RESUMEN
Background Biliary obstruction leads to an increase in biliary pressure within the biliary system, which induces the morphologic adaptation of the biliary tree. Purpose To observe and to quantify the morphologic characteristics of the adaptation in a bile duct ligation rat model and verify it in patients with biliary atresia in a three-dimensional (3D) manner using x-ray phase-contrast CT. Materials and Methods A bile duct ligation model was induced in 40 male Sprague-Dawley rats, which were divided into five groups: the control group (no ligation) and groups 2, 4, 6, and 8 weeks after bile duct ligation (eight animals in each group). Liver tissue samples (approximately 1.8 cm in length and 1.3 cm in height) were imaged by using phase-contrast CT and compared with histologic analysis. With a combination of phase-contrast CT and 3D visualization technology, the entire biliary system and the intrahepatic vascular system were quantitatively analyzed according to downstream, midstream, and upstream domains based on bile duct volume, surface area, and other parameters. Additionally, liver explant tissues from 28 patients with biliary atresia were studied to determine the impact of biliary tract reconstruction. Results To offset the increased biliary pressure within the biliary system, the ductular reaction in the downstream, midstream, and upstream domains manifested as dilatation, spiderweb-like looping, and interconnected honeycomb-like patterns, respectively. The most severe ductular reaction occurred in the upstream domain, and the relative surface area (mean, 0.02 µm-1 ± 0.01, 0.04 µm-1 ± 0.01, 0.07 µm-1 ± 0.02, and 0.10 µm-1 ± 0.02 for the 2-8-week groups, respectively; P < .01 among the groups) and volume fraction of ductules (mean, 16.54% ± 4.62, 19.69% ± 6.41, 26.92% ± 5.82, and 38.34% ± 10.36 for the 2-8-week groups, respectively; P < .01 among the groups except between the 2- and 4-week groups [P = .062]) significantly increased over time. In patients with biliary atresia, it was observed that both fibrosis and proliferative ductules regressed after successful biliary tract reconstruction following Kasai portoenterostomy. Furthermore, ductular reaction was accompanied by a progressive increase in the arterial supply but a loss of portal blood supply. Conclusion X-ray phase-contrast CT with three-dimensional rendering of the biliary system in a bile duct ligation rat model provides key insights into ductular reaction or biliary self-adaptation triggered by increased biliary pressure. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Vannier and Wang in this issue.
Asunto(s)
Colestasis/diagnóstico por imagen , Colestasis/patología , Imagenología Tridimensional/métodos , Hígado/diagnóstico por imagen , Hígado/patología , Tomografía Computarizada por Rayos X/métodos , Animales , Sistema Biliar/diagnóstico por imagen , Modelos Animales de Enfermedad , Ligadura , Hígado/irrigación sanguínea , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
MOF-based photoelectrocatalysis (PEC) using CO2 as an electron donor offers a green, clean, and extensible way to make hydrocarbon fuels under more tolerant conditions. Herein, basic principles of PEC reduction of CO2 and the preparation methods and characterization techniques of MOF-based materials are summarized. Furthermore, three applications of MOFs for improving the photoelectrocatalytic performance of CO2 reduction are described: (i) as photoelectrode alone; (ii) as a co-catalyst of semiconductor photoelectrode or as a substrate for loading dyes, quantum dots, and other co-catalysts; (iii) as one of the components of heterojunction structure. Challenges and future wave surrounding the development of robust PEC CO2 systems based on MOF materials are also discussed briefly.
RESUMEN
Transforming growth factor-beta 1 (TGF-ß1) plays a central role in hepatic progenitor cells- (HPCs-) mediated liver repair and fibrosis. However, different effects of TGF-ß1 on progenitor cells have not been described. In this study, both in vitro (HPCs cocultured with hepatic stellate cells (HSCs) in transwells) and in vivo (CCl4-injured liver fibrosis rat) systems were used to evaluate the impacts. We found that HPCs pretreated with TGF-ß1 for 12 hours inhibited the activation of HSCs, while sensitization for 48 hours increased the activation of HSCs. Consistent with these in vitro results, the in vivo fibrosis rat model showed the same time-dependent dual effect of TGF-ß1. Regression of liver fibrosis as well as normalization of serum aminotransferase and albumin levels was detected in the rats transplanted with HPCs pretreated with TGF-ß1 for 12 hours. In contrast, severe liver fibrosis and elevated collagen-1 levels were detected in the rats transplanted with HPCs pretreated with TGF-ß1 for 48 hours. Furthermore, the TGF-ß1-pretreated HPCs were shown to deactivate HSCs via enhancing SERPINE1 expression. Inhibition of SERPINE1 reversed the deactivation response in a dose-dependent manner.
RESUMEN
AIM: Angiogenesis is considered an important pathophysiological feature of portal hypertension. We investigated the ability of angiogenesis, as CD34-positive microvessel density (MVD), to differentiate portal pressure in a CCl4-induced rat cirrhosis model. METHODS: Cirrhosis was induced by intraperitoneal injection of carbon tetrachloride in 46 male adult Sprague-Dawley rats. A catheter connected to a highly sensitive pressure transducer was inserted into the portal vein to continuously record portal pressure. Fibrosis area, nodule size and MVD were assessed by image morphometry. RESULTS: Of 42 rats in which portal pressure was measured successfully, 27 (64%) had portal pressure ≥10 mmHg, defined as significant portal hypertension. MVD was 4.5-fold higher and fibrosis area 13.0-fold higher in rats with significant portal hypertension than in rats with portal pressure <10 mmHg. Portal pressure was significantly correlated with MVD (r=0.491, p<0.001) and fibrosis area (r=0.545, p<0.001) in all animals, but only MVD correlated with portal pressure (r=0.731 p<0.001) in rats with significant portal hypertension. The area under receiver operating characteristic curve for MVD in all rats was 0.953 (95% CI: 0.875-1.031) and optimum cutoff for MVD was 18/mm², with 96.3% sensitivity and 93.3% specificity. CONCLUSIONS: We found that MVD, measured by CD34 immunostaining, was better able than the fibrosis area to discriminate significant portal hypertension in rats, suggesting that MVD could be a surrogate marker for portal hypertension in patients with liver diseases.
Asunto(s)
Hipertensión Portal/diagnóstico , Neovascularización Patológica/patología , Animales , Antígenos CD34/genética , Antígenos CD34/metabolismo , Biomarcadores , Presión Sanguínea , Capilares/patología , Diagnóstico Diferencial , Hipertensión Portal/metabolismo , Hipertensión Portal/patología , Cirrosis Hepática Experimental/genética , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Neovascularización Patológica/genética , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND/AIM: Diffraction enhanced imaging (DEI) is a synchrotron radiation X-ray phase-contrast imaging technique that can better reveal the microstructure of biological soft tissues than conventional X-rays. The aim of this study is to investigate the angio-architectural changes of the liver during fibrosis, cirrhosis and its subsequent regression by applying synchrotron radiation based DEI. METHODS: DEI experiments were performed at the 4W1A station of Beijing Synchrotron Radiation Facility. Twenty-four Sprague-Dawley rats were induced with liver fibrosis by carbon tetrachloride (CCl4) for up to 10 weeks, after which spontaneous regression started and continued until week 30. Quantitative analysis of the DEI images yielded the mean vascular density and intercapillary distance, which was then re-confirmed by immunohistochemical analysis of CD34. RESULTS: Based on the DEI results, the mean vascular density was 1.4-fold higher in fibrotic rats (at week 6) and 2-fold higher in cirrhotic rats (at week 10) compared with the control (p<0.05). Accordingly, the intercapillary distance decreased to 563.89 ± 243.35 µm in fibrotic rats and 392.90 ± 92.68 µm in cirrhotic rats compared with 673.85 ± 214.16 µm in the control (p<0.05). During fibrosis regression at week 30, vascular density was 0.7-fold lower and intercapillary distance increased to 548.60 ± 210.94 µm as compared with cirrhotic rats (p<0.05).In parallel to the DEI results, immunohistochemical analysis of CD34 showed similar changes. CONCLUSION: Synchrotron-based DEI can conduct radiological as well as pathological analysis. Our results are consistent with previous reports indicating that angiogenesis is directly proportional to fibrosis progression. Furthermore, by clarifying the vascular characteristics of liver diseases, DEI reveals that cirrhosis cannot fully reverse during fibrosis regression.