Colorectal cancer liver metastases (CLM) treatment is very important given the high incidence of colorectal cancer with liver metastases, which are primarily treated by surgical resection. Transformational therapy s...Colorectal cancer liver metastases (CLM) treatment is very important given the high incidence of colorectal cancer with liver metastases, which are primarily treated by surgical resection. Transformational therapy such as systemic chemotherapy, hepatic arterial infusion (HAl), portal vein embolization (PVE), ablation therapy, and targeted therapy, should be applied to CLM patients who are unable to undergo immediate surgery to improve patients' survival and quality of life.展开更多
Background Haze or corneal subepithelial fibrosis is one of the common complications after refractive surgery procedures, such as photorefractive keratectomy (PRK), laser epithelial keratomileusis, and epipolis lase...Background Haze or corneal subepithelial fibrosis is one of the common complications after refractive surgery procedures, such as photorefractive keratectomy (PRK), laser epithelial keratomileusis, and epipolis laser in situ keratomileusis, which would result in refractive regression, decreased visual quality, and corneal opacification. Haze directly resulted from corneal fibrosis mediated by transforming growth factor β (TGFβ). SmadT, an inhibitory Smad, can inhibit TGFβ signal transduction. Recently, the effects of Smad7 on the inhibition of fibrosis in several organs have been studied, while little is known about the effects on cornea after PRK. This study was aimed to determine the effects of lentiviral-mediated Smad7 gene expression on corneal fibrosis in rats after PRK. Methods Four different experimental groups were established using right eyes of Sprague-Dawley rats. Thirty-two eyes underwent de-epithelialization only and served as a sham operation group (group 1). Ninety-six eyes underwent PRK operation and were further divided into group 2 (the PRK group) without lentivector administration, group 3 (the Lv-blank group) with control lentiviral vector without Smad7 administration, and group 4 (the Lv-Smad7 group) with Smad7 expressing lentiviral vector Smad7 administration. At 1 day, 1 week, 1 month, and 3 months after PRK, the transfection efficiency was determined by measuring the fluorescence signal as well as Smad7 protein and mRNA levels. Corneas were further processed for immunoblotting to assess the phosphorylation of Smad2 as a downstream event of TGFβ/Smad signaling. The expression of fibrotic markers, such as c(-smooth muscle actin (c(-SMA), Type III collagen (collagen III), and cell cycle-related marker Ki67, was measured by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results Lentivirus-mediated exogenous Smad7 gene expression in rat corneal tissue resulted in reduced activation of TGFβ/Smad signaling caused by downregulation of phosphorylation of Smad2. Smad7 also downregulated the expression of TGFβ2. Markers of cell proliferation and fibrosis, including Ki67, c(-SMA, and collagen III, were inhibited by Smad7 up to 3 months after PRK operation. Conclusion Smad7 gene transfer inhibits fibrogenic responses of cornea in rats after PRK.展开更多
In recent years,various transformable nanoparticles(NPs)were successfully prepared and widely utilized for biomedical applications.The sizes,surface charges or morphologies of transformable NPs would affect their be...In recent years,various transformable nanoparticles(NPs)were successfully prepared and widely utilized for biomedical applications.The sizes,surface charges or morphologies of transformable NPs would affect their behavior in physiological/pathological conditions including circulation,penetration,accumulation and retention etc.The other way round,the NPs could be precisely modulated in the specific physiological/pathological condition for precision theranostics of diseases.Herein,we summarized recent advances of transformable NPs for disease diagnostics and therapy.In this review,the transformation of NPs was divided into three groups including changes in size,surface charge and morphology,which was induced by internal stimuli,such as p H,enzyme,receptor or external stimuli,such as light,temperature etc.Moreover,we focused on the characterization of structural transformation in vivo,as well as the transformation-induced biological effects for theranostics of disease.展开更多
文摘Colorectal cancer liver metastases (CLM) treatment is very important given the high incidence of colorectal cancer with liver metastases, which are primarily treated by surgical resection. Transformational therapy such as systemic chemotherapy, hepatic arterial infusion (HAl), portal vein embolization (PVE), ablation therapy, and targeted therapy, should be applied to CLM patients who are unable to undergo immediate surgery to improve patients' survival and quality of life.
文摘Background Haze or corneal subepithelial fibrosis is one of the common complications after refractive surgery procedures, such as photorefractive keratectomy (PRK), laser epithelial keratomileusis, and epipolis laser in situ keratomileusis, which would result in refractive regression, decreased visual quality, and corneal opacification. Haze directly resulted from corneal fibrosis mediated by transforming growth factor β (TGFβ). SmadT, an inhibitory Smad, can inhibit TGFβ signal transduction. Recently, the effects of Smad7 on the inhibition of fibrosis in several organs have been studied, while little is known about the effects on cornea after PRK. This study was aimed to determine the effects of lentiviral-mediated Smad7 gene expression on corneal fibrosis in rats after PRK. Methods Four different experimental groups were established using right eyes of Sprague-Dawley rats. Thirty-two eyes underwent de-epithelialization only and served as a sham operation group (group 1). Ninety-six eyes underwent PRK operation and were further divided into group 2 (the PRK group) without lentivector administration, group 3 (the Lv-blank group) with control lentiviral vector without Smad7 administration, and group 4 (the Lv-Smad7 group) with Smad7 expressing lentiviral vector Smad7 administration. At 1 day, 1 week, 1 month, and 3 months after PRK, the transfection efficiency was determined by measuring the fluorescence signal as well as Smad7 protein and mRNA levels. Corneas were further processed for immunoblotting to assess the phosphorylation of Smad2 as a downstream event of TGFβ/Smad signaling. The expression of fibrotic markers, such as c(-smooth muscle actin (c(-SMA), Type III collagen (collagen III), and cell cycle-related marker Ki67, was measured by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results Lentivirus-mediated exogenous Smad7 gene expression in rat corneal tissue resulted in reduced activation of TGFβ/Smad signaling caused by downregulation of phosphorylation of Smad2. Smad7 also downregulated the expression of TGFβ2. Markers of cell proliferation and fibrosis, including Ki67, c(-SMA, and collagen III, were inhibited by Smad7 up to 3 months after PRK operation. Conclusion Smad7 gene transfer inhibits fibrogenic responses of cornea in rats after PRK.
基金supported by the National Natural Science Foundation of China(Nos.51573031,21373726,21303723,21603028 and 21573036)Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.11621505)+1 种基金CAS Key Research Program for Frontier Sciences(No.QYZDJ-SSW-SLH022)Key Project of Chinese Academy of Sciences in Cooperation with Foreign Enterprises(No.GJHZ1541)
文摘In recent years,various transformable nanoparticles(NPs)were successfully prepared and widely utilized for biomedical applications.The sizes,surface charges or morphologies of transformable NPs would affect their behavior in physiological/pathological conditions including circulation,penetration,accumulation and retention etc.The other way round,the NPs could be precisely modulated in the specific physiological/pathological condition for precision theranostics of diseases.Herein,we summarized recent advances of transformable NPs for disease diagnostics and therapy.In this review,the transformation of NPs was divided into three groups including changes in size,surface charge and morphology,which was induced by internal stimuli,such as p H,enzyme,receptor or external stimuli,such as light,temperature etc.Moreover,we focused on the characterization of structural transformation in vivo,as well as the transformation-induced biological effects for theranostics of disease.