Theranostics
·
2019
·
IF 8.063
Shuai Wang,Yanke Lin,Ziyue Zhou,Lu Gao,Zemin Yang,Feng Li,Baojian Wu
Controlling bilirubin to a low level is necessary in physiology because of its severe neurotoxicity. Therefore, it is of great interest to understand the regulatory mechanisms for bilirubin homeostasis. In this study, we uncover a critical role for circadian clock in regulation of bilirubin detoxification and homeostasis. Methods : The mRNA and protein levels of Bmal1 (a core clock gene), metabolic enzymes and transporters were measured by qPCR and Western blotting, respectively. Luciferase reporter, mobility shift and chromatin immunoprecipitation were used to investigate transcriptional gene regulation. Experimental hyperbilirubinemia was induced by injection of bilirubin or phenylhydrazine. Unconjugated bilirubin (UCB) and conjugated bilirubin were assessed by ELISA. Results : We first demonstrated diurnal variations in plasma UCB levels and in main bilirubin-detoxifying genes Ugt1a1 and Mrp2 . Of note, the circadian UCB levels were antiphase to the circadian expressions of Ugt1a1 and Mrp2. Bmal1 ablation abrogated the circadian rhythms of UCB and bilirubin-induced hepatotoxicity in mice. Bmal1 ablation also decreased mRNA and protein expressions of both Ugt1a1 and Mrp2 in mouse livers, and blunted their circadian rhythms. A combination of luciferase reporter, mobility shift, and chromatin immunoprecipitation assays revealed that Bmal1 trans-activated Ugt1a1 and Mrp2 through specific binding to the E-boxes in the promoter region. Further, Bmal1 ablation caused a loss of circadian time-dependency in bilirubin clearance and sensitized mice to chemical induced-hyperbilirubinemia. Moreover, bilirubin stimulated Bmal1 expression through antagonism of Rev-erbα, constituting a feedback mechanism in bilirubin detoxification. Conclusion : These data supported a dual role for circadian clock in regulation of bilirubin detoxification, generating circadian variations in bilirubin level via direct transactivation of detoxifying genes Ugt1a1 and Mrp2, and defending the body against hyperbilirubinemia via Rev-erbα antagonism. Thereby, our study provided a potential mechanism for management of bilirubin related diseases.
研究领域:
分子生物学
·
昼夜节律
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Wan Zhou,Wenbin Hu,Qiancheng Zhan,Minjun Zhang,Xinjie Liu,Wajid Hussain,Huibin Yu,Shenqi Wang,Lei Zhou
Hemoperfusion is a well-developed method for removing bilirubin from patients with hyperbilirubinemia. The performance of adsorbents is crucial during the process. However, most adsorbents used for bilirubin removal are not suitable for clinical applications, because they either have poor adsorption performance or limited biocompatibility. Patients with hyperbilirubinemia usually have distinctive yellow skin, indicating that collagen, a primary component of the skin, may be an effective material for absorbing bilirubin from the blood. Based on this idea, we designed and synthesized collagen (Col) and collagen-polyethyleneimine (Col-PEI) microspheres and employed them as hemoperfusion adsorbents for bilirubin removal. The microspheres have an efficient adsorption rate, higher bilirubin adsorption capacity, and competitive adsorption of bilirubin in the bilirubin/bovine serum albumin (BSA) solution. The maximum adsorption capacities of Col and Col-PEI microspheres for bilirubin are 150.2 mg/g and 258.4 mg/g, respectively, which are higher than those of most traditional polymer microspheres. Additionally, the microspheres exhibit excellent blood compatibility originating from collagen. Our study provides a new collagen-based strategy for the hemoperfusion treatment of hyperbilirubinemia.
研究领域:
医学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC CANCER
·
2023
·Vol. 23
·期 1
·1-11
·
IF 3.8
Huang Xiancong,Chen Yang,Yang Huan,Wang Ruting,Chen Zhongjian
PurposeThis study examines prognostic value of preoperative serum bilirubin, including unconjugated bilirubin (UCB), conjugated bilirubin (CB), and total bilirubin (TB), in esophageal squamous cell carcinoma (ESCC) patients who underwent curative resection.Methods Between May 2010 and December 2012, a total of 351 ESCC patients were retrospectively reviewed. All the patients underwent curative resection as their primary treatment. Clinicopathological features and overall survival (OS) rate were investigated. Kaplan-Meier curves were used to calculate the OS rate, and the prognostic factors were identified by Cox regression model. Besides, the potential inhibition effect of UCB on ESCC was investigated with both in vitro and in vivo models.Results The higher-level groups of UCB, CB, and TB demonstrated longer OS than their low counterparts, with hazard ratio (HR) values of 0.567 (95% CI: 0.424–0.759), 0.698 (95% CI: 0.522–0.933), and 0.602 (95% CI: 0.449–0.807), respectively. All three forms of bilirubin were identified as independent prognostic factors for patients with ESCC, and they were found to effectively stratify the survival risk of patients at TNM stage III. In vivo and in vitro models further confirmed the inhibitory effect of unconjugated bilirubin (UCB) on the proliferation of ESCC.Conclusion The findings of our study have shed new light on the prognostic value and biological functions of bilirubin in relation to ESCC. These results may contribute to a better understanding of the underlying mechanisms involved in ESCC tumorigenesis and provide potential therapeutic pathways for treating ESCC.
研究领域:
肿瘤学
·
医学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Chengyu Zhang,Lin Zhu,Jiaxing Zhang,Wenhang Wang,Yan Zeng,Shengping You,Wei Qi,Rongxin Su,Zhimin He
In this study, we aimed to develop B. subtilis spore coat protein A (CotA) for the enzymatic determination of bilirubin . Firstly, molecular docking and oxidation kinetic analysis confirmed the feasibility of CotA for oxidizing bilirubin . Secondly, CotA showed pH-preferable oxidization performance to direct bilirubin (DB) in acidic conditions and an alkaline-catalytic oxidation capacity to total bilirubin (TB). Mechanism analysis results confirm that the conformational changes of CotA, DB and UB caused by pH changes are responsible for the selective oxidation of DB and TB by CotA. Then, CotA exhibits better structural characteristics and enzymatic performance than M. verrucaria -derived bilirubin oxidase ( Mv -BOD). Besides, the strong anti-interference ability helps CotA adapt to complex catalytic environment in the detection of DB and TB. Our results prove that CotA can be used as a promising candidate bio-enzymatic detection reagent for DB and TB.
研究领域:
生物化学
·
医学检测
✓ 已验证
DOI
高影响因子
JOURNAL OF POLYMERS AND THE ENVIRONMENT
·
2022
·Vol. 31
·期 4
·1553-1567
·
IF 4.705
Liu Muhua,Zhang Wen,Zhang Panpan,Yuan Ling,Li Hao,Zhan Jinjie,Zhao Wenjun,Mei Xi
Hyperbilirubinemia is one of most severe clinical diseases, which is caused by the accumulation of unconjugated bilirubin. Electrospun nanofiber membranes used as highly efficient bilirubin adsorbents have been applied to remove the extra bilirubin in hemoperfusion for their high surface area and easy functionalized properties. In this work, Lysine (Lys) grafted polyacrylonitrile (PAN) electrospun nanofiber membranes doped with organic Hectorite (OHec) (Lys-HPAN@OHec) have been fabricated via a series of modified process, including pore forming, alkaline hydrolysis and grafting reaction. The obtained Lys-HPAN@OHec nanofiber membranes have been analyzed in detail and investigated the adsorption capacity for bilirubin. Compared with original PNA membranes, Lys-HPAN@OHec nanofiber membranes show an excellent bilirubin adsorption capacity and more stable rejection rate of bovine serum albumin (BSA). The maximum adsorption capacity of Lys-HPAN@OHec membranes for bilirubin is 64 mg/g, the adsorption process of Lys-HPAN@OHec membranes matched the Langmuir model well. In addition, dynamic adsorption reveals that the adsorption equilibrium time of Lys-HPAN@OHec membranes is about 2 h. Significantly, Lys-HPAN@OHec membranes have excellent biocompatibility and hemocompatibility. This study demonstrates that the novel Lys-HPAN@OHec membranes may provide a new way to treat hyperbilirubinemia.
研究领域:
生物医学工程
·
材料科学
·
临床医学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Guo Ma,Ying Zhang,Wenyan Chen,Zhifang Tang,Xiaoming Xin,Ping Yang,Xiaoqin Liu,Weimin Cai,Ming Hu
Bilirubin-related adverse reactions (ADR, e.g., jaundice and hyperbilirubinemia) induced by herbs rich in certain polyphenolic acids are widely reported. However, the causes and the mechanisms underlying these ADR are not well understood. The purpose of this article is to determine the mechanism by which certain polyphenolic acids inhibit UGT1A1-mediated bilirubin glucuronidation, leading to jaundice or hyperbilirubinemia. We investigated in vitro inhibitory effects on bilirubin glucuronidation of salvianolic acid A (SAA), salvianolic acid B (SAB), danshensu (DSS), protocatechuic aldehyde (PA), and rosmarinic acid (RA), as well as two Salvia miltiorrhiza injections (DSI and CDI) rich in polyphenolic acids. The results showed that average formation rates of three bilirubin glucuronides displayed a significant difference (p < 0.05) and the formation of monoglucuronide was favored regardless if an inhibitor was present or not. SAA, SAB, DSI, and CDI, but not DSS, PA, and RA, significantly inhibited human UGT1A1-mediated bilirubin glucuronidation via a mixed-type inhibitory mechanism. Average IC50 values of SAA, SAB, DSI, and CDI-mediated inhibition of bilirubin glucuronidation were bilirubin concentration-dependent, and their values (against total bilirubin glucuronidation) were in the range 0.44 ± 0.02 to 0.86 ± 0.04 μg/mL (for SAA), 4.22 ± 0.30 to 12.50 ± 0.93 μg/mL (for SAB), 9.29 ± 0.76 to 18.82 ± 0.63 μg/mL (for DSI), and 9.18 ± 2.00 to 22.36 ± 1.39 μg/mL (for CDI), respectively. In conclusion, SAA and its analog SAB are the main ingredients responsible for inhibition of bilirubin glucuronidation by DSI and CDI, whose use is associated with many high bilirubin-related ADR.
研究领域:
药理学
·
中药学
·
临床医学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Rui Su,Wei Liu,Gang Shi,Dongling Chen,Lihua Yan,Qian Li,Haichao Ni,Meili Yu,Liang Xu
Hyperbilirubinemia is primarily treated through hemoperfusion, a process that utilizes biomaterials as adsorbents to eliminate excessive bilirubin from the bloodstream. However, extracorporeal circuits are prone to thrombus formation due to the frequent use of blood-contacting devices, potentially leading to treatment failure and adverse clinical outcomes. In this study, using a resin substance treated with sulfated polysaccharides (GLU-ERM-0100), we present a reliable and safe approach for removing excessive bilirubin from blood. The resin’s pore size facilitates bilirubin adsorption, while sulfonic and hydroxyl groups incorporated within the material enable like-heparinization. GLU-ERM-0100 serves as a temporary blood-thinning agent, binding coagulation factors in the extracorporeal circuit, thereby eliminating the need for conventional anticoagulant medications. Both in vitro and animal studies demonstrate the material’s exceptional bilirubin adsorption capacity and effective anticoagulation properties.
研究领域:
医学工程
·
血液学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Lei Ouyang,Ling Yao,Rongmei Tang,Xiangliang Yang,Lihua Zhu
The concentration of bilirubin in serum is a key indicator for liver function, because excess bilirubin accumulation may lead to serious health problems like Jaundice. It is known that in comparison with total bilirubin, the concentration of hydrophobic free bilirubin is more closely associated with Jaundice because of its capability to cross the capillary walls and even blood-brain barrier. However, it is not easy to detect the low concentration of free bilirubin (∼ nM) in the presence of large amount of protein-bound bilirubin (> 150 μM), and no point-of-care detection tool is available. In the present work, direct detection of free bilirubin was realized by using surface enhanced Raman spectroscopy (SERS). By mimicking the in vivo chemical interaction between glucuronic acid and bilirubin, glucose functionalized Au nanoparticles were synthesized for selective capture and detection of free bilirubin. By developing a convenient detection procedure of using robust Au array chip and internal standard calibration method, the sensitive detection of free bilirubin with detection limit down to 0.1 nM was achieved on a handhold Raman spectrometer by monitoring its fingerprint spectra. The clinical applicability was demonstrated with analyzing the spiked and real blood samples. As a proof of concept, the binding constant between bilirubin and human serum albumin (HSA) was determined with the present method. The influence of the binding capacity of the HSA for bilirubin in the presence of competing molecule salicylate sodium was also quantitatively measured, which demonstrated the importance of detection of free bilirubin instead of total bilirubin for warning the risk of bilirubin encephalopathy.
研究领域:
分析化学
·
生物医学工程
·
纳米技术
·
临床诊断
·
光谱学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS
·
2019
·Vol. 19
·期 7
·1726
·
IF 3.031
Zhou Li,Wenxiang Xiao,Rongen Huang,Yajing Shi,Cheng Fang,Zhencheng Chen
Serum bilirubin is an important biomarker for the diagnosis of various types of liver diseases and blood disorders. A polydopamine/gold nanoclusters composite film was fabricated for the fluorescent sensing of free bilirubin. Bovine serum albumin (BSA)-stabilized gold nanoclusters (AuNCs) were used as probes for biorecognition. The polydopamine film was utilized as an adhesion layer for immobilization of AuNCs. When the composite film was exposed to free bilirubin, due to the complex that was formed between BSA and free bilirubin, the fluorescence intensity of the composite film was gradually weakened as the bilirubin concentration increased. The fluorescence quenching ratio (F0/F) was linearly proportional to free bilirubin over the concentration range of 0.8~50 μmol/L with a limit of detection of 0.61 ± 0.12 μmol/L (S/N = 3). The response was quick, the film was recyclable, and common ingredients in human serum did not interfere with the detection of free bilirubin.Keywords:free bilirubin;polydopamine;gold nanoclusters;fluorescent film
研究领域:
生物传感
·
医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2023
·
IF 8.6
Fangfang Wei,Feng Qi,Yangyang Li,Weiyu Dou,Tangye Zeng,Jing Wang,Zhikan Yao,Lin Zhang,Zhe Tang
Bilirubin is a serious toxin in the blood of liver failure patients, and the development of bilirubin adsorbent with high removal efficiency, excellent hemocompatibility is crucial to improve the efficacy of hemoperfusion therapy. Herein, PAN/PEI nanofiber membrane (NFM) with amino-rich and smooth surface structure was prepared through a more facile co-blended electrospun method. During simulated adsorption experiments in vitro , PAN/PEI NFMs exhibited a high adsorption capacity of 142.79 mg g −1 for free bilirubin at clinical bilirubin concentration (100 mg L -1 ) in patients with liver failure. In addition, the bilirubin removal efficiency in static adsorption exceeded 96% when the PAN/PEI NFMs addition was greater than 120 mg. In particular, PAN/PEI NFMs displayed excellent hemocompatibility, presented a low hemolysis rate (0.4%), favorable anti-adhesion properties for hemocyte and plasma protein, and had no significant effect on coagulation. The development of this facile method promotes the feasibility of nanofibrous membranes for the treatment of hyperbilirubinemia with significant implications for improving therapeutic efficacy.
研究领域:
材料科学
·
生物医学工程
·
血液透析
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Zhiwen Hu,Fangjiu He,Anxiong Liu,Xuan Zhao,Shuangquan Wu,Jian You,Qifa Ye,Xiaowen Shi,Zibiao Zhong,Ruilong Shao
Liver failure, marked by a rapid or progressive decline in liver function, leads to complications such as hyperbilirubinemia and infections, contributing to approximately 2 million global deaths each year. Current hemoperfusion methods for hyperbilirubinemia treatment are limited by their low adsorption selectivity and inadequate biosafety, necessitating better treatments. In this study, a chitosan-based HKUST-1 aerogel (HC) was developed as a highly selective, biosafe, and antibacterial adsorbent. The integration of HKUST-1 with chitosan formed an aerogel that achieved high bilirubin adsorption in vitro along with significant biosafety, anticoagulant properties, and antibacterial activity against Staphylococcus aureus and Escherichia coli. In an animal model of hyperbilirubinemia, the HC aerogel demonstrated 53.8% bilirubin clearance from the whole blood. These findings suggest that the HKUST-1/chitosan aerogel is a promising candidate for liver failure treatment, effectively combining bilirubin adsorption with infection control in complex blood environments.
研究领域:
生物医学工程
·
纳米材料
·
肝病学
·
吸附治疗
·
生物材料
·
感染控制
✓ 已验证
DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2024
·
IF 8.1
Wan Zhou,Minjun Zhang,Xinjie Liu,Wajid Hussain,Baoan Zhu,Huibin Yu,Shenqi Wang,Lei Zhou
Hemoperfusion is one of the most effective treatments for the removal of bilirubin from the blood. Chitosan (CS) has been widely investigated as a hemoperfusion adsorbent to remove bilirubin due to its biocompatibility and biodegradability. However, the limited adsorption capacity of CS for free bilirubin or albumin-rich bilirubin solution, and the strong adsorption for albumin, limit its extensive use. The goal of this work is to improve specific bilirubin adsorption of CS while reducing its adsorption for albumin. In this study, collagen (Col) was chosen as a ligand and grafted onto the surface of CS microspheres to form CS-Col microspheres and therefore to improve their adsorption performance for bilirubin. The maximum adsorption capacity of the CS-Col microspheres for bilirubin increases from 24.2 to 76.9 mg/g. The enhancement factor is higher than that of other CS-based adsorbents. Moreover, the adsorption of CS-Col microspheres for albumin is effectively reduced to 2.6 %, while maintaining good blood compatibility. Compared to other CS-based bilirubin adsorbents, our CS-Col microspheres have the advantage of specific adsorbing bilirubin against albumin due to introducing collagen. This work provides new directions for designing high-performance bilirubin adsorbents. Our CS-Col microspheres show great promise for the treatment of hyperbilirubinemia.
研究领域:
生物医学工程
·
材料科学
·
血液学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）