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Journal of the Mechanical Behavior of Biomedical Materials · 2022 · IF 4.042

Preparation and properties of nano silica-based bioactive glass/apatite/sodium alginate composite hydrogel

Yexiao Guan,Yanrui Mao,Jianguo Liao

In this paper, given the lack of osteogenic activity of sodium alginate (SA) hydrogel and to simulate the composition of natural bone, ionic-crosslinking NBG/n-HA/SA hydrogel scaffolds were prepared by using nano bioactive glass (NBG) and nano hydroxyapatite (n-HA) with high bioactivity as composite calcium sources and reinforcement phases, and D-gluconic acid δ-lactone (GDL) as the coagulant. The results showed that the mixture of the precursor forming the network had good injectability and plasticity. When the dosage of GDL was 0.75 g, the gelling time of the composite hydrogel could be regulated within 4–8 min, and the hydrogel had high compressive strength (170–220 kPa), as well. When the mass ratio of calcium source to SA was 1:1, the crosslinking network was relatively uniform with a considerable number of large pores around 40 μm in the structure. In the immersion experiment in vitro, it was found that the composite hydrogel could promote the deposition of bone-like apatite on the material's surface. Meanwhile, the cell experiments in vitro verified that the NBG/n-HA/SA composite hydrogel had good cytocompatibility without cytotoxicity. Moreover, the composite hydrogel could enhance the activity of ALP of mouse bone marrow mesenchymal stem cells , and thus, it had good osteogenic activity.

CAS / MDL: 90-80-2 9005-38-3
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 材料科学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Bioinspired self-healing injectable nanocomposite hydrogels based on oxidized dextran and gelatin for growth-factor-free bone regeneration

Wuchao Ma,Meilian Yang,Chao Wu,Shaoyun Wang,Ming Du

Hydrogels with great biocompatibility, biodegradability, and mechanical properties, combined with osteoconductivity, osteoinductivity, and osteointegration as biomaterials for bone regeneration without adding exogenous growth factors and cells are highly appealing but challenging. Here, inspired by organic-inorganic analogues of natural bone tissue and the adhesion chemistry of mussels, nanocomposite hydrogels with self-healing, injectable, adhesive, antioxidant, and osteoinductive properties (termed GO-PHA-CPs) were constructed by Schiff base cross-linking between dopamine-modified gelatin (Gel-DA) and oxidized dextran (ODex). Furthermore, the hydrogel network was enhanced by the introduction of polydopamine-functionalized nanohydroxyapatite (PHA) by improving the interfacial compatibility between the rigid inorganic particles and the flexible hydrogel matrix. Bioactive cod peptides (CPs) with osteogenic activity from Atlantic cod were further incorporated into the nanocomposite hydrogel. As a result, the multicomponent nanocomposite hydrogel favored the adhesion and spreading of MC3T3-E1 cells. The increased ALP activity suggested that GO-PHA-CPs hydrogels contributed to the osteogenic differentiation of MC3T3-E1 cells. The suitability of GO-PHA-CPs hydrogels for enhancing bone regeneration in vivo was further confirmed by the rat femoral defect model. Our results indicate that the multifunctional GO-PHA-CPs nanocomposite hydrogels without growth factors are a promising and effective candidate material for bone regeneration.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 材料科学 · 生物医学工程 · 组织工程 · 生物材料
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Mineralized Enzyme-Based Biomaterials with Superior Bioactivities for Bone Regeneration

Zhi Zhou,Yunshan Fan,Yingying Jiang,Sheng Shi,Chao Xue,Xinyu Zhao,Shuo Tan,Xin Chen,Chaobo Feng,Yancheng Zhu,Jiajun Yan,Zifei Zhou,Yunfei Zhao,Junjian Liu,Feng Chen,Shisheng He

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco’s modified Eagle’s medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for critical-sized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

CAS / MDL: 10043-52-4 9000-70-8
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨再生 · 干细胞生物学 · 酶学
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Analytical Methods · 2015 ·Vol. 7 ·期 23 ·9984-9991 · IF 1.821

An electrochemical biosensor for the activity assay of polynucleotide kinase and inhibitor screening

Qingming Zhang,Xue Li,Bingchen Li,Huanshun Yin,Shiyun Ai

A sensitive and selective electrochemical biosensor was fabricated for polynucleotide kinase (PNK) activity assay and inhibitor screening based on phos-tag-biotin mediated double signal amplification, where streptavidin and alkaline phosphatase-conjugated biotin (biotin-ALP) were used as the signal amplification units. After the immobilization of probe DNA on the electrode surface, it was hybridized with complementary DNA containing the 5′-OH terminal, the OH can be phosphorylated under the catalytic effect of PNK in the presence of ATP. The generated phosphate group at the 5′-terminal can be further recognized by phos-tag-biotin, where phos-tag-biotin was not only used as the specific recognition reagent for the phosphate group, but also the capture reagent for streptavidin to induce the further assembly of biotin-ALP. Under the catalytic effect of ALP, the substrate of p-nitrophenyl phosphate disodium salt hexahydrate (PNPP) can be hydrolyzed to produce p-nitrophenol (PNP). According to the relationship between the electrochemical response of PNP and the logarithmic value of PNK concentration, a linear range of 0.01–5 units per mL and a low detection limit of 0.0027 unit per mL were achieved. The developed method showed high selectivity. The inhibition effect of (NH4)2SO4 and Na2HPO4 was also evaluated and the IC50 values were calculated.

CAS / MDL: 333338-18-4
研究领域: 生物化学 · 分析化学 · 电化学 · 分子生物学
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2024 ·Vol. 28 ·期 23 ·e70271 · IF 4.3

The Molecular Mechanism Investigation of HBP-A Slows Down Meniscus Hypertrophy and Mineralisation by the Damage Mechanical Model

Zongrui Yang,Yuanyuan Feng,Mingcai Zhang,Yongming Liu,Yizhe Xiong,Xiang Wang,Ying Shi,Bo Chen,Zhengming Wang,Haiya Ge,Hongsheng Zhan,Zhibi Shen,Guoqing Du

HBP-A is the main active component of a traditional Chinese medicine Huaizhen Yanggan Capsule, for the remarkable treatment of knee osteoarthritis (KOA). This study aimed to elucidate the ameliorative effect of HBP-A on meniscus hypertrophy and mineralisation in KOA and the molecular mechanism of its action. An Hartley guinea pig model of KOA that underwent anterior cruciate ligament transection (ACLT) and a model of rat primary meniscus fibrochondrocytes (PMFs) were used to investigate the ameliorative effect of HBP-A on meniscal hypertrophy and calcification and its signal transduction mechanism of action. The results show that Guinea pig's meniscus width, as well as the area of meniscus calcification and meniscus and articular cartilage injury score, were significantly reduced in the HBP-A intervention group compared to the ACLT group. The expression levels of mtrix metalloproteinase 13 (MMP13), runt-related transcription factor 2 (Runx2), Indian hedgehog (Ihh), alkaline phosphatase (ALP), and ankylosis homologue (ANKH) at the protein and gene level significantly decreased in the HBP-A intervention group compared to the ACLT group. In vitro study, apoptosis, hypertrophy, and calcification of rat PMFs after 10% stretch force were significantly improved with HBP-A intervention. Western blot and RT-qPCR showed that hypertrophy, calcification, and p38 MAPK signalling pathway-related markers of PMFs were incredibly depressed in the HBP-A intervention group compared to the 10% stretch force group. In conclusion, HBP-A can slow down meniscus hypertrophy and mineralisation induced by abnormal mechanical loading, and its mechanism of action may be through the p38-MAPK signalling pathway.

CAS / MDL: 77-92-9
研究领域: 药理学 · 骨科 · 分子生物学 · 传统中药
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomaterials Advances · 2024 · IF 5.5

Carboxymethyl chitosan/alendronate sodium/Sr2+ modified TiO2 nanotube arrays enhancing osteogenic activity and antibacterial property

Kunpeng Jia,Changpeng Zuo,Yan Xu,Wenfu Ma,Lingtao Wang,Yan Ji,Jie Chen,Qiuyang Zhang,Changjiang Pan,Tingting Liu

Titanium and its alloys are widely used as orthopedic implants owing to their good mechanical properties and excellent corrosion resistance. However, the insufficient osteogenic activity and antibacterial properties hinder their clinical applications. To address these issues, TiO 2 nanotube arrays (TNT) were first fabricated on the TA2 alloy surface via an anodizing technique, and strontium ions (Sr 2+ ) were then loaded by hydrothermal reaction (TNT + Sr) and annealing treatment (TNT + A). Subsequently, the polydopamine layer (TNT + PDA) was constructed to immobilize the carboxymethyl chitosan and alendronate sodium (TNT + CA) mixture. The prepared coatings were thoroughly characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), X-ray photoelectron spectrometer (XPS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffractometer (XRD), and water contact angle measurement. The results confirmed that Sr 2+ ions, polydopamine, and carboxymethyl chitosan/alendronate sodium were successfully immobilized on the nanotubes. The coating of TNT + CA significantly enhanced the hydrophilicity, and effectively delayed the release of Sr 2+ and alendronate. The TNT + CA coating significantly promoted osteoblast adhesion and proliferation, and up-regulated the expressions of alkaline phosphatase (ALP), osteocalcin (OCN), and osteoblast-specific transcription factor (RUNX2). TNT + CA was able to rapidly induce in situ hydroxyapatite deposition from the simulated body fluid (SBF). Moreover, TNT + CA coating showed inhibition against Escherichia coli and Staphylococcus aureus (especially against Escherichia coli ). The prepared TNT + CA coating provides a novel strategy for enhancing bone affinity, improving osteoblast behaviors, and antibacterial properties of titanium-based biomaterials.

研究领域: 生物材料 · 骨科 · 表面工程 · 纳米技术 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2021 ·Vol. 188 ·期 12 ·1-9 · IF 5.833

Fluorescence and visual immunoassay of HIV-1 p24 antigen in clinical samples via multiple selective recognitions of CdTe QDs

Tang Zhuoyun,Wei Zeliang,Huang Ke,Wei Yinhao,Li Dongdong,Yan Shixin,Huang Jin,Geng Jia,Tao Chuanmin,Chen Piaopiao,Ying Binwu

Human immunodeficiency virus (HIV) infection inflicts significant economic and social burdens on many countries worldwide. Given the substantial morbidity and mortality from HIV infection, there is an urgent need for accurate and early detection of the virus. In this study, immunofluorescence and visual techniques are described that detect the HIV-1 p24 antigen, which relied on selective recognition of Ag + /Ag nanoparticles (Ag NPs) and Cu 2+ /Cu + using cadmium telluride quantum dots (CdTe QDs). After the sandwich immunoreactions were accomplished, the alkaline phosphatase (ALP) hydrolyzed L-ascorbic acid 2-phosphate (AAP) to form ascorbic acid (AA) that further reduces Ag + and Cu 2+ to Ag NPs and Cu + , respectively. This method was highly sensitive and selective and could detect as low as 1 pg/mL of p24 antigen by naked eyes and had a good linearity in the concentration range 1–100 pg/mL. When using Ag + and Cu 2+ as media, the limit of detection (LOD) of the new method was 0.3 pg/mL and 0.2 pg/mL, respectively. Compared with clinical electrochemiluminescence immunoassay (ECLIA) results and clinical data, this method demonstrated good consistency for the quantification of HIV-1 p24 antigen in 34 clinical serum samples. In addition, this method could accurately distinguish HIV from other viruses and infections such as hepatitis B virus , systemic lupus erythematosus , hepatitis C virus , Epstein-Barr virus , cytomegalovirus , lipemia , and hemolysis . Therefore, our dual-mode analysis method may provide additional solutions to identify clinical HIV infection. Graphical abstract An immunofluorescence and visualization dual-mode strategy for the detection of p24 antigen was constructed based on immune recognition reaction and a phenomenon that cadmium telluride quantum dots (CdTe QDs) can selectively recognize Ag + /Ag nanoparticles (Ag NPs) and Cu 2+ /Cu + .

研究领域: 病毒学 · 免疫学 · 医学诊断
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Optical Materials · 2023 ·Vol. 11 ·期 14 ·2300010 · IF 9

Surface Patterning Enhanced Visualization for Ultrasensitive Naked-Eye Detection and RGB-Based High-Density Information Storage

Yuanhua Zhang,Yan Qiu,Lan Xia,Long Yuan,Hailong Wu,Rui Shi,Anqi Chen,Kai Zhou,Mingxue Zhou,Kailian Zhang,Chunxiang Zhang,Zhining Xia,Qifeng Fu

The emerging visualization techniques have aroused wide interest for optical information detection and storage. However, they suffer from fairly limited optical information density and poor visual detection performance. Herein, an innovative surface patterning enhanced visualization (SPEV) approach is developed for ultrasensitive naked-eye detection and RGB-based high-density information storage. Through “ship covalently linked in bottle” method, a novel HP-UiO-66-NH 2 -based ratiometric fluorescent (RF) composite probe is fabricated, exhibiting remarkably enhanced CdTe QDs encapsulation efficiency and superior dual-sensing performance for F − and alkaline phosphatase (ALP). Then, the novel surface patterned CdTe QDs@HP-UiO-66-NH 2 hydrogel sensor is prepared, emitting multi-stimuli-responsive optical information with significantly improved abundance and dimensionality. The pseudo-color postprocessing of the fluorescence images is performed to convert the analyte-induced imperceptible color variations into easily perceptible color tonality change, resulting in ultra-high sensitivity and excellent accuracy for naked-eye quantitative detection of ALP and F − in human serum. Furthermore, the highly accurate pattern block-based RGB (PB-RGB) assay is demonstrated and the concept of RGB-based 3D patterning codes is presented for highly reliable extraction of quantitative color information and high-density information storage. The SPEV technique provides a universal route to realize instrument-free precise visual quantitative detection, high-density optical information storage, multi-stimuli-responsive encryption, and anti-counterfeiting.

研究领域: 光学传感 · 材料科学 · 纳米技术 · 生物医学工程 · 信息存储 · 化学传感器 · 荧光成像
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2019 · IF 4.784

Comparative study on hepatoprotection of pine nut (Pinus koraiensis Sieb. et Zucc.) polysaccharide against different types of chemical-induced liver injury models in vivo

Hang Qu,Xin Gao,Zhen-Yu Wang,Juan-Juan Yi

A novel polysaccharide (PNP80b-2) was obtained from Pinus koraiensis pine nut, which has been proved to possess good hepatoprotective effects in vitro . This study comprehensively investigated its hepatoprotective activities against different types of chemical-induced liver injury in vivo . Carbon tetrachloride, alcohol and acetaminophen were used as hepatic toxicants to establish chemical pollutant-induced liver injury (CILI) model, alcohol induced-liver injury (AILI) model and drug-induced liver injury (DILI) model, respectively. The results showed that PNP80b-2 prevented elevation of biomarkers for liver injury in each model, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL). The expression of cytochrome P450 in damaged hepatocytes was also downregulated. Additionally, PNP80b-2 enhanced hepatic antioxidant capacity through upregulating the expression of NRF2 and HO-1, thereby increasing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities and decreasing malondialdehyde (MDA) levels. The uncontrolled production of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) in CILI, AILI and DILI models was also suppressed by PNP80b-2. By contrast, PNP80b-2 exerted the strongest hepatoprotection against AILI model, through improving hepatic antioxidant capacity via NRF2/ARE pathway and regulating inflammation response. Thus, PNP80b-2 is a promising functional food to prevent AILI.

CAS / MDL: 56-23-5
研究领域: 药理学 · 肝病学 · 功能性食品 · 毒理学
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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

A novel type lavandulyl flavonoid from Sophora flavescens as potential anti-hepatic injury agent that inhibit TLR2/NF-κB signaling pathway

Yan Lin,Xing-Jun Chen,Jing-Jing Li,Lei He,Ya-Ru Yang,Fei Zhong,Ming-Hui He,Yi-Tong Shen,Bo Tu,Xu Zhang,Zhu Zeng

Ethnopharmacology relevance Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens , which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. Aim of the study This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1 ) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl 4 )-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. Materials and methods The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl 4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1β and cyclooxygenase-2 (COX2) in hepatic tissues were detected. Results The lavandulyl flavonoid (kurarinol A, 1 ) and the EtOAc extract from S. flavescens showed protective effects on CCl 4 -injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What’s more, we found that treatment with kurarinol A ( 1 ) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl 4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1β in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1β, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. Conclusion These findings demonstrated that the novel compound (kurarinol A, 1 ) possessed notable hepatoprotective activity against CCl 4 . It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl 4 , and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.

CAS / MDL: 8001-30-7 50-00-0
研究领域: 药理学 · 民族药理学 · 分子生物学 · 细胞生物学 · 毒理学
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EXPERIMENTAL CELL RESEARCH · 2023 · IF 3.7

Punicalagin attenuates TNF-α-induced oxidative damage and promotes osteogenic differentiation of bone mesenchymal stem cells by activating the Nrf2/HO-1 pathway

Lei Huang,Shunyi Lu,Mengxuan Bian,Jiayi Wang,Jieqin Yu,Jun Ge,Jian Zhang,Qintong Xu

Oxidative stress is one of the most important factors in changing bone homeostasis. Redox homeostasis plays a key role in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) for bone regeneration. Currently, this study assessed the effects of punicalagin (PUN) on BMSCs and HUVECs. Cell viability was determined by CCK-8 assay. A flow cytometry analysis was adopted to detect macrophage polarization. The production of reactive oxygen stress (ROS), glutathione (GSH), malonaldehyde (MDA) and superoxide dismutase (SOD) activities were evaluated by using commercially-available kits. Osteogenic capacity of BMSCs was evaluated by ALP activity, ALP staining and ARS staining. The expression of osteogenic-related proteins (OCN, Runx-2, OPN) and Nrf/HO-1 levles were evaluated by Western blotting. Osteogenic-related genes (Osterix, COL-1, BMP-4, ALP) were evaluated by RT-PCR. Migration ability and invasion ability of HUVECs were evaluated by wound healing assay and Transwell assay. Angiogenic ability was detected by tube formation assay and the expression of angiogenic-related genes (VEGF, vWF, CD31) were evaluated by RT-PCR. Results showed that PUN alleviated oxidative stress by TNF-α, enhanced osteogenic differentiation in BMSCs and angiogenesis in HUVECs. Moreover, PUN regulate immune microenvironment by promoting the polarization of M2 macrophages and reduce the oxidative stress related products by activating Nrf2/HO-1 pathway. Altogether, these results suggested that PUN can promote osteogenic capacity of BMSCs, angiogenesis of HUVECs, alleviate oxidative stress via Nrf2/HO-1 pathway, offering PUN as a novel antioxidant agent for treating bone loss diseases.

CAS / MDL: 30525-89-4
研究领域: 药理学 · 细胞生物学 · 分子生物学 · 干细胞研究 · 骨再生
✓ 已验证 产品关联 DOI PubMed 高影响因子
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