Toxicology Research
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2018
·Vol. 7
·期 6
·1205-1213
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IF 1.89
Qiu Xuan,Zhou Xiaobing,Miao Yufa,Li Bo
The kidney is one of the major target organs for drug-induced toxicity. During drug development, the traditional markers of nephrotoxicity indicate only severe and late damage, which leads to high costs. The new biomarkers are needed for a more sensitive and reliable evaluation of nephrotoxicity, especially for the regulatory accepted and validated in vitro model. We developed an in vitro model based on the HK-2 cell using the biomarkers of nephrotoxicity as endpoints for the evaluation of nephrotoxicity. The predictive performance of the biomarkers including LDH, GGT, KIM-1, clusterin, CysC, NGAL, TIMP-1, GSTπ and osteopontin was evaluated with 22 well characterized compounds. The area under the curve (AUC) values of KIM-1, clusterin, CysC and osteopontin ranged between 0.79 and 0.84. The combination of clusterin, KIM-1 and/or osteopontin improved the AUC value (ranging between 0.88 and 0.95) compared to one biomarker. Taken together, these results suggest that the model based on the HK-2 cell using clusterin, osteopontin, CysC and KIM-1 as endpoints would allow the prediction of nephrotoxicity at early preclinical stages.
研究领域:
毒理学
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药理学
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细胞生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Xinyuan Liu,Xin Liu,Wanqiu Xue,Quan-Li Li,Leping Wu,Chris Ying Cao
Collagen fibers reinforced by hydroxyapatite (HA) constitute the fundamental structures of natural bone and dentin, where non-collagenous proteins (NCPs) play a regulatory role in collagen fiber mineralization. However, the precise mechanism underlying this mineralization process remains controversial. Moreover, achieving mineralized materials with high-purity, high-mimetic, and high-efficiency, as well as elucidating the essential state of mineralized precursor, are key issues in making a breakthrough in collagen fiber mineralization. Herein, an osteopontin phosphorylated polypeptide (OPP) was designed to explore the biomimetic mineralization of collagen fibers through mineralized ion stabilization and collagen surface modification. OPP could stabilize calcium and phosphate, forming OPP-prenucleation clusters (OPP-PNCs) with small sizes and long-term stabilization. Additionally, OPP could bind to and modify collagen fibers, thereby reducing the interfacial energy. Compared to Bare-Collagen, OPP-Collagen remarkably enhanced the mineralization efficiency. Molecular dynamics simulations indicated that OPP-Collagen could sequester calcium and phosphate from OPP-PNCs to induce mineralization, while Bare-Collagen lacks this ability. This biomimetic mineralization strategy utilizing OPP-PNCs achieved both intrafibrillar and extrafibrillar mineralization of OPP-collagen fibers. The present study introduces a novel OPP-Collagen mineralization strategy that highlights the regulatory role of NCPs on the surface of natural collagen, offering valuable perspectives into the mechanisms underlying natural mineralization processes.
研究领域:
生物材料学
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分子生物学
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骨组织工程
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Shichao Xuan,Houxi Leng,Fengzhi Qiao,Meijun Liu,Wenhao Ding,Zhe Zhang,Huaxi Yi,Changhong Ma,Lanwei Zhang,Kai Lin
Osteopontin (OPN) is a multifunctional protein with diverse physiological roles, but its low content in bovine milk and poor selection of existing extraction methods pose a serious challenge to its efficient separation. Therefore, this study developed magnetic molecular imprinted polymers (MIPs) using methacrylic acid (MAA)-functionalized Fe3O4 nanoparticles as matrix and N-isopropylacrylamide/N-(3-(dimethylamino)propyl) methacrylamide (NIPAM/DMAPMA) as functional monomers via surface free radical polymerization. The synthesized magnetic surface molecularly imprinted materials exhibited a core–shell structure with Fe3O4 nanoparticles as the core and a thin imprinted polymer shell. FTIR and XPS confirmed the presence of amide groups involved in specific interactions. XRD indicated the crystalline nature of Fe3O4, while TGA demonstrated good thermal stability for repeated use. The MIPs exhibited a maximum adsorption capacity of 96.2 mg/g for OPN with an imprinting factor of 2.57, after pseudo-second-order kinetics and Langmuir isotherm model fitting with an R2 > 0.98. Optimal performance occurred at 33 °C. Selective adsorption experiments with OPN, BSA, LF, α-LA, and β-LG demonstrated that MIPs had 2–3 times higher adsorption capacity for OPN compared to the interfering proteins. Competitive adsorption studies indicated preferential binding toward OPN in mixed protein systems, demonstrating superior molecular recognition. The MIPs also maintained 75% of their initial adsorption capacity after four regeneration cycles. These magnetic MIPs represent the first application of surface molecular imprinting for OPN and offer a promising strategy for selective separation with advantages in selectivity, magnetic separability, and reusability for practical applications.
研究领域:
材料科学
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分析化学
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纳米技术
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蛋白质分离与纯化
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分子印迹
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PubMed
高影响因子
Advanced Science
·
2023
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IF 15.1
Bingyang Dai,Yuwei Zhu,Xu Li,Zuru Liang,Shunxiang Xu,Shian Zhang,Zhe Zhang,Shanshan Bai,Wenxue Tong,Mingde Cao,Ye Li,Xiaobo Zhu,Wei Liu,Yuantao Zhang,Liang Chang,Patrick Shu-hang Yung,Kevin Ki-wai Ho,Jiankun Xu,To Ngai,Ling Qin
The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to a multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, the mechanisms behind the role of IPFP on knee OA progression remain to be defined. Here, dysregulated osteopontin (OPN) and integrin β 3 signaling are found in the OA specimens of both human and mice. It is further demonstrated that IPFP-derived OPN participates in OA progression, including activated matrix metallopeptidase 9 in chondrocyte hypertrophy and integrin β 3 in IPFP fibrosis. Motivated by these findings, an injectable nanogel is fabricated to provide sustained release of siRNA Cd61 ( RGD− Nanogel/siRNA Cd61 ) that targets integrins. The RGD− Nanogel possesses excellent biocompatibility and desired targeting abilities both in vitro and in vivo. Local injection of RGD− Nanogel/siRNA Cd61 robustly alleviates the cartilage degeneration, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass in OA mice. Taken together, this study provides an avenue for developing RGD− Nanogel/siRNA Cd61 therapy to mitigate OA progression via blocking OPN-integrin β 3 signaling in IPFP.
研究领域:
骨科
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分子生物学
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纳米技术
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风湿病学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
·
IF 4.9
Qingfeng Luo,Yuyi Deng,Qiyuan Yang,Nanxin Zhao,Can Wang,Xingsheng Li
Osteopontin (OPN), highly expressed in foam cells, serves as a hallmark of atherosclerotic plaques and a potential target for site-specific drug delivery. In this study, we developed OPN-targeted liposomes (OPN LIP) co-loaded with curcumin and perfluoro-n-pentane (PFP) to enhance therapeutic efficacy against atherosclerosis. The liposomes exhibited uniform particle size, colloidal stability, favorable biocompatibility, and minimal cytotoxicity. In vitro experiments demonstrated efficient and time-dependent cellular uptake by ox-LDL–stimulated RAW264.7 foam cells. Upon exposure to low-intensity focused ultrasound (LIFU), the nanocarriers underwent acoustic cavitation-induced rupture, leading to rapid curcumin release and significant induction of apoptosis. OPN LIP treatment notably reduced IL-1α and TNF-α levels and aggravated apoptosis in foam cells. Transcriptomic analysis revealed modulation of inflammatory and apoptotic pathways, including TLR, NF-κB, and Mapk3 signaling. These findings highlight the potential of OPN LIP as an ultrasound-responsive, targeted nanoplatform capable of suppressing inflammation and foam cell viability, providing a promising approach for the treatment of atherosclerosis through combined physical and pharmacological strategies.
研究领域:
纳米医学
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心血管疾病
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药物递送
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超声治疗
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炎症生物学
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细胞凋亡研究
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DOI
高影响因子
FOOD HYDROCOLLOIDS
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2023
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IF 10.7
Yuqin Huang,Zerong Lu,Feitong Liu,Jonathan Lane,Juchun Chen,Xiong Fu,Qiang Huang,Ruibiao Hu,Bin Zhang
Encapsulation is usually adapted to improve probiotic viability under adverse environmental conditions, and used to ensure adequate amount of probiotics reach the distal gastrointestinal tract and achieve probiotic action. In the present study, sub-species of Bifidobacterium were encapsulated with pectin or alginate by an emulsification/internal gelation method. Bovine milk osteopontin (OPN) was used as an excipient with potential to improve the protection of the probiotics during processing and/or gastrointestinal digestion. Here, we reported that the use of OPN significantly improved probiotic viability during freeze drying and simulated infant gastrointestinal digestion. The viability of Bifidobacterium bifidum R0071 and Bifidobacterium breve M-16V loaded in pectin-based freeze-dried microcapsules with 0.5% OPN addition remained at over 10 6 CFU·g −1 after simulated infant digestion. In comparison, the microcapsules without OPN had a probiotic viability of only 10 3 CFU·g −1 . The protective effect of OPN was proven to be dose dependent. For example, the B. bifidum R0071 viability was 6.1 log CFU·g −1 after the gastrointestinal digestion for the pectin-based microencapsulation without OPN addition, while the value remained at 8.4 log CFU·g −1 when OPN concentration reached 5%. In this study, we also demonstrated that extracellular calcium ions could chelate with OPN molecules which could be attributed to preventing damage of the probiotic cell wall and the improved protective effective of microencapsulation. Overall, these results provide new insight into the use of OPN as a microencapsulation excipient to promote probiotic viability and its potential future application in functional foods such as infant formula with enhanced gut health.
研究领域:
食品科学
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营养学
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微生物学
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生物技术
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DOI
高影响因子
Analytical Methods
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2025
·
IF 2.6
Xue Kong,Yan Liu,Jinghui Lyu,Zheng-Zhi Yin,Yi Zhang
Osteopontin (OPN) is an important biomarker for reflecting osteoarthritic inflammation and endochondral ossification. In the field of electroanalysis, OPN belongs to non-electroactive protein, which is usually detected by means of an outer probe or biolabel. Here, a novel microsensor can directly electroanalyze OPN, which was constructed by coordinating surface molecularly imprinted polymer (SMIP) with a built-in electroactive probe of poly (methylene blue) (pMB) on an acupuncture needle microelectrode (ANME). The OPN template can be reversibly anchored using 4-mercaptophenylboric acid (4-MBPA) via a borate bond between phenylboronic acid and the external cis-diol of the glycoprotein. Methylene blue (MB) and dopamine (DA) were sequentially electropolymerized and grown around templates, which played pivotal roles in the detection signal from the built-in pMB through the imprinted nanocavities. After the recombination of OPN molecules with imprinted nanocavities, the current strength of built-in pMB could be impeded with a highly sensitive response. This microsensor shows a linear relationship to the concentration of OPN from 0.01 to 1000 ng mL-1 with a detection limit of 3 pg mL-1. The microsensor also exhibits high selectivity and stability, which is attributed to the recognizing ability of the imprinted nanocavities and the hindrance and anti-interference function of coated polydopamine (pDA). This strategy of preparing a sensor shows practical and scientific significance for functionalizing microelectrodes and constructing microsensors for non-electroactive glycoproteins. In the future, it will be fascinating to integrate this microsensor with the acupuncture technique.
研究领域:
生物医学工程
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分析化学
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PubMed
高影响因子
FASEB JOURNAL
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2025
·Vol. 39
·期 9
·e70608
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IF 4.2
Wentao Liu,Yuan Wang,Chen Liu,Bowei Shi,Xiaowei Xiong,Sheng Chen,Qianqian Huang,Li Wang,Guohua Zeng,Qiren Huang
Atherosclerosis (AS) is the primary pathological basis of many cardiovascular diseases, and the formation of foam cells plays a critical role in the progression of AS. Increasing evidence shows that a considerable proportion of foam cells derive from vascular smooth muscle cells (VSMCs) in atherosclerotic plaques. Osteopontin (OPN), a glycosylated protein secreted by cells, is supposed to promote the development of AS. However, the underlying mechanisms of OPN contributing to the AS progression remain unclear. Therefore, the purpose of the study is to investigate the effects and mechanisms of OPN on VSMC-foaming and AS. Mouse AS model was established by feeding ApoE −/− mice with high fat diet (HFD), and the foam cell model of murine aortic vascular smooth muscle cells (MOVAS) was induced with Ox-LDL. During modeling, both ApoE −/− mice and MOVAS were infected with mouse recombinant adenoviruses expressing OPN (Ad-OPN). Our results show that OPN aggravates vascular smooth muscle dysfunction and AS in the ApoE −/− mice fed with HFD. Besides, OPN reduces cholesterol efflux and further promotes the formation of VSMC-derived foam cells by decreasing the expressions of ABCA1 and ABCG1. Furthermore, OPN inhibits the phosphorylation of p38MAPK through binding to its membrane receptor CD44, thereby reducing the expressions of LXRα, ABCA1, and ABCG1. Our results demonstrate that OPN reduces the expression of cholesterol transporters ABCA1 and ABCG1 and promotes the formation of VSMC-derived foam cells, exacerbating the development of AS. The findings would provide a more powerful theoretical support for preventing and treating AS with OPN as the target. Graphical OPN binding to CD44 inhibits the phosphorylation of p38MAPK, thereby reducing the expression of downstream LXRα, ABCA1, and ABCG1, resulting in decreased cholesterol efflux and increased foaming of VSMCs, ultimately exacerbating atherosclerosis.
研究领域:
心血管疾病
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分子生物学
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PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2024
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IF 5.7
Qin Weng,Hang Li,Zhichao Fan,Yan Dong,Yuchen Qi,Peilin Wang,Cheng Luo,Jianjun Li,Xiang Zhao,Hua Yu
Background Osteopontin (OPN) is closely associated with tumorigenesis, growth, invasion, and immune escape and it serves as a plasma biomarker for hepatocellular carcinoma (HCC). Nevertheless, the accurate and rapid detection of low-abundance OPN still poses significant challenges. Currently, the majority of protein detection methods rely heavily on large precision instruments or involve complex procedures. Therefore, developing a simple, enzyme-free, rapid colorimetric analysis method with high sensitivity is imperative. Results In this study, we have developed a portable colorimetric biosensor by integrating the triple-helix aptamer probe (THAP) and catalytic hairpin assembly (CHA) strategy, named as T-CHA. After binding to the OPN, the trigger probe can be released from THAP, then initiates the CHA reaction and outputs the signal through the formation of a G-quadruplex/Hemin DNAzyme with horseradish peroxidase-like activity. Consequently, this colorimetric sensor achieves visual free-labeled detection without additional fluorophore modification and allows for accurate quantification by measuring the optical density of the solution at 650 nm. Under optimal conditions, the logarithmic values of various OPN concentrations exhibit satisfactory linearity in the range of 5 pg mL −1 to 5 ng mL −1 , with a detection limit of 2.04 pg mL −1 . Compared with the widely used ELISA strategy, the proposed T-CHA strategy is rapid (∼105 min), highly sensitive, and cost-effective. Significance The T-CHA strategy, leveraging the low background leakage of THAP and the high catalytic efficiency of CHA, has been successfully applied to the detection of OPN in plasma, demonstrating significant promise for the early diagnosis of HCC in point-of-care testing. Given the programmability of DNA and the universality of T-CHA, it can be readily modified for analyzing other useful tumor biomarkers.
研究领域:
生物标志物检测
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癌症诊断
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分子生物学
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生物技术
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PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1-19
·
IF 7.5
Xing Chunyang,Hu Wei,Zhao Liyuan
Background Osteosarcoma (OS) is one of the most common malignancies arising in bone. Hypoxia and immune regulation are pivotal in tumor biology. However, their combined effects and mechanisms in OS remain understudied. This study aimed to explore the role and mechanism of hypoxic-induced M2 macrophages in promoting the progression of OS.Methods Differentially expressed proteins in hypoxic macrophage supernatants were detected by antibody array. Cell functional experiments, siRNA-mediated gene silencing, and overexpression transfection were used to study osteopontin (OPN) and its supernatant effect. Bioinformatics analysis was applied to investigate downstream targets and pathways, and a xenograft model was established to assess in vivo effects.Results Our data revealed that hypoxic M2 macrophage supernatant enhanced OS malignancy and epithelial-mesenchymal transition, activating cancer pathways. Hypoxia upregulated OPN in M2 macrophages, and OPN inhibition reduced its tumor-promoting effect. Early growth response 3 (EGR3) was differentially expressed in OS cells treated with the supernatant, and its overexpression inhibited OS cell migration, reversing tumor promotion. Interferon-stimulated gene 15 (ISG15), a key differentially expressed gene related to OPN and EGR3 overexpression, inhibited OS cell proliferation and migration. Additionally, OPN increased retinoic acid-inducible gene I (RIG-I) expression and enhanced signal transducer and activator of transcription 3, nuclear factor kappa B, and extracellular signal-regulated kinase signaling, while EGR3 and ISG15 overexpression inhibited these effects. Silencing ISG15 restored pathway activation and reversed the inhibitory effect of EGR3 on OS cell migration. Dual-Luciferase reporter gene assay confirmed that EGR3 activates ISG15 transcription. OPN treatment upregulated DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression, and ChIP assays demonstrated that EGR3 overexpression enhanced DNMT1 binding to the EGR3 promoter. These findings suggest that OPN promotes OS malignancy by downregulating EGR3 and ISG15, and by enhancing RIG-I expression, as validated in a xenograft model of OS.Conclusion Our findings demonstrate that hypoxic-induced M2 macrophages promote OS progression through OPN-dependent mechanisms, including inhibition of EGR3 and ISG15 expression and upregulation of RIG-I.Graphical abstract
研究领域:
癌症生物学
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免疫学
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分子生物学
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细胞生物学
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肿瘤微环境
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信号转导
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PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
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2023
·
IF 2
Jing Guo,Chang-Yong Tong,Jian-Guang Shi,Xin-Jian Li,Xue-Qin Chen
Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
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