ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Lihua Feng,Yuanyuan Lang,Leke Sun,Weihong Shi,Xiangxiang Chen,Yanan Xia,Hengyi Xu,Yang Liu
Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in children’s daily necessities and foods, and their health hazards to children have attracted particular attention. Childhood is a critical time for accelerated bone growth and development. Current studies revealed that TiO 2 NPs exposure causes bone damage in juvenile rats; however, the underlying mechanism is unknown. Ghrelin is a polypeptide hormone that is considered to be a candidate factor for regulating bone growth and development. In this research, 3-week-old juvenile male rats were administered 0, 100 or 200 mg/kg TiO 2 NPs and 50 μg/kg ghrelin for 4 weeks to explore the underlying mechanism of TiO 2 NPs-induced bone damage, and the protective effect of ghrelin. Our results revealed that TiO 2 NPs resulted in decreased synthesis of bone growth-related hormones, disturbed bone metabolism, and destruction of bone structure. Further mechanism studies showed that TiO 2 NPs inhibited Wnt/β-catenin pathway, reduced collagen synthesis, inhibited chondrocyte proliferation and differentiation, promoted chondrocyte apoptosis, and inhibited endochondral osteogenesis, ultimately leading to long bone longitudinal growth retardation and osteoporosis. Ghrelin alleviated the negative effects of TiO 2 NPs-induced bone growth in juvenile rats by upregulating the Wnt/β-catenin signaling pathway. This study provided a reference for the clinical treatment of growth retardation and idiopathic short stature in juvenile children caused by environmental pollutants.
研究领域:
毒理学
·
内分泌学
·
儿科
·
骨骼生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2023
·Vol. 29
·期 1
·1-18
·
IF 5.7
Ye Binglu,Yuan Yawei,Liu Rui,Zhou Haitao,Li Yujie,Sheng Zhihao,Li Tianyu,Zhang Bing,Xu Zhendong,Li Yang,Liu Zhiqiang
Background Postpartum depression (PPD) is a prevalent mental disorder that negatively impacts mothers and infants. The mechanisms of vulnerability to affective illness in the postpartum period remain largely unknown. Drastic fluctuations in reproductive hormones during the perinatal period generally account for triggering PPD. However, the molecular mechanism underlying the PPD-like behaviors induced by the fluctuations in hormones has rarely been reported.Methods We utilized hormones-simulated pseudopregnancy (HSP) and hormones-simulated postpartum period (HSPP) rat models to determine how drastic fluctuations in hormone levels affect adult neurotransmission and contribute to depressive-like behaviors. The electrophysiological response of CA1 pyramidal neurons was evaluated by whole-cell patch clamping to identify the hormone-induced modulations of neurotransmission. The statistical significance of differences was assessed with One-way ANOVA and t-test (p < 0.05 was considered significant).Results Reproductive hormones withdrawal induced depressive-like behaviors and disturbed the balance of excitatory and inhibitory transmission in the pyramidal neurons in the hippocampus. Molecular analyses revealed that the blunted Wnt signaling might be responsible for the deficits of synaptic transmission and behaviors. Activation of Wnt signaling increased excitatory and inhibitory synaptic transmission in the hippocampus. Reactivation of Wnt signaling alleviated the anhedonic behaviors and abnormal synaptic transmission.Conclusion sRestoring Wnt signaling in the hormones-simulated postpartum period rat models remediated depression-related anhedonia symptoms and rebalanced the excitation/inhibition ratio by collectively enhancing the plasticity of GABAergic and glutamatergic synapses. The investigations carried out in this research might provide an alternative and prospective treatment strategy for PPD.
研究领域:
神经科学
·
分子生物学
·
精神病学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-15
·
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.
研究领域:
药理学
·
干细胞生物学
·
骨骼生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ARCHIVES OF ORAL BIOLOGY
·
2020
·
IF 1.931
Ying Bian,Juan Xiang
Background Osteogenic differentiation of human periodontal ligament cells (hPDLCs) is crucial for regenerate periodontal tissues. In this study, we investigated the function of salvianolic acid B (Sal B) in osteogenesis of hPDLCs. Methods HPDLCs were isolated from healthy third molar roots. HPDLCs at passage 3 were identified by morphological observation and immunohistochemistry of vimentin . The viability of hPDLCs incubated with Sal B at concentrations of 0μM, 0.1μM, 0.5μM, 1μM and 5μM were measured by CCK-8 assay. To evaluate the effect of Sal B on osteogenic differentiation of hPDLCs, the alkaline phosphatase (ALP) activity, osteogenic differentiation markers, and mineralized nodules were determined by ALP kit, qRT-PCR and alizarin red S staining, respectively. To confirm the function of Sal B in hPDLCs involved in Wnt/β-catenin signaling pathway , hPDLCs were incubated with Sal B or co-incubated with Sal B and DKK-1 (a inhibitor of Wnt/β-catenin). The levels of Wnt/β-catenin signaling pathway and osteogenic differentiation-associated indicators were then determined. Results HPDLCs showed a typical fibroblast-like and spindle-shaped, with vimentin-positive. The viability of hPDLCs had no obvious change with stimulation of Sal B at various doses. Sal B promoted the increase of ALP activity, osteogenic differentiation markers levels, mineralized nodules and activation of Wnt/β-catenin signaling pathway, and DKK-1 could block those effects of Sal B on hPDLCs. Conclusion Sal B promoted osteogenesis of hPDLCs through Wnt/β-catenin signaling pathway, which providing a potential drug for periodontitis treatment .
研究领域:
牙科学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yue Xiong,Chao He,Xun Lin,Ke Cheng,Fumei He,Jingxin Zhao,Mengjie Yang,Hong Gao,Fangjie He,Xiaopei Zhang,Zeqi Liu,Gan Liu,Wenbin Deng
Black phosphorus nanosheet (BPNS) has recently demonstrated intrinsic anti-tumor bioactivity, but its underlying molecular mechanism remains unclear, limiting its potential applications in biomedicine. In this study, we investigated the impact of BPNS on glioblastoma cells and observed a significant dose-dependent inhibition of invasion and migration. RNA sequencing analysis revealed downregulation of genes associated with the WNT/β-catenin and NOTCH signaling pathways, both linked to invasion and migration. Mechanistically, BPNS directly binds to CSNK2A2, reducing its kinase activity, which indirectly enhances GSK-3β kinase activity. As a result, GSK-3β increases the phosphorylation level of β-catenin, leading to its degradation and subsequent inhibition of downstream molecules in the WNT/β-catenin signaling pathway. Our study uncovers the inherent biological activity of BPNS in hindering glioblastoma invasion and migration and sheds light on the molecular mechanisms, offering new directions for the nanomaterial’s biomedical applications.
研究领域:
生物医学工程
·
癌症生物学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Journal of Advanced Research
·
2022
·
IF 12.822
Weiwei Tao,Jie Ruan,Ruyan Wu,Min Zhao,Tong Zhao,Mingming Qi,Sonata S.Y. Yau,Guangda Yao,Hongru Zhang,Yue Hu,Gang Chen
Introduction Adult hippocampal neurogenesis (AHN) is acknowledged to play a critical role in depression. Emerging evidence suggests that the Wnt/β-catenin pathway can modulate hippocampal neurogenesis. Crocin, a natural carotenoid, possesses antidepressant property. Yet, how it affects neurogenesis and exerts antidepressant response remains unknown. Objective To explore the role of AHN and Wnt/β-catenin in the antidepressant action of crocin. Methods Depressive-related behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and sexual behaviors were performed following crocin treatment. Neurogenesis was characterized via immunohistochemistry, immunofluorescence, Golgi staining and electrophysiology approach. Wnt/β-catenin signaling was examined with western blot analysis. The role of AHN Wnt/β-catenin cascade in crocin’s antidepressant response was assessed by conditional removal of glial fibrillary acidic protein (GFAP)-expressing newborn neural cells, temozolomide administration, microinfusion of Dkk1 or viral-mediated shRNA of Wnt3a. Results Crocin decreased the immobility duration in TST and FST without impairing the performance in sexual behaviors. Crocin boosted the proliferation and differentiation of progenitors, and promoted dendritic maturation and functional integration of hippocampal newborn neurons. Conditional removal of GFAP-expressing neural cells or temozolomide administration impaired the antidepressant response of crocin. Additionally, Wnt/β-catenin signaling was promoted following crocin treatment. In chronic unpredictable mild stress (CUMS) murine model, crocin treatment displayed antidepressant response in SPT, FST and TST, and restored the neurogenesis levels and Wnt/β-catenin signaling impaired by CUMS. Infusion of Dickkopf-1 (DKK1) or knockdown of Wnt3a in the hippocampus impaired the antidepressant response of crocin. Conclusion Crocin exerted antidepressant response, which was dependent on enhancement of AHN and activation of the Wnt/β-catenin pathway.
研究领域:
神经科学
·
药理学
·
分子生物学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Menglong Zhao,Danqing Wu,Weiqian Qiu,Hongchen Zhang,Min Chen,Haixia Zhou,Xiaoxia Ye,Zhong Han,Xiangchao Shi
4-anilinoquinazoline scaffold, a key structure in the development of EGFR-TKI anticancer drugs such as Gefitinib and Erlotinib, continues to drive advancements in non-small cell lung cancer (NSCLC) therapy. In this study, we synthesized a series of novel derivatives ( B3–B11 ). Structure-activity relationship (SAR) analysis revealed that electron-donating groups para-substituted at the 4-anilino position significantly enhanced antiproliferative activity. Notably, B10 incorporating an acrylamide group at the 4-anilino position demonstrated the most potent activity against NSCLC, with an IC 50 of 1.28 μM in A549 cells, nearly six times more effective than Gefitinib (7.81 μM). Acute toxicity studies confirmed that B10 is safe at doses below 50 mg/kg. In vivo studies using an A549 xenograft model showed a 46 % tumor growth inhibition (TGI) with B10 (25 mg/kg), surpassing the 21 % inhibition of Gefitinib at the same dose. Mechanistic studies revealed that B10 inhibited the AKT/GSK-3β/β-catenin signaling pathway, downregulating Wnt target genes (c-Myc, c-Jun), and reduced COX2 expression and IL-8 levels, showcasing its dual anti-inflammatory and antitumor effects. These results position B10 as a promising NSCLC therapeutic candidate, combining potent efficacy with a favorable safety profile, and enhance our understanding of the SAR and mechanism of action of 4-anilinoquinazoline derivatives.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Xuepeng Wang,Chunchun Zou,Changju Hou,Zhenyu Bian,Wu Jiang,Maoqiang Li,Liulong Zhu
Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have emerged as promising tools for promoting bone regeneration. This study investigates the functions of EVs derived from bone marrow-derived MSCs (BMSCs) in osteoporosis (OP) and the molecular mechanism. EVs were isolated from primary BMSCs in mice. A mouse model with OP was induced by ovariectomy. Treatment with EVs restored bone mass and strength, attenuated trabecular bone loss and cartilage damage, and increased osteogenesis while suppressing osteoclastogenesis in ovariectomized mice. In vitro , the EVs treatment improved the osteogenic differentiation of MC-3T3 while inhibiting osteoclastic differentiation of RAW264.7 cells. Microarray analysis revealed a significant upregulation of ubiquitin specific peptidase 7 (USP7) expression in mouse bone tissues following EV treatment. USP7 was found to interact with Yes1 associated transcriptional regulator (YAP1) and stabilize YAP1 protein through deubiquitination modification. YAP1-related genes were enriched in the Wnt/β-catenin signaling, and overexpression of YAP1 promoted the nuclear translocation of β-catenin. Functional experiments underscored the critical role of maintaining USP7, YAP1, and β-catenin levels in the pro-osteogenic and anti-osteoclastogenic properties of the BMSC-EVs. In conclusion, this study demonstrates that USP7, delivered by BMSC-derived EVs, stabilizes YAP1 protein, thereby ameliorating bone formation in OP through the Wnt/β-catenin activation.
研究领域:
干细胞生物学
·
骨生物学
·
分子生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2023
·Vol. 28
·期 3
·1-14
·
IF 3.4
Gui-Bo Liu,Yong-Xia Cheng,Hua-Min Li,Yong Liu,Li-Xin Sun,Qi Wu,Shang-Fu Guo,Ting-Ting Li,Chuan-Ling Dong,Ge Sun
Adipose tissue‑derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric‑secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription‑quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and β‑catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration‑dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α‑myosin heavy chain (α‑MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased β‑catenin accumulation in nucleus and decreased the protein expression of secreted frizzled‑related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation‑associated terms and Wnt pathways. Dead‑box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac‑specific markers and β‑catenin and enhanced the fluorescence intensity of α‑MHC and β‑catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin‑enhanced protein levels of cardiac‑specific markers and the fluorescence intensity of α‑MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17‑mediated regulation of the SFRP4/Wnt/β‑catenin axis.
研究领域:
干细胞生物学
·
心血管研究
·
分子生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Yiming Ren,Liang Li
Probiotics have numerous biological functions and clinical studies have reported that consuming probiotic foods could promote hair growth and hair follicle health. Bifidobacterium longum BB536 was selected to investigate the possibility of treating hair loss with Cell-Free Supernatant (CFS) of B. longum BB536 and the alleviation mechanism of CFS on dihydrotestosterone (DHT)-damaged human dermal papilla cells (HDPCs). The results showed that HDPCs treated with 10% CFS of B. longum BB536 for 24 h could significantly promote cell proliferation, repair cell damage, accelerate the process of cell cycle and increase the secretion of VEGF. The CFS of B. longum BB536 reduced the apoptosis rate of DHT-damaged HDPCs. In addition, it could reduce the level of pro-inflammatory factors and improve the alkaline phosphatase (ALP) activity. Metabolites of B. longum BB536 may increase the protein expression of Wnt10b, β-catenin and LEF-1 by activating Wnt/β-catenin signaling pathway and inhibit the expression of DHT-induced negative feedback factors DKK1 and GSK-3β, which alleviates the damage of DHT on HDPCs, some protein expression levels such as LEF-1 are close to minoxidil (common drugs for hair loss). So, metabolites of B. longum BB536 can be used as new treatment for hair loss due to its safety. This study provides theoretical basis for probiotics to prevent androgenic alopecia.
研究领域:
微生物学
·
细胞生物学
·
药理学
·
皮肤病学
✓ 已验证
产品关联
DOI
高影响因子
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.
研究领域:
神经科学
·
药理学
·
分子生物学
·
老年医学
✓ 已验证
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Zongting Shi,Jun He,Jian He,Yuan Xu
Hydrostatic pressure is known to regulate bovine nucleus pulposus cell metabolism, but its mechanism in human nucleus pulposus cells (HNPCs) remains obscure, which attracts our attention and becomes the focus in this study. Specifically, HNPCs were treated with SKL2001 (an agonist in the Wnt/β-catenin pathway) or XAV-939 (an inhibitor of the Wnt/β-catenin pathway), and pressurized under the hydrostatic pressure of 1, 3 and 30 atm. The viability, apoptosis and proteoglycan synthesis of treated HNPC were assessed by CCK-8, flow cytometry and radioisotope incorporation assays. The levels of extracellular matrix, Collagen-II, matrix metalloproteinase 3 (MMP3), Wnt-3a and β-catenin were measured by toluidine blue staining, immunocytochemistry and Western blot. Appropriate hydrostatic stimulation (3 atm) enhanced the viability and proteoglycan synthesis yet inhibited the apoptosis of HNPCs, which also up-regulated extracellular matrix and Collagen-II levels, and down-regulated MMP3, Wnt-3a and β-catenin levels in treated HNPCs. Furthermore, high hydrostatic pressure (30 atm) inhibited the viability and proteoglycan synthesis, and promoted the morphological change and apoptosis of HNPCs, which also down-regulated extracellular matrix and Collagen-II levels and up-regulated MMP3, Wnt-3a and β-catenin levels. Besides, SKL2001 reversed the effects of hydrostatic pressure (3 atm) on inhibiting Wnt-3a, β-catenin, and MMP3 levels and promoting Collagen-II level in HNPC; whereas, XAV-939 reversed the effects of high hydrostatic pressure (30 atm) on promoting MMP3, Wnt-3a, and β-catenin levels and inhibiting Collagen-II level and proteoglycan synthesis of HNPCs. Collectively, high hydrostatic pressure promoted the apoptosis and inhibited the viability of HNPCs via activating the Wnt/β-catenin pathway.
研究领域:
细胞生物学
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）