JOURNAL OF PHARMACY AND PHARMACOLOGY
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2022
·Vol. 75
·期 1
·129-138
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IF 4.81
Li Shi-ying,Shi Chuan-jian,Fu Wei-ming,Zhang Jin-fang
BackgroundBerberine, a non-prescription medicine clinically applied for diarrhoea and gastroenteritis. Recent studies have demonstrated that it possesses anti-tumour properties in colorectal cancer, but the exact molecular mechanism remains obscure.ObjectivesTo elucidate the underly molecular mechanisms of berberine in colorectal cancer from a perspective of epigenetics, and tried to explore the role of lincROR-Wnt/β-catenin molecular axis in the berberine induced the anti-tumour activity in colorectal cancer.MethodsThe effects of berberine on cell growth, cell cycle and apoptosis were examined in CRC cells. The in vivo effect of berberine on tumour growth was investigated using a xenograft mice model. Moreover, lincROR and Wnt/β-catenin signalling were detected by luciferase activity, qRT-PCR and western blotting assays.Key findingsBerberine suppressed cell growth in vitro via inducing cell cycle arrest and apoptosis in CRC cell, and inhibited tumourigenesis in vivo. LincROR was significantly down-regulated by berberine, inducing the inactivation of the canonical Wnt/β-catenin signalling, meanwhile, the overexpression of lincROR partially reversed the suppressive effects on tumour growth and Wnt/β-catenin signalling induced by berberine.ConclusionsBerberine inhibits tumour growth partially via regulating the lincROR-Wnt/β-catenin regulatory axis, which provides a strategy for the design of anti-tumour drugs for CRC patients after our advanced validation.
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高影响因子
Human Cell
·
2022
·Vol. 36
·期 1
·312-328
·
IF 4.374
Long Jianwu,Liu Longfei,Yang Xuefeng,Zhou Xiaojun,Lu Xianzhou,Qin Lei
Emerging evidence has uncovered that noncoding RNAs (ncRNAs) contribute to the development of hepatocellular carcinoma (HCC). Nevertheless, the functions of the majority of long ncRNAs (lncRNAs) in HCC are unknown. Here, we intend to probe the function of lncRNA NUTM2A-AS1 in the evolvement of HCC and the related mechanism. Expression levels of lncRNA NUTM2A-AS1, miR-186-5p and KLF7 mRNA in HCC tissues and adjacent non-tumor tissues were monitored. Gain- or loss-of-function assays were utilized to investigate the biological functions of lncRNA NUTM2A-AS1, miR-186-5p and KLF7 in HCC cell lines (including HCCLM3 and Huh7). Western blot was implemented for the detection of the epithelial–mesenchymal transition (EMT)-related proteins (including E-cadherin, Vimentin and Snail), KLF7, Wnt, β-catenin, and stemness-related proteins (Nanog, OCT4, YKL40, and CD133). Furthermore, the targeted associations between lncRNA NUTM2A-AS1, miR-186-5p, and KLF7 were verified by bioinformatics analysis, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. As a result, lncRNA NUTM2A-AS1 and KLF7 profiles were heightened in the HCC tissues versus adjacent normal tissues, while miR-186-5p had the opposite expression tendency. Up-regulation of lncRNA NUTM2A-AS1 was related to tumor size, advanced tumor stage, and lymph node metastasis of HCC patients. Functionally, overexpression of lncRNA NUTM2A-AS1 heightened HCC cells’ growth, invasion, EMT, and stemness and repressed their apoptosis by activating the Wnt/β-catenin pathway. In contrast, up-regulation of miR-186-5p or inhibition of KLF7 had reverse effects. In vivo, lncRNA NUTM2A-AS1 overexpression facilitated tumor growth and EMT, accompanied by declined miR-186-5p levels and enhanced KLF7 expression. The mechanistic studies revealed that miR-186-5p served as a common target of lncRNA NUTM2A-AS1 and KLF7. As hinted by the rescue experiments, NUTM2A-AS1 partly abated miR-186-5p-mediated anti-tumor effects in HCC cells, whereas KLF7 knockdown reversed the promotive effects of NUTM2A-AS1. LncRNA NUTM2A-AS1 accelerated the evolution of HCC by up-regulating the KLF7/Wnt/beta-catenin pathway through sponging miR-186-5p.
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高影响因子
PHYTOTHERAPY RESEARCH
·
2022
·Vol. 36
·期 10
·3969-3987
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IF 6.388
Yi Chen,Shasha Song,Yongfang Wang,Jia Zhu,Xinyu Li
Psoriasis (PSO), an immune-mediated chronic inflammatory skin disease, has seriously affected the quality of patients' life. It is urgent to find effective medicines with lower costs and less side effects. Baicalin (HQG) is the main bioactive substance from Scutellaria baicalensis with effects of anti-inflammation and immunoregulation. Herein, we explored the effect of oral HQG treating PSO and its potential mechanism. Firstly, network pharmacology was used to predict that HQG may act on Estrogen, TNF-alpha (tumor necrosis factor, TNF), interleukin-17 (IL-17) signaling pathways and Th17 cell differentiation, especially the key targets including TNF, Proto-oncogene tyrosine-protein kinase Src, Peroxisome proliferator-activated receptor gamma and Matrix metalloproteinase-9. Imiquimod (IMQ)-induced mice were then used to study the effects of HQG treating PSO. HQG could significantly ameliorate the skin lesions, decrease the level of inflammatory factors and inhibit Th1/Th17 cell differentiation in IMQ-induced mice. Finally, transcriptome analysis of skin lesions integrated with the prediction of network pharmacology further demonstrated that the potential mechanism may be associated with suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ. In conclusion, this study suggested that HQG may be a promising agent for further studies in the search for therapeutic strategies to treat PSO in the future.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yiyang Du,Tingxu Yan,Bo Wu,Bosai He,Ying Jia
Ethnopharmacological relevance Increased inflammatory response and disruption of neuroplasticity are important mechanisms in the hypothesis of the pathogenesis of depression. Thus, these two aspects are conducive to the development of treatments for depression. Suanzaoren Decoction (SZRD) is a classic traditional Chinese medicine compound for the treatment of insomnia, which can clinically relieve depression symptoms, but its antidepressant pharmacological mechanism remains to be elucidated. Aim of this study Based on the hypothesis of inflammation and neuroplasticity in depression, this study aimed to investigate the antidepressant effect of SZRD and its specific molecular mechanism through chronic unpredictable mild stress (CUMS) induced SD rat model and lipopolysaccharide (LPS) induced BV2 cell neuroinflammation model. Materials and methods The body weight and behavioral indexes of CUMS model rats treated with orally or without oral SZRD for 4 weeks were detected. Hematoxylin and eosin staining was used to observe brain pathological damage. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining was used to observe neuronal apoptosis. Immunofluorescence, ELISA kit and Western blotting were used to detect the inflammatory index Iba-1 and inflammatory factors, as well as the important inflammatory pathway TLR4/MyD88/NF-κB. Enzyme linked immunosorbent assay (ELISA) and western blotting were used to detect neuroplasticity indexes proteins-brain-derived neurotrophic factor (BDNF), presynaptic membrane protein-synaptophysin (SYP), and postsynaptic protein- 95(PSD95), and the key pathway Wnt/β-catenin. The possible mechanism of SZRD antidepressant was further explored in LPS-induced BV2 cells. Results In vivo and in vitro experiments showed that SZRD treatment significantly reversed the depression-like behaviors in rats, decreased the levels of inflammatory factors and increased the expression levels of BDNF, SYP, PSD95 in depression model rats. Furthermore, SZRD treatment inhibited the activation of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways and reduced the massive nuclear translocation of NF-κB and β-catenin. The addition of NF-κB pathway agonists could partially offset the inhibitory effect of SZRD on the Wnt pathway, and the addition of Wnt pathway agonists could also partially offset the inhibitory effect of SZRD on the TLR4 pathway. Conclusion This study suggestted that SZRD may exert its antidepressant effect by regulating TLR4/MyD88/NF-κB pathway and Wnt/β-catenin pathway in combination.
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Frontiers in Physiology
·
2021
·
IF 4.566
Wangzhou Kaixin,Lai Zhiying,Lu Zishao,Fu Wanren,Liu Cheng,Liang Zhengeng,Tan Yi,Li Conghui,Hao Chunbo
Human periodontal ligament cells (hPDLCs) play a vital role in cell regeneration and tissue repair with multi-directional differentiation potential. microRNAs (miRs) are implicated in the osteogenesis of hPDLCs. This study explored the mechanism of miR-143-3p in osteogenesis of hPDLCs. Osteogenic differentiation of isolated hPDLCs was induced. KLF5 expression during osteogenic differentiation of hPDLCs was detected and then silenced in hPDLCs. Binding relationship between KLF5 and miR-143-3p was predicted and verified. hPDLCs were treated with miR-143-3p mimic or overexpressing KLF5, and then osteogenic specific markers and mineralized nodules were measured. The key factors of the Wnt/β-catenin pathway during osteogenesis of hPDLCs were measured. KLF5 expression was upregulated during osteogenesis of hPDLCs. KLF5 silencing or miR-143-3p mimic reduced osteogenic specific markers and mineralized nodules. Overexpression of KLF5 could reverse the inhibitory effect of miR-143-3p on osteogenic differentiation. miR-143-3p mimic and KLF5 silencing inactivated the Wnt/β-catenin pathway. Activation of the Wnt/β-catenin pathway reversed the repression effect of miR-143-3p mimic on osteogenesis of hPDLCs. In conclusion, miR-143-3p inhibited osteogenic differentiation of hPDLCs by targeting KLF5 and inactivating the Wnt/β-catenin pathway.
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PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
·
2016
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IF 3.155
Jihui Wang,Yuan Liang,Luyang Jian,Jingwei Zhang,Shuai Liang,Shan Xiao,Bingnan Liu,Han Wang
Obesity has become a major health problem which is related with high-trans fatty acids diet. Adipogenic differentiation of adipose tissue-derived stromal cells (ADSCs) plays an important role in the development of adipose tissue . In order to determine the effect of trans fatty acids on adipogenic differentiation in ADSCs, cells were treated with linoelaidic acid, as well as linoleic acid and linolenic acid . We found that linoelaidic acid significantly increased the lipid droplet formation and triglyceride content compared with linoleic acid and linolenic acid. Linoelaidic acid also down-regulated the levels of β-catenin in cells and inhibited the accumulation of β-catenin in cell nuclei . Lithium chloride , an activator of Wnt/β-catenin pathway, antagonized the enhancement of linoelaidic acid on adipogenesis and up-regulated the levels of β-catenin in ADSCs. These results indicated that linoelaidic acid could enhance the adipogenic differentiation in ADSCs in vitro , which is partly due to the suppression of Wnt/β-catenin pathway.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Xianhua Zhang,Runfa Wu,Fasheng Liu,Min Huang,Xiaoyan Huang,Nannan Wang,Qianqian Huang,Minhong Zhang,Xinjun Liao,Huiqiang Lu,Lan Liao
The combustion of biomass (e.g., wood, agricultural residues) and coal releases significant amounts of guaiacol (GUA) and its derivatives, major constituents of PM2.5 that threaten human health and ecosystems. GUA can rapidly enter the Earth's water circulation system through atmospheric deposition. However, its potential threat to aquatic organism and humans remains poorly understood. Using zebrafish—a model organism with high genetic homology to humans, transparent embryos, and rapid development—we investigated GUA’s ecological effects. Zebrafish embryos were exposed to 0.08–0.24 mM GUA from 12 to 120 h post-fertilization (hpf). GUA induced craniofacial malformations, behavioral abnormalities (reduced locomotion, impaired stimuli response), and oxidative stress via reactive oxygen species (ROS) accumulation. Disrupted migration, proliferation, and differentiation of cranial neural crest cells (NCCs) were observed, alongside altered Wnt signaling pathway gene expression. Both astaxanthin (AST, an ROS scavenger) and C59 (a Wnt inhibitor) could mitigate craniofacial defects. These findings demonstrate that GUA reduces antioxidant capacity, impairs NCCs function, and disrupts Wnt signaling, leading to craniofacial deformities. This study highlights GUA’s ecological and health risks, providing insights into its toxic mechanisms.
研究领域:
毒理学
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发育生物学
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环境科学
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分子生物学
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水生毒理学
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高影响因子
ARCHIV DER PHARMAZIE
·
2025
·Vol. 358
·期 3
·e2400796
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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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高影响因子
Advanced Science
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2025
·
IF 14.1
Yuchien Hsu,Yunjiao He,Xiao Zhao,Feilong Wang,Fan Yang,Yufeng Zheng,Yongsheng Zhou,Dandan Xia,Yunsong Liu
Zinc (Zn) and its alloys are promising biomaterials for orthopedic applications due to their degradability and mechanical properties. Zn 2+ plays a crucial role in bone formation, but excessive early release may cause cytotoxicity and inhibit osseointegration. To solve this, we developed a near-infrared (NIR) light-controlled polycaprolactone/copper-sulfur (PCL/CuS) coating that slows degradation and enhances osseointegration of Zn alloys. The zinc–lithium (Zn–Li) substrate is encapsulated with PCL, reducing Zn 2+ release and maintaing biocompatibility. Controlled Zn 2+ release and mild photothermal therapy via CuS nanoparticles promoted osteogenesis. In vitro studies demonstrated enhanced cell proliferation and osteogenic differentiation. In vivo Micro-Computed Tomography (Micro-CT), Scanning Electron Microscopy-Energy Dispersive Spectroscopy (SEM-EDS), and immunohistochemical analyses confirmed improved osseointegration. Mechanistic studies using RNA sequencing and Western blotting revealed that the coating promotes osteogenesis by activating the Wnt/β-catenin and inhibiting NF-κB pathways. This NIR light-controlled PCL/CuS coating successfully regulates Zn alloy degradation, enhances osseointegration via controlled Zn 2+ release and mild photothermal therapy effct, presenting a promising avenue for orthopedic biomaterials.
研究领域:
生物材料
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骨科
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组织工程
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生物医学工程
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Small
·
2025
·
IF 12.1
Hao Tang,Yameng Yu,Xinxin Zhan,Feilong Wang,Dong Xiang,Yufeng Zheng,Hong Lin,Dandan Xia
Periodontitis is a prolonged inflammatory disease caused by bacterial infection. Oxidative stress induced by inflammation leads to excessive production of reactive oxygen species (ROS) and difficulties in bone tissue regeneration. ROS-scavenging agents regulate the periodontal tissue microenvironment, which is of great significance in the treatment of periodontitis. In this study, a zinc-cobalt bimetallic organic framework (Zn/Co-MOF) is constructed to alleviate local tissue inflammation and bone resorption in periodontitis by cascading antioxidant activity. In vitro experimental results show that the Zn/Co-MOF not only provides effective cellular protection against ROS attack in human bone marrow mesenchymal stem cells and osteoblast precursor cells (MC3T3-E1), but also promotes osteogenic differentiation. In vivo experiments in rat periodontitis models confirm that Zn/Co-MOFs can reduce local periodontal tissue inflammation, reduce osteoclasts, and promote the recovery of alveolar bone height defects, which is beneficial for the treatment of periodontitis. RNA sequencing results show that the Zn/Co-MOF promotes bone tissue regeneration mainly through activated Wnt pathways, which accelerate osteogenic differentiation. Overall, the Zn/Co-MOF exhibits antioxidant capacity and promotes bone regeneration, making it a promising strategy for the treatment of periodontitis.
研究领域:
牙科学
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材料科学
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再生医学
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生物化学
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高影响因子
LABORATORY INVESTIGATION
·
2023
·
IF 5
Ying Li,Yu Wang,Qinguang Zou,Shouqing Li,Fan Zhang
The transcription factor Krüppel-like factor (KLF) 3 is one of the members of the KLF family, which plays an important role in tumor progression. Nevertheless, the role of KLF3 in the growth and metastasis of gastric cancer (GC) still needs to be elucidated. Bioinformatics analysis showed that KLF3 was overexpressed in patients with GC, and the high expression of KLF3 was correlated with poor survival. KLF3 was also overexpressed in GC clinical samples and cell lines. In vitro functional role of KLF3 in GC cells was explored by a gain-of-function and loss-of-function assay. Overexpressed KLF3 promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition of GC cells, whereas suppressed KLF3 inhibited these biological behaviors. The clinical samples and bioinformatics analysis showed that WNT1 was also highly expressed in GC tumor tissues and positively correlated with KLF3 expression. The luciferase reporter assay and chromatin immunoprecipitation result confirmed that KLF3 could directly bind to the WNT1 promoter to increase the transcriptional activity of WNT1, thus regulating its expression. Overexpressed KLF3 enhanced the protein expression level of p-GSK3β(Ser9) and β-catenin, the key elements in the WNT/β-catenin signaling pathway. Repression of KLF3 decreased the level of p-GSK3β(Ser9) and β-catenin. Immunofluorescence images showed that KLF3 promoted nuclear β-catenin accumulation. Inhibition of WNT1 attenuated the proliferation, migration, and invasiveness of KLF3-overexpressing GC cells. Moreover, the xenograft mouse model confirmed that KLF3 promotes GC tumor growth and metastasis in vivo. Our results demonstrated that KLF3 activates the WNT/β-catenin signaling pathway via WNT1 to promote GC tumor growth and metastasis, indicating that repression of KLF3 may act as a potential therapeutic target for patients with GC.
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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生物信息学
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高影响因子
Bioengineering & Translational Medicine
·
2026
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IF 6.2
Lingyun Zhao,Anqi Li,Shijing Chen,Wei Hua,Ru Dai,Lingyu Pan,Meng Hu,Nan Huang,Runke Zhou,Yuanyuan Han,Lidan Xiong,Li Li
Stem cells and their paracrine factors hold promise for alopecia treatment, yet research on human skin-derived precursors (hSKPs), which are closely related to hair follicles in biological positioning and function, remains limited. We demonstrated that extracellular vesicles of human transformed skin-derived precursors (htSKP-EVs), harvested utilizing our directed induction, culture transition and gradient ultracentrifugation technology, exhibited superior efficiency and quality determined by transmission electron microscopy, nanoparticle tracking analysis, and detection of specific markers. Using CCK8, scratch assay, immunofluorescence, H&E staining, immunohistochemistry staining, dermoscope, qRT-PCR and Western blotting, it was found that htSKP-EVs significantly promoted the proliferation of hair follicle stem cells (hHFSCs) by effectively modulating the Wnt signaling pathway, thereby enhancing overall hair follicle growth. Notably, miR-221-3p, highly expressed in htSKP-EVs, suppressed DKK2 expression, activated the Wnt pathway in human dermal papilla cells (hDPCs), and induced hair follicles to enter and sustain the anagen phase, based on the aforementioned similar in vivo and in vitro experiments. These findings, validated in hHFSCs, hDPCs and human hair follicles in vitro and in a murine alopecia model in vivo, revealed the potential mechanism of htSKP-EVs in hair growth and identified a new therapeutic target for alopecia in regenerative medicine.
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