Anti-fibrotic effect of thalidomide through inhibiting TGF-beta-induced ERK1/2 pathways in bleomycin-induced lung fibrosis in mice.

OBJECTIVES: This study is designed to confirm the anti-fibrotic effect of thalidomide on bleomycin-induced lung fibrosis in a mouse model and to identify whether this anti-fibrotic effect is associated with inhibition of the transforming growth factor-beta (TGF-beta)-induced extracellular signal-regulated kinase1/2 (ERK1/2). METHODS AND MATERIALS: C57BL/6 female mice were administered blomycin sulfate. In cultured human lung fibroblasts, expressions of type I collagen, fibronectin, and either TGF-beta or IL-6 were measured after thalidomide treatment by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of ERK1/2, type I collagen, fibronectin, and TGF-beta1 from lung tissues of blomycin-induced mice and from mouse lung fibroblasts were evaluated using RT-PCR and western blotting. RESULTS: Thalidomide administration significantly inhibits TGF-beta1 mRNA expression in a dose-dependant manner following administration of IL-6 and IL-6R. In the analysis of BAL fluids, total BAL inflammatory cell counts, TGF-beta1, and IL-6 levels in thalidomide-treated mice were significantly reduced when compared with bleomycin-treated mice (p < 0.01, p < 0.01, and p < 0.001, respectively). Thalidomide inhibited total ERK1/2 and phospho-ERK1/2 expression after TGF-beta1 stimulation in the RT-PCR and western blotting. CONCLUSION: The results of our study suggest that the anti-fibrotic effect of thalidomide on lung fibrosis may be related to suppression of the TGF-beta1-induced ERK1/2 signaling pathway.

Pneumomediastinum and subcutaneous emphysema secondary to amyopathic dermatomyositis with cryptogenic organizing pneumonia in invasive breast cancer: a case report and review of literature.

Amyopathic dermatomyositis (ADM) is recognized as a variant phenotype of dermatomyositis and characterized by typical skin manifestations without evidence of muscular inflammation. While interstitial lung disease (ILD) is occasionally found as one of the lung manifestations in ADM patients, the development of a pneumomediastinum and/or subcutaneous emphysema in this disease entity is one of the extremely rare pulmonary complications. These latter complicated pulmonary manifestations have been usually reported in idiopathic ADM with ILD without any other associated medical conditions. We report a case presented with the spontaneous pneumomediastinum and subcutaneous emphysema in both ADM and cryptogenic organizing pneumonia during adjuvant chemotherapy based on cyclophosphamide for breast cancer.

Cyclosporine in Relapsed Subcutaneous Panniculitis-like T-Cell Lymphoma after Autologous Hematopoietic Stem Cell Transplantation.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare T-cell lymphoma characterized by involvement of the subcutaneous tissue of neoplastic T lymphocytes. SPTCL with hemophagocytic syndrome (HPS) is associated with an aggressive clinical course and treatment of SPTCL with HPS is not well established. Cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) therapy is not successful in most patients suffering from SPTCL with HPS. The role of high dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT) remains controversial. We report a case of relapsed SPTCL after CHOP chemotherapy and salvage chemotherapy followed by autologous HSCT, which had rapid improvement within weeks after cyclosporine and prednisolone. Immunosuppressive therapy may be an important and successful treatment option in SPTCL patients, even though they may have clinically aggressive disease.

Lymphocytic interstitial pneumonia in primary Sjögren's syndrome: a case report.

Sjögren's syndrome (SS) is an autoimmune disorder in which lymphocytes infiltrate the exocrine glands, resulting in the development of sicca symptoms. Lymphocytes may also invade various other organs and cause diverse symptoms. Interstitial pneumonia has been observed frequently in SS patients. Typically, the pneumonia responds well to systemic steroids, and fatal cases are rare. We experienced a case of lymphocytic pneumonia accompanied by SS and treated with cyclophosphamide pulse therapy, and we present details of the case herein.

Melittin attenuates liver injury in thioacetamide-treated mice through modulating inflammation and fibrogenesis.

Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Following injury, an acute inflammation response takes place resulting in moderate cell necrosis and extracellular matrix damage. Melittin, the major bioactive component in the venom of honey bee Apis mellifera, is a 26-residue amphipathic peptide with well-known cytolytic, antimicrobial and proinflammatory properties. However, the molecular mechanisms responsible for the anti-inflammatory activity of melittin have not been elucidated in liver fibrosis. We investigated whether melittin ameliorates liver inflammation and fibrosis in thioacetamide (TAA)-induced liver fibrosis. Two groups of mice were treated with TAA (200 mg/L, in drinking water), one of the groups of mice was co-treated with melittin (0.1 mg/kg) for 12 weeks while the other was not. Hepatic stellate cells (HSCs) were cultured with tumor necrosis factor α in the absence or presence of melittin. Melittin suppresses the expression of proinflammatory cytokines through the nuclear factor (NF)-κB signaling pathway. Moreover, melittin reduces the activity of HSCs in vitro, and decreases the expression of fibrotic gene responses in TAA-induced liver fibrosis. Taken together, melittin prevents TAA-induced liver fibrosis by inhibiting liver inflammation and fibrosis, the mechanism of which is the interruption of the NF-κB signaling pathway. These results suggest that melittin could be an effective agent for preventing liver fibrosis.

Biological characterization of nodal versus extranodal presentation of diffuse large B-Cell lymphoma using immunohistochemistry.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) of primary nodal (PN) or primary extranodal (PEN) origin may differ immunophenotypically, in that PEN lymphoma cells may originate from activated rather than germinal center B (GCB) cells. We evaluated the relationship between DLBCL clinicopathological features, including expression of B-cell differentiation markers, and primary tumor site. PATIENTS AND METHODS: Expression of CD10, Bcl-6, Bcl-2, and MUM1 was determined in paraffin-embedded tissues from 123 patients with DLBCL. RESULTS: Of the 123 patients with DLBCL, 40 (32.5%) had the GCB and 83 (67.5%) had the non-GCB phenotype. Fifty-one patients (42%) showed disease involvement at PEN sites, including 29 with disease in the gastrointestinal (GI) tract (14 in the stomach, 15 in the intestine). Of these 51 patients, 16 (31.4%) were classified with the GCB and 35 (68.5%) with the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes among primary sites. Of the 72 patients with PN DLBCL, 22 (31%) had the GCB and 50 (69%) had the non-GCB subtype. There were no differences in the frequencies of GCB and non-GCB subtypes between patients with PN and PEN DLBCL. Although lactate dehydrogenase (LDH) concentration > normal, stage >II, and rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) treatment were independent predictors of overall survival (OS), GCB subtype, and presence of PEN disease failed to predict survival upon multivariate analysis. CONCLUSION: There was no difference in GCB and non-GCB phenotypes between patients with PN and PEN DLBCLs. Additional studies are needed to further assess molecular differences between the two groups.

The protective effect of bee venom against ethanol-induced hepatic injury via regulation of the mitochondria-related apoptotic pathway.

Alcohol consumption increases apoptosis of hepatocytes. Death of hepatocytes is a characteristic feature of chronic liver disease for various causes. Bee venom (Apis mellifera) has been traditionally used for the treatment of various chronic diseases, such as chronic inflammatory arthritis and chronic liver disease. However, the precise mechanism for bee venom in chronic liver disease is not still cleared. To assess the effects of bee venom in chronic liver disease, we investigated the potential role of the bee venom in the ethanol-induced hepatocyte apoptosis. Bee venom treatment inhibited the apoptotic cell morphology and increased the cell viability in ethanol-induced hepatocyte apoptosis. With ethanol treatment, bee venom-treated hepatocytes increased activity of Bcl-2 and Bcl-xL, reduced activity of Bax, Caspase and PARP. In conclusion, bee venom treatment in ethanol-induced hepatocyte apoptosis occurred through the regulation of Bcl family with subsequent inactivation of the Caspase and PARP. These results suggest that bee venom could be an effective agent to reduce ethanol-induced hepatocyte apoptosis.

Intraneural reticular perineurioma of the hypoglossal nerve.

BACKGROUND: Intraneural perineurioma or reticular perineurioma, which is 1 variant of extraneural perineurioma, has been rarely reported in the head and neck region. METHODS: We report a case of a 52-year-old woman who wasseen with a swelling in the neck. A mass was found located on the medial aspect of the left submandibular gland and was palpated with a sponge-like texture. The mass was seen as a homogenous semisolid lesion on CT and ultrasound examination. RESULTS: Surgical exploration revealed expansion of the hypoglossal nerve. Microscopically, the tumor showed both pseudo-onion bulb, which is a feature of intraneural perineurioma, and reticular pattern with microcysts, which is a feature of reticular variant of extraneural perineurioma. The tumor cells were immunopositive for epithelial membrane antigen and human erythrocyte glucose transporter-1 (GLUT-1). CONCLUSION: An intraneural reticular perineurioma of the hypoglossal nerve should be included in the differential diagnosis of submandibular swelling.

Primary retroperitoneal mucinous cystadenocarcinoma: a case report and review of the literature.

Primary retroperitoneal mucinous cystadenocarcinoma is a rare tumor. Only about 30 such cases have been reported in the worldwide literature, and a few Korean cases have been reported. The pathogenesis is not clear, and coelomic metaplasia of the retroperitoneal mesothelium has gained wide support. There is no consensus on the appropriate treatment, but surgical exploration is needed for the diagnosis and treatment, and adjuvant chemotherapy may be recommended following complete surgical excision. The long-term prognosis has not been established. We report here on a 32-year-old woman who was diagnosed as having a retroperitoneal mucinous cystadenocarcinoma with mural nodules of sarcomatoid change. Tumor excision and adjuvant chemotherapy were done and the patient is doing well without any evidence of recurrence at 42 months postoperatively.

Antifibrotic effect via the regulation of transcription factor Sp1 in lung fibrosis.

The aim of this study is to evaluate the antifibrotic effect of ring-type Sp1 decoy oligonucleotides (ODNs) through blocking the transcription of transforming growth factor (TGF)-beta1 and its downstream target genes. In this experiment, the expression of TGF-beta1, metalloproteinase (MMP)-13, and fibronectin was decreased in the group with the treatment of the ring-type Sp1 decoy ODNs. Also, alpha-smooth muscle actin positive bronchial lining cells and alveolar epithelial cells were observed, especially around the lesions of extracellular matrix (ECM) deposition. These findings provide evidences for the finding of pulmonary epithelial-mesenchymal transition (EMT) and the effectiveness of Sp1 transcription factor as a target for the gene therapy on lung fibrosis.

The Effect of Ischemic Preconditioning in Rat Liver: The Expression of Interleukin-1 and Nuclear Factor-B

BACKGROUND: A short period of ischemia and reperfusion, called ischemic preconditioning, protects various tissues against subsequent sustained ischemic insult. Apoptosis of hepatocytes and sinusoidal endothelial cells are a critical mechanisms of injury in the ischemic liver. Because nuclear factor-B (NF-B) has a significant role in the cell survival, we hypothesized that ischemic preconditioning protects by inhibition of apoptosis through the expression of NF-B, induced by interleukin-1 (IL-1), which is known for enhancement of its transcription and activation. METHODS: We induced ischemia and reperfusion on rat liver, and performed in situ terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labelling assay and polymerase chain reaction for IL-1 mRNA and NF-B mRNA. RESULTS: Apoptosis of hepatocytes and sinusoidal endothelial cells, assessed by in situ TUNEL assay, was significantly reduced with preconditioning. The expression of IL-1 mRNA and NF-B mRNA are seen on discrete monoclonal bands around 344 and 356 base pairs, in comparison with normal rat liver, but, there was no significant difference between the ischemia-reperfusion group and the preconditioning group. CONCLUSIONS: We suggest that ischemic preconditioning confers dramatic protection against prolonged ischemia via inhibition of apotosis through the expression of IL-1 inducing NF-B and its activation. However, we need further study in the activity of NF-B, such as nucleotide shift assay, because the activity of NF-B is regulated by binding of the inhibitory protein, IB.