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The fimbria variations may have an influence on the development of periodontal disease.

High mobility group box1 protein (HMGB1) was originally discovered as a nuclear binding protein, and is known to play an important role in acute lung injury. However, the role of HMGB1 in pulmonary fibrosis has not been addressed. Therefore, we measured the HMGB1 levels in serum and bronchoalveolar lavage fluids (BALF) from patients with idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia, interstitial pneumonia associated with collagen vascular diseases, and hypersensitivity pneumonitis (HP) by enzyme-linked immunosorbent assay. We also assessed the HMGB1 expression in bleomycin-induced pulmonary fibrosis in mice, and examined the effect of anti-HMGB1 antibody and ethyl pyluvate, which inhibits the HMGB1 secretion from alveolar macrophages. In addition, we examined the effect of HMGB1 on fibroblast proliferation, apoptosis, and collagen synthesis in vitro. Serum HMGB1 levels were not significantly increased in interstitial lung diseases compared with control subjects. BALF HMGB1 levels were significantly increased in IPF and HP compared with control subjects. HMGB1 protein was predominantly detected in inflammatory cells and hyperplasic epithelial cells in IPF. In bleomycin-induced pulmonary fibrosis in mice, HMGB1 protein was predominantly up-regulated in bronchiolar epithelial cells at early phase and in alveolar epithelial and inflammatory cells in fibrotic lesions at later phase. Intraperitoneal injection of anti-HMGB1 antibody or ethyl pyluvate significantly attenuated lung inflammation and fibrosis in this model. HMGB1 significantly induced proliferation, but not apoptosis or collagen synthesis on cultured fibroblasts. HMGB1 may be a promising target against pulmonary fibrosis as well as acute lung injury.

MicroRNAs are involved in cancer pathogenesis and act as tumor suppressors or oncogenes. It has been recently reported that miR-148a expression is down-regulated in several types of cancer. The functional roles and target genes of miR-148a in prostate cancer, however, remain unknown. In this report, we showed that miR-148a expression levels were lower in PC3 and DU145 hormone-refractory prostate cancer cells in comparison to PrEC normal human prostate epithelial cells and LNCaP hormone-sensitive prostate cancer cells. Transfection with miR-148a precursor inhibited cell growth, and cell migration and invasion, and increased the sensitivity to anti-cancer drug paclitaxel in PC3 cells. Computer-aided algorithms predicted mitogen-and stress-activated protein kinase, MSK1, as a potential target of miR-148a. Indeed, miR-148a overexpression decreased expression of MSK1. Using luciferase reporter assays, we identified MSK1 as a direct target of miR-148a. Suppression of MSK1 expression by siRNA, however, showed little or no effects on malignant phenotypes of PC3 cells. In PC3PR cells, a paclitaxel-resistant cell line established from PC3 cells, miR-148a inhibited cell growth, and cell migration and invasion, and also attenuated the resistance to paclitaxel. MiR-148a reduced MSK1 expression by directly targeting its 3-UTR in PC3PR cells. Furthermore, MSK1 knockdown reduced paclitaxel-resistance of PC3PR cells, indicating that miR-148a attenuates paclitaxel-resistance of hormone-refractory, drug-resistant PC3PR cells in part by regulating MSK1 expression. Our findings suggest that miR148a plays multiple roles as a tumor suppressor and can be a promising therapeutic target for hormone-refractory prostate cancer especially for drug-resistant prostate cancer. MicroRNAs (miRNAs)2 are small non-coding RNAs composed of about 22-24 nucleotides and control protein expression through translational inhibition or mRNA degradation by binding to the 3Ј-untranslated region (3Ј-UTR) of target mRNAs (1). miRNAs regulate a number of biological processes such as development, proliferation, differentiation, and apoptosis. Aberrant expression of miRNA has been reported in a variety of cancers, some of which have been shown to act as tumor suppressors or oncogenes (2).MiR-148a expression is down-regulated in human breast cancer and undifferentiated gastric cancer (3, 4). DNA methylation-associated silencing of miR-148 expression is identified in human cancer cell lines established from lymph node metastasis of colon, melanoma, and head and neck cancer, suggesting its role for the development of metastasis (5). Direct targets of miR-148a so far reported include transcription growth factor-␤-induced factor 2 (TGIF2), DNA (cytosine-5-)-methyltransferase 3␤ (DNMT3b) and pregnane X receptor (PXR) (5-7). However, the functional roles and target genes of miR-148a in prostate cancer have not yet been documented.Mitogen-and stress-activated kinase 1 (MSK1), also known as ribosomal protein S6 kinase, 90kDa, polypeptide 5 (RPS6KA5), is a serine/threonine...

During the 1-year follow-up, the combination of OK and atropine 0.01% ophthalmic solution was more effective in slowing axial elongation than OK monotherapy in children with myopia.

Vascular endothelial growth factor (VEGF) is an angiogenesis factor with proinflammatory roles. Flt-1 is one of the specific receptors for VEGF, and soluble flt-1 (sflt-1) binds to VEGF and competitively inhibits it from binding to the receptors. We examined the role of VEGF in the pathophysiology of bleomycin-induced pneumopathy in mice, using a new therapeutic strategy that comprises transfection of the sflt-1 gene into skeletal muscles as a biofactory for anti-VEGF therapy. The serum levels of sflt-1 were significantly increased at 3–14 days after the gene transfer. Transfection of the sflt-1 gene at 3 days before or 7 days after the intratracheal instillation of bleomycin decreased the number of inflammatory cells, the protein concentration in the bronchoalveolar lavage fluid and with von Willebrand factor expression at 14 days. Transfection of the sflt-1 gene also attenuated pulmonary fibrosis and apoptosis at 14 days. Since the inflammatory cell infiltration begins at 3 days and is followed by interstitial fibrosis, it is likely that VEGF has important roles as a proinflammatory, a permeability-inducing, and an angiogenesis factor not only in the early inflammatory phase but also in the late fibrotic phase. Furthermore, this method may be beneficial for treating lung injury and fibrosis from the viewpoint of clinical application, since it does not require the use of a viral vector or neutralizing Ab.

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Isogenic mutants of Porphyromonas gingivalis which differ in the expression of fimbriae were used to examine the contribution of fimbriae in invasion of a human oral epithelial cell line (KB). At a multiplicity of infection of 100, the wild-type P. gingivalis strains 33277, 381, and A7436 exhibited adherence efficiencies of 5.5, 0.11, and 5.0%, respectively, and invasion efficiencies of 0.15, 0.03, and 0.10%, respectively. However, adherence to and invasion of KB cells was not detected with the P. gingivalis fimA mutants, DPG3 and MPG1. Adherence of P. gingivalis wild-type strains to KB cells was completely inhibited by the addition of hyperimmune sera raised to the major fimbriae. Examination by electron microscopy of invasion of epithelial cells by the P. gingivalis wild-type strain 381 revealed microvillus-like extensions around adherent bacteria; this was not observed with P. gingivalis fim mutants. Taken together, these results indicate that the P. gingivalis major fimbriae are required for adherence to and invasion of oral epithelial cells.