Engineered exosomes enriched in netrin-1 modRNA promote axonal growth in spinal cord injury by attenuating inflammation and pyroptosis

Lu Xiao,Xu Guangyu,Lin Zhidi,Zou Fei,Liu Siyang,Zhang Yuxuan,Fu Wei,Jiang Jianyuan,Ma Xiaosheng,Song Jian 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Spinal cord injury (SCI) brings a heavy burden to individuals and society, and there is no effective treatment at present. Exosomes (EX) are cell secreted vesicles containing molecules such as nucleic acids and proteins, which hold promise for the treatment of SCI. Netrin-1 is an axon guidance factor that regulates neuronal growth. We investigated the effects of engineered EX enriched in netrin-1 chemically synthetic modified message RNA (modRNA) in treating SCI in an attempt to find a novel therapeutic approach for SCI.Netrin-1 modRNA was transfected into bone marrow mesenchymal stem cells to obtain EX enriched with netrin-1 (EX-netrin1). We built an inflammatory model in vitro with lipopolysaccharide (LPS) in vitro to study the therapeutic effect of EX-netrin1 on SCI. For experiments in vitro, ELISA, CCK-8 assay, immunofluorescence staining, lactate dehydrogenase release experiments test, real-time quantitative polymerase chain reaction, and western blot were conducted. At the same time, we constructed a rat model of SCI. MRI, hematoxylin-eosin and Nissl staining were used to assess the extent of SCI in rats.In vitro experiments showed that EX had no effect on the viability of oligodendrocytes and PC12 cells. EX-netrin1 could attenuate LPS-induced inflammation and pyroptosis and accelerate axonal/dentritic growth in PC12 cells/oligodendrocytes. In addition, netrin-1 could activate the PI3K/AKT/mTOR signalling pathway upon binding to its receptor unc5b. When Unc5b and PI3K were inhibited, the effect of EX-netrin1 was weakened, which could be reversed by PI3K or mTOR activator. Our in vivo experiments indicated that EX-netrin1 could promote recovery in rats with SCI.We found that EX-netrin1 regulated inflammation, pyroptosis and axon growth in SCI via the Unc5b/PI3K/AKT/mTOR pathway, which provides a new strategy for the treatment of SCI.

Knockdown of lncRNA PVT1 Inhibits Vascular Smooth Muscle Cell Apoptosis and Extracellular Matrix Disruption in a Murine Abdominal Aortic Aneurysm Model

Zhang, Zhidong,Zou, Gangqiang,Chen, Xiaosan,Lu, Wei,Liu, Jianyang,Zhai, Shuiting,Qiao, Gang Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.3

This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient ($ApoE^{-/-}$) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased pro-inflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.

Flexural Behavior of Ultra-High Performance Concrete (UHPC) Deck with Joints subjected to an Improved Steel Wire Mesh (SWM) Treatment

Kaiwei Lu,Linpu Du,Fan Zhang,Xingxing Zou,Jingquan Wang 대한토목학회 2023 KSCE Journal of Civil Engineering Vol.27 No.5

Prefabricated Ultra-high performance concrete (UHPC) decks are often connected using UHPC wet joints to create the overall deck structure. The UHPC deck is, nevertheless, made weak by the fiber discontinuity at the contact interface. In this study, the fiber at the interface was made to serve as a bridge using an embedded steel wire mesh, and experiments were utilized to determine how the contact between the fiber and the steel bar affects the flexural behavior. The results show that the fiber significantly affects the ductility and flexural strength without reinforcement. The combined action of the fiber and reinforcement of the reinforced specimen somewhat increases the flexural capacity and ductility. The flexural capacity of decks with joints was finally calculated using three different ways, and it was found that the method that simplifies the tension and compression zones into rectangles is the most appropriate.

A novel pattern recognition protein of the Chinese oak silkmoth, Antheraea pernyi, is involved in the pro-PO activating system

Xia Lu Wan,Zhang Jing Hai,Ying Chen,You Lei Ma,Wen Jun Zou,Guo Yuan Ding,Wei Li,Ming Yi Zhao,Chun Fu Wu 생화학분자생물학회(구 한국생화학분자생물학회) 2013 BMB Reports Vol.46 No.7

Knockdown of lncRNA PVT1 Inhibits Vascular Smooth Muscle Cell Apoptosis and Extracellular Matrix Disruption in a Murine Abdominal Aortic Aneurysm Model

Zhidong Zhang,Gangqiang Zou,Xiaosan Chen,Wei Lu,Jianyang Liu,Shuiting Zhai,Gang Qiao 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.3

This study was designed to determine the effects of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) on vascular smooth muscle cell (VSMC) apoptosis and extracellular matrix (ECM) disruption in a murine abdominal aortic aneurysm (AAA) model. After injection of PVT1-silencing lentiviruses, AAA was induced in Apolipoprotein E-deficient (ApoE?/?) male mice by angiotensin II (Ang II) infusion for four weeks. After Ang II infusion, mouse serum levels of pro-inflammatory cytokines were analysed, and aortic tissues were isolated for histological, RNA, and protein analysis. Our results also showed that PVT1 expression was significantly upregulated in abdominal aortic tissues from AAA patients compared with that in controls. Additionally, Ang II treatment significantly increased PVT1 expression, both in cultured mouse VSMCs and in AAA murine abdominal aortic tissues. Of note, the effects of Ang II in facilitating cell apoptosis, increasing matrix metalloproteinase (MMP)-2 and MMP-9, reducing tissue inhibitor of MMP (TIMP)-1, and promoting switching from the contractile to synthetic phenotype in cultured VSMCs were enhanced by overexpression of PVT1 but attenuated by knockdown of PVT1. Furthermore, knockdown of PVT1 reversed Ang II-induced AAA-associated alterations in mice, as evidenced by attenuation of aortic diameter dilation, marked adventitial thickening, loss of elastin in the aorta, enhanced aortic cell apoptosis, elevated MMP-2 and MMP-9, reduced TIMP-1, and increased proinflammatory cytokines. In conclusion, our findings demonstrate that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.

Space-Time Pattern of Ion Flow Under AC/DC Hybrid Overhead Lines and Its Application

Qiao, Ji,Zou, Jun,Zhang, Jiangong,Lu, Yao,Lee, Jaebok,Ju, Mun-No IEEE 2018 IEEE transactions on power delivery Vol.33 No.5

<P>Building HVdc and HVac transmission lines in the same corridor or even on the same tower is an attractive way to extend electricity transport capacity where getting the new right of way is difficult. The resulting hybrid lines produce a new corona performance, such as ground-level hybrid electric field and ion current density, which are quite different from those of pure ac or dc lines. In this paper, inherent space-time pattern and characteristics of the information propagation in Lagrangian description are presented for the ion transport problem, that is, the ion density at a certain point has a direct relationship with its drift time. Based on this, the theoretical explanation is provided for the decoupling algorithm, by which the ground-level dc component can be solved with the ac conductors assumed to be at zero potential and vice versa. The simulation results show that the sinusoidal ac field has negligible influence on the dc ion drift time from conductor surface to ground, whereas stationary electric field generated by the grounded ac lines has a dominant effect. Therefore, ac energization has a rather low impact on ground-level quantities and the simplification of grounded ac conductors is quite reasonable.</P>

Xanthoceraside Induces Apoptosis in Melanoma Cells Through the Activation of Caspases and the Suppression of the IGF-1R/Raf/MEK/ERK Signaling Pathway

Qing Jiao,Libo Zou,Peng Liu,Qian Xu,Yifei Zhang,Ying Yu,Lu Zou,Tianyan Chi,Xuefei Ji 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.10

Xanthoceraside, a saponin extracted from the husks of Xanthoceras sorbifolia Bunge, suppresses inflammation and oxidative stress. However, the antitumor properties of xanthoceraside as well as its mechanism of action remain unclear. Therefore, we proposed to investigate its potential anticancer property. In this study, the viability of cells was measured by the MTT assay. Cell cycle and mitochondrial membrane potential were measured by flow cytometry, and the expressions of procaspase-9, procaspase-3, Cyto.c, Apaf-1, Bcl-2, Bcl-xL, Bad, p53, and IGF-1R/Raf/MEK/ERK were tested by Western blotting. Xanthoceraside significantly inhibited the proliferation of human melanoma A375.S2 cells in a concentration- and time-dependent manner but did not impair the viability of normal cells (peripheral blood mononuclear cells). Further analysis revealed that xanthoceraside induced apoptosis by activating caspase-3 and caspase-9 in a time-dependent manner through the mitochondrial pathway but did not activate caspase-8 in the cells. In addition, xanthoceraside inhibited the expression of the insulin-like growth factor-1 receptor (IGF-1R), which is an important prosurvival, antiapoptotic signaling growth factor receptor that is frequently overexpressed in cancer cells and used as a therapeutic target for multiple cancers. Interestingly, xanthoceraside also decreased the expression of Raf, p-MEK, and p-ERK, the downstream effectors of IGF-1R. Taken together, these findings indicate that xanthoceraside induces apoptosis through a mitochondria-mediated apoptotic pathway, which is induced by the downregulation of IGF-1R/Raf/MEK/ERK cascades in A375.S2 cells.

The NADPH oxidase AoNoxA in Arthrobotrys oligospora functions as an initial factor in the infection of Caenorhabditis elegans

Xin Li,Ying-Qian Kang,Yan-Lu Luo,Ke Qin Zhang,Cheng-Gang Zou,Lian-Ming Liang 한국미생물학회 2017 The journal of microbiology Vol.55 No.11

Reactive oxygen species (ROS) produced by NADPH oxidases can serve as signaling molecules to regulate a variety of physiological processes in multi-cellular organisms. In the nematophagous fungus Arthrobotrys oligospora, we found that ROS were produced during conidial germination, hyphal extension, and trap formation in the presence of nematodes. Generation of an AoNoxA knockout strain demonstrated the crucial role of NADPH oxidase in the production of ROS in A. oligospora, with trap formation impaired in the AoNoxA mutant, even in the presence of the nematode host. In addition, the expression of virulence factor serine protease P186 was up-regulated in the wild-type strain, but not in the mutant strain, in the presence of Caenorhabditis elegans. These results indicate that ROS derived from AoNoxA are essential for full virulence of A. oligospora in nematodes.

Road-friendliness of Fuzzy Hybrid Control Strategy Based on Hardware-in-the-Loop Simulations

Yan, Tian Yi,Li, Qiang,Ren, Kun Ru,Wang, Yu Lin,Zhang, Lu Zou Korean Society for Agricultural Machinery 2012 바이오시스템공학 Vol.37 No.3

Purpose: In order to improve road-friendliness of heavy vehicles, a fuzzy hybrid control strategy consisting of a hybrid control strategy and a fuzzy logic control module is proposed. The performance of the proposed strategy should be effectively evaluated using a hardware-in-the-loop (HIL) simulation model of a semi-active suspension system based on the fuzzy hybrid control strategy prior to real vehicle implementations. Methods: A hardware-in-the-loop (HIL) simulation system was synthesized by utilizing a self-developed electronic control unit (ECU), a PCI-1711 multi-functional data acquisition board as well as the previously developed quarter-car simulation model. Road-friendliness of a semi-active suspension system controlled by the proposed control strategy was simulated via the HIL system using Dynamic Load Coefficient (DLC) and Dynamic Load Stress Factor (DLSF) criteria. Results: Compared to a passive suspension, a semi-active suspension system based on the fuzzy hybrid control strategy reduced the DLC and DLSF values. Conclusions: The proposed control strategy of semi-active suspension systems can be employed to improve road-friendliness of road vehicles.

Research Articles : Off-Road Machinery System Engineering ; Road-friendliness of Fuzzy Hybrid Control Strategy Based on Hardware-in-the-Loop Simulations

( Tian Yi Yan ),( Qiang Li ),( Kun Ru Ren ),( Yu Lin Wang ),( Lu Zou Zhang ) 한국농업기계학회 2012 바이오시스템공학 Vol.37 No.3

Purpose: In order to improve road-friendliness of heavy vehicles, a fuzzy hybrid control strategy consisting of a hybrid control strategy and a fuzzy logic control module is proposed. The performance of the proposed strategy should be effectively evaluated using a hardware-in-the-loop (HIL) simulation model of a semi-active suspension system based on the fuzzy hybrid control strategy prior to real vehicle implementations. Methods: A hardware-in-the-loop (HIL) simulation system was synthesized by utilizing a self-developed electronic control unit (ECU), a PCI-1711 multi-functional data acquisition board as well as the previously developed quarter-car simulation model. Road-friendliness of a semi-active suspension system controlled by the proposed control strategy was simulated via the HIL system using Dynamic Load Coefficient (DLC) and Dynamic Load Stress Factor (DLSF) criteria. Results: Compared to a passive suspension, a semi-active suspension system based on the fuzzy hybrid control strategy reduced the DLC and DLSF values. Conclusions: The proposed control strategy of semi-active suspension systems can be employed to improve road-friendliness of road vehicles.