JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Zhang Qian,Chen Tiange,Chen Jianwei,Ai Ying,Chen Ziyang,Liu Ganzhi,Zhang Yi,Liu Boxun,Liu Jiacheng,Tang Zexuan,Lin Lin,Chen Xin,Xia Yuguo,Xu Tao,Liu Jinfang
Traumatic brain injury (TBI)-induced neuroinflammation, driven by inflammatory microglial polarization, continues to pose a significant regenerative and clinical challenge. Small extracellular vesicles (sEVs) have demonstrated great potential in mitigating post-TBI inflammation. Nevertheless, the limited yield and efficacy of sEVs produced via conventional two-dimensional (2D) culture systems (2D-sEVs) substantially hinder their clinical applicability. Moreover, effective strategies for the therapeutic application of sEVs in TBI treatment, along with an understanding of their underlying mechanisms, remain largely unexplored. In this study, we employed a 3D coaxial bioprinting method to encapsulate adipose-derived stem cells (ADSCs) within a hydrogel microfiber, facilitating 3D culturing and large-scale production of 3D-sEVs. Additionally, we utilized GelMA hydrogel for the sustained release of 3D-sEVs and evaluated their effects in LPS-activated microglia as well as in a TBI mouse model. Our results demonstrated that 3D culture significantly enhanced sEV production. GelMA improved sEV stability and prolonged sEV release up to 30 days in vivo. Compared to 2D-sEVs, 3D-sEVs offered superior therapeutic benefits. Specifically, 3D-sEVs substantially reduced neuroinflammation and brain tissue loss while accelerating motor function recovery in TBI mice. Furthermore, 3D-sEVs shifted pro-inflammatory microglia toward an anti-inflammatory polarization state, as evidenced by elevated expression levels of IL-4, IL-10, TGF-β, Arg1, and CD206, alongside reduced expression of IL-6, IL-1β, TNF-α, iNOS, and CD86, both in vitro and in vivo. Additionally, 3D-sEVs attenuated chemotaxis and migration in LPS-activated microglia. Further mechanistic exploration through RNA-seq, proteomic profiling, and GAS6 knockdown in 3D-sEVs, revealed that 3D-sEVs deliver growth arrest-specific protein 6 (GAS6) to modulate the transition of microglia from a pro-inflammatory to an anti-inflammatory state, thereby mitigating neuroinflammation following TBI. Our findings underscore the therapeutic promise of sEVs derived from 3D-cultured ADSCs in treating TBI via modulating microglia polarization. Graphical abstract
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-26
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IF 12.6
Zhou Peng,Chao Quan,Li Chen,Wang Ningjing,Guo Siqi,Wang Pingping,Ge Pingyuan,Li Caihong,Guo Rui,Yang Nianyun,Lu Zhangdi,Tang Zhishu,Zhang Qichun,Fu Tingming,Xiao Qingqing,Zhu Huaxu
The effective treatment of Alzheimer’s disease (AD) is challenging because of its complex and controversial pathological mechanisms. Moreover, multiple barriers, such as the blood–brain barrier (BBB), reduce drug delivery efficiency. Microglia-related neuroinflammation has recently attracted increasing attention as a possible cause of AD and has become a novel therapeutic target. Therefore, overcoming the BBB and targeted delivery of anti-inflammatory agents to microglia seem to be effective practical strategies for treating AD. A large proportion of natural active extracts possess exceptional immunomodulating capabilities. In this study, the cooperative delivery of berberine (Ber) and palmatine (Pal) by transferrin-decorated extracellular vesicles (Tf-hEVs-Ber/Pal), which can cross the BBB and precisely target microglia, was performed. This nanosystem effectively cleared amyloid β-protein (Aβ) aggregates, significantly regulated the neuroinflammatory environment both in vitro and in vivo and markedly altered the behavior and improved the cognitive and learning abilities of AD model mice. The efficacy of a microglia-targeting combined therapeutic approach for AD was demonstrated, which broadens the potential application of Chinese herbal ingredients.Graphical abstract
研究领域:
神经科学
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药理学
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纳米医学
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PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Cheng Ning,Cailing He,Ling Yan,Changhong Liu,Aijin Ma,Lei Zheng
The research aimed to investigate the underlying anti-inflammatory and antioxidative mechanisms of walnut-derived peptides in BV-2 microglia with H 2 O 2 -induced injury, and to further assess their neuroprotective properties against cognitive impairments caused by lipopolysaccharide (LPS) in mice. The findings indicated that both walnut-derived peptides NPFD and LDAF significantly inhibited ROS production in H 2 O 2 -injured BV-2 microglia and attenuated oxidative stress in BV-2 microglial cells via the Nrf2/keap1 signaling pathway. In addition, LDAF showed greater improvement in inflammatory than NPFD in H 2 O 2 -injured BV-2 microglia. Meanwhile, The MWM demonstrated that LDAF had the potential to mitigate memory impairments caused by LPS through normalizing the brain's inflammatory responses and reducing oxidative stress. And LDAF treatment improved neuronal cell morphology in the hippocampal region of mouse brain tissue and increased the number of Nissl bodies in neurons of injured mice. These results showed that LDAF was able to improve spatial cognitive ability in mice by reducing inflammation and oxidative stress.
研究领域:
神经生物学
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分子药理学
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免疫调节
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氧化应激
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神经退行性疾病
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营养干预
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信号转导
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高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yinghan Guo,Lulu Jin,Zhipeng Shen,Linfeng Fan,Xian Yu,Yirui Kuang,Lingxin Cai,Jiayin Zhou,Zihang Chen,Feng Yan,Jianmin Zhang,Minfeng Tong,Jianlie Yuan,Zhengwei Mao,Gao Chen
The malignant interaction between tumor cells and immune cells is one of the important reasons for the rapid progression and refractoriness of glioblastoma (GBM). As an essential metabolic center of M2 macrophages, the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the reduction of M2 macrophages. Nevertheless, the restriction of the blood-brain barrier (BBB) and non-specific cell targeting hinder the application of PERK inhibitors in GBM. Herein, the optimal NP-M-M2pep is developed successfully, which has shown the capacity of BBB penetration and specific targeting of M2 microglia. In addition to inhibiting the polarization of M2 microglia, the administration of iPERK@NP-M-M2pep reprogrammed M2 microglia into M1 ones in vitro via PERK/HIF-1α/glycolysis pathway. Efficient brain accumulation of nanoparticles is achieved after tail vein injection, with effective inhibition of GBM progression after one course of treatment. The glioma-associated microglia and macrophages (GAM) with M2 type are induced to M1 and the immunosuppressive TME is remodeled by upregulating immunostimulatory cells and downregulating immunosuppressive cells. In summary, the biomimetic membrane vesicles (BMVs) specifically delivered iPERK to GAMs offer an inspiring strategy to reprogram microglia polarization, re-educate immunosuppressive TME, and inhibit the progression of GBM.
研究领域:
肿瘤学
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神经科学
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免疫学
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PubMed
高影响因子
BMC Veterinary Research
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2024
·Vol. 20
·期 1
·1-11
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IF 2.3
Yang Yuxin,Hu XianWang,Wang Shuangshuang,Tian Yongxiang,Yang Keli,Li Chang,Wu Qiong,Liu Wei,Gao Ting,Yuan Fangyan,Guo Rui,Liu Zewen,Yang Yuying,Zhou Danna
Background Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic pathogen that causes encephalitis in humans and reproductive failure in pigs. The transmission of JEV between humans and animals poses a significant public health threat and results in substantial economic losses. Excessive inflammation in the central nervous system of JEV-infected patients is a major cause of mortality and disability. Rosmarinic acid (RA), a polyhydroxyphenolic compound isolated from medicinal herbs, has been preliminarily shown to possess anti-inflammatory properties and significantly inhibit JEV-induced neuroinflammation in mice. Results This study investigated the antiviral capacity and potential mechanisms of RA in JEV-infected cells. The results demonstrated that RA could inhibit JEV replication in vitro. Furthermore, the expression levels of inflammatory cytokines (including IL-6, IL-1β, CCL-2, and TNF-α), membrane receptors (including RIG-I, TLR3, TLR4, TLR7, and TLR8), NF-κB complex and p62/SQSTM1 were assessed using qPCR, ELISA, and Western blot, respectively. The findings indicated that RA significantly suppressed the expression of IL-6, IL-1α, TNF-α, and CCL-2 in JEV-infected BV-2 cells in a dose-dependent manner. Additionally, RA treatment downregulated the expression levels of RIG-I and p62, while p62 silencing inhibited the upregulation of inflammatory cytokines in JEV-infected BV-2 cells. Conclusion Our present study highlights the important role of RA-mediated reduction of RIG-I and p62 in microglia, conferring resistance to Japanese encephalitis virus-induced inflammation.
研究领域:
病毒学
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免疫学
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药理学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Ran Sun,Yan-Fang Wang,Xue Yang
The key to the treatment of multiple sclerosis (MS) is to promote the transition from inflammation-induced demyelination to remyelination. Polarization of microglia towards M1 or M2 phenotype is critical in this transition. Interferon induced protein with tetratricopeptide repeats 3 (IFIT3) is involved in inflammatory reaction and up-regulated in M1-polarized macrophages. However, its effect on microglia during MS has not been reported. In this paper, we demonstrated the important role of IFIT3 in selectively regulating microglia polarization. The expression of IFIT3 was increased when microglia were polarized towards M1, but did not change under M2 polarization. The knockdown of IFIT3 selectively inhibited M1 polarization, while M2 polarization was not affected by IFIT3 silencing. Furthermore, the activation of signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappa-B (NF-ĸB) signaling in M1 polarized microglia was suppressed by downregulating IFIT3. In experimental autoimmune encephalitis (EAE) mice, an animal model of MS, IFIT3 expression was upregulated. The disease progression, inflammatory infiltration and demyelination in the EAE mice were alleviated by silencing IFIT3. The inhibitory effects of IFIT3 knockdown on M1 polarization and STAT1 and NF-ĸB pathways were also confirmed in the spinal cord of EAE mice. In summary, our findings suggest that IFIT3 selectively intensified microglia polarization towards the pro-inflammatory M1 phenotype, and may contribute to the progression of MS.
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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PubMed
高影响因子
MOLECULES
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2026
·Vol. 31
·期 4
·671
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IF 5.1
Shumeng Liu,Yue Xing,Yue Na,Hao Wu,Chi Liu,Zhigang Wang,Ning Zhang,Xiuhong Wu,Fang Geng
Luteolin (Ltn), a natural flavonoid, effectively inhibits microglial activation in Alzheimer’s disease (AD) with promising therapeutic potential, but its efficacy is severely limited by the blood–brain barrier (BBB). To overcome this obstacle, this study prepared poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs)—designated as TGN/RAP12-RBC-NPs@Ltn—which were coated with red blood cell membranes (RBCm) functionalized with two peptides, TGN (TGNYKALHPHN) and RAP12 (EAKIEKHNHYQK). The results demonstrated that TGN significantly enhanced BBB permeability, while RAP12 enabled effective targeting and delivery of TGN/RAP12-RBC-NPs@Ltn to microglial mitochondria in the brain. In addition, the presence of RBCm significantly inhibited the phagocytosis of NPs by macrophages, exerting a notable role in immune evasion. Meanwhile, the study confirmed that encapsulating Ltn within NPs significantly enhanced cognitive function in APP/PS1 mice, modulated the expression of key mitochondrial metabolic enzymes—pyruvate dehydrogenase (PDH) and its phosphorylated forms (pS232PDH, pS293PDH, pS300PDH)—in microglia, thereby ameliorating mitochondrial dysfunction and effectively regulating the neuroinflammatory environment in the mouse brain, and ultimately contributed to therapeutic efficacy. From this, it could be seen that TGN/RAP12-RBC-NPs@Ltn could significantly enhance the therapeutic effect of Ltn on AD, providing an effective treatment strategy for delaying the progression of AD.
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高影响因子
COMPOSITES PART B-ENGINEERING
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2022
·
IF 11.322
Ye Li,Min Wang,Meng Sun,Xinxin Wang,Dandan Pei,Bo Lei,Ang Li
Traumatic brain injury (TBI) leads to high rates of morbidity and mortality worldwide with few effective treatments. Excessive oxidative stress and local inflammation at the injury site are considered as the critical factors that determine the therapeutic outcome. In our previous study, stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-Exo) promoted functional recovery of TBI by amelioration of neuro-inflammation. However, the effect was restricted due to unsustainable exosome release and existed oxidative stress that aggravate secondary insult of TBI. To obtain a long-time anti-inflammatory effect of SHED-Exo and attenuate oxidative stress simultaneously, we designed a bioactive antioxidant poly (citrate-gallic acid)-based hybrid hydrogel (FPGEGa) that encapsulate SHED-Exo for treating TBI. The thermosensitive, injectable, self-healing and antioxidant FPGEGa presented ultralong sustained release of SHED-Exo (above 21 days) and significantly decreased the intracellular ROS production of microglia in the central nervous system. FPGEGa carrying SHED-Exo (FPGEGa@SHED-Exo) exhibited better anti-inflammatory potential on microglia, by promoting M2 (anti-inflammatory) polarization and inhibiting M1 (pro-inflammatory) polarization. FPGEGa@SHED-Exo could improve the neuro-regeneration of TBI rats by rescuing damaged motor functions in rats as well as regenerating impaired cortical tissues. The present work suggested that SHED-Exo engineered bioactive antioxidative hydrogel may be promising in achieving satisfactory functional recovery in TBI and other related neurological disorders.
研究领域:
生物材料学
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神经科学
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再生医学
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高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2023
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IF 5.3
Li Liu,Rong Zhang,Chang Chen,Changbo Xia,Guangda Yao,Xiaogang He,Baomei Xia
It has been reported that Banxia-houpo decoction (BXHPD) serves as the anti-depressant treatment for a mild and severe depressive disease with limited side effects. The present study was performed to evaluate the protective effect of BXHPD on chronic unpredicted mild stress (CUMS)-induced depression and explore its effect on TrkA/Akt-mediated microglia polarization. The CUMS procedure was carried out, and the mice were intragastrically treated with BXHPD once daily. The selective TrkA inhibitor GW441756 was applied to further investigate the role of TrkA in BXHPD-mediated microglia polarization. The behaviour test including open field test (OFT), sucrose preference test (SPT), novelty-suppressed feeding test (NSFT), tail suspension test (TST) and forced swim test (FST) was performed. The concentrations of pro-inflammatory cytokines IL-6, TNF-α, IL-1β, IL-12 and anti-inflammatory cytokines IL-4, IL-10 were determined using Enzyme-linked immunosorbent assay. The population of Iba1+ cells and the length of microglia processes were observed under the fluorescence microscope. The mRNA expressions of Arg1, Ym1 and Fizzl1 were measured by PCR. The protein expressions of TrkA, p-Tyr490-TrkA, p-Ser473-Akt, p-Ser473-Akt1, p-Ser474-Akt2, p-CREB and Jmjd3 were detected by western blot. Our results showed that BXHPD attenuated CUMS-induced depressive-like behaviour, promoted anti-inflammatory cytokines, inhibited pro-inflammatory cytokines, suppressed microglia activation, promoted M2 phenotype-specific indices and upregulated the expressions of TrkA, p-Tyr490-TrkA, p-Ser473-Akt, p-Ser473-Akt1, p-Ser474-Akt2, p-CREB and Jmjd3. The above beneficial effect of BXHPD can be blocked by TrkA inhibitor GW441756. This work demonstrated that BXHPD exerted an anti-depressant effect by promoting M2 phenotype microglia polarization via TrkA/Akt pathway.
研究领域:
药理学
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神经科学
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精神病学
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DOI
PubMed
高影响因子
LIFE SCIENCES
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2018
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IF 3.234
Runxiao Lv,Lili Du,Lixin Zhang,Zhiqiang Zhang
Aims Spinal cord injury (SCI) is one of the most devastating central lesions, resulting in serious locomotor deficit. Polydatin is a glucoside of resveratrol with proven anti-cardiovascular, anti-inflammatory and anti-oxidative properties. The main purpose of this study was to investigate whether polydatin could alleviate SCI in rats and explore the underlying mechanisms. Materials and methods SCI rats induced by a weight-drop device were treated with intraperitoneal injection of 20 or 40 mg/kg polydatin. Then the locomotor function of SCI rats was evaluated by the Basso, Beattie and Bresnahan locomotor rating scale, spinal cord edema was measured by the wet/dry weight method, oxidative stress markers were detected by commercial kits and cell apoptosis status was measured by TUNEL staining. In addition, reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) production and apoptosis status were detected in murine microglia BV2 cells treated with 100 ng/ml lipopolysaccharides (LPS) and 4.0 μM polydatin. The expression of apoptosis-related proteins involved in nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway was measured by western blot. Key findings Our data showed that polydatin treatment improved locomotor performance of SCI rats, as well as reduced oxidative stress and inhibited apoptosis by enhancing Nrf2/HO-1 signaling. In addition, polydatin was found to up-regulate Nrf2 activity and the inhibitory effects of polydatin on oxidative stress and apoptosis in LPS-stimulated BV2 microglia was neutralized by silencing Nrf2 using specific siRNA. Significance We demonstrate that polydatin may protect the spinal cord from SCI by suppression of oxidative stress and apoptosis via improving Nrf2/HO-1 signaling in microglia.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
ACS Omega
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2019
·
IF 2.584
Shanshan Wang,Qian Luo,Yuefang Zhou,Peihong Fan
The healthy benefits of hemp (Cannabis sativa L.) seed have often been attributed to its oils and proteins. Recent studies reveal that hemp seed phenylpropionamides could also show various bioactivities. Continuation of our study on hemp seed provided a phenylpropionamide, coumaroylaminobutanol glucopyranoside (CLG). This work investigated the neuroprotective effect of CLG and its underlying mechanism using lipopolysaccharide-induced BV2 microglia. Our study demonstrated that CLG increased adenosine monophosphate-activated protein kinase (AMPK) expression, suppressed the nuclear factor-kappa B (NF-κB) signaling pathway by inhibiting the phosphorylation of IκBα and NF-κB p65 and decreased proinflammatory cytokine levels in a concentration-dependent manner. Furthermore, CLG reduced the production of cellular reactive oxygen species and stimulated the nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling pathway. Collectively, these results suggested that CLG effectively and simultaneously inhibited inflammatory responses and oxidative stress through the NF-κB and Nrf-2 signaling pathways. AMPK was also involved in the anti-inflammatory effect of CLG. This study provides new insights into the diverse bioactive constituents of hemp seed.
研究领域:
神经科学
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药理学
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分子生物学
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PubMed
高影响因子
Antioxidants
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2022
·Vol. 12
·期 1
·74
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IF 7.675
Wanying Liu,Ke Li,Menglin Zheng,Ling He,Tong Chen
The present study was conducted to evaluate the effect of genipin (GEN) on the microglia of diabetic cognitive impairment and explore its potential mechanism. Diabetic mice were induced by STZ/HFD, while GEN was intragastrically and intraventricularly treated. The human microglia cell HMC3 was induced by LPS/HG/PA. As a result, GEN attenuated diabetic symptoms and diabetic cognitive impairment-related behavior in novel object recognition, Morris water maze and passive avoidance tests. GEN inhibited M1 microglia polarization, lipid accumulation, oxidative stress and promoted mitochondrial fusion via FABP4/Mfn1. FABP4 overexpression, Mfn1 overexpression, selective FABP4 inhibitor BMS, and Mfn1 SiRNA were employed for investigating the mechanism. The inhibitory effect of GEN on ROS may be associated with NOX2 signaling and the translocation of p47phox/p67phox to the cell membrane. With the ROS scavenger NAC, it was proved that ROS participated in GEN-mediated inflammation and lipid accumulation. GEN inhibited the phosphorylation and nucleus translocation of NF-κB. GEN inhibited the ubiquitination of Mfn1, which was mediated by the E3 ligase Hrd1. GEN also enhanced microglia phagocytosis. Molecular docking predicted that GEN may interact with FABP4 by hydrogen bond at the S53 and R78 residues. In conclusion, GEN attenuated diabetic cognitive impairment by inhibiting inflammation, lipid accumulation and promoting mitochondrial fusion via FABP4/Mfn1 signaling.Keywords:diabetic cognitive impairment;genipin;microglia;FABP4;Mfn1
研究领域:
神经科学
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药理学
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糖尿病
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细胞生物学
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分子生物学
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PubMed
高影响因子
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