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Article ; Online: Extracellular vesicles as vehicles for drug delivery to the heart.

Ilahibaks, Nazma F / Lei, Zhiyong / Sluijter, Joost P G

2024

Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehae099
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Article: Editorial: Bone targeting nanoparticle drug delivery system in bone metabolism and bone-related tumor diseases.

Wang, Xing / Meng, Fenghua / Lei, Zhiyong / Fan, Daoyang / Lou, Bo

Frontiers in pharmacology

2022 Volume 13, Page(s) 1016631

Language	English
Publishing date	2022-09-20
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.1016631
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Article ; Online: Comparative analysis of lipid Nanoparticle-Mediated delivery of CRISPR-Cas9 RNP versus mRNA/sgRNA for gene editing in vitro and in vivo.

Walther, Johanna / Porenta, Deja / Wilbie, Danny / Seinen, Cornelis / Benne, Naomi / Yang, Qiangbing / de Jong, Olivier Gerrit / Lei, Zhiyong / Mastrobattista, Enrico

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

2024 Volume 196, Page(s) 114207

Abstract: The discovery that the bacterial defense mechanism, CRISPR-Cas9, can be reprogrammed as a gene editing tool has revolutionized the field of gene editing. CRISPR-Cas9 can introduce a double-strand break at a specific targeted site within the genome. ... ...

Abstract	The discovery that the bacterial defense mechanism, CRISPR-Cas9, can be reprogrammed as a gene editing tool has revolutionized the field of gene editing. CRISPR-Cas9 can introduce a double-strand break at a specific targeted site within the genome. Subsequent intracellular repair mechanisms repair the double strand break that can either lead to gene knock-out (via the non-homologous end-joining pathway) or specific gene correction in the presence of a DNA template via homology-directed repair. With the latter, pathological mutations can be cut out and repaired. Advances are being made to utilize CRISPR-Cas9 in patients by incorporating its components into non-viral delivery vehicles that will protect them from premature degradation and deliver them to the targeted tissues. Herein, CRISPR-Cas9 can be delivered in the form of three different cargos: plasmid DNA, RNA or a ribonucleoprotein complex (RNP). We and others have recently shown that Cas9 RNP can be efficiently formulated in lipid-nanoparticles (LNP) leading to functional delivery in vitro. In this study, we compared LNP encapsulating the mRNA Cas9, sgRNA and HDR template against LNP containing Cas9-RNP and HDR template. Former showed smaller particle sizes, better protection against degrading enzymes and higher gene editing efficiencies on both reporter HEK293T cells and HEPA 1-6 cells in in vitro assays. Both formulations were additionally tested in female Ai9 mice on biodistribution and gene editing efficiency after systemic administration. LNP delivering mRNA Cas9 were retained mainly in the liver, with LNP delivering Cas9-RNPs additionally found in the spleen and lungs. Finally, gene editing in mice could only be concluded for LNP delivering mRNA Cas9 and sgRNA. These LNPs resulted in 60 % gene knock-out in hepatocytes. Delivery of mRNA Cas9 as cargo format was thereby concluded to surpass Cas9-RNP for application of CRISPR-Cas9 for gene editing in vitro and in vivo.
MeSH term(s)	Humans ; Female ; Mice ; Animals ; Gene Editing/methods ; CRISPR-Cas Systems ; CRISPR-Associated Protein 9/genetics ; RNA, Guide, CRISPR-Cas Systems ; RNA, Messenger/genetics ; HEK293 Cells ; Tissue Distribution ; Nanoparticles ; DNA ; Liposomes
Chemical Substances	CRISPR-Associated Protein 9 (EC 3.1.-) ; RNA, Guide, CRISPR-Cas Systems ; Lipid Nanoparticles ; RNA, Messenger ; DNA (9007-49-2) ; Liposomes
Language	English
Publishing date	2024-02-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1065368-5
ISSN	1873-3441 ; 0939-6411
ISSN (online)	1873-3441
ISSN	0939-6411
DOI	10.1016/j.ejpb.2024.114207
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Article: Characterization of Key Odorants in Lushan Yunwu Tea in Response to Intercropping with Flowering Cherry.

Gao, Yinxiang / Lei, Zhiyong / Huang, Jigang / Sun, Yongming / Liu, Shuang / Yao, Liping / Liu, Jiaxin / Liu, Wenxin / Liu, Yanan / Chen, Yan

Foods (Basel, Switzerland)

2024 Volume 13, Issue 8

Abstract: Lushan Yunwu tea (LSYWT) is a famous green tea in China. However, the effects of intercropping tea with flowering cherry on the overall aroma of tea have not been well understood. In this study, headspace solid-phase microextraction (HS-SPME) coupled ... ...

Abstract	Lushan Yunwu tea (LSYWT) is a famous green tea in China. However, the effects of intercropping tea with flowering cherry on the overall aroma of tea have not been well understood. In this study, headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) was used for analysis. A total of 54 volatile compounds from eight chemical classes were identified in tea samples from both the intercropping and pure-tea-plantation groups. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and odor activity value (OAV) methods combined with sensory evaluation identified cis-jasmone, nonanal, and linalool as the key aroma compounds in the intercropping group. Benzaldehyde, α-farnesene, and methyl benzene were identified as the main volatile compounds in the flowering cherry using headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS). These findings will enrich the research on tea aroma chemistry and offer new insights into the product development and quality improvement of LSYWT.
Language	English
Publishing date	2024-04-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704223-6
ISSN	2304-8158
ISSN	2304-8158
DOI	10.3390/foods13081252
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Article ; Online: Cellular polyploidy in organ homeostasis and regeneration.

Fang, Juntao / de Bruin, Alain / Villunger, Andreas / Schiffelers, Raymond / Lei, Zhiyong / Sluijter, Joost P G

Protein & cell

2023 Volume 14, Issue 8, Page(s) 560–578

Abstract: Polyploid cells, which contain more than one set of chromosome pairs, are very common in nature. Polyploidy can provide cells with several potential benefits over their diploid counterparts, including an increase in cell size, contributing to organ ... ...

Abstract	Polyploid cells, which contain more than one set of chromosome pairs, are very common in nature. Polyploidy can provide cells with several potential benefits over their diploid counterparts, including an increase in cell size, contributing to organ growth and tissue homeostasis, and improving cellular robustness via increased tolerance to genomic stress and apoptotic signals. Here, we focus on why polyploidy in the cell occurs and which stress responses and molecular signals trigger cells to become polyploid. Moreover, we discuss its crucial roles in cell growth and tissue regeneration in the heart, liver, and other tissues.
MeSH term(s)	Humans ; Liver ; Hepatocytes ; Cell Cycle ; Polyploidy ; Homeostasis
Language	English
Publishing date	2023-08-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2543451-2
ISSN	1674-8018 ; 1674-8018
ISSN (online)	1674-8018
ISSN	1674-8018
DOI	10.1093/procel/pwac064
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Article ; Online: Circular RNAs in Cardiovascular Diseases: Regulation and Therapeutic Applications.

Wang, Lijun / Xu, Gui-E / Spanos, Michail / Li, Guoping / Lei, Zhiyong / Sluijter, Joost P G / Xiao, Junjie

Research (Washington, D.C.)

2023 Volume 6, Page(s) 38

Abstract: Cardiovascular disease is one of the leading causes of mortality worldwide. Recent studies have shown that circular RNAs (circRNAs) have emerged as important players in the prevention and treatment of cardiovascular diseases. circRNAs are a class of ... ...

Abstract	Cardiovascular disease is one of the leading causes of mortality worldwide. Recent studies have shown that circular RNAs (circRNAs) have emerged as important players in the prevention and treatment of cardiovascular diseases. circRNAs are a class of endogenous noncoding RNAs that are generated by back-splicing and are involved in many pathophysiological processes. In this review, we outline the current research progress on the regulatory roles of circRNAs in cardiovascular diseases. Further, new technologies and methods available for identifying, validating, synthesizing, and analyzing circRNAs, as well as their applications in therapeutics, are highlighted here. Moreover, we summarize the increasing insights into the potential use of circRNAs as circulating diagnostic and prognostic biomarkers. Finally, we discuss the prospects and challenges of circRNA therapeutic applications for cardiovascular disease therapy, with a particular focus on developing circRNA synthesis and engineering delivery systems.
Language	English
Publishing date	2023-01-13
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2639-5274
ISSN (online)	2639-5274
DOI	10.34133/research.0038
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Article ; Online: The Preparation, Structural Design, and Application of Electroactive Poly(vinylidene fluoride)-Based Materials for Wearable Sensors and Human Energy Harvesters.

Zhang, Weiran / Wu, Guohua / Zeng, Hailan / Li, Ziyu / Wu, Wei / Jiang, Haiyun / Zhang, Weili / Wu, Ruomei / Huang, Yiyang / Lei, Zhiyong

Polymers

2023 Volume 15, Issue 13

Abstract: Owing to their biocompatibility, chemical stability, film-forming ability, cost-effectiveness, and excellent electroactive properties, poly(vinylidene fluoride) (PVDF) and PVDF-based polymers are widely used in sensors, actuators, energy harvesters, etc. ...

Abstract	Owing to their biocompatibility, chemical stability, film-forming ability, cost-effectiveness, and excellent electroactive properties, poly(vinylidene fluoride) (PVDF) and PVDF-based polymers are widely used in sensors, actuators, energy harvesters, etc. In this review, the recent research progress on the PVDF phase structures and identification of different phases is outlined. Several approaches for obtaining the electroactive phase of PVDF and preparing PVDF-based nanocomposites are described. Furthermore, the potential applications of these materials in wearable sensors and human energy harvesters are discussed. Finally, some challenges and perspectives for improving the properties and boosting the applications of these materials are presented.
Language	English
Publishing date	2023-06-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527146-5
ISSN	2073-4360 ; 2073-4360
ISSN (online)	2073-4360
ISSN	2073-4360
DOI	10.3390/polym15132766
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Article ; Online: An aminocaproic acid-grafted chitosan derivative with superior antibacterial and hemostatic properties for the prevention of secondary bleeding.

Chen, Xiao-Juan / Lei, Zhi-Yong / Liu, Pan / Lei, Meng-Jie / Xu, Hang / Yu, Long-Jiang / Ao, Ming-Zhang

Carbohydrate polymers

2023 Volume 316, Page(s) 120988

Abstract: Uncontrolled bleeding is one of the leading causes of human mortality. Existing hemostatic materials or techniques cannot meet the clinical requirements for safe and effective hemostasis. The development of novel hemostatic materials has always been of ... ...

Abstract	Uncontrolled bleeding is one of the leading causes of human mortality. Existing hemostatic materials or techniques cannot meet the clinical requirements for safe and effective hemostasis. The development of novel hemostatic materials has always been of great interest. Chitosan hydrochloride (CSH), a derivative of chitin, is extensively used on wounds as an antibacterial and hemostatic agent. However, the formation of intra- or intermolecular hydrogen bonds between hydroxyl and amino groups limits its water solubility and dissolution rate and affects its effectiveness in promoting coagulation. Herein, we covalently grafted aminocaproic acid (AA) to the hydroxyl and amino groups of CSH via ester and amide bonds, respectively. The solubility of CSH in water (25 °C) was 11.39 ± 0.98 % (w/v), whereas the AA-grafted CSH (CSH-AA) reached 32.34 ± 1.23 % (w/v). Moreover, the dissolution rate of CSH-AA in water was 6.46 times higher than that of CSH. Subsequent studies proved that CSH-AA is non-toxic, biodegradable, and has superior antibacterial and hemostatic properties to CSH. Additionally, anti-plasmin activity can be exerted by the dissociated AA from the CSH-AA backbone, which can help to lessen secondary bleeding.
MeSH term(s)	Humans ; Hemostatics/chemistry ; Chitosan/chemistry ; Aminocaproic Acid/pharmacology ; Hemorrhage/drug therapy ; Hemorrhage/prevention & control ; Hemostasis ; Anti-Bacterial Agents/chemistry
Chemical Substances	Hemostatics ; Chitosan (9012-76-4) ; Aminocaproic Acid (U6F3787206) ; Anti-Bacterial Agents
Language	English
Publishing date	2023-05-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1501516-6
ISSN	1879-1344 ; 0144-8617
ISSN (online)	1879-1344
ISSN	0144-8617
DOI	10.1016/j.carbpol.2023.120988
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Article ; Online: Extracellular vesicle-mediated delivery of CRISPR/Cas9 ribonucleoprotein complex targeting proprotein convertase subtilisin-kexin type 9 (Pcsk9) in primary mouse hepatocytes.

Ilahibaks, Nazma F / Kluiver, Thomas A / de Jong, Olivier G / de Jager, Saskia C A / Schiffelers, Raymond M / Vader, Pieter / Peng, Weng Chuan / Lei, Zhiyong / Sluijter, Joost P G

Journal of extracellular vesicles

2024 Volume 13, Issue 1, Page(s) e12389

Abstract: The loss-of-function of the proprotein convertase subtilisin-kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low-density lipoprotein cholesterol (LDL-C) levels. Both CRISPR/Cas9 and CRISPR-based editor-mediated ... ...

Abstract	The loss-of-function of the proprotein convertase subtilisin-kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low-density lipoprotein cholesterol (LDL-C) levels. Both CRISPR/Cas9 and CRISPR-based editor-mediated Pcsk9 inactivation have successfully lowered plasma LDL-C and PCSK9 levels in preclinical models. Despite the promising preclinical results, these studies did not report how vehicle-mediated CRISPR delivery inactivating Pcsk9 affected low-density lipoprotein receptor recycling in vitro or ex vivo. Extracellular vesicles (EVs) have shown promise as a biocompatible delivery vehicle, and CRISPR/Cas9 ribonucleoprotein (RNP) has been demonstrated to mediate safe genome editing. Therefore, we investigated EV-mediated RNP targeting of the Pcsk9 gene ex vivo in primary mouse hepatocytes. We engineered EVs with the rapamycin-interacting heterodimer FK506-binding protein (FKBP12) to contain its binding partner, the T82L mutant FKBP12-rapamycin binding (FRB) domain, fused to the Cas9 protein. By integrating the vesicular stomatitis virus glycoprotein on the EV membrane, the engineered Cas9 EVs were used for intracellular CRISPR/Cas9 RNP delivery, achieving genome editing with an efficacy of ±28.1% in Cas9 stoplight reporter cells. Administration of Cas9 EVs in mouse hepatocytes successfully inactivated the Pcsk9 gene, leading to a reduction in Pcsk9 mRNA and increased uptake of the low-density lipoprotein receptor and LDL-C. These readouts can be used in future experiments to assess the efficacy of vehicle-mediated delivery of genome editing technologies targeting Pcsk9. The ex vivo data could be a step towards reducing animal testing and serve as a precursor to future in vivo studies for EV-mediated CRISPR/Cas9 RNP delivery targeting Pcsk9.
MeSH term(s)	Animals ; Mice ; Cholesterol, LDL ; CRISPR-Cas Systems ; Extracellular Vesicles ; Hepatocytes ; Proprotein Convertase 9/genetics ; Subtilisins ; Tacrolimus Binding Protein 1A
Chemical Substances	Cholesterol, LDL ; Pcsk9 protein, mouse (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; Subtilisins (EC 3.4.21.-) ; Tacrolimus Binding Protein 1A (EC 5.2.1.-)
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2683797-3
ISSN	2001-3078 ; 2001-3078
ISSN (online)	2001-3078
ISSN	2001-3078
DOI	10.1002/jev2.12389
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Article ; Online: Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells.

Wang, Jing / Liu, Shuqin / Meng, Xinxiu / Zhao, Xuan / Wang, Tianhui / Lei, Zhiyong / Lehmann, H Immo / Li, Guoping / Alcaide, Pilar / Bei, Yihua / Xiao, Junjie

Circulation research

2024 Volume 134, Issue 5, Page(s) 550–568

Abstract: Background: Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells ... ...

Abstract	Background: Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further determine whether B cell activation and antibody secretion play a role in this protection. Methods: Mice that were administered with doxorubicin (5 mg/kg per week, 20 mg/kg cumulative dose) received treadmill running exercise. The adoptive transfer of exercise-derived splenic B cells to μMT Results: Doxorubicin-administered mice that had undergone exercise training showed improved cardiac function, and low levels of cardiac apoptosis, atrophy, and fibrosis, and had reduced cardiac antibody deposition and proinflammatory responses. Similarly, B cell pharmacological and genetic depletion alleviated doxorubicin-induced cardiotoxicity, which phenocopied the protection of exercise. In vitro performed coculture experiments confirmed that exercise-derived B cells reduced cardiomyocyte apoptosis and fibroblast activation compared with control B cells. Importantly, the protective effect of exercise on B cells was confirmed by the adoptive transfer of splenic B cells from exercised donor mice to μMT Conclusions: Our results demonstrate that exercise training protects against doxorubicin-induced cardiotoxicity by upregulating Fc gamma receptor IIB expression in B cells, which plays an important anti-inflammatory role and participates in the protective effect of exercise against doxorubicin-induced cardiotoxicity.
MeSH term(s)	Mice ; Animals ; Cardiotoxicity/metabolism ; Myocytes, Cardiac/metabolism ; Doxorubicin/toxicity ; Apoptosis
Chemical Substances	Doxorubicin (80168379AG)
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.123.323346
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