AIM： To investigate whether high-fat-feeding is associ- ated with increased intestinal permeability via altera- tions in bile acid metabolism.METHODS： Male C57BI/6J mice were fed on a high-fat （n = 26） or low-fat ...AIM： To investigate whether high-fat-feeding is associ- ated with increased intestinal permeability via altera- tions in bile acid metabolism.METHODS： Male C57BI/6J mice were fed on a high-fat （n = 26） or low-fat diet （n = 24） for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile ac- ids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor （FXR） and tumor necrosis factor展开更多
The intensive crosstalk between the liver and the intestine performs many essential functions.This crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and...The intensive crosstalk between the liver and the intestine performs many essential functions.This crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites.The interaction between the gut microbiome and bile acids is bidirectional.The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes.Similarly,bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system.The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases,especially liver diseases.As essential mediators of the gut-liver crosstalk,bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1.Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases.We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.展开更多
Portal hypertension(PHT) is an important consequence of liver cirrhosis, which can lead to complications that adversely affect a patient's quality of life and survival, such as upper gastrointestinal bleeding, asc...Portal hypertension(PHT) is an important consequence of liver cirrhosis, which can lead to complications that adversely affect a patient's quality of life and survival, such as upper gastrointestinal bleeding, ascites, and portosystemic encephalopathy. In recent years, advances in molecular biology have led to major discoveries in the pathological processes of PHT, including the signaling pathways that may be involved: PI3 K-AKT-mTOR, RhoA/Rho-kinase, JAK2/STAT3, and farnesoid X receptor. However, the pathogenesis of PHT is complex and there are numerous pathways involved. Therefore, the targeting of signaling pathways for medical management is lagging. This article summarizes the progress that has been made in understanding the signaling pathways in PHT, and provides ideas for treatment of the disorder.展开更多
Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequ...Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesevelam, which may be given in combination with the opioid receptor agonist loperamide. Some patients are refractory to conventional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn's disease and a normal terminal ileum had been diagnosed with severe bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypokalemia and sodium depletion that made her dependent on twice weekly intravenous fluid and electrolyte infusions. Conventional therapies with colestyramine, colesevelam, and loperamide had no effect. Second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an average of 13 to an average of 7 per 24h and improved the patient's quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improve symptoms in patients with bile acid diarrhea.展开更多
X-ray-activated luminescence materials have broad application prospects in photodynamic therapy of deep tissue.Among them,X-ray-activated persistent luminescence materials(PLMs)exhibiting multiple emission peaks have ...X-ray-activated luminescence materials have broad application prospects in photodynamic therapy of deep tissue.Among them,X-ray-activated persistent luminescence materials(PLMs)exhibiting multiple emission peaks have drawn extensive attention for the ir capacity to achieve a combination of bioimaging and therapeutic functions.Here,we developed a novel PLM,LiYGeO_4:Bi^(3+),Pr^(3+),that simultaneously exhibits UV and NIR dual persistent luminescence(PersL)emissions after irradiation by X-ray.The material can be re peatedly excited by X-ray and emits similar lumine scence intensity every time,which shows good PersL stability.In addition,LiYGeO_4:Bi^(3+),Pr^(3+)exhibits photostimulated PersL properties by stimulation with a red light-emitting diode(LED)or NIR laser after long-term decay.This work provides a new choice of X-ray-excited PLMs with UV and NIR dual emission and the novel phosphor shows promise as a potential candidate for the integration of treatment and diagnosis of deep tumors.展开更多
A ten-month field research study was meticulously conducted at Robert Moses State Park (RMSP) on the south shore of Long Island, NY. The objective was to determine if aerial phenomena of an unknown nature exist over a...A ten-month field research study was meticulously conducted at Robert Moses State Park (RMSP) on the south shore of Long Island, NY. The objective was to determine if aerial phenomena of an unknown nature exist over a coastal location and to characterize their properties and behaviors. Primary and secondary field observation methods were utilized in this data-centric study. Forensic engineering principles and methodologies guided the study. The challenges set forward were object detection, observation, and characterization, where multispectral electro-optical devices and radar were employed due to limited visual acuity and intermittent presentation of the phenomena. The primary means of detection utilized a 3 cm X-band radar operating in two scan geometries, the X- and Y-axis. Multispectral electro-optical devices were utilized as a secondary means of detection and identification. Data was emphasized using HF and LF detectors and spectrum analyzers incorporating EM, ultrasonic, magnetic, and RF field transducers to record spectral data in these domains. Data collection concentrated on characterizing VIS, NIR, SWIR, LWIR, UVA, UVB, UVC, and the higher energy spectral range of ionizing radiation (alpha, beta, gamma, and X-ray) recorded by Geiger-Müller counters as well as special purpose semiconductor diode sensors.展开更多
基金Supported by The Foundation for Nutrition Research and the Finnish Funding Agency of Technology and Innovation
文摘AIM： To investigate whether high-fat-feeding is associ- ated with increased intestinal permeability via altera- tions in bile acid metabolism.METHODS： Male C57BI/6J mice were fed on a high-fat （n = 26） or low-fat diet （n = 24） for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile ac- ids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor （FXR） and tumor necrosis factor
基金Supported by National Science and Technology Major Project of China,No.2018ZX10302206.
文摘The intensive crosstalk between the liver and the intestine performs many essential functions.This crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites.The interaction between the gut microbiome and bile acids is bidirectional.The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes.Similarly,bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system.The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases,especially liver diseases.As essential mediators of the gut-liver crosstalk,bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1.Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases.We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.
基金Supported by the National Natural Science Foundation of China,No.81573948
文摘Portal hypertension(PHT) is an important consequence of liver cirrhosis, which can lead to complications that adversely affect a patient's quality of life and survival, such as upper gastrointestinal bleeding, ascites, and portosystemic encephalopathy. In recent years, advances in molecular biology have led to major discoveries in the pathological processes of PHT, including the signaling pathways that may be involved: PI3 K-AKT-mTOR, RhoA/Rho-kinase, JAK2/STAT3, and farnesoid X receptor. However, the pathogenesis of PHT is complex and there are numerous pathways involved. Therefore, the targeting of signaling pathways for medical management is lagging. This article summarizes the progress that has been made in understanding the signaling pathways in PHT, and provides ideas for treatment of the disorder.
文摘Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesevelam, which may be given in combination with the opioid receptor agonist loperamide. Some patients are refractory to conventional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn's disease and a normal terminal ileum had been diagnosed with severe bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypokalemia and sodium depletion that made her dependent on twice weekly intravenous fluid and electrolyte infusions. Conventional therapies with colestyramine, colesevelam, and loperamide had no effect. Second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an average of 13 to an average of 7 per 24h and improved the patient's quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improve symptoms in patients with bile acid diarrhea.
文摘目的探讨肝核受体(LXRs)激动剂T0901317对正常SD大鼠骨骼肌细胞中脂肪酸较运酶(FAT/CD36)基因mRNA表达的影响。方法将原代培养的5只SD大鼠骨骼肌细胞分为T0901317 1μmol/L作用组、0.5μmol/L作用组和未作用(阴性对照)组,采用SYBR Green I实时荧光定量聚合酶链反应(PCR)法检测各组SD大鼠骨骼肌细胞FAT/CD36基因mRNA表达水平,并进行比较分析。结果1μmol/L、0.5μmol/L作用组与阴性对照组比较,差异无显著性意义(P=0.116)。结论LXRs激动剂T0901317对SD大鼠骨骼肌细胞中FAT/CD36基因mRNA的表达水平没有明显作用,提示T0901317在促进SD大鼠骨骼肌细胞内脂肪酸的堆积作用尚无确切的证据。
基金Project supported by the National Natural Science Foundation of China(61705228,62105333)the Natural Science Foundation of Fujian Province,China(2019J05159)。
文摘X-ray-activated luminescence materials have broad application prospects in photodynamic therapy of deep tissue.Among them,X-ray-activated persistent luminescence materials(PLMs)exhibiting multiple emission peaks have drawn extensive attention for the ir capacity to achieve a combination of bioimaging and therapeutic functions.Here,we developed a novel PLM,LiYGeO_4:Bi^(3+),Pr^(3+),that simultaneously exhibits UV and NIR dual persistent luminescence(PersL)emissions after irradiation by X-ray.The material can be re peatedly excited by X-ray and emits similar lumine scence intensity every time,which shows good PersL stability.In addition,LiYGeO_4:Bi^(3+),Pr^(3+)exhibits photostimulated PersL properties by stimulation with a red light-emitting diode(LED)or NIR laser after long-term decay.This work provides a new choice of X-ray-excited PLMs with UV and NIR dual emission and the novel phosphor shows promise as a potential candidate for the integration of treatment and diagnosis of deep tumors.
文摘A ten-month field research study was meticulously conducted at Robert Moses State Park (RMSP) on the south shore of Long Island, NY. The objective was to determine if aerial phenomena of an unknown nature exist over a coastal location and to characterize their properties and behaviors. Primary and secondary field observation methods were utilized in this data-centric study. Forensic engineering principles and methodologies guided the study. The challenges set forward were object detection, observation, and characterization, where multispectral electro-optical devices and radar were employed due to limited visual acuity and intermittent presentation of the phenomena. The primary means of detection utilized a 3 cm X-band radar operating in two scan geometries, the X- and Y-axis. Multispectral electro-optical devices were utilized as a secondary means of detection and identification. Data was emphasized using HF and LF detectors and spectrum analyzers incorporating EM, ultrasonic, magnetic, and RF field transducers to record spectral data in these domains. Data collection concentrated on characterizing VIS, NIR, SWIR, LWIR, UVA, UVB, UVC, and the higher energy spectral range of ionizing radiation (alpha, beta, gamma, and X-ray) recorded by Geiger-Müller counters as well as special purpose semiconductor diode sensors.
