JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yan Hu,Lixi Tang,Zheng Wang,Honghan Yan,Xinzeyu Yi,Huimin Wang,Liya Ma,Changying Yang,Jiabing Ran,Aixi Yu
Immunoregulation mediated bone tissue engineering (BTE) has demonstrated huge potential in promoting repair of critical-size bone defects (CSBDs). The trade-off between stable immunoregulation function and extended immunoregulation period has posed a great challenge to this strategy. Here, we reported a 3D porous biodegradable Poly(HEMA- co -3APBA)/LUT scaffold, in which reversible boronic acid ester bond was formed between the 3APBA moiety and the catechol moiety of luteolin (LUT). The boronic acid ester bond not only protected the bioactivity of LUT but also extended the release period of LUT. The rationale behind the phenomenon of sustained LUT release was explained using a classical transition state theory. In vitro/in vivo assays proved the immunoregulation function of the scaffold in inducing M 2 polarization of both M 0 and M 1 M φ . The crosstalk between the scaffold treated Raw 264.7 and BMSCs were also investigated through the in vitro co-culture assay. The results demonstrated that the scaffold could induce immunoregulation mediated osteogenic differentiation of BMSCs. In addition, CSBDs model of SD rats was also applied, and the corresponding data proved that the scaffold could accelerate new bone formation, therefore promoting repair of CSBDs. The as-prepared scaffold might be a promising candidate for repair of CSBDs in the future.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Siming Huang,Wangshu Zhu,Fang Zhang,Guosheng Chen,Xiaoxue Kou,Xieqing Yang,Gangfeng Ouyang,Jun Shen
Triple-negative breast cancer (TNBC) is typically associated with poor prognosis due to its only partial response to chemotherapy and lack of clinically established targeted therapies coupled with an aggressive disease course. Aerobic glycolysis is a hallmark of reprogrammed metabolic activity in cancer cells, which can be repressed by small-interfering RNA (siRNA). However, the lack of effective carriers to deliver vulnerable siRNA restricts the clinical potentials of glycolysis-based gene therapy for TNBC. Herein, we develop a tumor-targeted, biomimetic manganese dioxide (MnO2)-shrouded metal–organic framework (MOF) based nanomedicine to deliver siRNA against pyruvate kinase muscle isozyme M2 (siPKM2), wherein PKM2 is a rate-limiting enzyme in glycolysis, to inhibit the reprogrammed glycolysis of TNBC. This MOF-based genetic nanomedicine shows excellent monodispersity and stability and protects siPKM2 against degradation by nucleases. The nanomedicine not only substantially blocks the glycolytic pathway but also improves intracellular hypoxia in TNBC cells, with a resultant O2-enhanced anticancer effect. In the mice orthotopic TNBC model, the nanomedicine shows a remarkable therapeutic effect. Meanwhile, the Mn2+ ions released from acid microenvironment-responsive MnO2 enable in vivo monitoring of the therapeutic process with magnetic resonance imaging (MRI). Our study shows great promise with this MRI-visible MOF-based nanomedicine for treating TNBC by inhibition of glycolysis via the RNA interference.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2019
·Vol. 9
·期 8
·1108-1113
·
IF 0.824
Fan Gaofu,Xu Zhenguo,Tang Jie,Liu Longyun,Dai Ruomeng
Objection: To study the effect of modified formulae for ellagic acid (EA) on wound healing and macrophage phenotype transformation in diabetic mice. Materials and Methods: 10 db/m mice regarded as normal group, Dividing 20 db/db mice as the model group and EA group, 10
in every group. Surgical operation on the back was made to prepare experimental wound models. External medicines were applied and changed dressings every other day and measurement. Wound tissues were gained when animals were sacrificed by anesthesia 7 days later. Pathological changes were
observed by HE and Masson staining methods, while using RT-PCR and IHC to measure mRNA and protein levels of MI/M2 type cytokines of the wound tissues. Results: Compared with the normal group, the wound area of db/db was greater (P < 0.001), while EA group less (P <
0.001). IL-12 and TNF-α mRNA and proteins levels in model group were higher (P < 0.001, respectively), while VEGF and TGF-βmRNA and proteins were lower. mRNA and protein levels of inflammato cytokines of EA group was all lower (P < 0.001), while
the growth factor were significantly higher (P < 0.001). Conclusion: Wound healing of db/db mice was delayed and modified formulae for EA had effects on wound healing. The way by decreasing the Ml type inf1ammatory factors and improving the M2 type growth factors might be
one of the mechanisms for wound healing.
研究领域:
医学
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Shuang Liang,Haiyan Ma,Yue Liu,Linna Hai,Yiwei Tian,Yangyang Sun,Zhaohui Wang
The initiation of tumor-specific T cell responses is critically dependent on antigen-presenting cells (APCs). Nevertheless, as the most dominant APCs in tumors, M2-like macrophages largely restrained T cell activation due to inefficient antigen cross-presentation. Herein, we rationally designed a nano-immunomodulator (FANP) to restore the antigen presentation capability of M2-like macrophages by amplifying stimulator of interferon genes (STING) activation. FANPs were fabricated by self-assembly of Fe 3+ and Raddeanin A (RA), which rapidly degraded when reaching tumor microenvironment. The released Fe 3+ induced the polarization of M2-like macrophages into M1 phenotype, followed by RA stimulation for amplified STING activation, allowing robust antigen cross-presentation and T cell-driven anti-tumor response, leading to effective tumor regression in both immunogenic and poor-immunogenic tumor models. Notably, FANPs exhibited intensive STING activation in human tumor samples, showing potential for clinical impact. Our work offers a simple and robust strategy to re-educate M2-like macrophages by augmenting STING activation for cancer immunotherapy.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HUMAN REPRODUCTION
·
2016
·Vol. 32
·期 1
·94-102
·
IF 4.621
Yuan Ming,Li Dong,An Min,Li Qiuju,Zhang Lu,Wang Guoyun
STUDY QUESTIONWhat are the features of peritoneal macrophage subgroups and T helper cells in the development of murine endometriosis?SUMMARY ANSWERDuring the development of endometriosis in a murine model, large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs) are polarized into M1 and M2 cells, respectively, and the proportions of T helper (Th) 1, Th17 and T regulatory (Treg) cells are increased.WHAT IS KNOWN ALREADYNumerous studies investigating the etiology and pathogenesis of endometriosis have focused on the polarization states of peritoneal macrophages in endometriosis models and patients, but the results are inconclusive. Further studies indicate that peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs, although their roles in endometriosis are unknown.STUDY DESIGN, SIZE, DURATIONThis study involves a prospective and randomized experiment. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group) according to the presence or absence of transplantation. The transplant periods are 0.25, 3, 14, 28 and 42 days.PARTICIPANTS/MATERIALS, SETTING, METHODSC57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of allogeneic endometrial segments. Dynamic changes of peritoneal macrophage subsets and polarization profiles were evaluated by flow cytometry (FCM). Macrophage morphology and density were assessed by cell counting under a microscope. Dynamic changes of Th1, Th2, Th17 and Treg cells were estimated by FCM.MAIN RESULTS AND THE ROLE OF CHANCEPeritoneal macrophages are composed of two distinct subsets: LPMs and SPMs. The proportion of SPMs increased immediately after peritoneal injection of endometrial tissues, whereas LPMs showed an opposite trend. Peritoneal macrophages differentiated into both M1 and M2 macrophages. The bidirectional polarization of macrophages was caused by the inverse trends of polarization of LPMs and SPMs. Consistently, the proportions of Th1, Th17 and Treg cells were all increased in mice with endometriosis.LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONIn this study, detection was only performed in a murine endometriosis model. Clinical data and more intervention experiments are required in understanding the roles of LPMs and SPMs in endometriosis.WIDER IMPLICATIONS OF THE FINDINGSThe dramatic changes of LPMs and SPMs in proportion and polarization profiles clarified the varying differentiation states of peritoneal macrophages. In addition, LPMs and SPMs may play different roles in the pathogenesis of endometriosis in different stages of endometriosis. Therefore, the new classification should be included in future relevant basic and clinical studies on endometriosis.STUDY FUNDING/COMPETING INTEREST(S)This research was supported totally by grant 81270671 from the National Natural Science Foundation of China. The authors report no conflict of interest.
研究领域:
免疫学
·
生殖医学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APOPTOSIS
·
2026
·Vol. 31
·期 2
·52
·
IF 8.1
Mao Dong,Sun Jufeng,Zhang Xiaowei,Wang Zhaoping,Zhang Yun
Colorectal cancer (CRC) is a malignant tumor originating from the epithelial cells of the colon and rectum. Interleukin enhancer binding factor 2 (ILF2), an emerging RNA-binding protein, has been implicated in the regulation of multiple cancer-related processes. However, its specific role in the pathogenesis and progression of CRC remains largely unexplored. In this study, we systematically investigated the functional role of ILF2 in CRC through multi-level experiments. ILF2 expression was first assessed in clinical CRC tissues via quantitative real-time PCR and western blot. Functional implications were further examined through gain-of-function and loss-of-function approaches. Cellular assays included CCK-8 proliferation, colony formation, Transwell migration/invasion, macrophage coculture, and flow cytometry for apoptosis, complemented by immunofluorescence staining. In vivo relevance was confirmed using xenograft models for tumor growth and metastasis. Mechanistically, Co-IP revealed a robust interaction between ILF2 and ILF3, while RIP, RNA pull-down and dual-luciferase reporter assays demonstrated direct binding of ILF3 to KLF16 mRNA, suggesting a novel regulatory axis in CRC progression. Our results demonstrated that both ILF2 mRNA and protein were significantly upregulated in colorectal cancer (CRC) tissues compared to matched peritumoral tissues. Functional assays revealed that ILF2 overexpression enhanced, whereas ILF2 knockdown suppressed, the proliferation, migration, and invasion capabilities of CRC cells in vitro. Additionally, ILF2 overexpression induced M0 macrophages to polarize toward an M2-like phenotype. Consistent with these findings, in vivo experiments indicated that ILF2 facilitated tumor growth and promoted liver metastasis in CRC. Our work suggests that ILF2 formed a complex with ILF3 to enhance the stability of KLF16 mRNA, thereby contributing to CRC progression through the regulation of KLF16. Graphical abstract A proposed working model of the ILF2/ILF3/KLF16/β-catenin axis in colorectal cancer progression. Hypothetical model illustrating that ILF2 binding to ILF3 stabilizes KLF16 mRNA, which in turn activates β-catenin signaling. This pathway ultimately promotes CRC cell proliferation, invasion, liver metastasis, and M2-type macrophage polarization.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2026
·
IF 12.5
Jingya Ruan,Ping Zhang,Jiaming Cheng,Lequan Yu,Yijin Wu,Yinuo Zheng,Yi Zhang,Tao Wang
Two glycans, ZJPr2–2-1 and ZJPr3–2-1 , were isolated from jujube fruits. Structural analysis revealed ZJPr2–2-1 (7.20 kDa) as a previously unreported pectin featuring main chain of →4)- α -D-Gal p A-(1→, →3,4)- α -D-Gal p A-(1→, and →3)- α -L-Rha p -(1→, with side chains containing →4)- α -L-Ara p -(1→, and t-4-deoxy-L- threo -hex-4-enopyranuronic acid (t- α -L-HexA), as well as two isolated fragments linked to →4)- β -D-Gal p A, →4)- α -D-Gal p A. Nevertheless, the absence of HMBC correlations precluded the structural elucidation of its connected side chain. Meanwhile, ZJPr3–2-1 was identified as the first plant-derived cyclic α -1,6-glucan heptasaccharide. Both glycans were found to promote M1 macrophage polarization (increased CD86 and decreased CD206 expression), and enhance the production of pro-inflammatory mediators (NO, iNOS, and TNF- α ) in RAW264.7 cells. The mechanism was supposed to associated with the direct ( ZJPr3–2-1 ) and indirect ( ZJPr2–2-1 ) activation of the Dectin-1/Syk signaling pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2026
·
IF 2.5
Min Chen,Wenhuan Chen,Xinyi Jiang,Shaomei Liang,Yingqiao Qin,Jiayi Tang,Yifei Li,Qifan Wu,Xue Liang,Pengcheng Wei,Kunpeng Liu,Sulan Luo
Influenza A virus (IAV) evolves rapidly through antigenic variation, leading to drug resistance and pandemic potential. To circumvent mutational escape, we employed a drug repurposing strategy targeting the evolutionarily conserved transmembrane domain (TMD) of the IAV M2 protei. Here, we report the discovery of Ajmaline, an antiarrhythmic alkaloid, as a broad-spectrum anti-IAV agent through virtual screening targeting the conserved transmembrane domain of the M2 protein. Molecular docking and 100-ns dynamics simulations revealed stable binding across multiple IAV subtypes (H1N1, H2N2, H5N1, H7N9). Cellular Thermal Shift Assay confirmed direct binding to wild-type and N31S mutant M2 protein. Ajmaline exhibited potent antiviral activity through dual mechanisms: direct inhibition of viral replication and upregulation of interferon-related genes (IFN-β, ISG56) coupled with suppression of apoptosis (Bax downregulation). In vivo, Ajmaline (15 mg/kg) improved survival to 83%, reduced pulmonary viral load, and alleviated lung pathology in H1N1-infected mice. These findings identify Ajmaline as a repurposed broad-spectrum antiviral candidate capable of overcoming existing drug resistance, providing a proof-of-concept for conserved-domain-targeting strategies in antiviral drug development.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2021
·
IF 3.503
Chun Li,Xin-You Pan,Mingyun Ma,Jun Zhao,Fengda Zhao,Ya-Ping Lv
Context Astragalus polysaccharin (APS), an extract of Astragalus propinquus Schischk, exerts antitumor effects in hepatocellular carcinoma (HCC).Objective This study investigated the mechanism of action of APS in HCC.Materials and methods Tumour-associated macrophages (TAMs) were treated with APS (0, 8, 16 mg/mL) for 24 h. APS (16 mg/mL)-treated TAMs were co-cultured with MHCC97H/Huh7 cells for 24 h. Finally, BALB/c nude mice were divided into PBS, APS (50 mg/kg), APS (100 mg/kg), APS (200 mg/kg) groups: mice were inoculated with Huh7 cells to construct tumour xenograft model, followed by administration of APS (50, 100, 200 mg/kg) or PBS daily for 30 days. Cell proliferation, migration, invasion, tumour growth, macrophage markers and proportions were measured.Results APS 16 mg/mL treatment enhanced the expression of M1 macrophage markers (iNOS, IL-1β and TNF-α) and M1 macrophage proportions, while reducing the expression of M2 macrophage markers (IL-10, Arg-1) and M2 macrophage proportions in TAMs. Moreover, the APS-mediated M1 phenotype of TAMs significantly repressed cell proliferation, migration and invasion of MHCC97H and Huh7 cells. Moreover, APS (50, 100, 200 mg/kg) enhanced M1 macrophage proportions and reduced M2 macrophage proportions in the tumour tissues, and thus inhibited tumour growth of HCC.Discussion and conclusions APS inhibits HCC-like phenotypes in a murine HCC model through repression of M2 polarization of TAMs. This work provides a novel theoretical basis for the application of APS in the clinical treatment of HCC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2023
·
IF 4.1
Xijie Zhou,Chenhao Ye,Liangfu Jiang,Xuwei Zhu,Feiya Zhou,Meizi Xia,Yiheng Chen
A diabetic wound is a refractory disease that afflicts patients globally. MicroRNA-146a-5p (miR-146a-5p) is reported to represent a potential therapeutic target for diabetic wounds. However, microRNA easily degrades in the wound microenvironment. This study extracted bone marrow mesenchymal stem cell (BMSC)-derived exosomes (EXO). Electroporation technology was used to load miR-146a-5p into EXO (labeled as EXO-miR-146a). The endothelial cells (human umbilical vein endothelial cells [HUVECs]) and macrophages were cocultured in transwell chambers in the presence of high glucose. Cell proliferation, migration, and angiogenesis were measured with cell counting kit 8, scratch, and tube forming assays, respectively. Flow cytometry was introduced to validate the biomarker of macrophages and BMSCs. The expression level of macrophage polarization-related proteins and tumor necrosis factor receptor-associated factor 6 (TRAF6) was assessed with western blotting analysis. The full-thickness skin wound model was developed to verify the in vitro results. EXO-miR-146a promoted the proliferation, migration, and angiogenesis of HUVECs in the hyperglycemic state by suppressing the TRAF6 expression in vitro . Additionally, EXO-miR-146a treatment facilitated M2 but inhibited M1 macrophage polarization. Furthermore, EXO-miR-146a enhances reepithelialization, angiogenesis, and M2 macrophage polarization, thereby accelerating diabetic wound healing in vivo . The EXO-miR-146a facilitated M2 macrophage polarization, proliferation, migration, and angiogenesis of HUVECs through TRAF6, thereby ameliorating intractable diabetic wound healing. These results established the basis for using EXO to deliver drugs and revealed mediators for diabetic wound treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STEM CELLS
·
2023
·
IF 5.2
Li Zhi-hui,Chen Jun-feng,Zhang Jing,Lei Zi-ying,Wu Li-li,Meng Shi-bo,Wang Jia-lei,Xiong Jing,Lin Deng-na,Wang Jun-yi,Gao Zhi-liang,Lin Bing-liang
Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale Horizons
·
2025
·
IF 6.6
Si-Ye Tong,Cong-Min Huo,Yu-Cheng Zuo,Shuo Gao,David Tai Leong,Wei Xue,Jing-Yi Zhu
Immunosuppression from the tumor microenvironment plays a key role in the failure of cancer immunotherapy. The presence of potassium ions (K+) from dying tumor cells creates an immunosuppressive environment that encourages tumor-associated macrophages (TAMs) to adopt a pro-tumor M2-like phenotype. Alleviating immune suppression from the high K+ environment might boost innate immunity and fight tumor growth. Herein, disulfide-rich mesoporous silica modified with 18-crown-6 ether was developed as a nanocarrier (D-C) to load ML133, encapsulating with the DiR-embedded macrophage membrane (CM) to create D-C/M@CM/DiR. We first saturated the phagocytosis of the mononuclear phagocyte system (MPS) with blank nanocarriers to enhance the tumor accumulation of D-C/M@CM/DiR, which was coated with the same CM. 18-Crown-6 ether captures K+ to reduce immunosuppression, while ML133 promotes the polarization of TAMs to an anti-tumor M1 phenotype by targeting the K+ channel protein Kir2.1 on their membranes. This strategy activates the anti-tumor immune response and effectively inhibits tumor growth.
研究领域:
肿瘤学
·
免疫学
·
药剂学
✓ 已验证
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）