Polymers
·
2026
·Vol. 18
·期 6
·774
·
IF 5.8
Peng Li,Xiaoxin Cheng,Wuwei Li,Haiqing Yang,Yubi Jiang
Laceration is one of the most common meniscus injuries, which can cause knee joint dysfunction. The treatment of meniscus injuries remains one of the greatest challenges in orthopedics. In this study, a three-dimensional sponge-like Poly(lactic acid)/Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (PLA/P(3HB-co-4HB)) scaffold with oriented microtubules was fabricated using an improved gradient thermal phase separation technique. The scaffold surface was modified by adsorbing gelatin. The surface-modified scaffolds and the unmodified scaffolds were divided into two groups. All preparation parameters were adjusted to meet tissue engineering requirements. The prepared scaffolds were tested for porosity, compression modulus, hydrophilicity, and degradability. Following scaffold preparation, induced differentiated rabbit bone marrow mesenchymal stem cells (BMSCs) were seeded to evaluate scaffold cytocompatibility. Cell proliferation was observed in the two scaffold groups, and cell viability was analyzed using CCK-8 assay, scanning electron microscopy (SEM), and confocal microscopy. Histological staining was performed to comparatively study cell synthetic function. Subsequently, tissue reconstruction and regeneration were evaluated following subcutaneous implantation of gelatin/PLA/P(3HB-co-4HB) scaffolds loaded with induced differentiated BMSCs in the dorsal regions of athymic nude mice. Results demonstrated that the gelatin/PLA/P(3HB-co-4HB) scaffold exhibited good cell compatibility, providing a suitable microenvironment for cell proliferation and differentiation. Furthermore, the scaffold supported the growth of seeded induced differentiated rabbit MSCs in vivo, maintaining meniscus cell phenotyping and function. The cell-laden scaffold has the potential to generate meniscus fibrocartilage.
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iScience
·
2026
·
IF 4.5
Hao Sun,Xiaojing Qi,Shihan Chen,Yanshuang Huang,Xixi Zheng,Yaosheng Li,Ni Li,Jing Shi,Donghang Xu,Xiaoxu Hao,Yanli Zhao,Xianzhen Yin,Yue Hu,Yinghua Ying,Qin Chen,Yang Xia,Zhen Gu,Xuejin Li,Jianqing Gao,Tianyuan Zhang
Stem cell therapy has demonstrated significant therapeutic potential. However, the relatively large cellular diameter increases the likelihood of entrapment within capillaries, impeding the migration of stem cells to disease foci. We herein propose an enucleation strategy to enhance cell deformability, significantly improving vascular transit efficiency. Computational modelling, combined with experimental investigations using a microfluidic platform, revealed that increased cellular deformability, rather than a reduction in diameter, plays a greater role in facilitating cell transit, thereby challenging traditional perspectives on the cell mechanics. Observations of pulmonary vasculature using optical tissue clearing and fluorescence micro-optical sectioning tomography confirmed the extensive distribution of enucleated cells and their reduced entrapment within fibrotic foci. Consequently, enucleated mesenchymal stem cells efficiently deliver mRNA to the fibrotic sites, significantly mitigating pulmonary fibrosis. Our findings provide new insights into the role of enucleation in facilitating cellular transit through constricted vasculature and the underlying mechanobiology of enhanced deformability.
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Stem Cell Research & Therapy
·
2025
·
IF 7.3
Jie Chen,Yiwei Zhao,Chongmai Zeng,Guoli Tian,Zhicai Feng,Yang Cao
Background Craniomaxillofacial sutures play a critical role in craniomaxillofacial development through continuous bone reconstruction and regeneration, processes modulated by mechanical tension. Bone suture stem cells (SuSCs) are central to these functions. Distraction osteogenesis, which promotes craniomaxillofacial suture growth, is a common therapeutic approach for craniofacial deformities. However, the underlying mechanisms by which mechanical forces drive suture and bone remodeling remain poorly understood, posing significant clinical challenges. Methods To investigate these mechanisms, we established a rapid maxillary expansion (RME) model in mice to widen the midpalatal suture. Single-cell RNA sequencing (scRNA-seq) was employed to identify subsets of SuSCs responsive to mechanical tension and analyze their differentiation potential under varying conditions. Further functional studies were conducted to explore the role of DALR anticodon binding domain containing 3 (Dalrd3) and its associated tRNA 3-methylcytosine (m3C) modification in SuSCs under mechanical tension. Results Our study identified a subset of SuSCs with multidirectional differentiation potential that shifted from a chondrogenic to an osteogenic trajectory in response to mechanical tension. Mechanical tension also upregulated Dalrd3 expression and its associated tRNA m3C modification in activated SuSCs. Knockdown of Dalrd3 in SuSCs significantly impaired osteogenic differentiation, proliferation, migratory capacity, and translational activity within the bone morphogenetic protein (BMP) signaling pathway. Furthermore, Dalrd3 knockdown suppressed the translational activity of inhibitor of DNA binding 3 (Id3), a key BMP-induced mediator of osteoblastogenesis. Restoring Id3 expression in Dalrd3-deficient SuSCs rescued their osteogenic, proliferative, and migratory functions. Conclusions These findings reveal a translational regulatory mechanism in SuSCs activated by mechanical tension and underscore the pivotal role of Dalrd3 in suture remodeling and bone formation. The insights provided by this study have the potential to guide targeted therapeutic strategies for optimizing distraction osteogenesis and other treatments for craniofacial deformities. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-025-04380-9.
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Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-17
·
IF 7.3
Du Dongdong,Wang Ting,Sun Yaodong,Zhang Yi,Zhang Bufan,Shao Jingrong,Yang Mengxue,Huang Chuan,Zuo Shengkai,Wu Naishi
Background The poor viability and paracrine function of transplanted mesenchymal stem cells (MSCs) hamper their therapeutic efficacy in ischemic heart injury treatment. Protein arginine methyltransferases (PRMTs) mediate arginine methylation and have important functions in cellular responses. However, the role of PRMTs in MSC-based therapies for ischemic heart injury remains unclear. The aim of this study was to investigate the effect of PRMT1 on MSC function and therapeutic efficacy using a mouse myocardial infarction (MI) model.Methods We isolated, cultured, and identified mouse adipose tissue-derived mesenchymal stromal cells (ADSCs). We used Furamidine, a PRMT1 inhibitor, and adenoviral shPRMT1 to study the effects of PRMT1 inhibition on ADSC proliferation, migration, and viability. We performed RNA sequencing and biochemical experiments to elucidate the molecular mechanisms of PRMT1 in ADSCs. Finally, we infected ADSCs with adenoviral shPRMT1 and administered an intramyocardial injection after MI. Cardiac function was evaluated using echocardiography and pathological staining, and ADSCs survival rates, cardiomyocyte apoptosis, and capillary density were evaluated using immunofluorescence staining.Results We found that PRMT1 was highly expressed in ADSCs and markedly upregulated in response to H2O2 challenge. Inhibition of PRMT1 by Furamidine or adenoviral shPRMT1 promoted ADSC proliferation and migration and reduced H2O2-induced ADSCs apoptosis. Mechanistically, PRMT1 inhibition significantly increased the expression of matrix metallopeptidase (MMP)-10, placenta growth factor (PlGF) and transforming growth factor (TGF)-β2 in ADSCs through transcription factor RUNX1. Blockage of RUNX1 abolished the proliferative and migratory effects of PRMT1 inhibition in ADSCs. Compared to ADSCs infected with the adenovirus-control, PRMT1 knockdown adenovirus markedly increased the survival and retention of transplanted ADSCs in injured hearts after MI. ADSCs with PRMT1 knockdown markedly improved cardiac function and alleviated cardiac fibrosis in mice after MI by reducing cardiomyocyte apoptosis and increasing capillary density.Conclusion sPRMT1 inhibition enhances the cardioprotective effect of ADSCs against MI through RUNX1-mediated production of MMP-10/PlGF/TGF-β2. Overall, PRMT1 inhibition is a promising strategy for augmenting MSCs therapeutic efficacy in ischemic cardiomyopathy.
研究领域:
心血管医学
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分子生物学
·
干细胞研究
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WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
·
2024
·Vol. 41
·期 1
·1-14
·
IF 4
Tan Xiaoli,Jiang Xiaobing,Chen Xiumei,Reymick Okwong Oketch,Zhu Chen,Tao Nengguo
Neofusicoccum parvum is one of the most hazardous pathogens causing mango fruit decay. The present study utilized trans -2-hexenal (TH), a typical antifungal component of plant essential oils (EOs), to control N. parvum both in vivo and in vitro, and attempted to explore the mechanisms involved. The findings showed that at concentrations greater than 0.4 µL/mL, TH exhibited exceptional antifungal activity against N. parvum in vitro. TH application led to the disruption of the structural integrity of both cell walls and cell membranes, with a particular impact on the latter, as evidenced by the dramatically increased propidium iodide level, as well as reduced total lipids and ergosterol content. Further DCFH-DA staining experiments showed that TH induced mycelial reactive oxygen species (ROS) accumulation, which exacerbated cell membrane lipid peroxidation. For easier application of TH, we fabricated aerogel-loaded TH (ALTH) materials, which demonstrated excellent antifungal activity in vitro. Infestation studies on fruits demonstrated that ALTH mitigated mango stem-end rot in a dose-dependent fashion, with a concentration of 40 µL/L showing efficacy comparable to the conventional fungicide prochloraz, while maintaining fruit quality. In light of these results, TH works by inducing ROS buildup and oxidative damage to the cell membrane of N. parvum , and is a particularly promising preservative for preventing postharvest infections in mangoes.
研究领域:
植物病理学
·
食品科学
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Scientific Reports
·
2024
·Vol. 14
·期 1
·1-12
·
IF 3.8
Wen Hong-jie,Zhu Shou-yan,Yang Hua-gang,Guo Feng-yong
Binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into bone, fat and cartilage. Therefore, it was important to analyze the molecular mechanism of SPA on osteogenic differentiation. We introduced transcript sequence data to screen out differentially expressed genes (DEGs) related to SPA-interfered BMSC. Protein–protein interaction (PPI) network of DEGs was established to screen biomarkers associated with SPA-interfered BMSC. Receiver operating characteristic (ROC) curve was plotted to evaluate the ability of biomarkers to discriminate between two groups of samples. Finally, we performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers ( Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14 ) were identified by hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly discriminate between normal differentiated and SPA-interfered BMSC. Moreover, we found that these biomarkers were mainly enriched in the pyrimidine metabolism pathway. We also constructed '71 circRNAs-14 miRNAs-5 mRNAs' and '10 lncRNAs-5 miRNAs-2 mRNAs' networks. Kntc1 and Asf1b genes were associated with rno-miR-3571. Nek2 and Asf1b genes were associated with rno-miR-497-5p. Finally, we found significantly lower expression of six biomarkers in the SPA-interfered group compared to the normal group by RT-qPCR. Overall, we obtained 6 biomarkers ( Cenpf, Kntc1, Nek2, Asf1b, Troap , and Kif14) related to SPA-interfered BMSC, which provided a theoretical basis to explore the key factors of SPA affecting osteogenic differentiation.
研究领域:
分子生物学
·
细胞生物学
·
医学
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Li Wen,Shi Zhiyuan,Jing Huaqing,Dou Yunsheng,Liu Xinyi,Zhang Mengyao,Qiu Zitong,Heger Zbynek,Li Nan
Dysregulation of extracellular matrix (ECM) homeostasis plays a pivotal role in the accelerated degradation of cartilage, presenting a notable challenge for effective osteoarthritis (OA) treatment and cartilage regeneration. In this study, we introduced an injectable hydrogel based on streamlined-zinc oxide (ZnO), which is responsive to matrix metallopeptidase (MMP), for the delivery of miR-17-5p. This approach aimed to address cartilage damage by regulating ECM homeostasis. The ZnO/miR-17-5p composite functions by releasing zinc ions to attract native bone marrow mesenchymal stem cells, thereby fostering ECM synthesis through the proliferation of new chondrocytes. Concurrently, sustained delivery of miR-17-5p targets enzymes responsible for matrix degradation, thereby mitigating the catabolic process. Notably, the unique structure of the streamlined ZnO nanoparticles is distinct from their conventional spherical counterparts, which not only optimizes the rheological and mechanical properties of the hydrogels, but also enhances the efficiency of miR-17-5p transfection. Our male rat model demonstrated that the combination of streamlined ZnO, MMP-responsive hydrogels, and miRNA-based therapy effectively managed the equilibrium between catabolism and anabolism within the ECM, presenting a fresh perspective in the realm of OA treatment.
研究领域:
医学
·
材料科学
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Stem Cells International
·
2018
·
IF 3.989
Yong-Heng Luo,Juan Chen,En-Hua Xiao,Qiu-Yun Li,Yong-Mei Luo
Demethylating agent zebularine is reported to be capable of inducing differentiation of stem cells by activation of methylated genes, though its function in hepatocyte differentiation is unclear. p38 signal pathway is involved in differentiation of hepatocytes and regulating of DNA methyltransferases 1 (DNMT1) expression. However, little is known about the impact of zebularine on bone marrow mesenchymal stem cells (BMMSCs) and p38 signaling during hepatic differentiation. The present study investigated the effects of zebularine on hepatic differentiation of rabbit BMMSCs, as well as the role of p38 on DNMT1 and hepatic differentiation, with the aim of developing a novel strategy for improving derivation of hepatocytes. BMMSCs were treated with zebularine at concentrations of 10, 20, 50, and 100 μM in the presence of hepatocyte growth factor; changes in the levels of hepatic-specific alpha-fetoprotein and albumin were detected and determined by RT-PCR, WB, and immunofluorescence staining. Expression of DNMT1 and phosphorylated p38 as well as urea production and ICG metabolism was also analyzed. Zebularine at concentrations of 10, 20, and 50 μM could not affect cell viability after 48 h. Zebularine treatment leads to an inhibition of DNMT activity and increase of hepatic-specific proteins alpha-fetoprotein and albumin in BMMSCs in vitro; zebularine addition also induced expression of urea production of and ICG metabolism. p38 signal was activated in BMMSCs simulated with HGF; inhibition of p38 facilitated the synthesis of DNMT1 and albumin in cells. Zebularine restrained DNMT1 and phosphorylated p38 which were induced by HGF. Therefore, this study demonstrated that treatment with zebularine exhibited terminal hepatic differentiation of BMMSCs in vitro in association with hepatocyte growth factor; p38 pathway at least partially participates in zebularine-induced hepatic differentiation of rabbit BMMSCs.
研究领域:
干细胞研究
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分子生物学
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细胞信号传导
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表观遗传学
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Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Shengnan Li,Wei Lv,Jiangna Xu,Jiaqing Yin,Yuqin Chen,Linfeng Liu,Xiang Cao,Wenjing Li,Zhen Li,Hua Chen,Hongliang Xin
Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H II phase transition of 1,2-dioleoyl -sn- glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Aiping Wang,Xuejian Cheng,Chengying Ding,Pengyue Zhao,Chong Cao,Lidong Cao,Manli Yu,Qiliang Huang
Traditional agrochemicals suffer from low utilization rates and high environmental exposure levels, posing threats to ecosystem security and limiting their practical application. Wheat stem rot is one of the world's major agricultural diseases caused by Fusarium pseudograminearum , which mainly affects the stem base of wheat. Improving the agent's deposition distribution and duration of action in the wheat rhizome is critical when applied through foliar spray or root application.to control this disease. Stimuli-responsive delivery systems can provide more effective crop protection while improving the safety of pesticides for non-target organisms and the environment. In this study, we developed pectin-modified pyraclostrobin nanocapsules (NCS@Pec) exhibiting dual responsiveness to pH and pectinase. Compared to conventional nanoemulsion (NEW), NCS@Pec demonstrated superior adhesion to wheat surfaces with 2.86-fold enhanced rainfastness. Root application reduced pyraclostrobin translocation to leaves while prolonging rhizosphere activity. At 14 days post-treatment, NCS@Pec maintained approximately 68% control efficacy. In addition, the selectivity coefficients of NCS@Pec between F. pseudograminearum and zebrafish were 2.67 and 7.09, significantly reducing environmental risks to aquatic life while maintaining fungicidal activity. These findings advance the application of carbohydrate polymers such as pectin in nanopesticide development and contribute to novel bioactive agent design and food security enhancement.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Cong He,Hairong Yu,Jiaqi Tian,Ziling Huang,Xue Yang,Jingru Zhang,Wenjing Chen,Yayue Zhang,Xuran Ding,Yabing Hua,Yuan He,Yan Liu,Ziming Zhao,Yihua Yang
The advancement of cell-based drug delivery systems (Cell-DDS) enables precise tumor targeting. Utilizing bone marrow mesenchymal stem cells (BMSC) as carriers, transferrin (Tf)-modified BMSC (BMSC Tf ) were engineered via sugar metabolism replacement and click chemistry. Liposomes co-encapsulating phthalocyanine (Pc) and oxygen-carrying perfluorohexane (PFH) were integrated with BMSC Tf through membrane fusion, constructing the Tf-functionalized delivery system Pc/O₂@BMSC Tf . This system achieved Pc loading efficiency of 1.7 μg per 10⁵ cells and an oxygen-carrying capacity of 11.2 μg per 10⁷ cells, demonstrating active tumor targeting, significant antitumor efficacy in vitro and in vivo , and high biocompatibility. At tumor sites, localized near-infrared irradiation triggered Pc-mediated ROS generation, while the nanoliposomes provided real-time oxygen replenishment, overcoming hypoxia to potentiate photodynamic therapy (PDT). This novel stem cell-based drug delivery system represents a promising strategy for targeted tumor therapy.
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Waste and Biomass Valorization
·
2018
·Vol. 10
·期 11
·3343-3350
·
IF 1.874
Chen Cheng,Jiang Linfeng,Ma Guanfeng,Jin Dongxue,Zhao Lisha,Ouyang Xinping
Abstract Lignin removal from lignocellulosic materials plays a great role in the utilization cellulose with high efficiency. In order to improve the quality of reconstituted tobacco sheet, lignin existed in tobacco stem was removed by enzymatic hydrolysis with laccase enhanced by weak alkali treatment together with the addition of Tween 80 into laccase treatment system. It is found that lignin was partially removed by laccase. The treatment of tobacco stem with NaHCO 3 resulted in the dissolution of lignin, and hence increased the porosity and specific surface area of the pretreated tobacco stem. Consequently, laccase could access to the tobacco stem more completely. The surface activity and dispersion of Tween 80 improved laccase activity, solubilization of degraded products of lignin, and contact interface between laccase and tobacco stem. The synergistic action of laccase, weak alkali and Tween 80 improved the ratio of lignin removal significantly, reaching as high as 40.3%. Graphical Abstract
研究领域:
生物化学
·
植物学
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危险品化学品经营许可证（带存储）