INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
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2024
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IF 3.4
Wenjia Tong,Conglei Song,Danqun Jin,Min Li,Zimei Cheng,Guoping Lu,Bin Yang,Fang Deng
Sepsis is a systemic inflammatory response caused by an infection, which can easily lead to acute lung injury. Quiescin Q6 sulfhydryl oxidase 1 (QSOX1) is a sulfhydryl oxidase involved in oxidative stress and the inflammatory response. However, there are few reports on the role of QSOX1 in sepsis-induced acute lung injury (SALI). In this study, mice model of SALI was constructed by intraperitoneal injection with lipopolysaccharide (LPS). The increased inflammatory response and lactate dehydrogenase activity in bronchoalveolar lavage fluid (BALF) indicated successful modeling. Increased QSOX1 expression was both observed in lung tissues and lung macrophages of sepsis mice accompanied by increased polarization of M1-type macrophages. To explore the role of QSOX1 in the SALI, lentivirus containing QSOX1-specific overexpression or knockdown vectors were used to change QSOX1 expression in LPS-treated RAW264.7 cells. QSOX1 suppressed LPS-induced M1 polarization and further inhibited inflammatory response in RAW264.7 cells. Interestingly, the phosphorylation of epidermal growth factor receptor (EGFR), the promoter of M1 polarization in macrophages, was found to be downregulated upon QSOX1 overexpression in RAW264.7 cells. Mechanically, the binding of QSOX1 to EGFR protein promoted EGFR ubiquitination and degradation, thereby down-regulating EGFR phosphorylation. Moreover, inhibiting EGFR expression or its phosphorylation restored the impact of QSOX1 silencing on M1 polarization and inflammation in the LPS-treated RAW264.7 cells. In summary, QSOX1 may exert anti-inflammatory effects in SALI by inhibiting EGFR phosphorylation-mediated M1 macrophage polarization. This presented a potential target for the treatment and prevention of SALI.
研究领域:
免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Green Energy & Environment
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2022
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IF 12.781
Shuairen Qian,Yuxin Chen,Binhang Yan,Yi Cheng
High activity and productivity of MoVNbTeO x catalyst are challenging tasks in oxidative dehydrogenation of ethane (ODHE) for industrial application. In this work, phase-pure M1 with 30 wt% CeO 2 composite catalyst was treated by oxygen plasma to further enhance catalyst performance. The results show that the oxygen vacancies generated by the solid-state redox reaction between M1 and CeO 2 capture active oxygen species in gas and transform V 4+ to V 5+ without damage to M1 structure. The space-time yield of ethylene of the plasma-treated catalyst was significantly increased, in which the catalyst shows an enhancement near ∼100% than that of phase-pure M1 at 400 °C for ODHE process. Plasma treatment for catalysts demonstrates an effective way to convert electrical energy into chemical energy in catalyst materials. Energy conversion is achieved by using the catalyst as a medium.
研究领域:
催化化学
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材料科学
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能源转换
✓ 已验证
DOI
高影响因子
Journal of Functional Foods
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2022
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IF 5.223
Suwen Liu,Zhang Lu,Chang Liu,Xuedong Chang,Buhailiqiemu Apudureheman,Shiguo Chen,Xingqian Ye
Castanea mollissima shells are a by-product of Chinese chestnut processing and contain many polyphenols. Macrophage polarization plays an important role in the progression of atherosclerosis (AS). We investigated the action of Castanea mollissima shell polyphenols (CSPs), with proanthocyanidin C1 and proanthocyanidin B1 as the main phenolic components, on macrophages. CSPs (40 μg/mL) significantly decreased inflammatory cytokines secretion in M1-type macrophages (p < 0.01). The addition of AG490, a JAK2 inhibitor, enhanced the regulatory effect of CSPs. CSPs also significantly upregulated the protein expressions of PPARγ, LXRα, and ABCA1/G1 (p < 0.01); however, this effect was inhibited by adding the PPARγ blocker GW9662. Therefore, CSPs possibly inhibit M1 type macrophage polarization to reduce inflammation by inhibiting the JAK2/STAT3 signaling pathway; however, it is not dependent on this. Furthermore, the activation of the PPARγ-LXRα-ABCA1/G1 pathway increases cholesterol efflux. Our study suggests that CSPs may act as functional food agents in the prevention of and adjuvant therapy for atherosclerosis.
研究领域:
药理学
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免疫学
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分子生物学
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心血管疾病
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产品关联
DOI
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2024
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IF 3.1
Liu Junhao,Yong Shuangshuang,Yin Sisi,Feng Jinhong,Lian Caihua,Chen Jie
Background Psoriasis is a common immune-related chronic inflammatory skin disease, often accompanied by significant itching, and once diseased, the course of the disease lasts for most of the lifetime. Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza , which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis. Methods An imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway. Results The results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines. Conclusions Collectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization.
研究领域:
药理学
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免疫学
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皮肤科
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炎症
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产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
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2024
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IF 3.2
Mi Tang,Min Wang,Zhirong Wang,Bo Jiang
Aortic aneurysm and dissection (AD) represent a critical cardiovascular emergency with an alarmingly high mortality rate. Recent research has spotlighted the overexpression of genes associated with the m6A modification in AD patients, linking them to the presence of inflammatory M1-type macrophages. Moreover, glycolysis is widely recognized as a key feature of inflammatory M1-type macrophages, but biomarkers linking glycolysis and macrophage function to promote disease progression in AD have not been reported. We conducted an analysis of aortic immune cell infiltration, macrophages, and m6A-related biomarkers in AD patients using bioinformatics techniques. Subsequently, we employed a combination of RT-PCR, WB, and immunofluorescence assays to elucidate the alterations in the expression of M1- and M2-type macrophages, as well as markers of glycolysis, following the overexpression of key biomarkers. These findings were further validated in vivo through the creation of a rat model of AD with knockdown of the aforementioned key biomarkers. The findings revealed that the m6A-modified related gene RBM15 exhibited heightened expression in AD samples and was correlated with macrophage polarization. Upon overexpression of RBM15 in macrophages, there was an observed increase in the expression of M1-type macrophage markers CXCL9 and CXCL10, alongside a decrease in the expression of M2-type macrophage markers CCL13 and MRC1. Furthermore, there was an elevation in the expression of glycolytic enzymes GLUT1 and Hexokinase, as well as HIF1α, GAPDH, and PFKFB3 after RBM15 overexpression. Moreover, in vivo knockdown of RBM15 led to an amelioration of aortic aneurysm in the rat AD model. This knockdown also resulted in a reduction of the M1-type macrophage marker iNOS, while significantly increasing the expression of the M2-type macrophage marker CD206. In conclusion, our findings demonstrate that RBM15 upregulates glycolysis in macrophages, thus contributing to the progression of AD through the promotion of M1-type macrophage polarization. Conversely, downregulation of RBM15 suppresses M1-type macrophage polarization, thereby decelerating the advancement of AD. These results unveil potential novel targets for the treatment of AD.
研究领域:
心血管疾病
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免疫学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Xin Tan,Renwang Sheng,Weikun Li,Yinghua Tao,Zonghao Liu,Ning Yang,Syeda Safia Hashmi,Feiling Feng,Fangzhou Liu,Liqin Ge
Microcapsules are advancing in immunotherapy, with both their core and shell being capable of loading immunoregulatory substances. Notably, microcapsules with intrinsic bioactivities can more directly modulate the immune microenvironment, while current research in this area remains scarce. Herein, immunomodulatory metal-phenolic microcapsules (mMPMs) is developed through the one-step assembly of dopamine-modified hyaluronic acid (HADA) and Fe III onto mannose-glycated bovine serum albumin microbubbles (Man-BSA MBs). Specifically, Man-BSA formed during the early stages of the Maillard reaction is sonicated to produce microbubbles as templates for capsule preparation. Subsequently, HADA is rapidly coated on the templates and coordinates with Fe III to form microcapsules after air escapes from MBs. Mass spectrometry analysis identifies abundant lysine glycation sites on Man-BSA, with the highest glycation site percentage reaching 94.88%. Man-BSA within mMPMs effectively promotes macrophage internalization, induces the accumulation of pro-inflammatory mediators, and thereby results in the M1 polarization of macrophages, as further corroborated by proteomic analysis. Consequently, the compelling anti-tumor effects of mMPMs are demonstrated both in vitro and in vivo. Overall, this work presents an immunomodulatory microcapsule that activates pro-inflammatory phenotype macrophages, which is a promising microcarrier to improve immunotherapeutic effects.
研究领域:
生物材料学
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免疫学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Lei Wang,Jinchun Wang,Lei Han,Tong Chen
The present work was conducted to research the potential mechanism of palmatine (PAL) on lipopolysaccharide (LPS)-caused acute lung injury (ALI). Network pharmacology and bioinformatic analyses were carried out. Mice were intragastrically treated with PAL and intratracheally stimulated with LPS. LPS-induced RAW264.7 cells were employed for the in vitro model. The MPO activity, W/D ratio, neutrophils, total cell number in BALF, and histopathological alteration were examined. The levels of TNF-α, IL-1β, IL-6, IL-18, IL-4, and IL-10 in serum, BALF, and supernatant were examined by ELISA. The mRNA expressions of iNOS, CD68, Arg1, Ym1, and CD206 and protein expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome were detected by PCR, WB, and immunofluorescence. The NAMPT inhibitor FK866, TLR2 inhibitor C29, CCR1 inhibitor BX471, NAMPT-overexpression (OE) plasmid, and TLR2-OE plasmid were used for mechanism research. As a result, PAL relieved the symptoms of ALI. PAL inhibited M1 phenotype indices and promoted M2 phenotype indices in both LPS-induced mice and RAW264.7 cells. PAL also inhibited the expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome. The treatments with FK866, NAMPT-OE plasmid, C29, TLR2-OE plasmid, and BX471 proved that PAL exerted its effect via NAMPT/TLR2/CCR1. Molecular docking suggested that PAL might combine with NAMPT. In conclusion, PAL ameliorated LPS-induced ALI by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling.
研究领域:
药理学
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免疫学
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呼吸病学
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生物化学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Lei Zhou,Leyuan Huang,Guanfeng He,Haixin Li,Manchun Liu,Jingwen Xu
Background Allergic rhinitis (AR) is a common IgE-mediated inflammatory disease of the nasal mucosa, involving immune–neural interactions such as mast cell activation, cytokine release, and transient receptor potential vanilloid 1 (TRPV1)-mediated neuronal sensitization. Xiao-Qing-Long-Tang (XQLT) is a classical traditional Chinese medicine used clinically for AR. However, its mechanisms, particularly in macrophage regulation and TRPV1 activity, remain not fully understood. Objective This study aimed to evaluate the therapeutic effects of XQLT in an ovalbumin (OVA)-induced AR mouse model and to investigate its molecular mechanisms focusing on immune regulation, macrophage-mediated inflammation, and TRPV1 channel activity. Methods The chemical composition of XQLT was analyzed by UPLC-Q Exactive Orbitrap-HRMS system. The therapeutic effectiveness of XQLT was assessed in an OVA-induced AR mouse model. Clinical symptoms, serum biomarkers (OVA-sIgE, interleukin-4 (IL-4), histamine), and histopathological changes were assessed. Transcriptomic analysis of nasal mucosa was performed to explore molecular pathways. The anti-inflammatory effects of XQLT were evaluated in LPS-stimulated RAW264.7 and bone marrow–derived macrophages by measuring NO, cytokine expression, and NF- κ B activation. TRPV1 involvement was examined using immunohistochemistry in AR mice model, calcium imaging in HEK293 cells overexpressing TRPV1, as well as molecular docking. Results XQLT treatment significantly reduced nasal rubbing and sneezing frequencies in AR mice, decreased serum OVA-sIgE, IL-4, and histamine levels, and ameliorated nasal and lung histopathological remodeling without observable toxicity. Transcriptomic profiling revealed that XQLT modulated DEGs associated with immune response, inflammatory signaling, olfactory transduction, and sensory perception of pain. In macrophages, XQLT suppressed LPS-induced NO production, downregulated IL-6, IL-1 β , CCL2, iNOS, and COX-2 expression, and inhibited NF- κ B nuclear translocation. Importantly, XQLT reduced TRPV1 expression in AR nasal mucosa and inhibited TRPV1-mediated calcium influx in HEK293 TRPV1-overexpressing cells. Zingiberis Rhizoma (Ganjiang) was identified as a key herb contributing to TRPV1 inhibition in XQLT, supported by molecular docking analysis. Conclusion XQLT alleviates AR symptoms and tissue remodeling through coordinated suppression of macrophage-mediated inflammation and TRPV1-dependent neurogenic pathways. These findings provide novel mechanistic insights into XQLT as a safe and promising multi-target therapy for AR.
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Yao Shi,Haojie Zhang,Shuang Li,Danqing Xin,Shiyang Li,Bing Yan,Shuanglian Wang,Chuanyong Liu
Background Inflammatory bowel disease (IBD) is a chronic disease with an unclear pathogenesis for which successful treatments are still lacking. It has been reported that procyanidin, a natural antioxidant, relieves colitis, but the specific mechanism is elusive. Purpose Our present study was designed to investigate the effects of procyanidin on colitis and the regulation of the M1 macrophage phenotype and related signaling pathways. Methods In vivo, we used two classic colitis models to observe the effect of procyanidin on macrophage polarization. In vitro, we further validated the therapeutic effect of procyanidin in the RAW264.7 cell line and peritoneal macrophages. Results The current findings provide new evidence that procyanidin ameliorated dextran sulfate sodium (DSS)-induced colitis by preventing the polarization of macrophages to the M1 type and downregulating the levels of proinflammatory factors in cells. We also showed that procyanidin prevented lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines and the activation of proinflammatory macrophages, which was achieved by activating the STAT3 and NF-κB pathways. Conclusions This is the first study to demonstrate that procyanidin alleviates experimental colitis by inhibiting the polarization of proinflammatory macrophages. These data reveal new ideas for the pathogenesis and treatment of inflammatory diseases.
研究领域:
免疫学
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药理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
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2025
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IF 2.8
Yunbing Chen,Xinping Li,Hongyi Yang,Gaoying Ran,Lifang Zhang,Shuguang Zeng
β-Tricalcium phosphate (β-TCP), frequently employed for bone tissue regeneration, can induce inflammation during the initial phases of implantation within the organism. However, mechanisms by which β-TCP nanoparticles (NPs) cause this inflammatory response is rarely reported. This project aims to investigate the causes of the macrophage inflammatory response induced by β-TCP NPs. Here, macrophage-like RAW264.7 cells were co-cultured with conditioned medium containing β-TCP NPs to identify the pathways through which β-TCP NPs influence inflammation and polarization of macrophages. This effect is achieved by modulating mitochondrial oxidative stress in the immune microenvironment. The results demonstrated that β-TCP NPs caused mitochondrial swelling, increased intracellular calcium ions, reduced mitochondrial membrane potential, as well as decreased the level of adenosine triphosphate (ATP) and translocase of outer mitochondrial membrane 20 (TOMM20). These NPs further lead to mitochondrial oxidative damage. These alterations promoted the polarization of macrophage to M1-type. Exogenous mitochondrial-targeted antioxidants could block this M1-type macrophage polarization. The findings of this work suggest that β-TCP NPs induce macrophage inflammation and contribute to M1 macrophage polarization, primarily through the activation of mitochondrial oxidative stress. These insights could guide the development of improved β-TCP formulations to mitigate inflammatory responses in bone regeneration applications.
研究领域:
生物材料学
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免疫学
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纳米医学
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骨生物学
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分子细胞生物学
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转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2024
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IF 4.6
Yu Shan,Yang Jinghui,Zhang Rui,Guo Qian,Wang Lu
Systemic inflammatory stimulus is a risk factor for the incidence of ischemic stroke and contributes to poorer clinical outcomes. Solute carrier 15A3 (SLC15A3) is a peptide/histidine transporter that is implicated in regulating inflammatory responses. However, whether SLC15A3 affects the progression of ischemic stroke associated with systemic inflammation is unclear. The transient middle cerebral artery occlusion (tMCAO) mice with LPS administration (LPS/tMCAO) were prepared as an in vivo model, and LPS-induced BV2 cells under oxygen–glucose deprivation (OGD) exposure were utilized as an in vitro model. We found that SLC15A3 was highly expressed in the ischemic penumbra of LPS/tMCAO mice, and its inhibition reduced infarct area, attenuated neurological deficit, recovered motor function, and mitigated apoptotic neurons. Knockdown of SLC15A3 suppressed the proinflammatory M1-type markers and promoted the levels of M2-associated genes. The in vitro results confirmed that SLC15A3 overexpression promoted microglia polarizing towards M1 subtypes, while SLC15A3 inhibition exerted an opposite effect. In addition, we demonstrated that the p65 signaling pathway and HIF1α were activated by LPS/OGD. Luciferase reporter assay showed that inhibiting p65 using its specific inhibitor BAY 11–7082 or silencing HIF1α using siRNAs reduced the transcriptional activity of SLC15A3 in LPS/OGD-induced BV2 cells. Results in NIH 3T3 cells also confirmed that p65 and HIF1α directly bound to the SLC15A3 promoter to activate SLC15A3 transcription. In conclusion, this work shows that SLC15A3 , transcriptionally activated by p65 and HIF1α, contributes to poor outcomes in ischemic stroke associated with systemic inflammation by promoting microglial cells polarizing towards M1 types.
研究领域:
神经科学
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免疫学
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分子生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
Theranostics
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2020
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IF 8.579
Tianlei Sun,Cheryl H. T. Kwong,Cheng Gao,Jianwen Wei,Ludan Yue,Jianxiang Zhang,Richard Dequan Ye,Ruibing Wang
Ulcerative colitis (UC) is featured with relapsing inflammation in the colon, where macrophages are recruited and polarized locally into M1 type to drive further inflammation. Pharmacotherapy of UC has exhibited limited efficacy, mostly due to the poor specificity. Methods: A macrophage-biomimetic nanomedicine was developed for targeted treatment of UC, which was derived from reactive oxygen species (ROS)-sensitive β-cyclodextrin, loaded with rosiglitazone, and coated with macrophage membrane. The ability of the nanomedicine in regulating macrophage polarization was examined at cellular level, and the macrophage-tropism driven targeted delivery into the inflammatory colon was investigated by ex vivo bio-imaging distribution assay. Furthermore, the nanomedicine's therapeutic efficacy was systemically examined in dextran sulfate sodium (DSS)-induced colitis model in mice. Results: The nanomedicine effectively polarized macrophages to M2 and protected epithelial cells from oxidative stress in vitro . In addition, macrophage-membrane led the nanomedicine to the inflammatory colon with a high targeting efficiency. In response to the elevated ROS in the inflammatory tissue, the nanomedicine released rosiglitazone specifically and regulated macrophage polarization in vivo . Macrophage membrane also assisted inflammation suppression by sequestering proinflammatory cytokines. Working in such a synergy, the nanomedicine exhibited significant therapeutic effects against UC in mice. Conclusions: This macrophage-biomimetic nanomedicine leverages the inflammatory tropism and inflammatory cytokine sequestration effects of macrophage membrane for targeted delivery and local inflammation suppression, the ROS-responsiveness of β-cyclodextrin-based matrix for specific payload release, and the macrophage-polarizing effect of rosiglitazone for inflammatory regulation, thereby exhibiting considerable therapeutic efficacy against UC in mice. This study offers important new insights on the design and development of biomimetic nanomaterials for inflammation regulations.
研究领域:
药理学
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纳米技术
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免疫学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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