BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical phy...BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics.AIM To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis.METHODS Eight-week-old male C57 BL/6 mice were divided into three groups randomly(control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin(HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids.RESULTS Oil red O staining indicated lipid accumulation in the liver after CCl_4 treatment.HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice onmorphological examination. Hemorheological tests included whole blood viscosity(mPas, γ = 10 s-1/γ = 100 s-1)(8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ±1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume(%)(51.00 ± 4.00, 42.00 ±5.00, and 40.00 ± 3.00), the content of plasma fibrinase(g/L)(3.80 ± 0.50, 2.90 ±0.80, and 2.30 ± 0.70), erythrocyte deformation index(%)(44.49 ± 5.81, 48.00 ±15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate(mm展开更多
A new carbazole tricationic salt,4,4'-(1E,1'E)-2,2'-(9-(2-(1-(2-hydroxyethyl)pyridinium-4-yl)ethyl)-9H-carbazole-3,6-diyl) bis(ethane-2,1-diyl) bis(1-(2-hydroxyethyl)pyridinium) iodide (THEPC) was synthesi...A new carbazole tricationic salt,4,4'-(1E,1'E)-2,2'-(9-(2-(1-(2-hydroxyethyl)pyridinium-4-yl)ethyl)-9H-carbazole-3,6-diyl) bis(ethane-2,1-diyl) bis(1-(2-hydroxyethyl)pyridinium) iodide (THEPC) was synthesized. Photophysical experiments have shown that THEPC has large two-photon excited fluorescence action cross-sections (33 GM in the presence of DNA),which ranks THEPC as a good biological fluorophore. The results from electronic absorption,circle dichroism and single-/two-photon fluorescence emission spectra suggest that THEPC can strongly bind to DNA,with an intrinsic binding constant of 5.79 × 106 L mol-1. THEPC has better photostability under one-or two-photon excitation conditions. Finally,the staining photos from two-photon fluorescence microscopy (TPM) show that THEPC can exclusively label the nucleus with high contrast and without image distortion. These remarkable properties and optimized imaging ability make THEPC an attractive DNA probe in TPM.展开更多
Two-photon excitation microscopy(2 PEM) has been known as a noninvasive and powerful bio-imaging tool for studying living cells, intact tissues and living animals because of their unique advantages such as localized e...Two-photon excitation microscopy(2 PEM) has been known as a noninvasive and powerful bio-imaging tool for studying living cells, intact tissues and living animals because of their unique advantages such as localized excitation, deep tissue penetration as well as less photo-damage. However, the major limitations that hinder its practical applications in biological systems are low two-photon absorption cross sections of conventional fluorescence probes. Conjugated polymer nanoparticles(CPNs) consisting of highly fluorescent conjugated polymers are promising fluorescent probes for 2 PEM due to their unique advantages including large two-photon absorption cross sections, high fluorescence quantum yield, good photo-stability and biocompatibility, facile chemical synthesis, tunable optical properties as well as versatile surface modifications. This account summarizes the recent efforts of our group on development of novel polyfluorene based CPNs as 2 PEM contrast agents for live cell imaging.展开更多
基金Beijing Municipal Natural Science Foundation,No.7162098
文摘BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics.AIM To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis.METHODS Eight-week-old male C57 BL/6 mice were divided into three groups randomly(control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin(HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids.RESULTS Oil red O staining indicated lipid accumulation in the liver after CCl_4 treatment.HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice onmorphological examination. Hemorheological tests included whole blood viscosity(mPas, γ = 10 s-1/γ = 100 s-1)(8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ±1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume(%)(51.00 ± 4.00, 42.00 ±5.00, and 40.00 ± 3.00), the content of plasma fibrinase(g/L)(3.80 ± 0.50, 2.90 ±0.80, and 2.30 ± 0.70), erythrocyte deformation index(%)(44.49 ± 5.81, 48.00 ±15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate(mm
基金supported by the National Natural Science Foundation of China (50673053, 50173015, 30771091 and 50721002)National Science Foundation of China/the Hong Kong Research Grants Council (50218001)
文摘A new carbazole tricationic salt,4,4'-(1E,1'E)-2,2'-(9-(2-(1-(2-hydroxyethyl)pyridinium-4-yl)ethyl)-9H-carbazole-3,6-diyl) bis(ethane-2,1-diyl) bis(1-(2-hydroxyethyl)pyridinium) iodide (THEPC) was synthesized. Photophysical experiments have shown that THEPC has large two-photon excited fluorescence action cross-sections (33 GM in the presence of DNA),which ranks THEPC as a good biological fluorophore. The results from electronic absorption,circle dichroism and single-/two-photon fluorescence emission spectra suggest that THEPC can strongly bind to DNA,with an intrinsic binding constant of 5.79 × 106 L mol-1. THEPC has better photostability under one-or two-photon excitation conditions. Finally,the staining photos from two-photon fluorescence microscopy (TPM) show that THEPC can exclusively label the nucleus with high contrast and without image distortion. These remarkable properties and optimized imaging ability make THEPC an attractive DNA probe in TPM.
基金supported by the Guangdong Innovative Research Team Program of China (201101C0105067115)the National Natural Science Foundation of China (21673155)+3 种基金the Young Scientists Fund of the National Natural Science Foundation of China (51603069)the Scientific Research Staring Natural Science Foundation of Guangdong Province, China (2016A030310432)the Fundamental Research Funds for the Central Universities and China Postdoctoral Science Foundation (2016M592485)Ministry of Education of Singapore (R-143-000-607-112)
文摘Two-photon excitation microscopy(2 PEM) has been known as a noninvasive and powerful bio-imaging tool for studying living cells, intact tissues and living animals because of their unique advantages such as localized excitation, deep tissue penetration as well as less photo-damage. However, the major limitations that hinder its practical applications in biological systems are low two-photon absorption cross sections of conventional fluorescence probes. Conjugated polymer nanoparticles(CPNs) consisting of highly fluorescent conjugated polymers are promising fluorescent probes for 2 PEM due to their unique advantages including large two-photon absorption cross sections, high fluorescence quantum yield, good photo-stability and biocompatibility, facile chemical synthesis, tunable optical properties as well as versatile surface modifications. This account summarizes the recent efforts of our group on development of novel polyfluorene based CPNs as 2 PEM contrast agents for live cell imaging.
