ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2023
·
IF 3.9
Yingying Chen,Wei Song,He Zhang,Xinping Ji
Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is a vital process in idiopathic pulmonary fibrosis (IPF), which results in the accumulation of fibroblasts and myofibroblasts and excessive extracellular matrix deposition. Based on RNA sequencing analysis and GEO dataset reanalysis, we screened out MICALL2, a gene upregulated in the lungs of IPF mice and alveolar epithelial type II (ATII) cells from IPF patients, and aimed to explore its role in IPF. We validated the expression of MICALL2 in bleomycin (BLM)-induced IPF mice and TGF-β1-stimulated ATII cells (primary murine ATII cells and A549 cells), and explored the role of MICALL2 in IPF by knockdown of MICALL2 in BLM-induced mice and TGF-β1-stimulated ATII cells. We found that MICALL2 was upregulated in the lungs of BLM-induced mice and TGF-β1-stimulated ATII cells. MICALL2-deficient mice had reduced fibrogenesis and restrained EMT upon BLM challenge. Knockdown of MICALL2 restrained the EMT process, in vitro, through impeding β‐catenin nuclear translocation. Mechanistically, we demonstrated that NPAS2 is directly bound to the promoter of MICALL2. Altogether, our data revealed transactivation of MICALL2 induced by NPAS2, contributing to activation of the Wnt/β-catenin pathway in ATII cells, thus leading to the EMT process and subsequent pulmonary fibrosis. Interfering with MICALL2 may represent an innovative therapeutic target to mitigate the extent of IPF.
研究领域:
肺科学
·
细胞生物学
·
分子生物学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Food Frontiers
·
2024
·
IF 7.4
Xiaxia Fan,Mangmang Feng,Dan Guo,Songtao Li,Yuxuan An,Jinmiao Tian,Zhuoyu Li
Chemoresistance is a major cause of breast cancer (BC) recurrence and metastasis, and chemotherapy resistance comes from tumor stemness. Our previous study showed that quinoa bran terpenoids (QBT) exhibited significant antitumor activity. In this study, we found that QBT increased the sensitivity of drug-resistant BC cells to the chemotherapeutic drugs adriamycin (ADR) and taxol (TAX). A novel lncRNA 667012 was identified along with QBT treatment. Moreover, overexpression of lncRNA 667012 promoted drug resistance, and the reduction of 667012 restored the drug sensitivity of resistant BC cells. More importantly, the findings revealed that lncRNA 667012 promoted stemness maintenance via the stemness-related Wnt pathway. Furthermore, the result showed that QBT reduced 667012 expression and inhibited the activation of β-catenin, thereby attenuating the stemness characteristics of BC and enhancing chemosensitivity. Consistently, the data were confirmed in the xenograft mice model. These results suggest that QBT could reverse chemoresistance by inhibiting stemness. It has the potential to be developed as a novel chemotherapeutic agent or chemosensitizer for BC treatment.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
植物科学
✓ 已验证
DOI
高影响因子
POLYMER
·
2020
·
IF 4.231
Baisong Zhao,Zi-Li Zheng,Wei Liu,Hua-Mo Yin,Ri-Tong Lan,Ling Xu,Jia-Zhuang Xu,Xingrong Song,Zhong-Ming Li
Nanotopographical and chemical cues were collectively introduced onto the poly(L-lactic acid) (PLLA) surface via alkali etching and polydopamine (PDA) coating. The surface pattern was made of dense-packed PLLA lamellae, and the PDA coating did not change the feature of surface topography . Both nanotopographical pattern and PDA coating showed long-term stability in cell culture medium for two weeks. In vitro evaluations displayed that there was a synergy between nanotopography and PDA coating on cell adhesion, proliferation, and differentiation of osteoblasts, even for a culture period of two weeks. This sustained effect was attributed to the activation of the wnt/β-catenin pathway. These results hold a promising prospect for the application of bone repair grafts.
研究领域:
生物材料
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组织工程
·
细胞生物学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Bioengineered
·
2022
·
IF 6.832
Zongting Shi,Jun He,Jian He,Yuan Xu
Hydrostatic pressure is known to regulate bovine nucleus pulposus cell metabolism, but its mechanism in human nucleus pulposus cells (HNPCs) remains obscure, which attracts our attention and becomes the focus in this study. Specifically, HNPCs were treated with SKL2001 (an agonist in the Wnt/β-catenin pathway) or XAV-939 (an inhibitor of the Wnt/β-catenin pathway), and pressurized under the hydrostatic pressure of 1, 3 and 30 atm. The viability, apoptosis and proteoglycan synthesis of treated HNPC were assessed by CCK-8, flow cytometry and radioisotope incorporation assays. The levels of extracellular matrix, Collagen-II, matrix metalloproteinase 3 (MMP3), Wnt-3a and β-catenin were measured by toluidine blue staining, immunocytochemistry and Western blot. Appropriate hydrostatic stimulation (3 atm) enhanced the viability and proteoglycan synthesis yet inhibited the apoptosis of HNPCs, which also up-regulated extracellular matrix and Collagen-II levels, and down-regulated MMP3, Wnt-3a and β-catenin levels in treated HNPCs. Furthermore, high hydrostatic pressure (30 atm) inhibited the viability and proteoglycan synthesis, and promoted the morphological change and apoptosis of HNPCs, which also down-regulated extracellular matrix and Collagen-II levels and up-regulated MMP3, Wnt-3a and β-catenin levels. Besides, SKL2001 reversed the effects of hydrostatic pressure (3 atm) on inhibiting Wnt-3a, β-catenin, and MMP3 levels and promoting Collagen-II level in HNPC; whereas, XAV-939 reversed the effects of high hydrostatic pressure (30 atm) on promoting MMP3, Wnt-3a, and β-catenin levels and inhibiting Collagen-II level and proteoglycan synthesis of HNPCs. Collectively, high hydrostatic pressure promoted the apoptosis and inhibited the viability of HNPCs via activating the Wnt/β-catenin pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
·
IF 6.551
Shaochen Pang,Yue Gao,Fengbang Wang,Yuanyuan Wang,Mengxi Cao,Wenjuan Zhang,Yong Liang,Maoyong Song,Guibin Jiang
Dressings coated with silver nanoparticle (AgNP) are widely used in the management of acute and chronic wounds. However, whether AgNP exerts toxicity on wound healing remains ambiguous. To demonstrate the effects of AgNP on wound healing, we precisely quantified the recovery speed of wound by taking advantage of the fin regeneration of zebrafish. This method also enabled assessment of the adverse effect of AgNP on various steps of wound healing in vivo . We revealed that AgNP treatment at the concentration of 2 μg/ml impaired fin regeneration when exposure was performed at the phases of epithelialization and the beginning of blastema formation. Cell proliferation of regenerative blastema was significantly decreased after AgNP exposure. But the canonical signals including Wingless/Integrated (Wnt), Notch and Fibroblast growth factor (Fgf) which play important roles in cell proliferation during fin regeneration were not modulated at 36 hours post amputation (hpa). Further study showed that AgNP impaired fin regeneration through declining amputation-induced ROS as early as epithelialized phase at 18 hpa, rather than inducing ROS generation. AgNP exposure also promoted recruitment of neutrophils in the early phase of wound healing, which suggests that this event dampened amputation-induced ROS. Overall, this study suggested that application of AgNP-coated dressings should be carefully considered at the beginning stage of wound healing.
研究领域:
纳米技术
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伤口愈合
·
斑马鱼生物学
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 8
·4439-4451
·
IF 4.486
Hongping Yu,Daoyu Zhu,Pei Liu,Qianhao Yang,Junjie Gao,Yigang Huang,Yixuan Chen,Youshui Gao,Changqing Zhang
Characteristic pathological changes in osteonecrosis of the femoral head (ONFH) include reduced osteogenic differentiation of bone mesenchymal stem cells (BMSCs), impaired osseous circulation and increased intramedullary adipocytes deposition. Osthole is a bioactive derivative from coumarin with a wide range of pharmacotherapeutic effects. The aim of this study was to unveil the potential protective role of osthole in alcohol-induced ONFH. In vitro, ethanol (50 mmol/L) remarkably decreased the proliferation and osteogenic differentiation of BMSCs and impaired the proliferation and tube formation capacity of human umbilical vein endothelial cell (HUVECs), whereas it substantially promoted the adipogenic differentiation of BMSCs. However, osthole could reverse the effects of ethanol on osteogenesis via modulating Wnt/β-catenin pathway, stimulate vasculogenesis and counteract adipogenesis. In vivo, the protective role of osthole was confirmed in the well-constructed rat model of ethanol-induced ONFH, demonstrated by a cascade of radiographical and pathological investigations including micro-CT scanning, haematoxylin-eosin staining, TdT-mediated dUTP nick end labelling, immunohistochemical staining and fluorochrome labelling. Taken together, for the first time, osthole was demonstrated to rescue the ethanol-induced ONFH via promoting bone formation, driving vascularization and retarding adipogenesis.
研究领域:
药理学
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骨科
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Environmental Chemistry and Ecotoxicology
·
2025
·
IF 8.2
Hongmin Lu,Ruoqi Wang,Xin Zhang,Yuze Dong,Hao Liu,Yunfan Zhang,Chengxue Ma,Mingwei Xing
Chronic exposure to fluoride and phenanthrene is recognized as a significant risk factor for neurobehavioral toxicity, and the gut-brain axis has been identified as a key mechanism in the development of anxiety behaviors following prolonged toxic insult. Nevertheless, the connections between gut microbiota disruption, serotonin (5-HT) production, and neurobehavioral toxicity induced by long-term co-exposure to fluoride and phenanthrene remain unclear. In this study, co-exposure model of phenanthrene and fluoride at environmentally relevant concentrations was established in zebrafish. Through comparative database analysis, anxiety behavior tests, 16S rRNA sequencing, metabolomics, qPCR, Western blotting, ELISA, flow cytometry, comet assay, histological analysis, and immunohistochemistry, the neurotoxic effects of fluoride or/and phenanthrene were investigated. In this study, neurobehavioral toxicity was observed in zebrafish following co-exposure to environmentally relevant concentrations of fluoride and phenanthrene, characterized by diminished swimming capacity and heightened anxiety behavior. The toxic mechanism was mediated through disruption of the microbiome–gut–brain axis homeostasis and suppression of the Wnt/β-catenin signalling pathway. Specifically, co-exposure decreased intestinal synthesis of 5-HT and impaired the blood–brain barrier. As the intestine serves as the primary source of 5-HT, its impairment (histopathological alterations, gut microbiota dysbiosis and metabolomics) led to dysregulation of the 5-HT system. Histopathological analysis of brain tissue revealed synaptic loss, nuclear pyknosis, and the presence of apoptotic bodies. Investigations into the molecular mechanisms indicated that fluoride or/and phenanthrene inhibited Wnt signalling, promoted β-catenin degradation, and induced neurological dysfunction, as evidenced by reductions in SYP and MAP2, which subsequently activated pro-apoptotic genes (Bax, Caspase9, and Caspase3) and inflammatory responses (decreased IL-10, elevated NF-κB, IL-6, TNF-α, and cleaved IL-1β). These alterations ultimately contributed to neurobehavioral deficits. Collectively, these findings indicate that fluoride and phenanthrene induce anxiety behavior and neurotoxicity, associated with perturbations in 5-HT metabolism, gut microbiota composition, oxidative stress, apoptosis, and neuroinflammation.
研究领域:
毒理学
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环境科学
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神经科学
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分子生物学
·
生态毒理学
✓ 已验证
产品关联
DOI
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2024
·
IF 4.8
Lu-Ping Wen,Shao-Wei Gao,Hua-Xian Chen,Qi Liu,Guo-Zhong Xiao,Hong-Cheng Lin,Qiu-Lan He
Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus , has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed A p c Min ∕ + mice. A p c Min ∕ + mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1 β , IL-6, and TNF- α ), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/ β -catenin pathway proteins (Wnt3a, β -catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed A p c Min ∕ + mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed A p c Min ∕ + mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/ β -catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV’s antitumor effects.
研究领域:
药理学
·
肿瘤学
·
胃肠病学
·
微生物学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
CELL
·
2025
·
IF 42.5
Daoming Chen,Zhou Yu,Wenbo Wu,Yingxue Du,Qianqian Du,Huanwei Huang,Yaqi Li,Ting Xuan,Ya-Chen Liang,Yang Liu,Zijuan Wang,Rina Su,Yi Zhao,Qi Li,Minmin Luo,Fengchao Wang,Ji Li,Cheng-Ming Chuong,Zhimiao Lin,Ting Chen
Hair loss affects millions globally, significantly impacting quality of life and psychological well-being. Despite its prevalence, effective strategies for promoting human hair growth remain elusive. By investigating congenital generalized hypertrichosis terminalis (CGHT), a rare genetic disorder characterized by excessive hair growth, we discover that chromatin deletions or an inverted duplication disrupt the topologically associating domain (TAD), leading to the upregulation of the potassium channel KCNJ2 in dermal fibroblasts. Mouse genetics demonstrate that KCNJ2-mediated membrane hyperpolarization in dermal fibroblasts promotes hair growth by enhancing fibroblasts Wnt signaling responses, involving a reduction in intracellular calcium levels. Notably, fibroblast membrane potential oscillates during the normal hair cycle, with hyperpolarization specifically associated with the growth phase. Inducing fibroblast membrane depolarization delays the growth phase, while KCNJ2-mediated hyperpolarization rescues hair loss in aging and androgenetic alopecia models. These results uncover a previously unrecognized role of fibroblast bioelectricity in tissue regeneration, offering novel therapeutic avenues for hair loss treatment.
研究领域:
皮肤病学
·
分子生物学
·
遗传学
·
细胞信号传导
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
QiuShi Wei,MinCong He,MeiHui Chen,ZhenQiu Chen,Fan Yang,HaiBin Wang,Jin Zhang,Wei He
Icariin, the major ingredient of Herba Epimedii, promotes the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and exerts protective effects against bone loss and increases bone regeneration, but the underlying signaling pathway by which icariin affects osteogenic differentiation remain unclear. Transcriptional coactivator with PDZ-binding motif (TAZ) is a transcriptional modulator of the Hippo signaling pathway, which plays an important role in the osteogenic differentiation of BMSCs by activating Runx2 gene during the terminal osteogenic differentiation. In this study, we found that 0.1 μM icariin markedly promoted the proliferation, calcium depositions, and osteogenic genes expression of rBMSCs. Icariin (0.1 μM) upregulated TAZ, Runx2, β-catenin, Osteopotin, and Dlx5 expression mainly at the early stage of osteogenic differentiation, and increased osteocalcin expression at the late stage. Our result further demonstrated that knockdown TAZ expression by lentivirus-mediated TAZ shRNA inhibited the icariin-induced osteogenic differentiation. Moreover, ICI 182780 (the estrogen receptor alpha inhibitor) or DKK1 (the Wnt/β-catenin pathway inhibitor), inhibited the icariin-induced increase in TAZ expression. Furthermore, icariin stimulated the activation of TAZ as evidenced by increased total TAZ protein and nuclear translocation, but these effects of icariin were blocked by ICI 182780 or DKK1. Taken together, our results demonstrate that icariin promotes the osteogenic differentiation of rBMSCs by increasing TAZ expression, and that the increased TAZ expression induced by icariin is mostly mediated by the ERα and Wnt/β-catenin pathway.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
骨再生
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Wenqi Wang,Xiaolong Wei,Hengshuo Gui,Tingxuan Yan,Bolong Xu,Konglin Wu,Huiyu Liu,Xianwen Wang
Highly effective antibacterial wound dressings are essential for improving the treatment of infected wounds. This study constructs a nitrogen-doped carbon-based silver single-atom/nanoparticle composite carrier (2% Ag SA/NP -NC) and anchors it in a cationic guar matrix (CG) to develop a smart dressing with synergistic antibacterial-healing-promoting function. Benefiting from the doped Ag SA/NP , the triple enzyme catalytic efficiencies of oxidase, peroxidase, and glutathione peroxidase are enhanced. Through the synergistic ROS burst mechanism, the biofilm matrix is effectively disintegrated and the bacterial membrane permeability is enhanced. Mechanistic studies show that the synergistic effect of Ag + /ROS triggers an “oxidative stress-metabolic inhibition” cascade reaction at the molecular level. The change in membrane permeability promotes the inward flux of Ag + , exacerbates the oxidative stress damage of bacteria, and downregulates the expression of genes related to sugar degradation, the TCA cycle, and the electron transport chain, leading to energy depletion and genetic material damage. Furthermore, the dressing activates the Wnt, MAPK, and PI3K-Akt signalling pathways to promote cell proliferation, angiogenesis, and epidermal growth to remodel the infection microenvironment. This antibacterial-tissue regeneration treatment provides a systematic solution for infected wound treatment.s
研究领域:
纳米技术
·
生物医学工程
·
材料科学
·
抗菌治疗
·
再生医学
·
生物化学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Xin Wei,Mingzhu Zuo,Qiongwen Liang,Shiwei Zhang,Jingmei Wang,Zhanfeng Li,Wenguang Yang,Fang Ma,Wangxiao He,Tianya Liu
Microsatellite-stable colorectal cancer (MSS-CRC) is characterized by poor immune infiltration and immune evasion, leading to rapid tumor progression and limited efficacy of current immunotherapies. The bioinformatics analysis revealed that the hyperactivation of the Wnt/β-catenin signaling pathway in MSS-CRC is instrumental in mediating immune suppression. Although inhibiting this pathway presents a therapeutic opportunity, no Wnt inhibitors have been clinically approved due to Wnt's essential role in maintaining tissue homeostasis, with inhibition in normal cells causing significant toxicity. To address it, we discovered that Wnt activation in colorectal cancer cells enhances macropinocytosis, particularly favoring the uptake of glycosylated proteins to meet increased nutrient demands. Building on this insight, we developed a glycosylated human serum albumin (GHSA) co-assembled with carnosic acid (CA), termed glycosylated human serum albumin-carnosic acid (GHSACA), which is selectively internalized by Wnt-activated colorectal cancer cells. This approach not only reduces off-target toxicity but also effectively inhibits the Wnt pathway, resulting in notable tumor inhibition and immune reactivation in murine models, while maintaining a favorable safety profile. This strategy offers a promising therapeutic solution by combining selective Wnt inhibition with enhanced immune activation in MSS-CRC, and highlights the potential of leveraging disease-specific cellular uptake mechanisms for designing nanomedicines, advancing the development of precision-targeted cancer therapies.
研究领域:
肿瘤学
·
免疫治疗
·
分子生物学
·
纳米医学
·
生物信息学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）