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Materials Today Bio · 2025 · IF 10.2

Polydopamine@Zinc Oxide Coated Macroporous Membrane for Antibacterial Protection and Early Pulp Repair in Pulpitis

Yumeng Guo,Fei Chen,Qian Wang,Siqi Huang,Ziyu Chen,Quan Zhou,Congju Li,Ying Zheng

Continuous decompression and drainage are a vital surgical strategy for managing severe tissue infections. In vital pulp therapy (VPT) for irreversible pulpitis, there is a clinical demand for advanced biomaterials capable of effectively sealing the pulp cavity, alleviating pulpal hypertension, preventing bacterial infiltration, and resolving acute pulp inflammation in bacteria-rich environments. In this study, we developed a polydopamine@zinc oxide nanoparticle (ZnO-NP)-coated polytetrafluoroethylene (PTFE) membrane with tunable Zn content ranging from 2.51 to 7.45 wt%. The polydopamine enhanced ZnO-NP adhesion to the PTFE membrane, enabling superior fluid permeability and robust antibacterial efficacy against E. faecalis and S. mutans , while maintaining excellent biocompatibility. In a minipig pulpitis model, the ZnO-coated membrane significantly outperformed iRootBP PLUS by promoting faster dentine bridge formation (934.0 ± 91.3 μm vs. 116.3 ± 45.4 μm), preserving the integrity of the underlying pulp tissue and inducing M2 macrophage polarization.These findings deomstrate that ZnO-functionalized fibrous membrane can address key challenges in VPT by alleviating pulp hypertension, preventing microbial invasion, and simultaneously promoting pulp tissue regeneration. This approach offers a promising strategy to enhance tharepeutic outcomes of vital pulp therapy.

CAS / MDL: 1314-13-2 62-31-7
研究领域: 生物材料 · 牙科医学 · 组织工程 · 纳米技术 · 生物医学工程
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Nano Today · 2024 · IF 13.2

ROS-responsive biomimetic nanovesicles to plaque microenvironment in targeted therapy of atherosclerosis

Zhanhao Zhou,Hongbing Lan,Hongyuan Tan,Yi Wang,Wei Chen,Samira Batur,Chuansheng Fu,Li Kong,Conglian Yang,Boning Niu,Yuanyuan Guo,Zhiping Zhang,Kai Huang

Atherosclerosis, characterized by the accumulation of inflammatory cells at localised inflammatory sites with a high concentration of reactive oxygen species (ROS), is a leading cause of cardiovascular morbidity and mortality worldwide. There is a paucity of studies that effectively coordinate the targeting of inflammatory microenvironment and the controlled release of biomimetic carriers. Here, in view of the oxidative stress and inflammatory characteristics observed in the plaque microenvironment of atherosclerosis lesions, we propose an anti-inflammatory M2 macrophage membrane-derived nanovesicles co-fused with lipids containing ROS-sensitive thioketal (TK) linker and loaded with rapamycin (Rapa) to form a biomimetic hybrid system (Rapa@TLNVs). Benefiting from the inflammatory tendency of vesicles and ROS response of TK, Rapa@TLNVs can be delivered to plaque lesions and responsively release Rapa to synergistically help suppressing inflammation. Additionally, Rapa@TLNVs can reduce foam cells formation and the proliferation of macrophages. Following the administration of Rapa@TLNVs to ApoE −/− mice, a series of effects have been observed, including reductions in the inflammatory response, lipid deposition and increased plaque stability. Consequently, this work exploits the characteristics of the atherosclerosis plaque microenvironment to provide a promising strategy for combating atherosclerosis. This may further enrich the application experience of biomimetic hybrid nanovesicle platforms in atherosclerosis therapy.

CAS / MDL: 53123-88-9
研究领域: 心血管疾病 · 纳米技术 · 药学 · 炎症
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Food Bioscience · 2024 · IF 4.8

Ginkgolide B alleviates glucolipid metabolism disorders and adipose tissue inflammation by inhibiting thromboxane A2 synthesis

Yufeng Dai,Jinxiang Chen,Jialong Fang,Shuxiao Liang,Hao Zhang,Haitao Li,Wei Chen

Thromboxane A 2 (TXA 2 ) is traditionally known for its role in inducing platelet aggregation, but our previous study has discovered its crucial involvement in hepatic glucolipid metabolism and adipose tissue inflammation. Ginkgolide B (GB), a naturally occurring terpene lactone, possesses various pharmacological functions through its antagonism of the platelet activating factor (PAF) receptor. However, the metabolic regulation mechanism link between the anti-obesity efficiency of GB and TXA 2 has remained elusive. Therefore, this research aimed to explore the potential of GB in protecting against obesity by inhibiting TXA 2 synthesis. The results showed that GB inhibited TXA 2 biosynthesis which shares a similar action with eicosapentaenoic acid (EPA) and aspirin. GB treatment ameliorated hyperglycemia by decreasing gluconeogenesis. Additionally, GB supplementation relieved hepatic lipid deposition and dyslipidemia. Furthermore, GB intervention promoted macrophage M2 polarization, thus mitigating adipose tissue inflammation. In summary, our study provided evidence that GB alleviated glucolipid metabolism disorders and adipose tissue inflammation through the inhibition of the TXA 2 pathway. These findings shed light on the mechanism underlying the anti-obesity efficacy of GB and lay foundations for the future use of GB as a functional dietary supplement to alleviate high-fat diet-induced obesity.

CAS / MDL: 506-32-1 9007-34-5
研究领域: 药理学 · 代谢 · 炎症 · 营养
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Dual-Mode Release of IL-4 and TCP from a PGA-SF Core–Shell Electrospinning Scaffold for Enhanced Bone Regeneration through Synergistic Immunoregulation and Osteogenesis

Xiao Jiang,Yutao Jian,Yuan Zhang,Juan Zhong,Qiulan Li,Xiaodong Wang,Xiaoshi Jia,Xiangnan Wu,Ke Zhao,Yitong Yao

The successful filling of bone defects remains challenging due to the incongruity between bone graft materials and the dynamic process of bone healing. Developing multifunctional materials matching the dynamic process of bone healing offers a viable solution to the current dilemma. Lines of evidence have shown that engineering osteoimmunomodulatory biomaterials can modulate the function of immune cells and thus promote bone regeneration. Herein, we utilized silk fibroin (SF) and polyglycolic acid (PGA) to create a PGA-SF core–shell fibrous scaffold, incorporating interleukin-4 (IL-4) and tricalcium phosphate (TCP) as a codelivery system (PGA/TCP-SF/IL-4), aiming to achieve an initial rapid release of IL-4 and sustained release of TCP. The PGA/TCP-SF/IL-4 scaffold mimicked the native bone structure and showed superior tenacity in the wetting regime. In vitro studies demonstrated that the PGA/TCP-SF/IL-4 scaffold significantly reduced the inflammatory response by upregulating the M2 macrophages, created a favorable microenvironment for osteogenesis, and facilitated osteogenic differentiation and mineralization. Implantation of the PGA/TCP-SF/IL-4 scaffold into the rat skull defect model notably increased the formation of new bones. IL-4 and TCP acted synergistically in attenuating inflammation and enhancing osteogenic differentiation. Overall, this multifunctional scaffold comprehensively considers the various demands in the bone defect region, which might have a significant potential for application in bone reconstruction.

研究领域: 生物材料 · 组织工程 · 骨愈合 · 免疫学 · 再生医学
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Advanced Science · 2025 · IF 14.1

Carrier-Free Nanocapsule with Dual-Target Capacity for Synergistically Restoring Inflammatory Microenvironment and Microbiota Dysbiosis in Colitis

Yingjie Chen,Yuhan Gao,Kaiyuan Huo,Zhaofan Jin,Wenchao Wang,Xingjie Zan,Yanlong Liu,Limeng Zhu,Jianfeng Yang

Inflammatory bowel disease (IBD) is a chronic inflammatory disease with limited therapeutic outcomes. Macrophages are the key gatekeepers of intestinal immune homeostasis and have vital influence on IBD. Hence, macrophages are recognized as attractive targets to develop new therapeutic. However, the therapy development has proven challenging due to the malignant biological chain between macrophage immune hyperresponsiveness and dysbiosis of intestinal microflora. Herein, a carrier-free nano-drug, PCNPs@PEG-Man, with dual-targeting function, is produced due to IBD lesion-specific positive charge and high expression of mannose receptor. With super resistance against extreme intraluminal conditions, PCNPs@PEG-Man showes stable ROS-scavenging properties thereby. Notably, the dual-targeting strategy enhances the endocytosis efficiency and intestinal retention time of the drug, which is conducive to the downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, and repair of the intestinal barrier. Additionally, it reshaped the dysbiosis of intestinal bacteria, revealing an optimized gut flora composition of probiotics. The mechanism of the carrier-free nano-drug mainly involves the elimination of oxidative stress, promoting macrophage M2 polarization, and restoring gut homeostasis. The synergistic effect inherent in this dual-targeting system presents an effective and safe approach to managing IBD, providing new insights into the treatment of intestinal ROS-mediated diseases associated with microbiota dysbiosis.

研究领域: 纳米医学 · 免疫学 · 胃肠病学 · 药理学 · 微生物学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Rigid nanoparticles for efficient tumor immunotherapy through mechanical force mediated reprogramming of tumor-associated macrophages

Zhihuang Zhang,Yan Peng,Liyan Qiu

The enrichment of M2-phenotype tumor-associated macrophages (TAMs) is the main factor to create an immunosuppressive microenvironment, which seriously attenuates antitumor treatment. Herein, we explored the capability of rigid nanoparticles to reprogram TAMs to the M1-like phenotype via mechanical force. We designed and synthesized amphiphilic copolymer PLA- b -PItEG initiated by the HO-Pd(II) complex. In contrast to polyethylene glycol, the hydrophilic PItEG segments have a helical conformation, which endows the self-assembled PLA- b -PItEG nanoparticles with stiff surface characteristics of higher Young’s modulus and hydrophobicity. The rigid nanoparticles displayed strong interaction with TAMs to produce greater deformation of cell membrane and activated mechanosensitive potassium ion channel. Consequently, rigid nanoparticles exerted a positive effect on the proinflammatory polarization of TAMs. The expression level of CD86, a typical M1 macrophage marker, was increased by 60% compared with that in the soft PEG-NP group while CD206, a typical M2 macrophage marker, was decreased. Furthermore, several M1-related cytokines such as TNF-α, IL12p40, IL-6 and IL-1β were upregulated. In vitro and in vivo immune responses triggered by rigid nanoparticles could significantly inhibit B16F10 tumor growth with 71.44% tumor inhibitory rate. This study offers new insight into the use of mechanical forces for tumor immunotherapy.

研究领域: 纳米技术 · 免疫治疗 · 癌症研究 · 生物医学工程
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Advanced Science · 2024 · IF 14.3

A Multifunctional Metal–Phenolic Nanocoating on Bone Implants for Enhanced Osseointegration via Early Immunomodulation

Jin Liu,Yilin Shi,Yajun Zhao,Yue Liu,Xiaoru Yang,Kai Li,Weiwei Zhao,Jianmin Han,Jianhua Li,Shaohua Ge

Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal–phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr 2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.

研究领域: 生物材料 · 组织工程 · 免疫学 · 骨科
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MOLECULAR NEUROBIOLOGY · 2024 · IF 4.6

SLC15A3 is transcriptionally regulated by HIF1α and p65 to worsen neuroinflammation in experimental ischemic stroke

Yu Shan,Yang Jinghui,Zhang Rui,Guo Qian,Wang Lu

Systemic inflammatory stimulus is a risk factor for the incidence of ischemic stroke and contributes to poorer clinical outcomes. Solute carrier 15A3 (SLC15A3) is a peptide/histidine transporter that is implicated in regulating inflammatory responses. However, whether SLC15A3 affects the progression of ischemic stroke associated with systemic inflammation is unclear. The transient middle cerebral artery occlusion (tMCAO) mice with LPS administration (LPS/tMCAO) were prepared as an in vivo model, and LPS-induced BV2 cells under oxygen–glucose deprivation (OGD) exposure were utilized as an in vitro model. We found that SLC15A3 was highly expressed in the ischemic penumbra of LPS/tMCAO mice, and its inhibition reduced infarct area, attenuated neurological deficit, recovered motor function, and mitigated apoptotic neurons. Knockdown of SLC15A3 suppressed the proinflammatory M1-type markers and promoted the levels of M2-associated genes. The in vitro results confirmed that SLC15A3 overexpression promoted microglia polarizing towards M1 subtypes, while SLC15A3 inhibition exerted an opposite effect. In addition, we demonstrated that the p65 signaling pathway and HIF1α were activated by LPS/OGD. Luciferase reporter assay showed that inhibiting p65 using its specific inhibitor BAY 11–7082 or silencing HIF1α using siRNAs reduced the transcriptional activity of SLC15A3  in LPS/OGD-induced BV2 cells. Results in NIH 3T3 cells also confirmed that p65 and HIF1α directly bound to the SLC15A3 promoter to activate SLC15A3 transcription. In conclusion, this work shows that SLC15A3 , transcriptionally activated by p65 and HIF1α, contributes to poor outcomes in ischemic stroke associated with systemic inflammation by promoting microglial cells polarizing towards M1 types.

研究领域: 神经科学 · 免疫学 · 分子生物学 · 病理生理学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Immunomodulatory gallium/glycyrrhizic acid hydrogels for treating multidrug-resistant Pseudomonas aeruginosa-infected pressure ulcers

Chaofan Zhang,Erya Cai,Xiaoliang Qi,XinXin Ge,Yajing Xiang,Jiajia Wang,Ying Li,Lizhang Lv,Hui Zheng,Yuna Qian,Wei Dong,He Li,Jianliang Shen

Current approaches to treating infected pressure ulcers (IPUs) tend to lack specificity. Such injuries frequently exhibit extended inflammation and slow tissue regeneration, largely due to a surplus of M1 macrophages in the impacted regions. While immunomodulatory hydrogels offer potential for targeted IPU care, facilitating a safe and efficient shift from M1 to M2 macrophages continues to be a considerable challenge. The wound's harsh microenvironment—marked by unchecked infections and reactive oxygen species—often undermines the effectiveness of these hydrogels. We unveil a custom-engineered hydrogel dressing specifically designed to have immunomodulatory properties for expediting the healing of IPUs. Consisting of intertwined polymer networks, this hydrogel incorporates gallium (Ga) ions-triggered self-assembled glycyrrhizic acid (GA). Crucially, both in vitro and in vivo examinations, along with RNA sequencing assessments, demonstrate that the Ga/GA combination successfully reduces the M1/M2 macrophage ratio under inflamed circumstances, thereby contributing to improved IPU wound recovery. In summary, our proposed immunomodulatory strategy provides a simple, secure, and highly efficacious method for managing IPUs.

CAS / MDL: 760-93-0 13494-90-1
研究领域: 生物医学工程 · 药剂学 · 伤口愈合 · 免疫学 · 传染病
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FITOTERAPIA · 2025 · IF 2.6

Eight new gelsedine-type oxindole alkaloids from Gelsemium elegans

Li-Li Ye,Meng-Yue Yang,Xiang-Hai Cai

Eight new gelsedine-type oxindole alkaloids and ten known analogues were isolated from the stems and leaves of Gelsemium elegans . Gelseansdine A ( 1 ) was an N 4 -deficient Gelsemium alkaloid, while gelseansdines E–H ( 12 , 14 , 16 – 17 ) represented a class of alkaloids polymerized with iridoid. Their structures were elucidated based on UV, HRESIMS, NMR spectroscopy, and electronic circular dichroism (ECD) data analyses. Additionally, the isolated compounds were screened for their inhibitory activity on macrophage M2 polarization.

CAS / MDL: 119-51-7
研究领域: 植物化学 · 药物化学 · 免疫学
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Biomaterials Advances · 2023 · IF 0

Matrix stiffness-induced platelet activation determines immunomodulation of macrophages

Ruiqiang Hang,Zhenlong Wang,Hui Wang,Yi Zhang,Yuyu Zhao,Long Bai,Xiaohong Yao

Although various bone defect repair materials have been used clinically, the influence of the material properties on bone repair and regeneration as well as the underlying mechanisms are not fully understood. We hypothesize that the material stiffness affects initial platelet activation during hemostasis phase, which in turn mediates subsequent osteoimmunomodulation of macrophages, finally determining clinical outcomes. To verify the hypothesis, the present work used polyacrylamide hydrogels with different stiffness (10, 70, and 260 kPa) as model materials to investigate matrix stiffness induced platelet activation behavior and its mediation on osteoimmunomodulation of macrophages. The results showed that the matrix stiffness was positively related with activation degree of platelets. However, the extracts of platelets incubated on middle-stiff matrix polarized macrophages to pro-healing M2 phenotype when compared with that on soft and stiff matrixes. ELISA results showed when compared with that on soft and stiff matrixes, the platelets incubated on middle-stiff matrix released more TGF-β and PGE 2 , both of which could polarize macrophages to M2 phenotype. The M2 macrophages could promote angiogenesis of endothelial cells and osteogenesis of bone marrow mesenchymal stem cells, two important and coupled processes involved in bone repair and regeneration. These findings suggest bone repair materials with 70 kPa stiffness can mediate proper platelet activation, which can polarize macrophages to pro-healing M2 phenotype, potentially contributing to bone repair and regeneration.

研究领域: 生物材料 · 免疫学 · 组织工程 · 骨科
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ZEITSCHRIFT FUR KRISTALLOGRAPHIE-NEW CRYSTAL STRUCTURES · 2023 ·Vol. 238 ·期 3 ·471-473 · IF 0.3

Crystal structure of catena-poly[triaqua-[bis(m2-4-(1H-1,2,4-triazol-1-yl)benzoato-k2O:O')-(4-(1H-1,2,4-triazol-1-yl)benzoato-k1O)-praseodymium (III) monohydrate], C27H26N9O10Pr

Li Liu,Huan-Mei Guo,Li-Li Liu,Xin-Ru Qian

C 27 H 26 N 9 O 10 Pr, monoclinic, P 2 1 / c , a  = 13.2280(12) Å, b  = 5.5628(5) Å, c  = 41.140(3) Å, β  = 105.109(2)°, V  = 2922.6(4) Å 3 , Z  = 4, R gt ( F ) = 0.0426, w R ref ( F 2 ) = 0.0803, T  = 298.15 K.

研究领域: 化学 · 材料科学
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