Amelioration of bleomycin-induced pulmonary fibrosis in a mouse model by a combination therapy of bosentan and imatinib.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is characterized by alveolitis, progressing into fibrosis. Due to the involvement of both endothelin and platelet-derived growth factor signaling in IPF, combination effects of a bosentan and imatinib were studied in mouse model of bleomycin-induced pulmonary fibrosis. METHODS: Mice subjected to bleomycin instillation (0.05 U) and were administered with either bosentan (100 mg/kg) and/or imatinib (50 mg/kg). Inflammatory cell count, total protein estimation in bronchoalveolar lavage fluid, lung edema, superoxide dismutase, catalase, myeloperoxidase activities, and Hematoxylin & Eosin staining were performed on day 7. Hydroxyproline content, α-smooth muscle actin (SMA), collagens I and III gene expression analysis, immunohistochemistry, matrix metalloproteinases-9 and -2 activities, trichrome and sirius red staining were performed on day 21. RESULTS: Combination treatment with bosentan and imatinib prevented bleomycin-induced mortality and loss of body weight more than the individual agents. On day 7, the combination therapy attenuated bleomycin-induced increase of total and differential inflammatory cell counts, total proteins, lung wet/dry weight ratio, myeloperoxidase activity, lung inflammatory cell infiltration more than individual agents alone. Bosentan but not imatinib ameliorated superoxide dismutase and catalase activities, which were lowered following bleomycin instillation. On day 21, combination therapy ameliorated bleomycin-induced increase of fibrosis score, collagen deposition, protein and gene expression of SMA, mRNA levels of collagens-I and -III, matrix metalloproteinase-9 and -2 activities more than monotherapy. CONCLUSION: Combination of bosentan and imatinib exerted more enhanced protection against bleomycin-induced inflammation and fibrosis than either of the agents alone.

Passion fruit peel extract attenuates bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis is a progressive fatal lung disease characterized by excessive collagen deposition, with no effective treatments. We investigated the efficacy of natural products with high anti-inflammatory activity, such as passion fruit peel extract (PFPE), in a mouse model of bleomycin-induced pulmonary fibrosis (PF). C57BL/6J mice were subjected to a single intratracheal instillation of bleomycin to induce PF. Daily PFPE treatment significantly reduced loss of body mass and mortality rate in mice compared with those treated with bleomycin. While bleomycin-induced PF resulted in elevated total numbers of inflammatory cells, macrophages, lymphocytes, and neutrophils in bronchoalveolar lavage fluid on both days 7 and 21, PFPE administration significantly attenuated these phenomena compared with bleomycin group. On day 7, the decreased superoxide dismutase and myeloperoxidase activities observed in the bleomycin group were significantly restored with PFPE treatment. On day 21, enhanced hydroxyproline deposition in the bleomycin group was also suppressed by PFPE administration. PFPE treatment significantly attenuated extensive inflammatory cell infiltration and accumulation of collagen in lung tissue sections of bleomycin-induced mice on days 7 and 21, respectively. Our results indicate that administration of PFPE decreased bleomycin-induced PF because of anti-inflammatory and antioxidant activities.

Microbiome and cancer immunotherapy.

Immunomodulation has become a promising and growing field of cancer research. Compelling results from a variety of studies provide strong evidence for the importance of commensal bacteria on oncologic outcomes and response to antitumor immunotherapies. The gut microbiome has emerged as a new prognostic biomarker and a potential therapeutic target to enhance the efficacy of immunotherapy.

Anticancer effects of brucine and gemcitabine combination in MCF-7 human breast cancer cells.

This study was designed to investigate the combination effects of brucine and gemcitabine, each with anticancer properties, in MCF-7 human breast cancer cells in culture. With regard to cell viability, effects of both the drugs and their combinations were inversely proportional to dose and time. For various proportional drug combinations studied, combination effects were analysed using CompuSyn software. The analyses revealed synergistic and/or additive effects regarding cell viability, anchorage-independent growth and cell migration. Combination analyses exhibited diversified impacts of the type of combination treatment, namely pretreatment with either drug followed by exposure to the other, or treatment with both drugs at the same time. Compared with untreated cells, combination treatment of asynchronised MCF-7 cells resulted in 17.2 × decrease in G2 phase, increasing G1 (2.1 × ) and S (1.5 × ) phase cells in cell cycle analysis. Brucine, either individually or in combination, but not gemcitabine, inhibited NF-kB subunit (p65) expression in MCF-7 cells.