American Journal of Translational Research
·
2025
·Vol. 17
·期 10
·8060
·
IF 1.6
Xia Tian,Zheng Han,Ye Yu,Jie Tan,Qingxi Zhu,Wei Chen,Shasha Huang,Xiaoli Chen,Meng Liu
Objective: To investigate the role of CDH17 in cisplatin (DDP) resistance in gastric cancer (GC) and to elucidate the potential molecular mechanisms. Methods: DDP-resistant GC cell lines were established, and CDH17 expression was silenced in these cells. Cell proliferation was assessed using the MTT assay. Cellular glycolytic activity was quantified, and apoptosis was assessed using flow cytometry. The expression of CDH17, β-catenin, key Warburg-related effector proteins, and Cleaved-caspase-3 was determined through molecular experiments. The Warburg effect inhibitor 2-DG and the Wnt/β-catenin signaling pathway agonist CP21R7 were applied to investigate the underlying molecular mechanism. Results: CDH17 was significantly upregulated in the DDP-resistant GC cells. CDH17 knockdown increased the sensitivity of GC cells to DDP, suppressed the Warburg effect, and inhibited the activation of the Wnt/β-catenin signaling pathway. Treatment with 2-DG reduced the chemoresistance in resistant GC cells. However, CP21R7 treatment promoted the Warburg effect in the DDP-resistant GC cells and partially attenuated the effects of CDH17 silencing on both the Warburg effect and DDP sensitivity. Conclusion: CDH17 silencing reversed DDP resistance in GC cells, primarily through inhibition of the Warburg effect mediated by the Wnt/β-catenin signaling pathway.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 19
·e70877
·
IF 4.2
Tonghao Yao,Liangliang Liu,Yibo Miao,Xinxin Li,Ying Yu,Rongyao Sun,Yining Zhang,Luping Cui,Xu Ma
Diabetes is a significant global chronic disease characterised by elevated mortality and disability rates due to persistent infections resulting from refractory wounds. Currently, effective treatment strategies are lacking. Adipose-derived stem cell extracellular vesicles (ADSC-EVs) have been shown to promote skin wound healing; however, their clinical application is impeded by low yield and heterogeneity. We successfully isolated high-yield extruded nanovesicles from adipose stem cells (ADSC-NVs), achieving yields over 30 times greater than those of ADSC-EVs while maintaining similar mor-phological characteristics. Our findings indicate that ADSC-NVs exhibit a dose-dependent en-hancement of proliferation and migration in primary human dermal fibroblasts (HDF) in vitro. Notably, the expression levels of proliferating cell nuclear antigen (PCNA), collagen type I (COL-I) and collagen type III (COL-III) were significantly upregulated in HDF following treatment with ADSC-NVs. RNA-seq analysis further revealed that the differentially expressed genes (DEGs) shared between the ADSC-NVs group and control group were predominantly enriched in the Wnt signalling pathway. Consistently, ADSC-NVs facilitate efficient diabetic wound healing while promoting proliferation and inhibiting inflammation via the Wnt/β-catenin signalling pathway. In summary, high-yield ADSC-NVs represent a promising alternative to ADSC-EVs for enhancing diabetic wound healing, providing novel insights and methodologies for improving therapeutic outcomes.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2022
·Vol. 75
·期 1
·129-138
·
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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FASEB JOURNAL
·
2023
·Vol. 37
·期 6
·e22964
·
IF 4.8
Fei Sun,Cheng An,Can Liu,Ying Hu,Yue Su,Zhixiang Guo,Hong Che,Shenglin Ge
Cardiac ischemia/reperfusion (I/R) injury is a complicated pathological event, which has close association with pyroptosis. This study uncovered the regulatory mechanisms of fat mass and obesity-associated protein (FTO) in NLRP3-mediated pyroptosis during cardiac I/R injury. H9c2 cells were stimulated with oxygen–glucose deprivation/reoxygenation (OGD/R). Cell viability and pyroptosis were detected by CCK-8 and flow cytometry. Western blotting or RT-qPCR was performed to analyze target molecule expression. NLRP3 and Caspase-1 expression was observed by immunofluorescence staining. IL-18 and IL-1β production was detected by ELISA. The total m6A and m6A level of CBL was determined by dot blot assay and methylated RNA immunoprecipitation-qPCR, respectively. The interaction between IGF2BP3 and CBL mRNA was confirmed by RNA pull-down and RIP assays. The protein interaction between CBL and β-catenin and β-catenin ubiquitination were evaluated by Co-IP. Myocardial I/R model was established in rats. We determined infarct size by TTC staining and pathological changes by H&E staining. LDH, CK-MB, LVFS, and LVEF were also assessed. FTO and β-catenin were down-regulated, while CBL was up-regulated by OGD/R stimulation. FTO/β-catenin overexpression or CBL silencing restrained OGD/R-induced NLRP3 inflammasome-mediated pyroptosis. CBL repressed β-catenin expression via ubiquitination and degradation. FTO reduced the mRNA stability of CBL by inhibiting m6A modification. CBL-mediated ubiquitination and degradation of β-catenin were involved in FTO-induced pyroptosis inhibition during myocardial I/R injury. FTO inhibits NLRP3-mediated pyroptosis to attenuate myocardial I/R injury via repressing CBL-induced ubiquitination degradation of β-catenin.
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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
·
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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PHYTOMEDICINE
·
2024
·
IF 6.7
Huizhen Tian,Qigang Pan,Jianfeng Wu,Juanjuan Liao,Yuwei Wan,Ke Pei,Qiong Liu,Lingbing Zeng,Yanli Cao,Qiaofa shi,Nanzhen Kuang,LiJuan Sun,Xiaomin Yu,Xiaotian Huang
Background Coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis and is currently lacking specific pharmacological treatments, highlighting the critical need for therapeutic development. Icariin (ICA), a prenylated flavonol glycoside, was previously found to exhibit several pharmacological effects, but its potential to combat CVB3 remains uninvestigated. Purpose This study aimed to elucidate the anti-CVB3 efficacy of ICA and elucidate its molecular mechanisms. Methods CVB3-infected HeLa cells, H9C2 cells and neonate rat ventricular cardiomyocytes (NRVCs) were selected as in vitro models, and were treated with ICA at 1 and 10 μM. Additionally, BALB/c mice that were infected with CVB3 via intraperitoneal injection were chosen as in vivo model and were treated with ICA or ribavirin over 3 days. The effect of ICA against CVB3 was determined by Cell Counting Kit-8 (CCK-8) assay, western blot, real-time fluorescence quantitative PCR (RT–qPCR), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and flow cytometry. Results In this study, it was found that ICA is capable of reducing CVB3 viral load both in vitro and in vivo . Mechanistic studies suggested that ICA prevents cardiomyocyte apoptosis by attenuating the S100 calcium binding protein A6 (S100A6)/β-catenin/c-Myc signaling pathway. Additionally, ICA inhibits the secretion of proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and CXC motif chemokine ligand 2 (CXCL2) in heart tissue, thereby mitigating CVB3-induced myocarditis. Moreover, ICA also regulates the immune response of CD4 + T, CD8 + T and Treg cells by changing the cells numbers in spleen tissue. Lastly, ICA can reduce the load of other enteroviruses (such as CVA6, CVA16 and EV71) in rhabdomyosarcoma (RD) cells as well. Conclusion Our findings indicate that ICA provides significant protection against CVB3 infection by modulating the S100A6/β-catenin/c-Myc signaling pathway, suggesting its potential use as a novel drug against CVB3 infection in clinical application.
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JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
·
2024
·Vol. 150
·期 7
·1-19
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IF 2.7
Chang Jing-Xia,Zhang Meng,Lou Li-Li,Chu He-Ying,Wang Hua-Qi
Purpose Kinase interacting with stathmin (KIS) is a serine/threonine kinase involved in RNA processing and protein phosphorylation. Increasing evidence has suggested its involvement in cancer progression. The aim of this study was to investigate the role of KIS in the development of lung adenocarcinoma (LUAD). Dual luciferase assay was used to explore the relationship between KIS and SOX4, and its effect on ID1/β-catenin pathway. Methods Real-time qPCR and western blot were used to assess the levels of KIS and other factors. Cell proliferation, migration, and invasion were monitored, and xenograft animal model were established to investigate the biological functions of KIS in vitro and in vivo. Results In the present study, KIS was found to be highly expressed in LUAD tissues and cell lines. KIS accelerated the proliferative, migratory and invasive abilities of LUAD cells in vitro, and promoted the growth of LUAD in a mouse tumor xenograft model in vivo. Mechanistically, KIS activated the β-catenin signaling pathway by modulating the inhibitor of DNA binding 1 (ID1) and was transcriptionally regulated by SOX4 in LUAD cells. Conclusion KIS, a target of SOX4, regulates the ID1-mediated enhancement of β-catenin to facilitate LUAD cell invasion and metastasis.
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BMC Cardiovascular Disorders
·
2024
·Vol. 24
·期 1
·1-11
·
IF 2
Lin Wei,Hou Lianglei,Tang Jialyu,Huang Anwu,Jia Zhuyin
In this study, we sought to investigate the mechanisms of action of miR-195-5p in the osteogenic differentiation of vascular smooth muscle cells (VSMCs), and thereby provide novel insights and a reference for the targeted therapy of arterial media calcification. VSMC differentiation was induced using sodium β-glycerophosphate, and we investigated the effects of transfecting cells with miR-195-5p mimics, vectors overexpressing Smad7, and the Wnt/β-catenin pathway inhibitor (KYA1797K) on VSMC differentiation by determining cell viability and apoptosis, and the mRNA and protein expression of factors associated with osteogenic differentiation and the Wnt/β-catenin pathway. The results revealed that miR-195-5p mimics enhanced the osteogenic differentiation of VSMCs induced by β-glycerophosphate, whereas the overexpression of Smad7 reversed this phenomenon. In addition, KYA1797K was found to promote the effects of Smad7 overexpression. In conclusion, by targeting, Smad7, miR-195-5p promotes the Wnt/β-catenin pathway. and thus the osteogenic differentiation of VSMCs. These findings will provide a reference for elucidating the mechanisms whereby miR-195-5p regulates osteogenic differentiation.
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Chemical Biology & Drug Design
·
2024
·Vol. 103
·期 1
·e14434
·
IF 3.2
Liyang Liu,Wusong Xue
Heaps of studies have verified the effects of thalidomide (THA) on colorectal cancer (CRC). Howbeit, the corresponding mechanism awaits illustration, which is the foothold of this study. Following the treatment of 0, 1.94, 7.75, or 19.36 μM THA, CRC cell viability, apoptosis, migration, and invasion were evaluated by methyl tetrazolium, flow cytometry, wound-healing, and transwell assays. Homeobox B7 (HOXB7) expression in CRC was analyzed and detected by bioinformatics analysis, quantitative real-time PCR or western blot. After the corresponding transfection or treatment with inhibitor of catenin-responsive transcription-3 (iCRT-3), abovementioned CRC cell biological behaviors as well as expression levels of HOXB7 and β-catenin were evaluated. 7.75 and 19.36 μM THA dwindled CRC cell viability, migration, and invasion, and facilitated apoptosis. HOXB7 upregulation was detected in CRC cells, which promoted the viability, migration, invasion, and β-catenin expression, and weakened the apoptosis of CRC cells. Also, HOXB7 upregulation counteracted the effects of THA on CRC cells. iCRT-3 restrained β-catenin expression, viability, migration, and invasion, whereas promoting the apoptosis of CRC cells. In addition, iCRT-3 antagonized the effects of overexpressed HOXB7 on CRC cells. THA inhibits the migration and invasion of CRC cells, which is achieved by suppressing HOXB7-mediated activation of Wnt/β-catenin signaling pathway.
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PATHOLOGY RESEARCH AND PRACTICE
·
2025
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IF 3.2
Ting-Ting Yang,Xin-Xin Ma,Xuan Zhang,Zhen-Qing Han,Shuang Zhang,Qi Wang,Hong-Wei Dong,Jia-Ren Liu
β-Ionone (BI) has shown the potent inhibitory malignant progression of multiple tumors including gastric cancer in vitro and in vivo. However, the mechanism by which BI inhibits gastric cancer remains to be clarified, especially in ferroptosis, which is a new form of programmed cell death. The aim of this study was to investigate whether BI could induce ferroptosis in gastric cancer and the underlying mechanisms. The results manifested that BI obviously inhibited cell viability and increased the Fe 2 + level, total reactive oxygen species (ROS) and lipid ROS levels and the malondialdehyde (MDA) concentrations, but reduced the mitochondrial membrane potential (MMP) and the expression of SLC7A11 and GPX4 in MKN45 cells and AGS cells ( P < 0.05 or P < 0.01). Besides, BI also arrested cell cycle and decreased the expression of Cyclin D1 and CDK4 ( P < 0.05 or P < 0.01). Mechanistically, BI reduced the levels of β-catenin and pGSK-3β/GSK-3β in MKN45 cells and AGS cells ( P < 0.05 or P < 0.01). Nevertheless, pretreatment with lithium chloride (LiCl), an inhibitor of GSK-3β, reversed BI-induced ferroptosis and cell cycle arrested in MKN45 cells ( P < 0.05). In addition, BI effectively inhibited the growth of gastric cancer xenografts and downregulated the levels of GPX4, SLC7A11, PCNA, β-catenin and pGSK-3β/GSK-3β ( P < 0.05 or P < 0.01). Collectively, our study reveals that BI inhibits proliferation of gastric cancer cells by induction ferroptosis via the Wnt/β-catenin signaling pathway and provides a novel therapy for gastric cancer.
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