JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Shudan Zheng,Zhenghao Zhou,Jie Ji,Yuxin Liu,Xiaodan Jiao,Xiaoyang Li,Yi Shen,Hao Hong,Xiaodong Han
Idiopathic pulmonary fibrosis (IPF) exhibits extremely high mortality rates. Targeted therapy, which utilizes specific drugs or other substances to identify and attack specific molecular targets in the lesion, holds promise as a potent means of treating IPF. M2 macrophages have been shown to express high levels of osteopontin (OPN) early in the onset of IPF and sustain this high expression to promote the progression of IPF. Intervention in OPN expression can effectively impede the development of fibrosis. While the technology for targeting proteins with siRNA has become increasingly mature, the targeted delivery of siRNA to resident M2 macrophages in the lungs remains challenging. In this study, we developed an engineered self-assembling OPN siRNA carrier complex based on a metal-polyphenol network (luteolin-Zr) and PEG conjugated with an M2 macrophage-targeting peptide (Pery-PEG-M2), termed siOPN@LuZ-M2, for the treatment of pulmonary fibrosis. Consequently, significant therapeutic effects were observed in both bleomycin-induced pulmonary fibrosis mouse models and human precision-cut lung slices (hPCLS) models. Importantly, luteolin, which is slowly released from siOPN@LuZ-M2 within cells, can gradually accumulate in fibrotic lung tissue, exerting an anti-inflammatory effect and further enhancing the treatment of IPF. It is worth mentioning that siOPN@LuZ-M2 can be labeled with 89 Zr, allowing for the detection of its in vivo distribution and metabolic behavior via PET-CT. This study presents a promising new image-guided molecular targeting strategy for the treatment of fibrosis.
研究领域:
药理学
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分子生物学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Qing-zhu Zhang,Hui-yuan Xu,Chao-yan Feng,Chu-hao Zhang,Kun Ren,Ying-ni Pan,Dong-mei Wang,Shu-meng Ren,Xiao-qiu Liu
Ethnopharmacological relevance The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus , with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones ( Lin Zheng ). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. Aim of study This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. Materials and methods The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD 3 were compared in vivo . Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. Results There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L - Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy ( P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. Conclusion The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD.
研究领域:
药理学
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民族药理学
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泌尿学
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传统中药
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Huan Chen,Jin Liu,Jia Zhang,Yuqian Chen,Yan Wang,Yuanjie Qiu,Huizhong Hu,Limin Chai,Qianqian Zhang,Qingting Wang,Manxiang Li
Bromodomain-containing protein 4 (BRD4) is recognized as a member of the bromodomain and extraterminal (BET) family that is involved in the airway inflammation and airway remodeling of asthma. However, the underlying mechanisms of BRD4 in airway smooth muscle cells (ASMCs) proliferation and airway remodeling remain unclear. Primary cultured rat ASMCs and ovalbumin (OVA)-induced rat asthma models were applied to address these issues in the present study. We showed that transforming growth factor β1 (TGF-β1) increased the protein expression of ubiquitin specific peptidase 22 (USP22), which deubiquitinated BRD4 therefore increased its expression, and then resulted in the upregulation of glioma-associated oncogene homolog 1 (GLI1) and osteopontin (OPN) leading to ASMCs proliferation. We further confirmed that induction of TGF-β1 sequentially upregulated USP22, BRD4, GLI1 and OPN leading to airway remodeling in OVA-induced rat asthma models, targeting TGF-β1/USP22/BRD4/GLI1/OPN pathway axis effectively attenuated airway remodeling and asthma development. Our study provides novel sights to understand the role of TGF-β1/USP22/BRD4/GLI1/OPN axis in airway remodeling, and targeting this pathway might have potential value for the prevention and treatment of asthma.
研究领域:
医学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Junpeng Liu,Ting Chu,Mimi Wan,Li Xiao,Yi Sun,Yunyu Gu,Xiao Wang,Zheng Song,Chunlan Xie,Linyan Zhang,Jihong Wang
The high recurrence rate of herpes simplex keratitis (HSK) is primarily attributed to the reactivation of herpes simplex virus type 1 (HSV-1) within the trigeminal ganglion (TG), a latent viral reservoir cannot be eradicated by current antiviral or anti-inflammatory therapies. This study aims to elucidate the novel immune mechanisms regulating viral reactivation within the TG and to develop a targeted therapeutic strategy based on this mechanism. We found that macrophages are the key effector cells inhibiting viral reactivation in recurrent HSK models, exerting their core antiviral function through the release of macrophage extracellular traps (METs) rather than neutrophil extracellular traps (NETs). Mechanistically, MET formation is highly dependent on the activity of peptidylarginine deiminase 2 (PAD2). Importantly, METs function not merely as physical capture structures but act as signaling vehicles by releasing osteopontin (OPN) as a key messenger. OPN activates the expression of the interferon-stimulated gene ISG15 in adjacent neurons, thereby establishing a previously unrecognized “PAD2-METs-OPN-Neuron ISG15” immune-neuron synergistic antiviral axis. To translate this mechanism into a therapeutic strategy, we engineered a lipid nanoparticle encapsulating a PAD2-overexpressing plasmid, which was further camouflaged with macrophage membranes to construct the biomimetic delivery system pPAD2@MNPs. Unlike conventional gene delivery platforms, this system leverages the “homing effect” via VLA-4/LFA-1 on the membrane surface binding to VCAM-1/ICAM-1 at inflammatory sites, this system achieves precise targeting of TG lesions. In vivo experiments confirmed that local administration of pPAD2@MNPs significantly upregulates PAD2 expression within the TG, effectively reducing viral load and improving corneal pathology scores. Furthermore, biosafety evaluations revealed no significant systemic toxicity or major organ damage induced by this nano-system. In summary, this study reveals a novel mechanism of immune-neuron crosstalk in regulating HSV-1 latency within the TG and provides a safe and effective targeted nanomedicine strategy for the radical treatment of recurrent HSK.
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产品关联
DOI
高影响因子
MATERIALS LETTERS
·
2016
·
IF 2.437
Huan Zhou,Shiqin Kong,Zhiwei Liu,Yan Pan,Yang Liu,Mingzhi Luo,Linhong Deng
Calcium polyphosphate (CPP) incorporated calcium alginate (CA) composite beads were prepared via adding sodium polyphosphate (STPP) contained sodium alginate (SA) solution dropwise to calcium chloride (CaCl 2 ) solution. In the process Ca 2+ ion may attach to the -COO − in SA because of electrostatic attraction. Additionally, there is an interaction of PP to Ca 2+ to generate CPP, inducing intermolecular crosslinkages between CA and CPP. The rotational rheometer showed STPP addition had no significant impacts on the rheological properties of SA solution. While a combination of SEM, AFM, FTIR and swelling behavior study demonstrated CPP was successfully formed within the gel network of CA gel beads and played an active role in restricting the movability of the alginate polymer chains. The in vitro study implied CPP can promote the expression of ALP , Col-I, OCN and OPN of osteoblasts.
研究领域:
材料科学
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生物医学工程
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细胞生物学
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
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IF 3.973
Meilin Shi,Shan Wang,Shaohui Zheng,Pingfu Hou,Lina Dong,Meijuan He,Chen Wu,Xiuli Zhang,Fengmei Zuo,Kai Xu,Jingjing Li
Multifunctional nanocarriers, which can be used for molecular imaging and drug delivery simultaneously, favor the fabrication of theranostic platforms in a less cost- and time-consuming way. Polyethylene glycol (PEG)-modified manganese dioxide (MnO 2 ) nanosheets (PEG-MnO 2 ), used as two-dimensional nanomaterials, not only possess the high surface-to-volume ratio necessary for drug delivery but also display a redoxable property in the tumor microenvironment, producing Mn 2+ ions for magnetic resonance imaging (MRI). In this study, we constructed a PEG-MnO 2 -OPN siRNA nanocomplex via a modular streptavidin bridge for the theranostic treatment of renal carcinoma in vitro and in vivo . This strategy of utilizing PEG-MnO 2 nanosheets for OPN siRNA delivery showed effective tumor growth inhibition of 786-O tumor-bearing mice, and such a process could be monitored by the activated T 1 -weight MRI, illustrating the promising potential of PEG-MnO 2 nanosheets for the fabrication of an MRI-based theranostic system.
研究领域:
生物医学工程
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药学
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癌症研究
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纳米技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2024
·
IF 2.3
Chao Han,Dingsong Lu,Suoping Yang,Chong Liu,Feng Guo,Kai Zhang,Peng Li
The design and construction of a new and excellent synthetic graft is of great significance in the field of bone defect repair and reconstruction. In this study, a dopamine modified chitosan hydrogel doped with Cu ions with a mild photothermal effect was designed to provide a better microenvironment to advance the bone repair via promote the angiogenesis and osteogenesis. Characterizations showed the successful synthesis of the material while it also presented excellent biocompatibility and mild photothermal effect under the irradiation of near-infrared light. Further, it could enhance the angiogenesis of HUVECs cells through promoting the ability of migration and tube formation and enhance the osteogenic differentiation of MC3T3-E1 cells via increasing the content of vital osteogenic factors including Runx2, Col-1, OPN, OCN, OSX, etc. The in vivo experiment also testified that it could promote the bone defect repair in rat models. These results indicate the multifunctional hydrogel is an ideal material for the treatment of bone defects and has good clinical application potential.
研究领域:
生物材料
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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
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
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2018
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IF 6.383
Ye He,Caiyun Mu,Xinkun Shen,Zhang Yuan,Ju Liu,Weizhen Chen,Chuanchuan Lin,Bailong Tao,Bin Liu,Kaiyong Cai
Titanium (Ti) and Ti-alloys were widely used in clinic orthopedics, however, the insufficient bone formation surrounding Ti-based implants still limited their biological performances. Surface modification of Ti substrates is essential to improve their interactions with bone-forming cells and bone tissue. In this study, we modified Ti substrates by coating peptide LL-37 onto micro-structured Ti substrates and aimed to (i) induce mesenchymal stem cells (MSCs) migration both in vitro and in vivo , (ii) facilitate osteogenic differentiation of MSCs and new bone formation. The surface micro-structured Ti substrates with hydroxyapatite deposition were fabricated by a two-step method including micro-arc oxidation (MAO) and hydrothermal treatment. LL-37 was loaded on micro-structured Ti substrates with the assistance of polydopamine coating. We confirmed that surface-modified Ti substrates benefited viability, adhesion, migration and osteogenic differentiation of MSCs in vitro . In a femur-defect rat model, the surface-modified Ti implants effectively induced CD29 + /CD90 + positive cells migration in one week after implantation. According to the results of H&E, Masson’s trichrome staining and immunohistochemical staining of OCN , OPN and collagen I, the targeted Ti implants exhibited significant new bone formation after implantation for 4 weeks. These results indicate that the surface modification of Ti samples facilitated bone formation through MSCs recruitment. Statement of Significance The inherent surface bioinertness of titanium (Ti) and Ti-alloys still limits their biological performances in clinical applications. Recently, the strategy of mesenchymal stem cells (MSCs) recruitment has been proposed to improve the osteointegration of bone implants. Herein, we reports the surface modification of Ti implants from the point of MSCs recruitment. Peptide LL-37 was coated on micro-structured Ti substrates to (i) recruit MSCs, (ii) regulate bio-physiological performance of MSCs, and (iii) facilitate bone formation in vivo. Our results improve the understanding of the interaction between Ti implants and MSCs, and provide a promising strategy of MSCs recruitment in the design of bone repair related biomaterials.
研究领域:
生物材料
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组织工程
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骨科
·
干细胞生物学
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产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Zuyun Yan,Tianshi Sun,Wei Tan,Zhicheng Wang,Jinpeng Yan,Jinglei Miao,Xin Wu,Pei Feng,Youwen Deng
In the system of magnesium-loaded scaffolds, the effect of magnesium ions (Mg 2+ ) on the osteogenesis induction is restricted due to the low transmembrane transport efficiency of Mg 2+ into the cell, which limits the application for bone defect repair. Inspired by the fact that magnetic field can regulate ion channel proteins on the cell membrane, magnetite nanoparticle is introduced into the poly (l-lactic acid) /magnesium oxide composite in this study, and a magnetic magnesium-loaded bone scaffold is prepared via selective laser sintering . Notably, the activities of the Mg 2+ channel protein (MAGT1) on the membrane of bone marrow mesenchymal stem cells (rBMSCs) are enhanced via magnetic torque effect (via integrin α V β 3/actin), under the action of static magnetic field (SMF), which promoted rBMSCs to capture Mg 2+ in the microenvironment and induced osteogenesis. In vitro experiments showed that the magnetic magnesium-loaded scaffold, under the action of SMF, can accelerate the inflow of Mg 2+ from surrounding microenvironment, which improved cellular activities, osteogenesis-related gene expression (ALP, Runx2, OCN, and OPN), and mineralization. Besides, in vivo skull defect repair experiments showed that the scaffolds possessed good ability to promote bone differentiation and new bone regeneration.
研究领域:
生物材料
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组织工程
·
生物医学工程
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细胞生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS RESEARCH
·
2021
·Vol. 36
·期 9
·1866-1882
·
IF 3.089
Wu Jin,Liu Yajing,Zhang Hao,Wu Yizhen,Chu Zhuangzhuang,Wu Qirong,Lu Mengmeng,Tang Chunbo
Abstract In this study, we presented that human bone mesenchymal stem cells (hBMSCs) showed superior adhesion and proliferation behaviors on polished silicon nitride (Si 3 N 4 ). Also, compared to Ti and ZrO 2 , Si 3 N 4 enhanced the osteogenic activities of hBMSCs indicated by increases in alizarin red S (ARS) staining, Ca 2+ concentration, and mRNA expression of RUNX2, OPN, OCN, and COL1. Furthermore, colony formation assays demonstrated significantly better antibacterial activities against oral pathogens Porphyromonas gingivalis (Pg), Staphylococcus aureus (SA), and Escherichia coli ( E. coli ) on Si 3 N 4 surface than Ti and ZrO 2 . Live/dead bacterial staining showed a large amount of dead Pg on Si 3 N 4 surfaces. The fact that Si 3 N 4 demonstrated advantages in osteogenic and antibacterial activities over Ti and ZrO 2 might be a reason for its potential use as non-metallic dental implant materials. However, more detailed studies with resolution techniques and preclinical studies are needed to confirm the Si 3 N 4 ’s osteogenic and antibacterial properties. Trial registration number PJ2019-066-001; date of registration: Jun 2019. Graphic abstract
研究领域:
牙科学
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生物材料
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细胞生物学
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Shuaijie Li,Liyan Zhang,Chunyu Liu,Jua Kim,Kun Su,Tingli Chen,Limin Zhao,Xiaomei Lu,Hao Zhang,Yinglin Cui,Xu Cui,Feng Yuan,Haobo Pan
Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro , the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.
研究领域:
生物材料
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组织工程
·
骨科
·
生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yuping Wang,Yiting Lei,Nan Wang,Jun Zhang,Wenguo Cui,Xiaoji Luo
The challenge of achieving graded regeneration of adjacent tissues remains significant in tissue repair and regeneration. For instance, the disruption of the microenvironment caused by “osteogenesis mobilization” often results in fibrosis of the regenerated cartilage, ultimately leading to osteoarthritis. Inspired by the utilization of activated carbon for adsorbing and filtering small particles in air purification and water treatment, we have designed an integrated hydrogel scaffold capable of absorbing the endogenous BMP-2 produced by “osteogenesis mobilization”, confining it to the bone defect area, and preventing its diffusion into the cartilage region, thereby facilitating physiological osteochondral gradient regeneration. The osteogenic layer of this integrated scaffold is NHAP-AHAMA-B2A, which captures the BMP-2 produced by “osteogenesis mobilization” and amplifies its osteogenic effect through the grafted peptide B2A. This upregulation enhances the expression of ALP, OCN, and OPN in MSCs within the osteogenic layer, promoting osteogenic differentiation. The chondrogenic layer, HAMA-B2A, utilizes the peptide B2A to upregulate the expression of COL II and ACAN in MSCs, fostering chondrogenic differentiation. This integrated HAMA-B2A/NHAP-AHAMA-B2A hydrogel scaffold confines the BMP-2 produced by “osteogenesis mobilization” to the bone defect area, prevents its diffusion into the cartilage defect area, and effectively utilizes it to induce stem cell osteogenic differentiation. Simultaneously, it induces stem cell chondrogenic differentiation in the cartilage defect area, achieving transparent cartilage regeneration. In summary, the osteogenic and chondrogenic layers of this integrated scaffold collaborate to achieve a physicochemical gradient regeneration of bone-cartilage.
研究领域:
组织工程
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再生医学
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生物材料科学
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骨科
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）