Frontiers in Oncology
·
2020
·
IF 4.848
Jiang Tao,Gao Wenyu,Lin Shengjie,Chen Hao,Du Bin,Liu Qing,Lin Xiaoyan,Chen Qiang
Background: Gastric cancer (GC) has a high morbidity and mortality rate, with peritoneal metastasis (PM) identified as the main site of metastasis. Our previous study found that FNDC1 has a higher frequency of mutations in patients with PM by high-throughput sequencing assay, suggesting that it may be associated with GC invasion and PM, however the specific mechanism remains unclear.Methods: First, the correlation between FNDC1 and PM and prognosis of GC was clarified by bioinformatics and clinicopathological analysis. Next, the effect of FNDC1 expression on the invasion and metastasis ability of GC was investigated in vivo and in vitro. Finally, the signaling pathways involved in the regulation of FNDC1 were explored.Results: FNDC1 was highly expressed in GC and was associated with PM and poor prognosis. FNDC1 was also associated with epithelial-mesenchymal transition (EMT) in GC cells. Through in vivo and in vitro experiments, it was clarified that knockdown of FNDC1 could inhibit the proliferation, invasion, and migration of GC cells. In addition, it was elucidated that FNDC1 promotes EMT through the Wnt/β-catenin signaling pathway.Conclusion: FNDC1 may be associated with the invasion of GC and PM after surgery. FNDC1 was highly expressed in GC tissues and cell lines, while significantly associated with poor DFS and OS in GC patients. Both univariate and multivariate analyses suggested that the expression of FNDC1 was an independent factor for GC. Knockdown of FNDC1 also significantly inhibited the proliferation, migration, and activity of GC cells. FNDC1 may promote EMT in GC cells through the regulation of Wnt/β-catenin signaling pathway. FNDC1 has the potential to be used as a predictor of PM and may also be studied in depth as a therapeutic target for GC, which has potential clinical utility and is worthy of further validation.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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高影响因子
NEUROSCIENCE
·
2026
·
IF 3.3
Xiaoyu Lin,Wanliang Du,Ruile Fang,Ying Ma,Yongjun Wang,Jialei Yang
Systemic inflammation worsens ischemic stroke by increasing brain injury, neurological deficits, and neuroinflammation. • Systemic inflammation enhances microglial NF-κB activity and promotes p65/β-catenin interaction. • Systemic inflammation downregulates microglial Wnt/β-catenin/CD36 axis and impairs microglial efferocytosis. • Lithium chloride restores Wnt/β-catenin signaling and microglial efferocytosis, improving stroke outcome under systemic inflammation. Systemic inflammation is associated with worse outcomes after ischemic stroke, but the underlying mechanisms remain poorly understood. Microglial efferocytosis limits post-stroke inflammation and promotes recovery, whereas Wnt/β-catenin signaling has been implicated in neuroprotection and in regulation of CD36, a key efferocytotic receptor. Here, we investigated whether systemic inflammation is associated with alterations in microglial Wnt/β-catenin/CD36 axis and efferocytosis during ischemic injury. Mice were pretreated with lipopolysaccharide (LPS) before transient middle cerebral artery occlusion/reperfusion (tMCAO/R), and BV2 microglia were exposed to LPS before oxygen-glucose deprivation/reoxygenation (OGD/R). LPS pretreatment markedly increased infarct volume, worsened neurological deficits, and amplified post-ischemic neuroinflammatory responses. These effects were accompanied by enhanced microglial NF-κB signaling, increased p65/β-catenin interaction, and reduced nuclear β-catenin, consistent with suppression of Wnt/β-catenin signaling. Reduced CD36 expression and impaired microglial efferocytosis were observed in parallel. Notably, pharmacological activation of Wnt/β-catenin signaling with lithium chloride (LiCl) restored CD36 expression and microglial efferocytosis under LPS-pretreated conditions, and was accompanied by smaller infarcts, improved neurological function, and attenuated neuroinflammation. Collectively, these findings show that LPS pretreatment exacerbates ischemic stroke and is associated with enhanced microglial NF-κB signaling, dysregulation of the Wnt/β-catenin/CD36 axis, and impaired microglial efferocytosis. These results support defective microglial efferocytosis as a potential biological link between systemic inflammation and aggravated ischemic injury and identify Wnt/β-catenin signaling as a candidate pathway for further therapeutic investigation Download: Download high-res image (128KB) Download: Download full-size image
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2023
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IF 5.3
Xiaojing Xing,Meichen Liu,Xuguang Wang,Qianxue Guo,Hongyue Wang,Wenxue Wang
Diffuse large B-cell lymphoma (DLBCL) is difficult to treat due to the high recurrence rate and therapy intolerance, so finding potential therapeutic targets for DLBCL is critical. FK506-binding protein 3 (FKBP3) contributes to the progression of various cancers and is highly expressed in DLBCL, but the role of FKBP3 in DLBCL and its mechanism are not clear. Our study demonstrated that FKBP3 aggravated the proliferation and stemness of DLBCL cells, and tumour growth in a xenograft mouse model. The interaction between FKBP3 and parkinsonism associated deglycase (PARK7) in DB cells was found using co-immunoprecipitation assay. Knockdown of FKBP3 enhanced the degradation of PARK7 through increasing its ubiquitination modification. Forkhead Box O3 (FOXO3) belongs to the forkhead family of transcription factors and inhibits DLBCL, but the underlying mechanism has not been reported. We found that FOXO3 bound the promoter of FKBP3 and then suppressed its transcription, eventually weakening DLBCL. Mechanically, FKBP3 activated Wnt/β-catenin signalling pathway mediated by PARK7. Together, FKBP3 increased PARK7 and then facilitated the malignant phenotype of DLBCL through activating Wnt/β-catenin pathway. These results indicated that FKBP3 might be a potential therapeutic target for the treatment of DLBCL.
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Experimental and Therapeutic Medicine
·
2023
·Vol. 26
·期 1
·1-10
·
IF 2.7
Shixiong Lei,Xilin Du,Kai Tan,Xiaojun He,Yejing Zhu,Shoujie Zhao,Zhenyu Yang,Gang Dou
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that cysteine rich protein 1 (CRP‑1) is dysregulated in several types of human cancer; however, its role in HCC is poorly understood. Therefore, the current study aimed to investigate the role of CRP‑1 in HCC. Western blotting and reverse transcription‑quantitative PCR results showed that CRP‑1 was upregulated in HCC cell lines. Furthermore, for in vitro experiments, CRP‑1 was knocked down and overexpressed in the HCC cell lines Hep 3B2.1‑7 and BEL‑7405, respectively. c‑Myc and proliferating cell nuclear antigen upregulation, and cleaved caspase 3 and poly(ADP‑ribose) polymerase downregulation suggested that CRP‑1 silencing could inhibit the proliferation and colony‑forming ability of HCC cells, and induce apoptosis. In addition, CRP‑1 overexpression promoted the malignant behavior of HCC cells and induced epithelial‑mesenchymal transition (EMT), as verified by E‑cadherin downregulation, and N‑cadherin and vimentin upregulation. Additionally, CRP‑1 overexpression promoted the nuclear translocation of β‑catenin, and activated the expression of cyclin D1 and matrix metalloproteinase‑7. Furthermore, inhibition of Wnt/β‑catenin signaling, following cell treatment with XAV‑939, an inhibitor of the Wnt/β‑catenin signaling pathway, abrogated the effects of CRP‑1 on enhancing the proliferation and migration of HCC cells. These findings indicated that the regulatory effect of CRP‑1 on HCC cells could be mediated by the Wnt/β‑catenin signaling pathway. Overall, CRP‑1 could promote the proliferation and migration of HCC cell lines, partially via promoting EMT and activating the Wnt/β‑catenin signaling pathway.
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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.
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Nutrients
·
2022
·Vol. 14
·期 15
·3042
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IF 6.706
Jun Chen,Zhiguang Duan,Yannan Liu,Rongzhan Fu,Chenhui Zhu
The metastasis of esophageal squamous cell carcinoma (ESCC) is a leading cause of death worldwide, however, it has a poor prognosis. Ginsenoside Rh4 is a rare saponin that has been shown to have potential antitumor effectiveness in ESCC. However, the utility of Rh4 in ESCC metastasis and its undiscovered mode of action has not yet been explored. In this study, we found that Rh4 could inhibit ESCC metastasis by regulating the Wnt/β-catenin signaling pathway and the level of c-Myc, which is an important transcription factor in cancer. In in vitro experiments, Rh4 could inhibit the migration and invasion of ESCC cells without affecting cell viability. In in vivo experiments, Rh4 restrained ESCC metastasis to the lymph nodes and lungs via the suppression of epithelial-mesenchymal transition (EMT). The Wnt agonist HLY78 promoted EMT and migration of ESCC cells, whereas treatment of Rh4 can attenuate the promotion effect of HLY78. The siRNA knocking out c-Myc can also significantly reduce the expression of EMT-related marker proteins. This study illustrates a new concept for further research on the mechanism of Rh4 in ESCC.Keywords:metastasis;ginsenoside Rh4;ESCC;Wnt/β-catenin;c-Myc
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
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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.
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高影响因子
Oncology Letters
·
2020
·Vol. 20
·期 4
·1-1
·
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.
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BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
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.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Wenli Cai,Keneng Cai,Zeyu Li,Xiaoru Zhang,Shuqing Gong,Lingling liao,Jiaying Gao,Quangang Xu,Ergang Liu,Jianming Liang,Yongzhuo Huang
The pathogenesis of androgenetic alopecia (AGA) is driven by heightened androgen receptor signaling, alongside contributing factors of oxidative stress, follicular inflammation, and impaired perifollicular angiogenesis. Existing treatments such as minoxidil and finasteride suffer from limited efficacy, systemic side effects, and high relapse rates. In this study, we developed a rosemary oil (RO)-based microemulsion (QAR ME) for the co-delivery of quercetin (QT) and adenosine (AD) to synergistically target multiple pathological pathways of AGA. Here, RO can not only serve as a component of the oil phase but also function as a functional excipient with inherent antioxidant activity. The optimized QAR ME formulation demonstrated high stability, a small uniform particle size (24.98 ± 0.41 nm). It not only improved the solubility of QT but also enhanced the skin penetration of each active component. In vitro and in vivo evaluations revealed that QAR ME effectively attenuated oxidative stress, suppressed inflammatory responses, promoted angiogenesis, and activated the Wnt/β-catenin pathway, leading to enhanced hair follicle regeneration. It is worth noting that during the 28-day continuous treatment, QAR ME did not show any adverse reactions, which indicates that this therapy has the potential for long-term treatment of AGA. These findings indicate that QAR ME is a promising topical nanotherapy for the safe and effective treatment of AGA.
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高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Yonglin Yu,Xinkun Shen,Zhong Luo,Yan Hu,Menghuan Li,Pingping Ma,Qichun Ran,Liangliang Dai,Ye He,Kaiyong Cai
Oxidative stress is commonly existed in bone degenerative disease (osteoarthritis, osteoporosis etc .) and some antioxidants had great potential to enhance osteogenesis. In this study, we aim to investigate the anti-oxidative properties of various TiO 2 nanotubes (TNTs) so to screen the desirable size for improved osteogenesis and reveal the underlying molecular mechanism in vitro . Comparing cellular behaviors under normal and oxidative stress conditions, an interesting conclusion was obtained. In normal microenvironment , small TNTs were beneficial for adhesion and proliferation of osteoblasts, but large TNTs greatly increased osteogenic differentiation . However, after H 2 O 2 (300 μM) treatment (mimicking oxidative stress), only large TNTs samples demonstrated superior cellular behaviors of increased osteoblasts' adhesion, survival and differentiation when comparing with those of native titanium (control). Molecular results revealed that oxidative stress resistance of large nanotubes was closely related to the high expression of integrin α5β1 (ITG α5β1), which further up-regulated the production of anti-apoptotic proteins (p-FAK, p-Akt, p-FoxO3a and Bcl2) and down-regulated the expression of pro-apoptotic protein (Bax). Moreover, we found that Wnt signals (Wnt3a, Wnt5a, Lrp5, Lrp6 and β-catenin) played an important role in promoting osteogenic differentiation of osteoblasts under oxidative condition.
研究领域:
材料科学
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生物材料
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细胞生物学
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生物医学工程
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高影响因子
ARCHIV DER PHARMAZIE
·
2025
·Vol. 358
·期 3
·e2400796
·
IF 3.6
Yating Guo,Meng Cao,Zhaohui Li,Hongfei Zhou,Zhuo Chen,Qianbin Li
Hyperactivation of the Wnt/β-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Based on a previously reported lead compound, iCRT14, a series of 2,4-thiazolidinedione derivatives were designed, synthesized, and evaluated in vitro for their antiproliferative activity against colon cancer cells. Compound 15k exhibited the most potent activity against the HCT116 and SW480 cell lines. Compound 15k inhibited Wnt/β-catenin signaling by disrupting the protein–protein interactions between β-catenin and TCF4. Compound 15k simultaneously inhibited tubulin polymerization, disorganized the microtubule network, and arrested the cell cycle at the G2/M phase, offering an additional mechanism of action and 15k induced cell apoptosis by activating caspase-3 and poly(ADP-ribose) polymerase. Additionally, compound 15k inhibited cell migration without affecting the levels of β-catenin protein. These results offer guidance for developing the current series as potential new anticancer therapeutics.
研究领域:
肿瘤学
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分子生物学
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药物化学
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