Pharmacology Research & Perspectives
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2021
·Vol. 9
·期 3
·e00791
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IF 2.794
Suoli Cheng,Xueqin Liu,Fan Gong,Xiaoling Ding,Xuebing Zhou,Cuiyun Liu,Fei Zhao,Xiaoliang Li,Jiandang Shi
The pathogenesis of steroid-induced avascular necrosis of femoral head (SANFH) is complex, and there is a lack of effective early prevention method. The aim of the present study was to evaluate the effect of dexamethasone (DEX) on the biological behavior of bone marrow mesenchymal stem cells (BMSCs) and to explore the possibility of DEX in the clinical treatment of SANFH. The effect of DEX on the proliferation of BMSCs was evaluated by Counting Kit-8 assay, western blot assay, and enzyme-linked immunosorbent assay. Flow cytometry and western blot assay were performed to detect the effect of DEX on the apoptosis of BMSCs. Quantitative real-time PCR and western blot assay were performed to detect the effect of DEX on the expression of endoplasmic reticulum stress (ERS)-related genes. Immunoblotting analysis was conducted for detecting the nuclear-cytoplasmic distribution of Nrf2. DEX could significantly inhibit the proliferation of BMSCs and promote apoptosis of BMSCs. DEX could increase the expression of PERK, ATF6, and IRE1a, and induce nuclear translocation of Nrf2. The addition of ML385 could reverse the effect of DEX on BMSCs. DEX could activate the PERK-Nrf2 pathway to promote ERS and finally affect the cell proliferation and apoptosis of BMSCs.
研究领域:
药理学
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细胞生物学
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干细胞研究
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骨科
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DOI
PubMed
高影响因子
CELL PROLIFERATION
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2023
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IF 8.5
Juanyu Zhou,Li He,Mengyou Liu,Xiaoxin Guo,Gang Du,La Yan,Zehong Zhang,Zhendong Zhong,Haiyang Chen
Sleep is essential for maintaining health. Indeed, sleep loss is closely associated with multiple health problems, including gastrointestinal disorders. However, it is not yet clear whether sleep loss affects the function of intestinal stem cells (ISCs). Mechanical sleep deprivation and sss mutant flies were used to generate the sleep loss model. qRT-PCR was used to measure the relative mRNA expression. Gene knock-in flies were used to observe protein localization and expression patterns. Immunofluorescence staining was used to determine the intestinal phenotype. The shift in gut microbiota was observed using 16S rRNA sequencing and analysis. Sleep loss caused by mechanical sleep deprivation and sss mutants disturbs ISC proliferation and intestinal epithelial repair through the brain–gut axis. In addition, disruption of SSS causes gut microbiota dysbiosis in Drosophila . As regards the mechanism, gut microbiota and the GABA signalling pathway both partially played a role in the sss regulation of ISC proliferation and gut function. The research shows that sleep loss disturbed ISC proliferation, gut microbiota, and gut function. Therefore, our results offer a stem cell perspective on brain–gut communication, with details on the effect of the environment on ISCs.
研究领域:
神经科学
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细胞生物学
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分子生物学
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微生物学
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DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2021
·
IF 9.078
Jianlong He,Min Hao,Jiazhi Duan,He Xia,Weiran Li,Hao Xue,Shuhua Wang,Wei Liu,Dong Li,Yuanhua Sang,Hong Liu
Neural stem cells (NSCs) based nerve repair is the most promising approach for neurodegenerative disease therapy. However, the long-time requirement for NSCs differentiation into mature neurons challenges the clinical applications of NSCs because of the missing of the best opportunity for nerve repair. In this work, we synthesized four kinds of one-dimensional (1D) hydroxyapatite (HAp) nanomaterials with different morphologies of short nanorod , long nanorod, short nanowire , and long nanowire. And we found that rapid differentiation of NSCs could be realized just by the endocytosis of 1D HAp nanomaterials with different lengths. Both the endocellular calcium ion (Ca 2+ ) release of HAp nanosturctures suffered a low pH in endosomes and their nanotopography can regulate the neural differentiation of NSCs, and their synergistic effect is the main reason for the acceleration of NSCs differentiation. The safe, rapid and low-cost approach for promoting NSCs differentiation supposed in this work will have great potential in clinical applications for therapy of neurodegenerative diseases.
研究领域:
材料科学
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神经科学
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干细胞研究
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生物医学工程
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DOI
高影响因子
Odontology
·
2023
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IF 2.5
Cui Zhao,Xu Yunhe,Wu Peng,Lu Ying,Tao Yongxin,Zhou Chuibing,Cui Ruting,Li Jingying,Han Rongpeng
Periodontal tissue regeneration engineering based on human periodontal ligament stem cells (hPDLSCs) provides a broad prospect for the treatment of periodontal disease. N-Acetyltransferase 10 (NAT10)-catalyzed non-histone acetylation is widely involved in physiological or pathophysiological processes. However, its function in hPDLSCs is still missing. hPDLSCs were isolated, purified, and cultured from extracted teeth. Surface markers were detected by flow cytometry. Osteogenic, adipogenic, and chondrogenic differentiation potential was detected by alizarin red staining (ARS), oil red O staining, and Alcian blue staining. Alkaline phosphatase (ALP) activity was assessed by ALP assay. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of key molecules, such as NAT10, Vascular endothelial growth factor A (VEGFA), PI3K/AKT pathway, as well as bone markers (RUNX2, OCN, OPN). RNA-Binding Protein Immunoprecipitation PCR (RIP-PCR) was used to detect the N4-acetylcytidine (ac4C) mRNA level. Genes related to VEGFA were identified by bioinformatics analysis. NAT10 was highly expressed in the osteogenic differentiation process with enhanced ALP activity and osteogenic capability, and elevated expression of osteogenesis-related markers. The ac4C level and expression of VEGFA were obviously regulated by NAT10 and overexpression of VEGFA also had similar effects to NAT10. The phosphorylation level of PI3K and AKT was also elevated by overexpression of VEGFA. VEGFA could reverse the effects of NAT10 in hPDLSCs. NAT10 enhances the osteogenic development of hPDLSCs via regulation of the VEGFA-mediated PI3K/AKT signaling pathway by ac4C alteration.
研究领域:
干细胞生物学
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分子生物学
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再生医学
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牙科科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Rui Zhang,Wenhang Li,Xiaodan Jiang,Xinyi Cui,Hongjie You,Zuoqing Tang,Wenlan Liu
Bone marrow mesenchymal stem cells (BMSCs) can effectively alleviate liver fibrosis, but the efficacy of cell therapy alone is insufficient. In recent years, a combination of traditional Chinese medicine (TCM) and cell therapy has been increasingly used to treat diseases in clinical trials. Ferulic acid (FA) is highly effective in treating liver fibrosis, and a combination of cells and drugs is being tested in clinical trials. Therefore, we combined BMSCs and Ferulic acid to treat CCl 4 -induced fibrosis and determine whether this combination was more effective than single treatment. We used BMSCs and FA to treat CCl 4 -induced fibrosis in rat models, observed their therapeutic effects, and investigated the specific mechanism of this combination therapy in liver fibrosis. We created a BMSC/hepatic stellate cell (HSC) coculture system and used FA to treat activated HSCs to verify the specific mechanism. Then, we used cytochalasin D and angiotensin II to investigate whether BMSCs and FA inactivate HSCs through cytoskeletal rearrangement. MiR-19b-3p was enriched in BMSCs and targeted TGF-β receptor II (TGF-βR2). We separately transfected miR-19b-3p into HSCs and BMSCs and detected hepatic stellate cell activation. We found that the expression of the profibrotic markers α-SMA and COL1-A1 was significantly decreased in the combination group of rats. α-SMA and COL1-A1 levels were also significantly decreased in the HSCs with the combination treatment. Cytoskeletal rearrangement of HSCs was inhibited in the combination group, and RhoA/ROCK pathway gene expression was decreased. Following angiotensin II treatment, COL1-A1 and α-SMA expression increased, while with cytochalasin D treatment, profibrotic gene expression decreased in HSCs. The expression of COL1-A1, α-SMA and RhoA/ROCK pathway genes was decreased in the activated HSCs treated with a miR-19b-3p mimic, indicating that miR-19b-3p inactivated HSCs by suppressing RhoA/ROCK signalling. In contrast, profibrotic gene expression was significantly decreased in the BMSCs treated with the miR-19b-3p mimic and FA or a miR-19b-3p inhibitor and FA compared with the BMSCs treated with the miR-19b-3p mimic alone. In conclusion, the combination therapy had better effects than FA or BMSCs alone. BMSC and FA treatment attenuated HSC activation and liver fibrosis by inhibiting cytoskeletal rearrangement and delivering miR-19b-3p to activated HSCs, inactivating RhoA/ROCK signalling. FA-based combination therapy showed better inhibitory effects on HSC activation.
研究领域:
药理学
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干细胞生物学
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肝病学
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分子生物学
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中医药
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DOI
PubMed
高影响因子
PLANT BIOLOGY
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2026
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IF 3.4
Y. Yang,Y. Jin,H. Cai,A. Ren,Y. Wan,Y. Liu
Insufficient light intensity diminishes stem mechanical strength of Paeonia lactiflora , adversely affecting the quality of cut flowers. However, the underlying mechanisms remain poorly understood. Through anatomical analysis and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) combined with LC-MS, the shading-induced changes of morphology and metabolism in fibre cells of P. lactiflora stems were comprehensively characterized for the first time. The results showed that shading inhibited secondary cell wall (SCW) thickening in fibre cells, leading to thinner SCWs and low stem mechanical strength. A total of 931 metabolites were detected in the full-sun and shade groups of P. lactiflora stem sections by MALDI MSI, and 25 significant differential metabolites were identified in the stem fibre cell zones by MS/MS fragmentations. The shading-induced differential metabolites in the fibre cell zones were primarily concentrated on various secondary metabolites with antioxidant defence properties, with their synthesis triggered by shade stress. It indicated that shading reduced P. lactiflora stem mechanical strength by inhibiting fibre SCW thickening, and this inhibition was closely correlated with an enhanced synthesis of defence metabolites in the fibre cells. This study lays a foundation for elucidating the cytological mechanism underlying shading that affects stem mechanical strength.
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2026
·
IF 10.4
Qiyan Chen,Fei Zhou,Yongxin Chen,Zheling Feng,Jingli Min,Lei Zhang,Tian Zhang,Ying Zheng,Jinming Zhang,Ligen Lin
Inducing white adipose tissue (WAT) browning is a promising strategy to combat obesity and metabolic disorders. However, current browning inducers often suffer from off-target effects and poor durability. Beige adipocytes, which can arise through de novo differentiation from adipose-derived stromal/stem cells (ASCs), offer a potential avenue for sustained thermogenesis. Here, we identified that forskolin (FSK) effectively induced the differentiation of C3H10T1/2 cells (a mesenchymal stem cell line) into beige adipocytes, evidenced by multilocular lipid droplets, enhanced mitochondrial biogenesis and function, and elevated uncoupling protein 1 expression. To overcome its poor bioavailability and lack of targeting specificity, we developed ASCs-targeting-peptide (ASP, sequence: GSWKYWFGEGGC) modified FSK nanoparticles (ASP@FSK NPs) by encapsulating FSK in the hybrid FDA-approved biodegradable polymers poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG)-ylated PLGA. ASP@FSK NPs selectively bind to glycanation site-deficient decorin (ΔDCN) receptors on ASCs, enabling prolonged retention and localized delivery within inguinal WAT (iWAT). In a high-fat diet-induced obesity model, local administration of ASP@FSK NPs significantly reduced body weight (∼30%), promoted de novo browning of iWAT, and alleviated liver steatosis in high-fat diet-induced obese mice, while expanding the therapeutic window of FSK and without apparent toxicity. Collectively, this study demonstrated that FSK could be developed as a potent inducer of de novo beige adipogenesis and targeted delivery of FSK to ASCs might provide a valuable strategy for the treatment of obesity. Statement of Significance Obesity and metabolic syndromes remain global health challenges, and strategies that induce white adipose tissue browning hold great therapeutic potential. However, existing browning agents are limited by systemic toxicity, off-target effects, and poor sustainability. This study addresses these critical gaps by demonstrating that forskolin (FSK) drives de novo beige adipocyte differentiation from mesenchymal stem cells. We further developed an adipose-derived stem cell-targeted nanoparticle system (ASP@FSK NPs) for localized and sustained delivery. In obese mice, ASP@FSK NPs efficiently promoted inguinal WAT browning, alleviated adiposity and hepatic steatosis, and expanded the therapeutic window of FSK without obvious toxicity. This work establishes a targeted and durable approach for WAT browning and obesity treatment by integrating a progenitor-directed biological strategy with precision nanomedicine. Download: Download high-res image (269KB) Download: Download full-size image
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高影响因子
Autophagy
·
2026
·
IF 18.6
Zhengran Li,Huiqing Zhao,Danjie Zhang,Jing Wei,Xiyue Tao Liu,Ruiyan Kong,Xuejing Ren,Hang Zhao,Xiaomin Fang,Jingyan Fu,Zhouhua Li
The self-renewal and differentiation of stem cells are tightly controlled to maintain tissue homeostasis. Failure in stem cell maintenance results in stem cell depletion and precocious aging. However, how stem cells are maintained still remains not fully understood. Here, through a large-scale RNAi screen for maintenance and proliferation of adult Drosophila intestinal stem cells (ISCs), we identify several subunits of V-ATPase including Vha68-2/ATP6V1A, required for ISC proliferation, differentiation and tissue regeneration. Inactivation of Vha68-2 results in accumulation of plasma membrane (PM)-derived structures in autophagosomes and lysosomes through Atg16 and Rab5. Furthermore, Vha68-2-defective ISCs undergo direct differentiation due to ectopic Notch activation. Mechanistically, Vha68-2 facilitates Notch receptor internalization and subsequent degradation in autolysosomes to quench ectopic Notch activation, thereby maintaining ISC fate. Truncated Notch product devoid of its extracellular domain is accumulated in autolysosomes upon Vha68-2 deficiency. The Notch products accumulated in autolysosomes still require further cleavage to drive ISC differentiation. The functions of Vha68-2 in macroautophagy/autophagy and ISC maintenance are evolutionarily conserved. Our results provide new insights into the underlying mechanism of how autophagy is involved in stem cell maintenance under physiological conditions.Abbreviations: aph-1: anterior pharynx defective 1; ATP6V1A: ATPase H+ transporting V1 subunit A; CASM: conjugation of ATG8s to single membranes; EB: enteroblast; EC: absorptive enterocyte; ER: endoplasmic reticulum; ISC: intestinal stem cell; kuz: kuzbanian; LTDR: LysoTracker Deep Red; LTR: LysoTracker Red; MARCM: mosaic analysis with a repressible cell marker; NECD: Notch extracellular domain; NICD: Notch intracellular domain; PM: plasma membrane; PAS: phagophore assembly site; SNARE: soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; TEM: transmission electron microscopy; TM: tunicamycin.
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高影响因子
Bioactive Materials
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2026
·
IF 23.6
Xudong Xie,Liangcong Hu,Yueman Zhang,Bobin Mi,Xiaoyue Xu,Chong Ding,Yiming Li,Fawwaz Al-Smadi,Xiangyu Chu,Yuan Xiong,Kunyu Zhang,Liming Bian,Guohui Liu
Dynamic mechanical signaling of the extracellular matrix is a key determinant of mesenchymal stem cell (MSC) fate, closely regulating their proliferation, differentiation and migration. Previously, we developed a highly cell-adaptive dynamic hydrogel (HA-ADA) that modulates MSC fate through unknown mechanisms. Here, using human bone marrow-derived mesenchymal stem cells (hMSCs), we found that sustained mechanical stimulation provided by HA-ADA hydrogel induced rapid spreading and significantly enhanced their osteogenic differentiation while inhibiting adipogenesis. Mechanistically, miRNA sequencing revealed that this process was mediated by the downregulation of miR-376a-3p and miR-127-5p, thereby relieving their inhibitory effect on the methyltransferase SETD7. Elevated SETD7 expression catalyzed methylation of β-catenin and accelerated its nuclear translocation. In the nucleus, β-catenin further formed a transcriptional complex with YAP to synergistically amplify downstream signals and potently activate the expression of Runx2, a key transcription factor for osteogenesis, which ultimately drove osteogenic differentiation and inhibited adipogenesis. The present study elucidated a novel mechanism by which cell-adaptive hydrogels regulate the β-catenin/YAP signaling loop through the miR-376a-3p/miR-127-5p-SETD7 axis, thereby determining the osteogenic/adipogenic differentiation of stem cells, which not only deepens our understanding of mechanotransduction but also provides new targets and material design strategies for bone regeneration.
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2026
·Vol. 63
·期 1
·518
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IF 5.5
Ma Ya-nan,Wang Zijie,Liang Yuchang,Tan Guoao,Hu Xiqi,Xia Ying
This study aims to investigate the effect of exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-Exo) on microglial polarization and its potential therapeutic role in Alzheimer’s disease (AD). OM-MSCs-Exo were isolated and purified from the mice olfactory mucosa, followed by phenotypic characterization. Proteins transferred by OM-MSCs-Exo were screened using proteomic analysis. The AD model was established in microglial cells and mice with Aβ 1–42 . Immunofluorescence and biochemical assays were employed to assess the impact of OM-MSCs-Exo and its secreted protein FGFR1 on microglial polarization. Protein–protein interactions and immunoprecipitation were used to identify the target proteins of FGFR1 in microglial cells. Additionally, the effects of OM-MSCs-Exo-induced microglial polarization on neuronal inflammation and cognitive function in mice were evaluated. OM-MSCs-Exo were successfully isolated and purified. FGFR1 was significantly upregulated in OM-MSCs-Exo compared to OM-MSCs. Aβ 1–42 induced M1 polarization and suppressed M2 polarization of microglia, which was reversed by OM-MSCs-Exo. FGFR1 overexpression in OM-MSCs-Exo further enhanced M2 polarization in microglial cells. Phospholipase C gamma 1 (PLCγ1) was identified as the target of FGFR1, and knocking down PLCγ1 reversed the effects of FGFR1-overexpressing OM-MSCs-Exo. OM-MSCs-Exo alleviated cognitive decline and neuroinflammation in AD mice, with FGFR1 overexpression further enhancing these effects. OM-MSCs-Exo promote M2 polarization of microglia in AD mice through the FGFR1/PLCγ1 pathway, alleviating neuronal inflammation and cognitive dysfunction.
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Deng Peishen,Zheng Manhong,Du Bing,Liu Changyu,Cheng Renyi,Liu Chaofeng,Wang Fang,Dong Hangyu,Shan Yan,Xu Yanhua
Repairing large-scale craniomaxillofacial bone defects is hindered by a limited availability of stem-cell sources and a low osteogenic efficiency. To address these challenges, Fe3O4 nanoparticles were modified with methacrylic anhydride (MAA) which helped to introduce photopolymerizable methacryloyl groups, resulting in MAA-Fe3O4 nanoparticles that exhibit excellent magnetic properties and colloidal stability. These nanoparticles were incorporated into gelatin methacryloyl (GelMA) and covalently crosslinked to form an injectable, photocurable GelMA-Fe3O4 magnetic composite hydrogel. This hydrogel provides a three-dimensional (3D) culture microenvironment for human dental follicle stem cells (hDFSCs), and upon encapsulation, osteogenesis was significantly enhanced under a 100 mT static magnetic field (SMF). In vitro, GelMA-Fe3O4 hydrogels demonstrated increased porosity and improved mechanical properties, thereby significantly promoting hDFSCs proliferation, adhesion, and spreading. Additionally, under SMF exposure, the expression of osteogenesis-related genes and proteins, including ALP, Runx2, Col-I, and OPN, was significantly upregulated. In a rat calvarial defect model, bone mineralization centers with multi-site distribution were observed in the GelMA-Fe3O4 + SMF group as early as 4 weeks postoperatively, leading to high-quality defect repair. The limitations of traditional 'peripheral-to-center’ unidirectional repair were overcome by this model of synchronous multi-site osteogenesis, maximizing bone regeneration with a minimal number of stem cells and providing an efficient, controllable tissue-engineering strategy for the clinical treatment of craniomaxillofacial bone defects.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Heng Zhou,Qiang Qin,Xiqin Li,Hanyu Ding,Chun Xu,Yan He,Qingsong Ye
Spinal cord injury (SCI) often causes permanent neurological deficits due to limited neuron regeneration and glial scar formation. Stem cell therapy is promising, but transplanted stem cells often differentiate into astrocytes rather than neurons under inflammatory conditions. To address this, a nuclei-targeting, histone acetylation–regulated lipid nanoparticle (LNP) was developed to direct stem cell fate. The LNP was functionalized with the MPG cell-penetrating peptide (LNP-MPG) for nuclei-targeting, greatly enhancing the transfection efficiency of dental pulp stem cells (DPSCs). It delivered a high-molecular-weight FGF2 (HMW-FGF2) plasmid to activate nuclear FGFR1, promoting CBP/p300-dependent histone H3 acetylation. This epigenetic modulation drove DPSCs to differentiate into neurons rather than astrocytes even under inflammatory conditions. In a mouse SCI model, DPSCs transfected with HMW-FGF2@LNP-MPG significantly promoted neuronal regeneration, reduced glial scarring, and improved motor function. Mechanistically, we further confirmed that the engineered DPSCs formed functional synaptic integration with V2a-linked circuitry, the core component of the spinal locomotor central pattern generator; specific ablation of V2a interneurons completely abolished the motor functional recovery induced by DPSC transplantation. These results demonstrate that this histone acetylation–regulated nano-converter effectively redirects stem cell fate and improves functional recovery, offering a promising therapeutic approach for SCI repair.
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高影响因子
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