BREAST CANCER RESEARCH AND TREATMENT
·
2023
·
IF 3.8
Lei Lei,Huang Yuan,Shi Lei,Ye Weiwu,Lv Xianmei,Ying Lisha,Yu Xingfei,Cheng Skye Hung-Chun,Zheng Yabing
Purpose Endocrine therapy is the anti-tumor therapy for human breast cancer but endocrine resistance was a major burden. It has been reported that Palbociclib and fulvestrant can be used in combination for the treatment of patients who are experiencing endocrine resistance. However, the underlying mechanism is unclear. In this study, we aimed to investigate the mechanism by which Palbocicilib affected ER-positive breast cancer, combined with fulvestrant. Methods We first detected the effect of palbociclib on cell survival, growth and cycle distribution separately by MTT, colony formation and flow cytometry. Then SNHG17 was screened as palbociclib-targeted LncRNA by LncRNA-seq, and the SNHG17-targeted mRNAs were selected by mRNA-seq for further determination. Subsequently, the underlying mechanism by which palbociclib promoted the cytotoxicity of fulvestrant was confirmed by qRT-PCR, western blot, and immunoprecipitation. Eventually, the xenograft model and immunohistochemistry experiments were used to validate the sensitization effect of palbociclib on fulvestrant and its mechanism in vivo. Results Palbociclib significantly enhanced the cytotoxicity of fulvestrant in fulvestrant-resistant breast cancer cell lines. Interestingly, this might be related to the lncRNA SNHG17 and the Hippo signaling pathway. And our subsequent western blotting experiments confirmed that overexpressing SNHG17 induced the down-regulation of LATS1 and up-regulated YAP expression. Furthermore, we found that the increased sensitivity of breast cancer cells was closely associated with the LATS1-mediated degradation of ER-α. The following animal experiments also indicated that overexpressing SNHG17 obviously impaired the anti-cancer effect of co-treatment of palbociclib and fulvestrant accompanied by decreased LATS1 and increased ER-α levels. Conclusion Palbociclib might sensitize the cytotoxicity of fulvestrant in ER-positive breast cancer cells by down-regulating SNHG17 expression, and then resulted in the LATS1-inactivated oncogene YAP and LATS1-mediated degradation of ER-α.
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DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Tingting He,Xuemei Liao,Shuangquan Gou,Genhua Liu,Qiaojian Duan,Zizhen Qin,Junli Yang,Yu Sun,Peng Zhao,Zhong Luo,Kaiyong Cai
Inducing immunogenic cell death (ICD) in cancer cells provides a promising approach in immunotherapy, however, oxidative stress relief and metabolic plasticity enhancement limit the immune-stimulating effect of traditional ICD inducer in sentinel lymph nodes (SLN), owing to the metabolism of fatty acids. In this article, a biocompatible green liposome CL-Lip was designed to not only selectively induce ICD in primary and metastatic 4T1 cells, but also relieved the immunosuppression in invasive SLN. CL-Lip is composed of engineered liposomes modified with linoleic acid and catalase, which synergistically trigger ICD, stimulate lipid peroxidation, PD-L1 carbonylation and effectively promote the maturation of dendritic cells and T cell differentiation. Moreover, catalase also downregulated the hypoxia level in SLN. Through cellular experiments and transcriptome analysis, it is proved that the ICD induction via CL-Lip is mediated by ROS generation, resulting from the YAP-dependent fatty acid oxidation (FAO) interference. Transcriptome analysis revealed that engineered CL-Lip diminishes YAP-dependent FAO pathway and effectively antagonizes the metabolic flexibility, thereby selectively triggering the metabolic dead-associated ICD process in both primary and metastatic 4T1 cells. In animal experiments, this little reported metabolic-driven ICD route not only significantly reduces metastatic foci, but also induces a “cold-to-hot” remodeling of SLN, resulting in the formation of a in situ tumor vaccine. These findings hold great significance for the development of next-generation ICD inducers and immunotherapy approaches.
研究领域:
肿瘤学
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免疫学
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代谢生物学
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分子生物学
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纳米医学
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转化医学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Lei Lin,Liming Xu,Weijie Sun,Lili Liang,Xiaoliang Qi,Yun-e Zhao
Cataract is the first leading cause of blindness in the world and posterior capsule opacification (PCO) is the most common long-term complication after surgery. The primary pathogenic processes contributing to PCO are the proliferation and migration of residual lens epithelial cells (LECs). This study aimed to explore the mild photothermal effect on LECs. Interestingly, this work finds that the mild photothermal effect significantly inhibited the proliferation and migration of LECs. The live cell fluorescence imaging reveals that the remodeling of the actin cytoskeleton and cell morphology attributed to the inhibition effect. Further mechanistic studies at molecular level suggest that the mild photothermal effect can regulate the phosphorylation of ERM, YAP, and Cofilin and thereby affect the proliferation and migration of LECs. In order to explore the potential clinical application of mild photothermal therapy for PCO prevention, PDA/PVA gel rings with photothermal effect is prepared by the repeated freeze-thaw method and conducted experiments in vivo, which achieved favorable PCO prevention effect. Overall, this study shows that the mild photothermal effect can regulate the proliferation and migration of LECs through cytoskeletal remodeling and the results of experiments in vivo demonstrate that mild photothermal effect is a promising approach for PCO prevention.
研究领域:
眼科学
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细胞生物学
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治疗学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 5.4
Shusen Yang,Min Wang,Siyue Liu,Yilin Zhang,Yushan Liu,Mingjie Yang,Wenba Wang,Pengli Wang,Junbo Zou,Jingtao Li,Shuguang Yan,Mingming Si,Hailiang Wei
Ethnopharmacological relevance Colorectal cancer(CRC) is one of the most common malignant tumors of the digestive system, and Traditional Chinese Medicine has shown good efficacy in its treatment and prognosis. Wumei Wan(WMW) is widely used in the treatment of digestive system and tumor diseases, with effects such as anti-diarrheal, anti-dysentery, and pain relief. Modern pharmacological studies suggest that its active ingredients have anti-inflammatory, antioxidant, and anti-tumor properties. However, there is still a lack of systematic research on the role of WMW in the prevention and treatment of CRC and its molecular mechanisms. Aim of this study The aim of this study is to clarify the key active components and primary mechanisms by which WMW inhibits the initiation and progression of CRC, utilizing a multi-faceted approach including chemical composition analysis, network pharmacology, multi-omics studies, molecular biology validation, and molecular simulations. Methods UHPLC-HRMS/MS was used to identify the chemical components in WMW decoction and post-administration serum, and network pharmacology analysis was combined to predict potential targets and signaling pathways. Key differential pathways were selected through combined transcriptomics and proteomics analysis, and the expression patterns of the FAK/Src/YAP axis in CRC were verified using the GEO database. An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model was constructed to assess the effects of WMW on survival rate, tumor burden, histological changes in the colon, and the expression of related proteins. The expression of downstream genes CTGF and Axin2 was detected via qRT-PCR, and the regulatory effects of WMW-containing serum on FAK/Src/YAP signaling were examined in the HCT116 cells model. Finally, molecular docking and molecular dynamics simulations were performed. Results UHPLC-HRMS/MS analysis identified 15 circulating components of WMW following administration. Network pharmacology analysis revealed 241 overlapping targets between WMW-related targets and CRC-associated genes, which were enriched in pathways related to inflammation regulation, cell proliferation, and focal adhesions, with FAK/Src/YAP-related signaling features emerging as a central network module. In the AOM/DSS-induced CRC model, WMW treatment was associated with changes in body weight, tumor burden, and colonic mucosal structure, along with reduced tissue expression levels of VEGF and p53. Multi-omics analyses showed coordinated alterations in pathways related to inflammation, proliferation, and extracellular matrix (ECM) remodeling following WMW intervention. Analysis of GEO datasets confirmed elevated expression of PTK2, Src, and YAP1 in CRC tissues, supporting aberrant focal adhesion-YAP-associated signaling features in clinical CRC. In vivo and in vitro experiments showed that WMW intervention was associated with reduced phosphorylation levels of FAK, Src, and YAP, decreased stress fiber formation, attenuated YAP nuclear localization, and lower expression of CTGF and PCNA. Molecular docking and molecular dynamics simulations indicated that several circulating components could stably interact with the FAK kinase domain, with auraptene exhibiting relatively favorable binding characteristics. Conclusion These findings suggest that WMW intervention is associated with coordinated alterations in inflammation-related signaling, cell proliferation, and extracellular matrix remodeling in CRC, with focal adhesion-YAP-related mechanotransduction representing a potential associated feature. This study provides integrated experimental evidence supporting further investigation of WMW and traditional Chinese medicine-based strategies targeting focal adhesion-associated signaling in CRC research.
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Xinyue Xu,Youwei Wang,Changhao Han,Jingsong Lin,Qingan Shen,Youyi Lan,Linjing Long,Xudong Tan,Jiankai Liu,Siyi Liu,Lanxinhui Luo,Mingqi Lv,Yuchan Zhang,Guixue Wang,Guangchao Zang
Without intervention, the natural wound healing process can often result in scarring, which can have detrimental effects on both the physical and mental well-being of patients. Therefore, it is crucial to develop biomaterials that can promote healing without scarring. Regulating the Yes-associated protein-1/PDZ-binding motif (YAP/TAZ) signaling pathway is possible to reduce excessive fibrosis of fibroblasts and proliferation of vascular endothelial cells, ultimately impacting scar formation. Arsenic trioxide (ATO), an ancient drug with medicinal and toxic properties, has shown promise in regulating this pathway. An ATO-loaded hydrogel dressing (ATO@CS/SA) was created to facilitate scarless wound healing, utilizing chitosan (CS) and sodium alginate (SA) to prevent direct contact of ATO with the wound tissue and minimize potential side effects. In vitro studies demonstrated that low concentrations of ATO did not impact cell viability and even promoted proliferation and migration. Co-culturing the hydrogel with fibroblasts and vascular endothelial cells led to decreased expression levels of YAP and TAZ. Animal studies over a 90-day period revealed significant inhibition of scar formation with this system. Histological experiments further confirmed that the decreased expression of YAP and TAZ was responsible for this outcome. In conclusion, when administered at the appropriate dose, ATO can be repurposed from a traditional poison to a therapeutic agent, effectively suppressing excessive cell fibrosis and blood vessel proliferation and offering a novel approach to scar-free treatment.
研究领域:
生物医学工程
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药学
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组织工程
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再生医学
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细胞生物学
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DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2021
·Vol. 22
·期 3
·2100416
·
IF 4.979
Wentao Shi,Lu Bian,Yiqing Wu,Zhe Wang,Yao Dai,Yanjun Zhou,Pengfei Meng,Qing Wang,Zhijian Zhang,Xijiang Zhao,Peng Zhao,Xiaojie Lu
In the present study, fibrin-based biomaterials made of zeolite imidazole framework-8 (ZIF-8) and fibrin gel (Z-FG) are fabricated with the aim of enhancing skull regeneration. X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet (UV)–vis spectrophotometry, Fourier transform infrared spectroscopy, and rheometry are used to characterize ZIF-8 and Z-FG. The influences of ZIF-8 on the physical properties of fibrin gel (e.g., porosity, modulus, and in vitro biodegradation) are investigated, and the effect of ZIF-8 concentration on fibrin gel properties in vitro is determined by seeding ectomesenchymal stem cells (EMSCs) over Z-FG. EMSC osteogenic differentiation reveals higher expression of bone-related proteins and higher calcium deposition and alkaline phosphatase activity, indicating that Z-FG may be a good osteoinductive biomaterial. Furthermore, these results show that the piezochannel and yes-associated protein (YAP) signaling pathway are involved in the differentiation process. In addition, the in vivo results demonstrate that Z-FG increases bone formation in critical-sized calvarial defects in rats. Thus, the developed composite scaffold may be a suitable biomaterial for skull tissue-engineering applications.
研究领域:
生物材料
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组织工程
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生物医学工程
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再生医学
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DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2023
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IF 3.8
Bing Liang,Xiongbin Chen,Min Li,Lingling Zhang,Xia Yang,Liangqin Shi,Yanju Gong,Yuanyuan Gong,Huan Xu,Xiao Wu,Zhong Jin,Yanru Wang,Luwei Liu,Xiaohong Yi,Lushuang Xie,Hua Zhong,Chongyang Shen,Yong Wang,Lan Yang
Context Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP).Objective To explore the effects and mechanisms of action of LWDH in PMOP.Materials and methods Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated.Results LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62.Discussion and conclusions LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.
研究领域:
药理学
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骨科
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干细胞生物学
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老年医学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2025
·
IF 4.2
Qianru Xiang,Xiao Chen,Enhui Tang,Zhi Chen,Zijun Xia,Wenzhen Liao
Current research indicates that insulin secretion deficiency in β-cells contributes to Type 2 diabetes mellitus (T2DM), which is associated with neuropeptide Y 1 receptor (Npy1r) overexpression from neuropeptide Y (NPY) system dysregulation. To date, limited literature has explored nobiletin (NOB) as a circadian modulator for restoring β-cell function through Npy1r regulation. This study investigates NOB's stimulatory effects on insulin secretion via Npy1r and clock-modulatory signaling to elucidate its underlying mechanism. The findings demonstrated that NOB ameliorated hyperglycemia and promoted insulin secretion in two distinct mouse models: T2DM induced by a high-fat diet with low-dose streptozotocin, and acute hyperglycemia triggered by NPY. Moreover, NOB reduced NPY family peptides in the serum and suppressed Npy1r overexpression in β-cells. Comprehensive investigations revealed that NOB mitigated Npy1r-mediated β-cell dysfunction through activating clock-modulatory signaling, evidenced by restored Bmal1::Luc bioluminescence rhythmicity in mouse insulinoma6 (MIN6) cells. Molecular docking confirmed a direct NOB-Npy1r interaction, while mechanistic analyses demonstrated modulation of the retinoic acid-related orphan receptors (RORs)/Bmal1-Yes-associated protein (Yap) pathway via Yap suppression and Bmal1 activation, based on the interventions with palmitic acid, BMS 193885 (Npy1r antagonist), and NPY. Therefore, this study provides evidence that NOB can protect β-cells from insulin secretion dysfunction by downregulating Npy1r expression and activating the RORs/Bmal1-Yap pathway.
研究领域:
内分泌学
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分子生物学
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时间生物学
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糖尿病研究
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药理学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Yingjun Yang,Kuankuan Han,Siyuan Huang,Kai Wang,Yuchen Wang,Shukai Ding,Le Zhang,Miao Zhang,Bingshe Xu,Shufang Ma,Yongtao Wang,Shengli Wu,Xinlong Wang
Over the past decades, the critical role of cellular contractility associated mechanotransduction in the regulation of cell functions has been revealed. In this case, numerous biomaterials have been chemically or structurally designed to manipulate cell behaviors through the regulation of cellular contractility. In particular, adhesive proteins including fibronectin, poly-l-lysine and collagen type I have been widely applied in various biomaterials to improve cell adhesion. Therefore, clarifying the effects of adhesive proteins on cellular contractility has been valuable for the development of biomaterials design. In this study, a reference-free traction force microscopy with a well-organized microdots array was designed and prepared to investigate the relationship between adhesive proteins, cellular contractility, and mechanotransduction. The results showed that fibronectin and collagen type I were able to promote the assembly of focal adhesions and further enhance cellular contraction and YAP activity. In contrast, although the poly-l-lysine supported cell spreading and elongation, it was inefficient in inducting cell contractility and activating YAP. Additionally, compared with cellular morphogenesis, cellular contraction was essential for YAP activation.
研究领域:
细胞生物学
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生物物理学
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生物材料科学
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机械生物学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 17
·4779-4791
·
IF 6.183
Chuanchuan Lin,Kun Xu,Ye He,Bailong Tao,Zhang Yuan,Ke Li,Xuemin Li,Zengzilu Xia,Kaiyong Cai
The paracrine function of mesenchymal stromal cells (MSCs) contributes a lot to tissue development, and it is regulated by various physical factors. Moreover, the extracellular matrix (ECM) of MSCs is dynamic, and its remodeling is always occurring. In particular, stiffness changes are prevalent. Accordingly, ECM stiffness changes may affect the paracrine function of MSCs, which has not been investigated much. In this study, for the first time, alginate hydrogels with different stiffening times were used to assess the influence of dynamic ECM stiffness changes on the paracrine function of MSCs. It was found that a stiffer matrix (14.72 ± 1.44 kPa) under static conditions without any additional treatment could significantly potentiate the paracrine function of MSCs compared to a soft matrix (2.44 ± 0.23 kPa). Furthermore, this promotion was regulated by the activation of Yes-associated protein (YAP), which was caused by the polymerization of F-actin. Intriguingly, in a dynamic system, the MSC-encapsulating matrix that stiffened on the third day had stronger YAP activation than the Static-Stiff matrix. However, this activation was weakened when MSCs were cultured in a matrix that stiffened on the fifth day. The results show that an increase in ECM mechanical dosing levels would promote the paracrine function of MSCs. Moreover, an effective mechanical dose that can influence the paracrine function of MSCs indeed exists.
研究领域:
细胞生物学
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组织工程
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生物力学
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DOI
PubMed
高影响因子
Journal of Oncology
·
2022
·
IF 4.501
Weiwei Wang,Lipei Wu,Jiale Tian,Wenhui Yan,Chunrun Qi,Wuchao Liu,Shihai Xuan,Anquan Shang
Application of extracellular vesicles (EVs) for cancer treatment has been well-documented. We probed into the potential role of cervical cancer cells-secreted EVs by transferring miR-146a-5p in cervical cancer. After characterization of miR-146a-5p expression in clinical cervical cancer tissue samples, gain- and loss-of-function experiments were implemented to test the effect of miR-146a-5p on the invasion, epithelial-mesenchymal transition (EMT), and anoikis in cervical cancer cells. EVs were isolated from high-metastatic cervical cancer cells, after which their effects on the malignant behaviors of low-metastatic cervical cancer cells were assessed in a co-culture system. Luciferase assay was implemented to validate the putative binding relationship between miR-146a-5p and WWC2, followed by further investigation of downstream pathway (Hippo-YAP). Finally, nude mouse lung metastasis model was developed for in vivo validation. miR-146a-5p was elevated in cervical cancer tissues and high miR-146a-5p expression promoted the metastatic potential of cervical cancer cells through enhancing their invasiveness and anoikis resistance, and inducing EMT. Furthermore, miR-146a-5p carried by EVs secreted by highly metastatic cervical cancer cells could promote the metastasis of low-metastatic cervical cancer cells. Mechanistically, miR-146a-5p targeted WWC2 to activate YAP, by which it inhibited the phosphorylation of cofilin, and promoted the process of cofilin-mediated depolymerization of F-actin to G-actin. In vivo data demonstrated that EVs-carried miR-146a-5p promoted tumor metastasis through the WWC2/YAP axis. Cancer-derived EVs delivered pro-metastatic miR-146a-5p to regulate the actin dynamics in cervical cancer, thereby leading to cancer metastasis. This experiment highlighted an appealing therapeutic modality for cervical cancer.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Xingyu Ouyang,Wei Yu,Jianguang Wang,Hui Wang,Shikun Wang,Gang Wang,Baifeng Sun,Xu Chen,Yang Liu,Wei Wang,Cunyi Fan
Peritendinous adhesion is one of the most common postoperative or posttraumatic complications of tendon injury, which severely limits functional rehabilitation and raises the risk of re-rupture. This study prepared a multifunctional composite composed of a “sandwich” electrospun nanofibrous membrane with sustained drug release property and adhesives for sutureless application. The composite was assessed here through microscopic, spectroscopic, wettability, rheological, mechanical, and drug release analyses. The results of these characterizations are consistent with the characteristics of anti-adhesion biomaterials. In addition, the anti-adhesion effectiveness was demonstrated in fibroblasts and rats. Briefly, the composite not only decreased the proliferation, viability, and penetration of fibroblasts but also repressed cell spreading on the material surface by regulating Yes-associated protein (YAP) and inhibited oxidative stress by scavenging reactive oxygen species (ROS) simultaneously in vitro. Meanwhile, histological analysis, functional tests, gross observation, and protein analysis in vivo showed that composite was effective in reducing tendon adhesion formation. Hence, we draw the conclusion that our composite can protect tendons from peritendinous adhesion after injury and provide a new direction for future application of peritendinous anti-adhesion.
研究领域:
生物医学工程
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材料科学
·
组织工程
·
药剂学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）