AIM: To identify the role of herbal compound 861 (Cpd 861) in the regulation of mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells (HSCs). METHODS: mRNA levels o...AIM: To identify the role of herbal compound 861 (Cpd 861) in the regulation of mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells (HSCs). METHODS: mRNA levels of collagen types I and III, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 2 (MMP-2), membrane type-1 matrix metalloproteinase (MT1-MMP), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor β1 (TGF-β1) in cultured-activated HSCs treated with Cpd 861 or interferon-γ, (IFN-γ,) were determined by real-time PCR. RESULTS: Both Cpd 861 and IFN-γ reduced the mRNA levels of collagen type Ⅲ, MMP-2 and TGF-β1. Moreover, Cpd 861 significantly enhanced the MMP-1 mRNA levels while down-regulated the TIMP-1 mRNA expression, increasing the ratio of MMP-1 to TIMP-1 to (6.3 + 0.3)- fold compared to the control group. CONCLUSION: The anti-fibrosis function of Cpd 861 may be mediated by both decreased interstitial collagen sythesis by inhibiting the transcription of collagen type Ⅲ and TGF-β1 and increased degradation of these collagens by up-regulating MMP-1 and down-regulating TIMP-1 mRNA levels.展开更多
Ultrasmall FeCo-graphitic carbon shell nanocrystals (FeCo/GC) are promising multifunctional materials capable of highly efficient drug delivery in vitro and magnetic resonance imaging in vivo. In this work, we demon...Ultrasmall FeCo-graphitic carbon shell nanocrystals (FeCo/GC) are promising multifunctional materials capable of highly efficient drug delivery in vitro and magnetic resonance imaging in vivo. In this work, we demonstrate the use of FeCo/GC for highly effective cancer therapy through combined drug delivery, tumor-selective near-infrared photothermal therapy, and cancer imaging of a 4T1 syngeneic breast cancer model. The graphitic carbon shell of the ~4 nm FeCo/GC readily loads doxorubicin (DOX) via π-π stacking and absorbs near-infrared light giving photothermal heating. When used for cancer treatment, intravenously administrated FeCo/GC-DOX led to complete tumor regression in 45% of mice when combined with 20 min of near-infrared laser irradiation selectively heating the tumor to 43-45 ℃. In addition, the use of FeCo/GC-DOX results in reduced systemic toxicity compared with free DOX and appears to be safe in mice monitored for over 1 yr. FeCo/GC-DOX is shown to be a highly integrated nanoparticle system for synergistic cancer therapy leading to tumor regression of a highly aggressive tumor model.展开更多
文摘AIM: To identify the role of herbal compound 861 (Cpd 861) in the regulation of mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells (HSCs). METHODS: mRNA levels of collagen types I and III, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 2 (MMP-2), membrane type-1 matrix metalloproteinase (MT1-MMP), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor β1 (TGF-β1) in cultured-activated HSCs treated with Cpd 861 or interferon-γ, (IFN-γ,) were determined by real-time PCR. RESULTS: Both Cpd 861 and IFN-γ reduced the mRNA levels of collagen type Ⅲ, MMP-2 and TGF-β1. Moreover, Cpd 861 significantly enhanced the MMP-1 mRNA levels while down-regulated the TIMP-1 mRNA expression, increasing the ratio of MMP-1 to TIMP-1 to (6.3 + 0.3)- fold compared to the control group. CONCLUSION: The anti-fibrosis function of Cpd 861 may be mediated by both decreased interstitial collagen sythesis by inhibiting the transcription of collagen type Ⅲ and TGF-β1 and increased degradation of these collagens by up-regulating MMP-1 and down-regulating TIMP-1 mRNA levels.
文摘Ultrasmall FeCo-graphitic carbon shell nanocrystals (FeCo/GC) are promising multifunctional materials capable of highly efficient drug delivery in vitro and magnetic resonance imaging in vivo. In this work, we demonstrate the use of FeCo/GC for highly effective cancer therapy through combined drug delivery, tumor-selective near-infrared photothermal therapy, and cancer imaging of a 4T1 syngeneic breast cancer model. The graphitic carbon shell of the ~4 nm FeCo/GC readily loads doxorubicin (DOX) via π-π stacking and absorbs near-infrared light giving photothermal heating. When used for cancer treatment, intravenously administrated FeCo/GC-DOX led to complete tumor regression in 45% of mice when combined with 20 min of near-infrared laser irradiation selectively heating the tumor to 43-45 ℃. In addition, the use of FeCo/GC-DOX results in reduced systemic toxicity compared with free DOX and appears to be safe in mice monitored for over 1 yr. FeCo/GC-DOX is shown to be a highly integrated nanoparticle system for synergistic cancer therapy leading to tumor regression of a highly aggressive tumor model.