PHYTOMEDICINE
·
2022
·
IF 6.656
Chuan Li,Liru Tian,Yihai Wang,Huan Luo,Jia Zeng,Peiqiang Su,Shulin Chen,Zhiheng Liao,Weimin Guo,Xiangjiu He,Shuqing Chen,Caixia Xu
Background Morinda officinalis (MO) is a herb used in Traditional Chinese Medicine (TCM) for the treatment of osteoporosis. M13, a MO-based anthraquinone compound is known to suppress osteoclast activity. However, whether M13 promotes MSCs osteogenic differentiation and its potential mechanism remains unknown. Purpose To examine the influence of M13 on MSCs proliferation and osteogenic differentiation and elucidate the underlying mechanism. Methods/Study designs The effect of M13 exposure on MSCs proliferation was assessed via CCK8 assay, clone formation assay, immunofluorescence, RT-qPCR, and Western blot. The M13-mediated osteogenesis in vitro and ex vivo were evaluated via ALP and Alizarin red S staining, osteogenesis-associated gene (Runx2, Col1a1 and Opn) expression, and fetal limb explants culture. Molecular docking was employed for target signal pathway screening. The potential signaling mechanisms of M13-promoted MSCs osteogenic differentiation were analyzed by introducing XAV939 (Wnt/β-catenin signaling inhibitor). Results M13 induced certain obvious positive effects on MSCs proliferation and osteogenic differentiation. Treatment with M13 enhanced MSCs viability and clone numbers. Meanwhile, M13 promoted osteogenic gene expression, enhanced ALP intensity and Alizarin red S staining in MSCs. In terms of mechanism, M13 strongly interacted with the docking site of the WNT signaling complex, thereby activating the Wnt/β-catenin pathway. Furthermore, the M13-mediated osteogenic effect was partially inhibited by XAV939 both in vitro and ex vivo , which confirmed that the Wnt/β-catenin axis is a critical regulator of M13-induced osteogenic differentiation of MSCs. Conclusion Our study elucidated for the first time that M13 significantly promoted osteogenic differentiation of MSCs via stimulation of the Wnt/β-catenin pathway in vitro and ex vivo .Our findings offered new additional evidence to support the MO or M13-based therapy of osteoporosis.
研究领域:
药理学
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细胞生物学
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分子生物学
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传统中药
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骨生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Feiran Zhou,Xinyi Hu,Weijing Feng,Minghui Li,Bin Yu,Chenxing Fu,Caiwen Ou
Intimal hyperplasia-induced restenosis is a common response to vascular endothelial damage caused by mechanical force or other stimulation, and is closely linked to vascular remodeling . Curcumin , a traditional Chinese medicine , exhibits potent protective effects in cardiovascular diseases; for example, it attenuates vascular remodeling. Although the suppressive effects of curcumin on diseases caused by vascular narrowing have been investigated, the underlying mechanisms remain unknown. Long non-coding RNAs (lncRNAs) regulate various pathological processes and affect the action of drugs. In the present study, we found that the curcumin remarkably downregulated the expression of lncRNA H19 and thereby inhibited intimal hyperplasia-induced vascular restenosis. Furthermore, the inhibition of the expression of H19 by curcumin resulted in the inactivation of the Wnt/β-catenin signaling. Overall, we show that curcumin suppresses intimal hyperplasia via the H19/Wnt/β-catenin pathway, implying that H19 is a critical molecule in the suppression of intimal hyperplasia after balloon injury by curcumin. These insights should be useful for potential application of curcumin as a therapeutic intervention in vascular stenosis.
研究领域:
分子生物学
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药理学
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心血管疾病
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
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IF 9.8
Yang Yang,Yue Tao,Xiaodong Yi,Guanyu Zhong,Yanyan Gu,Yunhe Cui,Ying Zhang
Typical plasticizer di (2-ethylhexyl) phthalate (DEHP) has been demonstrated to induce cardiotoxicity in zebrafish, but the potential molecular mechanisms involved have not been fully elucidated. Aryl hydrocarbon receptor (AhR), an essential protein for inducing developmental abnormalities, has been demonstrated to be activated by DEHP in other species, but whether the AhR signaling pathway also contributes to DEHP-mediated cardiac developmental toxicity in zebrafish remains unclear. Firstly, molecular docking simulations initially confirmed the possibility that DEHP has AhR agonistic activity. To further confirm this conjecture, this work analyzed the changes of cardiac-related indexes in zebrafish stressed by DEHP at individual, protein, and gene levels. The results showed that DEHP mediated cardiac phenotypic developmental defects, increased CYP1A1 activity, and oxidative stress as well as significant changes in the expression levels of key proteins and genes of AhR, Wnt/β-catenin, and Nrf2-Keap1 signaling pathways. Notably, the addition of AhR inhibitors effectively alleviated the above negative effects, indicating that the AhR signaling pathway and its crosstalk with the Wnt/β-catenin signaling pathway is an essential pathway for DEHP-mediated cardiac developmental toxicity. Overall, this work enriches the molecular mechanism of DEHP-mediated cardiac developmental defects in zebrafish and provides a reliable biomarker for future environmental risk assessment of DEHP.
研究领域:
环境科学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2025
·Vol. 31
·期 5
·e70437
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IF 5
Hai‐Qian Zhang,Yan Wang,Xiao Geng,Mingxin Dong,Ziwei Liu,Chengbiao Sun,Kaikai Yu,Wenwen Xin,Ye Xu,Na Xu,Wensen Liu
ANG‐modified liposomes encapsulating α‐melittin and resveratrol increase their blood–brain barrier penetration and GB cell selectivity. The combined treatment of α‐melittin with resveratrol markedly facilitates apoptosis and pyroptosis, and promotes the apoptosis–pyroptosis switch in the GB cells via downregulating the Wnt/β‐catenin signaling.
研究领域:
药理学
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肿瘤学
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神经科学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
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IF 3.743
Xiao-Jun Chen,Ying-Shan Shen,Min-Cong He,Fan Yang,Peng Yang,Feng-Xiang Pang,Wei He,Yan-ming Cao,Qiu-Shi Wei
Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory disease induced by glucocorticoids. Marrow mesenchymal stem cells (MSCs) differentiate into multiple bone matrix cells and have been used as cell-based therapies to treat ONFH. However, the osteogenesis of MSCs isolated from patients with SONFH is significantly decreased. Polydatin has been widely used in traditional Chinese remedies due to its multiple pharmacological actions. As shown in our previous study, Polydatin protects from oxidative stress and promotes BMSC migration. However, little is known about its role in BMSC (Bone marrow mesenchymal stem cells) osteogenesis; therefore, we further investigated the effect and mechanism of Polydatin in hBMSC osteogenesis. The ability of Polydatin to promote the proliferation and osteogenic differentiation of hBMSCs was determined using the MTT assay, ALP staining and the ALP activity assay. Next, qPCR and western blotting were performed to measure the levels of genes and proteins related to the osteogenesis of hBMSCs. Then, the effect of Polydatin on the nuclear translocation of β-catenin was determined using immunofluorescence staining. Polydatin (30 μM) markedly enhanced the proliferation of hBMSCs and alkaline phosphatase (ALP) activity. Additionally, it also significantly upregulated the expression of osteogenic genes (Runx2, osteopontin, DLX5, osteocalcin, collagen type I and BMP2) and components of the Wnt signaling pathway (β-catenin, Lef1, TCF7, c-jun, c-myc and cyclin D). These osteogenesis-potentiating effects of Polydatin were blocked by Noggin, an inhibitor of the BMP pathway, and DKK1, an inhibitor of the Wnt/β-catenin pathway. However, DKK1 did not affect Polydatin-induced BMP2 expression. Based on our results, Polydatin promotes the proliferation and osteogenic differentiation of hBMSCs through the BMP2-Wnt/β-catenin signaling pathway.
研究领域:
药理学
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干细胞研究
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骨科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
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2020
·Vol. 20
·期 4
·1-1
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IF 2.311
Peng He,Guoguang Xiong,Wei Guo,Guanjun Jiang,Yun Li,Hao Li
Long non‑coding RNA colon cancer associated transcript 2 (CCAT2) is dysregulated in a number of different types of human cancer, and affects cancer progression via the Wnt/β‑catenin signaling pathway. However, the roles of CCAT2 and the Wnt/β‑catenin signaling pathway in prostate cancer (PCa) are not completely understood. The present study aimed to investigate the potential mechanism of CCAT2 in PCa. In the present study, the reverse transcription‑quantitative PCR (RT‑qPCR) results indicated that CCAT2 expression was significantly upregulated in PCa tissues, and DU145 and PC3 cell lines compared with normal prostate tissues and the epithelial RWPE‑1 cell line, respectively. Functional assays indicated that CCAT2 downregulation inhibited DU145 and PC3 cell proliferation, cell cycle, migration and invasion. In addition, the luciferase reporter assay, RT‑qPCR and western blotting results indicated that CCAT2 regulated transcription factor 7 like 2 (TCF7L2) expression by binding to microRNA‑217. Further western blotting and TOPFlash assays indicated that CCAT2‑knockdown inhibited the Wnt/β‑catenin signaling pathway in DU145 and PC3 cell lines by inhibiting the expression of TCF7L2. However, CCAT2‑knockdown‑mediated effects were reversed by the Wnt/β‑catenin signaling pathway activator lithium chloride (LiCl). Further cell experiments suggested that LiCl treatment reversed CCAT2‑knockdown‑mediated inhibition of PCa cell proliferation, cell cycle, epithelial‑mesenchymal transition, migration and invasion. Overall, the results indicated that CCAT2 regulated PCa via the Wnt/β‑catenin signaling pathway; therefore, CCAT2 may exhibit key role during the progression of PCa and may serve as a therapeutic target for the disease.
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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癌症遗传学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-26
·
IF 12.6
Zhao Feng,Gong Liming,Wang Ping,Chen Dong,Cao Shijie,Yang Feifei,Tang Manqing,Meng Yuanyuan,Wang Yuming,Miao Lin,Li Yunfei,Huang Wei
In the absence of tumor antigen specificity, direct chemokine administration carries the risk of significant “on-target, off-tumor” toxicities, highlighting the need for small-molecule approaches with reduced immunogenicity. This study investigates the synergistic potential of norcantharidin (NCTD) and lomitapide (lomi) in selectively restoring CCL4 expression by deactivating the tumor intrinsic β-catenin pathway. Due to its similar lipophilicity to lomi and potential to suppress β-catenin, NCTD prodrug (C12) was selected to be co-encapsulated with lomi in a nanoparticle-mediated co-delivery system (NP“C12 + lomi”). The NP“C12 + lomi” formulation exhibited a high encapsulation rate, uniform particle size, and suitability for therapeutic use. It effectively inhibited the proliferation of 4T1 cells and restored CCL4 expression. In both primary breast tumor and surgically resected tumor mouse models, NP“C12 + lomi” significantly increased the proportion of CD8 + cells in primary tumors, blood, and lung metastases, approximately doubling their presence. This led to a prolongation of median survival in mice to 59 days. Furthermore, when combined with an immune checkpoint inhibitor, NP“C12 + lomi” substantially inhibited tumor growth and lung metastasis without affecting body weight or causing major tissue or organ damage. This was attributed to the controlled dissociation of the nanoparticle and the subsequent modulation of C12 and lomi, which mitigated CCL4-related toxicity. This study provides valuable insights into the safe production of chemokines using a small-molecule pair through a nanosystem and presents a robust chemo-immunological cascade therapy strategy, demonstrating significant efficacy against malignant metastatic tumors. Graphical abstract
研究领域:
肿瘤学
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免疫学
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药剂学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2020
·
IF 1.863
Yuanguo Xiong,Hao Lu,Hanlin Xu
Hepatic fibrosis (HF) is a common disease, with currently no available treatment. Galangin, a natural flavonoid extracted from Alpinia officinaruim Hance, has multiple effects demonstrated in previous studies. The aim of the present study was to explore the anti-fibrogenic effect of galangin in vitro, and research its potential molecular mechanisms. LX-2 cells were chosen as an in vitro HF model, and were treated with galangin in different concentrations. Cell viability was analyzed using Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis was measured using flow cytometry, and the anti-fibrogenic effect of galangin was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunofluorescence, and western blotting. The results show that the proliferation of LX-2 cells was efficiently inhibited by galangin, and apoptosis was induced in a dose-dependent manner. Both the mRNA and protein expression of α-SMA and collagen I were markedly downregulated. Galangin also inhibited the PI3K/Akt and Wnt/β-catenin signaling pathways and increased the Bax/Bcl-2 ratio. The results of this study suggest that galangin has an anti-fibrogenic effect and may represent a promising agent in the treatment of hepatic fibrosis.
研究领域:
药理学
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细胞生物学
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分子生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 105
·期 5
·e70113
·
IF 3.3
Ming Tong,Meng Liu,Liang Chen,Yi-he Lin,Qing Zheng
Liver fibrosis is pathologically associated with ferroptosis. Osthole (OST) has good therapeutic effects on liver fibrosis. Our study sought to investigate the pharmacological effects of OST on ferroptosis in hepatic stellate cells (HSCs) during the development of liver fibrosis and define the mechanisms involved. The in vivo model of liver fibrosis was established by CCl 4 treatment. MTT and EDU assays were used to assess cell viability and proliferation, respectively. The interaction between myocyte enhancer factor 2A (MEF2A) and Y-box binding protein 1 (YBX1) was analyzed by dual luciferase reporter and chromatin immunoprecipitation (ChIP) assays. OST treatment alleviated CCl 4 -induced liver fibrosis in mice by activating ferroptosis. OST induced ferroptosis in HSCs and inhibited the activation of HSCs in vitro, while these effects of OST were reversed by MEF2A overexpression or YBX1 overexpression. Mechanistically, MEF2A activated the Wnt/β-catenin signaling by transcriptionally facilitating YBX1 expression. As expected, the inactivation of Wnt/β-catenin signaling or YBX1 knockdown could reverse the regulatory effect of MEF2A upregulation on the activation of HSCs and ferroptosis in OST-treated HSCs. OST mitigated liver fibrosis by inducing ferroptosis in HSCs and repressing the activation of HSCs through inhibiting the MEF2A/YBX1/Wnt/β-catenin axis.
研究领域:
药理学
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分子生物学
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肝脏病学
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产品关联
DOI
PubMed
高影响因子
Cancer Communications
·
2023
·
IF 16.2
Shujie Chen,Lina Fan,Yifeng Lin,Yadong Qi,Chaochao Xu,Qiwei Ge,Ying Zhang,Qiwen Wang,Dingjiacheng Jia,Lan Wang,Jianmin Si,Liangjing Wang
Background The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is not well explored. Here, we elucidated the functional role of Bifidobacterium adolescentis ( B.a ) on CRC and investigated its possible mechanism on the manipulation of cancer-associated fibroblasts (CAFs) in CRC. Methods Different CRC animal models and various cell line models were established to explore the function of B.a on CRC. The single-cell RNA sequencing (scRNA-seq) or flow cytometry was used to detect the cell subsets in the TME of CRC. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), or immunofluorescence staining were performed to examine the activation of Wnt signaling and growth arrest specific 1 (GAS1) on CD143 + CAFs. Chromatin immunoprecipitation quantitative real-time PCR (CHIP-qPCR) was performed to investigate the regulation of transcription factor 4 (TCF4) on GAS1. Multi-immunofluorescence assay examined the expression level of CD143 and GAS1 on tissue microarray. Results We found that B.a abundance was significantly reduced in CRC patients from two independent cohorts and the bacteria database of GMrepo. Supplementation with B.a suppressed Apc Min/+ spontaneous or AOM/DSS-induced tumorigenesis in mice. scRNA-seq revealed that B.a facilitated a subset of CD143 + CAFs by inhibiting the infiltration of Th2 cells, while promoting the TNF-alpha + B cells in TME. CD143 + CAFs highly expressed GAS1 and exhibited tumor suppressive effect. Mechanistically, GAS1 was activated by the Wnt/β-catenin signaling in CD143 + CAFs. B.a abundance was correlated with the expression level of CD143 and GAS1. The level of CD143 + CAFs predicted the better survival outcome in CRC patients. Conclusions These results highlighted that B.a induced a new subset of CD143 + CAFs by Wnt signaling-regulated GAS1 to suppress tumorigenesis and provided a novel therapeutic target for probiotic-based modulation of TME in CRC.
研究领域:
癌症生物学
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微生物学
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分子生物学
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细胞生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Animal Nutrition
·
2025
·
IF 7.5
Li Dong,Yangshu Zhou,Mengxuan Wang,Qingqing Yuan,Guangzhi Qiu,Jun Liu,Hongrong Wang,Aimin Wu,Lihuai Yu,Daiwen Chen
This study aims to elucidate intestinal injury from the perspective of intestinal epithelial cell homeostasis and to explore the modulatory roles of terpine-4-ol (a major bioactive component of tea tree oil). Forty 28-day-old piglets (7.82 ± 0.43 kg) were randomly divided into 5 groups with 8 pigs per group. Piglets in the control (CON) and lipopolysaccharide (LPS) groups were fed a basal diet, while those in the remaining 3 groups were fed the basal diet supplemented with 30 (LTP), 60 (MTP), or 90 mg/kg terpine-4-ol (HTP), respectively. Piglets in the LPS and terpine-4-ol supplementation groups were intraperitoneally injected with 100 μg/kg BW of LPS at the end of the 21-day growth period. Six hours after injection, 6 piglets from each group were randomly selected and slaughtered to detect intestinal cell homeostasis. The results showed that the average daily weight gain (ADG) and average daily feed intake (ADFI) of piglets in MTP and HTP groups were higher than those in the CON group ( P < 0.05), whereas the feed conversion ratio (FCR) of piglets in LTP group were lower as compared to the CON group ( P < 0.05). Terpine-4-ol supplementation also decreased the diarrhea rate of piglets. Lipopolysaccharide challenge decreased the villus length and the ratio of villus length to crypt depth (V/C) in the jejunum ( P < 0.05), decreased the V/C ratio and increased the crypt depth in the ileum ( P < 0.05). In contrast, terpine-4-ol supplementation led to increased villus length and V/C ratio in the jejunum, raised the V/C ratio in the HTP group, and decreased crypt depth in the LTP and MTP groups in the ileum ( P < 0.05). Lipopolysaccharide reduced the number of Ki67 + cells and increased the number of caspase 3 + cells ( P < 0.05) in both the jejunum and ileum, whereas terpine-4-ol increased the number of Ki67 + cells in the crypts of the jejunum and ileum, while decreasing the number of caspase 3 + cells of the the ileum and in the jejunum of MTP and HTP groups ( P < 0.05). Lipopolysaccharide down-regulated the expression of the intestinal stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) ( P < 0.05, execpt for Lgr5 gene in the jejunum), while terpine-4-ol supplementation alleviated the effect. Lipopolysaccharide decreased the number of goblet cells and mucin 2 (Muc2) secretion ( P < 0.05), whereas the number of goblet cells and Muc2 secretion in the small intestine of MTP group was increased ( P < 0.05). In addition, LPS injection led to a reduction in the expression of endocrine cell marker chromogranin A and absorption cell marker villin ( P < 0.05). Conversely, terpine-4-ol increased the abundance of endocrine cells and absorption cells in the small intestine ( P <0.05). Moreover, LPS inhibited the expression of genes and proteins of wingless-type MMTV integration site family (Wnt)/β-catenin signaling pathway ( P < 0.05), whereas terpine-4-ol reversed this effect. In conclusion, terpine-4-ol supplementation improved growth performance, decreased diarrhea in piglets and alleviated the damage to the intestinal epithelial cell homeostasis under LPS challenge, probably via Wnt/β-catenin signaling activation. A dose of 60 mg terpine-4-ol per kilogram diet was recommended based on the present study.
研究领域:
畜牧学
·
兽医学
·
分子生物学
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药理学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2024
·
IF 3.3
Zhen Xu,Yilin Guo,Lu Wang,Jinquan Cui
HECW1 belongs to ubiquitin ligase (E3) HECT family, and is found to be involved in tumorigenesis and tumor progression. However, the function of HECW1 in cervical cancer (CC) remains unknown. Clinical analysis showed that HECW1 is significantly decreased in CC tumor tissues. Ectopic expression of HECW1 suppressed cell growth, promoting cell cycle arrest and apoptosis in CC cells, while downregulation of HECW1 reversed these trends, impeded proliferation and accelerated cell cycle progression of CC cells. Overexpressing of HECW1 reduced mitochondrial membrane potential and the protein expression of voltage-dependent anion channel 1 (VDAC1). In addition, upregulation of HECW1 inhibited nuclear β-catenin accumulation, downregulated β-catenin/TCF/LEF-mediated transcriptional activity and the expression of downstream gene c-Myc, whereas inhibition of HECW1 received opposite results. Further results confirmed HECW1 affects the protein expression of dishevelled-1 (DVL1), a potent activator of Wnt/β‐catenin, and inhibition of HECW1 inhibited the ubiquitination of DVL1, upregulating its expression. Inhibition of DVL1 restrained the promotion effect of HECW1 suppression on cell proliferation. In vivo experiments also verified that HECW1 suppression promoted the tumor formation of CC cells. Summary, we demonstrated that HECW1 inhibits CC cell proliferation and tumor formation by downregulating DVL1 induced Wnt/β‐catenin signaling pathway activation.
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
✓ 已验证
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）