated with unfolded protein responses (UPR), while the majority of down-regulated proteins were involved with the generation of precursor metabolites and energy metabolism in mitochondria. Although there was no difference in AKT signaling between EAM rat heart tissues and control rat heart tissues, the amounts and activities of extracellular signal-regulated kinase (ERK)-1/2 and ribosomal protein S6 (rpS6) were significantly increased. By comparing our data with the previously reported myocardial proteome of the Coxsackie viruses of group B (CVB)-mediated myocarditis model, we found that UPR-related proteins were commonly up-regulated in two murine myocarditis models. Even though only two out of 29 down-regulated proteins in EAM rat heart tissues were also dysregulated in CVB-infected rat heart tissues, other proteins known to be involved with the generation of precursor metabolites and energy metabolism in mitochondria were also dysregulated in CVB-mediated myocarditis rat heart tissues, suggesting that impairment of mitochondrial functions may be a common underlying mechanism of the two murine myocarditis models.</p> <p>Conclusions</p> <p>UPR, ERK-1/2 and S6RP signaling were activated in both EAM- and CVB-induced myocarditis murine models. Thus, the conserved components of signaling pathways in two murine models of acute myocarditis could be targets for developing new therapeutic drugs or methods aimed at treating enigmatic myocarditis.</p

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts

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A Case of Superficial Giant Basal Cell Carcinoma with Satellite Lesions on Scalp

Giant basal cell carcinoma (BCC), defined as a lesion greater than 5 cm at its largest diameter, is a rare variant of BCC. In contrast to small BCC, giant BCC develops on skin that is not exposed to sunlight, including the back, shoulder, groin and thigh. Most of the histopathologic subtypes of giant BCC are micronodular, morpheaform and nodular, but the superficial subtype is rare. Giant superficial BCC arising on the scalp is extremely rare. We report the case of giant superficial BCC with four satellite lesions on the scalp in a 53-year-old male without predisposing factors

Chronic Epstein-Barr virus infection causing both benign and malignant lymphoproliferative disorders

The Epstein-Barr virus (EBV) is oncogenic and can transform B cells from a benign to a malignant phenotype. EBV infection is also associated with lymphoid interstitial pneumonia (LIP). Here, we report the case of a 14-year-old boy who was diagnosed with a latent EBV infection and underlying LIP, without any associated immunodeficiency. He had been EBV-seropositive for 8 years. The first clinical presentations were chronic respiratory symptoms and recurrent pneumonia. The symptoms worsened in the following 2 years. The results of in situ hybridization were positive for EBV, which led to a diagnosis of LIP. The diagnosis was confirmed by the results of a thoracoscopic lung biopsy. The EBV titer of the bronchoalveolar lavage specimens obtained after acyclovir treatment was found to be fluctuating. The patient had latent EBV infection for 8 years, until presented at the hospital with intermittent abdominal pain and distension. Physical examination and pelvic computed tomography revealed a large mesenteric mass. A biopsy of the excised mass led to a diagnosis of Burkitt's lymphoma (BL). The patient received combination chemotherapy for 4 months, consisting of vincristine, methotrexate, cyclophosphamide, doxorubicin, and prednisolone. He is now tumor-free, with the LIP under control, and is being followed-up at the outpatient clinic. This is the first report of a Korean case of chronic latent EBV infection that developed into LIP and BL in a nonimmunocompromised child