EXPERIMENTAL CELL RESEARCH
·
2026
·Vol. 463
·期 2
·115195
·
IF 3.5
Zhenyi Lu,Hao Huang,Wanshu Lv,Jingjing Yan,Yumeng Shi,Jieli Ni,Yang Zhang,Rongyao Xu,Geng Wu,Shuyu Guo
Optn loss causes severe bone defects. • OPTN is vital for craniofacial bone development and OMSC osteogenesis. • OPTN cooperates with TRIP6 to recruit F-actin for mitophagy closure. • Actin-driven mitophagy dictates ACP packaging and EV-mediated release. The development of craniofacial bones is highly dependent on the intramembranous ossification process driven by orofacial mesenchymal stem cells (OMSCs). Optineurin (OPTN), a traditional mitophagy receptor, promotes OMSC matrix mineralization by mediating the extracellular release of amorphous calcium phosphate (ACP) through the initiation of mitophagy via liquid-liquid phase separation. However, the dynamic mechanisms by which OPTN regulates mitochondrial engulfment remain elusive. In this work, we show that in both zebrafish and mouse models, Optn absence causes systemic bone loss and craniofacial abnormalities. Mechanistically, OPTN recruits thyroid receptor-interacting protein 6 (TRIP6) to the surface of damaged mitochondria, inducing local F-actin polymerization and remodeling, which relies on cytoskeletal mechanical forces to support the bending and closure of the phagophore. The depletion of OPTN or TRIP6 significantly impairs mitophagy flux, triggering a massive accumulation of dysfunctional mitochondria. Overall, this study elucidates that the OPTN-TRIP6-F-actin axis ensures autophagosome closure through cytoskeletal remodeling, revealing a novel paradigm in which cytoskeletal mechanical regulation maintains mitochondrial homeostasis to orchestrate craniofacial osteogenesis. Download: Download high-res image (615KB) Download: Download full-size image
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2020
·
IF 7.489
Yuqing Niu,Bokai Zhang,Massimiliano Galluzzi
The specific binding of fluorescent probes or biomolecules to the actin cytoskeleton network is increasingly important for monitoring various complex cellular activities such as cell adhesion, proliferation, locomotion, endocytosis, and cell division. However, improving cell uptake and subcellular resolution is still the main obstacle for successful and wide application of cellular fluorescent probes. Here, we designed and synthesized an amphiphilic block polyurethane with peculiar photophysical properties of aggregation induced emission (AIE), which can be used in living cell imaging to promote selective visualization of cell structures. The AIE effect polyurethane (abbreviated as AIE-PU) was prepared by two-step polymerization of diisocyanate terminated polyethylene glycol and polycaprolactone with hydroxyl terminated AIE dye. A series of characterization techniques proved the successful synthesis of AIE-PU. Due to the amphiphilic chain segment of its linear block molecule, AIE-PU block copolymers can self-assemble into spherical nanoparticles in aqueous solution, showing relatively stable photophysical properties and good water dispersion. Cellular experiments demonstrated that AIE-PUs have low toxicity and high actin network affinity. Moreover, the uptake mechanism was studied by low temperature and metabolic inhibition experiments, showing that AIE-PU nanoparticles could be easily internalized into different living cells through energy-dependent endocytosis, and can be transported from the cellular periphery to the actin network via clathrin- and caveolae-dependent transport pathway. Upon binding with the actin network, the inter-chain AIE mechanism of the probe was significantly enhanced, which is pivotal for the long-term stable fluorescence imaging of actin microfilament network in living cells. Finally, compared with commercial actin dyes, this probe showed higher photostability, even after a longer retention time, without significant fluorescence quenching.
研究领域:
材料科学
·
生物医学工程
·
细胞生物学
·
光学成像
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2018
·Vol. 16
·期 1
·1-14
·
IF 5.294
Qin Yanxia,Chen Kui,Gu Weihong,Dong Xinghua,Lei Ruihong,Chang Yanan,Bai Xue,Xia Shibo,Zeng Li,Zhang Jiaxin,Ma Sihan,Li Juan,Li Shan,Xing Gengmei
Background Tumor metastasis is the primary cause of mortality in cancer patients. Migratory breast cancer cells in lymphatic and blood vessels seek new sites and form metastatic colonies in the lung and bone, and then these cancer cells often wreak considerable havoc. With advances in nanotechnology, nanomaterials and nanotechnologies are widely applied in tumor therapy. In this paper, small size fullerenol nanoparticles, which are separated by isoelectric focusing electrophoresis (IFE) for discrepancy of isoelectric point (pI), are used in the study of tumor metastasis.Results In this study, the commendable inhibition of tumor metastasis was uncovered by intravenous injection of purified fullerenol fraction with special surface charge and functional groups, which was separated by IFE for discrepancy of pI. By investigating the actin dynamics in several cancer cell lines, we found these small size fullerenol nanoparticles disturbed actin dynamics. Young’s modulus detection and cell migration assays revealed that fullerenol lowered stiffness and restrained migration of breast cancer cells. Filopodia, the main supporting structures of actin bundles, are important for cell motility and adhesion. Scanning electron microscopy showed that fullerenol reduced the number and length of filopodia. Simultaneously, the inhibition of integrin to form clusters on filopodias, which was likely induced by reorganizing of actin cytoskeleton, impacted cancer cell adhesion and motility.Conclusion sWith intravenous injection of these fullerenol nanoparticles, tumor metastasis is well inhibited in vivo. The underlying mechanism most likely to be attributed to the effect of fullerenol nanoparticles on disturbing actin dynamics. With the disordered actin fiber, cell function is varied, including decreased cell stiffness, reduced filopodia formation, and inactivated integrin.
研究领域:
纳米技术
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癌症生物学
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细胞生物学
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2026
·
IF 8.3
Jiayu Liu,Xiaoqiang Li,Haibo He,Peng Miao
Actin is one of the key proteins expressed in cellular life activities, which is also closely related with many human diseases. Herein, we develop a novel fluorescent method for globular actin (G-actin) assay based on the inhibition of nuclease-cleaved silver nanoclusters (AgNCs). The pristine DNA-templated AgNCs feature a fluorescence transition from green (Ag 13/14 NCs) to red (recombined Ag 10 NCs) triggered by the cleavage of deoxyribonuclease I (DNase I). In the presence of target G-actin, a stable complex forms by the interaction between G-actin and DNase I, thereby inhibiting the cleavage activity and subsequent fluorescence transition. Through monitoring the regulation of fluorescence emission, we ultimately achieve quantitative detection of G-actin. The proposed AgNCs based sensor is highly efficient and sensitive. It is also successfully applied to distinguish normal and cancer cells by measuring G-actin levels. This study not only provides a unique strategy for actin-based applications, but also inspires the engineering of DNA-templated nanomaterials.
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MOLECULAR THERAPY
·
2023
·
IF 12.4
Yang Qiu,Chuntao Lei,Jieyu Zeng,Yaru Xie,Yiling Cao,Qian Yuan,Hua Su,Zhentao Zhang,Chun Zhang
Focal segmental glomerulosclerosis (FSGS) is the most common glomerular disorder causing end-stage renal diseases worldwide. Central to the pathogenesis of FSGS is podocyte dysfunction, which is induced by diverse insults. However, the mechanism governing podocyte injury and repair remains largely unexplored. Asparagine endopeptidase (AEP), a lysosomal protease, regulates substrates by residue-specific cleavage or degradation. We identified the increased AEP expression in the primary proteinuria model which was induced by adriamycin (ADR) to mimic human FSGS. In vivo , global AEP knockout mice manifested increased injury-susceptibility of podocytes in ADR-induced nephropathy (ADRN). Podocyte-specific AEP knockout mice exhibited much more severe glomerular lesions and podocyte injury after ADR injection. In contrast, podocyte-specific augmentation of AEP in mice protected against ADRN. In vitro , knockdown and overexpression of AEP in human podocytes revealed the cytoprotection of AEP as a cytoskeleton regulator. Furthermore, transgelin, an actin-binding protein regulating actin dynamics, was cleaved by AEP, and, as a result, removed its actin-binding regulatory domain. The truncated transgelin regulated podocyte actin dynamics and repressed podocyte hypermotility, compared to the native full-length transgelin. Together, our data reveal a link between lysosomal protease AEP and podocyte cytoskeletal homeostasis, which suggests a potential therapeutic role for AEP in proteinuria disease.
研究领域:
分子生物学
·
肾脏病学
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PubMed
高影响因子
Letters in Drug Design & Discovery
·
2019
·Vol. 16
·期 12
·1378-1386
·
IF 0.953
Cai Xingchen,Huang Weiwei,Huang Yi,Xia Lihua,Liu Miao,Wang Mengke,Wang Wenchao,Li Qingyong
Background: The single-agent therapy was unable to provide an effective control of the malignant process, a well-established strategy to improve the efficacy of antitumor therapy is the rational design of drug combinations aimed at achieving synergistic effects. Objective: The
objective of this study is generating the new potential anticancer agents with synergistic activity. Owing to the unique mechanism of action of Camptothecin (CPT), it has shown abroad spectrum of anti-cancer activity against human malignancies, and growing evidence revealed that Nonsteroidal
Anti-Inflammatory Drugs (NSAIDs) reduce the risk of different kinds of cancers. So four CPT-NSAIDs conjugates were synthesized and evaluated. Methods: In this study, a series of novel CPT - NSAIDs derivatives were synthesized by esterification. These new compounds were evaluated for in
vitro antitumor activity against tumor cell lines A549, Hela, HepG2, HCT116 by MTT assay. To probe the required stabilities as prodrugs, stability tests were studied in human plasma. To further evaluate the stability of Ketoprofen-CPT in vivo, the female SD rats were used to determine the
pharmacokinetics following a single oral dose. Results: In vitro results showed that Ketoprofen-CPT and Naproxen-CPT conjugates possessed nice efficacy. In a molecular docking model, the two conjugates interacted with Topo I-DNA through hydrogen bonds, - stacking and
so on.In human plasma results showed that the prodrug was converted to ketoprofen and another compound. The female SD rats were used to determine the pharmacokinetics following a single oral dose, the half-life (t1/2) of Ketoprofen-CPT was approximately 12 h which was much longer than that
of CPT. Conclusion: Good activity was noted for some compounds will be helpful for the design of dualaction agents with most promising anti-cancer activity.
研究领域:
肿瘤学
·
药物化学
·
药理学
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高影响因子
Stress Biology
·
2024
·Vol. 4
·期 1
·1-15
·
IF 0
Li Yuan-Bao,Shen Ningning,Deng Xianya,Liu Zixuan,Zhu Shuai,Liu Chengyu,Tang Dingzhong,Han Li-Bo
The dynamic assembly of the actin cytoskeleton is vital for Magnaporthe oryzae development and host infection. The actin-related protein MoFim1 is a key factor for organizing the M. oryza e actin cytoskeleton. Currently, how MoFim1 is regulated in M. oryzae to precisely rearrange the actin cytoskeleton is unclear. In this study, we found that MoFim1 associates with the M. oryzae mitogen-activated protein (MAP) kinase Pmk1 to regulate actin assembly. MoFim1 directly interacted with Pmk1, and the phosphorylation level of MoFim1 was decreased in Δ pmk1 , which led to a change in the subcellular distribution of MoFim1 in the hyphae of Δ pmk1. Moreover, the actin cytoskeleton was aberrantly organized at the hyphal tip in the Δ pmk1 , which was similar to what was observed in the Δ mofim1 during hyphal growth . Furthermore, phosphorylation analysis revealed that Pmk1 could phosphorylate MoFim1 at serine 94. Loss of phosphorylation of MoFim1 at serine 94 decreased actin bundling activity. Additionally, the expression of the site mutant of MoFim1 S94D (in which serine 94 was replaced with aspartate to mimic phosphorylation) in Δ pmk1 could reverse the defects in actin organization and hyphal growth in Δ pmk1 . It also partially rescues the formation of appressorium failure in Δ pmk1. Taken together, these findings suggest a regulatory mechanism in which Pmk1 phosphorylates MoFim1 to regulate the assembly of the actin cytoskeleton during hyphal development and pathogenesis.
研究领域:
真菌学
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植物病理学
·
细胞生物学
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DOI
IEEE TRANSACTIONS ON INSTRUMENTATION AND MEASUREMENT
·
2026
·
IF 7
Chen Liu,Xue Zhou,Hanyu Bai,Yana Zhang,Yong Zhao,Xuegang Li
Beta-actin (ACTB), a highly conserved cytoskeletal protein, is frequently dysregulated in early-stage malignancies, making its sensitive and specific detection crucial for cancer screening. Here, we develop a reflective fiber-optic SPR biosensor functionalized with copper–glycine engineered WS₂ nanosheets for label-free ACTB detection. The Cu–glycine modification not only enables WS₂ surface amination for efficient antibody conjugation, but also introduces Cu²⁺-mediated near-infrared absorption to amplify the plasmonic resonance response. Combined with the intrinsically large surface area and high refractive index sensitivity of WS₂, this synergistic design markedly enhances both molecular binding and signal transduction. The resulting WS₂-NH₂-based sensor achieves a refractive index sensitivity of 1467.5 nm/RIU, representing a 1.67-fold enhancement over unmodified fiber probes. For ACTB detection, it delivers an ultralow detection limit down to 9.766 pM, a broadened linear range of 2.4–120 pM (5×expansion), and a biosensing sensitivity of 84.477 nm/nM (1.4× improvement). Furthermore, at 1 ng/mL, a rapid response time of 20 min is achieved, demonstrating applicability for trace-level biomarker screening. Integrating high sensitivity, broad dynamic range, amplified spectral response, and strong anti-interference capability, this plasmonic WS₂-NH₂-modified fiber platform enables highly selective, label-free ACTB quantification. These findings highlight its strong potential for early cancer diagnosis, biomarker monitoring, and precision medical applications.
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高影响因子
ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Le Li,Ting Liu,Meifang Wang,Yong'an Ren,Nan Jia,Huaiyu Bu,Gang Xie,Hang Xu,Yongli Wu,Xiangyuan Ouyang
Herein, we synthesized snowflake-like DNA crystals (SDC) via hybridization chain reaction and used it for the first time in the synthesis of copper nanoclusters with enhanced fluorescence. Atomic force microscopy (AFM) and laser confocal microscopy characterization confirmed that SDC/CuNCs are self-assembled successfully on SDC. Aggregation induced emission allows SDC/CuNCs to exhibit better stability and stronger emission intensity. Thus, we developed the “turn-on” label-free fluorescence detection method of actin based on SDC/CuNCs which offer simplicity, low cost, good selectivity , and high sensitivity. The detection limit was determined to be 0.0124 μg mL −1 , which was an order of magnitude lower than that of reported fluorescent methods (0.12 μg mL −1 ). Compared with previous method, the linear range is also much wider. We also performed standard recovery experiments in actual samples for evaluating the practicality of this strategy and proved that the capability of the proposed approach for the determination of actin is feasible and the interference from complex biological samples is negligible. These results indicate that SDC/CuNCs are expected to play a more important role in the field of biosensors .
研究领域:
材料科学
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生物传感
·
分析化学
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PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2026
·Vol. 31
·期 8
·
IF 4.1
Yulian Shi,Tingyu Fan,Rongmei Qu,Guosheng Wu,Xiangtian Li,Jiaxuan Liu,Ziyi Feng,Haopeng Wu,Jun Ouyang,Jingxing Dai
Background:
Bone tissue possesses strong regenerative potential, but large segmental bone defects often exceed its intrinsic capacity for self-healing. Human adipose-derived stem cells (hASCs) offer a promising cellular basis for bone regeneration owing to their robust osteogenic differentiation potential. However, the role of PDZ and LIM domain 2 (PDLIM2) play in hASC osteogenesis and its relationship with the Wnt/β-catenin signaling pathway remain poorly understood.
Methods:
Western blotting, immunofluorescence staining, Alizarin Red S staining, alkaline phosphatase activity assays, wound healing assays, and Transwell assays were employed to assess osteogenic differentiation, osteogenic capacity, and cellular migration. Lentivirus-mediated PDLIM2 knockdown, cytochalasin D (CytoD) intervention, microfilament stabilizer treatment, and β-catenin activator treatment were used as a means of validating the regulatory mechanism.
Results:
hASCs exhibited the ability to undergo osteogenic differentiation. During this osteogenic process, significant increases in PDLIM2, β-actin, and β-catenin expression were observed, with PDLIM2 expression reaching 2–3 times that of the control group on day 14, whereas β-actin and β-catenin levels peaked on day 7 (1.5–2 times those in the control group). Lentivirus-mediated PDLIM2 knockdown reduced β-actin expression by approximately 5-fold and β-catenin expression by approximately 1.7-fold, accompanied by cytoskeletal disorganization and impaired osteogenic differentiation. Actin microfilament integrity was found to regulate osteogenic marker expression and alkaline phosphatase activity, while CytoD treatment suppressed β-actin and β-catenin expression to approximately 50% of control levels and inhibited osteogenic differentiation. Knocking down PDLIM2 attenuated the responsiveness of hASCs to microfilament stabilizers and β-catenin activators.
Conclusions:
This study demonstrates that PDLIM2 may be functionally associated with β-catenin nuclear translocation, potentially through the remodeling of the actin cytoskeleton. These findings provide preliminary mechanistic insight and warrant further validation.
Keywords
PDLIM2human adipose-derived stem cells (hASCs)osteogenesiscytoskeletonβ-catenin
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高影响因子
CELL AND TISSUE RESEARCH
·
2022
·Vol. 390
·期 2
·293-313
·
IF 4.051
Li Zhen-Fang,Hao Shuang-Li,Wang Lan-Min,Qi Hong-Yu,Wang Jia-Ming,Tan Fu-Qing,Yang Wan-Xi
Spermatogenesis is a finely regulated process of germ cell proliferation and differentiation that leads to the production of sperm in seminiferous tubules. Although the mammalian target of rapamycin (mTOR) signaling pathway is crucial for spermatogenesis in mammals, its functions and molecular mechanisms in spermatogenesis remain largely unknown in nonmammalian species, particularly in Crustacea. In this study, we first identified es-Raptor (the core component of mTOR complex 1) and es-Rictor (the core component of mTOR complex 2) from the testis of Eriocheir sinensis . Dynamic localization of es-Raptor and es-Rictor implied that these proteins were indispensable for the spermatogenesis of E. sinensis. Furthermore, es-Raptor and es-Rictor knockdown results showed that the mature sperm failed to be released, causing almost empty lumens in the testis. We investigated the reasons for these effects and found that the actin-based cytoskeleton was disrupted in the knockdown groups. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was impaired and affected the expression of cell junction proteins. Further study revealed that es-Raptor and es-Rictor may regulate spermatogenesis via both mTORC1- and mTORC2-dependent mechanisms that involve es-rpS6 and es-Akt/es-PKC, respectively. Moreover, to explore the testis barrier in E. sinensis , we established a cadmium chloride (CdCl 2 )–induced testis barrier damage model as a positive control. Morphological and immunofluorescence results were similar to those of the es-Raptor and es-Rictor knockdown groups. Altogether, es-Raptor and es-Rictor were important for spermatogenesis through maintenance of the actin filament network and cell junctions in E. sinensis.
研究领域:
分子生物学
·
生殖生物学
·
甲壳动物学
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PubMed
高影响因子
Scientific Reports
·
2016
·
IF 5.228
Zhe Chen,Qing Luo,Chuanchuan Lin,Dongdong Kuang,Guanbin Song
Microgravity induces observed bone loss in space flight, and reduced osteogenesis of bone mesenchymal stem cells (BMSCs) partly contributes to this phenomenon. Abnormal regulation or functioning of the actin cytoskeleton induced by microgravity may cause the inhibited osteogenesis of BMSCs, but the underlying mechanism remains obscure. In this study, we demonstrated that actin cytoskeletal changes regulate nuclear aggregation of the transcriptional coactivator with PDZ-binding motif (TAZ), which is indispensable for osteogenesis of bone mesenchymal stem cells (BMSCs). Moreover, we utilized a clinostat to model simulated microgravity (SMG) and demonstrated that SMG obviously depolymerized F-actin and hindered TAZ nuclear translocation. Interestingly, stabilizing the actin cytoskeleton induced by Jasplakinolide (Jasp) significantly rescued TAZ nuclear translocation and recovered the osteogenic differentiation of BMSCs in SMG, independently of large tumor suppressor 1(LATS1, an upstream kinase of TAZ). Furthermore, lysophosphatidic acid (LPA) also significantly recovered the osteogenic differentiation of BMSCs in SMG through the F-actin-TAZ pathway. Taken together, we propose that the depolymerized actin cytoskeleton inhibits osteogenic differentiation of BMSCs through impeding nuclear aggregation of TAZ, which provides a novel connection between F-actin cytoskeleton and osteogenesis of BMSCs and has important implications in bone loss caused by microgravity.
研究领域:
生物医学工程
·
细胞生物学
·
干细胞研究
·
空间生物学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）