Pharmaceutics
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2020
·Vol. 12
·期 7
·613
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IF 4.421
Qing Min,Jiaoyan Liu,Yuchen Zhang,Bin Yang,Ying Wan,Jiliang Wu
Alginate-poloxamer (ALG-POL) copolymer with optimal POL content was synthesized, and it was combined with silk fibroin (SF) for building ALG-POL/SF dual network hydrogels. Hyaluronic acid(HA)/chitosan-poly(dioxanone)(CH-PDO) complex nanoparticles (NPs) with optimized composition and high encapsulation efficiency were employed as a vehicle for loading bone morphogenic protein-7 (BMP-7). BMP-7-loaded HA/CH-PDO NPs were incorporated into ALG-POL/SF hydrogel for constructing composite gels to achieve controlled release of BMP-7. These gels showed thermosensitive sol-gel transitions near physiological temperature and pH; and they were tested to be elastic, tough and strong. Some gels exhibited abilities to administer the BMP-7 release in nearly linear manners for a few weeks. Synovium-derived mesenchymal stem cells (SMSCs) were seeded into optimally fabricated gels for assessing their chondrogenic differentiation potency. Real-time PCR analyses showed that the blank ALG-POL/SF gels were not able to induce the chondrogenic differentiation of SMSCs, whereas SMSCs were detected to significantly express cartilage-related genes once they were seeded in the BMP-7-loaded ALG-POL/SF gel for two weeks. The synthesis of cartilaginous matrix components further confirmed that SMSCs seeded in the BMP-7-loaded ALG-POL/SF gel differentiated toward chondrogenesis. Results suggest that BMP-7-loaded ALG-POL/SF composite gels can function as a promising biomaterial for cartilage tissue engineering applications.Keywords:dual network hydrogel;complex nanoparticles;bone morphogenic protein-7;chondrogenic differentiation;synovium-derived mesenchymal stem cells
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2019
·
IF 4.527
Shaojun Liang,Shengxian Liang,Hui Zhou,Nuoya Yin,Francesco Faiola
2′,2′,4,4′-tetrabromo diphenyl ether (BDE-47), one of the most abundant congeners of commercial pentaBDE utilized as flame retardants , has been phased out of production due to its potential neural toxicity and endocrine disrupting activities, and yet still present in the environment. Several alternatives to BDE-47, including tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), tetrachlorobisphenol A (TCBPA) and decabromodiphenyl ether (BDE-209), are presently employed without restrictions and their potential toxic effects on human neural development are still unclear. In this study, we utilized a human neural stem cell (hNSC)-based system to evaluate the potential developmental neurotoxic effects of the above-mentioned five chemicals, at environment and human exposure relevant concentrations. We found that those compounds slightly altered the expression of hNSC identity markers ( SOX2 , SOX3 and NES ), without impairing cell viability or proliferation, in part by either modulating glycogen synthase kinase 3 beta (GSK3β) signaling (TBBPS, TCBPA and BDE-47), and slightly disturbing the NOTCH pathway (TBBPA, TBBPS and TCBPA). Moreover, the five chemicals seemed to alter hNSC differentiation by perturbing triiodothyronine (T3) cellular signaling. Thus, our findings suggest that the five compounds, especially TBBPS, TCBPA, and BDE-47, may affect hNSC self-renewal and differentiation abilities and potentially elicit neural developmental toxicity.
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Frontiers in Pharmacology
·
2024
·
IF 4.4
Rao Jian,Xie Haishu,Liang Zeyan,Yang Zhelun,Chen Pingping,Zhou Maochao,Xu Xiongjie,Lin Yike,Lin Fabin,Wang Rui,Wang Chunhua,Chen Chunmei
Background: Oxidative stress and apoptosis of neurons significantly contribute to the pathophysiological cascade of spinal cord injury (SCI). However, the role of hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles (H-sEVs) in promoting SCI repair remains unclear. Hence, the present study aims to investigate the regulatory effects of H-sEVs on neuronal oxidative stress and apoptotic responses following SCI.Methods: The administration of H-sEVs of SCI rats was assessed using behavioral evaluations such as Basso-Beattie-Bresnahan (BBB) scores, neuroelectrophysiological monitoring, and Catwalk gait analysis. Indices of oxidative stress (including superoxide dismutase [SOD], total antioxidant capacity [T-AOC], and malondialdehyde [MDA]) were measured. Neuronal survival was evaluated through Nissl staining, while the expression level of sirtuin 1 (SIRT1) was examined using immunohistochemical staining. Additionally, histological evaluation of lesion size was performed using hematoxylin-eosin (HE) staining. Tunel cell apoptosis staining and analysis of apoptosis-associated proteins (B-cell lymphoma-2 [Bcl2] and BCL2-Associated X [Bax]) were conducted through immunofluorescence staining and western blot, respectively. Furthermore, the model of oxidative stress was established using PC12 cells, and apoptosis levels were assessed via flow cytometry and western blot analysis. Importantly, to ascertain the critical role of SIRT1, we performed SIRT1 knockout experiments in PC12 cells using lentivirus transfection, followed by western blot.Results: Using those behavioral evaluations, we observed significant functional improvement after H-sEVs treatment. Nissl staining revealed that H-sEVs treatment promoted neuronal survival. Moreover, we found that H-sEVs effectively reduced oxidative stress levels after SCI. HE staining demonstrated that H-sEVs could reduce lesion area. Immunohistochemical analysis revealed that H-sEVs enhanced SIRT1 expression. Furthermore, Tunel cell apoptosis staining and western blot analysis of apoptosis-related proteins confirmed the anti-apoptotic effects of H-sEVs. The PC12 cells were used to further substantiate the neuroprotective properties of H-sEVs by significantly inhibiting neuronal death and attenuating oxidative stress. Remarkably, SIRT1 knockout in PC12 cells reversed the antioxidant stress effects induced by H-sEVs treatment. Additionally, we elucidated the involvement of the downstream Nrf2/HO-1 signaling pathway.Conclusion: Our study provides valuable insights into the effects of H-sEVs on neuronal oxidative stress and apoptosis after SCI. These findings underscore the potential clinical significance of H-sEVs-based therapies for SCI.
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Applied Biological Chemistry
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2024
·Vol. 67
·期 1
·1-17
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IF 2.3
Xue Jun,Gao Yu Ping
Acute myocardial infarction (AMI) has been treated via injectable hydrogels and biomaterial patches invented using tissue engineering advancements over the past decade. Yet the curative potential of injectable hydrogels and stem cells is limited. Here, we propose the development of an injectable and conductive hydrogel composed of oxidised macromolecular hyaluronic acid and chitosan-grafted aniline tetramer polymeric components. In an attempt to enhance the therapeutic potential of AMI therapy, mesenchymal stem cells derived from human umbilical cord blood (HUCB-MSC) have been integrated into the formulation of a conductive hydrogel. For reliable connection to the beating hearts, the hydrogel exhibited suitable adhesive properties. Hydrogel’s potent biocompatibility was determined by in vitro investigations of cell viability and proliferation of NRCMs and H9C2 cardiomyocytes. After myocardial injection, longer HUCB-MSCs survival length, cardiac functioning, and histology in SD rat myocardium were demonstrated, greatly associated by up-regulation and downregulation of cardiac-related relative gene expressions of angiogenic factors and inflammatory factors, respectively. The injectable hydrogel that contained HUCB-MSCs substantially enhanced the therapeutic benefits, indicating a potentially beneficial therapeutic approach to AMI therapy.
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BIOCHEMICAL PHARMACOLOGY
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2024
·
IF 5.3
Jin Wu,Xiang Li,Hepeng Nie,Yue Shen,Zixiang Guo,Catherine Huihan Chu,Kunzhan Cai,Chunbo Tang
Diabetes-related hyperglycemia inhibits bone marrow mesenchymal stem cell (BMSC) function, thereby disrupting osteoblast capacity and bone regeneration. Dietary supplementation with phytic acid (PA), a natural inositol phosphate, has shown promise in preventing osteoporosis and diabetes-related complications. Emerging evidence has suggested that circular (circ)RNAs implicate in the regulation of bone diseases, but their specific regulatory roles in BMSC osteogenesis in hyperglycemic environments remain elucidated. In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis . In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and triggered osteogenesis enhancement in BMSCs by targeting FOXO1 directly. Furthermore, circEIF4B inhibited the ubiquitin-mediated degradation of IGF2BP3, thereby stabilizing ITGA5 mRNA and promoting BMSC osteogenic differentiation. In vivo experiments, circEIF4B inhibition attenuated the effectiveness of PA treatment in diabetic rats with cranial defects. Collectively, our study identifies PA as a novel positive regulator of BMSC osteogenic differentiation through the circEIF4B/miR-186-5p/FOXO1 and circEIF4B/IGF2BP3/ITGA5 axes, which offers a new strategy for treating high glucose-mediated BMSC osteogenic dysfunction and delayed bone regeneration in diabetes.
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Materials Today Bio
·
2025
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IF 10.2
Xiaofei Zhang,Linzi Ma,Xiaotong Liu,Xingyu Zhou,Ao Wang,Yunhui Lai,Jun Zhang,Ying Li,Shiling Chen
Background Premature ovarian insufficiency (POI) refers to the severe decline or failure of ovarian function in women younger than 40 years of age. It is a serious hazard to women's physical and mental health, but current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exo) exhibit promising potential as a therapeutic approach for POI. However, their clinical application is hindered by their instability and low long-term retention rate in vivo . Methods and Results In this study, miR-21 was identified as the predominant miRNA with low-expression in follicular fluid exosomes of POI patients and was shown to possess antiapoptotic activity. Next, we loaded miR-21 agomir to MSC-Exo to form Agomir21-Exo, which significantly reversed the apoptosis of granulosa cells in vitro. Moreover, we successfully developed GelMA hydrogel microspheres for encapsulating Agomir21-Exo through microfluidic technology, named GelMA-Ag21Exo, which had good injectability and significantly enhanced the stability and long-term retention of Agomir21-Exo in mice through sustained release. The release of Agomir21-Exo from GelMA-Ag21Exo notably alleviated the apoptosis of ovarian granulosa cells and improved the ovarian reserve and fertility in POI mice. Conclusion Our findings illustrate that activating miR-21 through Agomir21-Exo could improve the function of ovarian granulosa cells. The GelMA-Ag21Exo enhanced the exosome-based therapeutic efficacy of the Agomir21-Exo in vivo . These findings provide a novel and promising treatment strategy for POI patients.
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STEM CELLS AND DEVELOPMENT
·
2019
·Vol. 28
·期 13
·871-881
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IF 3.147
Lin Li,Lisheng Chu,Cuicui Ren,Jun Wang,Siqi Sun,Tianyi Li,Yuanjun Yin
Bone marrow-derived mesenchymal stem cells (BMSCs) hold great promise for treating ischemic stroke owing to their capacity to secrete various trophic factors with potent angiogenic and neurogenic potentials. However, the relatively poor migratory capacity of BMSCs toward infarcted regions limits effective therapies for the treatment of stroke. The combination of BMSCs and pharmacological agent can promote the migration of BMSCs toward infarcted regions and improve the therapeutic effects after stroke. In this study, we aimed to investigate whether BMSCs combined with tetramethylpyrazine (TMP) enhanced BMSC migration into the ischemic brain, which had better therapeutic effect in the treatment of stroke. In a rat stroke model, we found that combination treatment significantly upregulated ischemic brain stromal-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) expressions, and promoted BMSCs homing toward the ischemic regions than BMSC monotherapy. Moreover, BMSCs combined with TMP synergistically increased the expression of vascular endothelial growth factor and brain-derived neurotrophic factor, promoted angiogenesis and neurogenesis, and improved functional outcome after stroke. These results suggest that combination treatment could not only enhance the migration of BMSCs into the ischemic brain but also act in a synergistic way to potentiate endogenous repair processes and functional recovery after ischemic stroke.
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Journal of Water Process Engineering
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2025
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IF 6.7
Dong-Can Lv,Meng-Ru Chen,Mei-Rong Song,Guang-Ce Jiang,Zhi-Min Wang
Conventional understanding of cationic dye adsorption on carbonaceous materials predominantly emphasizes electrostatic attraction. Herein, we report a ball-milled tobacco stem-derived activated carbon (BMTSAC) that exhibits superior adsorption capacity for methylene blue (MB) via a distinct and more resilient mechanism. Ball milling reduced the particle size to 440 nm and increased the specific surface area to 1171.5 m 2 /g, while concurrently modifying the surface chemistry and pore structure that fundamentally shifted the dominant adsorption pathway. The key finding is the dominance of non-electrostatic interactions, namely pore filling and π-π stacking, over electrostatic attraction. This was evidenced by the high MB uptake (520.7 mg/g) under highly acidic conditions (pH = 2.0), far below the point of zero charge (pH PZC = 3.0), and the material's robust performance under high ionic strength. The adsorption process followed the pseudo-second-order kinetic and Langmuir isotherm models, with a maximum adsorption capacity of 776.3 mg/g. The revelation of this mechanism shift underscores the superior potential of BMTSAC for treating complex industrial wastewater where pH fluctuates and ionic strength is high. After 5 cycles, BMTSAC maintained excellent reusability with only a 10.6 % capacity loss, further supporting its strong practical application prospects.
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CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Miaomiao Zhang,Chen Du,Shixin Xu,Jinxin Zhang,Junbo Jiang,Zhiyi Gao,Jierui Li,Bo Li,Li Xie,Wen Zhao
Current research primarily focuses on the effects of conductive fibrous membranes mediated electrical stimulation (ES) on stem cell behaviors. The role and mechanism of conductive fibrous membranes-mediated ES in regulating the paracrine function of adipose-derived stem cells (ADSCs) for tissue repair remain unexplored. This study aims to investigate the impact of ES mediated by poly (ε-caprolactone)/gelatin/Ti 3 C 2 T x MXene (PGM) fibrous membranes on the paracrine function of ADSCs. Our findings demonstrated that ES mediated by PGM fibrous membranes promoted the adhesion, spreading, proliferation, and migration of ADSCs. Furthermore, ES significantly enhanced the secretion of immunomodulatory and angiogenesis-related genes ( e.g. , hepatocyte growth factor (HGF) and transforming growth factor-β (TGF-β) and proteins ( e.g. , HGF and TGF-β) in the paracrine of ADSCs. Notably, the PGM@ES-CM group exhibited the highest secretion levels of factors promoting macrophage polarization and pro-angiogenic activity, with these secreted factors demonstrating functional efficacy in vitro assays and therapeutic potential in a full-thickness skin defect model. Mechanistically, the focal adhesion kinase (FAK)/extracellular-signal-regulated kinase (ERK) signaling pathway has been identified as a key regulatory pathway underlying ES-mediated modulation of paracrine function. Furthermore, an increase in intracellular Ca 2+ concentration, which mediated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, serves as another critical regulatory mechanism in the ES-mediated modulation of paracrine function. This study provides novel insights into developing advanced wound dressings that leverage biomaterial-mediated electrical signaling to orchestrate stem cell paracrine activity for tissue regeneration.
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Materials Today Bio
·
2022
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IF 10.761
Zhong Liu,Song Guo,Lanlan Dong,Peipei Wu,Kewei Li,Xinhua Li,Xiang Li,Hui Qian,Qiang Fu
Spinal cord injury (SCI) is a serious disease of the central nervous system that is associated with a poor prognosis; furthermore, existing clinical treatments cannot restore nerve function in an effective manner. Inflammatory responses and the increased production of reactive oxygen species (ROS) in the microenvironment of the lesion are major obstacles that inhibit the recovery of SCI. Small extracellular vesicles (sEVs), derived from mesenchymal stem cells, are suitable options for cell-free therapy and have been shown to exert therapeutic effects in SCI, thus providing a potential strategy for microenvironment regulation. However, the effective retention, controlled release, and integration of small extracellular vesicles into injured spinal cord tissue are still a major challenge. Herein, we fabricated an N-acryloyl glycinamide/gelatin methacrylate/Laponite/Tannic acid (NAGA/GelMA/LPN/TA, NGL/T) hydrogel with sustainable sEV release (sEVs-NGL/T) to promote the recovery of motor function after SCI. The newly developed functional sEVs-NGL/T hydrogel exhibited excellent antioxidant properties in an H 2 O 2 -simulated peroxidative microenvironment in vitro . Implantation of the functional sEVs-NGL/T hydrogel in vivo could encapsulate sEVs, exhibiting efficient retention and the sustained release of sEVs, thereby synergistically inducing significant restoration of motor function and urinary tissue preservation. These positive effects can be attributed to the effective mitigation of the inflammatory and ROS microenvironment. Therefore, sEVs-NGL/T therapy provides a promising strategy for the sEV-based therapy in the treatment of SCI by comprehensively regulating the pathological microenvironment.
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Molecular Medicine Reports
·
2021
·Vol. 23
·期 4
·1-10
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IF 2.952
Sining Feng,Shuai Wang,Shi Sun,Hao Su,Lixin Zhang
Spinal cord injury (SCI) remains a global challenge due to limited treatment strategies. Transcranial magnetic stimulation (TMS), bone marrow mesenchymal stem cell (BMSC) transplantation and downregulation of Raf/MEK/ERK signaling effectively improve SCI. The combination of BMSCs and TMS displays synergistic effects on vascular dementia. However, whether TMS displays a synergistic effect when combined with BMSC transplantation or Raf inhibitor (RafI) therapy for the treatment of SCI is not completely understood. The present study aimed to compare the therapeutic effect of monotherapy and combination therapy on SCI. In the present study, 8‑week‑old female Sprague Dawley rats were used to establish a model of SCI using the weight‑drop method followed by treatment with monotherapy (TMS, BMSCs or RafI) or combination therapy (TMS+BMSCs or TMS+RafI). The effect of monotherapy and combination therapy on locomotor function, pathological alterations, neuronal apoptosis and expression of axonal regeneration‑associated factors and Raf/MEK/ERK signaling‑associated proteins in the spinal cord was analyzed by Basso, Beattie and Bresnahan (BBB) scoring, hematoxylin and eosin staining, TUNEL‑neuronal nuclei (NeuN) staining and immunofluorescence or western blotting, respectively. The results demonstrated that compared with untreated SCI model rats, monotherapy significantly enhanced locomotor functional recovery, as evidenced by higher BBB scores, and slightly alleviated histopathological lesions of the spinal cord in SCI model rats. Furthermore, monotherapy markedly suppressed neuronal apoptosis and promoted axonal regeneration, as well as inhibiting astroglial activation in SCI model rats. The aforementioned results were demonstrated by significantly decreased numbers of apoptotic neurons, markedly decreased expression levels of glial fibrillary acidic protein (GFAP), significantly increased numbers of NeuN+ cells, markedly increased expression levels of growth‑associated protein 43 (GAP‑43) and significantly upregulated nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) expression levels in monotherapy groups (excluding the RafI monotherapy group) compared with untreated SCI model rats. In addition, monotherapy markedly suppressed activation of the Raf/MEK/ERK signaling pathway, as evidenced by significantly reduced p‑Raf/Raf, p‑MEK/MEK and p‑ERK/ERK protein expression levels in monotherapy groups (excluding the BMSC monotherapy group) compared with untreated SCI model rats. Notably, combination therapy further alleviated SCI‑induced spinal cord lesions and neuronal apoptosis, increased GAP‑43, NGF and BDNF expression levels, downregulated GFAP expression levels and inhibited activation of the Raf/MEK/ERK signaling pathway in SCI model rats compared with the corresponding monotherapy groups. Therefore, it was hypothesized that compared with monotherapy, combination therapy displayed an improved therapeutic effect on SCI by further suppressing Raf/MEK/ERK signaling. The results of the present study provided an important basis for the clinical application of combination therapy.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
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IF 3.575
Wenyu Chen
Excessive inflammation leads to periodontitis, which inhibits the osteogenic differentiation of human dental pulp stem cells (hDPSCs), irreversibly injured and difficultly repaired for the important dental pulp. Hence, it is necessary to study the functional gene to enhance the osteogenic differentiation of hDPSCs. Previous found that SNHG7 expression was increased in the osteogenic differentiation of hDPSCs. However, the regulatory functions of SNHG7 on osteogenic differentiation of hDPSCs in the inflammatory microenvironment still remains unknown. In this study, hDPSCs treatment with 50 ng/mL TNF-α to mimic the inflammatory microenvironment, then cultured in osteoblast differentiation medium for 14 days. SNHG7, miR-6512–3p, BSP , DSPP, DMP-1, RUNX2 and OPN in hDPSCs were detect by RT-qPCR. We found that SNHG7 expression was reduced during the osteogenic differentiation of hDPSCs after different concentrations TNF-α treatment. SNHG7 overexpression improved the TNF-α-induced suppression of calcium deposition, ALP activity, and the expression of BSP, DSPP, DMP-1, RUNX2 and OPN. Furthermore, SNHG7 can sponge with miR-6512–3p. miR-6512–3p expression was increased during the osteogenic differentiation of hDPSCs after different concentrations TNF-α treatment while inhibited after SNHG7 overexpression. knockdown of miR-6512–3p improved the TNF-α-induced suppression of calcium deposition, ALP activity, and the expression of BSP, DSPP, DMP-1, RUNX2 and OPN. Finally, miR-6512–3p overexpression reversed the effect of SNHG7 on the osteo/dentinogenic differentiation of TNF-α-treated hDPSCs. In conclusions, SNHG7 improves the osteogenic differentiation of hDPSCs by inhibiting miR-6512–3p expression under 50 ng/mL TNF-α-induced inflammatory environment, which provided potential targets for the treatment of periodontitis.
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