Scientific Reports
·
2020
·Vol. 10
·期 1
·1-7
·
IF 3.998
Wang Xueni,Liao Xiuling,Zhang Yimin,Wei Linyao,Pang Yuzhou
Schisandrin B (SchB) is the highest content of biphenyl cyclooctene lignans in Schisandra chinensis . It has been reported to have a variety of pharmacological effects, including anti-inflammatory, anti-oxidant, anti-cancer, heart protection, liver protection. In this study, we found that SchB can promote the proliferation of MC3T3-E1 subclone 14 cells. Meanwhile, we found that SchB can regulate the BMP2-SMADs signaling pathway by increasing gene and protein expression of those relative biomolecules. Furthermore, SchB can raise the RUNX2 and SP7 expression in both mRNA and protein levels. Since the role of BMP2-SMADs-RUNX2-SP7 signaling axis in osteoblast proliferation and differentiation has been well documented. The present experimental findings indicate that SchB could promote the proliferation and differentiation of osteoblasts through BMP2-SMADs-RUNX2-SP7 signaling axis.
研究领域:
药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
AQUACULTURE
·
2022
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IF 5.135
Hua Rong,Haoran Zhang,Lijun Ning,Kun Wu,Samwel Mchele Limbu,Qingchao Shi,Chuanjie Qin,Xiaobo Wen
The swim bladder performs various functions in fish, is consumed by humans and can be processed into high-grade fish glue (traditional high-value tonic). However, little is known on the optimum amount of proline (Pro) required for promoting collagen synthesis and deposition in fish swim bladder and the regulatory mechanism. This study explored the effects and optimum amount of dietary Pro supplementation on collagen synthesis and deposition in Chu's croaker ( Nibea coibor ) swim bladder and its possible molecular mechanism. A total of 450 juvenile fish (8.64 ± 0.14 g) were randomly stocked into 18 cages (25 fish per cage) in triplicate and fed Pro supplemented diets (0, 5, 10, 15, 20 and 25 g kg −1 ) for eight weeks. Another 225 fish (11.62 ± 0.15 g) were distributed randomly into control, Pro and Pro diet plus injected with specific inhibitor of Smad3 (SIS3) in order to inhibit the transforming growth factor beta (TGF-β)/Smads pathway. Pro supplementation up-regulated significantly the expression of genes involved in TGF-β/Smads pathway such as collagen, type I, alpha 1 ( col1a1 ) and 2 ( col1a2 ), TGF-β and Smad2/3 , and increased collagen content in the Chu's croaker swim bladder ( P < 0.05). The optimum dietary Pro supplementation for deposition of collagen in Chu's croaker swim bladder was 19.36 g kg −1 . The collagen content in the swim bladder positively correlated significantly with the mRNA expression of col1a1 , col1a2 , TGF-β and Smad2/3 genes ( P < 0.05). The optimum dietary Pro supplementation for maximum synthesis of collagen in Chu's croaker swim bladder was 13.25, 13.32 and 15.94 g kg −1 based on mRNA expression of Smads2 , Smads3 and col1a2 genes, respectively. SIS3 down-regulated the expression of col1a1 , col1a2 , TGF-β and Smad2/3 genes, subsequently decreased collagen deposition in the swim bladder ( P < 0.05). These results suggest that 13.25 to 19.36 g kg −1 Pro supplementation improve collagen synthesis and deposition in Chu's croaker swim bladder. The TGF-β/Smad signaling pathway regulates collagen synthesis and deposition in Chu's croaker swim bladder. Our results provide an understanding on the molecular mechanism of collagen synthesis and deposition in fish for producing collagen required for human food and fish glue.
研究领域:
水产养殖
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2018
·
IF 3.118
Yichuan Xiao,Jiantao Ye,Ying Zhou,Junjun Huang,Xiawen Liu,Biyun Huang,Liu Zhu,Bo Wu,Genshui Zhang,Yi Cai
AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways. It has been shown that activation of AMPK could inhibit fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby suppressing cardiac fibrosis. Baicalin , the major component found in skullcap, possesses multiple protective effects on the cardiovascular system. However, little is known about the effect of baicalin on cardiac fibrosis and the molecular mechanism by which baicalin exerts its anti-fibrotic effects has not been investigated. In this study, we revealed that baicalin could inhibit cell proliferation , collagen synthesis , fibronectin (FN) and Connective tissue growth factor (CTGF) protein expression in cardiac fibroblasts induced by angiotensin Ⅱ (Ang Ⅱ). It also ameliorated cardiac fibrosis in rats submitted to abdominal aortic constriction (AAC). Moreover, baicalin inhibited transforming growth factor-β (TGF-β)/Smads signaling pathway stimulated with Ang Ⅱ through activating AMPK. Subsequently, we also demonstrated that baicalin attenuated Ang Ⅱ-induced Smad3 nuclear translocation, and interaction with transcriptional coactivator p300, but promoted the interaction of p300 and AMPK. Taken together, these results provide the first evidence that the effect of baicalin against cardiac fibrosis may be attributed to its regulation on AMPK/TGF-β/Smads signaling, suggesting the therapeutic potential of baicalin on the prevention of cardiac fibrosis and heart failure.
研究领域:
心脏病学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Zihui Tang,Xiaojuan Li,Le Tian,Yuhao Sun,Xinyan Zhu,Fei Liu
Early intervention of liver fibrosis can prevent its further irreversible progression. Both excess reactive oxygen species (ROS) and transforming growth factor beta(TGF-β)/drosophila mothers against decapentaplegic protein (SMADS) pathway balance disorder promote the progression of hepatic stellate cell (HSC) activation, but existing therapeutic strategies failed to focus on those two problems. A new biomimetic mesoporous polydopamine nandrug (MPO) was constructed for liver fibrosis therapy with multiple targets and reliable biosafety. The MPO was formed by mesoporous polydopamine (mPDA) which has the effect of ROS elimination and encapsulated with anti-fibrotic drug -oxymatrine (OMT) which can intervene liver fibrosis targeting TGF-β/SMADSpathway. Particularly, the nanodrug was completed by macrophage-derived exosome covering. The MPO was confirmed to possess a desired size distribution with negative zeta potential and exhibite strong ROS scavenger ability. Besides, in vitro studies, MPO showed efficient endocytosis and superior intracellular ROS scavenging without cytotoxicity; in vivo studies, MPO effectively cleared the excessive ROS in liver tissue and balanced the TGF-β/SMADS pathways, which in turn inhibited HSC activation and showed superior anti-liver fibrosis therapeutic efficiency with good biological safety. Taken together, this work showed highlights the great potential of the MPO for ameliorating liver fibrosis via ROS elimination and TGF-β/SMADS balancing.
研究领域:
纳米医学
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药理学
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肝病学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2019
·Vol. 10
·期 1
·1-11
·
IF 4.627
Kong Yuanyuan,Hu Xiaoli,Zhong Yingqun,Xu Ke,Wu Buling,Zheng Jianmao
Background Magnesium (Mg 2+ )-enriched microenvironment promotes odontogenic differentiation in human dental pulp stem cells (DPSCs), but the regulatory mechanisms remain undefined. The aim of this work was to assess magnesium’s function in the above process and to explore the associated signaling pathway. Methods DPSCs underwent culture in odontogenic medium with the addition of 0, 1, 5, or 10 mM MgCl 2 . Intracellular Mg 2+ levels in DPSCs were evaluated flow cytometrically using Mag-Fluo-4-AM. Mg 2+ -entry was inhibited by TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB). RNA-Sequencing was carried out for assessing transcriptome alterations in DPSCs during odontogenic differentiation associated with high extracellular Mg 2+ . KEGG pathway analysis was performed to determine pathways related to the retrieved differentially expressed genes (DEGs). Immunoblot was performed for assessing magnesium’s role and exploring ERK/BMP2/Smads signaling. Results Mg 2+ -enriched microenvironment promoted odontogenic differentiation in DPSCs via intracellular Mg 2+ increase. Consistently, the positive effect of high extracellular Mg 2+ on odontogenic differentiation in DPSCs was blocked by 2-APB, which reduced Mg 2+ entry. RNA-sequencing identified 734 DEGs related to odontogenic differentiation in DPSCs in the presence of high extracellular Mg 2+ . These DEGs participated in many cascades such as MAPK and TGF-β pathways. Consistently, ERK and BMP2/Smads pathways were activated in DPSCs treated with high extracellular Mg 2+ . In agreement, ERK signaling inhibition by U0126 blunted the effect of high extracellular Mg 2+ on mineralization and odontogenic differentiation in DPSCs. Interestingly, BMP2, BMPR1, and phosphorylated Smad1/5/9 were significantly decreased by U0126, indicating that BMP2/Smads acted as downstream of ERK. Conclusions Mg 2+ -enriched microenvironment promotes odontogenic differentiation in DPSCs by activating ERK/BMP2/Smads signaling via intracellular Mg 2+ increase. This study revealed that Mg 2+ -enriched microenvironment could be used as a new strategy for dental pulp regeneration.
研究领域:
牙科研究
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干细胞生物学
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分子生物学
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细胞信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2020
·Vol. 9
·期 14
·2000318
·
IF 7.367
Zhenfei Huang,Yu He,Xiao Chang,Jieying Liu,Lingjia Yu,Yuanhao Wu,Yaqian Li,Jingjing Tian,Lin Kang,Di Wu,Hai Wang,Zhihong Wu,Guixing Qiu
3D-printed porous titanium–aluminum–vanadium (Ti6Al4V, pTi) scaffolds offer surgeons a good option for the reconstruction of large bone defects, especially at the load-bearing sites. However, poor osteogenesis limits its application in clinic. In this study, a new magnetic coating is successfully fabricated by codepositing of Fe 3 O 4 nanoparticles and polydopamine (PDA) on the surface of 3D-printed pTi scaffolds, which enhances cell attachment, proliferation, and osteogenic differentiation of hBMSCs in vitro and new bone formation of rabbit femoral bone defects in vivo with/without a static magnetic field (SMF). Furthermore, through proteomic analysis, the enhanced osteogenic effect of the magnetic Fe 3 O 4 /PDA coating with the SMF is found to be related to upregulate the TGF β -Smads signaling pathway. Therefore, this work provides a simple protocol to improve the osteogenesis of 3D-printed porous pTi scaffolds, which will help their application in clinic.
研究领域:
材料科学
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生物材料
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生物医学工程
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Endocrinology
·
2022
·
IF 6.055
Nian Ding,Chenghong Zheng
By establishing a rat diabetes model in rats with intervening treatment by Jiangtang Tongmai Prescription (JTTMP), this study explored the restorative pairing effect of JTTMP on diabetic lung injury. The model of type II diabetes model was used to establish the rat diabetes model, using a high-fat diet and streptozotocin (STZ) induction. Different doses of JTTMP and metformin were administered as a therapeutic to intervene, and blood was collected to assess the blood glucose level of each group of rats. HE (Hematoxylin and eosin (H&E) staining was performed to detect the morphological changes in rat lung tissue and enzyme-linked immunoassay ELISA was used to detect and quantify the expression of interleukin (IL)-6, TNF tumor necrosis factor-ɑa, and IL-1β in serum and the lung tissue of each group of rats. The level expression of TGF-β1 [transforming growth factor (TGF)-β1), SnoN (transcriptional co-repressor Ski-N terminal (SnoN)], Smad2, Smad3, Smad7, and other signaling pathway proteins were assessed by Western blot. In comparison with the normal control (NC) group, rats in the diabetes model (DM) group lost weight and showed significantly increased blood sugar levels. The levels of TGF-β1 and Smad2/3 were increased in the DM group but Smad7 decreased. After 8 weeks of JTTMP intervention, the level of TGF-β1 and Smad2/3 decreased but Smad7 increased, blood sugar decreased significantly and the expression of inflammatory factors in lung tissue decreased. Therefore, JTTMP may activate SnoN and the downstream TGF-β1/Smads signaling pathway to repair diabetic lung injury, which suggests its application has potential for future clinical treatment of diabetes with lung injury.
研究领域:
药理学
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内分泌学
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分子生物学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 45
·期 5
·e13723
·
IF 2.72
Yanyuan Zhou,Huan Lan,Zhewen Dong,Wenjing Cao,Zhen Zeng,Jia-Le Song
This study investigated the effects of proanthocyanidins (PCs) on ovarian fibrosis in letrozole-induced polycystic ovary syndrome (PCOS) in rats. The administration of PCs effectively reduced the body weight (BW) and relative ovarian weight in PCOS rats. ELISA results revealed that PCs significantly reduced the level of serum T, LH, LH/FSH in the PCOS group. In addition, qRT-PCR results revealed that treatment with PCs significantly increased the main antioxidant enzymes (Cat, Sod2, Gpx3, Mgst1, Gsta4, Sod1 and Prdx3) in PCOS rats. Also, the expression analysis of proteins by Western blotting revealed that PCs significantly decreased the level of TGF-βR1, p-Smad3, p-Smad2 and Smad4 and reversed the downregulation of Smad7 in PCOS rats. The study suggested that PCs improved ovarian fibrosis in PCOS rats by regulating the serum hormone level, inhibiting oxidative stress and suppressing the activation of the TGF-β1/Smads signaling pathway. Practical applications Currently, plant extracts are being widely used to treat female reproductive and metabolic disorders. Particularly, proanthocyanidins (PCs), the well-known natural polyphenolic compounds, which are a significant source of antioxidants present in many colored fruits, are consumed as fruits as well as a dietary supplement to prevent many disorders. Recent pharmacological studies have reported that PCs have many health beneficial properties, such as antioxidant activity, improving cholesterol homeostasis, blood lipid regulatory properties, microcirculation improvement effect, antitumor activity and anti-aging activity. Despite these properties of PCs, the antifibrosis effect of PCs has not been studied to date. The main purpose of this study was to research the role and the mechanisms of PCs in ovarian fibrosis in PCOS rats.
研究领域:
药理学
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生殖生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Pharmacology & Translational Science
·
2024
·
IF 4.9
Xiao-Yi Chen,Tian-Tian Wang,Qing Shen,Hao Ma,Zhan-Hua Li,Xi-Na Yu,Xiao-Feng Huang,Lin-Sen Qing,Pei Luo
In traditional Chinese medicine, Radix Astragali has played a vital role in treating progressive fibrotic diseases. One of its main active components, astragaloside IV, is a promising anti-fibrotic treatment despite its extremely low bioavailability. Our study aimed to optimize sodium astragalosidate (SA) by salt formation to improve solubility and oral absorption for anti-fibrotic therapy in vivo. Isoproterenol-induced myocardial fibrosis rat models and obese BKS-db mice presenting diabetic kidney fibrosis were used in this study. Daily oral administration of SA (20 mg/kg) for 14 days ameliorated cardiac fibrosis by reducing collagen accumulation and fibrosis-related inflammatory signals, including TNF-α, IL-1β, and IL-6. In db/db mice, SA (5,10, and 20 mg/kg per day for 8 weeks) dose-dependently alleviated lipid metabolism impairment and renal dysfunction when administered orally. Furthermore, Western blot and immunohistochemistry analyses demonstrated that SA treatment inhibited renal fibrosis by suppressing TGF-β1/Smads signaling. Taken together, our findings provide the oral-route medication availability of SA, which thus might offer a novel lead compound in preclinical trial-enabling studies for developing a long-term therapy to treat and prevent fibrosis.
研究领域:
药理学
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心脏病学
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肾病学
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传统中医
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分子生物学
✓ 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）