Molecular Medicine Reports
·
2024
·Vol. 30
·期 2
·1-15
·
IF 3.4
Jingxia Du,Yibo Dong,Jingjing Song,Hanqi Shui,Chengyao Xiao,Yue Hu,Shiyao Zhou,Shanshan Wang
Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the macrophage‑mediated inflammatory response may play a vital role in MIRI. Mesenchymal stem cells and, in particular, exosomes derived from these cells, may be key mediators of myocardial injury and repair. However, whether exosomes protect the heart by regulating the polarization of macrophages and the exact mechanisms involved are poorly understood. The present study aimed to determine whether exosomes secreted by bone marrow mesenchymal stem cells (BMSC‑Exo) harboring miR‑25‑3p can alter the phenotype of macrophages by affecting the JAK2/STAT3 signaling pathway, which reduces the inflammatory response and protects against MIRI. An in vivo MIRI model was established in rats by ligating the anterior descending region of the left coronary artery for 30 min followed by reperfusion for 120 min, and BMSC‑Exo carrying miR‑25‑3p (BMSC‑Exo‑25‑3p) were administered through tail vein injection. A hypoxia‑reoxygenation model of H9C2 cells was established, and the cells were cocultured with BMSC‑Exo‑25‑3p in vitro. The results of the present study demonstrated that BMSC‑Exo or BMSC‑Exo‑25‑3p could be taken up by cardiomyocytes in vivo and H9C2 cells in vitro. BMSC‑Exo‑25‑3p demonstrated powerful cardioprotective effects by decreasing the cardiac infarct size, reducing the incidence of malignant arrhythmias and attenuating myocardial enzyme activity, as indicated by lactate dehydrogenase and creatine kinase levels. It induced M1‑like macrophage polarization after myocardial ischemia/reperfusion (I/R), as evidenced by the increase in iNOS expression through immunofluorescence staining and upregulation of proinflammatory cytokines through RT‑qPCR, such as interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6). As hypothesized, BMSC‑Exo‑25‑3p inhibited M1‑like macrophage polarization and proinflammatory cytokine expression while promoting M2‑like macrophage polarization. Mechanistically, the JAK2/STAT3 signaling pathway was activated after I/R in vivo and in LPS‑stimulated macrophages in vitro, and BMSC‑Exo‑25‑3p pretreatment inhibited this activation. The results of the present study indicate that the attenuation of MIRI by BMSC‑Exo‑25‑3p may be related to JAK2/STAT3 signaling pathway inactivation and subsequent inhibition of M1‑like macrophage polarization.
研究领域:
心脏病学
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分子生物学
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干细胞研究
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炎症
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外泌体治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Xie Hanbin,Wei Cong,Xiong Chang,Huang Ziyan,Chen Chaojin,Xiao Xue,Zhang Linan,Lin Zhenjia,Yao Weifeng,Zhao Tianyu,Hei Ziqing
Intestinal ischemia/reperfusion (I/R) injury is a common life-threatening condition. Inflammatory dysregulation plays a crucial role in the pathological progression of intestinal I/R injury, indicating that controlling excessive inflammatory responses can be an effective strategy for mitigating I/R injury. Herein, after establishing a correlation between cell-free DNA (cfDNA) levels and postoperative inflammatory factors in samples from patients with intestinal I/R, we tested a cfDNA-scavenging approach for the treatment of intestinal I/R injury. Poly-ε-caprolactone (PCL) microspheres (Micro DEA2k) functionalized with a pH-responsive cationic polymer (DEA2k) to efficiently scavenge cfDNA were synthesized and evaluated.These microspheres exhibited enhanced cfDNA adsorption under inflammation-induced acidic conditions, along with low toxicity, reduced non-specific protein binding, and extended peritoneal retention. In a mouse model of intestinal I/R injury, the intraperitoneal injection Micro DEA2k effectively bound cfDNA, regulated the mononuclear phagocytic system, decreased the number of M1 macrophages, suppressed inflammation, and significantly improved the survival rate of the mice. These findings suggest that cfDNA scavenging using cationic microspheres has considerable potential for alleviating intestinal I/R injury. Graphical
研究领域:
药理学
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免疫学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Shurong Duan,Fei Wang,Jingwei Cao,Chunyan Wang
Introduction Intracerebral hemorrhage (ICH) is a devastating type of stroke with high mortality, and the effective therapies for ICH remain to be explored. Exosomes (Exos) have been found to play important roles in cell communication by transferring molecules, including microRNAs (miRNAs/miRs). MiRNAs are critical regulators of genes involved in many various biological processes and have been demonstrated to aggravate or alleviate brain damages induced by ICH. The aim of the present study was to investigate the effect of Exos derived from miR-146a-5p-enriched bone marrow mesenchymal stem cells (BMSCs-miR-146a-5p-Exos) on experimental ICH.Methods ICH was induced in adult male Sprague-Dawley rats by an intrastriatal injection of collagenase type IV. At 24 h after surgery, Exos were administrated. For detecting apoptotic cells, TUNEL staining was performed using an in situ Cell Death Detection Kit. Fluoro-Jade B staining was performed to detect degenerating neurons. Immunofluorescence assay was performed to detect the expression of myeloperoxidase (MPO) and OX-42. The binding of miR-146a-5p and its target genes was confirmed by luciferase reporter assay.Results At 24 h after surgery, BMSCs-miR-146a-5p-Exos administration significantly improved neurological function, reduced apoptotic and degenerative neurons, and inhibited inflammatory response. Furthermore, miR-146a-5p-enriched Exos obviously inhibited the M1 polarization of microglia after ICH in rats, accompanied by the reduced expression of pro-inflammatory mediators releasing by M1 microglia including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1). Finally, we observed that miR-146a-5p directly targeted interleukin-1 receptor-associated kinase1 (IRAK1) and nuclear factor of activated T cells 5 (NFAT5), which contributed to the inflammation response and the polarization of M1 microglia/macrophages.Conclusion We demonstrated that miR-146a-5p-riched BMSCs-Exos could offer neuroprotection and functional improvements after ICH through reducing neuronal apoptosis, and inflammation associated with the inhibition of microglial M1 polarization by downregulating the expression of IRAK1 and NFAT5.
研究领域:
神经科学
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干细胞生物学
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分子生物学
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神经病学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Dong Guo,Hui Liu,Sheng Zhao,Xinya Lu,Haoyu Wan,Yitao Zhao,Xinzhi Liang,Anbiao Zhang,Mengyuan Wu,Zhisheng Xiao,Ning Hu,Zhong Li,Denghui Xie
A detrimental feedback loop between hypoxia and oxidative stress consistently drives macrophage polarization toward a pro-inflammatory M1 phenotype, thus persistently aggravating rheumatoid arthritis (RA) progression. Herein, an enzyme-catalyzed nanoplatform with synergistic hypoxia-relieving and reactive oxygen species (ROS)-scavenging properties was developed using bovine serum albumin-bilirubin-platinum nanoparticles (BSA-BR-Pt NPs). Bilirubin was employed to eliminate ROS, while platinum exhibited a synergistic effect in scavenging ROS and simultaneously generated oxygen. In mice RA model, BSA-BR-Pt NPs treatment exhibited superior effects, resulting in significant improvements in joint inflammation, cartilage damage, and bone erosion, compared to methotrexate, the most widely used antirheumatic drug. Mechanistically, RNA-sequencing data and experimental results elucidated that BSA-BR-Pt NPs induced a re-polarization of hypoxic M1 macrophages to M2 macrophages via switching glycolysis to oxidative phosphorylation through the inhibition of HIF-1α pathway. Collectively, this research for the first time elaborated the underlying mechanism of enzyme-catalyzed nanoplatform in orchestrating macrophage polarization, and identified a novel therapeutic strategy for RA and other inflammatory disorders.
研究领域:
药理学
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免疫学
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纳米技术
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风湿病学
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 12
·1-9
·
IF 6.232
Su Zixian,Zhao Guangying,Dou Wenchao
Aflatoxin M1 (AFM1) residues in milk pose a major threat to human health, so there is an urgent need for a simple, rapid, and sensitive method for the determination of trace AFM1 in milk. In this study, a competitive immunochromatographic assay (ICA), using visual (PEI/PSS) 4 red silica nanoparticles (SiNPs) as signal amplification probes, was used for the highly sensitive detection of AFM1. The (PEI/PSS) 4 red SiNPs were used to label AFM1 monoclonal antibody (mAb) to prepare ICA for the detection of AFM1. After exploring the optimal conditions of mAb and immunoprobe dosage conditions, the lowest visual detection limit (VDL) of AFM1 in phosphate-buffered saline with Tween 20 (PBST, 10 mM, pH 7.4, containing 1% BSA, 3% sucrose, 1% trehalose, and 0.5% Tween 20) can reach 0.1 pg/mL. The intuitive visually visible value of AFM1 in both PBST and milk was 10 pg/mL. The results showed that the immunochromatographic system based on high chroma color (PEI/PSS) 4 red SiNPs has high sensitivity and broad application prospects for the detection of trace AFM1 residues in milk. The high chroma (PEI/PSS) 4 red SiNPs are expected to be a convenient biomarker for improving the sensitivity of immune chromatography bands.
The schematic diagram shows the detection principle. In this work, in the competitive experiment, (PEI/PSS) 4 red SiNPs were selected as visual labeling materials, and the specific antibody combined with the labeled material was selected as an immune probe. The AFM1-BSA antigen coupled with the macromolecular BSA was fixed on the T line of the nitrocellulose (NC) membrane. The AFM1 in sample solution competes with AFM1-BSA for the specific binding site of immune probe. The detection sensitivity of this method for AFM1 is obtained by judging the change of the red signal intensity produced by the positive sample, compared with the color at the T line of the negative sample.
研究领域:
食品安全
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分析化学
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纳米技术
·
生物技术
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Wenjia Xie,Yuxuan Wang,Jicenyuan Wu,Xu Wang,Jiaxin Wu,Bin Cheng,Hao Feng,Xinxu Huang,Xinting Cheng,Junyu Chen,Qianbing Wan,Jian Wang,Xibo Pei
Diabetic periodontitis is characterized by persistent and aggravated inflammation, largely driven by a reactive oxygen species (ROS) vicious loop in M1 macrophages driven by mitochondrial dysfunction. To disrupt this pathogenic cascade, we developed hierarchically targeted polymeric nanoparticles (MPPT NPs) by conjugating the tuftsin peptide for selective uptake by M1 macrophages and loading mitoquinone mesylate (MitoQ) to restore mitochondrial function after mitochondrial localization. For local retention and responsive drug release, MPPT NPs were incorporated into a ROS-responsive hydrogel (MTP hydrogel) constructed by cross-linking poly(vinyl alcohol) (PVA) with a ROS-cleavable linker (N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diaminium (TSPBA)). This constructed platform not only enabled the on-demand release of MPPT NPs but also provided additional ROS-scavenging ability. In vitro studies demonstrated that MTTP NPs effectively repaired oxidatively damaged mitochondria and suppressed NLRP3 inflammasome priming and activation. MTP hydrogel platform reduced pro-inflammatory cytokine release and rescued inflammation-induced osteogenic impairment. In a diabetic periodontitis rat model, local administration of the MTP hydrogel significantly attenuated periodontal tissue destruction and promoted alveolar bone regeneration, achieving BV/TV 1.5 times that of previous reports. Collectively, this hierarchically targeted and ROS-responsive platform disrupts the ROS vicious loop in M1 macrophages by repairing damaged mitochondria, offering a promising therapeutic strategy for the management of diabetic periodontitis.
研究领域:
纳米医学
·
牙科
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免疫学
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活性氧信号通路
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生物材料
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炎症性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Waimei Si,Xin Li,Bei Jing,Shiquan Chang,Yachun Zheng,Zhenni Chen,Guoping Zhao,Di Zhang
(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT-PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL-1β and IL-8 levels and increased serum IL-4 and TGF-β levels in CCI rats. Stigmasterol reduced IL-1β, COX-2, and TLR4 expression in the right sciatic nerve and IL-1β expression in the spinal cord. Stigmasterol reduced the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, COX-2, IL-1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL-10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)-induced microglia and decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, iNOS, COX-2, and IL-1β in LPS-treated microglia while increasing the expression of Arg-1 and IL-10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate NP.
研究领域:
药理学
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神经科学
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免疫学
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疼痛研究
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2019
·Vol. 44
·期 4
·1362-1370
·
IF 3.069
Xingshuang An,Xiaojie Shi,Hui Zhang,Yao Yao,Guangxian Wang,Qingqing Yang,Lianming Xia,Xia Sun
In this paper, a sensitive electrochemical immunosensor modified with graphene oxide–chitosan (GO–CS) and cerium oxide–chitosan (CeO2–CS) using screen-printed electrodes (SPEs) was developed for the determination of aflatoxin M1 (AFM1) in milk. Compared with other electrodes, SPEs are easy for quick detection and no polishing steps are required. Graphene oxide (GO) has strong electrical conductivity and a large specific surface area, which can accelerate the transfer of electrons and fix more anti-AFM1 antibodies (ab-AFM1) on SPEs. Compared with GO, cerium oxide (CeO2) nanoparticles have a smaller diameter, and CeO2 can be uniformly attached to the surface of the GO. Simultaneously, CeO2 has good redox properties and can further accelerate the transfer of electrons, thereby further amplifying the electrochemical signal of the sensor. Chitosan (CS) has strong complexation ability, which can uniformly disperse GO and CeO2. Herein, GO–CS and CeO2–CS gradually modified SPEs to improve their electrochemical response and immobilize more antibodies. The properties of the AFM1 immunosensor were studied via differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Under the optimal conditions, the immunosensor showed great reproducibility and high stability with a detection limit of 0.009 μg L−1. In addition, the immunosensor was successfully utilized for the determination of AFM1 in milk. This immunosensing principle will have broad prospects for the analysis of toxins in food, ensuring the safety of milk and dairy products.
研究领域:
食品安全
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分析化学
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电化学
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毒理学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Huiling Tang,Qiuping Li,Zhengqi Zha,Yuzhi Jiao,Baowei Yang,Zhaoyan Cheng,Ting Wang,Hongping Yin
Ulcerative colitis (UC) is a chronic inflammatory disease resulting from abnormal immune response to gut microflora translocating through damaged intestinal barrier. Xylan acetate ester (XylA) can increase colon short-chain fatty acids (SCFAs) levels and alleviate kidney disease by inhibiting inflammation through the G protein-coupled receptor pathway. Here, we synthesized and purified XylA, and then the effects and mechanisms of XylA on dextran sodium sulfate-induced UC in mice were investigated. The results showed that in mice, similar to the positive drug 5-aminosalicylic acid, oral administration of XylA significantly alleviated all UC symptoms, including weight loss, diarrhea, and hematochezia. Further mechanism studies revealed that XylA could repair the damaged colon structure and intestinal barrier function by increasing the expression of tight junction protein zonula occludens 1 and occludin, thus reducing LPS penetration. Moreover, XylA could also restrain intestinal inflammation via inhibiting LPS-TLR4 pathway, downregulating M1 macrophage polarization, and reducing proinflammatory cytokines expression, and in vitro cell experiments showed that these effects may be mediated by XylA derived SCFAs, particularly acetates, propionates and butyrates. All these results suggested that XylA may be a potential improving agent for UC treatment, and natural polysaccharides may represent a novel avenue for drug development of UC.
研究领域:
药理学
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免疫学
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胃肠病学
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炎症性肠病
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产品关联
DOI
PubMed
高影响因子
Toxins
·
2013
·Vol. 5
·期 5
·865-883
·
IF 2.129
Ning Gan,Jing Zhou,Ping Xiong,Futao Hu,Yuting Cao,Tianhua Li,Qianli Jiang
An ultrasensitive electrochemiluminescent immunoassay (ECLIA) for aflatoxins M1 (ATM1) in milk using magnetic Fe3O4-graphene oxides (Fe-GO) as the absorbent and antibody-labeled cadmium telluride quantum dots (CdTe QDs) as the signal tag is presented. Firstly, Fe3O4nanoparticles were immobilized on GO to fabricate the magnetic nanocomposites, which were used as absorbent to ATM1. Secondly, aflatoxin M1 antibody (primary antibody, ATM1 Ab1), was attached to the surface of the CdTe QDs-carbon nanotubes nanocomposite to form the signal tag (ATM1 Ab1/CdTe-CNT). The above materials were characterized. The optimal experimental conditions were obtained. Thirdly, Fe-GO was employed for extraction of ATM1 in milk. Results indicated that it can adsorb ATM1 efficiently and selectively within a large extent of pH from 3.0 to 8.0. Adsorption processes reached 95% of the equilibrium within 10 min. Lastly, the ATM1 with a serial of concentrations absorbed on Fe-GO was conjugated with ATM1 Ab1/CdTe-CNT signal tag based on sandwich immunoassay. The immunocomplex can emit a strong ECL signal whose intensity depended linearly on the logarithm of ATM1 concentration from 1.0 to 1.0 × 105pg/mL, with the detection limit (LOD) of 0.3 pg/mL (S/N= 3). The method was more sensitive for ATM1 detection compared to the ELISA method. Finally, ten samples of milk were tested based on the immunoassay. The method is fast and requires very little sample preparation, which was suitable for high-throughput screening of mycotoxins in food.Keywords:aflatoxin M1;Fe3O4-graphene nanocomposite;cadmium telluride-quantumn dots;milk;electrochemiluminescence immunoassay;mycotoxins
研究领域:
食品科学
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免疫学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 27
·20951-20960
·
IF 3.84
Shoulian Wei,Yong Liu,Zijun Yan,Ling Liu
A molecularly imprinted polymer was synthesized by a miniemulsion polymerization method using aflatoxin B1 as the molecular template, methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, Span80 and hexadecyl trimethyl ammonium bromide as the surfactants and n-hexadecane as the hydrophobic reagent in the presence of water. This imprinted polymer was characterized by FT-IR, 1H NMR, scanning electron microscopy, laser light scattering and adsorption experiments, in which the results showed good recognition and selectivity to aflatoxin B1 and M1. Using the prepared polymer as a solid phase extraction sorbent, a highly selective sample pre-treatment method combined with high performance liquid chromatography and fluorescence detection was developed for determination of aflatoxin B1 and M1 in foods and feeds. The limit of detection and limit of quantification of this method for aflatoxins M1 and B1 were 0.05 μg kg−1 and 0.16 μg kg−1, respectively. The average recovery values from barley, peanut oil, feed and beer spiked samples ranged from 83% to 96%. The precision ranged from 2.2% to 5.6% for these samples. The proposed method was found to be more effective and economical as a pre-treatment technique than regulation 2006/40/EC.
研究领域:
分析化学
·
食品科学
·
毒理学
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产品关联
DOI
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 08
·2157-2173
·
IF 5.7
Zhenfeng Liu,Wuming Zhou,Qingyang Liu,Zhirong Huan,Qiubo Wang,Xin Ge
Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos , has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α ) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.
研究领域:
药理学
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免疫学
·
心脏病学
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病理生理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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