PHYTOMEDICINE
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2025
·
IF 8.3
Hanfeng Xu,Jie Gao,Shiyong Fu,Zihao Liang,Ying Zhang,Huijuan Chen,Qin Zheng
Background Triple-negative breast cancer, the most aggressive breast cancer with highest metastatic capacity and the worst prognosis, accounts for 15% of breast cancer. According to prior studies, the natural active component genkwanin suppressed cell growth in estrogen-receptor-positive breast cancer. Nonetheless, its impact on triple-negative breast cancer and its target remains poorly understood. Purpose To explore the effects of genkwanin and identify the direct targets and cellular mechanism of genkwanin in triple-negative breast cancer. Study design The effects of genkwanin were investigated in SUM-159PT and MDA-MB-231 cells. Direct target protein of genkwanin were identified by Quantitative proteomics. The in-vivo effect of genkwanin on triple-negative breast cancer were investigated using mouse models. Methods The anti-metastasis effects of genkwanin were investigated by individual cell-tracking assay and 3D-on top assay. Quantitative proteomics was used to identify the target of genkwanin and microscale thermophoresis ligand-binding assay was performed to further confirmed it. In-vitro and in-vivo extreme limiting diluting assays were performed to investigate the inhibitory effect of stemness. Lung metastasis mouse model was used to evaluate the anti-metastasis effects of genkwanin. Results This study demonstrated that genkwanin could significantly attenuate migration and invasion in triple-negative breast cancer cells. Notably, genkwanin could efficiently modulate the stemness of breast cancer cells and improve its sensitivity to paclitaxel (PTX). Lysine demethylase 4C (KDM4C) was identified as the target of genkwanin and the in-vivo therapeutic effect of genkwanin was also confirmed in 4T1-luc lung metastasis model. Mechanically, genkwanin reduced KDM4C expression, which regulated the lysine demethylation of histone H3, thereby suppressing KLF14 transcription. KLF14 acts as a switch of lipid synthesis and regulates intracellular cholesterol levels, inhibiting cancer metastasis. Conclusion These results demonstrate genkwanin's therapeutic potential in triple-negative breast cancer and its effect on targeting metastasis.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Human Cell
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2025
·Vol. 38
·期 3
·1-14
·
IF 3.1
Zhu Xiao-Yu,Li Pi-Song,Qu Hui,Ai Xing,Zhao Zi-Ting,He Jia-Bei
Radiotherapy resistance, is usually caused by enhanced tumor stemness and poses a significant challenge in treating breast cancer (BRCA). In this study, we investigated the molecular regulatory mechanism of radiotherapy sensitivity in BRCA associated with replication factor C4 (RFC4) and insulin-like growth factor 2 mRNA binding protein 2 mRNA Binding Protein 2 (IGF2BP2). RFC4 expression was increased in BRCA cell lines and tissues, and high RFC4 expression in BRCA patients predicted the occurrence of lymphatic metastasis. RFC4-specific short hairpin RNA sequences or RFC4 coding sequences were subsequently cloned and inserted into plasmid vectors to downregulate or upregulate RFC4 expression. Knockdown of RFC4 attenuated stemness, as evidenced by a reduction in sphere formation and the downregulation of CD44 and SOX2. RFC4 silencing inhibited migration and invasion, promoted apoptosis, and improved sensitivity to radiotherapy (4-Gy X-ray). The results were detected by a wound healing assay, a transwell assay, and flow cytometry. The overexpression of RFC4 had the opposite effect on BRCA cells. Like RFC4 expression, IGF2BP2 expression was also increased in the cancer tissues of breast cancer patients. The results of the dual luciferase assay and RIP assay confirmed the binding of IGF2BP2 to the RFC4 mRNA coding sequence. Knockdown of RFC4 eliminated the effects of IGF2BP2 overexpression on increasing cell viability, invasion, the expression of stemness markers and radioresistance, suggesting that the effect of RFC4 on the stemness of BRCA cells was regulated by IGF2BP2. In conclusion, we reported that RFC4, a key regulator of BRCA progression, promoted radioresistance in BRCA and was positively regulated by IGF2BP2.
研究领域:
肿瘤学
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分子生物学
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医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Qingyu Yu,Huizhong Hao,Weitong Wang,Linhua Zhang,Chenlu Huang,Jianying Hao,Xinyu Yang,Dunwan Zhu,Junjie Li,Hong Sun
Due to the utilization of well-defined artificial niches, stem cell culture in a three-dimensional hydrogel matrix has been a promising method for obtaining sufficient seed cells. Although various hydrogels can support desirable cell proliferation, establishing a normalized hydrogel that adequately mimics the extracellular matrix (ECM), maintains stemness and allows for controlled release of stem cells remains a significant challenge. Herein, we report a hydrogel composed of sulfobetaine-modified dextran and gelatin to maintain stemness and enable the rapid release of adipose-derived stem cells (ADSCs). Dextran can effectively maintain multipotent phenotype of ADSCs by grafting zwitterionic groups. Gelatin can significantly improve the proliferation of ADSCs. The hydrogel network they form effectively mimics the ECM microenvironment, providing an advantage when used as a three-dimensional niche to promote cell proliferation. Most importantly, the disulfide-crosslinked hydrogels show specific photodegradation capability, which precisely enables the system to achieve controlled release and efficient harvest of ADSCs. The cell viability (90 %) and harvest ratio (64 %) were well maintained by light degradation compared with GSH and collagenase degradation. Overall, this study offers a universal stem cell niche based on photodegradable hydrogel that shows great promise in the field of ADSCs proliferation and harvest.
研究领域:
生物材料学
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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
CHEMICAL ENGINEERING JOURNAL
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2023
·
IF 15.1
Jiarong Xu,Qi Zeng,Xiuli Chen,Honglian Guo,Yusheng Gong,Rengui Xu,Peng Cao,Chunyu Wei,Fei Xiao,Dawei Jiang,Wei Chen
Dry skin, known as the xerosis, would induce deep cracks and fissures, leading to bleeding and increased risk of allergens and pathogens penetrating the skin, which may trigger allergic and irritant contact dermatitis as well as the severe infection. High-frequent administration of traditional emulsion or moisturizer often results in significantly reduced patient compliance/adherence and limited therapeutic efficacy. Microneedle (MN) patches have been extensively investigated due to their deep penetration through the epidermis for sustained release in a patient-friendly manner. In this study, an iron (III) cross-linked alginate microneedle patch (ICAMP) has been developed for long-term treatment of xerosis by delivering the ammonium lactate for local management. In order to achieve on-demand treatment, the microneedles were cross-linked with iron (III) which could be photodegraded into iron (II) by exposure to light at 405 nm, triggering microneedles to dissolve in the interstitial fluid for payload release. In such a way, the drug could be released in a well-tunable fashion by using a light-based controller, suggesting a regulated manner to treat xerosis especially under intense light radiation.
研究领域:
药剂学
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生物材料
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皮肤病学
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DOI
高影响因子
Journal of Physical Chemistry C
·
2022
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IF 4.177
Shuaigang Ge,Wenyong Jia,Bao Ke,Qilin Wei,Chengzhi Yang,Shangfei Yao,Hualin Zhao,Zi-An Li,Xianci Zhong,Bingsuo Zou
All-inorganic metal halide perovskite semiconductors have great potentials in lighting applications, but the effect of excitonic magnetic polarons (EMPs) in the transition metal (TM) ion-doped halide perovskites on their luminescence processes has not been extensively understood. Here, we have synthesized Mn2+-doped Rb3Cd2Cl7 perovskite powders with different doping amounts by a hydrothermal method. After Mn(II) is doped, Rb3Cd2Cl7 gives strong emission, though the Rb3Cd2Cl7 powder itself does not emit light. This emission originates from the intrinsic self-trapped exciton (STE) formation enhanced by the ferromagnetic Mn–Mn pair with spin–spin coupling, that is, the magnetic polaron whose astonishing luminescence at 587 nm has a quantum yield up to 147%. Some shallow trapped centers below the conduction band out of high d levels by localized EMPs after photoexcitation are proven to add to this luminescence process. The thermoluminescence phenomenon with rising temperature proves that these shallow trapped carriers are present with phonon and multiphonon notation, and their efficient transfer to the conduction band and the STE state occurs via the electron–phonon coupling during photoexcitation. This compound provides a new way for TM-doped perovskite material design and applications for magneto-optical and display technology.
研究领域:
材料科学
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光学
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半导体物理
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固体化学
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DOI
高影响因子
CANCER LETTERS
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2023
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IF 9.7
Jiaoshun Chen,Haoxiang Zhang,Chaoyang Xiu,Chenggang Gao,Shihong Wu,Jianwei Bai,Qiang Shen,Tao Yin
In eukaryotes, N 6 -methyladenosine (m6A) is the most prevalent epigenetic alteration. Methyltransferase-like 3 (METTL3) is a key player in the control of m6A, although its function in pancreatic cancer is incompletely understood. In this study, we examined the role that METTL3 plays in pancreatic cancer cell proliferation and stemness. We discovered that in pancreatic cancer cells, METTL3-mediated m6A alterations regulate ID2 as a downstream target. The stability of ID2 mRNA was decreased and m6A modification was effectively eliminated by METTL3 knockdown in pancreatic cancer cells. We also demonstrate that m6a-YTHDF2 is necessary for the METTL3-mediated stabilization of ID2 mRNA. Additionally, we show that ID2 controls the stemness molecules NANOG and SOX2 via the PI3K-AKT pathway to support pancreatic cancer growth and stemness maintenance. Our data suggest that METTL3 may post-transcriptionally upregulate ID2 expression in an m6A-YTHDF2-dependent manner to further promote the stabilization of ID2 mRNA, which may be a new target for pancreatic cancer treatment.
研究领域:
癌症生物学
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2021
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IF 4.539
Jing Wang,Jin Qu,Yuxing Liu,Shuo Wang,Xinle Liu,Yipeng Chen,Peiyao Qi,Guohao Miao,Xiaofei Liu
Hydrogel sensor has been widely researched for their flexibility and elasticity; however, its poor mechanical, anti-dry and anti-freezing properties hinder its application in wearable devices seriously. Herein, a flexible, ultra-tough, excellent self-recoverable, anti-dry and anti-freezing ionic EG/MoS 2 -PAAM-Fe 3+ organohydrogel was prepared by adding ethylene glycol to the MoS 2 -PAAM-Fe 3+ hydrogel using solvent exchange method. And due to the pyramid microstructures at the bottom, the “crocodile skin” gel sensor exhibited good pressure sensitivity (S = 0.06 kPa −1 ) and fast electrical response to monitoring human movements. The MoS 2 -based organohydrogel with comprehensive properties showed promising application potentials in the new generation of electronic materials and devices used at low temperatures.
研究领域:
材料科学
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生物医学工程
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DOI
高影响因子
IEEE Photonics Journal
·
2024
·Vol. 16
·期 6
·1-10
·
IF 2.1
Xin Jiang,Weilong Zhou,Wen Dong,Zhu Wang,Yifei Xie,Xinyue Tang,Zichun Le
Laser speckle caused by high coherence severely affects the image quality. The traditional optical approaches cannot effectively suppress speckles without compromising the coherence of the laser in the optical path. In this study, we develop a method in which a novel polymer-stabilized liquid crystal screen (PSLCS) was used to display images for efficient speckle suppression while preserving the coherence and high brightness of lasers. The scattering-induced fluctuations in the intensity of the light reflected from the PSLCS are evaluated to reveal decorrelation variation. The optimal parameters for suppressing speckles and obtaining a clear and high-resolution image via both laser projection and AR imaging are identified by adjusting the driving parameters. A speckle suppression efficiency of 67.34%, which exceeds that achieved by other similar methods, was achieved without using any additional optical elements. An experiment was implemented for verifying the performance of multi-plane AR imaging by a PSLCS, which, to our knowledge, is the first study to investigate the image quality and speckle suppression effect in AR imaging. The proposed cost-effective laser speckle suppression method enables high quality imaging, offering new possibilities for the application of LC-based optical materials and devices in display technology.
研究领域:
光学
·
显示技术
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Wanbing Pan,Rong Sun,Yaoyuan Yu,Yuxin Liu,Yinling Mu,Hanyan Gong,Hongxia Fan,Yingchao Zhang,Lutong He,Haibing He,Jingxin Gou,Xing Tang,Tian Yin,Yu Zhang
Effective management of posterior ocular segment disorders necessitates sustained retinal drug delivery and rational therapeutic selection. Despite significant advances, developing drug delivery systems that simultaneously achieve deep tissue penetration and prolonged ocular surface retention remains challenging. To bridge this gap, we engineered a borneol- decorated baicalein nanoemulsion in-situ gel (Bor/Bai-N@GEL) ophthalmic formulation for dry age-related macular degeneration (d-AMD). The system integrates a borneol-decorated baicalein nanoemulsion with an ion- sensitive hydrogel. Comparative analysis revealed Bor/Bai-N@GEL’s superior therapeutic performance, attributable to the prolonged ocular residence time and enhanced transcorneal permeability. Pharmacodynamic profiling demonstrated marked attenuation of inflammatory cytokines, oxidative markers, and apoptotic signaling in murine d-AMD models. In summary, our work provided a meaningful delivery strategy and research basis to treat fundus diseases. This approach offers the potential to conveniently treat early-stage d-AMD at home, improving patient adherence and overall treatment outcomes.
研究领域:
药剂学
·
眼科医学
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生物医学工程
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DOI
PubMed
高影响因子
Cellular Reprogramming
·
2018
·Vol. 20
·期 2
·99-106
·
IF 1.43
Mengya Zhao,Lin Li,Jundong Zhou,Xueyuan Cui,Qingmei Tian,Yaqing Jin,Yimin Zhu
Cancer stem cells (CSCs) are responsible for cancer initiating, recurrence, and drug resistance. Discovery of novel biomarkers for CSCs is helpful for early diagnosis and prognosis. Lung cancer stem cells (LCSCs) were closely related to the occurrence and development of lung cancer. In our study, the important role of miR-2861 in maintaining the stemness of LCSCs was investigated. The LCSC differentiation model was established through introducing serum into the medium of H460 spheres. miR-2861 expression was significantly higher in LCSCs no matter compared to the differentiation cells or normal cells. HDAC5 expression was positively correlated with miR-2861 in LCSCs, and knockdown of miR-2861 decreased the expression of HDAC5, which implied that HDAC5 may be involved in the differentiation of LCSCs mediated by miR-2861. The role of HDAC5 in the regulation of LCSC differentiation was further verified by the inhibitory effect of LMK-235 on the phosphorylation of ERK1/2, which was recognized as the regulator of CSC differentiation. Our study provided a better understanding of miR-2861 and HDAC5 axis in maintaining the stemness of LCSCs and laid a foundation for molecular targeted therapy.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Panpan Gu,Jinhu Liu,Tong Gao,Qingping Ma,Shuying Gao,Nan Li,Weihan Zhang,Zhenxing Xia,Qinglin Yang,Weiwei Mu,Shuang Liang,Shunli Fu,Shijun Yuan,Suyun Wei,Jie Liu,Yuxin Yang,Xiaoxin Yan,Yongjun Liu,Cong Wang,Na Zhang
GOx-mediated glucose depletion offers an alternative noninvasive strategy for tumor therapy, but its lower catalytic activity in vivo limits its clinical application. Herein, we designed a temperature-sensitive nano-GOx (NG) that was constructed by gold nanorods chemically modified with GOx (AuNRs-GOx) and coated with temperature-sensitive lipids. The chemical linkage could maintain the natural conformation of GOx, ensuring that NG exerted powerful catalytic activity within the tumor and initiated antitumor immune response through moderate starvation and mild photothermal therapy (mPTT) to coregulating dendritic cells (DCs) and tumor-associated macrophages (TAMs). Ulteriorly, VTNG was obtained by NG coloading with verteporfin (VP) and evofosfamide (TH-302). VTNG demonstrated temperature-sensitive triggered drug release when exposed to near-infrared laser irradiation. NG exacerbated the degree of TME hypoxia and facilitated the activation of TH-302. Meanwhile, VP enhanced tumor cell sensitivity by decreasing the stemness of the tumor cells, thus realizing the effective killing of tumor cells and further enhancing the therapeutic effect of NG. Notably, VTNG had a significant antitumor effect in melanoma models compared with first-line melanoma therapy and formed an immune memory effect. In conclusion, VTNG provided an effective approach to enhance the therapeutic effect of GOx for tumor treatment.
研究领域:
肿瘤学
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纳米医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ONCOGENE
·
2020
·Vol. 39
·期 17
·3588-3603
·
IF 7.971
Liu Xiaochen,Cui Jianfeng,Gong Li,Tian Fei,Shen Yangli,Chen Lipeng,Wang Yong,Xia Yangyang,Liu Lei,Ye Xiang,Wang Molin,Liu Guangyi,Jiang Baichun,Shao Changshun,Zou Yongxin,Gong Yaoqin
CUL4B, which acts as a scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes, participates in a variety of biological processes. Previous studies have shown that CUL4B is often overexpressed and exhibits oncogenic activities in a variety of solid tumors. However, the roles and the underlying mechanisms of CUL4B in bladder cancer (BC) were poorly understood. Here, we showed that CUL4B levels were overexpressed and positively correlated with the malignancy of BC, and CUL4B could confer BC cells increased motility, invasiveness, stemness, and chemoresistance. The PIK3CA/AKT pathway was identified as a critical downstream mediator of CUL4B-driven oncogenicity in BC cells. Furthermore, we demonstrated that CRL4B epigenetically repressed the transcription of miR-372/373, via catalyzing monoubiquitination of H2AK119 at the gene cluster encoding miR-372/373, leading to upregulation of PIK3CA and activation of AKT. Our findings thus establish a critical role for the CUL4B-miR-372/373-PIK3CA/AKT axis in the pathogenesis of BC and have important prognostic and therapeutic implications in BC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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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）