Nature Communications
·
2026
·
IF 18.1
Chun-Hui Duan,Pei-Pei Liu,Xin Sun,Wen-Hui Ma,Jia-Ying Pang,Zi-Han Zhang,Xiao Li,Lin-Fei Jiao,Hong-Zhen Du,Zhao-Qian Teng,Hou-Zao Chen,Chang-Mei Liu
Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is a rare and severe encephalopathy linked to neurodevelopmental disorders, yet the connection between metabolic dysfunction and impaired neurogenesis remains unclear. In this study, we demonstrate that the loss of Echs1 in neural stem/progenitor cells (NSPCs) leads to fatty acid accumulation, which hinders proliferation and differentiation while promoting apoptosis. Mechanistically, Echs1 deficiency increases crotonyl-CoA levels, resulting in global histone crotonylation (Kcr) with an enrichment of H3K9cr. Neurodevelopmental gene promoters, such as the endoplasmic reticulum (ER) stress regulator Atf4 , acquire H3K9cr. Atf4 then upregulates fatty acid synthase ( Fasn ), creating a feed-forward loop that exacerbates lipid accumulation. Inhibiting Fasn can rescue these defects. Alleviating ER stress through tauroursodeoxycholic acid (TUDCA) or Atf4 inhibition restores neurogenesis in vitro and enhances survival in vivo. This study uncovers an Echs1 -H3K9cr- Atf4 - Fasn axis that links metabolism to neurogenesis through epigenetic reprogramming and suggests TUDCA as a potential treatment for ECHS1D. In neural stem cells, ECHS1 deficiency rewires metabolism, driving a histone crotonylation-dependent feedback loop that impairs neurogenesis. The study reveals a mechanistic link between mitochondrial fatty acid oxidation and brain development and suggests tauroursodeoxycholic acid as a potential therapy.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·Vol. 24
·期 1
·578
·
IF 15
Zhao Zinan,Mutailipu Muladili,Mei Tianxiao,Cui Ran,Wang Yongkun,Liu Fuguo,Dong Chunxiu,Jia Wenwen,Liu Zhongmin,Chen Bo,Le Wenjun,Hu Yihui
Severe acute pancreatitis (SAP) is a life-threatening inflammatory disorder with an approximate mortality rate of 40%. Current therapeutic approaches fail to address its complex pathological microenvironment, necessitating novel synergistic strategies. Although mesenchymal stem cells (MSCs) exhibit therapeutic potential, their efficacy is significantly compromised by SAP-associated oxidative stress, hyperinflammation, and gut dysbiosis. Herein, we engineered MSCs with antioxidant nanozyme PDA@MnO x , named PDA@MnO x -MSCs ( Abbr. E-MSCs), to establish a regulatory network for SAP therapy. The PDA@MnO x nanozymes not only scavenge reactive oxygen species (ROS) to protect MSCs from oxidative damage but also enable in vivo T 1 -weighted MRI tracking. E-MSCs demonstrated enhanced anti-inflammatory effects, evidenced by reduced levels of TNF-ɑ and IL-6, and restored gut microbiota homeostasis, characterized by increased Bacteroidetes abundance. This further alleviated pancreatic necrosis and systemic inflammation. Notably, the synergistic interaction among PDA@MnO x nanozymes, MSCs, and the pathological microenvironment restored ROS-inflammation-microbiota homeostasis, significantly improving SAP outcomes. This study provides a multifunctional strategy integrating therapeutic efficacy, in vivo tracking, and gut microbiota modulation for SAP treatment. Graphical
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JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Zhang Qian,Chen Tiange,Chen Jianwei,Ai Ying,Chen Ziyang,Liu Ganzhi,Zhang Yi,Liu Boxun,Liu Jiacheng,Tang Zexuan,Lin Lin,Chen Xin,Xia Yuguo,Xu Tao,Liu Jinfang
Traumatic brain injury (TBI)-induced neuroinflammation, driven by inflammatory microglial polarization, continues to pose a significant regenerative and clinical challenge. Small extracellular vesicles (sEVs) have demonstrated great potential in mitigating post-TBI inflammation. Nevertheless, the limited yield and efficacy of sEVs produced via conventional two-dimensional (2D) culture systems (2D-sEVs) substantially hinder their clinical applicability. Moreover, effective strategies for the therapeutic application of sEVs in TBI treatment, along with an understanding of their underlying mechanisms, remain largely unexplored. In this study, we employed a 3D coaxial bioprinting method to encapsulate adipose-derived stem cells (ADSCs) within a hydrogel microfiber, facilitating 3D culturing and large-scale production of 3D-sEVs. Additionally, we utilized GelMA hydrogel for the sustained release of 3D-sEVs and evaluated their effects in LPS-activated microglia as well as in a TBI mouse model. Our results demonstrated that 3D culture significantly enhanced sEV production. GelMA improved sEV stability and prolonged sEV release up to 30 days in vivo. Compared to 2D-sEVs, 3D-sEVs offered superior therapeutic benefits. Specifically, 3D-sEVs substantially reduced neuroinflammation and brain tissue loss while accelerating motor function recovery in TBI mice. Furthermore, 3D-sEVs shifted pro-inflammatory microglia toward an anti-inflammatory polarization state, as evidenced by elevated expression levels of IL-4, IL-10, TGF-β, Arg1, and CD206, alongside reduced expression of IL-6, IL-1β, TNF-α, iNOS, and CD86, both in vitro and in vivo. Additionally, 3D-sEVs attenuated chemotaxis and migration in LPS-activated microglia. Further mechanistic exploration through RNA-seq, proteomic profiling, and GAS6 knockdown in 3D-sEVs, revealed that 3D-sEVs deliver growth arrest-specific protein 6 (GAS6) to modulate the transition of microglia from a pro-inflammatory to an anti-inflammatory state, thereby mitigating neuroinflammation following TBI. Our findings underscore the therapeutic promise of sEVs derived from 3D-cultured ADSCs in treating TBI via modulating microglia polarization. Graphical abstract
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MATERIALS & DESIGN
·
2025
·
IF 7.9
Chao Ju,Jun Zhao,Tianli Yang,Qing Yu,Feng Zhao,Cheng Shao,Luwei Xu,Xiaozhi Zhao,Liuhua Zhou
Renal ischemia–reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) in a variety of clinical settings. Current therapeutic interventions are significantly constrained by limitations include low drug specificity, requisite repeated administration, and a paucity of effective treatments. Although mesenchymal stem cells (MSCs) based therapies exhibit treatment prospects for mitigating renal IRI, low retention and translational efficacy still hinder clinical application. To address these pivotal limitations, this study employed an innovative combinatorial approach integrating genetic engineering with cell sheet technology. Specifically, we generated genetically engineered CX3CR1 overexpressing MSCs sheets to investigate their therapeutic effects and mechanism in attenuating renal IRI in a rat model. Results showed that CX3CR1-MSCs cell sheets were positive for CD31, CD34, α-SMA and Fibronectin. In vivo, these sheets amplified MSCs paracrine effects, promoted the recruitment and polarization of M2 macrophage phenotype, stimulated renal vascularization, and inhibited fibrosis and inflammation. In vivo imaging in animals revealed genetically engineered cell sheets markedly improved the retention of MSCs in the kidney, enhancing both cell engraftment and paracrine therapeutic action. Our results indicate that CX3CR1-engineered MSCs sheets offer superior prevention against renal IRI.
研究领域:
肾脏病学
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再生医学
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干细胞治疗
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分子生物学
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组织工程
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Scientific Reports
·
2025
·Vol. 15
·期 1
·1-13
·
IF 3.9
Chen Juanli,Wei Chuanfei,Zhang Yingchao,Chen Qingfa,Li Xuemei,Zhang Wei,Zhang Xiaoping,Han Fabin
Alzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) plaques, leading to neuronal death. Notably, there are no therapeutically efficacious treatments for this disorder. This study investigates the neuroprotective mechanisms of curcumin. In vitro experiments demonstrated that curcumin significantly promoted the proliferation of neural stem cells (NSCs) derived from E16 mouse embryos. Additionally, in the APP/PS1 transgenic mouse model, curcumin improved cognitive function, as evidenced by a shorter escape latency and increased platform crossing frequency in the Morris water maze test and enhanced novel object recognition. Histological analysis showed that curcumin reduced Aβ accumulation in the hippocampal and cortical regions. Molecular studies revealed that curcumin upregulated the expression of BDNF and enhanced phosphorylation of CREB. Collectively, these findings indicate that curcumin exerts neuroprotective effects through multiple mechanisms, including promoting NSC proliferation, reducing Aβ accumulation, and the potential modulation of the BDNF-CREB signaling pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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神经退行性疾病
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Advanced Healthcare Materials
·
2025
·
IF 9.6
Xujing Chen,Xiang Wang,Mingzhu He,Jingjing Kang,Jiangpeng Gu,Yongchun Wei,Jingqi Li,Bowei Li,Xiaoqin Hong,Xiang Mao,Dingbin Liu,Hong Cai
Wound healing represents a major clinical concern, disrupted by cellular dysfunction due to infection, metabolic imbalance, and immune response, resulting in physical and economic burden to the patients. Despite the widespread recognition of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in wound healing research, ensuring their release and retention at the wound site and maximizing their therapeutic efficacy remain significant challenges. To address these issues, a self-adaptive multifunctional hydrogel is introduced that allows the self-adaptive release of MSC-EVs at the wound sites. This approach prevents the rapid clearance of MSC-EVs, enabling them to effectively activate wound healing signaling pathways and promote angiogenesis, cell migration, proliferation, and re-epithelialization. Moreover, the incorporation of gallic acid (GA) endows the hydrogel with antibacterial, anti-inflammatory, and antioxidant properties, which synergistically enhance the reparative effects of MSC-EVs. The potential of the MSC-EV-embedded multifunctional hydrogel is evaluated in a methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness wound mouse model, demonstrating its high performance in accelerating the healing of infected complex wounds.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
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IF 5.9
Liping Zhang,Yanyan Wang,Wenxin Qiu,Shuangling Liu,Shengxuan Xu,Hongwei Wang,Lin Yuan
Neural differentiation of embryonic stem cells (ESCs) holds significant therapeutic potential for the treatment of neurodegenerative diseases. A cell conversion strategy was developed to induce neural differentiation of ESCs by utilizing exosomes (Exo) derived from mesenchymal stem cells (MSCs) as efficient delivery vehicles for retinoic acid (RA) and fibroblast growth factor 2 (FGF2). The abundant surface proteins and phospholipid bilayer of Exo provided protective effects for FGF2 and RA, 88 % of RA remained within the Exo, and the residual amount of exosome-bound FGF2 was nearly 5-fold higher than that of free FGF2, after storage at 4 °C for 5 days. Exo co-loaded with RA and FGF2 exhibited excellent biocompatibility and promoted cell proliferation, resulting in a 3.3-fold higher proliferation over the free RA+FGF2 within 3 days. Neural differentiation was enhanced through dual signaling pathways mediated by RA and FGF2, leading to a nearly 3-fold increase in the relative expression of neuronal marker genes and 8.3-fold increase in the number of differentiated neural cells, compared to the RA+FGF2 group by day 7. This approach significantly enhanced both the efficiency and yield of neural differentiation, presenting a promising nanomedicine strategy by applying engineered Exo to guide the neural lineage commitment of ESCs.
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Journal of Materials Chemistry A
·
2026
·
IF 9.5
Yongjie Lao,Yusheng Wang,Qiao Zhang,Feipeng Du,Chak-Yin Tang,Chi-Pong Tsui,Yunfei Zhang
Sustainable solutions are needed for global freshwater shortages. Solar-driven interfacial water evaporation technology for saltwater desalination and wastewater purification is promising due to its low-carbon and energy-efficient nature. In this study, we develop a high-performance solar evaporator based on a copper nanoparticle (CuNPs)-modified poly (aniline-co-pyrrole)/polyvinyl alcohol (CuNPs@PANI-PPy/PVA) composite sponge. The material consists of a porous polyvinyl alcohol (PVA) sponge substrate composited with a CuNPs@PANI-PPy photothermal layer, which leverages a metal-polymer synergistic effect to overcome the limitations of single-component photothermal materials, including narrow absorption of sunlight and low solar energy utilization efficiency. Moreover, a bionic stem-shaped evaporator structure that does not need to float on the water surface was designed to achieve directional capillary water delivery, ensuring that there is always an adequate water supply at the evaporation interface while preventing heat loss downward due to excessive water supply.The CuNPs@PANI-PPy/PVA sponge achieves an exceptional evaporation rate of 3.84 kg m-2 h-1 with a remarkable energy efficiency of 98.9% under 1 sun irradiation. Furthermore, the evaporator demonstrated outstanding salt resistance; the evaporator maintained a remarkable average evaporation rate of 3.63 kg m-2 h-1 in a 15 wt% NaCl solution. Additionally, the material exhibited excellent purification capabilities for both saline water and organic dye-contaminated wastewater. Therefore, this work proposes a method that combines conductive copolymers with metal nanoparticles to design highly efficient and durable solar photothermal materials, and optimizes the structure of the evaporator based on a bionic stem design, providing a feasible approach for scalable practical desalination projects.
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Smart Medicine
·
2023
·Vol. 2
·期 1
·e20220037
·
IF 0
Yimeng Shu,Hui Shen,Minghua Yao,Jie Shen,Guo-Yuan Yang,Hangrong Chen,Yaohui Tang,Ming Ma
Mesenchymal stem cell (MSC)-based therapy has provided a promising strategy for the treatment of ischemic stroke, which is still restricted by the lack of long-term cell tracking strategy as well as the poor survival rate of stem cells in ischemic region. Herein, a dual-functional nanoprobe, cobalt protoporphyrin-induced nano-self-assembly (CPSP), has been developed through a cobalt protoporphyrin IX (CoPP) aggregation-induced self-assembly strategy, which combines CoPP and superparamagnetic iron oxide (SPION) via a simple solvent evaporation-driven method. Without any additional carrier materials, the obtained CPSP is featured with good biocompatibility and high proportions of active ingredients. The SPIONs in CPSPs form a cluster-like structure, endowing this nano-self-assembly with excellent T 2 -weighted magnetic resonance (MR) imaging performance. Furthermore, the CoPP released from CPSPs could effectively protect MSCs by upregulating heme oxygenase 1 (HO-1) expression. The in vivo cell tracing capacity of CPSPs is confirmed by monitoring the migration of labeled MSCs with MR imaging in a middle cerebral artery occlusion mouse model. More importantly, the sustained release of CoPP from CPSPs improves the survival of transplanted MSCs and promotes neural repair and neurobehavioral recovery of ischemic mice. Overall, this work presents a novel dual-functional nanoagent with an ingenious design for advancing MSC-based therapy.
研究领域:
生物医学工程
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神经科学
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干细胞治疗
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分子影像学
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DOI
Pharmaceutics
·
2026
·Vol. 18
·期 3
·363
·
IF 6.9
Meitong Liu,Kai Wang,Can Zeng,Yijiang Jia,Jiaqi Wang,Ayijiang Taledaohan,Yuji Wang,Xiaobing Guan
Purpose:Due to the lack of effective local therapeutic strategies for oral squamous cell carcinoma (OSCC), this study aimed to develop a novel gelatin/lignin hydrogel loaded with mesenchymal stem cell (MSC)-derived exosomes enriched in microRNA-185 (miR-185 EV) for intraoral delivery, followed by systematic evaluation of its therapeutic efficacy and underlying molecular mechanisms.Materials and Methods:The gelatin/lignin hydrogel was prepared and subsequently loaded with miR-185 EV. The physicochemical properties of the hydrogel, including microstructure, swelling behavior, chemical composition, and rheological characteristics, were systematically evaluated. Next, the stability, viscosity, biocompatibility, and exosome release kinetics of the hydrogel were further assessed. A 4-nitroquinoline-1-oxide (4NQO)-induced mouse tongue carcinogenesis model was established to assess the in vivo antitumor activity of the hydrogel via intraoral administration. Moreover, a proteomic analysis was conducted to investigate the molecular mechanisms of miR-185 EV on OSCC.Results:The miR-185 EV-loaded gelatin/lignin hydrogel exhibited favorable physicochemical properties, stability, and biocompatibility while prolonging the tissue retention time of miR-185 EV. In vivo antitumor efficacy experiments showed that the miR-185 EV-loaded hydrogel significantly inhibited tumor occurrence and alleviated epithelial dysplasia. Immunohistochemical analyses revealed significant suppression of tumor proliferation and epithelial–mesenchymal transition (EMT) of the hydrogel. Proteomic analysis indicated that miR-185 EV suppressed OSCC progression by downregulating interleukin-1β (IL-1β), consequently inhibiting the NF-κB signaling pathway.Conclusion:The findings demonstrate the successful development of the miR-185 EV-loaded gelatin/lignin hydrogel that represents an effective nanomedicine platform for intraoral drug delivery, providing a promising strategy for the clinical treatment of OSCC.
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ACS Nano
·
2026
·
IF 17.3
Li He,Hongrui Ji,Ju Huang,Jinxiao Yan,Shuoqi Tian,Shiyu Liu,Shizhe Chen,Yanwen Hao,Yuanchao Kang,Hui Yang,Ning Cui
Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) have emerged as a promising therapeutic modality, owing to their potent immunomodulatory and tissue repair capabilities. However, the lack of high-efficiency and high-purity isolation strategies remains a major barrier to the clinical translation of BMSC-Exos. Herein, we rationally designed a high-performance TIM4@MGO magnetic bead system through the functionalization of magnetic graphene oxide (MGO) with T cell immunoglobulin and mucin domain-containing protein 4 (TIM4), which enables the rapid and efficient isolation of exosomes within only 30 min. First, in the presence of Ca2+, TIM4 immobilized on the surface of magnetic beads specifically recognizes and binds to phosphatidylserine (PS) exposed on the exosomal membrane, enabling the selective capture of exosomes. Moreover, the large specific surface area of MGO substantially increases the loading density of TIM4, thereby markedly enhancing the binding capacity and recovery efficiency of the exosomes. Subsequently, chelation of Ca2+ by EDTA induces charge reversal of the TIM4 domain, triggering highly reversible dissociation of the TIM4–PS interaction. This thus allows for the efficient release of exosomes under mild physiological conditions while preserving their structural and functional integrity. Additionally, TIM4@MGO retained over 84% of the initial isolation efficiency even after three consecutive reuse cycles, demonstrating exceptional reusability in practical applications. In vitro experiments confirmed that BMSC-Exos isolated via TIM4@MGO markedly promoted L929 cell proliferation and accelerated scratch wound healing. Proteomic profiling further revealed that BMSC-Exos isolated by TIM4@MGO were significantly enriched in proteins associated with extracellular matrix remodeling and the TNF signaling pathway, implying their potential role in fibrosis regulation. In a mouse pulmonary fibrosis model, compared with those isolated by ultracentrifugation and polyethylene glycol precipitation methods, TIM4@MGO-isolated BMSC-Exos exerted superior therapeutic efficacy in mitigating lung tissue structural damage and attenuating fibrotic progression. Collectively, this study establishes a high-efficiency, high-purity, and reusable exosome isolation technique, offering robust technical support for both fundamental research and the clinical translation of BMSC-Exo therapeutics.
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高影响因子
Molecular Medicine Reports
·
2025
·Vol. 33
·期 1
·1-10
·
IF 3.5
Hongwei Xiao,Jianfeng Li,Wei Huang,Yi Qin
Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.
研究领域:
分子医学
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遗传学
·
病理学
·
药理学
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危险品化学品经营许可证（带存储）