BMC Oral Health
·
2024
·Vol. 24
·期 1
·1-15
·
IF 2.6
Zou Yin,Mei Xue,Wang Xinhe,Zhang Xuan,Wang Xun,Xiang Wen,Lu Naiyan
Background Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels.Methods Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration.Results
The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p < 0.0001), osteocalcin (Ocn, p < 0.0001), type collagen (Col , p < 0.0001), bone morphogenetic protein-2 (Bmp2, p < 0.0001), Smad1 (p = 0.0006), and runt-related transcription factor 2 (Runx2, p < 0.0001) were all significantly upregulated.Conclusion s
EMSCs/BPNs-containing fibrin-KGM hydrogels accelerated the recovery of the alveolar bone defect in rats by effectively up-regulating the expression of osteogenesis-related genes, promoting the formation and mineralisation of bone matrix.
研究领域:
牙科治疗
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组织工程
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干细胞生物学
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材料科学
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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
Theranostics
·
2024
·
IF 12.4
Maojiao Li,Qi Tang,Chengcheng Liao,Zhuo Wang,Siyuan Zhang,Qingqing Liang,Cheng Liang,Xiaodong Liu,Jingyi Zhang,Weidong Tian,Li Liao
Rationale: Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs undergo apoptosis shortly after transplantation and produce apoptotic extracellular vesicles (ApoEVs). This study aims to clarify the potential role of ApoEVs from apoptotic MSCs in ameliorating osteoporosis and molecular mechanism. Methods: In this study, Dio-labeled bone marrow mesenchymal stem cells (BMSCs) were injected into mice to track BMSCs apoptosis and ApoEVs production. ApoEVs were isolated from BMSCs after inducing apoptosis, the morphology, size distribution, marker proteins expression of ApoEVs were characterized. Protein mass spectrometry analysis revealed functional differences in proteins between ApoEVs and BMSCs. BMSCs were adopted to test the cellular response to ApoEVs. Ovariectomy mice were used to further compare the ability of ApoEVs in promoting bone formation. SiRNA and lentivirus were used for gain and loss-of-function assay. Results: The results showed that BMSCs underwent apoptosis within 2 days after being injected into mice and produce a substantial quantity of ApoEVs. Proteomic analysis revealed that ApoEVs carried a diverse functional array of proteins, and easily traversed the circulation to reach the bone. After being phagocytized by endogenous BMSCs, ApoEVs efficiently promoted the proliferation, migration, and osteogenic differentiation of BMSCs. In an osteoporosis mouse model, treatment of ApoEVs alleviated bone loss and promoted bone formation. Mechanistically, ApoEVs carried Ras protein and activated the Ras/Raf1/Mek/Erk pathway to promote osteogenesis and bone formation in vitro and in vivo . Conclusion: Given that BMSC-derived ApoEVs are high-yield and easily obtained, our data underscore the substantive role of ApoEVs from dying BMSCs to treat bone loss, presenting broad implications for cell-free therapeutic modalities.
研究领域:
干细胞生物学
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骨生物学
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再生医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Peijun Sun,Huixian Chen,Xiaoyu Fan,Jiayi Wang,Lujie Lu,Guangchao Yang,Jining Liu,Weifeng Yao,Feng Ding,Jie Ding,Jianmei Liu,Tulin Lu,Lihong Chen
Ethnopharmacological relevance Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated. Aim of the study To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action. Materials and methods UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds. Results Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation. Conclusion Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage.
研究领域:
药理学
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中药学
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心脏病学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Food Chemistry-X
·
2024
·
IF 6.5
Peng Wang,Haifan Wang,Yang Xiao,Jialiang Zou,Hongping Chen,Lin Chen,Fu Wang,Yuan Hu,Youping Liu
In this study, comprehensive and systematic nontargeted metabolomics analysis was performed with the metabolites of Zangju peel ( Citrus reticulata cv. Manau Gan, CRZP, which has been cultivated for over 400 years in Derong County, China.) at four different mature stages. A total of 1878 metabolites were identified, among which flavonoids were the most abundant (62.04 %), and identified 62 key differential metabolites significantly affected by maturity. Based on biological activity measurements, CRZP showed better antioxidant activity, lipase inhibition ability, inhibition of adipogenic differentiation in 3TT-L1 cells and promotion of lipid metabolism, with the biological activity of CRZP at different maturity stages being associated with key differential metabolite. Thus, CRZP is natural antioxidants and possess anti-obesity potential, and industrial production needs to consider the Maturity stage of its collection.
研究领域:
植物科学
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代谢组学
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药理学
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食品科学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Chang Liu,Rui Zhou,Baiqiao Chen,Xinran Yan,Lei Guo,Yixin Tang,Xu Zuo,Xiaoping Guo,Haiyang Yu,Jie Chen,Zhaopei Guo,Fang Wang,Caina Xu
The pathogenesis of acute lung injury (ALI) is characterized by an uncontrolled inflammatory response, marked by excessive production of reactive oxygen species (ROS) and the infiltration of inflammatory cells, particularly macrophages, which play a pivotal role in disease progression. The synergistic effect of ROS scavenging and macrophage repolarization provides a promising strategy for effective ALI treatment. Herein, we developed a novel type of self-assembling nanomicelles, which were composed of poly-L-glutamic acid (PLG) and 4-Hydroxymethyl phenylboronic acid (PBA). The nanomicelles (PPDex micelles) had a high drug-loading capacity for dexamethasone (Dex) based on boronic ester bonds, which exhibited reversible cleavage under inflammatory conditions characterized by elevated levels of ROS or decreased pH values. These PPDex micelles revealed rapid drug-responsive release behavior in the inflammatory environment, and in vivo studies demonstrated their efficacy in modulating cytokines, inhibiting oxidative stress, and promoting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, which ultimately suppressed the progression of ALI. Moreover, the PPDex micelles had the effective ability to effectively suppress the NF-кB and ROS/NLRP3 inflammatory pathways. Therefore, this study presented a novel and potent therapeutic strategy for ALI treatment, which could promote the clinical application of polymer nanomicelles in the treatment of ALI.
研究领域:
药理学
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纳米医学
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呼吸病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Qin Xianyan,Zhang Luhan,Miao Yang-Bao,Jiang Linxi,Zou Liang,Wang Qin,Shi Yi
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by painful swelling and inflammation, arising from the immune system attacking on healthy cells. However, arthritic sites often experience increased lymph flow, hastening drug clearance and potentially reducing treatment effectiveness. To address this challenge, an in situ size amplification has been proposed to reduce lymphatic clearance and thereby enhance arthritis therapy. This system has been developed based on a conjugate of dexamethasone (Dex) and polysialic acid (PSA), linked via an acid-sensitive linker, supplemented with bis-5-hydroxytryptamine (Bis-5HT) on the PSA backbone. Under physiological conditions, the system autonomously assembles into stable nanoparticles (PD5NPs), facilitating prolonged circulation and targeted delivery to inflamed joints. Upon arrival at arthritic joints, Bis-5HT reacts to elevated myeloperoxidase (MPO) levels and oxidative stress, prompting particle aggregation and in-situ size amplification. This in situ size amplification nanocarrier effectively reduces lymphatic clearance and serves as reservoirs for sustained Dex release in acidic pH environments within arthritic sites, thus continuously alleviating RA symptoms. Moreover, investigation on the underlying mechanism elucidates how the in situ size amplification nanocarrier influences the transportation of PD5NPs from inflamed joints to lymphatic vessels. Our study offers valuable insights for optimizing nanomedicine performance in vivo and augmenting therapeutic efficacy.Graphical
研究领域:
药理学
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纳米医学
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免疫学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Jiachen Liang,Xinyue Huang,Kaiqi Qin,Hui Wei,Jiaxin Yang,Bin Liu,Zengjie Fan
Enhancing defective cartilage repair by creating a bionic cartilage hydrogel supplemented with in situ electromagnetic stimulation, replicating endogenous electromagnetic effects, remains challenging. To achieve this, a unique three-phase solvent system is designed to prepare a magnetoelectric bionic cartilage hydrogel incorporating piezoelectric poly(3-hydroxybutyric acid-3-hydroxyvaleric acid) (PHBV) and magnetostrictive triiron tetraoxide nanoparticles (Fe 3 O 4 NPs) into sodium alginate (SA) hydrogel to form a dual-network, semi-crosslinked chain entanglement structure. The synthesized hydrogel features similar composition, structure, and mechanical properties to natural cartilage. In addition, after the implantation of cartilage, the motion-driven magnetoelectric-coupled cyclic transformation model is triggered by gentle joint forces, initiating a piezoelectric response that leads to magnetoelectric-coupled cyclic transformation. The freely excitable and cyclically enhanced electromagnetic stimulation it can provide, by simulating and amplifying endogenous electromagnetic effects, obtains induced defective cartilage repair efficacy superior to piezoelectric or magnetic stimulation alone.
研究领域:
生物材料学
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再生医学
·
生物力学
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产品关联
DOI
PubMed
高影响因子
Virulence
·
2024
·
IF 5.5
Xin Wang,Feiyang Pu,Xuanye Yang,Xili Feng,Jiayou Zhang,Kai Duan,Xuanxuan Nian,Zhongren Ma,Xiao-Xia Ma,Xiao-Ming Yang
Influenza A virus (IAV) poses threat to patients receiving immunosuppressive medications since they are more susceptible to infection with severe symptoms, and even death. Understanding the direct effects of immunosuppressants on IAV infection is critical for optimizing immunosuppression in these patients who are infected or at risk of influenza virus infection. We profiled the effects of ten immunosuppressants, explored the antiviral mechanisms of immunosuppressants and demonstrated the combination effects of immunosuppressants with the antiviral drug oseltamivir in IAV-infected cell models. We found that mycophenolic acid (MPA) strongly inhibited viral RNA replication via depleting cellular guanosine pool. Treatment with 6-Thioguanine (6-TG) promoted viral protein degradation through proteasomal pathway. Filgotinib blocked mRNA splicing of matrix protein 2, resulting in decreased viral particle assembly. Furthermore, combined treatment with immunosuppressants and oseltamivir inhibited IAV viral particle production in an additive or synergic manner. Our results suggest that MPA, 6-TG and filgotinib could be the preferential choices for patients who must take immunosuppressants but at risk of influenza virus infection.
研究领域:
药理学
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病毒学
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免疫学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 5
·1055
·
IF 4.6
Qi Chen,Hui He,Yanghong Zhu,Xiang Li,Junhao Fang,Zhexi Li,Panghui Liu,Lin Zhou,Yufang Pan,Guoyu Wu
Individuals infected with COVID-19 often experience the distressing discomfort of pharyngitis. Thus, it is crucial to develop novel drugs to improve therapeutic options. In this study, we investigated the interaction between bioactive compounds isolated from Acanthopanax trifoliatus (L.) Merr and proteins associated with COVID-19 and pharyngitis through in silico analysis. Several molecules demonstrated high affinities to multiple targets, indicating significant potential for alleviating pharyngitis and other COVID-19-related symptoms. Among them, rutin and isochlorogenic acid C, two major components in Acanthopanax trifoliatus (L.) Merr ethanol extracts, were further experimentally demonstrated to exhibit strong inhibitory effects against SARS-CoV-2 and to possess significant anti-inflammatory activities. Inhibition of over 50% in several key genes was observed, demonstrating the efficacy of in silico methods in identifying high-affinity target binders. Our findings provide a theoretical foundation for the development of Acanthopanax trifoliatus (L.) Merr as a novel multi-target therapeutic agent for both COVID-19 and pharyngitis.
研究领域:
药理学
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生物信息学
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病毒学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Yingxin Liu,Fangliang Li,Tao Fei,Xue Lin,Lu Wang,Zhonghua Liu
Aquilaria sinensis leaves have long been consumed as a popular replacement tea for lowering postprandial blood glucose levels, but their specific functional components remain unclear. In this study, Aquilaria sinensis leaf-tea 70 % ethanol extract (ALTE) exhibited excellent anti-α-glucosidase activity (IC 50 = 6.93 ± 1.91 μg/mL) and promoted glucose consumption ability in 3 T3-L1 preadipocyte cells. Subsequently phenolic compositions of ALTE were identified for the first time. After that, five potential α -glucosidase inhibitors (α-GIs) including cynaroside-3,5-diglucose, malvidin 3-glucose, epicatechin, epigallocatechin gallate, and dihydromyricetin in ALTE were screened using a targeted bio-affinity ultrafiltration-HPLC/MS method. Moreover, these five α -GIs all showed good anti-α-glucosidase effects and glucose consumption-promoting ability. Furthermore, the binding properties and inhibition mechanisms of five α-GIs to α-glucosidase were further analyzed via enzyme inhibition kinetics, molecular docking, and molecular dynamics simulation. This study confirms that Aquilaria sinensis leaf-tea is effective in preventing post-hyperglycemia in vitro models, suggesting potential for future research in human trials.
研究领域:
植物化学
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药理学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Mingyu Zhang,Chunyu Xiang,Xin Zhen,Wenqi Luo,Xiaodong He,Fengshuo Guo,Renrui Niu,Wanguo Liu,Rui Gu
Traumatic spinal cord injury typically occurs at significant depths and triggers rapid and severe physiological responses. It is commonly accompanied by oxidative stress disorders, lipid peroxidation, accumulation of toxic aldehydes, and edema among other symptoms. The management of this condition requires intricate surgical procedures and vigilance against postoperative complications. Slow wound healing is a major clinical challenge. In this study, we developed an injectable hydrogel-based smart drug delivery platform (OPDL gel) for the treatment of cord injuries and integrated postoperative wound care. The hydrogel encapsulates the glucocorticoid dexamethasone (Dex) through a borate ester bond and can respond to degradation caused by reactive oxygen species (ROS) and pH changes in the microenvironment of spinal cord injuries. The OPDL gel was injected into the lesion with a degradation period of 60 h, enabling a controlled and intelligent release of Dex. Additionally, poly-ε-lysine macromolecules within the gel can absorb toxic aldehydes present in the microenvironment via Schiff base reactions, thereby mitigating secondary progression of spinal cord injury. When locally applied to spinal cord injuries, the gel demonstrated good biocompatibility and had a protective effect on damaged neural structures. In addition, OPDL gel also exhibited excellent bactericidal properties, achieving a 100% kill rate against microorganisms within 80 min and providing wound healing care comparable to a commercial product, Tegaderm™. Therefore, this multifunctional hydrogel drug-loading platform represents a novel approach for integrated treatment strategies in the clinical setting to address spinal cord injuries.
研究领域:
生物材料学
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神经科学
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药剂学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Wei Sun,Hongwei Wu,Yiyang Yan,Xianzhu Zhang,Xudong Yao,Rui Li,Jingyi Zuo,Wenyue Li,Hongwei Ouyang
The reconstruction of large osteoarticular defects caused by tumor resection or severe trauma remains a clinical challenge. Current metal prostheses exhibit a lack of osteo-chondrogenic functionality and demonstrate poor integration with host tissues. This often results in complications such as abnormal bone absorption and prosthetic loosening, which may necessitate secondary revisions. Here, we propose a paradigm-shifting “living prosthesis” strategy that combines a customized 3D-printed hollow titanium humeral prosthesis with engineered bone marrow condensations presenting bone morphogenetic protein-2 (BMP-2) and transforming growth factor–β3 (TGF-β3) from encapsulated silk fibroin hydrogels. This innovative approach promotes in situ endochondral defect regeneration of the entire humeral head while simultaneously providing immediate mechanical support. In a rabbit model of total humerus resection, the designed “living prosthesis” achieved weight, macroscopic and microscopic morphologies that were comparable to those of undamaged native joints at 2 months post-implantation, with organized osteochondral tissues were regenerated both around and within the prosthesis. Notably, the “living prosthesis” displayed significantly higher osteo-integration than the blank metal prosthesis did, as evidenced by a 3-fold increase in bone ingrowth and a 2-fold increase in mechanical pull-out strength. Furthermore, the "living prosthesis" restored joint cartilage function, with rabbits exhibiting normal gait and weight-bearing capacity. The successful regeneration of fully functional humeral head tissue from a single implanted prosthesis represents technical advance in designing bioactive bone prosthesis, with promising implications for treating extreme-large osteochondral defects.
研究领域:
骨科
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组织工程
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再生医学
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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
危险品化学品经营许可证（带存储）