JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Tao Bo,Chenfei Wang,Dingjin Yao,Qiuyu Jiang,Yitong Zhao,Feifei Wang,Wei He,Weiyi Xu,Hao Zhou,Ming Li,Si Zhang,Ruyi Xue
Gene delivery to macrophages holds great promise for cancer immunotherapy. However, traditional gene delivery methods exhibit low transfection efficiency in macrophages. The star -shaped topological structure of polymers is known to encapsulate genes inside their cores, thereby facilitating sustained release of the genetic material. Herein, combining the structural advantages of star polymers and the transfection advantages of poly (β-amino ester)s (PAEs), we developed a novel linear oligomer grafting-onto strategy to synthesize a library of multi-terminal star structured PAEs (SPAEs), and evaluated their gene delivery efficiency in various tissue cells. The transfection with human hepatocellular carcinoma cells (HepG2, HCC-LM3 cells and MHCC-97H cells), rat normal liver cells (BRL-3 A cells), human ovarian cancer cells (A2780 cells), African green monkey kidney cells (Vero cells), human cervical cancer cells (HeLa cells), human chondrosarcoma cells (SW1353 cells), and difficult-to-transfect human epidermal keratinocytes (HaCaT cells) and normal human fibroblast cells (NHF cells) showed that SPAEs exhibited superior transfection profile. The GFP transfection efficiency of top-performing SPAEs in HeLa cells (96.1%) was 2.1-fold, and 3.2-fold higher compared to jetPEI and Lipo3000, respectively, indicating that the star-shaped topological structure can significantly enhance the transfection efficiency of PAEs. More importantly, the top-performing SPAEs could efficiently deliver Nod2 DNA to difficult-to-transfect RAW264.7 macrophages, with a high transfection efficiency of 33.9%, which could promote macrophage M1 polarization and enhanced CD8+ T cell response in co-incubation experiments. This work advances gene therapy by targeting difficult-to-transfect macrophages and remodeling the tumor immune microenvironment.
研究领域:
生物技术
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药学
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免疫学
·
癌症研究
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DOI
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Ying-kun Zhi,Jing Li,Lang Yi,Rui-li Zhu,Jin-fang Luo,Qing-ping Shi,Sha-sha Bai,Yan-wu Li,Qun Du,Jia-zhong Cai,Liang Liu,Pei-xun Wang,Hua Zhou,Yan Dong
Background Sinomenine (SIN) is an anti-inflammatory drug that has been used for decades in China to treat arthritis . In a previous study, SIN acted on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit inflammatory responses in macrophages, which indicates a new anti-inflammatory mechanism of SIN. However, the level of α7nAChR was increased in the inflammatory responses and was downregulated by SIN in vitro, so the underlying mechanisms of SIN acting on α7nAChR remain unclear. Purpose To analyze the role of α7nAChR in inflammation and the effect and mechanism of SIN regulation of α7nAChR. Methods The effects of SIN on α7nAChR in endotoxemic mice and LPS-stimulated macrophages were observed. Nicotine (Nic) was used as a positive control, and berberine (Ber) was used as a negative control targeting α7nAChR. The antagonists of α7nAChR, α-bungarotoxin (BTX) and mecamylamine (Me), were used to block α7nAChR. In RAW264.7 macrophage cells in vitro , α7nAChR short hairpin RNA (shRNA) was used to knock down α7nAChR. Macrophage polarization was analyzed by the detection of TNF-α, IL-6, iNOS, IL-10, Arg-1, and Fizz1. U0126 was used to block ERK phosphorylation. The cytokines α7nAChR, ERK1/2, p-ERK1/2 and Egr-1 were detected. Results SIN decreased the levels of TNF-α, IL-6 and the expression of α7nAChR increased by LPS in endotoxemic mice. The above effects of SIN were attenuated by BTX. In the α7nAChR shRNA transfected RAW264.7 cells, compared with the control, α7nAChR was knocked down, and M1 phenotype markers (including TNF-α, IL-6, and iNOS) were significantly downregulated, whereas M2 phenotype markers (including IL-10, Arg-1, and Fizz1) were significantly upregulated when stimulated by LPS. SIN inhibited the expression of p-ERK1/2 and the transcription factor Egr-1 induced by LPS in RAW264.7 cells, and the above effects of SIN were attenuated by BTX. The expression of α7nAChR was suppressed by U0126, which lessened the expression of p-ERK1/2 and Egr-1. Conclusions SIN acts on α7nAChR to inhibit inflammatory responses and downregulates high expression of α7nAChR in vivo and in vitro . The increase of α7nAChR expression is correlated with inflammatory responses and participates in macrophage M1 polarization. SIN downregulates α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1, which contributes to inhibiting macrophage M1 polarization and inflammatory responses.
研究领域:
免疫学
·
药理学
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细胞生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
·
2021
·
IF 4.034
Yuanyuan Hui,Haishuai Peng,Fuxin Zhang,Lei Zhang,Liu Yufang,Aiqing Zhao,Rong Jia,Bini Wang,Yuxuan Song
ABSTRACT Aflatoxin M 1 (AFM 1 ) is a common toxin in dairy products that causes acute and chronic human health disorders. Thus, the development of a rapid and accurate AFM 1 detection method is of vital importance for food safety monitoring. This work was to develop a novel electrochemical aptasensor for sensitive and specific determination of AFM 1. The dendritic-like nanostructure was formed on the gold electrode surface by layer-by-layer assembly of gold-silver core-shell nanoparticles modified with DNA conjugates. In the presence of AFM 1 , the specific recognition between AFM 1 and Apt caused the disassociation of the DNA controlled dual [email protected] conjugates from the surface of the electrode, causing less methylene blue to bind to the surface and weakening the electrochemical signal. The more AFM 1 there is, the weaker the electrochemical signal. Transmission electron microscope results showed that the successfully synthesized [email protected] nanoparticles exhibited a core-shell structure with Au as core and Ag as shell, and their average diameter was about 30 nm. Under optimal conditions, the electrochemical aptasensor showed a wide detection ranging from 0.05 ng mL −1 to 200 ng mL −1 , and a low detection limit of 0.02 ng mL −1 . Moreover, the proposed strategy has been successfully applied to the detection of AFM 1 in cow, goat, and sheep milk samples with satisfactory recoveries ranging from 91.10% to 104.05%. This work can provide a novel rapid detection method for AFM 1 , and also provide a new sensing platform for the detection of other toxins.
研究领域:
食品安全
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分析化学
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纳米技术
·
电化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Ni Ding,Gangjian Luo,Huiting Li,Chengyuan Xing,Yuanji Gao,Wenjie Xi,Weijie Wu,Dan Wang,Lei Zheng,Yang Kang,Xinjin Chi
The mortality rate of sepsis remains high despite improvements in the diagnosis and treatment of sepsis using symptomatic and supportive therapies, such as anti-infection therapy and fluid resuscitation. Nucleic acid-based drugs have therapeutic potential, although their poor stability and low delivery efficiency have hindered their widespread use. Herein, it is confirmed that miR-223 can polarize proinflammation M1 macrophages to anti-inflammation M2 macrophages. A pH-sensitive nano-drug delivery system comprising β-cyclodextrin-poly(2-(diisopropylamino)ethyl methacrylate)/distearoyl phosphoethanolamine-polyethylene glycol (β-CD-PDPA/DSPE-PEG) is synthesized and developed to target M1 macrophages and miR-223 is encapsulated into nanoparticles (NPs) for sepsis treatment. NPs/miR-223 demonstrated in vitro pH responsiveness with favorable biosafety, stability, and high delivery efficiency. In vivo studies demonstrate that NPs/miR-223 are preferentially accumulated and retained in the inflammation site, thereby reducing inflammation and improving the survival rate of mice with sepsis while exhibiting ideal biosafety. Mechanically, NPs/miR-223 regulates macrophage polarization by targeting Pknox1 and inhibiting the activation of the NF-κB signaling pathway, thereby achieving an anti-inflammatory effect. Collectively, it is demonstrated that the miRNA delivery vector described here provides a new approach for sepsis treatment and accelerates the advancement of nucleic acid drug therapy.
研究领域:
药学
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生物医学工程
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免疫学
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纳米技术
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2021
·
IF 4.079
Hongzhi Chen,Haichao Chu,Qian Jiang,Cong Wang,Yue Tian
Perioperative neurocognitive disorder (PND) frequently occurs in elderly patients following anesthesia, and is associated with pro-inflammatory activation of microglia in hippocampus. In this study, sevoflurane , a commonly used inhaled anesthetic in clinic, was used to induce PND-like symptoms in aged SD rats (18–20 months). Data from novel object recognition and Y-maze tests first confirmed that aged SD rats exposed to 2% sevoflurane for 5 h developed cognitive impairment . Microglia preferred to polarizing towards pro-inflammatory M1 subtype (iNOS+Iba-1 +) in rat hippocampus post sevoflurane exposure, but not anti-inflammatory M2 subtype (Arg-1 +Iba-1 +). Microarray data identified interferon regulatory factor 6 (Irf6) as one (Fold change = −2.52, p = 0.006) of the 15 downregulated genes in hippocampus of the rats exposed to sevoflurane. Co-immunofluorescence data further illustrated that sevoflurane decreased Irf6 expression in hippocampal microglia. In vitro, sevoflurane enhanced lipopolysaccharide-induced M1 polarization of BV-2 cells and inhibited interleukin-4 induced M2 polarization. Interestingly, manipulation of Irf6 expression hardly affected M1 polarization. However, Irf6 overexpression further augmented the inhibitory effects on M2 polarization, and its silencing showed opposite effects. In addition, such M2 polarization-promoting effects of Irf6 knockdown may be associated with induction of peroxisome proliferator activated receptor gamma expression. Collectively, these findings suggest that Irf6 downregulation in hippocampal microglia may be a compensatory mechanism against sevoflurane-induced PND in the elderly.
研究领域:
神经科学
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麻醉学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2022
·Vol. 18
·期 8
·1809
·
IF 6.058
Xu Ai-Hua,Yang Yang,Shao Yang,Jiang Man-Yu,Sun Yong-Xin
Poly(ADP-ribose)polymerase family member 14 ( PARP14 ), which is an intracellular mono(ADP-ribosyl) transferase, has been reported to promote post-stroke functional recovery, but its role in spinal cord injury (SCI) remains unclear. To investigate this, a T10 spinal cord contusion model was established in C57BL/6 mice, and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression. We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury, accompanied by obvious neuronal apoptosis , severe neuroinflammation , and slight bone loss. Furthermore, PARP14 levels were elevated in microglia after SCI, PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia (anti-inflammatory phenotype) to M1-polarized microglia (pro-inflammatory phenotype) that may have been mediated by the signal transducers and activators of transcription (STAT) 1/6 pathway. Next, microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γ and interleukin-4, respectively. The results showed that PARP14 knockdown promoted microglia M1 polarization , accompanied by activation of the STAT1 pathway . In addition, PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway . In conclusion, these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.
研究领域:
神经科学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2023
·
IF 4.8
Yi-Jin Wu,Sa-Sa Zhang,Qin Yin,Ming Lei,Qi-Hai Wang,Wen-Gang Chen,Ting-Ting Luo,Peng Zhou,Cong-Lan Ji
Background α-Mangostin (MG) showed the potentials in alleviating experimental arthritis, inhibiting inflammatory polarization of macrophages/monocytes, and regulating peroxisome proliferators-activated receptor γ (PPAR-γ) and silent information regulator 1 (SIRT1) signals. The aim of this study was to analyze the correlations among the above-mentioned properties.Methods Antigen-induced arthritis (AIA) was established in mouse, which was treated with MG in combination with SIRT1/PPAR-γ inhibitors to clarify the role of the two signals in the anti-arthritic actions. Pathological changes were systematically investigated. Phenotypes of cells were investigated by flow cytometry. Expression and co-localization of SIRT1 and PPAR-γ proteins in joint tissues were observed by the immunofluorescence method. Finally, clinical implications from the synchronous up-regulation of SIRT1 and PPAR-γ were validated by experiments in vitro.Results SIRT1 and PPAR-γ inhibitors (nicotinamide and T0070097) reduced the therapeutic effects of MG on AIA mice, and abrogated MG-induced up-regulation of SIRT1/PPAR-γ and inhibition of M1 polarization in macrophages/monocytes. MG has a good binding affinity to PPAR-γ, and MG promoted the co-expression of SIRT1 and PPAR-γ in joints. Synchronously activating SIRT1 and PPAR-γ was revealed to be necessary by MG to repress inflammatory responses in THP-1 monocytes.Conclusion MG binds PPAR-γ and excites this signaling to initiate ligand-dependent anti-inflammatory activity. Due to certain unspecified signal transduction crosstalk mechanism, it then promoted SIRT1 expression and further limited inflammatory polarization of macrophages/monocytes in AIA mice.
研究领域:
免疫学
·
药理学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2022
·
IF 5.304
Mengran Wang,Linqing Shan,Xianglong Kong,Ruiyan Pan,Haiwei Wang,Jin Zhou,Jingjing Ming
Monitoring the information of aflatoxin M1 (AFM1) is of great significance for food safety since its widespread presence in milk and other dairy products. In view of this, we developed a label-free fluorescence DNA walker based on self-protected DNAzyme for determination of AFM1. By inserting the AFM1 aptamer into DNAzyme, the complete DNAzyme was split into two separated parts and designed to be an arch-like shield to avoid its degradation in complex matrix. This excellent structure of DNAzyme and the report probe were pre-assembled on the surface of gold nanoparticles (AuNPs). Through the high efficiency affinity between AFM1 and its aptamer, the DNAzyme could be activated and show its high catalytic cleavage towards its substrate of report probe. The releasing G-quardruplex (G4) of this report probe from AuNPs could combine with berberine and exhibit obvious fluorescence values. Under optimized experimental conditions, the AFM1 detection limit was achieved at 6.40 ng/L. This DNA walker exhibited good selectivity, reproductivity and stability. Furthermore, the feasibility for analysis in real sample of our method was performed towards the target spiked in milk, indicating its potential application for real sample determination.
研究领域:
分析化学
·
食品科学
·
纳米技术
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2021
·
IF 4.952
Yin Zheng,Li Li,Zekun Jin,Peipei An,Shang-Tian Yang,Yongtao Fei,Gongliang Liu
The use of Schleiferilactobacillus ( S. ) harbinensis M1 as a starter culture, has been shown to improve the organoleptic quality of fermented soymilk, but its contribution to nutrient transformation and health-related functionality remains unclear. This study characterized the biotransformation of carbohydrates, isoflavones , proteins and free amino acids, as well as the antioxidant and antiproliferative activities of soymilk fermented by S. harbinensis M1. After fermentation, soybean carbohydrates were mainly converted into lactic acid (76.68 mmol/L) and acetic acid (8.19 mmol/L), isoflavone glucosides (daidzin and genistin) were partially converted to aglycones (daidzein and genistein). Soybean proteins were extensively hydrolyzed into oligopeptides and free amino acids, and the soluble peptide fraction (451-189 Da) increased from 4.6% to 86%. Whole-genome sequencing of S. harbinensis M1 revealed a 3,592,195 bp circular chromosome with 53.02% (G + C) content and 3375 coding genes. Metabolic prediction revealed the enzymes required for carbohydrate/pyruvate metabolism and isoflavone biotransformation. The whole proteolytic system was predicted, including peptide transport system and 66 genes encoding proteinases/peptidases. S. harbinensis M1 significantly ( p < 0.05) improved the antioxidant activity and antiproliferative effects of soymilk against HepG2/MCF-7 cells. These findings suggest that S. harbinensis M1 can be used as a proteolytic starter-culture to make functional fermented foods .
研究领域:
食品科学
·
微生物学
·
基因组学
·
营养学
·
生物化学
✓ 已验证
DOI
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·
IF 5.5
Xin Li,Huimei Shi,Di Zhang,Bei Jing,Zhenni Chen,Yachun Zheng,Shiquan Chang,Li Gao,Guoping Zhao
Background This study aimed to investigate the potential mechanism of paeonol in the treatment of neuropathic pain. Methods Relevant mechanisms were explored through microglial pseudotime analysis and the use of specific inhibitors in cell experiments. In animal experiments, 32 SD rats were randomly divided into the sham operation group, the chronic constrictive injury (CCI) group, the ibuprofen group, and the paeonol group. We performed behavioral testing, ELISA, PCR, Western blotting, immunohistochemistry, and immunofluorescence analysis. Results The pseudotime analysis of microglia found that RhoA, Rock1, and p38MAPK were highly expressed in activated microglia, and the expression patterns of these genes were consistent with the expression trends of the M1 markers CD32 and CD86. Paeonol decreased the levels of M1 markers (IL1β, iNOS, CD32, IL6) and increased the levels of M2 markers (IL10, CD206, ARG-1) in LPS-induced microglia. The expression of iNOS, IL1β, RhoA, and Rock1 was significantly increased in LPS-treated microglia, while paeonol decreased the expression of these proteins. Thermal hyperalgesia occurred after CCI surgery, and paeonol provided relief. In addition, paeonol decreased the levels of IL1β and IL8 and increased the levels of IL4 and TGF-β in the serum of CCI rats. Paeonol decreased expression levels of M1 markers and increased expression levels of M2 markers in the spinal cord. Paeonol decreased IBA-1, IL1β, RhoA, RhoA-GTP, COX2, Rock1, and p-p38MAPK levels in the spinal dorsal horn. Conclusion Paeonol relieves neuropathic pain by modulating microglial M1 and M2 phenotypes through the RhoA/p38 MAPK pathway.
研究领域:
药理学
·
神经科学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Siqi Geng,Baoru Fang,Ke Wang,Fang Wang,Yiqing Zhou,Yike Hou,M. Zubair Iqbal,Yanping Chen,Zhangsen Yu
Photothermal therapy (PTT) is a promising technology that can achieve the thermal ablation of tumors and induce immunogenic cell death (ICD). However, relying solely on the antitumor immune responses caused by PTT-induced ICD is insufficient to suppress tumor metastasis and recurrence effectively. Fortunately, multifunctional nanoformulation-based synergistic photothermal immunotherapy can eliminate primary and metastatic tumors and inhibit tumor recurrence for a long time. Herein, we select polydopamine (PDA) nanoparticles to serve as the carrier for our nanomedicine as well as a potent photothermal agent and modulator of macrophage polarization. PDA nanoparticles are loaded with the insoluble immune adjuvant Imiquimod (R837) to construct PDA(R837) nanoformulations. These straightforward yet highly effective nanoformulations demonstrate excellent performance, allowing for successful triple-negative breast cancer (TNBC) treatment through synergistic photothermal immunotherapy. Moreover, experimental results showed that PDA(R837) implementation of PTT is effective in the thermal ablation of primary tumors while causing ICD and releasing R837, further promoting dendritic cell (DC) maturation and activating the systemic antitumor immune response. Furthermore, PDA(R837) nanoformulations inhibit tumor metastasis and recurrence and achieve M1 phenotype macrophage polarization, achieving long-term and excellent antitumor efficacy. Therefore, the structurally simple PDA(R837) nanoformulations provide cancer treatment and have excellent clinical translational application prospects.
研究领域:
纳米技术
·
癌症研究
·
免疫治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Ranran Ma,Weiwei Peng,Yanli Xie,Nazish Muzaffar,Weibin Ma,Yuhui Yang,Qian Li,Hang Jia
Aflatoxin B1 (AFB1), the most toxic and prevalent mycotoxin in food and feed, and its hydroxylated metabolite aflatoxin M1 (AFM1), common in dairy products, pose serious health risks. Effective degradation of these toxins is thus a key goal in food safety. In this study, Bacillus subtilis HNGD-Mq02 was isolated and assessed for its ability to degrade AFB1 and AFM1. Under optimal conditions (50 °C, pH 7), the fermentation broth achieved 94.06 and 98.26% degradation, respectively. Ultrahigh-performance liquid chromatography–mass spectrometry (UHPLC-MS) analysis confirmed that both mycotoxins were converted into less-toxic compounds. Zebrafish assays and Ames tests further verified the reduced toxicity of the degradation products. In practical application, the strain reduced AFB1 by 72.90% in corn flour and AFM1 by 42.25% in milk powder. Fermentation also led to partial improvements in nutritional quality. These results highlight the potential of B. subtilis HNGD-Mq02 for enhancing the safety and value of food and feed products.
研究领域:
食品科学
·
微生物学
·
毒理学
·
生物技术
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）