CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Guanlu Shen,Xinxin Si,Lei Qiang,Yihao Liu,Zhiyang Yin,Jing Shan,Pengfei Zheng
Growth plate injuries in children and adolescents often lead to bone bridge formation, resulting in limb deformities due to the limited self-repair capacity of the growth plate. The limitations of traditional treatments prompted interest in the role of the extracellular matrix (ECM) and mechanical environment in tissue repair. Recent research showed that 3D hydrogels could mimic ECM to regulate mesenchymal stem cells (MSCs) differentiation, with MSCs sensing matrix viscoelasticity via Piezo1 and responding through the ROCK signaling pathway. This study aimed to develop a 3D biomimetic hydrogel composed of acellular cartilage matrix methacryloyl (ACMMA) and gelatin methacryloyl (GelMA), with adjustable viscoelasticity via blue light crosslinking time. Hydrogels with low (5 s) and high (20s) modulus were fabricated and loaded with bone marrow mesenchymal stem cells (BMSCs). Results demonstrated that the 5 s hydrogel promoted chondrogenic differentiation and inhibited osteogenesis, effectively preventing bone bridge formation and enhancing growth plate repair in vivo . Mechanistic studies confirmed that the 5 s group did not activate the Piezo1-ROCK pathway, supporting its role in chondrogenic differentiation.
研究领域:
生物医学工程
·
组织工程
·
干细胞研究
·
生物材料
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
CELL PROLIFERATION
·
2023
·
IF 8.5
Guanhui Cai,Yahui Lu,Weijie Zhong,Ting Wang,Yingyi Li,Xiaolei Ruan,Hongyu Chen,Lian Sun,Zhaolan Guan,Gen Li,Hengwei Zhang,Wen Sun,Minglong Chen,Wei-Bing Zhang,Hua Wang
Macrophages are multifunctional immune system cells that are essential for the mechanical stimulation-induced control of metabolism. Piezo1 is a non-selective calcium channel expressed in multifarious tissues to convey mechanical signals. Here, a cellular model of tension was used to study the effect of mechanical stretch on the phenotypic transformation of macrophages and its mechanism. An indirect co-culture system was used to explore the effect of macrophage activation on bone marrow mesenchymal stem cells (BMSCs), and a treadmill running model was used to validate the mechanism in vivo for in vitro studies. p53 was acetylated and deacetylated by macrophages as a result of mechanical strain being detected by Piezo1. This process is able to polarize macrophages towards M2 and secretes transforming growth factor-beta (TGF-β1), which subsequently stimulates BMSCs migration, proliferation and osteogenic differentiation. Knockdown of Piezo1 inhibits the conversion of macrophages to the reparative phenotype, thereby affecting bone remodelling. Blockade of TGF-β I, II receptors and Piezo1 significantly reduced exercise-increased bone mass in mice. In conclusion, we showed that mechanical tension causes calcium influx, p53 deacetylation, macrophage polarization towards M2 and TGF-β1 release through Piezo1. These events support BMSC osteogenesis.
研究领域:
免疫学
·
细胞生物学
·
力学生物学
·
骨生物学
✓ 已验证
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2025
·
IF 5.1
Qian Chen,Huaxing Zhang,Yuhong Chen,Yangxuan Peng,Yuhan Yao,Hongmei Xue,Qi Guo,Danyang Tian,Lin Xiao,Xu Teng,Mingqi Zheng,Bing Xiao,Yuming Wu,Sheng Jin
Aims The present study aimed to investigate the direct link between trimethylamine N-oxide (TMAO) and diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF). Materials and methods Diastolic dysfunction is the main manifestation of HFpEF, so the “two-hit” mouse HFpEF model are used. After treated with high-fat diet (HFD) and N [w] -nitro-l-arginine methyl ester (L-NAME) for 8 weeks, the cardiac function, myocardial fibrosis, oxidative stress levels, and molecular alterations were assessed. Key findings The HFpEF mice displayed a declined diastolic function, characterized by an increase in the E/E' ratio, accompanied by a significant increase in plasma brain natriuretic peptide levels and cardiac fibrosis and down-regulation of SERCA2 expression, while, DMB treatment improved diastolic function. Subsequently, TMAO was injected intraperitoneally into the mice for 1 month and found that TMAO induced diastolic dysfunction. In addition, we found that either the HFD and L-NAME or TMAO treatment down-regulated Piezo1 expression, and the cardiomyocyte-specific Piezo1 knockout mice (Piezo1 ΔCM ) also had diastolic dysfunction. Moreover, the NOX4 expression was up-regulated and the reactive oxygen species levels were increased in the heart tissues of Piezo1 ΔCM or TMAO-treated mice, which was reversed by a Piezo1 activator (Yoda1) in the TMAO-treated mice. Yoda1 also reversed diastolic dysfunction in the HFpEF mice. Significance In conclusion, our data revealed that TMAO-induced oxidative stress injury by down-regulating Piezo1 to be involve in cardiac diastolic dysfunction of HFpEF. It should be noted that this preclinical study did not evaluate HFpEF-related symptoms such as exercise intolerance or pulmonary congestion, which warrant further validation.
研究领域:
心脏病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cells
·
2024
·Vol. 13
·期 20
·1697
·
IF 5.1
Kai Ni,Bo Che,Rong Gu,Chunhong Wang,Yan Pan,Jingjing Li,Lei Liu,Mingzhi Luo,Linhong Deng
Severe asthma is characterized by increased cell volume (hypertrophy) and enhanced contractile function (hyperresponsiveness) of the airway smooth muscle cells (ASMCs). The causative relationship and underlying regulatory mechanisms between them, however, have remained unclear. Here, we manipulated the single-cell volume of in vitro cultured human ASMCs to increase from 2.7 to 5.2 and 8.2 × 103μm3as a simulated ASMC hypertrophy by culturing the cells on micropatterned rectangular substrates with a width of 25 μm and length from 50 to 100 and 200 μm, respectively. We found that as the cell volume increased, ASMCs exhibited a pro-contractile function with increased mRNA expression of contractile proteins, increased cell stiffness and traction force, and enhanced response to contractile stimulation. We also uncovered a concomitant increase in membrane tension and Piezo1 mRNA expression with increasing cell volume. Perhaps more importantly, we found that the enhanced contractile function due to cell volume increase was largely attenuated when membrane tension and Piezo1 mRNA expression were downregulated, and an auto-regulatory loop between Piezo1 and YAP mRNA expression was also involved in perpetuating the contractile function. These findings, thus, provide convincing evidence of a direct link between hypertrophy and enhanced contractile function of ASMCs that was mediated via Piezo1 mRNA expression, which may be specifically targeted as a novel therapeutic strategy to treat pulmonary diseases associated with ASMC hypertrophy such as severe asthma.
研究领域:
肺生物学
·
细胞生物学
·
分子生物学
·
生物物理学
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PATHOLOGY
·
2024
·
IF 4.7
N.I.N.G. HAN,N.A. YU,L.I. YU
Diabetic retinopathy (DR) is the major ocular complication of diabetes mellitus caused by chronic hyperglycemia, which leads to incurable blindness. Currently, the effectiveness of therapeutic interventions is limited. This study aimed to investigate the function of piezo-type mechanosensitive ion channel component 1 (PIEZO1) and its potential regulatory mechanism in DR progression. The results showed that PIEZO1 expression was upregulated in the retinal tissues of streptozotocin-induced diabetic mice and high glucose (HG)-triggered Müller cells. Functionally, the knockdown of PIEZO1 improves the abnormal retinal function of diabetic mice and impedes inflammatory cytokine secretion and gliosis of Müller cells under HG conditions. Mechanistic investigations utilizing RIP-qPCR, MeRIP-qPCR, and luciferase reporter assays demonstrated that PIEZO1 was a downstream target of methyltransferase-like 3 (METTL3). These studies revealed that METTL3-mediated N6-methyladenosine (m6A) modification within the coding sequence of PIEZO1 mRNA significantly shortened its half-life. In HG-stimulated cells, there was a negative regulatory relationship between PIEZO1 and YTH domain family 2 (YTHDF2), a recognized m6A reader. The loss of YTHDF2 resulted in an extended half-life of PIEZO1 in cells with overexpression of METTL3, indicating that the effect of METTL3 on the mRNA stability of PIEZO1 was dependent on YTHDF2. Taken together, this study demonstrated the protective role of the PIEZO1 silencing in DR development, and the degradation of PIEZO1 mRNA is accelerated by METTL3/YTHDF2-mediated m6A modification.
研究领域:
分子生物学
·
细胞生物学
·
神经科学
·
糖尿病研究
·
眼科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Genjiang Zheng,Chen Yang,Wei Yu,Ye Tian,Zeng Xu,Jia Liu,Shatong He,Yunhao Wang,Zhihao Yue,Xiaodong Wu,Hongyu Zhou,Bo Hu,Wei-En Yuan,Huajiang Chen
Paralysis resulting from spinal cord injury (SCI) arises from the limited regenerative capacity of axons. Mechanical factors have recently emerged as crucial regulators of axon regeneration, complementing or even surpassing chemical cues. In this study, we demonstrated that extracellular matrix stiffness, a key mechanical signal, not only modulated the regenerative capacity of neuronal axons in spinal cord with aging, but significantly fine-tuned axon pathfinding through negative-durotaxis pattern. So, it is imperative to develop a scaffold with biomimetic mechanical guidance properties to promote neural axon regeneration after SCI. Strikingly, inspired by the robust adhesive mechanism of mussels, we developed a facile strategy to synthesize catechol-modified HAMA hydrogel (HAMA@CA) that mimics native spinal cord tissue properties, effectively modulates the biomechanical microenvironment, enhances tissue–implant adhesion, and ultimately promotes spinal cord integration after SCI. Mechanistically, HAMA@CA hydrogel regulates neuronal axon pathfinding following a negative durotaxis pattern, coinciding with changes in mechanosensitive signaling and actomyosin contractility via the Piezo1/RhoA/MLC pathway. RNA-seq analysis also confirms mechanical-mediated SCI repairing by HAMA@CA. These results demonstrates that HAMA@CA rationally combined with mechanical and biochemical cues create promising tissue-engineered strategies to facilitate the repair of SCI. This innovative strategy holds significant promise for future clinical applications in the field.
研究领域:
神经科学
·
生物医学工程
·
组织工程
·
机械生物学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2022
·Vol. 18
·期 23
·2201123
·
IF 15.153
Jing Li,Yao Zhang,Zhichao Lou,Mingxi Li,Lin Cui,Zhenrong Yang,Lijuan Zhang,Yu Zhang,Ning Gu,Fang Yang
Neural stem cells (NSCs) are used to treat various nervous system diseases because of their self-renewal ability and multidirectional differentiation potential. However, an insufficient ability to track their migration in vivo and poor control over their survival and differentiation efficiency are two major critical challenges for clinical application. Here, it is shown that when magnetic nanobubbles (MNBs), which are assembled from magnetic nanoparticles, are internalized by NSCs, intramembrane volumetric oscillation of the MNBs induces an increase in intracellular hydrostatic pressure and cytoskeleton force, resulting in the activation of the Piezo1-Ca 2+ mechanosensory channel. This subsequently triggers the BMP2/Smad biochemical signaling pathway, leading to differentiation of NSCs into the neuronal phenotype. Signaling through the Piezo1-Ca 2+ -BMP2/Smad pathway can be further accelerated by application of an external shear stress force using low-intensity pulsed ultrasound. More importantly, magnetic resonance imaging and ultrasound imaging surveillance of NSCs based on MNB labeling can be leveraged to provide NSC therapeutic outcomes. Both the in vitro and in vivo findings demonstrate that a bubble nanostructure-induced physical force can modulate and control the mechanical signaling pathway regulating stem cell development.
研究领域:
神经科学
·
生物医学工程
·
干细胞生物学
·
医学影像学
·
力学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Baohong Li,Zichao Chen,Zhenyong Zhang,Hui Liu,Dongli Han,Haolin Yang,Zhen Zhang
Background: Breast cancer bone metastasis is closely associated with the bone microenvironment. Zuogui Pill (ZGP), a clinically approved formulation in China, effectively regulates the bone microenvironment for the prevention and treatment of osteoporosis. Purpose: Few reports have utilized the ZGP for bone metastasis models. This study investigated the intervention and bone-protective properties of ZGP against breast cancer bone metastasis, explored the potential mechanism, and screened for its active compositions by molecules fishing. Methods: To investigate the intervention efficacy of ZGP and its protein-level mechanism of action, the mouse bone metastasis model and in vitro cell co-culture model were constructed. Affinity ultrafiltration, molecular docking, cellular thermal shift assay and physical scale detection were used to investigate the affinity components of the RANKL protein in ZGP. Results: The administration of ZGP combined with zoledronic acid inhibited the development of tumors and secondary lung metastasis in mice. This translated to a prolonged survival period and enhanced quality of life. ZGP could disrupt the malignant cycle by modulating the Piezo1-Notch-1-GPX4 signaling pathway in the "bone-cancer" communication in the cell co-culture model. Furthermore, 25 chemical components of ZGP were identified, with 10 active compounds exhibiting significant affinity for the RANKL protein. Conclusion: The findings of this work highlighted ZGP's potential for intervening in the progression of breast cancer bone metastasis. Thus, this investigation served as an experimental foundation for expanding the application scope of ZGP and for advancing drug development efforts in bone metastasis treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·
IF 29.4
Haitao Guan,Wei Wang,Zichao Jiang,Boyu Zhang,Zhipeng Ye,Judun Zheng,Wei Chen,Yuhui Liao,Yingze Zhang
Osteoporosis, characterized by an imbalance in bone homeostasis, is a global health concern. Bone defects are difficult to heal in patients with osteoporosis. Classical drug treatments for osteoporotic bone defects have unsatisfactory efficacy owing to side effects and imprecise delivery problems. In this study, a magnetic aggregation-induced bone-targeting poly(lactic-co-glycolic acid, PLGA)-based nanocarrier (ZOL-PLGA@Yoda1/SPIO) is synthesized to realize dual-targeted delivery and precise Piezo1-activated therapy for osteoporotic bone defects. Piezo1 is an important mechanotransducer that plays a key role in regulating bone homeostasis. To achieve dual-targeting properties, ZOL-PLGA@Yoda1/SPIO is fabricated using zoledronate (ZOL)-decorated PLGA, superparamagnetic iron oxide (SPIO), and Piezo1-activated molecule Yoda1 via the emulsion solvent diffusion method. Bone-targeting molecular mediation and magnetic aggregation-induced properties can jointly and effectively achieve precise delivery to localized bone defects. Moreover, Yoda1 loading enables targeted and efficient mimicking of mechanical signals and activation of Piezo1. Experiments in vivo and in vitro demonstrate that ZOL-PLGA@Yoda1/SPIO can activate Piezo1 in bone defect areas of osteoporotic mice, improve osteogenesis through YAP/β-catenin signaling axis, promote a well-coordinated osteogenesis–angiogenesis coupling, and significantly accelerate bone reconstruction within the defects without noticeable side effects. Overall, this novel dual-targeting nanocarrier provides a potentially effective strategy for the clinical treatment of osteoporotic bone defects.
研究领域:
生物医学工程
·
纳米技术
·
骨生物学
·
力学生物学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2026
·
IF 5.3
Fenqian Yuan,Jingkang Yong,Xueming Liu,Yifeng Wang,Dan Zhao
Background Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy in which epithelial–mesenchymal transition (EMT) contributes to tumor progression. Piezo1 and Galectin-1 have each been implicated in cancer progression, but their functional relationship in HNSCC remains incompletely understood. We investigated Piezo1-associated mechanosensitive signaling and its potential relationship with Galectin-1 in HNSCC. Methods Public transcriptomic and proteomic analyses were integrated with validation using 16 paired oral squamous cell carcinoma (OSCC) tumor and adjacent non-tumor specimens. Functional studies were performed in HNSCC cell lines using genetic and pharmacological modulation of PIEZO1/Piezo1 and Galectin-1-associated signaling. Two independent SCC-9 xenograft studies were conducted in separate cohorts (n = 6 per group): one comparing vehicle, Yoda1, and GsMTx4, and the other comparing vehicle, GsMTx4, OTX008, and their combination. Results Piezo1 was consistently upregulated in HNSCC datasets, OSCC tissues, and HNSCC cell lines, whereas its association with survival was modest and not uniformly reproduced across analytical platforms. Piezo1 activation was associated with increased Ca 2+ -associated signaling, nuclear YAP1 accumulation, and EMT-related phenotypes, whereas PIEZO1 silencing and pharmacological inhibition of mechanosensitive channel activity attenuated these effects. Galectin-1 emerged as a Piezo1-responsive candidate effector associated with YAP1 signaling and EMT-related phenotypes. OTX008 treatment reduced proliferation, wound closure, invasion, and EMT-related marker changes. In xenografts, combined GsMTx4 and OTX008 treatment produced greater reductions in tumor growth, Ki67 positivity, endpoint CD31 fluorescence intensity, and EMT-associated marker changes than either monotherapy at the tested doses. Conclusion These findings support an important contribution of Piezo1-associated mechanosensitive signaling to EMT-related phenotypes and tumor progression in HNSCC and support Galectin-1 as a functionally relevant, Piezo1-responsive candidate effector associated with YAP1 signaling. The greater antitumor effects observed with combined GsMTx4 and OTX008 treatment support further investigation of co-targeting mechanosensitive channel activity and Galectin-1 in HNSCC.
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Zichen Yang,Rongjie Li,Lulu An,Xiaoyou Zhang,Jianwei Cheng,Yanni Cai,Yang Li,Haiqing Dong,Yongyong Li,Yan Li
Mechanosensitive signaling pathways in immune cells drive exhaustion and ultimately facilitate tumor immune escape. In situ mechanical modulation strategies, leveraging the tumor’s mechanical features, may provide a distinctive perspective for immunotherapy. We repurpose conventional silica nanocarriers from mere “drug delivery vehicles” into “Piezo1 mechanotransduction modulators” by precisely tuning their mechanical properties to directly intervene in tumor-associated macrophages (TAMs) mechanosignaling. Our study revealed that Piezo1 acts as a mechano-immunological switch in tumors: its downregulation in large tumors promotes M2-like TAMs polarization, whereas its upregulation in small tumors drives M1-mediated antitumor immunity. This directly couples mechanical cues to immune reprogramming during cancer progression. To target this pathway, we engineered mesoporous silica nanoparticles (mSNs) with tunable stiffness (253–1084.5 MPa), which were loaded with the Piezo1 agonist Yoda1 and TAMs-targeting peptide CRV (YmSNs@CRV) to precisely modulate TAMs mechanosignaling. Results demonstrated that softer 20% mSN achieved dual regulation of both macrophage phenotypic reprogramming and exosome-mediated communication via Piezo1 activation. Specifically, softer 20% mSNs enhanced pro-inflammatory markers (CD80), increased cytokine secretion, and promoted exosome production 5-fold more effectively than stiffer 80% mSNs. Proteomic analysis revealed that exosomes from 20% mSN-treated macrophages activated the TCR signaling, amplifying immune responses. In vivo, 20% YmSNs@CRV improved tumor penetration, repolarized TAMs toward an antitumor phenotype, and boosted cytotoxic T cell infiltration, significantly inhibiting tumor growth. This study integrates the mechanical characteristics of tumor tissues and proposes an “in situ mechanical dual-regulation” strategy, which combines mechano-regulated TAMs reprogramming with exosome-triggered immune responses, introducing a distinctive mechano-immunotherapeutic paradigm.
研究领域:
肿瘤免疫学
·
纳米医学
·
力学生物学
·
免疫治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL AND MOLECULAR MEDICINE
·
2026
·
IF 12.9
Chen Fan-feng,Zhang Yin-he,Wu Zi-chang,Du Kaiyi,Chen Xinyuan,Lu Yang,Hu Qianqian,Du Anyu,Du Shenghu,Wang Jian,Shi Keqing,Chen Zimiao,He Zili,Zhou Kailiang,Xiao Jian
Acute limb ischemia–reperfusion injury (ALIRI) prominently involves microvascular dysfunction, with notable contributions from damage to microvascular endothelial cells (MECs). Previous research suggests that the mechanosensitive ion channel Piezo1 becomes active in response to mechanical stress conditions, including ischemia and trauma. However, its precise function within the ALIRI context remains elusive. Notably, the expression of Piezo1 was markedly elevated postreperfusion in mouse hind limb ischemia/reperfusion (I/R) models, implicating its crucial involvement in limb survival. Employing specific inhibitors of cell death pathways, the study delineated key molecular drivers of ferroptosis during limb damage. Here evaluations of limb vitality, western blot, quantitative PCR and immunofluorescence implicated that activation of Piezo1 by its agonist exacerbates I/R-induced microvascular perfusion deficits, tissue swelling, skeletal muscle damage and increased tissue infarction and MECs damage. Conversely, these detrimental impacts were mitigated through pharmacological blockade of Piezo1 or specific deletion of Piezo1 in MECs. Comprehensive untargeted metabolomic analysis revealed significant changes primarily in glycerophospholipid and arachidonic acid metabolism pathways. Further experiments demonstrated that RNA interference-mediated inhibition of cytosolic phospholipase A2 (cPLA2) and acyl-CoA synthetase long-chain family member 4 (ACSL4) negated the protective effects against ferroptosis and limb damage that were observed with Piezo1 deletion. Moreover, this study confirmed that protein kinase C phosphorylates ACSL4, which mediates Piezo1-induced ferroptosis and exacerbates limb damage, as shown through immunoprecipitation studies. In summary, Piezo1 contributes to the exacerbation of microvascular and skeletal muscle damage in ALIRI by facilitating the cPLA2-dependent release of arachidonic acid and promoting ACSL4-driven lipid peroxidation, thereby intensifying ferroptosis in MECs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）