CERAMICS INTERNATIONAL
·
2023
·
IF 5.2
Weijian Kong,Yinlong Zhao,Yang Xiaoyu,Jing Chen,Yihang Chen,Zhengyang Zhao,Xiaonan Chen,Feng Wang,Chuan Fu
The massive death of nerve cells and the inflammatory microenvironment resulting from the release of reactive oxygen species after spinal cord injury (SCI) hinders the subsequent reconstruction of motor function. Owing to complex pathological changes, combination therapy is a potential new way to treat SCI. In this study, a novel multifunctional hydrogel containing an MXene-Au complex was constructed, and neural stem cells (NSCs) loaded in the hydrogel were combined with electrical stimulation to promote the recovery of motor function after SCI in rats. The constructed MAu-GelMA hydrogel had good reactive oxygen species-scavenging ability, electrical conductivity , and antibacterial ability. Simultaneously, electrical stimulation promoted the proliferation and differentiation of NSCs into nerve cells and promoted the establishment of synaptic connections between neurons. In the rat SCI model, combined treatment using MAu-GelMA hydrogel carrying NSCs and electrical stimulation reduced the formation of cavities and glial scars, enhanced neuronal differentiation and myelin regeneration of NSCs in the injured area, and promoted the recovery of motor function after SCI. In conclusion, in this study, we constructed a novel multifunctional hydrogel capable of carrying NSCs, which upon combining with electrical stimulation during treatment, effectively promoted the recovery of motor function in rats with SCI, thereby providing a new combination therapy strategy for SCI.
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EXPERIMENTAL CELL RESEARCH
·
2023
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IF 3.7
Lei Huang,Shunyi Lu,Mengxuan Bian,Jiayi Wang,Jieqin Yu,Jun Ge,Jian Zhang,Qintong Xu
Oxidative stress is one of the most important factors in changing bone homeostasis. Redox homeostasis plays a key role in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) for bone regeneration. Currently, this study assessed the effects of punicalagin (PUN) on BMSCs and HUVECs. Cell viability was determined by CCK-8 assay. A flow cytometry analysis was adopted to detect macrophage polarization. The production of reactive oxygen stress (ROS), glutathione (GSH), malonaldehyde (MDA) and superoxide dismutase (SOD) activities were evaluated by using commercially-available kits. Osteogenic capacity of BMSCs was evaluated by ALP activity, ALP staining and ARS staining. The expression of osteogenic-related proteins (OCN, Runx-2, OPN) and Nrf/HO-1 levles were evaluated by Western blotting. Osteogenic-related genes (Osterix, COL-1, BMP-4, ALP) were evaluated by RT-PCR. Migration ability and invasion ability of HUVECs were evaluated by wound healing assay and Transwell assay. Angiogenic ability was detected by tube formation assay and the expression of angiogenic-related genes (VEGF, vWF, CD31) were evaluated by RT-PCR. Results showed that PUN alleviated oxidative stress by TNF-α, enhanced osteogenic differentiation in BMSCs and angiogenesis in HUVECs. Moreover, PUN regulate immune microenvironment by promoting the polarization of M2 macrophages and reduce the oxidative stress related products by activating Nrf2/HO-1 pathway. Altogether, these results suggested that PUN can promote osteogenic capacity of BMSCs, angiogenesis of HUVECs, alleviate oxidative stress via Nrf2/HO-1 pathway, offering PUN as a novel antioxidant agent for treating bone loss diseases.
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高影响因子
GREEN CHEMISTRY
·
2023
·Vol. 25
·期 15
·5968-5978
·
IF 9.8
Jiahui Wei,Haonan Zhang,Shengcheng Zhai,Hao Ren,Huamin Zhai
Pure subcritical water autohydrolysis is an economical and green biorefinery method and potentially applicable technology. Elucidating and regulating the energy input effects on the structural dissociation and chemical depolymerization of lignocellulosic biomass will progress the industrialization of pure subcritical water autohydrolysis biorefineries. In this work, a method for determining the degree of tissue dissociation was invented. Combined with the analysis of the microstructure, ultrastructure, chemical composition, and aggregation state, this paper reveals the process and mechanism of the P-factor effect as an energy input measurement on the bio-structural dissociation and chemical depolymerization during naked oat stem autohydrolysis. A method of using the P-factor to regulate the biostructural dissociation and chemical depolymerization was developed. For the first time, a critical point for the autohydrolysis of naked oat stem in pure subcritical water between 170–210 °C was found to be at a P-factor = 233, around which an essential change in biostructural dissociation and chemical depolymerization occurred. The findings indicate that the control of naked oat-stem tissue and cell dissociation, ultrastructure, and chemical depolymerization can be accomplished using the P-factor as an energy input measurement for autohydrolysis. The revealed mechanism and method created in this study enable the stepwise separation of gramineae tissues, cells, and major chemical components, enabling a full-composition multi-purpose biorefinery of lignocellulose.
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Drug Design Development and Therapy
·
2022
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IF 4.319
Shurong Duan,Fei Wang,Jingwei Cao,Chunyan Wang
Introduction Intracerebral hemorrhage (ICH) is a devastating type of stroke with high mortality, and the effective therapies for ICH remain to be explored. Exosomes (Exos) have been found to play important roles in cell communication by transferring molecules, including microRNAs (miRNAs/miRs). MiRNAs are critical regulators of genes involved in many various biological processes and have been demonstrated to aggravate or alleviate brain damages induced by ICH. The aim of the present study was to investigate the effect of Exos derived from miR-146a-5p-enriched bone marrow mesenchymal stem cells (BMSCs-miR-146a-5p-Exos) on experimental ICH.Methods ICH was induced in adult male Sprague-Dawley rats by an intrastriatal injection of collagenase type IV. At 24 h after surgery, Exos were administrated. For detecting apoptotic cells, TUNEL staining was performed using an in situ Cell Death Detection Kit. Fluoro-Jade B staining was performed to detect degenerating neurons. Immunofluorescence assay was performed to detect the expression of myeloperoxidase (MPO) and OX-42. The binding of miR-146a-5p and its target genes was confirmed by luciferase reporter assay.Results At 24 h after surgery, BMSCs-miR-146a-5p-Exos administration significantly improved neurological function, reduced apoptotic and degenerative neurons, and inhibited inflammatory response. Furthermore, miR-146a-5p-enriched Exos obviously inhibited the M1 polarization of microglia after ICH in rats, accompanied by the reduced expression of pro-inflammatory mediators releasing by M1 microglia including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1). Finally, we observed that miR-146a-5p directly targeted interleukin-1 receptor-associated kinase1 (IRAK1) and nuclear factor of activated T cells 5 (NFAT5), which contributed to the inflammation response and the polarization of M1 microglia/macrophages.Conclusion We demonstrated that miR-146a-5p-riched BMSCs-Exos could offer neuroprotection and functional improvements after ICH through reducing neuronal apoptosis, and inflammation associated with the inhibition of microglial M1 polarization by downregulating the expression of IRAK1 and NFAT5.
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Regenerative Biomaterials
·
2022
·
IF 5.763
Li Jing,Yan Shunshun,Han Weiju,Dong Zixuan,Li Junliang,Wu Qi,Fu Xiaoling
Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) can deliver a variety of bioactive factors to create a favorable local microenvironment, thereby holding huge potential in chronic wound repair. However, free sEVs administrated intravenously or locally are usually cleared rapidly, resulting in an insufficient duration of the efficacy. Thus, strategies that enable optimized retention and release profiles of sEVs at wound sites are desirable. Herein, we fabricated novel functional phosphoethanolamine phospholipid-grafted poly-l-lactic acid micro/nanofibers (DSPE-PLLA) to carry and retain sEVs from rat adipose MSCs, enabling the slow local release of sEVs. Our results showed that sEVs@DSPE-PLLA promoted the proliferation, migration and gene expression (Col I, Col III, TGF-β, α-SMA, HIF-1α) of fibroblasts. It also promoted keratinocyte proliferation. In addition, sEVs@DSPE-PLLA helped polarize macrophages toward the M2 phenotype by increasing the expression of anti-inflammatory genes (Arginase 1, CD 206, IL-10) and inhibiting the expression of pro-inflammatory genes (IL-1β, TNF-α). Further in vivo study in diabetic rat models showed that sEVs@DSPE-PLLA improved the wound-healing process by alleviating the inflammatory responses, stimulating cell proliferation, collagen deposition and angiogenesis. These results highlight the potential of using DSPE-grafted scaffolds for extracellular vesicle immobilization and suggest sEVs@DSPE-PLLA micro/nanofibers as promising functional wound dressings for diabetic wounds.
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Biofabrication
·
2022
·Vol. 14
·期 4
·045006
·
IF 11.061
Jiahui Lai,Chong Wang,Jia Liu,Shangsi Chen,Chaoyu Liu,Xiangxuan Huang,Jing Wu,Yue Pan,Yuancai Xie,Min Wang
Compared to other conventional scaffold fabrication techniques, three-dimensional (3D) printing is advantageous in producing bone tissue engineering scaffolds with customized shape, tailored pore size/porosity, required mechanical properties and even desirable biomolecule delivery capability. However, for scaffolds with a large volume, it is highly difficult to get seeded cells to migrate to the central region of the scaffolds, resulting in an inhomogeneous cell distribution and therefore lowering the bone forming ability. To overcome this major obstacle, in this study, cell-laden bone tissue engineering scaffolds consisting of osteogenic peptide (OP) loaded β-tricalcium phosphate (TCP)/poly(lactic-co-glycolic acid) (PLGA) (OP/TCP/PLGA, designated as OTP) nanocomposite struts and rat bone marrow derived mesenchymal stem cell (rBMSC)-laden gelatin/GelMA hydrogel rods were produced through 'dual-nozzle' low temperature hybrid 3D printing. The cell-laden scaffolds exhibited a bi-phasic structure and had a mechanical modulus of about 19.6 MPa, which was similar to that of human cancellous bone. OP can be released from the hybrid scaffolds in a sustained manner and achieved a cumulative release level of about 78% after 24 d. rBMSCs encapsulated in the hydrogel rods exhibited a cell viability of about 87.4% right after low temperature hybrid 3D printing and could be released from the hydrogel rods to achieve cell anchorage on the surface of adjacent OTP struts. The OP released from OTP struts enhanced rBMSCs proliferation. Compared to rBMSC-laden hybrid scaffolds without OP incorporation, the rBMSC-laden hybrid scaffolds incorporated with OP significantly up-regulated osteogenic differentiation of rBMSCs by showing a higher level of alkaline phosphatase expression and calcium deposition. This 'proof-of-concept' study has provided a facile method to form cell-laden bone tissue engineering scaffolds with not only required mechanical strength, biomimetic structure and sustained biomolecule release profile but also excellent cell delivery capability with uniform cell distribution, which can improve the bone forming ability in the body.
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INDUSTRIAL CROPS AND PRODUCTS
·
2022
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IF 6.449
Jiahui Wei,Hao Ren,Huamin Zhai,Shengcheng Zhai
Green, efficient depolymerization of lignocellulose is a prerequisite and the key in high-value utilization of its components. Understanding of the changes in morphological chemistry of the cell wall, related to the biomass recalcitrance, is critical for optimizing the processing conditions of cell wall deconstruction. Thus, herein, based on our previous studies, subcritical water autohydrolysis of naked oat stems was conducted at 190 °C and 1.18 MPa for 0–60 min. The depolymerization behaviors of tissues and cell walls were monitored dynamically at 10 min intervals. The micro-and ultrastructural changes of autohydrolyzed residue sections were analyzed. Parenchyma tissue commenced dissociation after 10 min at 190 ℃, whereas mechanical tissue dissociation occurred after 40 min at 190 ℃, along with interlayer separation of the secondary walls of sclerenchyma fibers. The autofluorescence changes of lignin showed that the order of regional lignin removal in tissues was from sieve tubes and companion cells to parenchyma cells, and finally to sclerenchyma fibers and vessel elements. The turning point of tissue and cell wall structural depolymerization of naked oat stems under subcritical water autohydrolysis conditions occurred after 40 min at 190 ℃ and 1.18 MPa. Under this condition, the degree of tissue dissociation was as high as 80%, while the fiber cell morphology remained intact. Dynamic changes in the tissue and cell wall structures and cell morphologies of naked oat stems maintained at 190 ℃ for various durations were captured by differentiating the use of the optical microscope, fluorescence microscope , and scanning electron microscope . The extensive, detailed assay data yield novel insights into the dynamic depolymerization mechanism of lignocellulosic composite cell walls under subcritical water autohydrolysis conditions.
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Bioactive Materials
·
2023
·
IF 18.9
Yuanyuan Jin,Jiabin Zhang,Yanteng Xu,Ke Yi,Fenfang Li,Huicong Zhou,Haixia Wang,Hon Fai Chan,Yeh-Hsing Lao,Shixian Lv,Yu Tao,Mingqiang Li
Reactive oxygen species (ROS)-associated oxidative stress, inflammation storm, and massive hepatocyte necrosis are the typical manifestations of acute liver failure (ALF), therefore specific therapeutic interventions are essential for the devastating disease. Here, we developed a platform consisting of versatile biomimetic copper oxide nanozymes (Cu NZs)-loaded PLGA nanofibers (Cu [email protected] nanofibers) and decellularized extracellular matrix (dECM) hydrogels for delivery of human adipose-derived mesenchymal stem/stromal cells-derived hepatocyte-like cells (hADMSCs-derived HLCs) (HLCs/Cu [email protected] /dECM). Cu [email protected] nanofibers could conspicuously scavenge excessive ROS at the early stage of ALF, and reduce the massive accumulation of pro-inflammatory cytokines, herein efficiently preventing the deterioration of hepatocytes necrosis. Moreover, Cu [email protected] nanofibers also exhibited a cytoprotection effect on the transplanted HLCs. Meanwhile, HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF therapy. The dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of HLCs. In addition, the pro-angiogenesis activity of Cu [email protected] nanofibers also facilitated the integration of the whole implant with the host liver. Hence, HLCs/Cu [email protected] /dECM performed excellent synergistic therapeutic efficacy on ALF mice. This strategy using Cu [email protected] nanofiber-reinforced dECM hydrogels for HLCs in situ delivery is a promising approach for ALF therapy and shows great potential for clinical translation.
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Scientific Reports
·
2026
·
IF 4.9
Yi Tingting,Xu Mei,Wang Lihua,Wang Pengwei
Recently, mesenchymal stem cells (MSCs), valued for their multipotent properties, have attracted significant attention in disease therapy. Transforming growth factor-β1(TGF-β1), a cytokine involved in regulating cellular stress responses, is closely associated with neurological function and the differentiation of MSCs. The primary purpose of this research was to assess the neuroprotective capacity of exosomes from TGF-β1-pretreated human umbilical cord mesenchymal stem cells (hUCMSCs) on neuronal injury in epilepsy. In this study, we established epileptic models using male C57BL/6 mice and hippocampal Neurons. Exosomes from TGF-β1- pretreated hUCMSCs were characterized via transmission electron microscopy (TEM) combined with nanoparticle tracking analysis (NTA) and were then applied as a therapeutic intervention. Our research demonstrated that TGF-β1 upregulated the level of the long non-coding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) in hUCMSC-derived exosomes. Exosomes from TGF-β1-pretreated hUCMSCs enhanced neuronal viability, inhibited apoptosis, and reduced inflammation and oxidative stress levels, whereas UCA1 knockdown reversed these beneficial effects. Furthermore, lncRNA UCA1 directly binds to miR-132. Knockdown of UCA1 upregulated miR-132 levels and downregulated SIRT1 expression; this downregulation could be rescued by inhibiting miR-132. In vivo, we further observed that exosomes from TGF-β1-pretreated hUCMSCs alleviated neuronal damage in the hippocampal CA3 region, inhibited glial activation, and suppressed the increase of related inflammatory factors. In contrast, UCA1 knockdown produced the opposite effects. The in vivo findings paralleled the results of the in vitro cell experiments. In conclusion, these results demonstrated that exosomes from TGF-β1-pretreated hUCMSCs exert anti-epileptic effects by modulating the lncRNA UCA1 / miR-132 / SIRT1 axis.
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FISH & SHELLFISH IMMUNOLOGY
·
2023
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IF 4.7
Fei Sun,Yingbo Wu,Yuanxing Zhang,Qin Liu,Qiyao Wang,Xiaohong Liu
Large yellow croaker ( Larimichthys crocea ) farm industry in China suffered from huge economic loss caused by Pseudomonas plecoglossicida infection. Due to multi-antibiotic resistance, efficient vaccines are urgent to be developed to combat this pathogen. In this study, an inactivated vaccine was developed with an aluminium adjuvant (Alum) plus ginseng stem and leaf saponins (GSLS). As a result, the relative percentage survival (RPS) against P. plecoglossicida was up to 67.8 %. Comparatively, RPS of groups that vaccinated with only inactivated vaccine and vaccine containing Alum or Montanide™ 763A as adjuvant were 21.8 %, 32.2 % and 62.1 %, respectively. Assays for total serum protein and serum lysozyme activity in group vaccinated with inactivated vaccine plus Alum + GSLS adjuvant were significantly higher than that in control group. Moreover, specific antibody in serum elicited a rapid and persistent level. According to the expression of some immune related genes , inactivated vaccine plus Alum + GSLS adjuvant induced a stronger cellular immune response which was vital to defend against P. plecoglossicida . In conclusion, our study demonstrated that the compound Alum and GSLS adjuvant is a potential adjuvant system to develop LYC vaccine.
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Small
·
2020
·Vol. 16
·期 52
·2004879
·
IF 11.459
Liang Zhao,Yingli Luo,Qiaoyi Huang,Ziyang Cao,Xianzhu Yang
Blocking immune checkpoint pathways with an antibody or small interfering RNA (siRNA) has become a promising method to reactivate antitumor responses for cancer treatment. However, both blockade strategies achieve only temporary inhibition of these immune checkpoints. Herein, a photoswitched CRISPR/Cas9 system for genomic disruption of the PD-L1 gene is developed to achieve permanent blockade of the PD-1/PD-L1 pathway; this system is constructed by using a photoactivated self-degradable polyethyleneimine derivative and the plasmid pX330/sgPD-L1 (expression of the Cas9 protein and single-guide RNA targeting PD-L1). Under light irradiation, this photoswitched CRISPR/Cas9 system efficiently genetically disrupts the PD-L1 gene in not only bulk cancer cells but also cancer stem-like cells. As a result, the photoswitched CRISPR/Cas9 system significantly increases the infiltration of CD8 + T cells into tumor tissue, leading to effective activation of a T cell-mediated antitumor response against cancer cells and cancer stem-like cells. This study provides an alternative strategy to block the PD-1/PD-L1 pathway for efficacious immune checkpoint therapy.
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Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-11
·
IF 5.116
Liao Naishun,Shi Yingjun,Wang Yingchao,Liao Fangyu,Zhao Bixing,Zheng Youshi,Zeng Yongyi,Liu Xiaolong,Liu Jingfeng
Background Although it has been preclinically suggested that adipose tissue-derived mesenchymal stem cell (ADSC)-based therapy could effectively treat chronic liver diseases, the hepatic engraftment of ADSCs is still extremely low, which severely limits their long-term efficacy for chronic liver diseases. This study was designed to investigate the impact of antioxidant preconditioning on hepatic engraftment efficiency and therapeutic outcomes of ADSC transplantation in liver fibrotic mice.Methods Liver fibrosis model was established by using intraperitoneal injection of carbon tetrachloride (CCl4) in the male C57BL/6 mice. Subsequently, the ADSCs with or without antioxidant pretreatment (including melatonin and reduced glutathione (GSH)) were administrated into fibrotic mice via tail vein injection. Afterwards, the ADSC transplantation efficiency was analyzed by ex vivo imaging, and the liver functions were assessed by biochemical analysis and histopathological examination, respectively. Additionally, a typical hydrogen peroxide (H2O2)-induced cell injury model was applied to mimic the cell oxidative injury to further investigate the protective effects of antioxidant preconditioning on cell migration, proliferation, and apoptosis of ADSCs.Results Our data showed that antioxidant preconditioning could enhance the therapeutic effects of ADSCs on liver function recovery by reducing the level of AST, ALT, and TBIL, as well as the content of hepatic hydroxyproline and fibrotic area in liver tissues. Particularly, we also found that antioxidant preconditioning could enhance hepatic engraftment efficiency of ADSCs in liver fibrosis model through inhibiting oxidative injury.Conclusion sAntioxidant preconditioning could effectively improve therapeutic effects of ADSC transplantation for liver fibrosis through enhancing intrahepatic engraftment efficiency by reducing oxidative injuries. These findings might provide a practical strategy for enhancing ADSC transplantation and therapeutic efficiency.
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