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Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways
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作者 Da-zhuang Lu Li-jun Zeng +8 位作者 Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第3期208-221,共14页
Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy pre... Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved. 展开更多
关键词 BMPs/SMAD bone loss cinobufotalin hBMMSCs OSTEOGENESIS OSTEOPOROSIS wnt/β-catenin signaling pathways
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Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions
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作者 Yi-Mei Wang Zheng-Wei Luo +5 位作者 Yu-Lin Shu Xiu Zhou Lin-Qing Wang Chun-Hong Liang Chao-Qun Wu Chang-Ping Li 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第3期979-990,共12页
BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and th... BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to GC.Therefore,it is necessary to find a novel drug that is inexpensive and preventive to against GC.AIM To explore the effects of H.pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),H.pylori+MNU,and Moluodan groups.We first created an H.pylori infection model in the H.pylori+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control group.Moluodan was fed to mice in the Moloudan group ad libitum.The general condition of mice were observed during the whole experiment period.Gastric tissues of mice were grossly and microscopically examined.Through quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were detected.RESULTS Mice in the H.pylori+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control group.QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the H.pylori+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control group.CONCLUSION H.pylori can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of PLGC.Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC. 展开更多
关键词 Helicobacter pylori Gastric cancer wnt/β-catenin signaling pathway Moluodan
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Pachymic acid exerts antitumor activities by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B
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作者 Hao Zhang Kun Zhu +5 位作者 Xue-Feng Zhang Yi-Hui Ding Bing Zhu Wen Meng Qing-Song Ding Fan Zhang 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2024年第4期170-180,共11页
Objective:To determine the inhibitory effects of pachymic acid on lung adenocarcinoma(LUAD)cells and elucidate its underlying mechanism.Methods:CCK-8,wound healing,Transwell,Western blot,tube formation,and immunofluor... Objective:To determine the inhibitory effects of pachymic acid on lung adenocarcinoma(LUAD)cells and elucidate its underlying mechanism.Methods:CCK-8,wound healing,Transwell,Western blot,tube formation,and immunofluorescence assays were carried out to measure the effects of various concentrations of pachymic acid on LUAD cell proliferation,metastasis,angiogenesis as well as autophagy.Subsequently,molecular docking technology was used to detect the potential targeted binding association between pachymic acid and protein tyrosine phosphatase 1B(PTP1B).Moreover,PTP1B was overexpressed in A549 cells to detect the specific mechanisms of pachymic acid.Results:Pachymic acid suppressed LUAD cell viability,metastasis as well as angiogenesis while inducing cell autophagy.It also targeted PTP1B and lowered PTP1B expression.However,PTP1B overexpression reversed the effects of pachymic acid on metastasis,angiogenesis,and autophagy as well as the expression of Wnt3a andβ-catenin in LUAD cells.Conclusions:Pachymic acid inhibits metastasis and angiogenesis,and promotes autophagy in LUAD cells by modulating the Wnt/β-catenin signaling pathway via targeting PTP1B. 展开更多
关键词 Pachymic acid Lung adenocarcinoma Protein tyrosine phosphatase 1B wnt/β-catenin signaling pathway METASTASIS ANGIOGENESIS AUTOPHAGY
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Harnessing the power of Calculus bovis:Anti-cancer properties and Wnt pathway modulation in hepatocellular carcinoma
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作者 Himanshi Goyal Sachin Parwani +1 位作者 Kaneez Fatima Jyotdeep Kaur 《World Journal of Gastroenterology》 SCIE CAS 2024年第41期4496-4502,共7页
In this manuscript,we comment on the article,which explores the anti-cancer effects of Calculus bovis(CB)in tumor biology.We highlight its potential,particularly in hepatocellular carcinoma(HCC),where it inhibits the ... In this manuscript,we comment on the article,which explores the anti-cancer effects of Calculus bovis(CB)in tumor biology.We highlight its potential,particularly in hepatocellular carcinoma(HCC),where it inhibits the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways and induces apoptosis.CB contains compounds such as oleanolic acid and ursolic acid that target interleukin-6,mitogen-activated protein kinase 8,vascular endothelial growth factor,and caspase-3,offering anti-inflammatory and hepatoprotective benefits.The manuscript also discusses CB sativus(CBS),an artificial substitute,which has shown efficacy in reducing hepatic inflammation and oxidative stress in animal models.We emphasize the need for further research on the effects of CBS on the gut-liver axis and gut microbiota,and on targeting Wnt signaling and M2 tumor-associated macrophage as potential therapeutic strategies against HCC. 展开更多
关键词 Calculus bovis Liver cancer Tumor-associated macrophages M2 polarization wnt signaling pathway
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Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types 被引量:1
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作者 Dan Qiao Xiao-Yan Liu +5 位作者 Lie Zheng Ya-Li Zhang Ren-Ye Que Bing-Jing Ge Hong-Yan Cao Yan-Cheng Dai 《World Journal of Clinical Cases》 SCIE 2023年第9期1963-1973,共11页
BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide,with the fourth highest mortality among all cancers.Reportedly,in addition to adenomas,serrated polyps,which account for 15%-30%of CRCs,can al... BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide,with the fourth highest mortality among all cancers.Reportedly,in addition to adenomas,serrated polyps,which account for 15%-30%of CRCs,can also develop into CRCs through the serrated pathway.Sessile serrated adenomas/polyps(SSAs/Ps),a type of serrated polyps,are easily misdiagnosed during endoscopy.AIM To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types.METHODS From January 2021 to December 2021,patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital,affiliated with Shanghai University of Traditional Chinese Medicine.Thirty cases each of large intestine damp-heat(Da-Chang-Shi-Re,DCSR)syndrome and spleen-stomach weakness(Pi-Wei-Xu-Ruo)syndrome were reported.Baseline comparison of the general data,typical tongue coating,colonoscopy findings,and hematoxylin and eosin findings was performed in each group.The expression of the Wnt pathway-related proteins,namelyβ-catenin,adenomatous polyposis coli,and mutated in colorectal cancer,were analyzed using immunohistochemistry.RESULTS Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types(P=0.001).The other aspects did not differ between the two groups.The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups,which was manifested asβ-catenin protein translocation into the nucleus.However,SSAs/Ps patients with DCSR syndrome had more nucleation,higherβ-catenin expression,and negative regulatory factor(adenomatous polyposis coli and mutated in colorectal cancer)expression(P<0.0001)than SSA/P patients with Pi-Wei-Xu-Ruo syndrome.In addition,the SSA/P size was linearly correlated with the related protein expression.CONCLUSION Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis.A high-quality colonoscopic diagnosis was essential.The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine. 展开更多
关键词 Sessile serrated adenomas/polyps wnt signaling pathway Large intestine damp-heat syndrome Spleen-stomach weakness syndrome
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The Role and Mechanism of LncRNA-p21 in Regulating Gastric Cancer Metastasis by Mediating Wnt/β-Catenin Signaling Pathway 被引量:1
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作者 Peng Liu Haizhe Chang +3 位作者 Xinyu Peng Xiu Zhang Jianjun Zhang Jiusong Luan 《Journal of Clinical and Nursing Research》 2023年第3期143-148,共6页
Objective:To study the mechanism of lncRNA p21 inhibiting the growth and metastasis of human gastric cancer SGC7901/GES-1 cells by mediating the Wnt/β-catenin signaling pathway.Methods:Lentiviral overexpression of ln... Objective:To study the mechanism of lncRNA p21 inhibiting the growth and metastasis of human gastric cancer SGC7901/GES-1 cells by mediating the Wnt/β-catenin signaling pathway.Methods:Lentiviral overexpression of lncRNA-p21 in human gastric cancer SGC7901/GES-1 cell transfections was observed and analyzed for in vitro migration,invasion,cell morphology and proliferation.Besides.Wnt/β-catenin signaling pathway was tested for direct involvement in lncRNA-p21-mediated inhibition of gastric cancer cell growth and proliferation.Wnt/β-catenin signaling pathway was validated using Li-C1.Results:Gastric cancer SGC7901/GES-1 cells in the overexpression of lncRNA-p21 showed changes in stellate morphology,low invasion,or spindle-shaped morphology.LncRNA-p21 inhibited the growth and proliferation of gastric cancer SGC7901/GES-1 cells both in vivo and in vitro,and Wnt/β-catenin signaling pathway mediated the proliferation,invasion,and migration of lncRNA-p21 on gastric cancer SGC7901/GES-1 cells.Conclusion:LncRNA-p21 can inhibit the growth and metastasis of gastric cancer SGC7901/GES-1 cells in vitro and in vivo,and the inhibition of lncRNA p21 is mainly mediated by inhibiting the Wnt/β-catenin signaling pathway. 展开更多
关键词 LncRNA-p21 wnt/beta-catenin signaling pathway Gastric cancer
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Effects of curcumin on uterine leiomyoma in a rat model by inhibiting β-catenin/Wnt signaling pathway
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作者 Wen-Xian Li Jia-Li Bai +4 位作者 Li Fu Ya-Jing Zhu Ge Fan Bing Yang Cheng-Liang Yin 《Precision Medicine Research》 2023年第2期1-7,共7页
Background:Women with uterine leiomyomas may suffer severe symptoms.To avoid risks of side effects,it is necessary to develop an optimal agent to shrink leiomyomas with fewer side effects and a lower recurrence rate.C... Background:Women with uterine leiomyomas may suffer severe symptoms.To avoid risks of side effects,it is necessary to develop an optimal agent to shrink leiomyomas with fewer side effects and a lower recurrence rate.Curcumin may have a lower side effect in uterine leiomyoma treatment.Methods:We established the estrogen-and-progesterone-induced murine model of uterine leiomyoma.Next,we determined the expression of related genes of the β-catenin/Wnt signaling pathway by western blot,reverse transcription-polymerase chain reaction,and immunohistochemistry.We also noticed the morphological changes in uterine tissues by hematoxylin-eosin staining.Results:Curcumin plays an important role in Wnt/β-catenin signaling pathway-related expression including β-catenin,adenomatous polyposis coli,glycogen synthase kinase-3β,Wnt-11,and serum hormone concentrations.Conclusions:Curcumin could the down-regulation of serum hormone concentrations and inhibition of the β-catenin/Wnt signaling pathway in the treatment of uterine leiomyoma. 展开更多
关键词 LEIOMYOMA CURCUMIN wnt signaling pathway ESTROGENS PROGESTERONE
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Effects of Qigongwan on Wnt/β-catenin Signaling Pathway in Rats with Polycystic Ovary syndrome
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作者 Xiaojun LI Yunchao WEI +2 位作者 Haitao XIE Bin YANG Jinghong XIE 《Medicinal Plant》 CAS 2023年第4期69-73,83,共6页
[Objectives] To explore the therapeutic effect and mechanism of Qigongwan on PCOS model rats by detecting the changes in sex hormone levels in rats with polycystic ovary syndrome (PCOS), and observing the effects of o... [Objectives] To explore the therapeutic effect and mechanism of Qigongwan on PCOS model rats by detecting the changes in sex hormone levels in rats with polycystic ovary syndrome (PCOS), and observing the effects of ovarian pathological morphological changes, apoptosis and expression of Wnt/β-β catenin signaling pathway protein. [Methods] Ten of 40 female SD rats were randomly selected as the normal group, and the other 30 rats were treated with letrozole combined with high-fat diet to establish the PCOS rat model. After successful modeling, the model group was randomly divided into Qigongwan group, positive Daying-35 (Ethinylestradiol and Cyproterone Acetate Tablets) group and model group, with 10 rats in each group. Qigongwan group was given 14.7 g/(kg·d) by gavage, Daying-35 group was given 0.21 mg/(kg·d) by oral gavage, and normal group and model group were given the same amount of distilled water, and the intervention lasted for 21 d. ELISA method was used to detect the levels of hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E 2) and progesterone (P) in serum. HE staining was used to observe the pathological morphological changes of ovarian tissues;TUNEL staining was used to observe apoptosis of ovarian tissue granule cells;the expression of Wnt, β-catenin protein in rat ovarian tissue was detected by immunohistochemistry. [Results] (i) Compared with the model group, Qigongwan group and Daying-35 group could significantly increase serum E 2 and P levels, significantly reduce serum T levels ( P <0.01), significantly reduce serum LH levels and LH/FSH ratio ( P <0.01), and increase serum FSH levels ( P <0.05) in different degrees. (ii)The results of HE staining showed that compared with the model group, Qigongwan and Daying-35 groups could improve follicular development and reduce atretic follicles in different degrees. Compared with Daying-35 group, the number of GC layers in Qigongwan group was significantly increased. (iii) The results of TUNEL staining showed that compared with the model group, the rate of TUNEL-positive cells in the Qigongwan group and Daying-35 group decreased significantly ( P <0.01). (iv) The immunohistochemical results showed that compared with the model group, the expression levels of wnt and β-catenin in the Qigongwan group and the Daying-35 group increased in different degrees ( P <0.05), and the expression range increased. [Conclusions] Qigongwan can regulate the secretion level of sex hormones such as FSH and LH, improve the pathological damage of ovarian tissue, and inhibit apoptosis of ovarian granule cells, and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway. 展开更多
关键词 Qigongwan Polycystic ovary syndrome(PCOS) Granulosa cells wnt/β-catenin signaling pathway APOPTOSIS RAT
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TCM Intervention on Wnt/β-Catenin signaling pathway in the treatment of diabetic nephropathy
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作者 WEI Ting-ting MENG Li-feng +2 位作者 LI Li-rong ZHANG Peng HUANG Xue-xia 《Journal of Hainan Medical University》 CAS 2023年第16期76-80,共5页
Diabetic nephropathy(DN)is the most serious microvascular complication of diabetes mellitus,which is highly prevalent worldwide.Abnormal activation of Wnt/β-catenin signaling pathway is an important mechanism of rena... Diabetic nephropathy(DN)is the most serious microvascular complication of diabetes mellitus,which is highly prevalent worldwide.Abnormal activation of Wnt/β-catenin signaling pathway is an important mechanism of renal damage induced by hyperglycemia.Many studies have shown that TCM has the advantages of high efficiency and safety in the prevention and treatment of DN.Some TCM monomers and compounds repair podocyte function and inhibit transdifferentiation process by inhibiting the activation of Wnt/β-catenin signaling pathway,thus playing a protective role in kidney.Based on this,this paper will review the existing research results and related mechanisms of TCM intervention in Wnt/β-catenin signaling pathway in the treatment of DN,in order to promote the more effective and reasonable application of TCM in clinical practice. 展开更多
关键词 wnt/β-catenin signaling pathway Diabetic nephropathy Traditional Chinese Medicine
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Cycloartane Glycosides from the Roots of Cimicifuga foetida with Wnt Signaling Pathway Inhibitory Activity 被引量:3
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作者 Di-Fan Zhu Guo-Lei Zhu +4 位作者 Ling-Mei Kong Ni-Man Bao Lin Zhou Yin Nian Ming-Hua Qiu 《Natural Products and Bioprospecting》 CAS 2015年第2期61-67,共7页
Four new 9,19-cycloartane triterpenoids,cimilactone E(1),cimilactone F(2),20-O-(E)-butenoyl-23-epi-26-deoxyactein(3),and 20,12b-O-diacetylcimiracemonol-3-O-b-D-xylopyranoside(4),together with four known constituents(5... Four new 9,19-cycloartane triterpenoids,cimilactone E(1),cimilactone F(2),20-O-(E)-butenoyl-23-epi-26-deoxyactein(3),and 20,12b-O-diacetylcimiracemonol-3-O-b-D-xylopyranoside(4),together with four known constituents(5–8)were isolated from the roots of Cimicifuga foetida.The new structures were elucidated by extensive spectroscopic analysis.In addition,compounds 7 and 8 showed significant Wnt signaling pathway inhibitory activity,with IC50 values of 3.33 and 13.34 lM,respectively,using the luciferase reporter gene assay. 展开更多
关键词 Cimicifuga foetida 9 19-Cycloartane triterpenoids Cimilactone-type wnt signal pathway Luciferase activity
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Roles of Wnt/β-catenin signaling pathway related microRNAs in esophageal cancer 被引量:2
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作者 Chao-Yang Chu Rui Wang Xian-Li Liu 《World Journal of Clinical Cases》 SCIE 2022年第9期2678-2686,共9页
MicroRNAs(mi RNAs)are endogenous,noncoding,single-stranded small RNAs that regulate expression of tumor suppressor genes and oncogenes and are involved in almost all tumor-related processes.Mi RNA dysregulation plays ... MicroRNAs(mi RNAs)are endogenous,noncoding,single-stranded small RNAs that regulate expression of tumor suppressor genes and oncogenes and are involved in almost all tumor-related processes.Mi RNA dysregulation plays an important role in the occurrence and development of esophageal cancer through specific signal pathways,including the Wnt/β-catenin signaling pathway,and is closely related to the malignant characteristics of esophageal cancer.The interaction between mi RNAs and the Wnt/β-catenin signaling pathway,which is specifically expressed in esophageal cancer tissues,shows potential as a new biomarker and therapeutic target.This article reviews the role of mi RNAs related to the Wnt pathway in the carcinogenesis of esophageal carcinoma and its role in Wnt signal transduction.The content of this review can be used as the basis for formulating or improving the treatment strategy of esophageal cancer. 展开更多
关键词 wnt signal pathway MICRORNA Esophageal cancer Esophageal cancer tissues
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Activation of canonical Wnt signaling pathway promotes proliferation and self-renewal of rat hepatic oval cell line WB-F344 in vitro 被引量:16
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作者 Ying Zhang Xin-Min Li Fu-Kui Zhang Bao-En Wang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第43期6673-6680,共8页
AIM: To investigate the effect of activation of canonical Wnt signaling pathway on the proliferation and differentiation of hepatic oval cells in vitro. METHODS: WB-F344 cells were treated with recombinant Wnt3a (2... AIM: To investigate the effect of activation of canonical Wnt signaling pathway on the proliferation and differentiation of hepatic oval cells in vitro. METHODS: WB-F344 cells were treated with recombinant Wnt3a (20, 40, 80, 160, 200 ng/mL) in serum-free medium for 24 h. Cell proliferation was measured by Brdu incorporation analysis; untreated WB-F344 cells were taken as controls. After treatment with Wnt3a (160 ng/mL) for 24 h, subcellular localization and protein expression of p-catenin in WB-F344 cells treated and untreated with Wnt3a were examined by immunofluorescence staining and Western blot analysis. CyclinD1 mRNA expression was determined by semi-quantitative reverse-transcript polymerase chain reaction (RT-PCR). The mRNA levels of some phenotypic markers (AFP, CK-19, ALB) and two hepatic nuclear factors (HNF-4, HIVF-6) were measured by RT-PCR. Expressions of CK-19 and AFP protein were detected by Western blot analysis. RESULTS: Wnt3a promoted proliferation of WB-F344 cells. Stimulation of WB-F344 cells with recombinant Wnt3a resulte^l in accumulation of the transcriptional activator β-catenin, together with its translocation into the nuclei, and up-regulated typical Wnt target gene CyclinD1. After 3 d of Wnt3a treatment in the absence of serum, WB-F344 cells retained their bipotential to express several specific phenotypic markers of hepatocytes and cholangiocytes, such as AFP and CK-19, following activation of the canonical Wnt signaling pathway. CONCLUSION: The canonical Wnt signaling pathway promotes proliferation and self-renewal of rat hepatic oval cells. 展开更多
关键词 Canonical wnt signaling pathway Oval cells Cell proliferation Self-renewal of cells
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Mutations in components of the Wnt signaling pathway in gastric cancer 被引量:11
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作者 Kai-Feng Pan Wan-Guo Liu +2 位作者 Lian Zhang Wei-Cheng You You-Yong Lu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第10期1570-1574,共5页
AIM: To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta- catenin) ... AIM: To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta- catenin) exon3 mutations in 70 GCs. METHODS: The presence of mutations was identified by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography and direct DNA sequencing. Beta-catenin expression was detected by immunohistochemical analysis. RESULTS: Among the 70 GCs, 5 (7.1%) had mutations in one or two of these three components. A frameshift mutation (1 bp deletion) in exon7 of AXIN2 was found in one case. Four cases, including the case with a mutation in AXIN2, had frameshift mutations and missense mutations in AXIN1. Five single nucleotide polymorphisms (SNPs), 334 C>T, 874 C>T, 1396 G>A, 1690 C>T and 1942 T>G, were identified in AXIN1. A frameshift mutation (27 bp deletion) spanning exon3 of CTNNB1 was observed in one case. All four cases with mutations in AXIN1 and AXIN2 showed nuclear beta- catenin expression. CONCLUSION: These data indicate that the mutationsin AXIN1 and AXIN2 may contribute to gastric carcino- genesis. 展开更多
关键词 AXIN1 AXIN2 Β-CATENIN wnt signaling pathway Gastric cancer
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Down-regulation of mi R-30a-3p/5p promotes esophageal squamous cell carcinoma cell proliferation by activating the Wnt signaling pathway 被引量:13
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作者 Bo Qi Yan Wang +7 位作者 Zhi-Jun Chen Xiang-Nan Li Yu Qi Yang Yang Guang-Hui Cui Hai-Zhou Guo Wei-Hao Li Song Zhao 《World Journal of Gastroenterology》 SCIE CAS 2017年第45期7965-7977,共13页
AIM To investigate the potential role of micro RNA-30 a(mi R-30 a) in esophageal squamous cell carcinoma(ESCC).METHODS Expression of mi R-30 a-3 p/5 p was analyzed using microarray data and fresh ESCC tissue samples. ... AIM To investigate the potential role of micro RNA-30 a(mi R-30 a) in esophageal squamous cell carcinoma(ESCC).METHODS Expression of mi R-30 a-3 p/5 p was analyzed using microarray data and fresh ESCC tissue samples. Both in vitro and in vivo assays were used to investigate the effects of mi R-30 a-3 p/5 p on ESCC cell proliferation. Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis was performed to explore underlying mechanisms involved in ESCC,and then,assays were carried out to verify the potential molecular mechanism of mi R-30 a in ESCC.RESULTS Low expression of mi R-30 a-3 p/5 p was closely associated with advanced ESCC progression and poor prognosis of patients with ESCC. Knock-down of mi R-30 a-3 p/5 p promoted ESCC cell proliferation. Increased mi R-30 a-3 p/5 p expression inhibited the Wnt signaling pathway by targeting Wnt2 and Fzd2.CONCLUSION Down-regulation of mi R-30 a-3 p/5 p promotes ESCC cell proliferation by activating the Wnt signaling pathway through inhibition of Wnt2 and Fzd2. 展开更多
关键词 mi R-30a-3p/5p Proliferation Esophageal squamous cell carcinoma wnt signaling pathway wnt2 Fzd2
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Effects of Er-Zhi-Wan on Microarchitecture and Regulation of Wnt/β-catenin Signaling Pathway in Alveolar Bone of Ovariectomized Rats 被引量:6
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作者 孙为 王远勤 +2 位作者 晏奇 卢锐 施斌 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2014年第1期114-119,共6页
Recent studies have shown that Er-Zhi-Wan(EZW), a traditional Chinese medicine consisting of Herba Ecliptae(HE) and Fructus Ligustri Lucidi(FLL), had a definite antiosteoporotic effect on osteoporotic femur, but... Recent studies have shown that Er-Zhi-Wan(EZW), a traditional Chinese medicine consisting of Herba Ecliptae(HE) and Fructus Ligustri Lucidi(FLL), had a definite antiosteoporotic effect on osteoporotic femur, but its effect on osteoporosis of alveolar bone remains unknown. In the present study, we investigated the effects of Er-Zhi-Wan(EZW) on the microarchitecture and the regulation of Wnt/β-catenin signaling pathway in the alveolar bone of ovariectomized rats. Thirty Sprague-Dawley rats were randomly divided into three groups: sham operation group(sham, n=10), ovariectomy(OVX) group(n=10), and OVX with EZW treatment group(EZW group, n=10). From one week after ovariectomy, EZW(100 mg/mL) or vehicle(distilled water) was fed(1 mL/100 g) once per day for 12 weeks until the sacrifice of the rats. The body weights were measured weekly. After sacrifice, the sera and mandible were collected and routinely prepared for the measurement of alveolar trabecular microarchitecture, serum levels of E2, bone-specific alkaline phosphatase(BALP) and tartrate-resistant acid phosphatase 5b(TRAP5b), as well as mandibular mRNA expression of Wnt/β-catenin signaling pathway molecules wnt3a, low-density lipoprotein receptor-related protein 5(LRP5), β-catenin and dickkopf homolog 1(DKK1). The results showed that EZW treatment significantly prevented the body weight gain, degradation of alveolar trabecular microarchitecture and alveolar bone loss in the OVX rats. Furthermore, we observed that EZW could increase the serum levels of E2 and BALP, and decrease levels of serum TRAP5b in EZW group compared with vehicle group. In addition, RT-PCR results revealed that EZW upregulated the expression levels of wnt3a, LRP5 and β-catenin, and reduced the expression of DKK1 in OVX rats. Taken together, our results suggested that EZW may have potential anti-osteoporotic effects on osteoporotic alveolar bone by stimulating Wnt/LRP5/β-catenin signaling pathway. 展开更多
关键词 OSTEOPOROSIS Er-Zhi-Wan alveolar bone wnt signaling pathway
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Involvement of the Wnt signaling pathway and cell apoptosis in the rat hippocampus following cerebral ischemia/reperfusion injury 被引量:2
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作者 Bin Liu Jing Tang +3 位作者 Shiying Li Yuqin Zhang Yan Li Xiaoliu Dong 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第1期70-75,共6页
We investigated the role of the Wnt signaling pathway in cerebral ischemia/reperfusion injury by examining β-catenin and glycogen synthase kinase-3β protein expression in the rat hippocampal CA1 region following acu... We investigated the role of the Wnt signaling pathway in cerebral ischemia/reperfusion injury by examining β-catenin and glycogen synthase kinase-3β protein expression in the rat hippocampal CA1 region following acute cerebral ischemia/reperfusion. Our results demonstrate that cell apoptosis increases in the CA1 region following ischemia/reperfusion. In addition, β-catenin and glycogen synthase kinase-3β protein expression gradually increases, peaking at 48 hours following reperfusion. Dickkopf-1 administration, after cerebral ischemia/reperfusion injury, results in decreased cell apoptosis, and β-catenin and glycogen synthase kinase-3β expression, in the CA1 region. This suggests that β-catenin and glycogen synthase kinase-3β, both components of the Wnt signaling pathway, participate in cell apoptosis following cerebral ischemia/reperfusion injury. 展开更多
关键词 neural regeneration brain injury Oickkopf-1 wnt signaling pathway cell apoptosis β-catenin glycogen synthase kinase-3β protein cerebral ischemia/reperfusion injury grant-supported paper NEUROREGENERATION
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Wnt-/-β-catenin pathway signaling in human hepatocellular carcinoma 被引量:9
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作者 Jaques Waisberg Gabriela Tognini Saba 《World Journal of Hepatology》 2015年第26期2631-2635,共5页
The molecular basis of the carcinogenesis of hepatocellular carcinoma(HCC) has not been adequately clarified, which negatively impacts the development of targeted therapy protocols for this overwhelming neoplasia. The... The molecular basis of the carcinogenesis of hepatocellular carcinoma(HCC) has not been adequately clarified, which negatively impacts the development of targeted therapy protocols for this overwhelming neoplasia. The aberrant activation of signaling in the HCC is primarily due to the deregulated expression of the components of the Wnt-/-β-catenin. This leads to the activation of β-catenin/T-cell factor-dependent target genes that control cell proliferation, cell cycle, apoptosis, and cell motility. The deregulation of the Wnt pathway is an early event in hepatocarcinogenesis. An aggressive phenotype was associated with HCC, since this pathway is implicated in the proliferation, migration, and invasiveness of cancer cells, regarding the cell's own survival. The disruption of the signaling cascade Wnt-/-β-catenin has shown anticancer properties in HCC's clinical evaluations of therapeutic molecules targeted for blocking the Wnt signaling pathway for the treatment of HCC, and it represents a promising perspective. The key to bringing this strategy in to clinical practice is to identify new molecules that would be effective only in tumor cells with aberrant signaling β-catenin. 展开更多
关键词 CARCINOMA HEPATOCELLULAR wnt signaling pathway Beta catenin wnt proteins RECEPTORS
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Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway 被引量:7
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作者 Kai Gao Yan-song Wang +5 位作者 Ya-jiang Yuan Zhang-hui Wan Tian-chen Yao Hai-hong Li Pei-fu Tang Xi-fan Mei 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第6期951-957,共7页
The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guid- ance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the... The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guid- ance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord iniury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, caspase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental fndings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury. 展开更多
关键词 nerve regeneration spinal cord injury RAPAMYCIN wnt/β-catenin signaling pathway apoptosis CASPASE-3 brain-derived neurotrophic factor NEUROPROTECTION loss of neurons NSFC grants neural regeneration
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MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells 被引量:8
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作者 Fu-Bing Yu Juan Sheng +3 位作者 Jia-Man Yu Jing-Hua Liu Xiang-Xin Qin Bo Mou 《World Journal of Gastroenterology》 SCIE CAS 2020年第6期627-644,共18页
BACKGROUND Colorectal cancer(CRC)is one of the most common malignancies worldwide.AIM To explore the expression of microRNA miR-19a-3p and Forkhead box F2(FOXF2)in patients with CRC and the relevant mechanisms.METHODS... BACKGROUND Colorectal cancer(CRC)is one of the most common malignancies worldwide.AIM To explore the expression of microRNA miR-19a-3p and Forkhead box F2(FOXF2)in patients with CRC and the relevant mechanisms.METHODS Sixty-two CRC patients admitted to the hospital were enrolled into the study group,and sixty healthy people from the same period were assigned to the control group.Elbow venous blood was sampled from the patients and healthy individuals,and blood serum was saved for later analysis.MiR-19a-3p mimics,miR-19a-3p inhibitor,miR-negative control,small interfering-FOXF2,and short hairpin-FOXF2 were transfected into HT29 and HCT116 cells.Then quantitative polymerase chain reaction was performed to quantify the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells,and western blot(WB)analysis was conducted to evaluate the levels of FOXF2,glycogen synthase kinase 3 beta(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),β-catenin,p-β-catenin,α-catenin,Ncadherin,E-cadherin,and vimentin.The MTT,Transwell,and wound healing assays were applied to analyze cell proliferation,invasion,and migration,respectively,and the dual luciferase reporter assay was used to determine the correlation of miR-19a-3p with FOXF2.RESULTS The patients showed high serum levels of miR-19a-3p and low levels of FOXF2,and the area under the curves of miR-19a-3p and FOXF2 were larger than 0.8.MiR-19a-3p and FOXF2 were related to sex,tumor size,age,tumor-nodemetastasis staging,lymph node metastasis,and differentiation of CRC patients.Silencing of miR-19a-3p and overexpression of FOXF2 suppressed the epithelialmesenchymal transition,invasion,migration,and proliferation of cells.WB analysis revealed that silencing of miR-19a-3p and FOXF2 overexpression significantly suppressed the expression of p-GSK-3β,β-catenin,N-cadherin,and vimentin;and increased the levels of GSK-3β,p-β-catenin,α-catenin,and Ecadherin.The dual luciferase reporter assay confirmed that there was a targeted correlation of miR-19a-3p with FOXF2.In addition,a rescue experiment revealed that there were no differences in cell proliferation,invasion,and migration in HT29 and HCT116 cells co-transfected with miR-19a-3p-mimics+sh-FOXF2 and miR-19a-3p-inhibitor+si-FOXF2 compared to the miR-negative control group.CONCLUSION Inhibiting miR-19a-3p expression can upregulate the FOXF2-mediated Wnt/β-catenin signaling pathway,thereby affecting the epithelial-mesenchymal transition,proliferation,invasion,and migration of cells.Thus,miR-19a-3p is likely to be a therapeutic target in CRC. 展开更多
关键词 MiR-19a-3p Forkhead box F2 wnt/β-catenin signaling pathway Biological function Colorectal cancer Western blot
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Expression analysis of eight amphioxus genes involved in the Wnt/β-catenin signaling pathway 被引量:1
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作者 Jing WANG Guang LI +2 位作者 Guang-Hui QIAN Jun-Hao HUA Yi-Quan WANG 《Zoological Research》 CAS CSCD 2016年第3期136-143,共8页
The Wnt/β-catenin signaling pathway plays a crucial role in the embryonic development of metazoans. Although the pathway has been studied extensively in many model animals, its function in amphioxus, the most primiti... The Wnt/β-catenin signaling pathway plays a crucial role in the embryonic development of metazoans. Although the pathway has been studied extensively in many model animals, its function in amphioxus, the most primitive chordate, remains largely uncharacterized. To obtain basic data for functional analysis, we identified and isolated seven genes (Lrp5/6, Dvl, APC, Ckla, CklS, Gsk3β, and Gro) of the Wnt/β-catenin signaling pathway from the amphioxus (Branchiostoma floridae) genome. Phylogenetic analysis revealed that amphioxus had fewer members of each gene family than that found in vertebrates. Whole-mount in situ hybridization showed that the genes were maternally expressed and broadly distributed throughout the whole embryo at the cleavage and blastula stages. Among them, Dvl was expressed asymmetrically towards the animal pole, while the others were evenly distributed in all blastomeres. At the mid-gastrula stage, the genes were specifically expressed in the primitive endomesoderm, but displayed different patterns. When the embryo developed into the neurula stage, the gene expressions were mainly detected in either paraxial somites or the tail bud. With the development of the embryo, the expression levels further decreased gradually and remained only in some pharyngeal regions or the tail bud at the larva stage. Our results suggest that the Wnt/β-catenin pathway might be involved in amphioxus somite formation and posterior growth, but not in endomesoderm specification. 展开更多
关键词 wnt/β-catenin signaling pathway GENEEXPRESSION AMPHIOXUS Whole-mount in situ hybri-dization EMBRYO
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