International Journal of Stem Cells
·
2021
·
IF 2.5
Qiong Li,Lei Huang
Background and Objectives MiR-148a-3p has been reported to regulate the differentiation of marrow stromal cell osteoblast. In this study, whether miR-148a-3p regulated the odontoblastic differentiation of human dental pulp stem cells (hDPSCs) or not was explored. Methods and Results The hDPSCs were isolated and identified via flow cytometry. Targets of miR-148a-3p were identified via bioinformatics and dual-luciferase reporter assay. After the cell was cultured in the odontogenic differentiation medium or infected, cell viability, invasion, and odontoblastic differentiation were detected via MTT, transwell, and Alizarin Red S staining, respectively. The miR-148a-3p, Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions were determined by RT-qPCR and Western blot. The hDPSCs odontoblastic differentiation downregulated the miR-148a-3p expression and upregulated Wnt1 expression. Wnt1 was determined as the target for miR-148a-3p. MiR-148a-3p mimic and siWnt1 suppressed the cell viability, invasion, and odontoblastic differentiation of hDPSCs and inhibited the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. In contrast, miR-148a-3p inhibitor and overexpressed Wnt1 promoted the cell viability, invasion, and odontoblastic differentiation of hDPSCs, and upregulated the Wnt1, β-catenin, DSPP, DMP-1, RUNX2, OCN, and Smad4 expressions. Also, miR-148a-3p mimic and inhibitor reversed the effects of Wnt1 overexpression and siWnt1. Conclusions MiR-148a-3p modulated the invasion and odontoblastic differentiation of hDPSCs through the Wnt1/β-catenin pathway.
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高影响因子
CANCER GENE THERAPY
·
2022
·Vol. 30
·期 2
·335-344
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IF 5.854
Liu Jian,Mai Yumiao,Wang Yingjie,Chen Zhiwei,Wang Fei,Wei Huixia,Yao Qianghua
RAB3D, a small Ras-like GTPase involved in regulating secretory pathway, plays a cancer-promoting role in several solid tumors. However, its role in leukemogenesis remains unknown yet. Acute myeloid leukemia (AML) is a common acute leukemia with a high mortality. Here, we found the higher expression of RAB3D in bone marrow mononuclear cells derived from AML patients ( n = 54) versus healthy participants ( n = 20). The following loss- and gain-of-function experiments demonstrated that RAB3D promoted growth, enhanced colony formation and accelerated G1/S transition of U937, THP-1 and KG-1 AML cells. RAB3D silencing inhibited tumorigenesis of AML cells in vivo and delayed AML cells-induced death of mice. Interestingly, the expression of RAB3D is positively correlated with that of an oncogene mouse double minute 2 (MDM2) in bone marrow mononuclear cells of AML patients ( r = 0.923, p < 0.001). Intracellular MDM2 was conjugated with more ubiquitins and degraded faster when RAB3D was silenced. A commonly therapeutic target of AML, β-catenin signaling, was activated by RAB3D overexpression, but deactivated after MDM2 was silenced. The RAB3D-induced proliferation acceleration and β-catenin activation were abolished by MDM2 knockdown, implying that RAB3D function by stabilizing MDM2. In addition, c-MYC, a β-catenin downstream effector, was recruited directly to the RAB3D gene promoter (-360/-349 and -136/-125 sites) and induced its transcription. Collectively, this study demonstrates that RAB3D may exacerbate the malignant behaviors of AML cells through forming a positive feedback loop with MDM2/β-catenin/c-MYC signaling. RAB3D might be a novel target of clinical AML treatment.
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Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-15
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IF 5.116
Shen Ying-Shan,Chen Xiao-Jun,Wuri Sha-Na,Yang Fan,Pang Feng-Xiang,Xu Liang-Liang,He Wei,Wei Qiu-Shi
Objectives Polydatin (PD), extracted from Polygonum cuspidatum , has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/β-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis. Materials and methods hBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA. Results In vitro, 30 μM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2 , Osteopontin , DLX5 , β-catenin , TAZ , and Osteocalcin ( OCN ). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/β-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model. Conclusion Taken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/β-catenin pathway.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhong-hao Zhang,Ying-hong Pei,Zhi-hao Duan,Tao Gao,Shi-ling Feng,Zi-zhong Tang,Yang-er Chen,Sheng-lin Hu,Shu Yuan,Wei Wang,Xiao-rong Yan,Ya-ying Pu,Ming Yuan
Alzheimer's disease (AD) is prevalent in the elderly, with amyloid-β (Aβ) playing a critical role in its progression. Polysaccharides have garnered increasing attention due to their low toxicity and diverse applications in alleviating AD-like symptoms. However, the potential of ginger leaf polysaccharide in mitigating AD-like symptoms has been rarely investigated. In this study, we isolated a polysaccharide (GLP1) from ginger leaf and evaluated its efficacy and underlying mechanisms in alleviating AD-like symptoms using Caenorhabditis elegans and PC12 cells. GLP1 ameliorated AD-like symptoms in C. elegans , as evidenced by a 41.50 % increase in head thrashing frequency and an 87.13 % increase in body bending frequency. Furthermore, GLP1 mitigated cognitive decline by 76.51 %. Additionally, GLP1 enhanced the activity of acetylcholinesterase in C. elegans and maintained the integrity of neural system function. Moreover, GLP1 improved the survival rate of PC12 cells under Aβ induction by activating the Wnt/β-catenin pathway, which also resulted in a reduction in the release of inflammatory factors, specifically IL-1β by 21.15 %, IL-6 by 39.98 %, and TNF-α by 19.66 %. Notably, FITC-labeled GLP1 could be absorbed by PC12 cells. These compelling findings underscored the therapeutic potential of GLP1 in alleviating Aβ-induced AD-like symptoms and supported the advancement of ginger leaf resource utilization.
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npj Science of Food
·
2025
·Vol. 9
·期 1
·1-9
·
IF 7.8
Ye Xiang,Chen Wen,Yan Fujie,Zheng Xiaodong,Tu Pengcheng
In late-stage type 2 diabetes mellitus (T2DM), impaired islet β cell function leads to absolute insulin deficiency, thereby disrupting blood glucose homeostasis. GLP-1, an incretin hormone, stimulates insulin secretion from islet β cells post-meals. This study investigated the effects of anthocyanin cyanidin-3-O-glucoside (C3G) on GLP-1 secretion using STC-1 (intestinal endocrine L cells) and NIT-1 (islet β cells). In a co-culture system, C3G treatment increased GLP-1 secretion in STC-1 cells, promoting insulin release in NIT-1 cells under high glucose. Mechanistically, C3G activated the PPARβ/δ-β-catenin-TCF-4 pathway in STC-1 cells, enhancing PG precursor transcription and GLP-1 synthesis.Inhibiting PPARβ/δ with GSK0660 blocked this C3G-induced upregulation. Overall, C3G stimulates GLP-1 secretion from intestinal L cells via this pathway, indirectly boosting insulin release from β cells. These findings enhance T2DM mechanism understanding and suggest the potential of C3G in GLP-1-based T2DM therapy.
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JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
·
2020
·
IF 1.466
Zhibing Qiu,Wen Chen,Yafeng Liu,Ben Jiang,Li Yin,Xin Chen
Down-regulated lncRNA AC061961.2 in dilated cardiomyopathy (DCM) patients was previous reported. Whether AC061961.2 has regulatory effect on DCM still need exploration. Here, we tried to investigate the effect of AC061961.2 on DCM. After DCM model rat was established through injecting Adriamycin, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) were measured by echocardiography. Histopathological changes and apoptosis were detected by hematoxylin-eosin, Masson staining, and TUNEL. After cardiomyocytes were isolated and identified by immunofluorescence, DCM cell model was established by injecting adriamycin. After transfected with overexpressed-AC061961.2 plasmids, cell apoptosis was detected by flow cytometry. The expressions of AC061961.2, β-catenin, Axin2, c-Myc, CRP78, CHOP, Caspase-3, Bcl-2, and Bax in cardiomyocytes and heart tissues were detected by RT-qPCR or western blot. LVEDD and LVESD were increased while LVEF and LVFS were decreased in DCM rats. The histopathological of heart tissues showed a typical sign of DCM. Apoptosis were increased in heart tissues of DCM rats. In DCM rats, the expressions of AC061961.2, β-catenin, Axin2, c-Myc, and Bcl-2 were decreased, the expressions of CRP78, CHOP, Caspase-3, and Bax were increased. After the overexpression of AC061961.2, levels of β-catenin, Axin2, c-Myc, and Bcl-2 were increased, while levels of CRP78, CHOP, Caspase-3, and Bax were decreased, compared with that in DCM cardiomyocytes. LncRNA AC061961.2 overexpression inhibited endoplasmic reticulum stress induced apoptosis in DCM rats and cardiomyocytes via activating Wnt/β-catenin pathway.
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Food Bioscience
·
2025
·
IF 5.9
Yutong Ma,Jiaxi Li,Shuyu Liu,Wenlong Yu,Yaxin Sang,Xianghong Wang
Sulforaphane (SFN), a bioactive compound derived from cruciferous vegetables, exhibits chemopreventive properties agains various malignancies. Colitis-associated colorectal cancer (CAC) is a malignancy that develops through chronic inflammation-driven carcinogenesis in patients with long-standing inflammatory bowel disease. This study demonstrates a novel mechanism by which SFN protects against CAC through the simultaneous regulation of the Wnt/β-catenin signaling pathway and gut microbiota. Using an azoxymethane(AOM)/dextran sulfate salt sodium(DSS)-induced CAC mouse model to systematically evaluate SFN's therapeutic potential. Comprehensive assessments included histopathological examination, molecular analysis of inflammatory cytokines and proliferation markers, 16S rDNA sequencing for gut microbiota characterization, short-chain fatty acid (SCFA) profiling, and mechanistic investigation of Wnt/β-catenin pathway components. The experimental results showed that SFN intervention significantly alleviated clinical symptoms in mice, reduced inflammatory cytokine levels (IFN-γ, interferon-gamma; IHC, immune histochemical; IL-17, interleukin-17; IL-6, interleukin-6; MPO, myeloperoxidase) and suppressed proliferation markers (PCNA, proliferating cell nuclear antigen, antigen identified by monoclonal antibody Ki-67, Ki-67). Notably, SFN administration significantly restored the levels of major SCFAs, including acetate, propionate, and butyrate, which were markedly reduced in CAC mice. Mechanistically, SFN inhibited the Wnt/β-catenin signaling pathway by down-regulating the expression of β-catenin, cyclin D1 and c-myc expression. Concurrently, SFN restored gut microbial diversity, increased beneficial bacteria, and reduced pathogenic genera. The observed increase in SCFAs levels was correlated with these microbial improvements, and orrelation analysis further linked these microbial shifts to clinical improvements. Our findings reveal that SFN mitigates CAC progression by coordinated modulation of both Wnt/β-catenin signaling and gut microbiota, with the restoration of SCFAs production representing a key functional outcome, highlighting its potential as a multi-target dietary intervention for colorectal cancer prevention.
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高影响因子
BIOFACTORS
·
2019
·Vol. 45
·期 6
·950-958
·
IF 3.598
Haihua Zhang,Qiumei Shi,Weixiao Nan,Yaqi Wang,Shiyong Wang,Fuhe Yang,Guangyu Li
The regeneration of proliferation potential of dermal papilla (DP) cells contributes to the treatment of hair loss disorders. Ginkgolide B (GKB) and bilobalide (BB) are two functional components isolated from Ginkgo biloba that can promote hair growth. In the current study, the effect of GKB or BB on DP cell viability and the related signaling was assessed. Hair follicles were isolated from minks, and the growth of hair follicles was measured under the administration of GKB or BB. DP cells isolated from minks were also subjected to GKB or BB. The administration of GKB or BB induced the growth of hair follicles. The viability of DP cells was also increased by GKB or BB as illustrated by methyl thiazolyl tetrazolium and flow cytometry detection. Moreover, the secretion of VEGF was enhanced by GKB or BB. At molecular level, the activities of Akt, ERK1/2, and β-catenin were induced by GKB, whereas BB only increased the activities of Akt and β-catenin. In conclusion, although the two components influenced the β-catenin signaling activity in distinct mechanisms, they both increased the viability of DP cells and promoted the cycle of hair follicles.
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PHYTOMEDICINE
·
2026
·
IF 11.3
Yeqiu Xu,Junrui Jonathan Hai,Duan Sun,Yihan Yang,Chen Wang,Xinan Zhang,Huanli Xu,Yajin Liao,Xianjun Qu,Bo Han,Weishi Liang,Yong Hai
Background Distractive spinal cord injury (DSCI) is a severe complication of spinal deformity correction surgery, causing early disruption of the blood–spinal cord barrier (BSCB). However, the molecular mechanisms that translate mechanical stress into vascular endothelial dysfunction remain unclear, and effective pharmacological strategies targeting this process are lacking. Purpose This study aimed to investigate the therapeutic effects of sodium rutin (NaR), a water-soluble derivative of rutin, on BSCB disruption following DSCI, and to elucidate the underlying molecular mechanisms. Methods In vivo rat DSCI models and in vitro mechanical distraction models of spinal cord microvascular endothelial cells were employed. The therapeutic effects of oral NaR administration on locomotor function and BSCB permeability in rats following DSCI were systematically evaluated. Mechanistic investigations targeting the SIRT1/β-catenin axis and oxidative stress were conducted utilizing RNA sequencing, interventions with small interfering RNA and SIRT1 inhibitors, alongside standard molecular biology techniques. Results NaR treatment dose-dependently improved locomotor recovery in DSCI rats and significantly reduced BSCB permeability by restoring the expression of tight junction proteins. Mechanical distraction caused a significant downregulation of SIRT1 in endothelial cells. NaR treatment upregulated SIRT1 expression and promoted its nuclear-to-cytoplasmic translocation. This upregulation of SIRT1 was associated with significant inhibition of mitochondrial oxidative stress. Furthermore, oxidative stress was found to promote β-catenin phosphorylation and subsequent degradation via the ubiquitin-proteasome pathway. NaR stabilized β-catenin through SIRT1-mediated antioxidant effects, promoting its nuclear translocation and the downstream expression of tight junction genes. Consequently, by repairing the BSCB, NaR restricted the infiltration of immune cells (CD68 + macrophages/microglia and MPO + neutrophils) into the spinal parenchyma, thereby attenuating secondary neuroinflammation. Conclusion The SIRT1/β-catenin axis may serve as a critical mechanotransduction pathway regulating BSCB integrity. NaR protects the BSCB after DSCI by restoring SIRT1 activity, suppressing oxidative stress, and stabilizing β-catenin signaling. NaR may be a promising pharmacological strategy for the treatment of DSCI. In brief: Hai et al. identify a mechanism by which mechanical distraction disrupts the blood-spinal cord barrier through suppression of SIRT1 and oxidative destabilization of β-catenin. Oral sodium rutin restores barrier integrity, limits inflammation, and thus improves locomotor recovery, highlighting a vascular-targeted therapeutic strategy for distraction-induced spinal cord injury Download: Download high-res image (296KB) Download: Download full-size image
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Bioengineering & Translational Medicine
·
2026
·
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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TISSUE & CELL
·
2022
·
IF 2.586
Yuan Xu,Jian He,Jun He
Purpose The treatment of intervertebral disc degeneration is limited, cyanidin can protect chondrocytes from degeneration. This research investigated the effect of cyanidin on human nucleus pulposus cells (HNPC) metabolism and its mechanism. Methods HNPC were treated with cyanidin, XAV-939 (inhibitor of Wnt/β-catenin signaling) and SKL2001 (activator of Wnt/β-catenin signaling), and pressurized at 1, 3, and 30 atm. Quantitative real-time PCR and Western blot were used to assess the expressions of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), Collagen-II, Aggrecan , Wnt-3a and β-catenin in treated HNPC. Cell counting kit-8 was used to detect the HNPC cell viability . Radioisotope incorporation method was used to assess the proteoglycan synthesis rate of HNPC. The level of cell matrix was detected by toluidine blue staining. Results Proper hydrostatic pressure of 3 atm could elevate cell viability, proteoglycan synthesis and the level of cell matrix of HNPC, while high hydrostatic pressure of 30 atm reduced the above effects. Cyanidin and XAV-939 reversed the promoting effect of 30 atm pressure on Wnt/β-catenin signaling pathway and the inhibiting effect on cell viability, proteoglycan synthesis and the level of cell matrix. Subsequently, SKL2001 further reversed the function of cyanidin on HNPC. Conclusion Cyanidin attenuated the high hydrostatic pressure-induced degradation of cellular matrix of HNPC via blocking the Wnt/β-catenin signaling pathway. Our findings in this research provided a basis for in vitro experiment of cyanidin and a theoretical fundament on this disease.
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Drug Design Development and Therapy
·
2022
·
IF 4.319
Shanshan Jia,Pin Guo,Junhua Lu,Xujun Huang,Laming Deng,Yan Jin,Lanyan Zhao,Xiaofang Fan
Background Curcumol exhibits anti-inflammatory effect, but its effect on chronic asthma lacked research. Therefore, this study explored the role of curcumol in asthma.Methods A chronic asthmatic mice model was established by ovalbumin induction. After treatment with curcumol, airway resistance in mice was detected by forced oscillation technique. The histopathological features of airway tissues, pulmonary inflammation, and inflammation cell recruitment in the bronchoalveolar lavage fluid (BALF) of mice were detected by hematoxylin-eosin staining. Collagen deposition in the airways of mice was examined by Masson staining. The secretion of ovalbumin-IgE, IL-4, IL-5, IL-13 in mouse serum and VEGFA secretion in BALF were analyzed by ELISA. Finally, the expressions of β-catenin, Wnt5a, VEGFA, TGF-β1, Fibronectin, and MMP-9 in mice lung tissues were determined by Western blot or immunohistochemical.Results Curcumol attenuated airway hyperresponsiveness, airway remodeling, and pulmonary inflammation in chronic asthmatic mice. Curcumol relieved collagen deposition in airway tissues, inflammation cell recruitment in BALF, and reduced the up-regulation of serum ovalbumin-IgE, IL-4, IL-5, and IL-13 and BALF VEGFA in chronic asthmatic mice. In addition, curcumol attenuated the up-regulated expressions of β-catenin, Wnt5a, VEGFA, TGF-β1, Fibronectin, and MMP-9 in the lung tissues of chronic asthmatic mice, but curcumol treatment did not show such effects on healthy mice.Conclusion Our findings revealed that curcumol could ameliorate lung inflammation and airway remodeling by inhibiting the abnormal activation of the Wnt/β-catenin pathway in chronic asthmatic mice, indicating that curcumol could be used as a novel anti-asthma drug for basic and clinical research.
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