INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Lanxi Xu,Yan Feng,Xintian Zheng,Meiyu Wang,Yan Fang,Lin Li,Jiadong Xu,Yani Zhang,Weiru Jiang,Lisheng Chu
Neuronal loss following ischemic stroke (IS) is a major cause of long-term neurological dysfunction. Neural stem cell (NSC) transplantation holds great potential for neural tissue repair, but exogenous NSCs often over-differentiate into astrocytes, resulting in glial scar formation and poor neuronal maturation, which limits clinical application. Astragaloside IV (AS-IV), a plant-derived monomer, has been shown to regulate the proliferation, migration, and differentiation of endogenous NSCs. This study investigated whether AS-IV preconditioning could promote the neurogenesis of transplanted NSCs and improve functional recovery after IS. Primary NSCs were cultured and exposed to various concentrations of AS-IV, and 100 μM was selected for further use. A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established, and AS-IV-preconditioned or untreated EGFP-labeled NSCs were transplanted into the striatum. Brain injury was assessed histologically. Neurological recovery was evaluated using the modified Neurological Severity Score, grip strength, adhesive removal, and Morris water maze tests. Immunofluorescence staining was used to assess graft survival, differentiation fate, synapse formation, and glial scar area. In vitro experiments explored the involvement of the miR-199a-5p/Caveolin-1 signaling pathway. AS-IV preconditioning significantly improved the survival and neuronal differentiation of grafted NSCs, reduced astrocytic lineage commitment and glial scar formation, and enhanced synaptic reconstruction. These effects were associated with improved sensorimotor and cognitive function. In conclusion, AS-IV pretreatment of NSCs promoted neuronal lineage commitment, inhibited glial scarring, and facilitated functional recovery after ischemic stroke. Targeting the miR-199a-5p/Caveolin-1 axis may offer a novel strategy for optimizing NSC-based therapy in stroke.
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LWT-FOOD SCIENCE AND TECHNOLOGY
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2022
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IF 6.056
Lu Liang,Yuchen Liu,Yuxin Liu,Siyi Gan,Xuejin Mao,Yuanxing Wang
The herbal tea made from the leaves and stems of Cyclocarya paliurus is thought to be more flavorful than those made from the leaves only. However, evidence supporting this view is not available yet. 53 VOCs and 54 non-VOCs were identified via HS-SPME-GC-MS and UPLC-Q-TOF/MS, respectively, which were found to vary dramatically in three groups of samples (combination of stems and leaves, separated leaves, and separated stems). 11 VOCs and 18 non-VOCs potential markers are responsible for the change of metabolic effects through the biosynthesis of flavonoids, the synthesis of terpenoids, and the oxidation of fatty acids and carotenoids. In response, the stems were effective to enhance fatty odors, the initial astringency and bitterness and the aftertaste of sweetness of the leaves. Stems are conducive to increasing total phenolic content, total flavonoid content and antioxidant capacity of Cyclocarya paliurus herbal extract because of the increase in polyphenols. In addition, the stems have the potential to be used as raw materials for nerolidol and polyphenols extraction. This study has been the first to determine the contribution of stem to the flavor of Cyclocarya paliurus herbal tea and these results provide the theoretical basis for making Cyclocarya paliurus herbal tea with stems.
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NEUROREPORT
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2025
·Vol. 36
·期 16
·988
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IF 1.7
Zhong Zhihong,Xu Canxin,Chen Xiao,Lin Dong,Bian Liuguan
Plain Language Summary Background Intracerebral hemorrhage (ICH) induces secondary brain injury, driven in part by oxidative stress caused by hemin, a toxic hemoglobin breakdown product. Cortical astrocytes, critical for maintaining redox homeostasis, are vulnerable to hemin-induced oxidative damage, exacerbating neuronal injury. Induced pluripotent stem cell–derived neural progenitor cells (iPSC-NPCs) have shown therapeutic potential in brain injury models by promoting neural repair, but their ability to protect astrocytes against hemin toxicity remains unexplored. We hypothesized that iPSC-NPCs coculture mitigates hemin-induced oxidative stress in astrocytes by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathway. Materials and methods Astrocytes were exposed to hemin with or without iPSC-NPC coculture. We assessed cell viability, reactive oxygen species (ROS) accumulation, apoptosis, and the role of the Nrf2/HO-1 pathway using small-interfering RNA. Results iPSC-NPC coculture significantly reduced hemin-induced oxidative damage by promoting Nrf2 nuclear translocation and upregulating HO-1, thereby decreasing ROS and apoptosis. Silencing Nrf2 abolished these protective effects. Conclusion Our findings demonstrate that iPSC-NPCs protect astrocytes from hemin toxicity via the Nrf2/HO-1 pathway, suggesting a novel therapeutic strategy for ICH-induced oxidative injury. Plain Language Summary Intracerebral hemorrhage (ICH) can cause brain damage due to oxidative stress from hemin, a toxic breakdown product of hemoglobin. This study explored whether induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) can protect astrocytes, which are crucial for brain health, from hemin-induced damage. Researchers found that when astrocytes were cocultured with iPSC-NPCs, oxidative stress and cell death were reduced. This protective effect was linked to the activation of the Nrf2/HO-1 antioxidant pathway. Silencing Nrf2 negated the benefits, highlighting the pathway's importance. These findings suggest iPSC-NPCs could be a promising treatment for oxidative injury in ICH. Text is machine generated and may contain inaccuracies. FAQ
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ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2022
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IF 3.511
Qinghui Han,Shuguang Wang,Dawei Chen,Di Gan,Tao Wang
Tendon injuries are common clinical issues resulted from tissue overuse and age-related degeneration. Previous sutdies have suggested that exosomes secreted by mesenchymal stem cells (MSCs) contribute to tissue injury repair. Here, we provide evidence for a critical role of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes in reducing tendon injury by activating the RhoA signaling. Treatment of primary injured tenocytes with hucMSC exosomes increases cell proliferation and invasion, which correlates with increased RhoA activity. RhoA mediates the effects of hucMSC exosomes, as treatment of primary injured tenocytes with the RhoA inhibitor, CCG-1423, abolishes the effects of hucMSC exosomes on cell proliferation and invasion. Mechanistically, we observe that hucMSC exosomes induce the expression of a microRNA, miR-27b-3p, which targets and suppresses ARHGAP5, a negative regulator of RhoA. Consistent with this observation, ARHGAP5 overexpression suppresses the effects of hucMSC exosomes on cell proliferation and invasion, while knockdown of ARHGAP5 rescues these effects. Finally, we demonstrate the functional significance of our findings in vivo using an Achilles tendon injury model and show that treatment with exosomes reduces tendon injury in rats, which correlates with increased RhoA activity and reduced ARHGAP5 expression. Taken together, our findings highlight a critical role of hucMSC exosomes in reducing tendon injury via miR-27b-3p-mediated suppression of ARHGAP5, resulting in RhoA activation, and leading to increased cell proliferation and invasion of primary injured tenocytes.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
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IF 5.2
Yunpeng Li,Fengzhen Cui,Huanwen Tang
Evaluating endocrine-disrupting chemicals (EDCs) risk such as mono-butyl phthalate (MBP) and bisphenol A (BPA) raises a pressing question: can doses deemed safe for each individual exposure become hazardous in combination? This study aimed to determine whether environmentally relevant concentrations of MBP and BPA exert synergistic neurotoxicity and to elucidate the underlying molecular mechanisms using an integrated multi-omics approach. Exposure concentrations (20 nM each) were derived from epidemiological biomonitoring data. Primary neural stem cells (NSCs) were used to detect CCK-8, reactive oxygen species (ROS), and apoptosis Synergy was evaluated using the Bliss independence model and two-way ANOVA. Transcriptomic (RNA-seq) and untargeted metabolomic (LC–MS) profiling were performed, followed by integrative pathway analysis. Three-dimensional (3D) brain organoids were used to validate the main findings. Co-exposure to MBP and BPA at equimolar concentrations synergistically reduced cell proliferation (BlissΔ >0, E _Observed = 0.371 vs. E _Bliss = 0.163) and synergistically elevated intracellular ROS (interaction index = 2.21, p = 0.0066; two-way ANOVA interaction p = 0.033). Transcriptomic and metabolomic analyses converged on glutathione metabolism as the most significantly dysregulated pathway in the co-exposure group. Integrated multi-omics analysis revealed ferroptosis may serve as the primary mode of synergistic cell death. Three-dimensional brain organoids confirmed the ferroptosis signature, with significantly decreased GPX4 and SLC7A11 protein expression and concomitantly increased ACSL4 in the co-exposure group. In summary, MBP and BPA co-exposure at human-relevant doses synergistically induces neurotoxicity in NSCs through glutathione metabolism disruption and subsequent ferroptosis. These findings underscore the importance of evaluating chemical mixtures rather than individual compounds in neurodevelopmental risk assessment.
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Small
·
2019
·Vol. 15
·期 51
·1905001
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IF 10.856
Min Hao,Jianlong He,Chunhua Wang,Chao Wang,Baojin Ma,Shan Zhang,Jiazhi Duan,Feng Liu,Yu Zhang,Lin Han,Hong Liu,Yuanhua Sang
The fate of stem cells at the single cell level with limited communication with other cells is still unknown due to the lack of an efficient tool for highly accurate molecular detection. Moreover, the conditional sensitivity of biological experiments requires a sufficient number of parallel experiments to support a conclusion. In this work, a microfluidic single cell chip is designed for use with a protein chip to investigate the effect of hydroxyapatite (HAp) on the osteogenic differentiation of human adipose-derived stem cells (hADSCs) in situ at the single cell level. By successfully detecting secretory proteins in situ, it is found that the HAp nanorods enhance osteogenic differentiation at the single cell level. In the chip, the single cell seeding approach confirms the osteogenic differentiation of the hADSCs, which endocytoses HAp, by reducing the influence of the factors secreted by neighboring differentiating cells. Most importantly, more than 7000 microchambers provide a sufficient number of parallel experiments for statistical analysis, which ensure a high level of repeatability of the HAp nanorod-induced osteogenic differentiation. The microfluidic chip comprising single cell culture microchambers with in situ detection capability is a promising tool for research on cell behavior or cell fate at the single cell level.
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JOURNAL OF NANOBIOTECHNOLOGY
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2024
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IF 10.6
Lu Liu,Nan Zhou,Songning Fu,Linlin Wang,Yadong Liu,Changfeng Fu,Feng Xu,Weiying Guo,Yanhua Wu,Jin Cheng,Jun Dai,Yipeng Wang,Xiaofeng Wang,Qiwei Yang,Yuanyi Wang
The close spatial and temporal connection between osteogenesis and angiogenesis around type H vasculature is referred as “osteogenesis-angiogenesis coupling”, which is one of the basic mechanisms of osteogenesis. Endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and their specific lineage constitute important cluster that participate in the regulation of osteogenesis and angiogenesis in bone microenvironment. However, the regulatory mechanism of osteogenesis-angiogenesis coupling under the condition of bone healing has not been unveiled. In this study, we demonstrated that the exosome derived from ECs (EC-exo) is an initiator of type H blood vessels formation, and EC-exo acts as a mediator in orchestrating osteogenesis-angiogenesis coupling by enhancing BMSC osteogenic differentiation and EC angiogenesis both in monolayer and stereoscopic co-culture system of primary human cells. The transcriptome array indicated that zinc finger and BTB domain containing 16 ( ZBTB16 ) is a key gene in EC-exo-mediated osteogenesis, and ZBTB16 is indispensable in EC-exo-initiated osteogenesis-angiogenesis coupling. Mechanistically, EC-exo up-regulated the expression of ZBTB16 in BMSCs, thereby promoting osteoprogenitor phenotype transformation; the osteoprogenitors further promote ECs which constitute type H vessel (H-ECs) generation by activating HIF-1α pathway; and the H-ECs conversely promotes osteogenic differentiation of BMSCs. The crosstalk between BMSCs and ECs triggered by EC-exo constitutes a positive feedback loop that enhances osteogenesis-angiogenesis coupling. This study demonstrates that EC-exo can become an effective therapeutic tool to promote bone regeneration and repair. Graphical
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Biomaterials Science
·
2021
·Vol. 9
·期 8
·3005-3018
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IF 6.843
Chengqiang Wang,Haixia Xu,Chun Liu,Ziyue Peng,Ruoxing Min,Zhiming Zhang,Jianjun Li,Yanglei Jin,Yihan Wang,Zhihao Li,Jiasong Guo,Lixin Zhu
The osteonecrosis of femoral head (ONFH), a common refractory disease, is still not fully understood today. Hypoxia caused by ischemia is not only an important pathogenic factor but also a critical challenge for the survival of seed cells in the tissue engineering therapy of ONFH. To explore an efficient strategy to treat ONFH by targeting hypoxia, newly designed CaO2/gelatin microspheres were composited with 3D printed polycaprolactone/nano-hydroxyapatite (PCL/nHA) porous scaffold, sodium alginate/gelatin hydrogel, and bone marrow mesenchymal stem cells (BMSCs) to develop a novel tissue engineering scaffold and then transplanted into the core depression area of the ONFH rabbit model. The current data demonstrated that CaO2/gelatin microspheres can constantly release oxygen for 19 days. In vitro assays with BMSCs illustrated that scaffolds have high biocompatibility and are favorable for cell proliferation in extreme hypoxia (1% O2). The in vivo study demonstrated that the transplanted scaffold with oxygen-generating microspheres significantly enhanced the osteogenic and angiogenic effects compared to the scaffold without microspheres. Further assessments revealed that microspheres in the scaffold can reduce the local cell apoptosis and enhance the survival of grafted cells in the host. Collectively, the present study developed a novel oxygen slow-releasing composite scaffold, which can facilitate tissue engineering efficiency for treating the osteonecrosis of the femoral head by enhancing the angiogenesis and survival of grafted stem cells.
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Advanced Healthcare Materials
·
2022
·Vol. 11
·期 15
·2200386
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IF 11.092
Jile Xie,Jiaying Li,Jinjin Ma,Meimei Li,Xingran Wang,Xinya Fu,Yanxia Ma,Huilin Yang,Bin Li,Saijilafu
Because of the limited regenerative ability of the central nervous system (CNS), effective treatments for spinal cord injury (SCI) are still lacking. After SCI, neuron loss and axon regeneration failure often result in irreversible functional impairment. The calcium overload induced by the N-methyl-D-aspartate receptor (NMDAR) overactivation is critical for cell death in SCI. It has been reported that the magnesium ion (Mg 2+ ) can competitively block the NMDAR and reduce the calcium influx, and that sonic hedgehog (Shh) and retinoic acid (RA) are the critical regulators of neuronal differentiation of endogenous neural stem cells (NSCs). Here, magnesium oxide (MgO)/poly ( l -lactide-co- ε -caprolactone) (PLCL) scaffold loaded with purmorphamine (PUR, a Shh signaling agonist) and RA is developed and its feasibility in SCI repair is tested. The results showed that the Mg 2+ released from MgO attenuated cell apoptosis by blocking the calcium influx, and the PUR/RA promoted the recruitment and neuronal differentiation of endogenous NSCs, thereby reducing the glial scar formation at the SCI lesion site. Furthermore, implantation of PUR/RA-loaded MgO/PLCL scaffold facilitates the partial recovery of a locomotor function of SCI mouse in vivo. Together, findings from this study imply that PUR/RA-loaded MgO/PLCL scaffold may be a promising biomaterial for the clinical treatment of SCI.
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International Wound Journal
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2022
·Vol. 19
·期 5
·1023-1038
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IF 3.099
Dong Zheng,Tong Chen,Long Han,Songwei Lv,Jianjian Yin,Kaiyuan Yang,Yuji Wang,Nanwei Xu
The cartilage repair and regeneration show inadequate self-healing capability and have some complications, which are inordinate challenges in clinical therapy. Biopolymeric injectable hydrogels, a prominent type of cell-carrier as well tissue engineering scaffolding materials, establish promising therapeutic potential of stem cell-based cartilage-regeneration treatment. In addition, injectable scaffolding biomaterial should have rapid gelation properties with adequate rheological and mechanical properties. In the present investigation, we developed and fabricated the macromolecular silk fibroin blended with polylysine modified chitosan polymer (SF/PCS) using thermal-sensitive glycerophosphate (GP), which contains effective gelation ability, morphology, porosity and also has enhanced mechanical properties to induce physical applicability, cell proliferation and nutrient exchange in the cell-based treatment. The developed and optimised injectable hydrogel group has good biocompatibility with human fibroblast (L929) cells and bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, it was found that SF/PCS hydrogel group could sustainably release TGF-β1 and efficiently regulate cartilage-specific and inflammatory-related gene expressions. Finally, the cartilage-regeneration potential of the hydrogel groups embedded with and without BMSCs were evaluated in SD rat models under histopathological analysis, which showed promising cartilage repair. Overall, we conclude that the TGF-β1-SF/PCS injectable hydrogel demonstrates enhanced in vitro and in vivo tissue regeneration properties, which lead to efficacious therapeutic potential in cartilage regeneration.
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JOURNAL OF SEPARATION SCIENCE
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2023
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IF 3.1
Wei-Qi Yang,Qi Huang,Meng-Qi Wu,Quan-Xi Mei,Yuan-Sheng Zou,Zheng-Ming Qian,Dan Tang
To reveal the utilization value of leaf, stem, and root of Artemisia argyi , a rapid online liquid microextraction combined with a high-performance liquid chromatography coupled with 2,2-nitrogen-di (3-ethyl-benzothiazole-6-sulfonic acid) diammonium salt antioxidant assay system was established for analysis of antioxidants in the leaf, stem, and root of A. argyi , and a calibration quantitative method of antioxidant activity with equivalent chlorogenic acid was proposed. Thirty-three positive peaks were identified; among them, 12 compounds were found that possess good antioxidant activity including eleven organic acids (components 2–4, 8, 11–14, 17, 19, and 21) and one flavonoids (component 22). The proposed calibration quantitative method avoided the influence of content of compound and compared the extent of radical scavenging capacity of five antioxidant compounds, which were ranked as follow: 3,5-dicaffeoylquinic acid > 3,4-dicaffeoylquinic acid ≈ 4,5-dicaffeoylquinic acid > 1,4-dicaffeoylquinic acid > chlorogenic acid. In conclusion, this study provided composition and biological potential for the future development of the leaf, stem, and root of A. argyi . It is believed that the online liquid microextraction combined with high-performance liquid chromatography based antioxidant assay system can be widely used for the rapid screening of natural antioxidant components in the different parts of natural products.
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Journal of Biomaterials and Tissue Engineering
·
2019
·Vol. 9
·期 12
·1635-1643
·
IF 0.824
Feng Song,Liu Jingming,Ramalingam Murugan
The main aim of this study was to develop a 3D printed stem cell-responsive polyethylene glycol diacrylate (PEGDA) and sodium alginate (SA) composite hydrogel system (PEGDA/SA) loaded with basic fibroblast growth factor (bFGF) suitable for dental pulp tissue engineering. The PEGDA/SA
loaded with bFGF (PEGDA/SA-bFGF) at different concentration ratios were 3D printed via stereolithography (SLA) under optimal processing conditions, followed by ionic crosslinking. The morphological and porous structure of the 3D printed PEGDA/SA-bFGF constructs and release profile of the bFGF
were analyzed. The cellular compatibility of the hydrogel constructs was evaluated using human dental pulp stem cells (hDPSCs)in vitro. Subsequently, biocompatibility and tissue regenerative potential of the hydrogel constructs were evaluated in immunodeficient mice model. The in
vitro cell culture results of PEGDA/SA-bFGF constructs exhibited high cell compatibility and supported cell proliferation, irrespective of their concentration ratios. Thein vivo animal experiment results showed that the hDPSCs-laden PEGDA/SA (PEGDA/SA-hDPSCs) group failed to form
a good pulp structure even at various concentration ratios. When the mass ratio of PEGDA/SA was 25:1, hDPSCs-laden PEGDA/SA-bFGF (PEGDA/SA-bFGF-hDPSCs) group also failed to form dental pulp-like tissue but a partial loose connective tissue formation was observed. However, when the mass ratio
of PEGDA/SA reduces to 20:1 ~ 15:1, the PEGDA/SA-bFGF-hDPSCs group tends to form a well-organized pulp structure post 4 weeks implantation, thus highlighting the potential of this particular hydrogel scaffolding system for dental pulp tissue regenerative applications.
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