@article{wang_hu_popowski_liu_zhu_mei_li_hu_dinh_wang_et al._2024, title={Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2}, volume={15}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-024-45628-x}, abstractNote={Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2, protecting the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates its deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protects hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercepts the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and shows comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as a broad-spectrum protectant against existing and emerging virus variants.}, number={1}, journal={NATURE COMMUNICATIONS}, author={Wang, Zhenzhen and Hu, Shiqi and Popowski, Kristen D. and Liu, Shuo and Zhu, Dashuai and Mei, Xuan and Li, Junlang and Hu, Yilan and Dinh, Phuong-Uyen C. and Wang, Xiaojie and et al.}, year={2024}, month={Mar} } @article{koo_cheng_udani_baghdasarian_zhu_li_hall_tsubamoto_hu_ko_et al._2024, title={Optimizing cell therapy by sorting cells with high extracellular vesicle secretion}, volume={15}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-024-49123-1}, abstractNote={Abstract Critical challenges remain in clinical translation of extracellular vesicle (EV)-based therapeutics due to the absence of methods to enrich cells with high EV secretion. Current cell sorting methods are limited to surface markers that are uncorrelated to EV secretion or therapeutic potential. Here, we utilize a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach is applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibit distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintain high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improves heart functions compared to treatment with low-secreting MSCs. These findings highlight the therapeutic importance of EV secretion in regenerative cell therapies and suggest that selecting cells based on EV secretion could enhance therapeutic efficacy.}, number={1}, journal={NATURE COMMUNICATIONS}, author={Koo, Doyeon and Cheng, Xiao and Udani, Shreya and Baghdasarian, Sevana and Zhu, Dashuai and Li, Junlang and Hall, Brian and Tsubamoto, Natalie and Hu, Shiqi and Ko, Jina and et al.}, year={2024}, month={Jun} } @article{wang_li_shi_zhu_hu_dinh_cheng_2023, title={A SARS-CoV-2 and influenza double hit vaccine based on RBD-conjugated inactivated influenza A virus}, volume={9}, ISSN={["2375-2548"]}, url={https://doi.org/10.1126/sciadv.abo4100}, DOI={10.1126/sciadv.abo4100}, abstractNote={The circulating flu viruses merging with the ongoing COVID-19 pandemic raises a more severe threat that promotes the infectivity of SARS-CoV-2 associated with higher mortality rates. Here, we conjugated recombinant receptor binding domain (RBD) of SARS-CoV-2 spike protein onto inactivated influenza A virus (Flu) to develop a SARS-CoV-2 virus-like particle (VLP) vaccine with two-hit protection. This double-hit vaccine (Flu-RBD) not only induced protective immunities against SARS-CoV-2 but also remained functional as a flu vaccine. The Flu core improved the retention and distribution of Flu-RBD vaccine in the draining lymph nodes, with enhanced immunogenicity. In a hamster model of live SARS-CoV-2 infection, two doses of Flu-RBD efficiently protected animals against viral infection. Furthermore, Flu-RBD VLP elicited a strong neutralization activity against both SARS-CoV-2 Delta pseudovirus and wild-type influenza A H1N1 inactivated virus in mice. Overall, the Flu-RBD VLP vaccine is a promising candidate for combating COVID-19, influenza A, and coinfection.}, number={25}, journal={SCIENCE ADVANCES}, author={Wang, Zhenzhen and Li, Zhenhua and Shi, Weiwei and Zhu, Dashuai and Hu, Shiqi and Dinh, Phuong-Uyen C. and Cheng, Ke}, year={2023}, month={Jun} } @article{mei_li_wang_zhu_huang_hu_popowski_cheng_2023, title={An inhaled bioadhesive hydrogel to shield non-human primates from SARS-CoV-2 infection}, volume={2}, ISSN={1476-1122 1476-4660}, url={http://dx.doi.org/10.1038/s41563-023-01475-7}, DOI={10.1038/s41563-023-01475-7}, abstractNote={The surge of fast-spreading SARS-CoV-2 mutated variants highlights the need for fast, broad-spectrum strategies to counteract viral infections. In this work, we report a physical barrier against SARS-CoV-2 infection based on an inhalable bioadhesive hydrogel, named spherical hydrogel inhalation for enhanced lung defence (SHIELD). Conveniently delivered via a dry powder inhaler, SHIELD particles form a dense hydrogel network that coats the airway, enhancing the diffusional barrier properties and restricting virus penetration. SHIELD's protective effect is first demonstrated in mice against two SARS-CoV-2 pseudo-viruses with different mutated spike proteins. Strikingly, in African green monkeys, a single SHIELD inhalation provides protection for up to 8 hours, efficiently reducing infection by the SARS-CoV-2 WA1 and B.1.617.2 (Delta) variants. Notably, SHIELD is made with food-grade materials and does not affect normal respiratory functions. This approach could offer additional protection to the population against SARS-CoV-2 and other respiratory pathogens.}, journal={Nature Materials}, publisher={Springer Science and Business Media LLC}, author={Mei, Xuan and Li, Junlang and Wang, Zhenzhen and Zhu, Dashuai and Huang, Ke and Hu, Shiqi and Popowski, Kristen D. and Cheng, Ke}, year={2023}, month={Feb} } @article{wang_hu_zhu_li_cheng_liu_2023, title={Comparison of extruded cell nanovesicles and exosomes in their molecular cargos and regenerative potentials}, volume={16}, ISSN={["1998-0000"]}, DOI={10.1007/s12274-023-5374-3}, abstractNote={Extracellular vesicles (EVs) generated from mesenchymal stem cells (MSCs) play an essential role in modulating cell-cell communication and tissue regeneration. The clinical translation of EVs is constrained by the poor yield of EVs. Extrusion has recently become an effective technique for producing a large scale of nanovesicles (NVs). In this study, we systematically compared MSC NVs (from extrusion) and EVs (from natural secretion). Proteomics and RNA sequencing data revealed that NVs resemble MSCs more closely than EVs. Additionally, microRNAs in NVs are related to cardiac repair, fibrosis repression, and angiogenesis. Lastly, intravenous delivery of MSC NVs improved heart repair and cardiac function in a mouse model of myocardial infarction.Supplementary material (Figs. S1-S4) is available in the online version of this article at 10.1007/s12274-023-5374-3.}, number={5}, journal={NANO RESEARCH}, author={Wang, Xianyun and Hu, Shiqi and Zhu, Dashuai and Li, Junlang and Cheng, Ke and Liu, Gang}, year={2023}, month={May}, pages={7248–7259} } @article{zhu_liu_huang_li_mei_li_cheng_2023, title={Intrapericardial long non-coding RNA–Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair}, volume={44}, ISSN={0195-668X 1522-9645}, url={http://dx.doi.org/10.1093/eurheartj/ehad114}, DOI={10.1093/eurheartj/ehad114}, abstractNote={Abstract}, number={19}, journal={European Heart Journal}, publisher={Oxford University Press (OUP)}, author={Zhu, Dashuai and Liu, Shuo and Huang, Ke and Li, Junlang and Mei, Xuan and Li, Zhenhua and Cheng, Ke}, year={2023}, month={Mar}, pages={1748–1760} } @article{luo_li_bao_zhu_chen_li_xiao_wang_zhang_liu_et al._2023, title={Pericardial Delivery of SDF-1 α Puerarin Hydrogel Promotes Heart Repair and Electrical Coupling}, volume={9}, ISSN={["1521-4095"]}, DOI={10.1002/adma.202302686}, abstractNote={Abstract}, journal={ADVANCED MATERIALS}, author={Luo, Li and Li, Yuetong and Bao, Ziwei and Zhu, Dashuai and Chen, Guoqin and Li, Weirun and Xiao, Yingxian and Wang, Zhenzhen and Zhang, Yixin and Liu, Huifang and et al.}, year={2023}, month={Sep} } @article{zhang_zhu_wei_wu_cui_liuqin_fan_yang_wang_xu_et al._2022, title={Corrigendum to ‘A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model’ [Acta Biomaterialia 2019, 86, 223-234] (Acta Biomaterialia (2019) 86 (223–234), (S174270611930042X), (10.1016/j.actbio.2019.01.022))}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85127693999&partnerID=MN8TOARS}, DOI={10.1016/j.actbio.2022.03.049}, journal={Acta Biomaterialia}, author={Zhang, Y. and Zhu, D. and Wei, Y. and Wu, Y. and Cui, W. and Liuqin, L. and Fan, G. and Yang, Q. and Wang, Z. and Xu, Z. and et al.}, year={2022} } @article{fan_li_shen_wang_liu_zhu_wang_li_popowski_ou_et al._2022, title={Decoy Exosomes Offer Protection Against Chemotherapy-Induced Toxicity}, volume={9}, ISSN={["2198-3844"]}, DOI={10.1002/advs.202203505}, abstractNote={Abstract}, journal={ADVANCED SCIENCE}, author={Fan, Miao and Li, Hang and Shen, Deliang and Wang, Zhaoshuo and Liu, Huifang and Zhu, Dashuai and Wang, Zhenzhen and Li, Lanya and Popowski, Kristen D. and Ou, Caiwen and et al.}, year={2022}, month={Sep} } @article{hu_zhu_li_cheng_2022, title={Detachable Microneedle Patches Deliver Mesenchymal Stromal Cell Factor-Loaded Nanoparticles for Cardiac Repair}, volume={9}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.2c03060}, abstractNote={Intramyocardial injection is a direct and efficient approach to deliver therapeutics to the heart. However, the injected volume must be very limited, and there is injury to the injection site and leakage issues during heart beating. Herein, we developed a detachable therapeutic microneedle (MN) patch, which is comprised of mesenchymal stromal cell-secreted factors (MSCF)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) in MN tips made of elastin-like polypeptide gel, with a resolvable non-cross-linked hyaluronic acid (HA) gel as the MN base. The tips can be firmly inserted into the infarcted myocardium after base removal, and no suture is needed. In isolated neonatal rat cardiac cells, we found that the cellular uptake of MSCF-NP in the cardiomyocytes was higher than in cardiac fibroblasts. MSCF-NP promoted the proliferation of injured cardiomyocytes. In a rat model of myocardial infarction, MN-MSCF-NP treatment reduced cardiomyocyte apoptosis, restored myocardium volume, and reduced fibrosis during the cardiac remodeling process. Our work demonstrated the therapeutic potential of MN to deliver MSCF directly into the myocardium and provides a promising treatment approach for cardiac diseases.}, journal={ACS NANO}, author={Hu, Shiqi and Zhu, Dashuai and Li, Zhenhua and Cheng, Ke}, year={2022}, month={Sep} } @article{wang_popowski_zhu_abad_wang_liu_lutz_de naeyer_demarco_denny_et al._2022, title={Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine}, volume={7}, ISSN={["2157-846X"]}, url={https://doi.org/10.1038/s41551-022-00902-5}, DOI={10.1038/s41551-022-00902-5}, abstractNote={The first two mRNA vaccines against infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that were approved by regulators require a cold chain and were designed to elicit systemic immunity via intramuscular injection. Here we report the design and preclinical testing of an inhalable virus-like-particle as a COVID-19 vaccine that, after lyophilisation, is stable at room temperature for over three months. The vaccine consists of a recombinant SARS-CoV-2 receptor-binding domain (RBD) conjugated to lung-derived exosomes which, with respect to liposomes, enhance the retention of the RBD in both the mucus-lined respiratory airway and in lung parenchyma. In mice, the vaccine elicited RBD-specific IgG antibodies, mucosal IgA responses and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile in the animals' lungs, and cleared them of SARS-CoV-2 pseudovirus after a challenge. In hamsters, two doses of the vaccine attenuated severe pneumonia and reduced inflammatory infiltrates after a challenge with live SARS-CoV-2. Inhalable and room-temperature-stable virus-like particles may become promising vaccine candidates.}, journal={NATURE BIOMEDICAL ENGINEERING}, author={Wang, Zhenzhen and Popowski, Kristen D. and Zhu, Dashuai and Abad, Blanca Lopez de Juan and Wang, Xianyun and Liu, Mengrui and Lutz, Halle and De Naeyer, Nicole and DeMarco, C. Todd and Denny, Thomas N. and et al.}, year={2022}, month={Jul} } @article{popowski_moatti_scull_silkstone_lutz_lópez de juan abad_george_belcher_zhu_mei_et al._2022, title={Inhalable dry powder mRNA vaccines based on extracellular vesicles}, volume={5}, ISSN={2590-2385}, url={http://dx.doi.org/10.1016/j.matt.2022.06.012}, DOI={10.1016/j.matt.2022.06.012}, abstractNote={Respiratory diseases are a global burden, with millions of deaths attributed to pulmonary illnesses and dysfunctions. Therapeutics have been developed, but they present major limitations regarding pulmonary bioavailability and product stability. To circumvent such limitations, we developed room-temperature-stable inhalable lung-derived extracellular vesicles or exosomes (Lung-Exos) as mRNA and protein drug carriers. Compared with standard synthetic nanoparticle liposomes (Lipos), Lung-Exos exhibited superior distribution to the bronchioles and parenchyma and are deliverable to the lungs of rodents and nonhuman primates (NHPs) by dry powder inhalation. In a vaccine application, severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein encoding mRNA-loaded Lung-Exos (S-Exos) elicited greater immunoglobulin G (IgG) and secretory IgA (SIgA) responses than its loaded liposome (S-Lipo) counterpart. Importantly, S-Exos remained functional at room-temperature storage for one month. Our results suggest that extracellular vesicles can serve as an inhaled mRNA drug-delivery system that is superior to synthetic liposomes.}, number={9}, journal={Matter}, publisher={Elsevier BV}, author={Popowski, Kristen D. and Moatti, Adele and Scull, Grant and Silkstone, Dylan and Lutz, Halle and López de Juan Abad, Blanca and George, Arianna and Belcher, Elizabeth and Zhu, Dashuai and Mei, Xuan and et al.}, year={2022}, month={Sep}, pages={2960–2974} } @article{zhu_liu_huang_wang_hu_li_li_cheng_2022, title={Intrapericardial Exosome Therapy Dampens Cardiac Injury via Activating Foxo3}, volume={131}, ISSN={["1524-4571"]}, url={https://doi.org/10.1161/CIRCRESAHA.122.321384}, DOI={10.1161/CIRCRESAHA.122.321384}, abstractNote={ Background: Mesenchymal stem cell (MSC)-derived exosomes are well recognized immunomodulating agents for cardiac repair, while the detailed mechanisms remain elusive. The Pericardial drainage pathway provides the heart with immunosurveillance and establishes a simplified model for studying the mechanisms underlying the immunomodulating effects of therapeutic exosomes. }, number={10}, journal={CIRCULATION RESEARCH}, author={Zhu, Dashuai and Liu, Shuo and Huang, Ke and Wang, Zhenzhen and Hu, Shiqi and Li, Junlang and Li, Zhenhua and Cheng, Ke}, year={2022}, month={Oct}, pages={E135–E150} } @article{li_lv_zhu_mei_huang_wang_li_zhang_hu_popowski_et al._2022, title={Intrapericardial hydrogel injection generates high cell retention and augments therapeutic effects of mesenchymal stem cells in myocardial infarction}, volume={427}, ISSN={["1873-3212"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85113941738&partnerID=MN8TOARS}, DOI={10.1016/j.cej.2021.131581}, abstractNote={Although cell therapy has shown potential efficacy in the treatment of heart diseases, one challenge is low cellular retention rate and poor engraftment. We sought to perform a head-to-head comparison on cell retention and therapeutic benefits of intramyocardial (IM) injection and intrapericardial cavity (IPC) injection of adult stem cells in hydrogel. Mouse green fluorescent protein (GFP)-labeled mesenchymal stem cells (MSCs) were combined in extracellular matrix (ECM) hydrogel and injected into the pericardial cavity or the myocardium of the heart of C57BL/6 mice that had been subjected to a myocardial infarction. The IPC injection, as an alternative cell delivery route, led to better cardiac function in our mouse model with myocardial infarction, which was showed by echocardiographies in the short term (2 weeks) and the long term (6 weeks). This result was attributed to 10-fold higher engraftment of MSCs injected via IPC route (42.5 ± 7.4%) than that of MSCs injected intramyocardially (4.4 ± 1.3%). Immunohistochemistry data revealed better cellular proliferation, less apoptosis, and better vascular regeneration in the myocardium after IPC delivery of MSCs. CD63-RFP exosome labeling system showed that heart cells including cardiomyocytes absorbed MSC-exosomes at higher rates when MSCs were injected via IPC route, compared to the results from IM injections, indicating more extensive paracrine activity of MSCs after IPC injections. What is more, the feasibility and safety of IPC injection were demonstrated in a porcine model with minimally invasive procedure. Intrapericardial cavity injection gave a promising solution for the low retention issue of MSCs in the infarcted heart.}, journal={CHEMICAL ENGINEERING JOURNAL}, publisher={Elsevier BV}, author={Li, Junlang and Lv, Yongbo and Zhu, Dashuai and Mei, Xuan and Huang, Ke and Wang, Xianyun and Li, Zhenhua and Zhang, Sichen and Hu, Shiqi and Popowski, Kristen D. and et al.}, year={2022}, month={Jan} } @article{cheng_zhu_huang_caranasos_2022, title={Minimally invasive delivery of a hydrogel-based exosome patch to prevent heart failure}, volume={169}, ISSN={["1095-8584"]}, DOI={10.1016/j.yjmcc.2022.04.020}, abstractNote={Coronary heart disease (CHD) has been the number one killer in the United States for decades and causes millions of deaths each year. Clinical treatment of heart ischemic injury relieves symptoms in the acute stage of CHD; however, patients with an infarcted heart muscle can develop heart failure (HF) due to chronic maladaptive remodeling. Regenerative therapy has been studied as a potential treatment option for myocardial infarction (MI) and HF. Cardiac patches have been designed and tested to increase therapeutic retention and integration. However, the delivery usually requires invasive surgical techniques, including open-chest surgeries and heart manipulation. Those procedures may cause chronic adhesions between the heart anterior wall and the chest wall. This study created and tested an injectable ExoGel by embedding mesenchymal stem cell (MSC) -derived exosomes into a hyaluronic acid (HA) hydrogel. ExoGel was injected into the pericardial cavity of rats with transverse aortic constriction (TAC) induced heart failure. ExoGel therapy reduced LV chamber size and preserved wall thickness. The feasibility and safety of ExoGel injection were further confirmed in a pig model.}, journal={JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY}, author={Cheng, George and Zhu, Dashuai and Huang, Ke and Caranasos, Thomas G.}, year={2022}, month={Aug}, pages={113–121} } @article{zhang_zhang_zhu_li_wang_li_mei_xu_cheng_zhong_2022, title={Nanoparticles functionalized with stem cell secretome and CXCR4-overexpressing endothelial membrane for targeted osteoporosis therapy}, volume={20}, ISSN={["1477-3155"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85122993345&partnerID=MN8TOARS}, DOI={10.1186/s12951-021-01231-6}, abstractNote={Abstract}, number={1}, journal={JOURNAL OF NANOBIOTECHNOLOGY}, author={Zhang, Chi and Zhang, Wei and Zhu, Dashuai and Li, Zhenhua and Wang, Zhenzhen and Li, Junlang and Mei, Xuan and Xu, Wei and Cheng, Ke and Zhong, Biao}, year={2022}, month={Jan} } @article{yao_huang_zhu_chen_jiang_zhang_mi_xuan_hu_li_et al._2021, title={A Minimally Invasive Exosome Spray Repairs Heart after Myocardial Infarction}, volume={15}, ISSN={["1936-086X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85110404046&partnerID=MN8TOARS}, DOI={10.1021/acsnano.1c00628}, abstractNote={Myocardial infarction (MI) remains the most common cause of death worldwide. Many MI survivors will suffer from recurrent heart failure (HF), which has been recognized as a determinant of adverse prognosis. Despite the success of improved early survival after MI by primary percutaneous coronary intervention, HF after MI is becoming the major driver of late morbidity, mortality, and healthcare costs. The development of regenerative medicine has brought hope to MI treatment in the past decade. Mesenchymal stem cell (MSC)-derived exosomes have been established as an essential part of stem cell paracrine factors for heart regeneration. However, its regenerative power is hampered by low delivery efficiency to the heart. We designed, fabricated, and tested a minimally invasive exosome spray (EXOS) based on MSC exosomes and biomaterials. In a mouse model of acute myocardial infarction, EXOS improved cardiac function and reduced fibrosis, and promoted endogenous angiomyogenesis in the post-injury heart. We further tested the feasibility and safety of EXOS in a pig model. Our results indicate that EXOS is a promising strategy to deliver therapeutic exosomes for heart repair.}, number={7}, journal={ACS NANO}, publisher={American Chemical Society (ACS)}, author={Yao, Jialu and Huang, Ke and Zhu, Dashuai and Chen, Tan and Jiang, Yufeng and Zhang, Junyi and Mi, Lijie and Xuan, He and Hu, Shiqi and Li, Junlang and et al.}, year={2021}, month={Jul}, pages={11099–11111} } @article{mei_zhu_li_huang_hu_li_abad_cheng_2021, title={A fluid-powered refillable origami heart pouch for minimally invasive delivery of cell therapies in rats and pigs}, volume={2}, ISSN={["2666-6340"]}, url={https://doi.org/10.1016/j.medj.2021.10.001}, DOI={10.1016/j.medj.2021.10.001}, abstractNote={Cardiac repair after heart injury remains a big challenge and current drug delivery to the heart is suboptimal. Repeated dosing of therapeutics is difficult due to the invasive nature of such procedures.We developed a fluid-driven heart pouch with a memory-shaped microfabricated lattice structure inspired by origami. The origami structure allowed minimally invasive delivery of the pouch to the heart with two small incisions and can be refilled multiple times with the therapeutic of choice.We tested the pouch's ability to deliver mesenchymal stem cells (MSCs) in a rodent model of acute myocardial infarction and demonstrated the feasibility of minimally invasive delivery in a swine model. The pouch's semi-permeable membrane successfully protected delivered cells from their surroundings, maintaining their viability while releasing paracrine factors to the infarcted site for cardiac repair.In summary, we developed a fluid-driven heart pouch with a memory-shaped microfabricated lattice structure inspired by origami. The origami structure allowed minimally invasive delivery of the pouch to the heart with two small incisions and can be refilled with the therapeutic of choice.}, number={11}, journal={MED}, publisher={Elsevier BV}, author={Mei, Xuan and Zhu, Dashuai and Li, Junlang and Huang, Ke and Hu, Shiqi and Li, Zhenhua and Abad, Blanca Lopez de Juan and Cheng, Ke}, year={2021}, month={Nov}, pages={1253-+} } @article{zhang_zhu_li_huang_hu_lutz_xie_mei_li_neal-perry_et al._2021, title={A stem cell-derived ovarian regenerative patch restores ovarian function and rescues fertility in rats with primary ovarian insufficiency}, volume={11}, ISSN={["1838-7640"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85114771196&partnerID=MN8TOARS}, DOI={10.7150/thno.61690}, abstractNote={Rationale: Primary ovarian insufficiency (POI) normally occurs before age 40 and is associated with infertility. Hormone replacement therapy is often prescribed to treat vasomotor symptom, but it cannot restore ovarian function or fertility. Stem cell therapy has been studied for the treatment of POI. However, the application of live stem cells has suffered from drawbacks, such as low cell retention/engraftment rate, risks for tumorigenicity and immunogenicity, and lack of off-the-shelf feasibility. Methods: We developed a therapeutic ovarian regenerative patch (ORP) that composed of clinically relevant hydrolysable scaffolds and synthetic mesenchymal stem cells (synMSCs), which are microparticles encapsulating the secretome from MSCs. The therapeutic potency of ORP was tested in rats with cisplatin induced POI injury. Results:In vitro studies revealed that ORP stimulated proliferation of ovarian somatic cells (OSCs) and inhibited apoptosis under injury stress. In a rat model of POI, implantation of ORP rescued fertility by restoring sexual hormone secretion, estrus cycle duration, and follicle development. Conclusion: ORP represents a cell-free, off-the-shelf, and clinically feasible treatment for POI.}, number={18}, journal={THERANOSTICS}, author={Zhang, Sichen and Zhu, Dashuai and Li, Zhenhua and Huang, Ke and Hu, Shiqi and Lutz, Halle and Xie, Mengjie and Mei, Xuan and Li, Junlang and Neal-Perry, Genevieve and et al.}, year={2021}, pages={8894–8908} } @article{xie_li_zhang_zhu_mei_wang_cheng_li_wang_cheng_2021, title={A trifunctional contraceptive gel enhances the safety and quality of sexual intercourse}, volume={6}, ISSN={["2452-199X"]}, url={https://doi.org/10.1016/j.bioactmat.2020.11.031}, DOI={10.1016/j.bioactmat.2020.11.031}, abstractNote={Current contraceptive methods come with a number of drawbacks, including low efficacy, in the case of commercial contraceptive gels, and a reduction in the quality of sexual intercourse, in the case of condoms. Adding pharmacologically-active agents to contraceptive gels holds the potential to improve sexual experience, and hardbor safety and hygiene. In this study, we fabricated a carbomer-based contraceptive gel consisting of three agents: tenofovir, gossypol acetate, and nitroglycerin (TGN), with pH adjusted to 4.5 (to be compatible with the vagina). In vitro, the gossypol component of the contraceptive gel proved to be an effective spermicide. When the concentration of gossypol acetate was 10 mg/ml, the spermicidal ability reached 100% after 30 s. In addition, tenofovir in the gel significantly inhibited lentiviral transfection efficiency in cell-containing media. In 6 pairs of rats, the gel successfully prevented all females from conceiving after successful mating. Moreover, increased sexual frequency and enhanced erection, which were promoted by the nitroglycerin in the components, were observed in male rats that had the gel applied to their penises. This novel TGN contraceptive gel yielded a higher contraceptive success rate than that of the commercial contraceptive gel (Contragel®). In addition, it has the added benefits to prevent sexually transmitted diseases and improve male libido and erectile function during sexual intercourse. Combining three FDA-approved and marketed agents together, our trifunctional TGN gel has a great potential for further translation and commercialization.}, number={6}, journal={BIOACTIVE MATERIALS}, publisher={Elsevier BV}, author={Xie, Mengjie and Li, Junlang and Zhang, Sichen and Zhu, Dashuai and Mei, Xuan and Wang, Zhenzhen and Cheng, Xiao and Li, Zhenhua and Wang, Shaowei and Cheng, Ke}, year={2021}, month={Jun}, pages={1777–1788} } @misc{zhang_zhu_mei_li_li_xie_xie_wang_cheng_2021, title={Advances in biomaterials and regenerative medicine for primary ovarian insufficiency therapy}, volume={6}, ISSN={["2452-199X"]}, url={https://doi.org/10.1016/j.bioactmat.2020.12.008}, DOI={10.1016/j.bioactmat.2020.12.008}, abstractNote={Primary ovarian insufficiency (POI) is an ovarian dysfunction that affects more than 1 % of women and is characterized by hormone imbalances that afflict women before the age of 40. The typical perimenopausal symptoms result from abnormal levels of sex hormones, especially estrogen. The most prevalent treatment is hormone replacement therapy (HRT), which can relieve symptoms and improve quality of life. However, HRT cannot restore ovarian functions, including secretion, ovulation, and fertility. Recently, as part of a developing field of regenerative medicine, stem cell therapy has been proposed for the treatment of POI. Thus, we recapitulate the literature focusing on the use of stem cells and biomaterials for POI treatment, and sum up the underlying mechanisms of action. A thorough understanding of the work already done can aid in the development of guidelines for future translational applications and clinical trials that aim to cure POI by using regenerative medicine and biomedical engineering strategies.}, number={7}, journal={BIOACTIVE MATERIALS}, publisher={Elsevier BV}, author={Zhang, Sichen and Zhu, Dashuai and Mei, Xuan and Li, Zhenhua and Li, Junlang and Xie, Mengjie and Xie, Halle Jiang Williams and Wang, Shaowei and Cheng, Ke}, year={2021}, month={Jul}, pages={1957–1972} } @misc{li_hu_zhu_huang_mei_abad_cheng_2021, title={All Roads Lead to Rome (the Heart): Cell Retention and Outcomes From Various Delivery Routes of Cell Therapy Products to the Heart}, volume={10}, ISSN={["2047-9980"]}, url={https://doi.org/10.1161/JAHA.120.020402}, DOI={10.1161/JAHA.120.020402}, abstractNote={Abstract}, number={8}, journal={JOURNAL OF THE AMERICAN HEART ASSOCIATION}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Li, Junlang and Hu, Shiqi and Zhu, Dashuai and Huang, Ke and Mei, Xuan and Abad, Blanca Lopez de Juan and Cheng, Ke}, year={2021}, month={Apr} } @article{chingale_zhu_cheng_huang_2021, title={Bioengineering Technologies for Cardiac Regenerative Medicine}, volume={9}, ISSN={2296-4185}, url={http://dx.doi.org/10.3389/fbioe.2021.681705}, DOI={10.3389/fbioe.2021.681705}, abstractNote={Cardiac regenerative medicine faces big challenges such as a lack of adult cardiac stem cells, low turnover of mature cardiomyocytes, and difficulty in therapeutic delivery to the injured heart. The interaction of bioengineering and cardiac regenerative medicine offers innovative solutions to this field. For example, cell reprogramming technology has been applied by both direct and indirect routes to generate patient-specific cardiomyocytes. Various viral and non-viral vectors have been utilized for gene editing to intervene gene expression patterns during the cardiac remodeling process. Cell-derived protein factors, exosomes, and miRNAs have been isolated and delivered through engineered particles to overcome many innate limitations of live cell therapy. Protein decoration, antibody modification, and platelet membranes have been used for targeting and precision medicine. Cardiac patches have been used for transferring therapeutics with better retention and integration. Other technologies such as 3D printing and 3D culture have been used to create replaceable cardiac tissue. In this review, we discuss recent advancements in bioengineering and biotechnologies for cardiac regenerative medicine.}, journal={Frontiers in Bioengineering and Biotechnology}, publisher={Frontiers Media SA}, author={Chingale, Mira and Zhu, Dashuai and Cheng, Ke and Huang, Ke}, year={2021}, month={Jun} } @article{liu_lutz_zhu_huang_li_dinh_gao_zhang_cheng_2021, title={Bispecific Antibody Inhalation Therapy for Redirecting Stem Cells from the Lungs to Repair Heart Injury}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85096756888&partnerID=MN8TOARS}, DOI={10.1002/advs.202002127}, abstractNote={Abstract}, number={1}, journal={Advanced Science}, author={Liu, M. and Lutz, H. and Zhu, D. and Huang, K. and Li, Z. and Dinh, P.-U.C. and Gao, J. and Zhang, Y. and Cheng, K.}, year={2021} } @misc{zhu_cheng_2021, title={Cardiac Cell Therapy for Heart Repair: Should the Cells Be Left Out?}, volume={10}, ISSN={["2073-4409"]}, url={https://doi.org/10.3390/cells10030641}, DOI={10.3390/cells10030641}, abstractNote={Cardiovascular disease (CVD) is still the leading cause of death worldwide. Coronary artery occlusion, or myocardial infarction (MI) causes massive loss of cardiomyocytes. The ischemia area is eventually replaced by a fibrotic scar. From the mechanical dysfunctions of the scar in electronic transduction, contraction and compliance, pathological cardiac dilation and heart failure develops. Once end-stage heart failure occurs, the only option is to perform heart transplantation. The sequential changes are termed cardiac remodeling, and are due to the lack of endogenous regenerative actions in the adult human heart. Regenerative medicine and biomedical engineering strategies have been pursued to repair the damaged heart and to restore normal cardiac function. Such strategies include both cellular and acellular products, in combination with biomaterials. In addition, substantial progress has been made to elucidate the molecular and cellular mechanisms underlying heart repair and regeneration. In this review, we summarize and discuss current therapeutic approaches for cardiac repair and provide a perspective on novel strategies that holding potential opportunities for future research and clinical translation.}, number={3}, journal={CELLS}, publisher={MDPI AG}, author={Zhu, Dashuai and Cheng, Ke}, year={2021}, month={Mar} } @article{li_wang_dinh_zhu_popowski_lutz_hu_lewis_cook_andersen_et al._2021, title={Cell-mimicking nanodecoys neutralize SARS-CoV-2 and mitigate lung injury in a non-human primate model of COVID-19}, volume={6}, url={https://doi.org/10.1038/s41565-021-00923-2}, DOI={10.1038/s41565-021-00923-2}, abstractNote={Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date. Angiotensin-converting enzyme 2 (ACE2) plays a fundamental role in SARS-CoV-2 pathogenesis because it allows viral entry into host cells. Here we show that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection. In mice, these LSC-nanodecoys were delivered via inhalation therapy and resided in the lungs for over 72 h post-delivery. Furthermore, inhalation of the LSC-nanodecoys accelerated clearance of SARS-CoV-2 mimics from the lungs, with no observed toxicity. In cynomolgus macaques challenged with live SARS-CoV-2, four doses of these nanodecoys delivered by inhalation promoted viral clearance and reduced lung injury. Our results suggest that LSC-nanodecoys can serve as a potential therapeutic agent for treating COVID-19.}, number={8}, journal={Nature Nanotechnology}, publisher={Springer Science and Business Media LLC}, author={Li, Zhenhua and Wang, Zhenzhen and Dinh, Phuong-Uyen C. and Zhu, Dashuai and Popowski, Kristen D. and Lutz, Halle and Hu, Shiqi and Lewis, Mark G. and Cook, Anthony and Andersen, Hanne and et al.}, year={2021}, month={Aug}, pages={942–951} } @article{hu_li_shen_zhu_huang_su_dinh_cores_cheng_2021, title={Exosome-eluting stents for vascular healing after ischaemic injury}, volume={5}, ISSN={["2157-846X"]}, url={https://doi.org/10.1038/s41551-021-00705-0}, DOI={10.1038/s41551-021-00705-0}, abstractNote={Drug-eluting stents implanted after ischaemic injury reduce the proliferation of endothelial cells and vascular smooth muscle cells and thus neointimal hyperplasia. However, the eluted drug also slows down the re-endothelialization process, delays arterial healing and can increase the risk of late restenosis. Here we show that stents releasing exosomes derived from mesenchymal stem cells in the presence of reactive oxygen species enhance vascular healing in rats with renal ischaemia-reperfusion injury, promoting endothelial cell tube formation and proliferation, and impairing the migration of smooth muscle cells. Compared with drug-eluting stents and bare-metal stents, the exosome-coated stents accelerated re-endothelialization and decreased in-stent restenosis 28 days after implantation. We also show that exosome-eluting stents implanted in the abdominal aorta of rats with unilateral hindlimb ischaemia regulated macrophage polarization, reduced local vascular and systemic inflammation, and promoted muscle tissue repair. Exosome-eluting stents implanted in rats after ischaemic injury accelerate vascular healing and promote tissue regeneration.}, number={10}, journal={NATURE BIOMEDICAL ENGINEERING}, publisher={Springer Science and Business Media LLC}, author={Hu, Shiqi and Li, Zhenhua and Shen, Deliang and Zhu, Dashuai and Huang, Ke and Su, Teng and Dinh, Phuong-Uyen and Cores, Jhon and Cheng, Ke}, year={2021}, month={Oct}, pages={1174–1188} } @article{wang_hu_li_zhu_wang_cores_cheng_liu_huang_2021, title={Extruded Mesenchymal Stem Cell Nanovesicles Are Equally Potent to Natural Extracellular Vesicles in Cardiac Repair}, volume={13}, ISSN={["1944-8252"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85119954105&partnerID=MN8TOARS}, DOI={10.1021/acsami.1c08044}, abstractNote={Mesenchymal stem cells (MSCs) repair injured tissues mainly through their paracrine actions. One of the important paracrine components of MSC secretomes is the extracellular vesicle (EV). The therapeutic potential of MSC-EVs has been established in various cardiac injury preclinical models. However, the large-scale production of EVs remains a challenge. We sought to develop a scale-up friendly method to generate a large number of therapeutic nanovesicles from MSCs by extrusion. Those extruded nanovesicles (NVs) are miniature versions of MSCs in terms of surface marker expression. The yield of NVs is 20-fold more than that of EVs. In vitro, cell-based assays demonstrated the myocardial protective effects and therapeutic potential of NVs. Intramyocardial delivery of NVs in the injured heart after ischemia-reperfusion led to a reduction in scar sizes and preservation of cardiac functions. Such therapeutic benefits are similar to those injected with natural EVs from the same MSC parental cells. In addition, NV therapy promoted angiogenesis and proliferation of cardiomyocytes in the post-injury heart. In summary, extrusion is a highly efficient method to generate a large quantity of therapeutic NVs that can potentially replace extracellular vesicles in regenerative medicine applications.}, number={47}, journal={ACS APPLIED MATERIALS & INTERFACES}, publisher={American Chemical Society (ACS)}, author={Wang, Xianyun and Hu, Shiqi and Li, Junlang and Zhu, Dashuai and Wang, Zhenzhen and Cores, Jhon and Cheng, Ke and Liu, Gang and Huang, Ke}, year={2021}, month={Dec}, pages={55767–55779} } @article{li_zhu_hui_bi_yu_huang_hu_wang_caranasos_rossi_et al._2021, title={Injection of ROS-Responsive Hydrogel Loaded with Basic Fibroblast Growth Factor into the Pericardial Cavity for Heart Repair}, volume={31}, ISSN={["1616-3028"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85100498082&partnerID=MN8TOARS}, DOI={10.1002/adfm.202004377}, abstractNote={Abstract}, number={15}, journal={ADVANCED FUNCTIONAL MATERIALS}, author={Li, Zhenhua and Zhu, Dashuai and Hui, Qi and Bi, Jianing and Yu, Bingjie and Huang, Zhen and Hu, Shiqi and Wang, Zhenzhen and Caranasos, Thomas and Rossi, Joseph and et al.}, year={2021}, month={Apr} } @article{zhu_li_huang_caranasos_rossi_cheng_2021, title={Minimally invasive delivery of therapeutic agents by hydrogel injection into the pericardial cavity for cardiac repair}, volume={12}, ISSN={["2041-1723"]}, url={https://doi.org/10.1038/s41467-021-21682-7}, DOI={10.1038/s41467-021-21682-7}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, author={Zhu, Dashuai and Li, Zhenhua and Huang, Ke and Caranasos, Thomas G. and Rossi, Joseph S. and Cheng, Ke}, year={2021}, month={Mar} } @article{zhu_hou_qian_jin_hao_pan_wang_wu_liu_wang_et al._2021, title={Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery}, volume={12}, url={https://doi.org/10.1038/s41467-021-24804-3}, DOI={10.1038/s41467-021-24804-3}, abstractNote={Abstract}, number={1}, journal={Nature Communications}, author={Zhu, Dashuai and Hou, Jingli and Qian, Meng and Jin, Dawei and Hao, Tian and Pan, Yanjun and Wang, He and Wu, Shuting and Liu, Shuo and Wang, Fei and et al.}, year={2021}, month={Jul} } @article{hu_wang_li_zhu_cores_wang_li_mei_cheng_su_et al._2021, title={Platelet membrane and stem cell exosome hybrids enhance cellular uptake and targeting to heart injury}, volume={39}, ISSN={["1878-044X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85107566346&partnerID=MN8TOARS}, DOI={10.1016/j.nantod.2021.101210}, abstractNote={Exosomes from mesenchymal stem cells have been largely studied as therapeutics to treat myocardial infarctions. However, exosomes injected for therapeutic purposes face a number of challenges, including competition from exosomes already in circulation, and the internalization/clearance by the mononuclear phagocyte system. In this study, we hybrid exosomes with platelet membranes to enhance their ability to target the injured heart and avoid being captured by macrophages. Furthermore, we found that encapsulation by the platelet membranes induces macropinocytosis, enhancing the cellular uptake of exosomes by endothelial cells and cardiomyocytes strikingly. In vivo studies showed that the cardiac targeting ability of hybrid exosomes in a mice model with myocardial infarction injury. Last, we tested cardiac functions and performed immunohistochemistry to confirm a better therapeutic effect of platelet membrane modified exosomes compared to non-modified exosomes. Our studies provide proof-of-concept data and a universal approach to enhance the binding and accumulation of exosomes in injured tissues.}, journal={NANO TODAY}, author={Hu, Shiqi and Wang, Xianyun and Li, Zhenhua and Zhu, Dashuai and Cores, Jhon and Wang, Zhenzhen and Li, Junlang and Mei, Xuan and Cheng, Xiao and Su, Teng and et al.}, year={2021}, month={Aug} } @article{hu_li_shen_zhu_huang_su_dinh_cores_cheng_2021, title={Publisher Correction: Exosome-eluting stents for vascular healing after ischaemic injury}, volume={5}, url={https://doi.org/10.1038/s41551-021-00727-8}, DOI={10.1038/s41551-021-00727-8}, abstractNote={A Correction to this paper has been published: https://doi.org/10.1038/s41551-021-00727-8.}, number={10}, journal={Nature Biomedical Engineering}, author={Hu, Shiqi and Li, Zhenhua and Shen, Deliang and Zhu, Dashuai and Huang, Ke and Su, Teng and Dinh, Phuong-Uyen and Cores, Jhon and Cheng, Ke}, year={2021}, month={Apr}, pages={1239} } @article{liu_guo_huang_he_zhu_zhang_peng_che_feng_2020, title={Anti-neuroinflammatory effects of dimethylaminomylide (DMAMCL, i.e., ACT001) are associated with attenuating the NLRP3 inflammasome in MPTP-induced Parkinson disease in mice}, volume={383}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85078981773&partnerID=MN8TOARS}, DOI={10.1016/j.bbr.2020.112539}, abstractNote={Parthenolide (PTL) is a natural compound with anti-inflammatory and antioxidant properties and is an active ingredient extracted from the medicinal plant Tanacetum parthenium. ACT001 is derived from parthenolide and is a fumarate form of dimethylaminomylide (DMAMCL). Its effect is equivalent to that of PTL, but it is more stable in plasma and has lower acquisition costs. Related reports indicate that NLRP3-mediated neuroinflammation is involved in the progression of Parkinson's disease (PD). In our research, we explored whether ACT001 alleviates NLRP3-mediated neuroinflammation in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results revealed that ACT001 reduces movement impairment and cognitive deficit in PD mice. In addition, it alleviates dopaminergic neurodegeneration in the nigrostriatal pathway and inhibits oxidative stress, the inflammatory response and activation of the NLRP3 inflammasome in the midbrain of MPTP-induced PD mice. Moreover, it attenuates microglial activation in the nigrostriatal pathway. Overall, our study showed that ACT001 alleviates NLRP3-mediated neuroinflammation in PD mice induced by MPTP.}, journal={Behavioural Brain Research}, author={Liu, Q. and Guo, X. and Huang, Z. and He, Q. and Zhu, D. and Zhang, S. and Peng, Z. and Che, Y. and Feng, X.}, year={2020} } @article{wang_shang_chen_wang_zhu_liu_zhang_chen_wu_wu_et al._2020, title={Delivery of mscs with a hybrid β-sheet peptide hydrogel consisting igf-1c domain and d-form peptide for acute kidney injury therapy}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85086660555&partnerID=MN8TOARS}, DOI={10.2147/IJN.S254635}, abstractNote={Purpose By providing a stem cell microenvironment with particular bioactive constituents in vivo, synthetic biomaterials have been progressively successful in stem cell-based tissue regeneration by enhancing the engraftment and survival of transplanted cells. Designs with bioactive motifs to influence cell behavior and with D-form amino acids to modulate scaffold stability may be critical for the development and optimization of self-assembling biomimetic hydrogel scaffolds for stem cell therapy. Materials and Methods In this study, we linked naphthalene (Nap) covalently to a short D-form peptide (Nap-DFDFG) and the C domain of insulin-like growth factor-1 (IGF-1C) as a functional hydrogel-based scaffolds, and we hypothesized that this hydrogel could enhance the therapeutic efficiency of human placenta-derived mesenchymal stem cells (hP-MSCs) in a murine acute kidney injury (AKI) model. Results The self-assembling peptide was constrained into a classical β-sheet structure and showed hydrogel properties. Our results revealed that this hydrogel exhibited increased affinity for IGF-1 receptor. Furthermore, cotransplantation of the β-IGF-1C hydrogel and hP-MSCs contributed to endogenous regeneration post-injury and boosted angiogenesis in a murine AKI model, leading to recovery of renal function. Conclusion This hydrogel could provide a favorable niche for hP-MSCs and thereby rescue renal function in an AKI model by promoting cell survival and angiogenesis. In conclusion, by covalently linking the desired functional groups to D-form peptides to create functional hydrogels, self-assembling β-sheet peptide hydrogels may serve as a promising platform for tissue-engineering and stem cell therapy.}, journal={International Journal of Nanomedicine}, author={Wang, H. and Shang, Y. and Chen, X. and Wang, Z. and Zhu, D. and Liu, Y. and Zhang, C. and Chen, P. and Wu, J. and Wu, L. and et al.}, year={2020}, pages={4311–4324} } @article{zhang_zhang_zhu_jiao_zhao_sun_che_feng_2020, title={Effects of 17β-trenbolone exposure on sex hormone synthesis and social behaviours in adolescent mice}, volume={245}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85076629997&partnerID=MN8TOARS}, DOI={10.1016/j.chemosphere.2019.125679}, abstractNote={17β-Trenbolone (17β-TBOH) is an endocrine disruptor that has been widely reported in aquatic organisms. However, little is known about the effect of 17β-TBOH on mammals, particularly on the development of adolescents. Through a series of behavioural experiments, exposure to at 80 μg kg −1 d −1 and 800 μg kg −1 d −1 17β-TBOH during puberty (from PND 28 to 56, male mice) increased anxiety-like behaviours. Exposure to the low dose of 80 μg kg −1 d −1 resulted in a clear social avoidance behaviour in mice. The two doses affected testicular development and endogenous androgen synthesis in male mice. In addition, 17β-TBOH exposure altered the differentiation of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex (mPFC). These results reveal the effects of 17β-TBOH on the behaviours, gonadal and neurodevelopment of adolescent mammals. In addition, the inhibition of the secretion of endogenous hormones and decrease in the formation of the myelin sheath in mPFC may be associated with the 17β-TBOH-induced behavioural changes in mice.}, journal={Chemosphere}, author={Zhang, S. and Zhang, S. and Zhu, D. and Jiao, Z. and Zhao, X. and Sun, M. and Che, Y. and Feng, X.}, year={2020} } @article{liang_li_ren_jia_guo_li_zhang_hu_zhu_shen_et al._2020, title={Light-triggered NO-releasing nanoparticles for treating mice with liver fibrosis}, volume={13}, ISSN={["1998-0000"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85086369757&partnerID=MN8TOARS}, DOI={10.1007/s12274-020-2833-6}, number={8}, journal={NANO RESEARCH}, author={Liang, Hongxia and Li, Zhenhua and Ren, Zhigang and Jia, Qiaodi and Guo, Linna and Li, Shasha and Zhang, Hongyu and Hu, Shiqi and Zhu, Dashuai and Shen, Deliang and et al.}, year={2020}, month={Aug}, pages={2197–2202} } @article{midgley_wei_zhu_gao_yan_khalique_luo_jiang_liu_guo_et al._2020, title={Multifunctional natural polymer nanoparticles as antifibrotic gene carriers for CKD therapy}, volume={31}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85092260644&partnerID=MN8TOARS}, DOI={10.1681/ASN.2019111160}, abstractNote={ Significance Statement Progressive fibrosis, the underlying pathophysiologic process of CKD, is driven by myofibroblasts and activated profibrotic cells. Treatments targeting these cells for the reversal and amelioration of CKD are lacking. Experimental cytokine therapies administered locally are constrained by low bioavailability and transient activity, but nanoparticles can circumvent this and offer noninvasive kidney-targeted delivery of antifibrotic biologics, such as bone morphogenetic protein 7 (BMP7) and hepatocyte growth factor (HGF)–NK1 (HGF/NK1). The authors used nanoparticles containing plasmid DNA expressing either BMP7 or NGF/NKI enclosed in biocompatible natural materials for intravenous delivery of gene therapy to CKD mouse models. Delivery of BMP7 reversed the progression of fibrosis and regenerated tubules; delivery of HGF/NK1 halted CKD progression by eliminating collagen fiber deposition. Nanoparticle gene therapy shows potential as a noninvasive approach to treat CKD. }, number={10}, journal={Journal of the American Society of Nephrology}, author={Midgley, A.C. and Wei, Y. and Zhu, D. and Gao, F. and Yan, H. and Khalique, A. and Luo, W. and Jiang, H. and Liu, X. and Guo, J. and et al.}, year={2020}, pages={2292–2311} } @article{zhang_luo_zhang_zhu_midgley_song_khalique_zhang_zhuang_kong_et al._2020, title={Particle-based artificial three-dimensional stem cell spheroids for revascularization of ischemic diseases}, volume={6}, url={https://doi.org/10.1126/sciadv.aaz8011}, DOI={10.1126/sciadv.aaz8011}, abstractNote={Material technology can simulate hypoxic stem cells for vascular regeneration, providing new insights into synthetic biology.}, number={19}, journal={Science Advances}, publisher={American Association for the Advancement of Science (AAAS)}, author={Zhang, Ran and Luo, Wenya and Zhang, Yue and Zhu, Dashuai and Midgley, Adam C. and Song, Hao and Khalique, Anila and Zhang, Haoqi and Zhuang, Jie and Kong, Deling and et al.}, year={2020}, month={May} } @article{zhang_shang_chen_midgley_wang_zhu_wu_chen_wu_wang_et al._2020, title={Supramolecular Nanofibers Containing Arginine-Glycine-Aspartate (RGD) Peptides Boost Therapeutic Efficacy of Extracellular Vesicles in Kidney Repair}, volume={14}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85091586638&partnerID=MN8TOARS}, DOI={10.1021/acsnano.0c05681}, abstractNote={Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EVs) have been recognized as a promising cell-free therapy for acute kidney injury (AKI), which avoids safety concerns associated with direct cell engraftment. However, low stability and retention of MSC-EVs have limited their therapeutic efficacy. RGD (Arg-Gly-Asp) peptide binds strongly to integrins, which have been identified on the surface of MSC-EV membranes, yet RGD has not been applied to EV scaffolds to enhance and prolong bioavailability. Here, we developed RGD hydrogels, which we hypothesized could augment MSC-EV efficacy in the treatment of AKI models. In vivo tracking of the labeled EVs revealed that RGD hydrogels increased retention and stability of EVs. Integrin gene knockdown experiments confirmed that EV-hydrogel interaction was mediated by RGD-integrin binding. Upon intrarenal injection into mouse AKI models, EV-RGD hydrogels provided superior rescuing effects to renal function, attenuated histopathological damage, decreased tubular injury and promoted cell proliferation in early phases of AKI. RGD hydrogels also augmented anti-fibrotic effects of MSC-EVs in chronic stages. Further analysis revealed that the presence of microRNA let-7a-5p in MSC-EVs served as the mechanism contributing to the reduced cell apoptosis and elevated cell autophagy in AKI. In conclusion, RGD hydrogels facilitated MSC derived let-7a-5p-containing-EVs, improving reparative potential against AKI. This study developed an RGD-scaffold to increase the EV integrin-mediated loading and in-turn improved therapeutic efficacy in renal repair, therefore this strategy shed light on MSC-EVs application as cell-free treatment for potentiated efficiency.}, number={9}, journal={ACS Nano}, author={Zhang, C. and Shang, Y. and Chen, X. and Midgley, A.C. and Wang, Z. and Zhu, D. and Wu, J. and Chen, P. and Wu, L. and Wang, X. and et al.}, year={2020}, pages={12133–12147} } @article{yan_mi_midgley_du_huang_wei_liu_ma_zhi_zhu_et al._2020, title={Targeted Repair of Vascular Injury by Adipose-Derived Stem Cells Modified with P-Selectin Binding Peptide}, volume={7}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85083704027&partnerID=MN8TOARS}, DOI={10.1002/advs.201903516}, abstractNote={Abstract}, number={11}, journal={Advanced Science}, author={Yan, H. and Mi, X. and Midgley, A.C. and Du, X. and Huang, Z. and Wei, T. and Liu, R. and Ma, T. and Zhi, D. and Zhu, D. and et al.}, year={2020} } @article{liu_zhang_zhu_tang_che_feng_2020, title={The parthenolide derivative ACT001 synergizes with low doses of L-DOPA to improve MPTP-induced Parkinson's disease in mice}, volume={379}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85075482549&partnerID=MN8TOARS}, DOI={10.1016/j.bbr.2019.112337}, abstractNote={L-3,4-dihydroxyphenylalanine (L-DOPA) is currently the main drug used to treat Parkinson's disease (PD). However, long-term use of l-DOPA causes substantial side effects, and we hope to find a biological active ingredient that synergizes with a low-dose of l-DOPA to achieve the same therapeutic effect as that of a high-dose of l-DOPA. The natural product parthenolide (PTL) is the active ingredient in the medicinal plant feverfew (Tanacetum parthenium) and has antioxidant and anti-inflammatory properties. ACT001, a fumarate salt form of dimethylaminomicheliolide (DMAMCL), is a derivative of parthenolide and has comparable effects to those of PTL but exhibits higher stability in the plasma and is available at a lower cost. In our study, we used ACT001 in combination with l-DOPA to treat 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease in mice. Specifically, ACT001 significantly reduced motor dysfunction and dopaminergic neurodegeneration in MPTP-treated mice. Furthermore, ACT001 abolished MPTP-induced α-synuclein overexpression, astrocyte activation and interleukin-1β (IL-1β) production in the substantia nigra and striatum of the mouse brain. In addition, ACT001 increased the levels of the anti-apoptotic signalling molecule Bcl-2 and the pAkt/Akt ratio and reduced the levels of the pro-apoptotic signalling molecule Bax and the activation of Caspase3 in the substantia nigra and striatum. We found that the effects of the co-administration of ACT001 and l-DOPA (5 mg/kg) were equivalent to those of the administration of 8 mg/kg l-DOPA in MPTP-induced Parkinson's disease in mice. Then, this evidence suggests that l-DOPA + ACT001 may be used for the treatment of PD.}, journal={Behavioural Brain Research}, author={Liu, Q. and Zhang, S. and Zhu, D. and Tang, X. and Che, Y. and Feng, X.}, year={2020} } @article{zhang_zhu_wei_wu_cui_liuqin_fan_yang_wang_xu_et al._2019, title={A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model}, volume={86}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85060326213&partnerID=MN8TOARS}, DOI={10.1016/j.actbio.2019.01.022}, abstractNote={Myocardial infarction (MI) leads to the loss of cardiomyocytes, left ventricle (LV) dilation, and cardiac dysfunction, eventually developing into heart failure. Most of the strategies for MI therapy require biomaterials that can support tissue regeneration. In this study, we hypothesized that the extracellular matrix (ECM)-derived collagen I hydrogel loaded with histone deacetylase 7 (HDAC7)-derived-phosphorylated 7-amino-acid peptide (7Ap) could restrain LV remodeling and improve cardiac function after MI. An MI model was established by ligation of the left anterior descending coronary artery (LAD) of C57/B6 mice. The 7Ap-loaded collagen I hydrogel was intramyocardially injected to the infarcted region of the LV wall of the heart. After local delivery, the 7Ap-collagen increased neo-microvessel formation, enhanced stem cell antigen-1 positive (Sca-1+) stem cell recruitment and differentiation, decreased cellular apoptosis, and promoted cardiomyocyte cycle progression. Furthermore, the 7Ap-collagen restricted the fibrosis of the LV wall, reduced the infarct wall thinning, and improved cardiac performance significantly at 2 weeks post-MI. These results highlight the promising implication of 7Ap-collagen as a novel candidate for MI therapy. STATEMENT OF SIGNIFICANCE: The mammalian myocardium has a limited regenerative capability following myocardial infarction (MI). MI leads to extensive loss of cardiomyocytes, thus culminating in adverse cardiac remodeling and congestive heart failure. In situ tissue regeneration through endogenous cell mobilization has great potential for tissue regeneration. A 7-amino-acid-peptide (7A) domain encoded by a short open-reading frame (sORF) of the HDAC7 gene. The phosphorylated from of 7A (7Ap) has been reported to promote in situ tissue repair via the mobilization and recruitment of endogenous stem cell antigen-1 positive (Sca-l+) stem cells. In this study, 7Ap was shown to improve H9C2 cell survival, in vitro. In vivo investigations in a mouse MI model demonstrated that intra-myocardial delivery of 7Ap-loaded collagen hydrogel promoted neovascularization, stimulated Sca-l+ stem cell recruitment and differentiation, reduced cardiomyocyte apoptosis and promoted cell cycle progression. As a result, treated infarcted hearts had increased wall thickness, had improved heart function and exhibited attenuation of adverse cardiac remodeling, observed for up to 2 weeks. Overall, these results highlighted the positive impact of implanting 7Ap-collagen as a novel constituent for MI repair.}, journal={Acta Biomaterialia}, author={Zhang, Y. and Zhu, D. and Wei, Y. and Wu, Y. and Cui, W. and Liuqin, L. and Fan, G. and Yang, Q. and Wang, Z. and Xu, Z. and et al.}, year={2019}, pages={223–234} } @article{wang_shang_chen_wang_zhu_liu_zhang_chen_wu_wu_et al._2019, title={Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85109309821&partnerID=MN8TOARS}, DOI={10.2139/ssrn.3485132}, abstractNote={By providing an appropriate microenvironment, synthetic biomaterials have been progressively successful in stem cell-based tissue regeneration by enhancing the engraftment and survival of transplanted cells. The designs with bioactive motifs to influence cell behavior and with D-form amino acid to modulate scaffold stability will be critical for the development and optimization of self-assembling biomimetic hydrogel scaffolds for stem cell therapy. In this study, we linked naphthalene (Nap) covalently conjugated a short D-form peptide (Nap-DFDFG) to C domain of insulin-like growth factor-1 (IGF-1C) as a functional peptide-based scaffold. Our purpose is to provide a functional self-assembling peptide hydrogel with encapsulated human placenta derived mesenchymal stem cells (hP-MSCs) and thereby to enhance the therapeutic efficiency of hP-MSCs in murine acute kidney injury (AKI) model. Our results revealed that a typical β-sheet conformation was confirmed and this self-assembling peptide hydrogel exhibited higher affinity with IGF-1 receptor. Furthermore, this hydrogel could provide a favorable niche for hP-MSCs and thereby ameliorate renal function in an AKI model by promoting cell survival and angiogenesis. In conclusion, by covalently linking the desired functional group to D-form peptide to create a functional hydrogel, this self-assembling β-sheet peptide hydrogel will serve as a promising platform for future tissue-engineering and stem cell therapy.}, journal={SSRN}, author={Wang, H. and Shang, Y. and Chen, X. and Wang, Z. and Zhu, D. and Liu, Y. and Zhang, C. and Chen, P. and Wu, J. and Wu, L. and et al.}, year={2019} } @article{qi_li_yun_zhang_huang_zhou_yan_wei_liu_zhang_et al._2019, title={Lactobacillus maintains healthy gut mucosa by producing L-Ornithine}, volume={2}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85070997928&partnerID=MN8TOARS}, DOI={10.1038/s42003-019-0424-4}, abstractNote={Abstract}, number={1}, journal={Communications Biology}, author={Qi, H. and Li, Y. and Yun, H. and Zhang, T. and Huang, Y. and Zhou, J. and Yan, H. and Wei, J. and Liu, Y. and Zhang, Z. and et al.}, year={2019} } @article{li_liu_zhu_che_feng_2019, title={Preparation of levodopa-loaded crystalsomes through thermally induced crystallization reverses functional deficits in Parkinsonian mice}, volume={7}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85063456111&partnerID=MN8TOARS}, DOI={10.1039/c8bm01098f}, abstractNote={The prepared levodopa loaded crystalsomes are nanoscale crystals and controlling levodopa release which improving MPTP-induced behavioral impairments and pathological features of mice.}, number={4}, journal={Biomaterials Science}, author={Li, X. and Liu, Q. and Zhu, D. and Che, Y. and Feng, X.}, year={2019}, pages={1623–1631} } @article{liu_zhu_jiang_tang_lang_yu_zhang_che_feng_2019, title={Resveratrol synergizes with low doses of L-DOPA to improve MPTP-induced Parkinson disease in mice}, volume={367}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85063438332&partnerID=MN8TOARS}, DOI={10.1016/j.bbr.2019.03.043}, abstractNote={L-DOPA (L-3,4-dihydroxyphenylalanine) relieves symptoms of Parkinson disease (PD), but long-term use can cause serious side effects. Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RV), a polyphenolic compound derived from grapes and red wine that has antioxidant activity, has been shown to have neuroprotective effects. RV was investigated to enhance the therapeutic effect of L-DOPA in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson disease. Mice received a saline or RV injection (10 mg/kg/day), then 2 h later, saline or MPTP (15 mg/kg/day) was administered for 7 consecutive days. Saline or L-DOPA (5 or 8 mg/kg/day) was injected post-administration of MPTP for the last 2 consecutive days. Our results indicated that RV alleviated MPTP-induced loss of dopaminergic neurons and attenuated astroglial activation in the nigrostriatal pathway. In parallel, RV reduced the expression of α-synuclein in the striatum. In addition, RV also increased levels of the anti-apoptotic signalling molecule Bcl-2, reduced levels of the pro-apoptotic signalling molecule Bax, and reduced activation of caspase-3 in the striatum. Specifically, RV significantly reduced motor dysfunction in MPTP-treated mice. Furthermore, the RV-treated group showed less IL-1β and an enhanced pAkt/Akt ratio, which promoted dopamine neuron survival in the striatum. We found that the effects of co-administration of RV with L-DOPA (5 mg/kg) were equivalent to those of administration of 8 mg/kg L-DOPA in MPTP-induced PD mice. Therefore, with fewer side effects, L-DOPA can be effectively used in the treatment of PD over a long period of time.}, journal={Behavioural Brain Research}, author={Liu, Q. and Zhu, D. and Jiang, P. and Tang, X. and Lang, Q. and Yu, Q. and Zhang, S. and Che, Y. and Feng, X.}, year={2019}, pages={10–18} } @article{hou_pan_zhu_fan_feng_wei_wang_qin_zhao_yang_et al._2019, title={Targeted delivery of nitric oxide via a ‘bump-and-hole’-based enzyme–prodrug pair}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85059459174&partnerID=MN8TOARS}, DOI={10.1038/s41589-018-0190-5}, abstractNote={The spatiotemporal generation of nitric oxide (NO), a versatile endogenous messenger, is precisely controlled. Despite its therapeutic potential for a wide range of diseases, NO-based therapies are limited clinically due to a lack of effective strategies for precisely delivering NO to a specific site. In the present study, we developed a novel NO delivery system via modification of an enzyme-prodrug pair of galactosidase-galactosyl-NONOate using a 'bump-and-hole' strategy. Precise delivery to targeted tissues was clearly demonstrated by an in vivo near-infrared imaging assay. The therapeutic potential was evaluated in both rat hindlimb ischemia and mouse acute kidney injury models. Targeted delivery of NO clearly enhanced its therapeutic efficacy in tissue repair and function recovery and abolished side effects due to the systemic release of NO. The developed protocol holds broad applicability in the targeted delivery of important gaseous signaling molecules and offers a potent tool for the investigation of relevant molecular mechanisms.}, number={2}, journal={Nature Chemical Biology}, author={Hou, J. and Pan, Y. and Zhu, D. and Fan, Y. and Feng, G. and Wei, Y. and Wang, H. and Qin, K. and Zhao, T. and Yang, Q. and et al.}, year={2019}, pages={151–160} } @article{feng_li_zhu_zhang_song_zhang_chen_du_yao_2018, title={Expression and clinical significance of CXC-chemokine ligand 5 in renal cell carcinoma}, volume={45}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85061286356&partnerID=MN8TOARS}, DOI={10.3969/j.issn.1000-8179.2018.16.636}, number={16}, journal={Chinese Journal of Clinical Oncology}, author={Feng, G. and Li, H. and Zhu, D. and Zhang, Y. and Song, G. and Zhang, Z. and Chen, M. and Du, J. and Yao, X.}, year={2018}, pages={838–843} } @article{shafiq_zhang_zhu_zhao_kim_kim_kong_2018, title={In situ cardiac regeneration by using neuropeptide substance P and IGF-1C peptide eluting heart patches}, volume={5}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85073764097&partnerID=MN8TOARS}, DOI={10.1093/rb/rby021}, abstractNote={Abstract Cardiovascular diseases cause huge socio-economic burden worldwide. Although a mammalian myocardium has its own limited healing capability, scaffold materials capable of releasing stem cell recruiting/engrafting factors may facilitate the regeneration of the infarcted myocardium. The aim of this research was to develop cardiac patches capable of simultaneously eluting substance P (SP) and insulin-like growth factor-1C (IGF-1C) peptide. Polycaprolactone/collagen type 1-based patches with or without SP and IGF-1C peptide were fabricated by co-electrospinning, which exhibited nanofibrous morphology. SP and IGF-1C/SP patches recruited significantly higher numbers of bone marrow-mesenchymal stem cells than that of the negative control and patch-only groups in vitro. The developed patches were transplanted in an infarcted myocardium for up to 14 days. Mice underwent left anterior descending artery ligation and received one of the following treatments: (i) sham, (ii) saline, (iii) patch-only, (iv) IGF-1C patch, (v) SP patch and (vi) IGF-1C/SP patch. SP and IGF-1C/SP patch-treated groups exhibited better heart function and attenuated adverse cardiac remodeling than that of the saline, patch-only and individual peptide containing cardiac patches. SP patch and IGF-1C/SP patch-treated groups also showed higher numbers of CD31-positive vessels and isolectin B4-positive capillaries than that of other groups. IGF-1C/SP-treated group also showed thicker left ventricular wall in comparison to the saline and patch-only groups. Moreover, IGF-1C/SP patches recruited significantly higher numbers of CD29-positive cells and showed less numbers of Tunel-positive cells compared with the other groups. These data suggest that SP and IGF-1C peptides may act synergistically for in situ tissue repair.}, number={5}, journal={Regenerative Biomaterials}, author={Shafiq, M. and Zhang, Y. and Zhu, D. and Zhao, Z. and Kim, D.-H. and Kim, S.H. and Kong, D.}, year={2018}, pages={303–316} } @article{zhang_liu_zhang_zhu_qi_cao_fang_che_han_he_et al._2018, title={Prostaglandin E2 hydrogel improves cutaneous wound healing via M2 macrophages polarization}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85056754206&partnerID=MN8TOARS}, DOI={10.7150/thno.27385}, abstractNote={Wound healing is regulated by a complex series of events and overlapping phases. A delicate balance of cytokines and mediators in tissue repair is required for optimal therapy in clinical applications. Molecular imaging technologies, with their versatility in monitoring cellular and molecular events in living organisms, offer tangible options to better guide tissue repair by regulating the balance of cytokines and mediators at injured sites. Methods: A murine cutaneous wound healing model was developed to investigate if incorporation of prostaglandin E2 (PGE2) into chitosan (CS) hydrogel (CS+PGE2 hydrogel) could enhance its therapeutic effects. Bioluminescence imaging (BLI) was used to noninvasively monitor the inflammation and angiogenesis processes at injured sites during wound healing. We also investigated the M1 and M2 paradigm of macrophage activation during wound healing. Results: CS hydrogel could prolong the release of PGE2, thereby improving its tissue repair and regeneration capabilities. Molecular imaging results showed that the prolonged release of PGE2 could ameliorate inflammation by promoting the M2 phenotypic transformation of macrophages. Also, CS+PGE2 hydrogel could augment angiogenesis at the injured sites during the early phase of tissue repair, as revealed by BLI. Furthermore, our results demonstrated that CS+PGE2 hydrogel could regulate the balance among the three overlapping phases—inflammation, regeneration (angiogenesis), and remodeling (fibrosis)—during cutaneous wound healing. Conclusion: Our findings highlight the potential of the CS+PGE2 hydrogel as a novel therapeutic strategy for promoting tissue regeneration via M2 macrophage polarization. Moreover, molecular imaging provides a platform for monitoring cellular and molecular events in real-time during tissue repair and facilitates the discovery of optimal therapeutics for injury repair by regulating the balance of cytokines and mediators at injured sites.}, number={19}, journal={Theranostics}, author={Zhang, S. and Liu, Y. and Zhang, X. and Zhu, D. and Qi, X. and Cao, X. and Fang, Y. and Che, Y. and Han, Z.-C. and He, Z.-X. and et al.}, year={2018}, pages={5348–5361} } @article{li_wei_li_zhu_nie_zhou_lou_dong_wu_che_et al._2017, title={Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85008397816&partnerID=MN8TOARS}, DOI={10.1186/s12906-016-1526-x}, abstractNote={Xian-Fang-Huo-Ming-Yin (XFHM), a traditional herbal formula, has been used to treat sores and carbuncles for hundreds of years in Asia. Nowadays, its clinical effects in treatment of rheumatoid arthritis (RA) have been validated. In this study, we want to study its possible molecular mechanisms of regulating the differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis (CIA) mice for RA treatment.A high performance liquid chromatography-electrospray ionization/mass spectrometer (HPLC-ESI/MSn) system was used to analyze the constituents of XFHM granules. An arthritics mouse model was induced by collagen and leflunomide (LEF) was used as a positive control medicine. Pathological changes at the metatarsophalangeal joint were studied through Safranin O and immunohistochemical staining. The differentiation of T, B and NK cells was examined by flow cytometry and pro-inflammatory cytokines were assayed using an Inflammation Antibody Array assay. The expression of key molecules of the nuclear factor κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways in spleen were studied by western-blot analysis.In our study. 21 different dominant chemical constituents were identified in XFHM. Treatment with XFHM suppressed the pathological changes in arthrosis of CIA. Additionally, XFHM down-regulated the proliferation and differentiation of CD3+ T cells and CD3-CD19+ B cells significantly. However, XFHM had no significant effect on CD3-NK1.1+ NK cells. Further study showed that the production of pro-inflammatory cytokines had been suppressed by inhibiting the activation of NF-κB and JAK/STAT signaling.XFHM can regulate and maintain the immunologic balance of lymphocytic immunity and inhibit the production of pro-inflammatory cytokines, thus suppressing the pathological changes of RA. Therefore, XFHM may be used as an application of traditional medicine against RA in modern complementary and alternative therapeutics.}, number={1}, journal={BMC Complementary and Alternative Medicine}, author={Li, J. and Wei, Y. and Li, X. and Zhu, D. and Nie, B. and Zhou, J. and Lou, L. and Dong, B. and Wu, A. and Che, Y. and et al.}, year={2017} } @article{li_sun_li_zhu_jia_jiao_wang_kong_zhao_xu_et al._2017, title={PEGylation corannulene enhances response of stress through promoting neurogenesis}, volume={5}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85016312774&partnerID=MN8TOARS}, DOI={10.1039/c7bm00068e}, abstractNote={The synthesized PEGylation corannulene nanoparticles was examined in neural functions, which have effects on improving behavioral response to stress and promoting neurogenesis.}, number={4}, journal={Biomaterials Science}, author={Li, X. and Sun, D. and Li, X. and Zhu, D. and Jia, Z. and Jiao, J. and Wang, K. and Kong, D. and Zhao, X. and Xu, L. and et al.}, year={2017}, pages={849–859} } @article{li_ma_xu_zhu_li_che_chen_feng_2017, title={Puerarin and Amlodipine Improvement of d-Galactose-Induced Impairments of Behaviour and Neurogenesis in Mouse Dentate Gyrus: Correlation with Glucocorticoid Receptor Expression}, volume={42}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85027870475&partnerID=MN8TOARS}, DOI={10.1007/s11064-017-2366-x}, abstractNote={Glucocorticoid receptors (GRs) exert actions on the hippocampus that are important for memory formation. There are correlations between vascular dysfunctions and GR-related gene expression. Both vascular dysfunction and GR gene expression decline occur during the ageing process. Therefore, hypotensors, which have effects on improving vascular dysfunction, may be able to ameliorate GR gene expression decline in ageing mice and improve ageing-mediated memory deficits. In this study, we hypothesized that hypotensors could alleviate the decline of GR gene expression and ameliorate age-induced learning and memory deficits in a D-gal-induced ageing mice model. In line with our hypothesis, we found that chronic D-gal treatment decreased GR and DCX expression in the hippocampus, leading to learning and memory deficits. Amlodipine (AM) and puerarin (PU) treatment improved GR gene expression decline in the hippocampus and ameliorated the learning and memory deficits of D-gal-treated mice. These changes correlated with enhanced DCX expression and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Furthermore, PU treatment conveyed better effects than AM treatment, but combination therapy did not enhance the effects on improving GR expression. However, we did not find evidence of these changes in non-D-gal-treated mice that lacked GR gene expression decline. These results suggest that AM and PU could improve D-gal-induced behavioural deficits in correlation with GR gene expression.}, number={11}, journal={Neurochemical Research}, author={Li, X.Y. and Ma, J. and Xu, J. and Zhu, D.S. and Li, A. and Che, Y.Z. and Chen, D.Y. and Feng, X.Z.}, year={2017}, pages={3268–3278} } @article{jia_yang_jiao_li_zhu_yang_yang_che_lu_feng_2017, title={Rhein and polydimethylsiloxane functionalized carbon/carbon composites as prosthetic implants for bone repair applications}, volume={12}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85029145036&partnerID=MN8TOARS}, DOI={10.1088/1748-605X/aa6e27}, abstractNote={A major issue in bone tissue engineering is the selection of biocompatible materials for implants, to reduce unwanted inflammatory reactions and promote cell adhesion. Bone tissue growth on suitable biomedical implants can shorten recovery and hospitalization after surgery. Therefore, a method to improve tissue–implant integration and healing would be of scientific and clinical interest. In this work, we permeated polydimethylsiloxane (PDMS) into carbon/carbon (C/C) composites (PDMS–C/C) and then coated it with 4,5-dihydroxyanthraquinone-2-carboxylic acid (rhein) to create rhein–PDMS–C/C to increase its biocompatibility and reduce the occurrence of inflammatory reactions. We measured in vitro adhesion and proliferation of MC3T3-E1 cells and bacteria to evaluate the biocompatibility and antimicrobial properties of C/C, PDMS–C/C, and rhein–PDMS–C/C. In vivo, x-ray and micro-CT evaluation three, six and nine weeks after surgery revealed that rhein–PDMS–C/C was more effective than PDMS–C/C and C/C composite in terms of antibacterial activity, cell adhesion and tissue growth. Compared with C/C and PDMS–C/C, rhein–PDMS–C/C could be suitable for clinical applications for bone tissue engineering.}, number={4}, journal={Biomedical Materials (Bristol)}, author={Jia, Z. and Yang, C. and Jiao, J. and Li, X. and Zhu, D. and Yang, Y. and Yang, J. and Che, Y. and Lu, Y. and Feng, X.}, year={2017} } @article{feng_zhang_li_nie_zhu_wang_liu_gao_liu_he_et al._2016, title={IGF-1 C domain-modified hydrogel enhances cell therapy for AKI}, volume={27}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84975522975&partnerID=MN8TOARS}, DOI={10.1681/ASN.2015050578}, abstractNote={Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan–IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan–IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI.}, number={8}, journal={Journal of the American Society of Nephrology}, author={Feng, G. and Zhang, J. and Li, Y. and Nie, Y. and Zhu, D. and Wang, R. and Liu, J. and Gao, J. and Liu, N. and He, N. and et al.}, year={2016}, pages={2357–2369} }