INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Jinren Liu,Yifei Jiang,Linghui Zhong,Jiajia Lu,Rongrong Li,Yifei Pei,Linyi Tang,Meng Sun,Meng Lv,Xingmin Shi,Fuliang Gong,Xili Wu
Macrophage-mediated tumor clearance is frequently restricted by the immunosuppressive tumor microenvironment. This study investigates the immunomodulatory effects of plasma-activated medium (PAM) on macrophage pro-inflammatory activation and antitumor function. Murine RAW264.7 and primary bone marrow-derived macrophages were treated with PAM generated by a helium atmospheric pressure plasma jet. Phenotypic changes and underlying signaling mechanisms were assessed. Functional enhancements in macrophage recruitment and tumor engulfment were quantified using chemotaxis and 3D confocal co-culture assays with Panc02 pancreatic cancer cells. Results show that PAM promotes macrophage activation by increasing spatial recruitment via pro-inflammatory chemokine secretion and enhancing tumor cell engulfment. Mechanistically, PAM drives this functional shift through hierarchical activation of the TLR4/NF-κB and PI3K/AKT signaling cascades. Furthermore, while hydrogen peroxide alone triggers a compensatory upregulation of the inhibitory SIRPα receptor, the reactive oxygen and nitrogen species (RONS) in PAM bypass this negative feedback to directly downregulate SIRPα. These findings demonstrate that PAM-mediated oxidative modulation effectively suppresses the “don't-eat-me” signal and enhances innate antitumor immunity, providing a potential strategy for cancer immunotherapy.
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PubMed
高影响因子
PeerJ
·
2024
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IF 2.3
Junli Du,Chao Chen,Jie Chen
Background Cirsilineol is a trimethoxy and dihydroxy flavonoid isolated from plant species such as Artemisia vestita and has a variety of pharmacological properties. This study analyzed whether cirsilineol could prevent postoperative cognitive dysfunction (POCD). Methods A POCD mouse model induced by anesthesia/surgery induction and a cell model established with hydrogen peroxide (H 2 O 2 )-induced microglia BV-2 were employed to explore the efficacy of cirsilineol on POCD. The cognition function of the mice were assessed by carrying out behavioral tests (Morris water maze test and Y-maze test). We assessed the activation and polarization status of microglia using immunofluorescence analysis and detected the expression levels of CD86 and CD206 using the quantitative PCR (qPCR). Subsequently, cell viability was determined by CCK-8 assay and apoptosis was assessed using Calcein-AM/PI staining. Meanwhile, superoxide dismutase (SOD) and malondialdehyde (MDA) levels in plasma and cell culture medium were detected using chemiluminescence. Finally, the phosphorylation levels of JAK/STAT signaling pathway-related proteins were analyzed by Western blot. Results Cirsilineol reduced the escape latency and times of crossing island and increased spontaneous alternation (SA) rate, restoring the cognitive dysfunctions of POCD-modeled mice. Meanwhile, POCD elevated CD86 expression and malondialdehyde content and lowered the level of SOD; however, cirsilineol promoted CD206 expression and generation of SOD and inhibited malondialdehyde production. In H 2 O 2 -induced microglia BV-2, cirsilineol treatment increased SOD content and suppressed the generation of reactive oxygen species (ROS) and malondialdehyde, modulating microglia M1/M2 polarization and JAK/STAT pathway. Conclusion Cirsilineol prevented against POCD by attenuating oxidative stress and modulating microglia M1/M2 polarization, providing novel insights for the management of POCD.
研究领域:
药理学
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神经科学
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外科手术
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分子生物学
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FOOD CONTROL
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2015
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IF 2.806
Xiya Zhang,Kai Wen,Zhanhui Wang,Haiyang Jiang,Ross C. Beier,Jianzhong Shen
A rapid lateral flow fluorescent microsphere immunochromatographic test strip (FM-ICTS) assay has been developed for the detection of aflatoxin M 1 (AFM 1 ) residues in milk. For this purpose, an ultra-sensitive anti-AFM 1 monoclonal antibody (MAb) 1D3 was prepared and identified. The IC 50 value of the MAb 1D3 for AFM 1 was 23 ng/L, and the cross-reactivity (CR) of the MAb with aflatoxin M 2 , aflatoxin B 1 , aflatoxin B 2 , aflatoxin G 1 and aflatoxin G 2 was 18%, 9%, <0.15%, 43% and <0.3%, respectively. The MAb was covalently conjugated with carboxylate-modified FMs, and the FMs were used as the label in a competitive immunochromatography assay. Using a moderate hapten-to-protein coupling ratio (˜2) in the coating antigen resulted in improved immunoassay sensitivity. Under optimal conditions, the IC 50 value of the assay was 36.3 ng/L with the limit of detection (LOD) of 4.4 ng/L in milk samples using a fluorescence reader, and the recoveries of AFM 1 in spiked milk samples ranged from 76.6 to 110.8% with coefficient of variation (CV) of 4–14.7%. The whole procedure could be completed within 30 min. The results demonstrated that the FM-ICTS assay is easy to conduct, rapid, highly sensitive and specific for the detection of AFM 1 residues in milk.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Tingting Liu,Tao Han,Congyan Liu,Chang Ge,Xi Jiang,Yuping Liu,Fei Kong,Xiangyu Su,Jiachen Shi,Wenting Su,Xiaoqi Li,Yan Chen,Huangqin Zhang,Qiuling Ma,Ding Qu
M1 polarization of tumor-associated macrophages (TAMs) is a promising approach to breaking through therapeutic barriers imposed by the immunosuppressive tumor microenvironment (TME). As a clinically-used immunopotentiator for cancer patients after chemotherapies; however, the immunomodulatory mechanism and potential of polyporus polysaccharide (PPS) remains unclear. Here, we present mannose-decorated PPS-loaded superparamagnetic iron-based nanocomposites (Man/PPS-SPIONs) for synergistic M1 polarization of TAMs and consequent combinational anti-breast cancer therapy. Once internalized by M2-like TAMs, PPS released from Man/PPS-SPIONs induces the M1 polarization via IFN-γ secretion and downstream NF-κB pathway activating. The SPIONs within the nanocomposites mediate a Fenton reaction, producing OH· and activating the subsequent NF-κB/MAPK pathway, further facilitating the M1 polarization. The Man/PPS-SPIONs thereby establish a positive feedback loop of M1 polarization driven by the “IFN-γ-Fenton-NF-κB/MAPK” multi-pathway, leading to a series of anti-tumoral immunologic responses in the TME and holding promising potential in combinational anticancer therapies. Our study offers a new strategy to amplify TME engineering by combinational natural carbohydrate polymers and iron-based materials.
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CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Pengchong Wang,Ying Zhang,Hengyu Lei,Jie Yu,Qinyuan Zhou,Xianpeng Shi,Yaning Zhu,Dan Zhang,Peng Zhang,Ke Wang,Kai Dong,Jianfeng Xing,Yalin Dong
Herein, hyaluronic acid (HA) and β-cyclodextrin (β-CD) is used to form targeted drug delivery platform HCPC/DEX NPs with previously prepared carbon dots (CDs) as cross-linker, dexamethasone (DEX) is loaded for rheumatoid arthritis (RA) treatment. The drug loading capacity of β-CD and M1 macrophage targeting of HA were utilized for efficient delivery of DEX to the inflammatory joints. Because of the environmental responsive degradation of HA, DEX can be released in 24 h and inhibit the inflammatory response in M1 macrophages. The drug loading of NPs is 4.79 %. Cellular uptake evaluation confirmed that NPs can specifically target to M1 macrophages via HA ligands, the uptake of M1 macrophages is 3.7 times that of normal macrophages. In vivo experiments revealed that NPs can accumulate in RA joints to alleviate inflammation and accelerate cartilage healing, the accumulation can be observed in 24 h. The cartilage thickness increased to 0.45 mm after HCPC/DEX NPs treatment, indicating its good RA therapeutic effect. Importantly, this study was the first to utilize the potential acid and reactive oxygen species responsiveness of HA to release drug and prepare M1 macrophage targeting nanodrug for RA treatment, which provides a safe and effective RA therapeutic strategy.
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高影响因子
ACS Nano
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2023
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IF 17.1
Xiaomin Liu,Mingkun Wang,Yichao Jiang,Xinyi Zhang,Changrong Shi,Fantian Zeng,Yatong Qin,Jinmin Ye,Jiaying Hu,Zijian Zhou
Macrophages play a crucial role in immune activation and provide great value in the prognosis of cancer treatments. Current strategies for prognostic evaluation of macrophages mainly target the specific biomarkers to reveal the number and distribution of macrophages in the tumors, whereas the phenotypic change of M1 and M2 macrophages in situ is less understood. Here, we designed an ultrasmall superparamagnetic iron oxide nanoparticle-based molecular imaging nanoprobe to quantify the repolarization of M2 to M1 macrophages by magnetic resonance imaging (MRI) using the redox-active nitric oxide (NO) as a vivid chemical target. The nanoprobe equipped with O-phenylenediamine groups could react with the intracellular NO molecules during the repolarization of M2 macrophages to the M1 phenotype, leading to electrical attraction and colloidal aggregation of the nanoprobes. Consequently, the prominent changes of the T1 and T2 relaxation in MRI allow for the quantification of the macrophage polarization. In a 4T1 breast cancer model, the MRI nanoprobe was able to reveal macrophage polarization and predict treatment efficiency in both immunotherapy and radiotherapy paradigms. This study presents a noninvasive approach to monitor the phenotypic changes of M2 to M1 macrophages in the tumors, providing insight into the prognostic evaluation of cancer treatments regarding macrophage-mediated immune responses.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Qianqian Zheng,Gui Mei,Ping Cheng,Yahong Li,Qingfeng Zhang,Mingwei Ye
Given the demonstrated mitigating effect of omega-9 monounsaturated fatty acids (ω-9MUFAs) on lipopolysaccharide (LPS)-induced acute lung injury (ALI), we deeply explored corresponding mechanisms. Sprague-Dawley rats experienced ALI modeling, and received ω-9 MUFAs (3 mg/kg) injection via the tail vein. Post incubation in 100 ng/mL phorbol-12-myristate-13-acetate and 100 ng/mL LPS for 24 h each, THP-1 macrophages were transfected with shHSPH1 and c-MYC overexpression plasmid. Lung injury detection depended on H&E staining. Levels of inflammation-related factors were detected by ELISA. Levels of inflammation-related factors, heat shock protein family H (Hsp110) member 1 (HSPH1), c-MYC, stimulator of interferon response CGAMP interactor 1 (STING) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) were measured by qRT-PCR. Levels of pyroptosis-related factors, HSPH1, c-MYC, STING, NLRP3, and M1 macrophage biomarkers were assayed by Western blot. Proportion of M1 macrophages and pyroptosis were detected by flow cytometry. Localization of HSPH1 and CD68 was measured by immunofluorescence assay. ω-9MUFAs reduced the inflammation, the proportion of M1 and pyroptotic macrophages and levels of HSPH1, c-MYC, STING and NLRP3 in ALI rats. The expression positions of HSPH1 and CD68 were overlapped in ALI rat lung tissue. HSPH1 silencing reversed the changes in inflammation, the proportion of M1 and pyroptotic macrophages and levels of c-MYC, STING and NLRP3 in LPS-induced THP-1 macrophages, and c-MYC overexpression offset these effects of HSPH1 silencing. Collectively, ω-9MUFAs ameliorated LPS-induced ALI by regulating HSPH1/c-MYC expression, down-regulating M1 macrophage polarization and pyroptosis.
研究领域:
免疫学
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分子生物学
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病理学
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高影响因子
ANALYTICA CHIMICA ACTA
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2026
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IF 6.1
Qinghai Hu,Kangwei Shen,Yunzheng Wang,Xuejun Kang,Lanling Chu
Background Aflatoxin M 1 (AFM 1 ), a highly toxic hydroxylated metabolite of aflatoxin B 1 , is a major contaminant of concern in milk and dairy products, posing significant risks to food safety and public health. Since AFM 1 contamination is closely associated with feed quality, storage conditions, climatic factors, and farm management, reliable AFM 1 detection is important for supporting quality control and safety assessment of dairy products. However, the determination of trace AFM 1 in dairy matrices remains challenging, as complex matrix components may compromise analyte recognition specificity and signal readout. Accordingly, the development of a rapid, sensitive, and matrix-tolerant analytical method is highly desirable for practical AFM 1 monitoring. Results Herein, we developed an integrated analytical strategy combining nanofiber-packed solid-phase extraction (PFSPE) with an aptamer-mediated fluorescence resonance energy transfer (FRET) assay for AFM 1 detection. Four types of polystyrene-polyvinylpyrrolidone (PS-PVP) nanofibers containing different amounts of montmorillonite (MMT) were fabricated by electrospinning and used as sorbents for the PFSPE of AFM 1 . The FRET sensing system was tailored for AFM 1 recognition and enabled rapid signal transduction via target-induced changes in energy transfer efficiency. Both the PFSPE and the FRET-based assay contribute to rapid and accurate AFM 1 determination. Under optimized conditions, the proposed method exhibited satisfactory linearity, recoveries (89.5-95.8%), precisions (RSDs ≤7.4%), and a limit of detection of 0.16 μg/kg. Moreover, the method was successfully applied to the detection of AFM 1 in real milk samples. Significance This work provides an effective analytical strategy for AFM 1 detection by integrating electrospun nanofiber-assisted matrix cleanup and target enrichment with an aptamer-mediated FRET assay, thereby improving the reliability of fluorescence analysis in complex milk matrices and providing a practical platform for rapid screening and preliminary monitoring of AFM 1 contamination in dairy products.
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Journal of Ginseng Research
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2026
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IF 7.5
Lei Quan,Yue Gao,Chen Zhang,Yue Ding,Sijuan Sun,Xinran Tai,Qingqing Yu,Dong Wang,Yumei Wang
Background Breast cancer ranks among the most prevalent malignant tumors in women worldwide, with lung metastasis accounting for over 90% of fatalities. Despite this high mortality, effective targeted therapies remain insufficient. Although ponatinib (PNT) shows potential for treating breast cancer lung metastasis (BCLM), its delivery requires optimization. This study aims to construct a biomimetic nanomedicine for targeted delivery of PNT, thereby efficiently treating BCLM. Methods Ginsenoside Rg3 (Rg3) can serve as a substitute for cholesterol as a membrane support material while also acting as an adjuvant in cancer treatment. We replaced cholesterol with Rg3 to prepare PNT-Rg3-Lipo liposomes, extracted the cell membrane of M1 macrophages to coat it on the surface of PNT-Rg3-Lipo, and obtained biomimetic nano MM/PNT-Rg3-Lipo. The characterization of biomimetic nanomedicines was conducted, and the functionality of biomimetic nanomedicines was evaluated at both animal and cellular levels. Results The macrophage membrane-modified MM/PNT-Rg3-Lipo retains most proteins found on M1-type macrophages, including the characteristic proteins integrin α4 and β1. This macrophage membrane-modified MM/PNT-Rg3-Lipo reduces macrophage phagocytosis, while enhancing uptake by metastatic breast cancer cells. In vitro , macrophage membrane-modified MM/PNT-Rg3-Lipo exhibits a stronger cytotoxic effect on breast cancer cells compared to free PNT. In vivo , MM/PNT-Rg3-Lipo shows a lower hemolysis rate, demonstrating its safety. Macrophage membrane modification guides liposomes to lung metastatic sites, leading to localized drug release and consequential inhibition of breast cancer lung metastases. Conclusion The biomimetic macrophage membrane-coated liposomes, MM/PNT-Rg3-Lipo, which we have innovatively prepared, exhibit promising therapeutic effects against breast cancer lung metastases.
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Journal of Functional Foods
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2026
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IF 3.9
Zexuan Wu,Yonghong Long,Fugang Huang,Ze Yang,Yanzuo Wu,Yihong Gan,Xiufang Chen,Guanqun Xie
Capsaicin (CAP), the pungent compound in chili peppers, is well-known for its anti-inflammatory properties, yet its role in autoimmune immunometabolism remains unexplored. In a murine model of Collagen-Induced Arthritis,CAP markedly attenuated joint swelling, cartilage damage, and bone erosion. Mechanistically, CAP targeted HIF-1α, leading to a coordinated suppression of both BNIP3-mediated mitophagy and the characteristic glycolytic shift in M1 macrophages. This dual metabolic suppression was recapitulated in human THP-1-derived M1-like macrophages, where it inhibited M1 polarization and reduced pro-inflammatory cytokine secretion. Collectively, these data identify CAP as a food-derived immunometabolic modulator that alleviates rheumatoid arthritis (RA) by concurrently disrupting mitophagy and glycolysis in M1 macrophages via HIF-1α.
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JOURNAL OF MOLECULAR STRUCTURE
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2017
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IF 1.753
Guanfan Chen,Mengzhuo Tang,Xiufang Fu,Fenmin Cheng,Xianghua Zou,Jingpei Wang,Rongjin Zeng
Sulfide anions are not only generated as a byproduct from industrial processes but also as a crucial kind of element in biological systems. Therefore, fluorescent probes for detecting sulfide anion with sensitive and selective characters are highly popular. In this study, we report a highly sensitive and selective fluorescent sensor M1 for detection of sulfide anion based on the steric hindrance effect, where the recognition unit, dinitrobenzenesulfonate ester group is linked to aromatic ortho -position in the porphyrin , and correspondingly the fluorescence of fluorescein is efficiently quenched. Compared with the sensors with recognition unit linked to the other aromatic positions, the fluorescent sensor M1 has a lower fluorescence background. Furthermore, the corresponding fluorescence responses ( F/F0 ) of M1 for mercapto amino-acid GSH, Hcy and Cys, were all far lower than the relative fluorescence ratio F/F0 values for S 2− . It means that M1 is sensitive and selective to detection of S 2− , and has an anti-disturbance ability to the biologically-relevant thiols, GSH, Hcy and Cys, and has the prospect of application in the exact detection of sulfide anions in living organisms. This approach offers some useful insights for realizing sensitive and selective fluorescent turn-on sensing in the detection assays for other analytes.
研究领域:
生物化学
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分析化学
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高影响因子
HUMAN REPRODUCTION
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2016
·Vol. 32
·期 1
·94-102
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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
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生殖医学
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病理学
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