Materials Today Bio
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2025
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IF 10.2
Chao Xiang,Chaoyu Pu,XueMei Zhong,Yong Wang,Weiyong Song,Xingkuan Wang,Kemiao Chen,Kai Li,Yue Luo,Ke Jiang,Dianming Jiang
Traditional antibiotics are often ineffective against biofilm-associated infections, and biofilm-induced macrophage immune evasion directly halts the wound healing process. Disrupting biofilms and regulating macrophage immune functions are critical to improving wound healing. In this study, we synthesized g-C 3 N 4 with peroxidase (POD) enzyme activity via thermal polymerization and copper alginate microspheres (CAM) via gas cutting. These were co-encapsulated into GelMA hydrogels to form a functionalized wound repair system (GelMA/CAM@g-C 3 N 4 ) with both anti-biofilm and local immune microenvironment remodeling capabilities. In vitro, this system exhibited excellent biocompatibility and promoted endothelial cell migration, vascular formation, and CD31 expression. It also polarized macrophages toward the M1 phenotype, restoring their pro-inflammatory functions, upregulating inflammatory cytokines (IL-1, IL-6, TNF-α), and inhibiting Staphylococcus aureus and Escherichia coli . In vivo, the system suppressed S. aureus growth, promoted angiogenesis and collagen deposition, and reshaped the pathological microenvironment to achieve wound repair and regeneration. Conclusions: This system offers a new therapeutic strategy for chronic infectious wounds.
研究领域:
生物医学工程
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伤口愈合
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免疫学
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微生物学
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材料科学
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高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-11
·
IF 16.6
Ma Dingren,Lian Qiyu,Zhang Yexing,Huang Yajing,Guan Xinyi,Liang Qiwen,He Chun,Xia Dehua,Liu Shengwei,Yu Jiaguo
The structure-activity relationship in catalytic ozonation remains unclear, hindering the understanding of activity origins. Here, we report activity trends in catalytic ozonation using a series of single-atom catalysts with well-defined M 1 -N 3 C 1 (M: manganese, ferrum, cobalt, and nickel) active sites. The M 1 -N 3 C 1 units induce locally polarized M − C bonds to capture ozone molecules onto M atoms and serve as electron shuttles for catalytic ozonation, exhibiting excellent catalytic activities (at least 527 times higher than commercial manganese dioxide). The combined in situ characterization and theoretical calculations reveal single metal atom-dependent catalytic activity, with surface atomic oxygen reactivity identified as a descriptor for the structure-activity relationship in catalytic ozonation. Additionally, the dissociation barrier of surface peroxide species is proposed as a descriptor for the structure-activity relationship in ozone decomposition. These findings provide guidelines for designing high-performance catalytic ozonation catalysts and enhance the atomic-level mechanistic understanding of the integral control of ozone and methyl mercaptan.
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TISSUE & CELL
·
2024
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IF 2.7
Xiuchao Shang,Yesheng Jin,Yuan Xue,Xiaoyun Pan,Haiquan Zhu,Xiangsheng Meng,Zhihai Cao,Yongjun Rui
This study aimed to investigate the effects of E26-transformation-specific variant-2 (ETV2) overexpression on wound healing in a cutaneous wound (CW) model and clarify associated mechanisms. pLVX-ETV2 lentivirus expressing ETV2 was constructed and infected into BMSCs to generate ETV2-overexpressed BMSCs (BMSCs+pLVX+ETV2). The RT-PCR assay was applied to amplify ETV2, VE-cadherin, vWF, ARG-1, IL-6, iNOS, TGF-β, IL-10, TNF-α. Western blot was used to determine expression of VE-cadherin and vWF. ETV2 induced differentiation of BMSCs into ECs by increasing CDH5/CD31, triggering tube-like structures, inducing Dil-Ac-LDL positive BMSCs. ETV2 overexpression increased the gene transcription and expression of VE-cadherin and vWF (P<0.01). Transcription of M1 phenotype specific iNOS gene was lower and transcription of M2 phenotype specific ARG-1 gene was higher in the RAW264.7+BMSCs+ETV2 group compared to the RAW264.7+BMSCs+pLVX group (P<0.01). ETV2 overexpression (RAW264.7+BMSCs+ETV2) downregulated IL-6 and TNF-α, and upregulated IL-10 and TGF-β gene transcription compared to RAW264.7+BMSCs+pLVX group (P<0.01). ETV2-overexpressed BMSCs promoted wound healing in CW mice and triggered the migration of BMSCs to the wound region and macrophage activation. ETV2-overexpressed BMSCs promoted collagen fibers and blood vessel formation in the wound region of CW mice. In conclusion, this study revealed a novel biofunction of ETV2 molecule in the wound healing process. ETV2 overexpression in BMSCs promoted wound healing in CW mice by triggering BMSCs differentiation into endothelial cells and modulating the transformation of M1 pro-inflammatory and M2 anti-inflammatory macrophages in vitro and in vivo .
研究领域:
细胞生物学
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分子生物学
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伤口愈合
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干细胞研究
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免疫学
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高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2026
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IF 7.3
Zhang Guoyu,Cao Yi,Wu Xingxin,Liu Hanfang,Zeng Min,Sun Xiuzhong,Huang Song,Liang Jing,Li Gaofei,Shen Huimin,Wang Peng George,Wang Chaojie,Fang Dong,Wang Jiajia,Xie Songqiang,Ma Jing
Non-small-cell
lung cancer (NSCLC) is considered as a predominant
contributor to cancer-related mortality with significant infiltration
by TAMs. HMGB1 plays a key role in modulating immune evasion, but
the mechanisms of HMGB1 in anti-NSCLC immunotherapy remain unclear.
In this study, we first identified that cisplatin-resistant A549 CisR
overexpresses HMGB1 and has hyperactivated autophagy, while cisplatin-sensitive
A549 cells exhibit the opposite reaction. Using a HMGB1-targeted modulator,
Naphplatin, we show that normalizing HMGB1 in both A549 and A549 CisR
cell lines significantly triggers HMGB1-mediated inherent metabolic
plasticity in tumors, thus releasing it to the thresholds required
for macrophage activation. Mechanistically, in tumors, HMGB1 at threshold
levels can effectively translocate to the cytoplasm from the nucleus,
initiating lysosomal metabolism. Meanwhile, in macrophages, tumor-derived
HMGB1 binds to RAGE, thereby promoting polarization toward the M1
macrophage phenotype. This study uncovers a divergent metabolic program
mediated by HMGB1 and demonstrates its role in lysosomal metabolic
plasticity.
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Communications Biology
·
2025
·Vol. 8
·期 1
·1-15
·
IF 5.1
Wang Yue,Wang Yang,Tong Fei,Gao Qianqian,Li Baoxuan,Zhao Yan
Preeclampsia is one of the most common pregnancy disorders, and characterized by insufficient trophoblast invasion and placental inflammation. Our RNA sequencing results showed that OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) was downregulated in placenta from preeclampsia patients, compared with the healthy control. Clinical and experimental data demonstrated that OTUB2 was expressed in macrophages. Gain- and loss-of-function experiments revealed that OTUB2 overexpression blocked M1 polarization of macrophages, and attenuated macrophages-induced apoptosis, and impaired migration and invasion of trophoblasts. Moreover, OTUB2 alleviated LPS-induced preeclampsia-like symptoms in rats, including hypertension, proteinuria, inflammation in placenta and insufficient infiltration of trophoblasts. Additionally, OTUB2 mediated deubiquitination of nuclear receptor subfamily 4 group A member 1 (NR4A1) and suppressed its degradation, and the Cys51 is crucial for catalytic activity of OTUB2. The effects of OTUB2 were partially reversed by shNR4A1. In conclusion, OTUB2 suppressed macrophage M1 polarization, macrophages-induced trophoblast damage, and restrained experimental preeclampsia in rodents by mediating deubiquitination of NR4A1. These findings may provide novel insight for clinical prevention and diagnosis of preeclampsia.
研究领域:
生殖医学
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免疫学
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分子生物学
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病理学
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药理学
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PHYTOMEDICINE
·
2025
·
IF 8.3
Xin Li,Qilong Li,Ning Jiang,Kexin Zheng,Yiwei Zhang,Xiaoyu Sang,Ying Feng,Ran Chen,Qijun Chen
Background The property of dihydroartemisinin (DHA) in promoting host immunohomeostasis, apart from its potent antimalarial activity, has been well-recognized. However, the mechanism of DHA in activating macrophages to enhance host resistance to malaria remains unexplored. Purpose This study investigated the molecular mechanism by which DHA promotes the polarization of macrophages toward the M1 phenotype during the treatment of malaria. Methods The mouse macrophage cell line RAW 264.7 or the macrophages isolated from mice were stimulated with Plasmodium berghei ANKA infected red blood cells (iRBC) in the presence of DHA. The macrophage phenotypes in both in vivo and in vitro were determined using cytometric bead array and flow cytometry. To dissect the molecular mechanisms underlying macrophage responses to DHA, we initially profiled the expression of 90 genes associated with innate immunity, including the entire NLR family, in macrophages stimulated with DHA. This targeted screen strikingly revealed that only Nlrp12 was significantly upregulated among all tested NLR genes. The function of Nlrp12 was further dissected by Nlrp12 knockdown in macrophages with recombinant lentiviruses encoding Nlrp12 -specific shRNA, within the context of DHA treatment. To comprehensively define the molecular consequences of Nlrp12 deficiency, we performed an integrated analysis by combining single-cell RNA sequencing with label-free quantitative proteomic profiling. This allowed us to systematically characterize the complex transcriptomic and proteomic dynamics in DHA-treated macrophages upon Nlrp12 deletion. Results DHA induced macrophage polarization to M1 phenotype and enhanced phagocytosis by up-regulating the expression of NLRP12. Nlrp12 -knockdown in macrophages reduced the expression of M1 type-associated genes, resulting in a significantly increased expression of the translocator protein (TSPO), which suppressed the secretion of inflammation-associated cytokines and blunting macrophage M1 polarization. The results of single cell RNA sequencing further revealed that DHA promoted the conversion of classical M1 macrophages into lipocalin-2 (Lcn2) high M1 macrophages. Conclusion The activation of NLRP12 induced by DHA is crucial for M1 macrophage polarization, which plays a significant role in the clearance of Plasmodium parasites.
研究领域:
免疫学
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寄生虫学
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分子生物学
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高影响因子
Frontiers in Pharmacology
·
2021
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IF 5.811
Botao Wang,Lei Yang,Tianyu Liu,Jing Xun,Yuzhen Zhuo,Lanqiu Zhang,Qi Zhang,Ximo Wang
The poor immunotherapy of pancreatic cancer is mainly due to its complex immunosuppressive microenvironment. The Mediterranean diet contributes to low cancer incidence. Hydroxytyrosol (HT) derived from olive oil has multiple health-promoting effects, but its therapeutic effect on pancreatic cancer remains controversial. Here, we evaluated the inhibitory effect of HT on mouse pancreatic cancer, and the effect of HT on the immune microenvironment. We found that HT can inhibit the proliferation of Panc 02 cells through signal transducer and activator of transcription (STAT) 3/Cyclin D1 signaling pathway. In the tumor-bearing mice treated with HT, the orthotopic pancreatic tumors were suppressed, accompanied by a decrease in the proportion of myeloid-derived suppressor cells (MDSCs) and an increase in the proportion of M1 macrophages. In addition, we found that HT inhibited the expression of immunosuppressive molecules in bone marrow (BM)-derived MDSCs, as well as down-regulated CCAAT/enhancer-binding protein beta (C/EBPβ) and phosphorylation of STAT3. Moreover, HT enhanced the anti-tumor effect of anti-CD47 antibody in vivo . HT combined with plumbagin (PLB) induced more Panc 02 cells death than HT or PLB alone. This combination therapy not only inhibited the accumulation of MDSCs, but also promoted the infiltration of CD4 + and CD8 + T cells in the tumors. In summary, HT is a potential immunomodulatory drug for the treatment of pancreatic cancer.
研究领域:
肿瘤学
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免疫学
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药理学
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分子生物学
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高影响因子
BRAIN RESEARCH BULLETIN
·
2026
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IF 4.5
Jing Chen,HongYinLong Cui,MingKui Zhao,XiaoHan Du,Wen Chen
Alpk1 overexpressed in microglia of SE models. • Knockdown of Alpk1 alleviated the symptoms in epileptic rats. • Knockdown of Alpk1 represses M1-microglial activation. • Effects of Alpk1 knockdown are via suppressing JAK2/STAT3 signaling. Background Epilepsy is a chronic brain disorder characterized by recurrent, highly synchronous abnormal neuronal discharges leading to cerebral dysfunction. This study investigates the role of alpha kinase 1 (ALPK1), a pattern recognition receptor, in epilepsy. Methods ALPK1 expression and distribution were analyzed using the GSE190452 dataset and a pilocarpine-induced rat model. An adeno-associated virus delivering Alpk1 shRNA was injected intra-hippocampally into model rats, followed by seizure monitoring. Pathological changes were assessed via hematoxylin and eosin and Nissl staining. Primary microglia and BV2 cells transfected with Alpk1 siRNA were stimulated with kainic acid. Immunofluorescence, quantitative real-time polymerase chain reaction, and Western blot were used to evaluate M1 microglial marker and pro-inflammatory cytokines. Gene Set Enrichment Analysis (GSEA) was performed to identify potential signaling associated with Alpk1 function. Results ALPK1 was widely distributed and highly expressed in epileptic microglia. Alpk1 knockdown alleviated seizure symptoms in rats, including hippocampal damage, Nissl body loss, reduced Racine scores, and decreased daily seizure frequency and duration. Both in vivo and in vitro , Alpk1 knockdown downregulated the M1 marker inducible nitric oxide synthase and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6). GSEA indicated Alpk1 activates Janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) signaling. Stat3 overexpression reversed the inhibitory effects of Alpk1 knockdown on M1 activation and inflammation. Conclusion ALPK1 is highly expressed in epileptic microglia. Silencing Alpk1 alleviates M1-microglial activation and inflammation in epilepsy by inhibiting the JAK2/STAT3 signaling.
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International Journal of Nanomedicine
·
2026
·
IF 8.7
Xueying Bai,Xingzhi Han,Wenjing Wang,Ning Wang,Li Li,Jing Hu,Qun Zhang,Xiaoping Qian
Purpose: Immunotherapy has attracted increasing attention in cancer treatment, but its efficacy is greatly limited due to the low immunogenicity of tumors and immunosuppressive tumor microenvironment (TME). To address this, we constructed a biomimetic M1 macrophage membrane-Camouflaged nanoplatform (M1@CTP) for the co-delivery of the natural antitumor compound Tanshinone IIA (Tan IIA) and the immunogenic cell death (ICD) inducer Copper-diethyldithiocarbamate (CuET) to enhance antitumor immunity.Methods: CuET/Tan IIA/PLGA (CTP) nanoparticles were synthesized using a previously reported two-step emulsification method. Subsequently, these nanoparticles were then coated with induced M1 macrophage membranes to obtain M1@CTP. We systematically characterized their morphology, physicochemical properties, and environmental stability. In vitro studies assessed cytotoxicity, immune activation, and tumor-targeting capability. Subsequently, the antitumor efficacy and modulation of the TME were assessed in vivo. Finally, the biosafety of the nanoplatform was evaluated via histopathological and biochemical analyses.Results: Endowed by M1 macrophage membran coating, M1@CTP enables immune evasion and tumor homing, thereby prolonging systemic circulation time and achieving efficient tumor accumulation. Our study demonstrates that M1@CTP synergistically induces potent ICD, promotes dendritic cell maturation, and remodels the TME, leading to the infiltration of cytotoxic T lymphocytes. This process effectively converts “cold” tumors into “hot” ones and elicits a robust systemic antitumor immune response with favorable safety profiles. In addition, M1@CTP significantly enhanced the efficacy of immune checkpoint inhibitors in cold tumor models.Conclusion: This study provides an innovative and precise immunotherapy nanoplatform that coordinately modulates the TME and induces robust antitumor immunity, offering a promising strategy to overcome current limitations in immunotherapy.
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高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Dongqin Xu,Wenhao Zhao,Yiting Feng,Xiao Wen,Hanxiao Liu,Jie Ping
Background Nonalcoholic fatty liver (NAFL), recognized as one of the most common causes of chronic liver diseases , is increasingly prevalent worldwide. Pentoxifylline , a derivative of theobromine extracted from Theobroma cacao and tea, has been studied for effects on blood viscosity , tissue oxygenation and inflammation. However, its effects on hepatic lipid accumulation and the potential mechanisms remain unclear. Purpose This study aimed to investigate the therapeutic effects of pentoxifylline on high-fat diet-induced NAFL and to explore the corresponding molecular mechanisms. Methods NAFL mice were injected with or without 25, 50 or 100 mg/kg pentoxifylline for 2 weeks. Hepatic steatosis was observed by haematoxylin-eosin staining and Oil Red O staining, the levels of serum total cholesterol , triglyceride were detected by biochemical kits, and insulin resistance was evaluated by glucose and insulin tolerance tests. In addition, we measured the frequencies of macrophage and its polarization subsets in the liver using flow cytometry and immunofluorescence. The expressions of proteins associated with macrophage polarization signaling pathways were assessed by Western blotting and flow cytometry histograms. Molecular docking and cellular thermal shift assay were conducted to identify and verify the target protein of pentoxifylline in macrophage. Results Pentoxifylline significantly alleviated hepatic lipid accumulation, reduced blood lipid levels and improved insulin resistance. Strikingly, the excessive M1 macrophages in NAFL development was abolished by pentoxifylline . And pentoxifylline was further evidenced it failed to reduce hepatocyte lipid accumulation in the absence of macrophages in vitro . Mechanistically, pentoxifylline competed with LPS for binding to toll-like receptor 4, dramatically inhibiting the TLR4/MyD88/NF-κB signaling pathway. Conclusion Pentoxifylline attenuated NAFL by inhibiting hepatic macrophage M1 polarization, indicating that pentoxifylline could be a therapeutic candidate for NAFL. This study first observed that M1 macrophages were increased in NAFL mice and then revealed the molecule targeted by pentoxifylline. In addition, we provided evidence that macrophage targeting may be an emerging strategy for NAFL treatment .
研究领域:
药理学
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肝病学
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免疫学
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分子生物学
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代谢学
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MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 10
·703
·
IF 5.4
Wu Leiying,Liao Shanxiao,Dong Alideertu,Hu Xue,Lv Zhiyong,Guo Yuchun,Wu Haixia
A novel aptasensor for the detection of aflatoxin M1 (AFM1) was developed based on the fluorescence resonance energy transfer (FRET) effect between gold nanoparticles (AuNPs) and FAM-labeled cDNA (FAM-cDNA). Additionally, magnetic nanoparticles (Fe 3 O 4 NPs) were attached with AuNPs to construct a Fe 3 O 4 @AuNPs system that was easy to separate by the external magnetic field. In this aptasensor, FAM-labeled cDNA and Fe 3 O 4 @AuNPs acted as donor and acceptor, respectively. In the presence of target AFM1, the aptamer of this aptasensor specifically recognized with AFM1, resulting in a turn-on fluorescence signal due to target-induced dissociation of FAM-cDNA from the FRET pair. The morphology, size and functional group of Fe 3 O 4 @AuNPs were characterized by TEM, XRD and FT-IR. The UV-vis absorption spectroscopy and fluorescence spectroscopy were used to determine the construction of Fe 3 O 4 @AuNPs@Apt@FAM-cDNA aptasensor. Under optimal conditions, the linear concentration range of 1-100 ng/mL, limit of detection (LOD) of 0.20 ng/mL, and recoveries of 99%~101% of the aptasensor were obtained. Overall, this aptasensor with satisfied sensitivity and selectivity are promising to be applied in the detection of other biochemical analytes in the future. Graphical
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2026
·
IF 5
Ziran He,Zhenhua Zhang,Li Ding,Shan Long,Liu Yang,Ce Hu,MengXue Long,Zhiqiang Liu
APOC2 is upregulated in triple-negative breast cancer and correlates with reduced M1 macrophage infiltration. • APOC2 promotes TNBC cell proliferation, migration, and invasion while suppressing M1 macrophage polarization. • The E3 ubiquitin ligase KLHL1 interacts with APOC2 and promotes its degradation via the ubiquitin-proteasome pathway. • KLHL1 overexpression enhances M1 macrophage polarization and inhibits TNBC progression both in vitro and in vivo. Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by an immunosuppressive tumor microenvironment and resistance to chemotherapy. Previous studies have indicated that apolipoprotein C-II (APOC2) is involved in the immune microenvironment of several malignancies and is upregulated in breast cancer; however, the molecular mechanisms through which APOC2 regulates the immune microenvironment in TNBC remain poorly understood. In the present study, we found that APOC2 was upregulated in TNBC tissues and was negatively correlated with M1 macrophage infiltration. APOC2 overexpression in 4 T1 cells promoted tumor progression by enhancing cell proliferation, migration, and invasion, while suppressing M1 macrophage polarization. In addition, KLHL1, a substrate adaptor for the Cullin3-RING E3 ubiquitin ligase complex, was found to interact with APOC2, and KLHL1 overexpression reversed the biological effects induced by APOC2. Mechanistically, KLHL1 promoted APOC2 protein degradation through the ubiquitin–proteasome pathway, thereby enhancing M1 macrophage polarization and suppressing the malignant behavior of tumor cells. Finally, in vivo xenograft experiments demonstrated that APOC2 reduced M1 macrophage polarization and increased tumor weight and volume, whereas KLHL1 overexpression counteracted the oncogenic effects of APOC2. Collectively, these findings reveal that activation of the KLHL1/APOC2 axis enhances M1 macrophage polarization and inhibits TNBC progression, providing novel insights into the immune regulatory mechanisms underlying TNBC development. Download: Download high-res image (104KB) Download: Download full-size image
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