INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Minrui Ji,Zaixin Yuan,Yang Zhu,Fei Han,Caichou Zhao,Xinyu Yu,Zhichao Chen,Yaoyu Huang,Haozhe Jiang,Lei Shi,Cong Ye,Fuyin Wan,Ran Tao,Zhenyu Zhou
The management of open bone defects poses a formidable challenge in clinical practice, primarily due to issues such as profuse bleeding, inflammation, bacterial infections, and compromised bone fracture healing. To tackle these complexities, we have devised a novel hemostatic powder, namely the compound strontium-based chitosan quaternary ammonium salt hemostatic powder (QCS@SrT-TA). This innovative powder leverages the self-assembly of tripolyphosphate and strontium ions, facilitated by a positively charged core cross-linker. Furthermore, its surface has been strategically modified with polyphenol and positively charged macromolecules, imparting unique properties. The mesoporous architecture of QCS@SrT-TA facilitates rapid moisture absorption, enhancing its efficacy. In preclinical studies using rat tail artery amputation and liver bleeding models, QCS@SrT-TA exhibited remarkable performance, significantly reducing both bleeding time and volume (62.39 ± 2.89 mg, 35.33 ± 4.16 s in tail amputation, 63.7 ± 5.19 mg, 62.33 ± 9.61 s in liver bleeding). Notably, the positively charged strontium ions and quaternary ammonium salts within the powder were effective in removing bacteria, minimizing the risk of infection. Beyond hemostasis, QCS@SrT-TA demonstrates additional therapeutic benefits. It polarizes M2 macrophage phenotypes and promotes angiogenesis within bone defect sites, accelerating bone healing processes. Ultimately, a substantially enhanced and notable functional recovery is achieved. In summary, the rapid hemostatic, potent antibacterial, anti-inflammatory, and angiogenesis-promoting characteristics of QCS@SrT-TA hold immense promise as a groundbreaking clinical treatment strategy for open bone defects.
研究领域:
生物医学工程
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创伤修复
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材料科学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yun Liu,Ziying Zhang,Yu Xia,Mengnan Ran,Qing Wang,Quanxin Wu,Wenhua Yu,Cao Li,Shiying Li,Ning Guo
In addition to tumor cells, M2-like tumor-associated macrophages (TAMs) also promote tumor progression. Accordingly, the strategy of targeted depletion or repolarization of M2-like TAMs becomes attractive. Here, we report a dual-targeting nanoagent SAMMH to tumor cells and M2-like TAMs for combinatorial tumor treatment. After co-loading the sonosensitizer spafloxacin (SPX) and oxidative phosphorylation inhibitor atavaquone (ATO) into hollow MnO 2 , the addition of Fe 3+ and tannic acid-immobilized hyaluronic acid (HA) caused the formation of SAMMH through generating metal-polyphenol networks (MPNs) coatings outside. In vitro endocytosis assays demonstrated the efficient internalization of SAMMH by both tumor cells and M2-like TAMs through the specific CD44-HA interactions. The GSH-sensitive degradation of SAMMH results in the continuous release of SPX and ATO. Meanwhile, SAMMH could catalyze the endogenous H 2 O 2 to extra O 2 , thus improving the therapeutic effect via the combination of Mn 2+ -induced CDT and O 2 -generation/O 2 -economy dual-enhanced sonodynamic therapy (SDT). Interestingly, SAMMH had a good targeted M2-like TAMs depleting capacity and could promote M2-to-M1 TAMs transformation by CDT-enhanced SDT, leading to a combinational anti-tumor effect. This dual-targeting nanoagent is a promising candidate to achieve CDT-enhanced SDT against both tumor cells and M2-like TAMs, thus providing new insights for the development of highly effective antitumor therapeutics.
研究领域:
癌症治疗
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纳米医学
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药学
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生物医学工程
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Yiyang Huang,Yichang Xu,Ziyan Huang,Jiannan Mao,Yujian Hui,Min Rui,Xinzhao Jiang,Jie Wu,Zhouye Ding,Yu Feng,Yong Gu,Liang Chen
The bone immune microenvironment can influence the occurrence and progression of bone defects. To date, research on promoting macrophage M2 polarization to improve bone injury repair has been insufficient. In this study, we designed an injectable poly(L-lactic acid) (PLLA) porous microsphere that forms calcium phosphate crystals on its surface by binding to melatonin, followed by bionanomimetic mineralization in vitro. The microsphere is injectable and degradable, and its release of melatonin (MT) and calcium phosphate (CaP) crystals promotes macrophage M2 polarization, reprogramming of macrophages, and enhanced osteogenesis. After LPS stimulation, the proportion of M2-polarized macrophages in the MS@CaP@MT group was 39.2 ± 2.7%, significantly higher than that in other groups (P < 0.05). Further, in the MS@CaP@MT group, rats exhibited bone mineral densities of 129.4 ± 12.8 mg cc−1 at 2 weeks and 171.6 ± 13.6 mg cc−1 at 4 weeks in the defect area, which were significantly higher than those in other groups (P < 0.05). Using an animal model of femoral condylar defects, we demonstrated that MT PLLA porous microspheres loaded with calcium phosphate crystals can improve the immune microenvironment and form a microsphere-centered osteogenesis model. This significantly accelerates bone defect repair and provides a potential strategy for bone defect treatment.
研究领域:
生物材料
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组织工程
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免疫学
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骨科
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2026
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IF 5.4
Yifan Guo,Fang Hu,Allan Zijian Zhao,Yingjuan Zeng,Haoying Chen,Ai Wang,Xiaoxi Li,Li Cong
Introduction Omega-3 polyunsaturated fatty acids (PUFAs) have been widely reported to exert beneficial effects in type 1 diabetes mellitus (T1DM). However, the mechanisms by which Omega-3 PUFAs influence pancreatic islet function through the gut-islet axis remain incompletely understood. This study aimed to investigate whether Omega-3 PUFAs-associated alterations in gut microbiota composition and their metabolites are involved in the modulation of the pancreatic islet microenvironment in T1DM, and to explore the potential immunological mechanisms underlying these effects. Methods Fecal microbiota transplantation (FMT) was performed to evaluate the effects of Omega-3 PUFAs-associated gut microbiota in non-obese diabetic (NOD) mice. Immune cell composition and inflammatory status within pancreatic islets were analyzed using transcriptomic profiling, flow cytometry, and immunohistochemistry. Metabolomics analysis was performed to investigate the association among Omega-3 PUFAs, gut microbiota, and microbiota-related metabolites. In vitro co-culture systems were further established to evaluate the effects of selected metabolites on macrophage polarization and insulin production and secretion in pancreatic β-cells. Results Omega-3 PUFAs treatment and FMT were associated with reduced islet inflammation and a marked enrichment of the Eubacterium coprostanoligenes group ( E. coprostanoligenes ). Enhanced M2 macrophage polarization was observed in the islet microenvironment of FMT mice. Among gut microbiota metabolites, 18β-glycyrrhetinic acid (18β-GA) showed a strong association with E. coprostanoligenes , and in vitro experiments suggested a potential involvement of E. coprostanoligenes in the metabolic conversion process related to 18β-GA. In co-culture systems, 18β-GA promoted macrophage polarization toward an M2-like phenotype, which was accompanied by increased insulin production and secretion in pancreatic β-cells. Conclusion These findings suggest that Omega-3 PUFAs-associated alterations in gut microbiota composition and 18β-GA-related metabolic changes may contribute to the modulation of the pancreatic immune microenvironment and β-cells function in T1DM. This study provides additional insights into lipid-microbiota-immune interactions relevant to T1DM and supports further investigation of microbiota-associated immune regulation.
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INORGANIC CHEMISTRY
·
2025
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IF 4.7
Guozhu Ren,Tingyu Pan,Yue Xu,Jingyu Wang,Lingdong Wang,Ruiping Deng,Shihong Zhou,Long Tian,Xiaojie Wu,Liang Zhou
Since the O–H and N–H oscillators of solvent molecules attached to ytterbium ion (Yb3+) and C–H oscillators existing in the inner coordination sphere of Yb3+ would quench the excited energy of Yb(III), which leads to low quantum yields (QYs) of Yb(III) complexes, we aimed to design a ligand that could block solvent molecules and C–H oscillators out of the first coordination sphere of Yb3+. Herein, a series of novel polycyclic aromatic dicarboxylate ligands are designed and synthesized to effectively protect Yb3+ from solvent molecules and efficiently sensitize Yb3+ luminescence, while the cost and sophistication of the synthesis are satisfactory. Therein, [Yb(MO–DPyPDA)2](DIEA) exhibited a considerable QY of 5.20% and a long luminescent lifetime of 102 μs in CD3OD. The single-crystal structure demonstrates that there are no solvent molecules and C–H oscillators existing in the inner coordination sphere of Yb3+, which is conducive to alleviating the quenching effect. Meanwhile, we also carried out experiments to verify that it was thermodynamically feasible for ligands to sensitize the luminescence of center ion through internal redox processes. Moreover, several groups of near-infrared organic light-emitting diodes based on [Yb(DTFM-DPyPDA)2](DIEA) were fabricated based on the solution-processing method, and the highest irradiance of 110,284 μW/m2 was realized by optimizing the device structure.
研究领域:
材料科学
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光学
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化学
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PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Jia Fu,Wei Zhao,Na Liang,Shaoping Sun
The treatment outcomes of chemotherapy are far from satisfactory due to suboptimal cellular uptake and inadequate intracellular release of antitumor drugs. Meanwhile, M2-like tumor associated macrophages (TAMs) in the tumor microenvironment promote cancer growth and metastasis. The combined strategy of chemotherapy and reprogramming M2-like TAMs within tumor microenvironment has emerged as a novel paradigm for cancer therapy. Hence, a pH-sensitive double-targeted inclusion complex was constructed for combined cancer therapy through the controlled paclitaxel (PTX) delivery and re-education of M2-like TAMs. The inclusion complex employed arginine and biotin modified hydroxypropyl-β-cyclodextrin (Arg-CD-Bio) as the host, with benzimidazole and mannose modified hyaluronic acid (BM-HA-Man) as the pH-sensitive plug. PTX was encapsulated in the inclusion complex. In vitro experiments indicated that the Arg-CD-Bio/BM-HA-Man inclusion complex could facilitate the specific release of PTX at the tumor site. The inclusion complex could be effectively internalized by M2-like TAMs and MCF-7 cells and further reprogramme M2-like TAMs to M1-like TAMs. In vivo antitumor therapy in 4T1 tumor-bearing mice had achieved remarkable suppression efficacy. These results suggested that the PTX-loaded Arg-CD-Bio/BM-HA-Man inclusion complex was a promising platform for efficient cancer treatment.
研究领域:
药学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2022
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IF 7.033
Biling Jiang,Yamin Zhang,Yuce Li,Yu Chen,Shanshan Sha,Liang Zhao,Danqi Li,Jingjing Wen,Jiajia Lan,Yuchen Lou,Hua Su,Chun Zhang,Jintao Zhu,Juan Tao
Background Mycophenolate mofetil (MMF), for which the bioactive metabolite is mycophenolic acid (MPA), is a frequently used immunosuppressant for systemic lupus erythematosus (SLE). However, its short half-life and poor biodistribution into cells and tissues hinder its clinical efficacy. Our dextran mycophenolate-based nanoparticles (MPA@Dex-MPA NPs) have greatly improved the pharmacokinetics of MMF/MPA. We here tested the therapeutic efficacy of MPA@Dex-MPA NPs against SLE and investigated the underlying mechanism. Methods The tissue and immune cell biodistributions of MPA@Dex-MPA NPs were traced using live fluorescence imaging system and flow cytometry, respectively. Serological proinflammatory mediators and kidney damage were detected to assess the efficacy of MPA@Dex-MPA NPs treatments of MRL/ lpr lupus-prone mice. Immune cell changes in the kidney and spleen were further analyzed post-treatment via flow cytometry. Bone marrow-derived macrophages were used to investigate the potential mechanism. Results MPA@Dex-MPA NPs exhibited superior therapeutic efficacy and safety in the MRL/ lpr mice using significantly lower administration dosage (one-fifth) and frequency (once/3 days) compared to MMF/MPA used in ordinary practice. The overall prognosis of the mice was improved as they showed lower levels of serological proinflammatory mediators. Moreover, kidney injury was alleviated with reduced pathological signs and decreased urine protein-creatinine ratio. Further investigations of the underlying mechanism revealed a preferential penetration and persistent retention of MPA@Dex-MPA NPs in the spleen and kidney, where they were mostly phagocytosed by macrophages. The macrophages were found to be polarized towards a CD206 + M2-like phenotype, with a downregulation of surface CD80 and CD40, and reduced TNF-α production in the spleen and kidney and in vitro. The expansion of T cells was also significantly inhibited in these two organs. Conclusion Our research improved the efficacy of MPA for MRL/ lpr mice through synthesizing MPA@Dex-MPA NPs to enhance its tissue biodistribution and explored the possible mechanism, providing a promising strategy for SLE therapy.
研究领域:
免疫学
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药学
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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 EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2022
·Vol. 41
·期 1
·1-15
·
IF 12.658
Cao Yi,Tu Yi,Xiong Jianbo,Tan Shengxing,Luo Lianghua,Wu Ahao,Shu Xufeng,Jie Zhigang,Li Zhengrong
Background Extracellular vesicles (EVs) derived from tumor-associated macrophages are implicated in the progression and metastasis of gastric cancer (GC) via the transfer of molecular cargo RNAs. We aimed to decipher the impact of microRNA (miR)-15b-5p transferred by M2 macrophage-derived EVs in the metastasis of GC.Methods Expression of miR-15b-5p was assessed and the downstream genes of miR-15b-5p were analyzed. GC cells were subjected to gain- and loss-of function experiments for miR-15b-5p, BRMS1, and DAPK1. M2 macrophage-derived EVs were extracted, identified, and subjected to co-culture with GC cells and their biological behaviors were analyzed. A lung metastasis model in nude mice was established to determine the effects of miR-15b-5p on tumor metastasis in vivo.Results miR-15b-5p was upregulated in GC tissues and cells as well as in M2 macrophage-derived EVs. miR-15b-5p promoted the proliferative and invasive potentials, and epithelial-mesenchymal transition (EMT) of GC cells. M2 macrophage-derived EVs could transfer miR-15b-5p into GC cells where it targeted BRMS1 by binding to its 3’UTR. BRMS1 was enriched in the DAPK1 promoter region and promoted its transcription, thereby arresting the proliferative and invasive potentials, and EMT of GC cells. In vivo experiments demonstrated that orthotopic implantation of miR-15b-5p overexpressing GC cells in nude mice displayed led to enhanced tumor metastasis by inhibiting the BRMS1/DAPK1 axis.Conclusion sOverall, miR-15b-5p delivered by M2 macrophage-derived EVs constitutes a molecular mechanism implicated in the metastasis of GC, and may thus be considered as a novel therapeutic target for its treatment.
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CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Dan Wu,Xiangyi Wu,Qichen Luan,Qing Tang,Lu Fan,Xin Shou,Xia Gao,Xiaoyun Qian,Yuanjin Zhao
Excessive reactive oxygen species (ROS) generated by wounds and bacterial infection are the great obstacles for diabetic wound closure. Here, we present a novel dual ROS-scavenging and antibacterial microneedle array patch with M2 macrophage-derived extracellular vesicles (M2-EVs) encapsulation for diabetic wound healing. The microneedle patch with a core–shell structure is composed of hyaluronic acid (HA) and PFP hydrogel crosslinked by polyvinyl alcohol (PVA)/2-formylphenylboronic acid (2-FPBA)/polyetherimide (PEI). When exposed to high levels of ROS existed in the wound, the dynamic covalent bonds of the hydrogel network can dissociate and subsequently release M2-EVs from the HA core. Benefitting from ROS-scavenging properties, antibacterial activities, and macrophage polarization driven by M2-EVs, the microneedle patch could effectively promote wound closure in diabetic animal models. These results indicated that the proposed ROS-scavenging microneedle patches with EVs delivery are promising for variety of difficult-to-heal wounds in clinical application.
研究领域:
生物医学工程
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伤口愈合
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材料科学
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药学
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高影响因子
Food Science & Nutrition
·
2025
·Vol. 13
·期 11
·e71234
·
IF 3.8
Liang Xue,Chun Cao
Inflammatory bowel disease (IBD) is a complex chronic intestinal inflammatory disease involving immune, genetic and environmental interactions. A disrupted balance in the polarization of intestinal macrophages is a key pathogenic link. This study explored whether octanoic acid (OA)‐rich enteral nutrition (EN) regulated intestinal M1/M2 macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway to alleviate IBD. First, to assess the effects of OA‐rich EN on IBD, four groups were established: the sham, IBD, IBD + EN, and IBD + OA‐rich EN. Second, to verify the regulatory role of intestinal M1/M2 macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway, six groups were established: the sham, IBD, IBD + OA‐rich EN, IBD + OA‐rich EN with intraperitoneal injections of IFNγ, AS1517499, or SR202. RAW264.7 cells were also used to observe how OA influences LPS/IFNγ‐induced M1 polarization. OA‐rich EN notably alleviated IBD symptoms, activated the PPARγ/STAT‐1/STAT‐6 pathway and remodeled the M1/M2 polarization balance of intestinal macrophages. These effects were greater than those in the IBD + EN group. Blocking the activation of PPARγ, activating STAT‐1 or inhibiting STAT‐6 reversed the protective effect of OA‐rich EN on remodeling the M1/M2 polarization balance of intestinal macrophages and IBD symptoms. In vitro experiments further confirmed that OA regulated macrophage polarization via the PPARγ/STAT‐1/STAT‐6 pathway. This is the first confirmation that OA‐rich EN alleviates IBD by activating PPARγ/STAT‐1/STAT‐6 to regulate macrophage polarization, highlighting its potential as a nutritional therapy for IBD. Octanoic acid‐rich enteral nutrition could regulate the M1/M2 polarization of intestinal macrophages and simultaneously repair the intestinal mucosal barrier by activating the PPARγ/STAT‐1/STAT‐6 pathway, thereby significantly alleviating inflammatory bowel disease‐induced intestinal injury.
研究领域:
免疫学
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胃肠病学
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营养科学
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分子生物学
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DOI
PubMed
高影响因子
RARE METALS
·
2026
·Vol. 45
·期 9
·e70620
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IF 12.1
Minghe Jiang,Ruikai Zhu,Shurong Chen,Xuwen Pan,Leiyuan Peng,Yaohui Huang,Wenquan Lv,Mingjing Yin,Xiaoxuan Guan,Mingyang Jiang,Ming Gao,Wei Wang,Yan Liu
en This link goes to a English section zh This link goes to a Chinese section Cisplatin-related acute kidney injury (CP-AKI) is a serious complication of cisplatin (CP) treated patients with cancer with high morbidity and mortality rates. It is directly related to the abnormal accumulation of CP in renal tubular epithelial cells, causing metabolic toxicity, DNA damage, and oxidative stress. Herein, we developed a polyphenol nanozyme (SrEG) by the coordination of strontium ions (Sr 2+ ) and epigallocatechin gallate. It was demonstrated that SrEG, combined with NIR irradiation, exhibited excellent capabilities of scavenging various types of reactive oxygen species (ROS). It was also determined that SrEG + NIR efficiently eliminated intracellular ROS levels, inhibited inflammation related cytokines expression, and induced macrophage M2 directional polarization, thus preventing cellular damage. By intravenous (IV) administration, SrEG was efficiently accumulated in the kidney and gradually degraded. Accordingly, the administration of SrEG + NIR offered the perfect therapeutic effects in CP-AKI rats by inhibiting the PI3K/AKT pathway, thus accelerating kidney function repair. Overall, the strategy of SrEG + NIR showed substantial clinical promise as a potential therapeutic strategy in ROS-related diseases. 摘要 en This link goes to a English section zh This link goes to a Chinese section 顺铂相关的急性肾损伤(CP-AKI)是癌症患者进行顺铂(CP)治疗时的严重并发症,具有较高的致病率和死亡率。CP-AKI与CP在肾小管上皮细胞中的异常积聚直接相关,从而导致代谢毒性、DNA损伤和氧化应激。在此,我们通过锶离子(Sr 2+ )和表没食子儿茶素没食子酸酯的配位开发了一种多酚纳米酶(SrEG)。结果表明,SrEG结合近红外光照展现出优异的清除各种类型活性氧(ROS)的能力。而且SrEG + NIR有效地降低细胞内ROS水平,抑制炎症相关因子的表达,并诱导巨噬细胞M2定向极化,从而防止细胞损伤。通过静脉注射(IV)给药,SrEG在肾脏中有效积聚并逐渐降解。因此,SrEG + NIR的治疗策略通过抑制PI3K/AKT通路,从而加速肾功能修复,为CP-AKI大鼠提供了完美的治疗效果。总体而言,SrEG + NIR作为ROS相关疾病的潜在治疗策略显示出巨大的临床前景。
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INFLAMMATION
·
2026
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IF 5.4
Ren Niansheng,Li Ruixi,Tao Qiang,Hong Shengjie,Wang Jicai,Zha Jiandong,Wang Shikai,Zhang Guangquan
Chronic pancreatitis (CP) is a chronic disease characterized by pancreatic fibrosis driven by pancreatic stellate cell activation and M2 polarization of macrophages. Nicotinamide n-methyltransferase (NNMT) is a methylase critically involved in fibrosis. Galectin-3 (LGALS3), a member of the galectin family, drives M2 macrophage polarization. This study explores the roles of NNMT and LGALS3 in CP. CP was induced in C57BL/6 mice via repeated intraperitoneal injections of 50 µg/kg cerulein. NNMT was upregulated in pancreatic tissues of CP mice, especially in mouse pancreatic stellate cells (mPSCs). Functional inhibition of NNMT in mPSCs, via lentiviral short-hairpin RNA-mediated knockdown or treatment with NNMT inhibitor, suppressed mPSC activation, proliferation, and migration. Moreover, conditioned medium from mPSCs with NNMT inhibition reduced M2 polarization of bone marrow-derived macrophages (BMDMs). In vivo, intraperitoneal administration of 20 mg/kg NNMT inhibitor for 28 days alleviated pancreatic collagen deposition and macrophage M2 polarization, resulting in reduced pancreatic fibrosis. RNA sequencing and bioinformatics analysis identified LGALS3 as a potential downstream target of NNMT. NNMT inhibition downregulated LGALS3 expression in mPSCs, and chromatin immunoprecipitation - quantitative polymerase chain reaction (ChIP-qPCR) confirmed that this suppression was associated with increased trimethylation of lysine 27 on histone H3 (H3K27me3) enrichment at the LGALS3 promoter. Lentivirus-mediated LGALS3 overexpression reversed the inhibitory effect of NNMT knockdown on BMDM M2 polarization. In conclusion, inhibition of NNMT alleviates mPSC activation and suppresses mPSC-induced macrophage M2 polarization via H3K27me3-mediated repression of LGALS3 transcription, with the ultimate effect of mitigating cerulein-induced pancreatic fibrosis.
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