Nature Chemical Biology
·
2024
·
IF 12.9
Wang Shiwen,Liu Min,Hu Dongping,Dong Zhicheng,Zhao Zhong
Superoxide anion is thought to be a natural by-product with strong oxidizing ability in all living organisms and was recently found to accumulate in plant meristems to maintain stem cells in the shoot and undifferentiated meristematic cells in the root. Here we show that the DNA demethylase repressor of silencing 1 (ROS1) is one of the direct targets of superoxide in stem cells. The Fe–S clusters in ROS1 are oxidized by superoxide to activate its DNA glycosylase/lyase activity. We demonstrate that superoxide extensively participates in the establishment of active DNA demethylation in the Arabidopsis genome and that ARABIDOPSIS RESPONSE REGULATOR 12 acts downstream of ROS1-mediated superoxide signaling to maintain stem cell fate. Our results provide a mechanistic framework for superoxide control of the stem cell niche and demonstrate how redox and DNA demethylation interact to define stem cell fate in plants.
研究领域:
植物生物学
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表观遗传学
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干细胞生物学
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DOI
PubMed
高影响因子
Med
·
2026
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IF 13.3
Jie Yu,Shuhua Yin,Jiong Li,Yilin Zhang,Xiuli Zhong,Nuo Zhou,Wei Li,Yixin Wang,Renke Li,Minjie Sun,Zhaoting Li
Background Pulmonary fibrosis is a fatal disease with limited therapeutic options. Aberrant activation of the integrated stress response (ISR) disrupts proteostasis and promotes fibrogenesis, yet effective strategies for targeted ISR regulation in fibrotic diseases remain insufficiently explored. Methods Here, we engineered mesenchymal stem cells (MSCs) as living carriers for targeted co-delivery of ISRIB and nicotinamide mononucleotide (NMN). ISRIB- and NMN-loaded liposomes were conjugated onto MSCs through cleavable linkers (M-Lip@IN), enabling MSC-mediated homing and microenvironment-responsive cargo release in fibrotic lesions. Findings M-Lip@IN effectively accumulated in fibrotic lungs and promoted local liposome release. ISRIB directly regulated pathological ISR activation, whereas NMN supported NAD(H)-SIRT1-related metabolic homeostasis, collectively enabling coordinated regulation of epithelial stress responses. Augmented by MSC-mediated biological support, M-Lip@IN reduced collagen deposition, inhibited profibrotic signaling, improved epithelial cell composition, promoted lung repair, and ameliorated bleomycin-induced pulmonary fibrosis, with additional antifibrotic effects observed in carbon-tetrachloride-induced liver fibrosis. Conclusions Our study presents an engineered MSC-based platform that integrates lesion targeting, responsive drug release, and coordinated regulation of epithelial stress responses. By combining ISR modulation with metabolic resilience, M-Lip@IN restores stress homeostasis, improves epithelial cell composition, and promotes lung repair. These findings support targeted ISR regulation as a potential therapeutic strategy for pulmonary fibrosis and other fibrotic diseases. Funding This work was supported by the Shenzhen Science and Technology Program, the Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, the University Development Research Start-up Fund, and the Pengcheng Peacock Project Special Fund.
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
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IF 11
Li S,Chen X,Zhao H,Ma R,Wang Y,Wang G,Zhang K,Xia X,Ma X,Wu B,Huang Y,Shu Z,Guo J,Tao Y,Gui S,Ding Y,Peng C.
Mechanical debridement and systemic antibiotics, as current therapeutic modalities for periodontitis, suffer from limitations, including insufficient local efficacy and bacterial resistance. Herein, a dual-mode injectable hydrogel (A-CC-PBA@ZIF-8@CAPE Gel) has been designed and prepared for enhancing the therapeutic efficacy through targeted anti-infection and rectification of the dysregulated mitochondrial function of mesenchymal stem cells (MSCs) in inflammatory state. Both the in vitro antibacterial evaluation and molecular dynamics simulation confirmed the phenyl boronic acid (PBA)-modification boosted the antimicrobial efficacy against periodontal pathogenic bacteria. In addition to the targeted antibacterial efficacy, A-CC-PBA@ZIF-8@CAPE Gel exhibited remarkable capacity to scavenge ROS, ameliorate inflammatory response, relieve oxidative stress, and restore the mitochondrial function of MSCs under inflammatory conditions by activating the SIRT1/p-AMPK/PGC-1α pathway, thereby promoting the osteogenic differentiation of MSCs. In rat periodontitis model, A-CC-PBA@ZIF-8@CAPE Gel markedly reduced bone defects and ROS levels, attenuated inflammation, and restored alveolar bone height, demonstrating robust therapeutic potential in chronic inflammatory conditions. In summary, this study presents a promising therapeutic approach for periodontitis, characterized by targeted antibacterial infection, anti-inflammation, and bone regeneration.
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2026
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IF 8.7
Yulian Li,Tong Jin,Xin Guan,Chao Han,Wei Zou,Liming Shen,Jing Liu
Introduction Glioblastoma, the most aggressive form of brain tumor, continues to present significant therapeutic challenges, including the limited delivery of drugs posed by the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB), severe systemic toxicity associated with conventional chemotherapy, and the complexity arising from tumor heterogeneity.Methods To overcome these challenges, this study developed a novel biomimetic drug delivery system. Specifically, we prepared poly(lactic-co-glycolic acid) (PLGA) nanoparticles co-loaded with the chemotherapeutic agent doxorubicin (DOX) and the natural polyphenol curcumin (CUR), and subsequently functionalized them with the membrane of human umbilical cord mesenchymal stem cells (hUC-MSCs), which possess inherent tumor-homing capability.Results In vitro studies demonstrated that the hUC-MSCs membrane coating significantly enhanced targeted recognition and cellular uptake by glioblastoma cells, and the biomimetic nanoplatform exhibited superior synergistic cytotoxicity and induced greater cellular apoptosis compared to free drug combinations and uncoated nanoparticles. Antitumor mechanism analysis indicated that biomimetic nanoplatform inhibited glioblastoma migration, invasion, and angiogenesis. In vivo anti-tumor efficacy studies showed that the biomimetic nanoparticles effectively suppressed the growth of tumor. Notably, CUR contributed to the system by amplifying the anticancer activity of DOX and alleviating its associated toxicity.Discussion This work demonstrates that hUC-MSC membrane-camouflaged PLGA nanoparticles enable successful co-delivery of DOX and CUR, offering a promising strategy to address the critical barriers of delivery and toxicity in GBM chemotherapy, supported by their excellent in vitro targeting, in vivo anti-tumor efficacy, and reduced toxicity profile.
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DOI
PubMed
高影响因子
Cell Metabolism
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2026
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IF 37
Jinbao Ye,Qianyi Wan,Xingzhu Liu,Yawen Deng,Zehong Zhang,Haiou Chen,Chaoxin Gao,Shiyu Zhang,Yuedan Zhu,Jinhua Yan,Yu Yuan,Yi Chen,Haiyang Chen
The liver is known to play a pivotal role in modulating blood glucose homeostasis through intrahepatic glucose metabolism. Here, we reveal a unique mechanism by which fatty liver exacerbates hyperglycemia through remote communication from hepatocytes to intestinal stem cells (ISCs), independent of enhanced intrahepatic gluconeogenesis. Mechanistically, hepatocyte-derived alkaline phosphatase (ALP) targets α2δ-1 in ISCs to promote the membrane translocation of Ca v 1.2. This process triggers increased intracellular calcium levels, which subsequently activates the calcineurin/NFATC2 signaling axis, thereby inhibiting SOX21 expression. Then, decreased expression of SOX21 downregulated bone morphogenetic protein 7 (BMP7), ultimately hindering ISCs differentiation into intestinal L-cells. Consequently, the levels of hypoglycemic enteroendocrine hormones secreted by L-cells are decreased, thereby promoting hyperglycemia. Therapeutically, inhibiting ALP synthesis in fatty liver independently reduces blood glucose and synergistically enhances the hypoglycemic effect of metformin. Our study highlights the role of liver-gut communication in regulating the fate of ISC differentiation and blood glucose homeostasis.
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
·Vol. 24
·期 1
·258
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IF 15
Jiang Junbo,Zhang Cailing,Gao Chen,Zhang Haiyang,Cai Guiyuan,Zheng Yunsheng,Kuang Yuxing,Xu Guangqing,Lan Yue
Conductive nerve scaffolds have emerged as a promising alternative to autologous grafts for promoting nerve regeneration. However, optimizing the electroactive properties of scaffold materials and elucidating their regulatory mechanisms on neural stem cell (NSC) differentiation remain critical challenges. Magnetic graphene oxide (MGO), an innovative nanomaterial integrating magnetic responsiveness with two-dimensional carbon-based conductivity, exhibits potential for modulating neural regeneration. Nevertheless, its application in guiding NSC fate within nanofibrous scaffolds is still limited. In this study, a multifunctional MGO-gelatin–polycaprolactone (PCL) composite nanofibrous scaffold—termed the MGO Functionalized Nanofibrous Neural Scaffold—was developed via electrospinning technology, functionalized with superparamagnetic Fe₃O₄ nanoparticles and graphene oxide nanosheets. This design enhanced the scaffold’s mechanical properties, electroactivity, biocompatibility, and structural stability. In vitro experiments demonstrated that the MGO Nanofibrous Scaffold not only supported NSC adhesion and proliferation but also significantly promoted differentiation toward excitatory neuronal phenotypes, suppressed excessive astrocyte activation, and maintained synaptic plasticity and functional maturity. RNA-Seq analysis revealed that the scaffold was associated with the enrichment of key neurogenesis-related pathways, including neurotrophic factor and Wnt-related pathways, which correlated with directed neuronal differentiation and functional maturation of NSCs. Further validation using dorsal root ganglion (DRG) models confirmed its efficacy in accelerating axonal regeneration. Collectively, the MGO Nanofibrous Neural Scaffold constructs an optimized electrophysiological microenvironment conducive to neuronal commitment and nerve fiber regeneration. These findings underscore its significant potential in regulating NSC differentiation and neuronal growth, highlighting the value of multifunctional graphene-based composites in neural tissue engineering. Graphical abstract
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DOI
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
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2026
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IF 9.1
Jialin Yang,Xiang Meng,Qiang An,Xiangting Li,Ayipaiyili Yuetikuer,Xingbang Wan,Shihui Zhang,Xiuzheng Zhuang,Hao Zhan
Tobacco stem (TS), a nitrogen-rich lignocellulosic biowaste, presents challenges for clean thermal utilization because its significant fuel-bound nitrogen converts into NO x pollutants during combustion. While hydrothermal carbonization (HTC) offers a promising pretreatment for source-level denitrogenation, existing HTC methods remain inadequate, typically removing less than 70% of nitrogen and leaving high residual nitrogen in hydrochar. Here, we propose an alkali-assisted HTC strategy employing potassium carbonate (K 2 CO 3 ) as a promoter to enhance nitrogen removal from TS. Under optimized conditions (210 °C, 5 g/100 mL solid-liquid ratio, 30 min), adding only 3 wt% K 2 CO 3 achieved a remarkable nitrogen removal efficiency exceeding 90%. reducing the nitrogen content in the resulting hydrochar to as low as 0.70 wt%, comparable to that of conventional woody and herbaceous biomass. Mechanistic insights revealed that CO 3 2− ion plays a crucial role by enhancing protein hydrolysis, facilitating C N bond cleavage, promoting heterocyclic-N deamination, and suppressing nitrogen-fixation pathways such as Maillard reactions. Despite this effective denitrogenation, the fuel properties of the resulting hydrochar were not superior to those of conventional hydrochar, exhibiting a calorific value of 14.68 MJ·kg −1 , a fuel ratio of 0.19, a comprehensive combustion index of 12.37 × 10 −7 , and a combustion activation energy of 55.53 kJ·mol −1 . These characteristics are attributed to the limited carbonization degree (H/C: 1.77, O/C: 0.84), ash enrichment (ash density: 124.34%), and the catalytic effect of K + . This work successfully demonstrates an efficient catalytic hydrothermal route for converting nitrogen-rich tobacco waste into low-nitrogen hydrochar suitable for use as a solid biofuel, while also highlighting the need for further optimization of hydrochar quality within the carbonate-assisted HTC framework.
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产品关联
DOI
高影响因子
ACS Applied Nano Materials
·
2025
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IF 5.5
Shengnan Zhang,Hongxian Zhou,Xin Liu,Yantong Wu,Shuran Yang,Jia Yin,Mohammad H. Shubair,Mingzhu Zhang
Periodontitis, a chronic inflammatory disease, leads to the progressive destruction of tooth-supporting tissues, and current treatments fall short of fully restoring periodontal regeneration. Dental pulp stem cells (DPSCs) have shown great promise for periodontal regeneration due to their ability to differentiate into multiple cell types and modulate immune responses. However, clinical use of DPSCs remains challenging due to poor cell retention, dependence on scaffolds, and high costs. Additionally, excessive reactive oxygen species (ROS) in the periodontal microenvironment hinder stem cell proliferation and differentiation, further limiting their regenerative potential. To address these challenges, we developed ultrafine cerium oxide nanoparticles (CeO2NPs) and engineered DPSCs (E-DPSCs) by incorporating these antioxidant nanozymes via endocytosis. The modified E-DPSCs exhibited enhanced proliferation, migration, and osteogenic differentiation under normal conditions. Crucially, under oxidative stress, E-DPSCs effectively neutralized ROS, reduced apoptosis, and maintained their osteogenic capacity. In vivo studies further demonstrated that E-DPSCs significantly enhanced periodontal regeneration compared to unmodified DPSCs. These findings highlight E-DPSCs as a promising solution to overcome current limitations in stem cell therapy, offering a more effective strategy for periodontal repair and regeneration.
研究领域:
牙科学
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纳米医学
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干细胞研究
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再生医学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Tengteng Ji,Bing Fang,Ming Zhang,Le Cheng,Xinlei Yuan,Yutong Jin,Fang Wu,Chenyan Zheng,Yumeng Ma
Oat beta-glucan has been reported to be beneficial to glucose and lipid metabolism in human and animal studies. However, weight-loss was shown only in animal studies, whereas human studies reported an improvement in hyperlipidemia. This study investigated the effects of oat beta-glucan on obesity and related metabolic disturbances at the doses based on the Chinese recommended daily intake of 100 g of whole grains which contain approximately 10 % β-glucan. Our data showed that 200 mg/kg efficiently blocked the process of obesity as determined by significantly decreased body weight (7.57 g) and adipose tissue mass (5.24 g) after the 4-week intervention. Lower serum low-density lipoprotein cholesterol (0.32 mmol/L) and reduced atherosclerosis were also observed. Oat beta-glucan improved hepatic lipid metabolism at the low dose (100 mg/kg) and restored it to normal levels in lean mice at the high dose. To our knowledge, our study is the first to analyze the effects of oat beta-glucan on adipose stem cells and reveal the anti-obesity mechanism of oat β-glucan is modulating the adipose stem cell microenvironment. This study determined an efficient supplementary dose for blocking high-fat diet-induced obesity, which not only improved lipid metabolism but also altered stem cell composition in adipose tissue.
研究领域:
营养学
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代谢生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-16
·
IF 15.7
Wang Ran,Qi Yilin,Liu Jinjin,Li Yang,An Hongde,Wang Heping,Song Jie,Hu Wenzhuo,Wu Shaochun,Yu Leqian,Chen Yao,Xue Xue
Embryonic stem cells (ESC) are pluripotent, with the potential to differentiate into multiple cell types, making them a valuable tool for regenerative medicine and disease therapy. However, common culture methods face challenges, including strict operating procedures and high costs. Currently, Leukemia inhibitory factor (LIF), an indispensable bioactive protein for ESC culture, is typically applied to maintain self-renewal and pluripotency, but its instability and high cost limit its effectiveness in stable culture conditions. Hence, we have developed an innovative strategy using a soluble nanomaterial, metal-organic polyhedra (MOPs), to effectively maintain the self-renewal and pluripotency of ESC. The selected amino-modified vanadium-based MOP not only exhibits excellent biocompatibility and high stability but also possesses similar or even superior biological functions compared to commercial LIF. Due to the precise structure of MOPs, the active site responsible for maintaining ESC pluripotency has been identified and regulated at the molecular level. The new ESC culture method significantly reduces costs, simplifies preparation, and enhances the practicality of biopharmaceutical preparation and storage. This represents the first case of using MOPs to maintain self-renewal of ECS, opening an avenue for introducing advanced materials into the development of innovative ESC culture methods.
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
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IF 8
Yayu Wang,Jie Yao,Lizhao Cai,Tong Liu,Xiaogang Wang,Ye Zhang,Zhiying Zhou,Tingwei Li,Minyi Liu,Renfa Lai,Xiangning Liu
Background Current drugs used for osteoporosis therapy show strong adverse effects. Stem cell-derived extracellular vesicles (EVs) provide another choice for osteoporosis therapy. Mouse mesenchymal stem cells (mMSCs)-derived EVs promote bone regeneration; however, their clinical application is limited due to non-specific tissue targeting. Alendronate specifically targets bone tissue via hydroxyapatite. Therefore, EVs were combined with alendronate to generate Ale-EVs by “click chemistry” to facilitate EVs targeting bone via alendronate/hydroxyapatite binding.Methods Ale-EVs were characterized based on size using dynamic light scattering analysis and morphology was visualized by transmission electron microscopy. Hydroxyapatite affinity of Ale-EVs was detected by flow cytometry. Bone targeting of Ale-EVs was tested by ex vivo fluorescent imaging. Cell viability was assessed by using WST-8 reduction assay kit for testing the ability of Ale-EVs to promote mMSCs proliferation. Alkaline phosphatase experiment was used to detect ability of Ale-EVs to promote differentiation of mouse mesenchymal stem cells in vitro. Western blotting and Q-PCR assay were used to detect the early marker of osteogenic differentiation. Antiosteoporotic effects of Ale-EVs were detected in ovariectomy (OVX)-induced osteoporosis rat model. The safety of the Ale-EVs in vivo was measured by H&E staining and serum markers assay.Results In vitro, Ale-EVs had high affinity with hydroxyapatite. Also, ex vivo data indicated that Ale-EVs-DiD treatment of mice induced strong fluorescece in bone tissues compared with EVs-DiD group. Furthermore, results suggested that Ale-EVs promoted the growth and differentiation of mouse MSCs. They also protected against osteoporosis in ovariectomy (OVX)-induced osteoporotic rats. Ale-EVs were well tolerated and no side effects were found, indicating that Ale-EVs specifically target bone and can be used as a new therapeutic in osteoporosis treatment.Conclusion We used the Ale-N3 to modify mouse mesenchymal stem cells-derived extracellular vesicles by copper-free “click chemistry” to generate a Ale-EVs system. The Ale-EVs had a high affinity for bone and have great potential for clinical applications in osteoporosis therapy with low systemic toxicity.
研究领域:
干细胞研究
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骨骼生物学
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药物递送系统
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再生医学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
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2015
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IF 5.578
Shixuan Chen,Junbin Shi,Min Zhang,Yinghua Chen,Xueer Wang,Lei Zhang,Zhihui Tian,Yuan Yan,Qinglin Li,Wen Zhong,Malcolm Xing,Lu Zhang,Lin Zhang
The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed in vitro investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF. In vivo, full-thickness skin defects were made on the backs of db/db mice to mimic diabetic ulcers. It was revealed that the hydrogel can inhibit pro-inflammatory M1 macrophage expression. After hydrogel association with BMSCs treated the wound, significantly greater wound contraction was observed in the hydrogel + BMSCs group. Histology and immunohistochemistry results confirmed that this treatment contributed to the rapid healing of diabetic skin wounds by promoting granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction, and re-epithelialization. These results show that a hydrogel laden with BMSCs may be a promising therapeutic strategy for the management of diabetic ulcers.
研究领域:
干细胞生物学
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伤口愈合
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糖尿病
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药剂学
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生物医学工程
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DOI
PubMed
高影响因子
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