JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-20
·
IF 9.429
Wu Longlong,Tian Xuan,Zuo Huaiwen,Zheng Weiping,Li Xiang,Yuan Mengshu,Tian Xiaorong,Song Hongli
Background Steatotic livers tolerate ischemia–reperfusion injury (IRI) poorly, increasing the risk of organ dysfunction. Ferroptosis is considered the initiating factor of organ IRI. Heme oxygenase oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) (HO-1/BMMSCs) can reduce hepatic IRI; however, the role of ferroptosis in IRI of steatotic grafts and the effect of HO-1/BMMSCs-derived exosomes (HM-exos) on ferroptosis remain unknown.Methods A model of rat liver transplantation (LT) with a severe steatotic donor liver and a model of hypoxia and reoxygenation (H/R) of steatotic hepatocytes were established. Exosomes were obtained by differential centrifugation, and the differentially expressed genes (DEGs) in liver after HM-exo treatment were detected using RNA sequencing. The expression of ferroptosis markers was analyzed. microRNA (miRNA) sequencing was used to analyze the miRNA profiles in HM-exos.Results We verified the effect of a candidate miRNA on ferroptosis of H/R treated hepatocytes, and observed the effect of exosomes knockout of the candidate miRNA on hepatocytes ferroptosis. In vitro, HM-exo treatment reduced the IRI in steatotic grafts, and enrichment analysis of DEGs suggested that HM-exos were involved in the regulation of the ferroptosis pathway. In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis.Conclusion Ferroptosis is involved in the IRI during LT with a severe steatotic donor liver. miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis, thereby attenuating graft IRI, which might be a promising strategy to treat IRI in steatotic grafts.Graphical Abstract
研究领域:
分子生物学
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细胞生物学
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移植学
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肝病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2025
·
IF 2.8
Saisai Ling,Ying Jin,Cuiyao He,Lisha Fu,Yuhua Deng,Xiaohui Qi,Zhenglei Wang,Yiying Wu
Tacrolimus is a potent macrolide immunosuppressant widely used in pediatric liver transplant patients. However, its narrow therapeutic window and significant inter-individual pharmacokinetic differences result in a poor correlation between blood concentrations and administered doses. To support its individualized dose, a sensitive, fast and robust ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed to measure tacrolimus concentrations in whole blood of pediatric liver transplant patients. The method employed acetonitrile for protein precipitation, and sample separation was achieved using an Acquity UPLC CSH C 18 column (2.1 × 50 mm, 1.7 μm) with gradient elution. The mobile phase consisted of ammonium solution–water (0.5:1000, v /v) and methanol. The method demonstrated good linearity within a concentration range of 0.20–50.00 ng/mL. The intra- and inter-day precisions of tacrolimus in whole blood were less than 13.5 %, with the accuracy ranged from −7.2 % to 13.0 %. Selectivity, carryover, matrix effects, recovery, dilution reliability, and stability all met the standards set by relevant guidelines. The established UPLC–MS/MS method was successfully applied to measure the concentration of tacrolimus in the whole blood of pediatric liver transplant patients and support its individualized dose. Under the rapid UPLC–MS/MS method, 25 (65.8 %) patients required a dose increase, 3 (7.9 %) patients needed a dose reduction, and 10 (26.3 %) patients maintained their original dosage without adjustment.
研究领域:
药理学
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临床医学
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分析化学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2023
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IF 6.2
Xinghui Yu,Yongqiang Ma,Siyuan Liu,Chunchun Qi,Weiqi Zhang,Wen Xiang,Zhaoxian Li,Kai Yang,Shaoxian Duan,Xinrao Du,Jian Yu,Yan Xie,Zicheng Wang,Wentao Jiang,Li Zhang,Xiaodong Lin
Post-operative pathogenic infections in liver transplantation seriously threaten human health. It is essential to develop novel methods for the highly sensitive and rapid detection of Staphylococcus aureus ( S. aureus ). Interestingly, the combination of the property of bacteria to secrete hydrogen peroxidase , bacterial metabolism-triggered-chemiluminescence (CL)-based bioassays can be as a candidate point-of-care testing (POCT) for the detection of S. aureus against the CL substrate Luminol and hydrogen peroxide without excitation light sources. Here, a CL-based strategy with stable and visualized CL intensity was fabricated according to a hybrid biomimetic enzyme of copper-Hemin metal-organic framework, which enhances the biological enzyme activity while improving the stability and sensitivity of the assay. By further integrating S. aureus -specific capture and one-step separation of the antibody-modified Fe 3 O 4 NPs (Fe 3 O 4 NPs@Ab), the portable device integrated smartphone enables CL-based POCT for specific detection of S. aureu s in the range of 10 1 –10 6 CFU/mL with a limit of detection as low as 1 CFU/mL. Specifically, S. aureus can be eliminated after detection with high antibacterial efficiency due to the excellent photothermal properties of Fe 3 O 4 NPs@Ab. The developed multifunctional platform has the advantages of simplicity of operation and low cost, indicating great potential in clinical applications.
研究领域:
医学微生物学
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临床检验
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生物化学
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产品关联
DOI
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 13
·3559-3568
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IF 7.59
Peng Liu,Lifei Yang,Aihua Shi,Yerong Qian,Xin Liu,Dinghui Dong,Xufeng Zhang,Yi Lv,Junxi Xiang
Veno-venous bypass (VVB) is necessary for maintaining hemodynamic and internal environment stabilities in complex liver surgeries. However, the current VVB strategies require systematic anticoagulation and are time-consuming, leading to unexpected complications. This study aims to overcome these limitations by using a novel magnetic artificial blood vessel constructed with heparin-PLCL core–shell nanofibers. Coaxial electrospinning was used to fabricate core–shell nanofibers with heparin encapsulated into the core layer. The microstructure, physical and chemical properties, hemocompatibility, and heparin release behavior were characterized. The regional anticoagulation magnetic artificial vessel was constructed with these nanofibers and used to perform VVB in a rat liver transplantation model for in vivo evaluation. The core–shell nanofibers appeared smooth and uniform without apparent defects. Fluorescence and TEM images indicated that heparin was successfully encapsulated into the core layer. In addition, the in vitro heparin release test presented a two-phase release profile, burst release at day 1 and sustained release from days 2 to 14, which resulted in better hemocompatibility. The VVB could be rapidly deployed in 3.65 ± 0.83 min by the magnetic artificial vessel without systemic anticoagulation. Moreover, the novel device could reduce portal pressure and abdominal organ congestion, protect intestinal function, and increase the survival rate of liver transplantation with a long anhepatic phase from 0 to 65%. In summary, VVB can be rapidly deployed using regional anticoagulation magnetic artificial blood vessels without systemic anticoagulation, which is promising for improving patient outcomes after complex liver surgery.
研究领域:
生物医学工程
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材料科学
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移植外科
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Yan Liu,Feng Qi,Lun-Jian Xiang,Zhu-Jun Yi,Sheng-Wei Li
Background: Donation after circulatory death (DCD) livers are limited by mandatory warm ischemia and are more susceptible to ischemia‒reperfusion injury (IRI). Inflammation and oxidative stress play key roles in the development of hepatic IRI, and Rutaecarpine (Rut) has anti-inflammatory and anti-oxidative stress effects. The aim of this study was to investigate whether Rut can alleviate hepatic IRI in liver transplantation (LT) and to explore the underlying mechanisms.Methods: Rat DCD LT and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established to clarify the effect of Rut on hepatic IRI. The key molecules involved in the hepatoprotective effects of Rut were identified through joint analysis of data from LT patients and drug targets. The target was further validated by in silico, in vivo and in vitro experiments.Results: Rut significantly alleviated liver dysfunction, pathological injury, and apoptosis and improved the survival rate of the rats subjected to LT. In addition, Rut significantly inhibited inflammatory response and oxidative stress. Rut also had similar effects on OGD/R-induced hepatocyte injury. Mechanistically, bioinformatics analysis and in vivo and in vitro experiments revealed that PDE4B may be a key target by which Rut exerts its protective effect, and molecular docking and cellular thermal shift assay confirmed this result. The function of PDE4B was studied via gene intervention technology, and the results showed that PDE4B can aggravate hepatic IRI. Furthermore, PDE4B overexpression abrogated the protective effect of Rut on the liver in LT.Conclusion: Rut alleviates hepatic IRI by targeting PDE4B to inhibit inflammation and oxidative stress. These findings highlight the potential of Rut as a drug candidate for the treatment of patients undergoing LT.
研究领域:
药理学
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移植学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Siqi Li,Tiemei Zheng,Yusen Li,Xiaoli Wang,Yanjun Jiang,Pengyu Huang
Therapeutic liver grafts (Livergraft, 10 mm × 3 mm) were developed by biocasting bioorthogonal gelatin with in vitro -expanded primary hepatocytes (3 × 10 7 cells/mL). The bioorthogonal gelatin composed of methyltetrazine-modified gelatin (Gel-T) and norbornene-modified gelatin (Gel N), which were synthesized by reacting methyltetrazine-NHS ester and cis-5-Norbornene- endo -2,3-dicarboxylic anhydride with the amino groups of gelatin, respectively. Uniform mixing of in vitro -expanded primary hepatocytes with Gel-T and Gel-N triggered an immediate bioorthogonal reaction between norbornene and methyltetrazine, resulting in solidification to form Livergraft within 10 min. The resulting Livergraft exhibited a well-defined 3D architecture with pore sizes of 100–400 μm. Remarkably, hepatocytes within Livergraft proliferated and self-organized into cell aggregates with an average diameter of 118 μm after three days of in vitro 3D culture. This strategy was faclie and efficient, requiring neither external triggers ( e.g. , UV light), Matrigel pre-incubation, nor specialized equipment. Livergraft transplantation effectively compensated liver function in mice undergoing 90 % hepatectomy, with five out of twelve mice surviving long-term. On the 5th day after hepatectomy, the caudate lobe was significantly enlarged, and the liver function indicators (ALT, AST, and ALP) were consistent with those of normal mice. Comparative characterization demonstrated that bioorthogonal gelatin outperformed GelMA in supporting hepatocyte function and tissue formation, demonstrating its potential as a promising material for functional liver tissue fabrication.
研究领域:
生物医学工程
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组织工程
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再生医学
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肝病学
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生物材料
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
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2024
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IF 15.8
Ruibing Feng,Yu Fan,Xinya Zhang,Lanmei Chen,Zhang-Feng Zhong,Yitao Wang,Hua Yu,Qing-Wen Zhang,Guodong Li
Acute liver failure (ALF) is a rare and serious condition characterized by major hepatocyte death and liver dysfunction. Owing to the limited therapeutic options, this disease generally has a poor prognosis and a high mortality rate. When ALF cannot be reversed by medications, liver transplantation is often needed. However, transplant rejection and the shortage of donor organs still remain major challenges. Most recently, stem cell therapy has emerged as a promising alternative for the treatment of liver diseases. However, the limited cell delivery routes and poor stability of live cell products have greatly hindered the feasibility and therapeutic efficacy of stem cell therapy. Inspired by the functions of mesenchymal stem cells (MSCs) primarily through the secretion of several factors, we developed an MSC-inspired biomimetic multifunctional nanoframework (MBN) that encapsulates the growth-promoting factors secreted by MSCs via combination with hydrophilic or hydrophobic drugs. The red blood cell (RBC) membrane was coated with the MBN to enhance its immunological tolerance and prolong its circulation time in blood. Importantly, the MBN can respond to the oxidative microenvironment, where it accumulates and degrades to release the payload. In this work, two biomimetic nanoparticles, namely, rhein-encapsulated MBN (RMBN) and N-acetylcysteine (NAC)-encapsulated MBN (NMBN), were designed and synthesized. In lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced and acetaminophen (APAP)-induced ALF mouse models, RMBN and NMBN could effectively target liver lesions, relieve the acute symptoms of ALF, and promote liver cell regeneration by virtue of their strong antioxidative, anti-inflammatory, and regenerative activities. This study demonstrated the feasibility of the use of an MSC-inspired biomimetic nanoframework for treating ALF.
研究领域:
药学
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生物医学工程
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肝病学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2024
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IF 12.8
Feixiang Luo,Mingqian Li,Yuguo Chen,Shifei Song,Haiyang Yu,Peng Zhang,Chunsheng Xiao,Guoyue Lv,Xuesi Chen
Acute rejection is a life-threatening complication after liver transplantation. Immunosuppressants such as tacrolimus are used to inhibit acute rejection of liver grafts in clinic. However, inefficient intragraft accumulation may reduce the therapeutic outcomes of tacrolimus. Here, an enzyme-responsive nanoparticle is developed to selectively enhance the accumulation of tacrolimus in liver allograft through enzyme-induced aggregation to refine immunotherapeutic efficacy of tacrolimus. The nanoparticles are composed of amphiphilic tacrolimus prodrugs synthesized by covalently conjugating tacrolimus and matrix metalloproteinase 9 (MMP9)-cleavable peptide-containing methoxy poly (ethylene glycol) to poly ( l -glutamic acid). Upon exposure to MMP9, which is overexpressed in rejected liver allografts, the nanoparticles undergo a morphological transition from spherical micellar nanoparticles to microscale aggregate-like scaffolds. Intravenous administration of MMP9-responsive nanoparticles into a rat model of acute liver graft rejection results in enhanced nanoparticle accumulation in allograft as compared to nonresponsive nanoparticles. Consequently, the MMP9-responsive nanoparticles significantly inhibit intragraft inflammatory cell infiltration and proliferation, maintain intragraft immunosuppressive environment, alleviate graft damage, improve liver allograft function, abate weight loss and prolong recipient survival. This work proves that morphology-switchable enzyme-responsive nanoparticles represent an innovative strategy for selectively enhancing intragraft accumulation of immunosuppressive agents to improve treatment of liver allograft rejection.
研究领域:
药学
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纳米技术
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移植免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2023
·Vol. 14
·期 2
·555-570
·
IF 5.4
Huang Jian,Wang Zhengji,Chen Zihe,Huang Chunxin,Wang Ying,Li Xing,Lv Weiyang,Qi Guiqiang,Liu Huilin
Celastrol (CST) has positive pharmacological effects on various cancers, but clinical application is limited because of poor water solubility and systemic toxicity. Ferric oxide (Fe 3 O 4 ) has a large specific surface area and can be functionalized by inorganic modification to form complex magnetic drug delivery systems. Herein, Fe 3 O 4 was surface-modified with citric acid and polyethylene glycol (PEG) (via) the Mitsunobu reaction and then covalently bound to CST. Finally, magnetic microbubbles (MMBs) containing perfluoropropane (C 3 F 8 ) and Fe 3 O 4 -PEG 2K -CST particles were constructed with poly(lactic-co-glycolic acid) (PLGA) as the shell membrane. In vitro studies showed that ultrasound-mediated MMBs exhibited improved inhibition of VX2 cell proliferation compared to inhibition achieved using MMBs without ultrasound mediation, blank MMBs, or free CST. In ultrasound mode, MMBs have favorable imaging properties. After the application of a high mechanical index, MMBs collapse through the cavitation effect, releasing their internal Fe 3 O 4 -PEG 2K -CST. The CST is then delivered to the tumor microenvironment under acidic conditions. In magnetic resonance imaging T2 mode, a specific hypointense signal was observed in the tumor area compared with that before treatment, whereas no significant change occurred in the signal intensity of the surrounding organs. After treatment, pathological examination of tumor-bearing rabbit tissues showed that iron elements accumulated in several apoptosis cells in the tumor area, with no apparent abnormalities found in other areas. Thus, ultrasound-mediated MMBs could significantly improve the drug uptake of solid tumors and inhibit tumor growth with favorable biological safety. Graphical Abstract
研究领域:
药理学
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纳米技术
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肿瘤学
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生物医学工程
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医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 23
·
IF 11.7
Bo Deng,Yue Ma,Jialyu Huang,Runbang He,Miaomiao Luo,Lina Mao,Enhua Zhang,Yuanyuan Zhao,Xiaoli Wang,Qiangsong Wang,Mingchang Pang,Yilei Mao,Huayu Yang,Lanxia Liu,Pengyu Huang
The utilization of three-dimensional (3D) bioprinting technology to create a transplantable bioartificial liver emerges as a promising remedy for the scarcity of liver donors. This study outlines our strategy for constructing a 3D-bioprinted liver, using in vitro–expanded primary hepatocytes recognized for their safety and enhanced functional robustness as hepatic cell sources for bioartificial liver construction. In addition, we have developed bioink biomaterials with mechanical and rheological properties, as well as printing capabilities, tailored for 3D bioprinting. Upon heterotopic transplantation into the mesentery of tyrosinemia or 90% hepatectomy mice, our 3D-bioprinted liver effectively restored lost liver functions, consequently extending the life span of mice afflicted with liver injuries. Notably, the inclusion of an artificial blood vessel in our 3D-bioprinted liver allowed for biomolecule exchange with host blood vessels, demonstrating, in principle, the rapid integration of the bioartificial liver into the host vascular system. This model underscores the therapeutic potential of transplantation for the treatment of liver failure diseases.
研究领域:
组织工程
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再生医学
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生物医学工程
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肝病学
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移植学
✓ 已验证
DOI
PubMed
高影响因子
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