ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Zhen Xu,Keli An,Rui Yang,Shihao Wang,Yiye Fan,Keru Feng,Hongyan Wang,Junwen Qian,Yufei Ma,Guiqin Bai
Uterine scarring after cesarean section is a major cause of secondary infertility and uterine rupture, and its formation is closely associated with disruption of the mechanical microenvironment at incision sites, yet its mechanobiological basis and effective mechano-regulatory therapies remain poorly defined. We identify focal adhesion kinase (FAK)-mediated mechanotransduction as a key driver of post-cesarean uterine scar formation. To target this process, we developed FAK-PTC-Lipo@MN, a biodegradable microneedle patch composed of gelatin methacryloyl (GelMA) and ε-poly-L-lysine-glycidyl methacrylate (EPLGMA), enabling sustained local delivery of FAK-PROTAC-loaded liposomes. In a rat cesarean-section model, FAK-PTC-Lipo@MN reduced inflammatory infiltration, collagen deposition, myometrial thickening, and tissue stiffness, thereby suppressing uterine scar formation. Transcriptomic analysis further showed a shift of uterine repair mode from fibrotic toward regenerative repair, with activation of Wnt/Notch-related pathways and downregulation of ECM-associated fibrotic signaling. Functionally, FAK-PTC-Lipo@MN promoted uterine functional recovery and improved key reproductive outcomes (e.g., conception time, fetal number, and fetal weight) after cesarean section. Mechanistically, released FAK-PTC-Lipo induced FAK degradation and inhibited its activation, thereby reducing F-actin polymerization, cell traction forces, ECM remodeling and tension, and N-cadherin-dependent fibroblast collective migration. This study establishes FAK-targeted mechanotherapy as a promising strategy for uterine incision regeneration and reproductive function restoration after cesarean section.
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DOI
高影响因子
PLoS One
·
2026
·Vol. 21
·期 6
·e0351846
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IF 2.8
Ming Liu,Xiaomei Liao,Fangchao Wang,Pengqing Jiao,Zhongkai Wang
Acquired drug resistance is a major cause of failure in gastric cancer treatment. The protein tyrosine phosphatase receptor type E (PTPRE) plays an oncogenic role in certain tumours; however, its function in chemotherapy-resistant gastric cancer remains unclear. Therefore, we analysed PTPRE expression in gastric cancer using The Cancer Genome Atlas. In vitro experiments were then conducted to investigate the effects of PTPRE on the resistance of cancer cells to 5-fluorouracil (5-FU) and its potential mechanisms. The results were further validated in vitro using xenograft studies. We found that PTPRE is upregulated in gastric cancer tissues and participates in the induction of 5-FU resistance. Mechanistic studies revealed that PTPRE suppressed ferroptosis in gastric cancer cells and promoted 5-FU resistance by activating the Src/FAK pathway to upregulate TRIB3 expression. In summary, PTPRE suppresses ferroptosis in gastric cancer cells via the Src/FAK/TRIB3 signalling pathway, thereby inducing 5-FU resistance. Intervention with PTPRE and its downstream targets may represent a potential approach for the clinical treatment of 5-FU-resistant gastric cancer.
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DOI
PubMed
高影响因子
Advanced Science
·
2025
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IF 14.1
Zhengrong Chen,Wenxin Yang,Yong Tang,Qianqian Dong,Kui Huang,Jiulin Tan,Jie Zhang,Juan Cai,Qixiu Yu,Qijie Dai,Jianzhong Xu,Shuquan Guo,Ce Dou,Fei Luo
Osteoporotic bone defects are challenging to repair due to imbalances in bone resorption and formation, coupled with insufficient vascularization. To address these issues, it develops a trifunctional hydrogel (SF-ZIF@NA) designed to selectively inhibit osteoclast activity and enhance vascularized bone regeneration. By enzymatically removing sialic acid, SF-ZIF@NA prevents precursor osteoclasts (pOCs) from fusing into bone-resorbing mature osteoclasts (mOCs), thereby preserving pOCs and their anabolic functions. Additionally, the hydrogel releases Zinc ion (Zn 2 ⁺) in response to acidic conditions, promoting osteogenesis and angiogenesis. In vitro results confirmed that SF-ZIF@NA impedes osteoclast fusion, enhances platelet-derived growth factor-BB (PDGF-BB secretion from pOCs, and activates the FAK (focal adhesion kinase) signaling pathway to stimulate vascularized bone formation. In osteoporotic bone defect models, SF-ZIF@NA accelerated bone repair with increased bone density and vascularization. These findings demonstrate that SF-ZIF@NA offers a targeted and multifunctional strategy for osteoporotic bone regeneration by concurrently modulating osteoclast activity and promoting angiogenesis.
研究领域:
生物材料学
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骨组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Nana Long,Youwei Zuo,Jian Li,Renxiu Yao,Xiao Zhang,Hongping Deng
Background Atopic dermatitis (AD) is characterized by epidermal barrier impairment and immune-driven inflammation. Strategies that restore barrier architecture while constraining inflammation are of therapeutic interest. Purpose To evaluate the barrier-reparative and anti-inflammatory effects of β-myrcene (MYR) in experimental atopic dermatitis and to investigate whether ECM–FAK/Src–YAP signaling is associated with these effects. Methods A 2,4-dinitrochlorobenzene (DNCB)-induced murine model of AD-like dermatitis was evaluated by transepidermal water loss (TEWL), histopathology, dermal collagen organization, filaggrin (FLG) immunofluorescence, and circulating inflammatory mediators. Integrated skin transcriptomic and proteomic analyses and public human AD transcriptomic datasets were used to identify MYR-associated pathways. In primary human keratinocytes stimulated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), YAP localization, FAK Tyr397 and Src Tyr416 phosphorylation, YAP/TAZ target genes, barrier markers, and inflammatory outputs were assessed. Peptide 17 was used to examine the contribution of YAP-dependent transcription. Results MYR reduced dermatitis severity and epidermal hyperplasia, lowered TEWL, partially restored FLG immunofluorescence, and preserved dermal collagen organization in DNCB-challenged mice. Multi-omics profiling identified MYR-associated changes in extracellular matrix (ECM)–receptor interaction, focal adhesion, cytoskeletal remodeling, epidermal differentiation, and immune-related programs. In inflamed keratinocytes, MYR was associated with increased FAK and Src phosphorylation, YAP nuclear accumulation, CCN1/CCN2 expression, and barrier-marker expression, together with reduced inflammatory mediator production. Peptide 17 attenuated MYR-associated YAP nuclear accumulation and several downstream transcriptional responses. These findings support the participation of YAP-dependent signaling but do not establish MYR as a direct regulator of FAK, Src, or YAP or demonstrate a strictly linear signaling sequence. Conclusion MYR produced barrier-restorative and anti-inflammatory effects in experimental atopic dermatitis. The results identify ECM–FAK/Src–YAP signaling as a candidate pathway associated with the MYR response, with pharmacological inhibition providing partial functional evidence for a YAP-dependent component. Download: Download high-res image (265KB) Download: Download full-size image
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DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Tao Wei,Lei Liu,Xiaoying Zhou
Airway smooth muscle (ASM) is a prominent effecter in maintaining bronchial muscle contraction and responsible for airway hyper-responsiveness (AHR); the phenotype change and over-proliferation of airway smooth muscle cells (ASMCs) play key roles in the pathogenesis of asthma. The aim of this study was to investigate the anti-proliferation effects of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDE) on ASMCs and the possible underline mechanisms. Cell proliferation rates were determined by MTT assay; matrix metalloproteinases-2 (MMP-2) activity was examined by gelatin zymography; cell proliferation and migration were appraised by in-vitro cell-gap closure assessment; protein expressions of p38, Bcl-2 and FAK of ASMCs were evaluated by western blotting and Ca 2+ influx of cells was measured by confocal laser microscope. Our data demonstrated that the proliferation, migration and MMP-2 expressions of ASMCs were inhibited by CDAE or CDE; the protein expressions of p38, Bcl-2 and FAK in ASMCs were substantially reduced by CDAE and CDE detected by western blotting or immunocytochemistry; also the increased calcium influx has been observed instantaneously after ASMCs were stimulated by CDAE or CDE. These findings suggested that Cortex Dictamni extracts might have inhibitory effects on ASMCs over-proliferation which could be one of the underline mechanisms for the therapy of asthma.
研究领域:
药理学
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呼吸病学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Huanliang Chen,Wenzhi Tu,Yue Lu,Yingzi Zhang,Yiqing Xu,Xuming Chen,Meiling Zhu,Yong Liu
Radiation therapy offers limited clinical benefits for patients with pancreatic cancer, partly as a result of the predominantly immunosuppressive microenvironment characteristic of this specific type of cancer. A large number of abnormal blood vessels and high-density fibrous matrices in pancreatic cancer will lead to hypoxia within tumor tissue and hinder immune cell infiltration. We used low-dose X-ray irradiation, also known as low-dose radiation therapy (LDRT), to normalize the blood vessels in pancreatic cancer, while simultaneously administering an inhibitor of focal adhesion kinase (FAK) to reduce pancreatic cancer fibrosis. We found that this treatment successfully reduced pancreatic cancer hypoxia, increased immune cell infiltration, and increased sensitivity to radiation therapy for pancreatic cancer.
研究领域:
肿瘤学
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免疫学
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放射肿瘤学
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DOI
PubMed
高影响因子
Biomaterials Advances
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2025
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IF 6
Haoqing Liu,Kepeng Hu,Chengwei Wu,Weiming Lin,Wenjian Weng,Xiaojun Long,Zhangfa Song,Kui Cheng
Bone tissue is mainly composed of collagen and hydroxyapatite, and has intrinsic electroactivity. The ability of biomaterials to mimic physiological microenvironmental cues holds significant potential for enhancing therapeutic outcomes by activating the intrinsic repair capabilities of cells and tissues. The microenvironment of bone tissue contains abundant collagen and electrophysiological signals, which play a crucial role in regulating, repairing, and regenerating its daily homeostasis. Creating surface potentials on biomaterials has proven to be an efficient method for promoting osteogenic differentiation. However, how to construct a collagen rich environment with different surface potentials and its biological effects remains unexplored. In this study, a biomimetic electrical microenvironment was created on the surface of the PVTF film through polarization and collagen modification. In this microenvironment, collagen with varying surface potentials can replicate the extracellular microenvironment of natural bone tissue. The biomimetic microenvironment has the potential to enhance the bioactivity of the material, particularly in terms of improving stem cell adhesion, promoting osteogenic differentiation, and accelerating bone regeneration in vivo. Further integrin inhibition assays and PCR analyses revealed that the biomimetic microenvironment promoted osteogenic differentiation by activating integrin α2β1 on the cell surface, which in turn triggered the FAK/ERK signaling pathway and upregulated the expression of osteogenesis-related genes. These findings provide valuable insights into the biological effects of surface potential and biochemical signals on osteogenesis at the material surface and offer a novel surface modification strategy to enhance the therapeutic efficacy of tissue engineering.
研究领域:
生物材料学
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组织工程
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骨生物学
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分子细胞生物学
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生物医学工程
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信号转导
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再生医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2018
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IF 8.097
Bolin Tang,Junjun Zhuang,Liming Wang,Bo Zhang,Suya Lin,Fei Jia,Lingqing Dong,Qi Wang,Kui Cheng,Wenjian Weng
The binding of cell integrins to proteins adsorbed on the material surface is a highly dynamic process critical for guiding cellular responses. However, temporal dynamic regulation of adsorbed proteins to meet the spatial conformation requirement of integrins for a certain cellular response remains a great challenge. Here, an active CoFe2O4/poly(vinylidene fluoride-trifluoroethylene) nanocomposite film, which was demonstrated to be an obvious surface potential variation (ΔV ≈ 93 mV) in response to the applied magnetic field intensity (0–3000 Oe), was designed to harness the dynamic binding of integrin-adsorbed proteins by in situ controlling of the conformation of adsorbed proteins. Experimental investigation and molecular dynamics simulation confirmed the surface potential-induced conformational change in the adsorbed proteins. Cells cultured on nanocomposite films indicated that cellular responses in different time periods (adhesion, proliferation, and differentiation) required distinct magnetic field intensity, and synthetically programming the preferred magnetic field intensity of each time period could further enhance the osteogenic differentiation through the FAK/ERK signaling pathway. This work therefore provides a distinct concept that dynamically controllable modulation of the material surface property fitting the binding requirement of different cell time periods would be more conducive to achieving the desired osteogenic differentiation.
研究领域:
材料科学
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生物材料
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生物医学工程
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Zhou Hao,Wang Wei,Cai Zedong,Jia Zhou-Yan,Li Yu-Yao,He Wei,Li Chen,Zhang Bang-Le
Chemotherapy and immunotherapy have shown no significant outcome for unresectable pancreatic ductal adenocarcinoma (PDAC). Multi-drug combination therapy has become a consensus in clinical trials to explore how to arouse anti-tumor immunity and meanwhile overcome the poorly tumoricidal effect and the stroma barrier that greatly hinders drug penetration. To address this challenge, a comprehensive strategy is proposed to fully utilize both the ferroptotic vulnerability of PDAC to potently irritate anti-tumor immunity and the desmoplasia-associated focal adhesion kinase (FAK) to wholly improve the immunosuppressive microenvironment via sustained release of drugs in an injectable hydrogel for increasing drug penetration in tumor location and averting systematic toxicity. The injectable hydrogel ED-M@CS/MC is hybridized with micelles loaded with erastin that exclusively induces ferroptosis and a FAK inhibitor defactinib for inhibiting stroma formation, and achieves sustained release of the drugs for up to 12 days. With only a single intratumoral injection, the combination treatment with erastin and defactinib produces further anti-tumor performance both in xenograft and Kras G12D -engineered primary PDAC mice and synergistically promotes the infiltration of CD8 + cytotoxic T cells and the reduction of type II macrophages. The findings may provide a novel promising strategy for the clinical treatment of PDAC.
研究领域:
肿瘤学
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药学
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免疫学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2020
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IF 8.758
Chao Liu,Mouyuan Sun,Yu Wang,Tianer Zhu,Guanchen Ye,Dongqi You,Lingqing Dong,Wenquan Zhao,Kui Cheng,Wenjian Weng,Yu Shrike Zhang,Mengfei Yu,Huiming Wang
Titanium dioxide (TiO2) photofunctionalization has been demonstrated as an effective surface modification method for the osseointegration of implants. However, the insufficient understanding of the mechanism underlying photofunctionalization limits its clinical applications. Here, we report an ultraviolet (UV) radiant energy-dependent functionalization on TiO2 nanodots (TN) surfaces. We found the cell adhesion, proliferation, and osteogenic differentiation gradually increased with the accumulation of UV radiant energy (URE). The optimal functionalizing treatment energy was found to be 2000 mJ/cm2, which could regulate cell-specific behaviors on TN surfaces. The enhanced cell behaviors were regulated by the adsorption and functional site exposure of the extracellular matrix (ECM) proteins, which were the result of the surface physicochemical changes induced by the URE. The correlation between the URE and the reconstruction of surface hydroxyl groups was considered as an alternative mechanism of this energy-dependent functionalization. We also demonstrated the synergistic effects of FAK-RHOA and ERK1/2 signaling pathways on mediating the URE-dependent cell behaviors. Overall, this study provides a novel insight into the mechanisms of photofunctionalization, guiding the design of implants and the clinical practice of photofunctionalization.
研究领域:
材料科学
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生物材料
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生物医学工程
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细胞生物学
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DOI
PubMed
高影响因子
ACS Nano
·
2025
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IF 16
Yuanhao Zhang,Miaomiao Zhang,Jinyao Zheng,Zongjia Li,Qianyu Guo,Ying Chen,Yu Chen,Xiue Jiang,Jilin Tang
The mechanical properties of nanocarriers and the ability of tumor cells to sense mechanical cues are critical factors in regulating cellular internalization. During epithelial–mesenchymal transition (EMT), tumor cells undergo changes that enhance their invasiveness, but how these changes affect their ability to sense mechanical cues, thereby impacting drug delivery efficiency and treatment effects, is still unknown. Here, we synthesized chitosan nanoparticles (CSNPs) with different Young’s moduli ranging from 0.325 to 18.25 MPa. Our findings revealed that as EMT progresses, tumor cells exhibited enhanced internalization capacity, attributing to the elevated integrin expression by EMT. During the cellular internalization of CSNPs with different Young’s moduli, the stiffer CSNPs displayed more internalization in tumor cells. It was due to the upregulation of p-FAK expression after the integrin of cells sensed stronger mechanical cues generated by stiffer CSNPs, resulting in promoted F-actin polymerization, ultimately achieving more cellular internalization. After loading doxorubicin (DOX) into CSNPs (DOX-CSNPs), the stiffer DOX-CSNPs exhibited higher inhibitory ability, with mesenchymal phenotype tumor cells displaying the highest treatment effect. Taken together, our work demonstrated how the mechanical properties of nanocarriers affect cellular internalization across different EMT stages and provided a mechanical-based nanocarrier engineering strategy for cells undergoing EMT.
研究领域:
纳米技术
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癌症生物学
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力学生物学
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药物递送
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
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2022
·Vol. 74
·期 9
·1241-1250
·
IF 4.81
Huang Wenwen,Zhou Xiaoying
ObjectivesTo examine the possible anti-histamine effects of dipotassium glycyrrhizinate (DG), a dipotassium salt of glycyrrhizic acid, on histamine-mediated lung fibroblast activation, differentiation and proliferation; to investigate the potential and underlying mechanisms for pulmonary fibrosis (PF) treatment.MethodsRat primary lung fibroblasts were extracted to establish cell models; histamine, DG and loratadine (LTD, a histamine receptor antagonist) were applied. Cell proliferation, migration and cell cycle were explored; intracellular signal proteins were detected; mitochondrial membrane potential was examined.Key findingsThe anti-histamine effects of DG were found in a similar pattern of LTD on lung fibroblasts. DG inhibited histamine-induced cell activation, proliferation and migration; DG altered histamine-mediated mitochondrial membrane potentials. DG reduced the histamine-induced PAR-2 (a tryptase receptor) expression to impair mast cell tryptase co-working. Histamine-induced expressions of MMP-2, FAK, TNF-α, P38, iNOS were decreased by DG, while Bax and caspase-3, P53 were increased by DG against histamine effects. Histamine drove cells from G0/G1 to S phases, whereas DG rested cells by inhibiting G0/G1 and G2/M phases.ConclusionsThis study provided the evidences that DG can inhibit histamine-induced effects on lung fibroblasts and promote apoptosis of abnormally activated lung fibroblasts, implicating its potential therapeutic mechanisms against PF development, also for those histamine-related diseases.
研究领域:
药理学
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呼吸医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）