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JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY · 2017 · IF 1.591

Citric acid-loaded W1/O/W2 multiple emulsions efficiently remove colonic ammonia both in vitro and in vivo

Tengfei Bian,Xiujuan Zhang,Gaohong He,Zhijun Duan,Chunxu Dong,Xiangcun Li,Nana Guo

Hepatic encephalopathy (HE) is a neuropsychiatric disorder caused by chronic and acute liver diseases. It is believed that ammonia played an important role on the pathogenesis of the disease. Herein, acid-loaded water-in-oil-in-water (W1/O/W2) multiple emulsions with over 95% encapsulation efficiency were prepared and used to absorb colonic ammonia. The study of citric acid release from W1 to W2 in bulk deionized water indicated that only 17% acid released in 8 hours, which proved the stability of the multiple emulsions and hence prevented the intestine from being irritated by acid burst release. In vitro, the W1/O/W2 emulsion could remove around 90% ammonia in 1.5 hours from either the 3 mmol/L ammonia solution or the artificial colonic fluid with 1 and 0.5 mmol/L ammonia without acidifying the artificial colonic fluid. In vivo, compared with lactulose, W1/O/W2 emulsions could efficiently reduce the blood ammonia to the similar level in the rat models with HE without increasing the water content in feces. All these results indicated a potential application of W1/O/W2 multiple emulsions for the treatment of HE.

CAS / MDL: 4618-18-2
研究领域: 医学 · 药剂学
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-22 · IF 15.7

Chemotactic Zn micromotor for treatment of high blood ammonia-associated hepatic encephalopathy

Feng Ye,Gao Chao,Peng Xiuyun,Chen Bin,Ding Miaomiao,Du Dailing,Rong Jinghui,Lv Qi,Wilson Daniela A.,Tu Yingfeng,Peng Fei

Hepatic fibrosis involves hepatocyte damage, causing blood ammonia accumulation, which exacerbates liver pathology and crosses the blood-brain barrier, inducing hepatic encephalopathy. It is meaningful to construct a therapeutic platform for targeted ammonia clearance. In this work, a biocompatible water-powered Zn micromotor is constructed as an ammonia chemotaxis platform, which can be actuated by the water splitting reaction and the self-generated Zn 2+ gradient. It can propel towards NH 3 ·H 2 O source through the formation of complex ions [Zn(NH 3 ) 1 ](OH) + and [Zn(NH 3 ) 2 ](OH) + , representing a generalizable chemotaxis strategy via coordination reaction. In vivo, biomimetic collective behavior allows precise navigation and reduction of the intrahepatic ammonia level, reshaping the pathological microenvironment. This mechanism, operating in a green, zero-waste manner, facilitates integration of these micromotors into the domain of biological regulation. Such environment environment-adaptive platform is favorable for targeted treatment of hepatic fibrosis and hepatic encephalopathy caused by hyperammonemia, which is expected to provide inspiration for future personalized and precision medicine.

CAS / MDL: 7446-20-0
研究领域: 生物医学工程 · 肝脏病学 · 纳米医学
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Metabolomics · 2014 ·Vol. 11 ·期 3 ·559-570 · IF 3.965

A pilot study of the onset of hepatic encephalopathy (OHE) in mice induced by thioacetamide and the protective effect of taurine by holistic metabolic characterization

Wei Dan-Dan,Wang Jun-Song,Li Ming-Hui,Guo Ping-Ping,Dong Ge,Yang Ming-Hua,Kong Ling-Yi

Hepatic encephalopathy (HE) is a severe neuropsychiatric complication due to acute or chronic liver failure. In this work, an acute thioacetamide induced HE mice model was established to investigate the metabolic events in the onset of HE (OHE) and the protective role of taurine (TAU). Sera for biochemical evaluation, and livers and cortexes for histopathological inspection and NMR-based metabolomic investigation were collected. Principal component analysis and orthogonal partial least squares-discriminant analysis were performed to excavate differential metabolites of OHE, and explore the protective role of TAU. Metabolites pathway analysis was performed on significant metabolites selected based on loading/S-plots and fold change plots to identify biologically meaningful metabolic patterns and relevant pathways. The most affected pathways in OHE mice were those along the liver–brain axis: among them, the alanine, aspartate and glutamate metabolism was the most important. TAU showed better performance in improving the disturbed metabolism in the cortex than in the liver of OHE mice. This pilot study based on metabolomics approach and pathway analysis should help to understand HE systematically, and to develop new therapy for HE.

研究领域: 医学 · 生物学
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NATURE MEDICINE · 2025 · IF 50

The gut–brain axis underlying hepatic encephalopathy in liver cirrhosis

He Xiaolong,Hu Mengyao,Xu Yi,Xia Fangbo,Tan Yang,Wang Yuqing,Xiang Huiling,Wu Hao,Ji Tengfei,Xu Qian,Wang Lei,Huang Zhenhe,Sun Meiling,Wan Yu,Cui Peng,Liang Shaocong,Pan Yuan,Xiao Siyu,He Yan,Song Ruixin,Yan Junqing,Quan Xin,Wei Yingge,Hong Changze,Liao Weizuo,Li Fuli,El-Omar Emad,Chen Jinjun,Qi Xiaolong,Gao Jie,Zhou Hongwei

Up to 50–70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut–brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus , increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus . Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut–liver–brain axis and identify a promising therapeutic and predictive target for HE.

研究领域: 胃肠病学 · 微生物学 · 神经科学
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npj Flexible Electronics · 2025 ·Vol. 9 ·期 1 ·1-11 · IF 15.5

Stacking growth of ionically conductive MOF on biofabrics enables reliable NH3 sensor for hepatic encephalopathy diagnosis

Liu Kai,Xu Yifan,Tian Xiaozhu,Liang Junxuan,Zhao Zhihui,Wang Jun,Zhang Ziqi,Zhang Kewei,Yang Song

Aiming at the poor selectivity of electrically conductive metal-organic framework (EC-MOF) chemoresistive materials, this study develops a breakthrough room temperature ammonia (NH 3 ) sensor by stacking ionically conductive MOF (IC-MOF) on an environmentally friendly biofabric. The synergism between ionic conductivity, tailored metal-nitrogen interaction, and fabric porosity enables the sensor with high response ( R 0 / R g  = 14.7 towards 1 ppm NH 3 ), low detection limit (36 ppb), and remarkable selectivity (coefficient >5.12 against common organic interferents). Notably, the optimized sensor yields a sixfold enhancement in response as compared with traditional EC-MOF powders. A linear regression model validated by fivefold cross-validation achieves 98.4% accuracy in NH 3 concentration prediction, while the kNN classifier shows 96% accuracy in gas identification (tested on 192 samples). Preliminary clinical tests show that the sensor can clearly differentiate the exhaled NH 3 signals of four patients with HE from those of healthy individuals, demonstrating the potential for non-invasive diagnostics.

研究领域: 传感器与生物传感器 · 材料科学 · 纳米技术 · 医学诊断 · 分析化学 · 呼吸系统疾病 · 可穿戴电子器件
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Brain and Behavior · 2024 ·Vol. 14 ·期 7 ·e3621 · IF 2.6

The effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [18F]PBR146 in-vivo neuroinflammation imaging study

Xiang Kong,Song Luo,Shi Yao Wu,Jun Zhang,Gui Fen Yang,Guang Ming Lu,Long Jiang Zhang

Introduction Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [ 18 F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [ 18 F]PBR146 micro-PET/CT. Methods Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. Results The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [ 18 F]PBR146 in BDL+NS group was significantly higher than other groups ( p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella. Conclusions RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [ 18 F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.

CAS / MDL: 50-21-5
研究领域: 肝病学 · 神经病学 · 药理学 · 影像科学 · 微生物学
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