NEUROPHARMACOLOGY
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2025
·
IF 4.6
Xiaofan Li,Guang Shi,Wanshu Guo,Kaishu Wen,Yifei Liu,Jiayue Cheng,Meichi Liu,Yuehui Yang,Xinyu Fan
DNA methylation plays a pivotal role in neuroprotection after ischemic stroke. Oxytocin, a neuropeptide renowned for its involvement anti-inflammatory and antioxidant activities, emerges as a promising candidate for the treatment of stroke. Here, we employed a transient middle cerebral artery occlusion (tMCAO) rat model to explore the underlying mechanisms of oxytocin's therapeutic potential. We utilized the Morris Water Maze, novel object recognition, and intruder tests to assess spatial memory, cognitive memory, and social memory abilities in rats, respectively. RNA sequencing and Western blotting were employed to detect alterations in mRNA expression and protein expression levels in the hippocampus. Daily oxytocin administration (0.1 and 1.0 mg/kg, subcutaneous) for seven days significantly reduced infarct volume, restored the expression of 1100 genes, including NQO1 and HO1, and robustly promoted hippocampal neurogenesis in tMCAO rats. These effects translated into enhanced neurological function and improved learning and memory abilities. Remarkably, our findings reveal that oxytocin-induced neurogenesis is intimately linked to the activation of the Wnt3a/β-catenin signaling pathway with Nrf2 as a key downstream target. Furthermore, it is possible that oxytocin, acting through its receptors, inhibited the tMCAO-induced binding of DNMT1 to MeCP2, thereby preventing the increase in DNA methylation at the Wnt3a gene. In summary, our study implies a possible involvement of oxytocin in the activation of the DNMT1-mediated Wnt3a/β-catenin signaling pathway. It may contribute to enhancing hippocampal neurogenesis and ameliorating memory impairments in rats with ischemic stroke. This hints that oxytocin holds great promise as a potential therapeutic agent for promoting post-stroke neurogenesis.
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Molecular Medicine Reports
·
2025
·Vol. 33
·期 1
·1-10
·
IF 3.5
Hongwei Xiao,Jianfeng Li,Wei Huang,Yi Qin
Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.
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CELLULAR SIGNALLING
·
2026
·
IF 4.7
Yunhe Xu,Yao Wang,Miao Yu,Yang Li,Fuxin Wan,Xiaoning Wang
Periodontitis (PD), a common inflammatory disorder causing irreversible periodontal degradation, is linked to systemic issues. Orthodontic tooth movement (OTM) in the context of PD worsens bone loss, which severely compromises orthodontic treatment stability and increases the risk of treatment failure. This study aims to thoroughly investigate the protective effects of Columbianadin (CBN) against PD/OTM-induced alveolar bone injury and dissect its underlying molecular mechanisms. To induce osteogenic differentiation, MC3T3-E1 cells were maintained in a specialized osteogenic induction medium supplemented with ascorbic acid and β-glycerophosphate. In vitro experiments using MC3T3-E1 cells revealed that CBN treatment substantially fostered osteoblastic differentiation, as reflected by elevated alkaline phosphatase (ALP) activity and robust matrix mineralization. Mechanistically, CBN enhanced SIRT1-mediated β-catenin deacetylation, whereas EX527-driven SIRT1 inhibition reduced β-catenin activity in differentiated cells. A rat OTM model within the framework of PD was established to document alveolar bone loss. We found that CBN exerted a protective effect on alveolar bone mass in PD/OTM rats, as it not only promoted alveolar bone formation but also inhibited bone resorption. CBN treatment also suppressed pro-inflammatory cytokine secretion in the alveolar bone of PD/OTM rats. Network pharmacology analysis identified potential target genes involved in CBN-mediated osteogenic differentiation. In summary, CBN protects against PD/OTM-induced alveolar bone damage in a SIRT1/β-catenin-dependent manner, suggesting CBN as a promising candidate for treating periodontal and OTM-related bone disorders.
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Frontiers in Pharmacology
·
2020
·
IF 4.225
Xie Jing,Luo Feng-xian,Shi Chong-ying,Jiang Wei-wei,Qian Ying-yan,Yang Ming-rong,Song Shuang,Dai Tian-yi,Peng Lei,Gao Xiao-yu,Tao Liang,Tian Yang,Sheng Jun
Moringa oleifera Lam. (M. oleifera) is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. M. oleifera has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of M. oleifera alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), β-catenin, phosphorylated glycogen synthase 3β, and vascular endothelial growth factor, and suppressed production of prostaglandin E2 (PGE2). Furthermore, FH535 (β-catenin inhibitor) and MOA reversed PGE2-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. In vivo experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and β-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/β-catenin signaling pathway.
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BIOORGANIC CHEMISTRY
·
2022
·
IF 5.307
Yongxi Dong,Mingji Liu,Yongqing Mao,Shuxia Wu,Jinlan Wen,Jun Lu,Yaxin Yang,Shiyang Ruan,Lei Li,Xinyun Liu,Jiquan Zhang,Shanggao Liao,Li Dong
Carnosic acid could disrupt the β-catenin/BCL9 protein-protein interaction and inhibit β-catenin dependent transcription, thereby reduce the incidence of colorectal cancer induced by abnormal activation of Wnt/β-catenin signalling pathway. However, its activity was weak (IC 50 for SW480: 28.2 ± 2.05 μM) and total synthesis was difficult. During the structural simplification of natural products, S0 was revealed to be the basic pharmacophore of carnosic acid. Subsequent structural optimization of S0 led to the discovery of S11 as a possible anticancer agent with prominent proliferation inhibition effect (IC 50 for SW480: 9.56 ± 0.91 μM) and best selectivity index (SI = 3.0) against Wnt hyperactive cancer cells. Futher mechanism investigation through TOP/FOP dual luciferase reporter assay, immunofluorescence, co-immunoprecipitation, microscale thermophoresis, downstream oncoprotein expression and cell apoptosis showed that compound S11 could significantly inhibit the proliferation of SW480 cells via obvioudsly decreasing the nucleus translocation of β-catenin and effectively disrupting β-catenin/BCL9 protein-protein interaction. Additionally, cell migration, molecule docking, in vitro stability and solubility assays were also conducted. Overall, S11 was worthy of in-depth study as a potential inhibitor for the Wnt/β-catenin pathway and its discovery also proved that the structural simplification of natural products was still one of the effective methods to find new lead compounds or candidate drugs.
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Oxidative Medicine and Cellular Longevity
·
2021
·
IF 6.543
Yanxia Ma,Yu Liu,Linxin Teng,En Luo,Dekang Liu,Fuqiong Zhou,Kaiyuan Wang,Weiping Chen,Lei Bi
Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3β/β-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.
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ACTA BIOCHIMICA POLONICA
·
2021
·Vol. 68
·期 4
·725-732
·
IF 2.149
Ziyan Wu,Zhong Zhou,Weiguo Zhang,Yi Yu
MicroRNA (miR)-21 has been found to be overexpressed in osteosarcoma (OS). The aim of the present study was to investigate the effect of miR-21-5p on the Warburg effect and stemness maintenance in OS cells and its potential molecular mechanism. Herein, miR-21-5p was overexpressed or inhibited in MG-63 cells via transfection with mimics or inhibitors. The effect of miR-21-5p on cell viability, apoptosis, Warburg effect and stemness maintenance were explored in OS cells. The results demonstrated that miR-21-5p inhibition suppressed MG-63 cell viability and enhanced their apoptosis. Additionally, miR-21-5p inhibition attenuated the stemness maintenance of MG-63 cells, as demonstrated by the reduced proportion of CD133-positive MG-63 cells, the decrease in tumorsphere formation capacity, and the downregulation of Sox2, Oct4, and Nanog proteins. Moreover, miR-21-5p inhibition suppressed the Warburg effect in MG-63 cells, as indicated by the decrease in glucose uptake, lactic acid production, and ATP level and the downregulation of proteins involved in the Warburg effect (GLUT1, LDHA, HK2, and PKM2). Furthermore, the results suggested that the effect of miR-21-5p suppression on stemness and the Warburg effect may be associated with the decreased activity of the Wnt/β-catenin pathway in OS cells. Our findings suggest a novel potential biomarker for OS therapy.
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Environmental Technology & Innovation
·
2026
·
IF 7.3
Wenjie Wang,Xulong Fan,Yaquan Cao,Ruolin Shi,Ping Wang,Gaofeng Liang
Benzophenone-3 (BP-3), a common ultraviolet (UV) filter widely used in sunscreens, has raised increasing concern because early-life exposure may interfere with normal neurodevelopment. In this study, we fabricated a 3D inverse-opal polyethylene glycol diacrylate (PEGDA) scaffold and established a scaffold-supported brain organoid model for in vitro evaluation of BP-3-induced neurotoxicity. The scaffold was characterized by scanning electron microscopy (SEM), which revealed a highly ordered porous morphology with uniform pore size. It also showed good biocompatibility for organoid culture. BP-3 exposure induced concentration- and time-dependent toxicity in brain organoids, with more pronounced effects observed at 50 and 100 μM after 72 h of exposure. Under these defined exposure conditions, BP-3 was associated with increased oxidative stress, calcium-related functional changes, impaired membrane integrity, increased cytotoxicity, reduced expression of synaptic structural markers, and altered Wnt/β-catenin-related protein expression. These findings suggest that BP-3 exposure may disrupt early neurodevelopment-related processes in this model and is associated with synaptic-related alterations and Wnt/β-catenin dysregulation. Overall, this study supports the applicability of scaffold-supported brain organoids as an in vitro platform for evaluating BP-3-induced neurotoxic responses under controlled experimental conditions.
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PLoS One
·
2025
·Vol. 20
·期 6
·e0326978
·
IF 2.6
Chang Chen,Qiqi Yun,Juanli Ran,Ziyao Zhou,Pengxiang Zhang,Rong Li
Objective
This study investigated the interplay between Hippo-YAP and β-catenin signaling in regulating odontogenic differentiation of human dental pulp stem cells (DPSCs) and explored its potential implications for dentin-pulp regeneration.
Methods
Using lentivirus-mediated YAP overexpression/silencing, β-catenin siRNA knockdown, and pharmacological Wnt inhibition (via WIF-1), we assessed DPSC proliferation, migration, mineralization, and molecular markers (via qRT-PCR, immunofluorescence). In vivo validation employed subcutaneous transplantation of DPSC-seeded scaffolds in immunocompromised mice.
Results
YAP activation enhanced DPSC proliferation (1.44-fold), migration (1.39-fold), invasion (1.54-fold), and differentiation, as evidenced by elevated ALP activity (1.46-fold) and mineralization (1.36-fold). We observed transcriptional upregulation of odontogenic markers (RUNX2, DSPP, DMP1, OCN, ALP) and Wnt pathway components (β-catenin, Cyclin D1, c-Myc). Immunofluorescence revealed coordinated YAP and β-catenin expression patterns during differentiation. β-catenin silencing or Wnt inhibition abolished YAP-mediated functional enhancements and simultaneously suppressed YAP expression, partially confirming bidirectional regulation. In vivo , YAP-overexpressing DPSCs exhibited 1.27- to 1.62-fold induction of dentin-specific markers and β-catenin, whereas YAP silencing impaired these markers expression.
Conclusions
Our findings demonstrate that coordinated YAP and β-catenin signaling drives DPSC odontogenesis, with potential implications for dentin regeneration. Although reciprocal regulation is evident, direct molecular interactions require further validation.
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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
·
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
·
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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