ADVANCES IN POLYMER TECHNOLOGY
·
2020
·
IF 1.539
Lei Li,Yan Li,Cheng Miao,Rui Liu
This study was to explore the therapeutic effect and mechanism of puerarin (PUE) combined with PEGylated nanoparticles on a rat cerebral infarction cell model. In this context, PEG-PLGA/PUE nanoparticles were prepared by the thin-film hydration method, and the toxicity of PEG-PLGA/PUE nanoparticles to brain capillary endothelial cell (BCEC) was detected by MTT. The BCEC/TF cell model was obtained by induction of BCEC cells with TNF-α. The BCEC/TF cell model was identified by immunofluorescence; the protein expression was detected by western blotting; the expression level of miR-424 in cells was measured by RT-qPCR; the targeting relationship between miR-424 and PDCD4 was confirmed by dual-luciferase reporter assay. We found that PEG-PLGA/PUE nanoparticles prepared by the thin-film hydration method had uniform particle size, regular shape, and good stability and were not toxic to cells. The vWF was widely expressed in the cytoplasm in BCECs. The BCEC/TF cell model was obtained after TNF-α treatment, and tissue factor (TF) was widely expressed on the cell membrane of BCEC/TF cells. Furthermore, it was observed that the PEG-PLGA/PUE nanoparticles showed better therapeutic effect on the BCEC/TF cell model than PUE. PEG-PLGA/PUE nanoparticles and PUE inhibited the expression of PDCD4 protein by increasing the expression of miR-424 in BCEC/TF cells. In summary, the therapeutic effect of PEG-PLGA/PUE nanoparticles on the in vitro cell model of cerebral infarction is better than that of PUE. Moreover, PEG-PLGA/PUE inhibits the expression of PDCD4 protein by lowering the expression level of miR-424 in cells, thereby reducing the hazard of cerebral infarction.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2025
·
IF 4.8
Feng-Hua Xu,Xiao Sun,Jun Zhu,Ling-Yang Kong,Yuan Chang,Ning Li,Wen-Xiang Hui,Cong-Peng Zhang,Yi-Ming Cheng,Wen-Xin Han,Zhi-Min Tian,Yan-Ning Qiao,Dong-feng Chen,Lei Liu,Da-Yun Feng,Jing Han
Background Recent research has made significant progress in elucidating gastrointestinal complications following acute cerebral infarction (ACI), which includes disorders in intestinal motility and dysbiosis of the gut microbiota. Nevertheless, the role of the gut (which is acknowledged as being the largest immune organ) in the immunoreactive effects of polydopamine nanoparticles (PDA) on acute ischemic stroke remains inadequately understood. In addition to its function in nutrient absorption, the gut acts as a protective barrier against microbes. Systemic immune responses, which are triggered by the disruption of gut barrier integrity, are considered as one of the mechanisms underlying acute ischemic stroke, with the gut-brain axis (GBA) playing a pivotal role in this process. Methods In this study, we used a PDA intervention in an ACI model to investigate ACI-like behavior, intestinal barrier function, central and peripheral inflammation, and hippocampal neuron excitability, thus aiming to elucidate the mechanisms through which PDA improves ACI via the GBA. Results Our findings indicated that as ACI mice experienced dysbiosis of the gut microbiota and intestinal barrier damage, the levels of proinflammatory factors in the serum and brain significantly increased. Additionally, the activation of astrocytes in the hippocampal region and neuronal apoptosis were observed in ACI mice. Importantly, our study is the first to provide evidence demonstrating that PDA effectively suppresses the neuroimmune interactions of the gut-brain axis and significantly improves intestinal epithelial barrier integrity. Conclusion We hope that our discoveries will serve as a foundation for further explorations of the therapeutic mechanisms of PDA in ACI, particularly in elucidating the protective roles of gut microbiota and intestinal barrier function, as well as in the development of more targeted clinical interventions for ACI.
研究领域:
医学
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神经科学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2024
·
IF 3.5
Xiao-Ye Lu,Qian-Yi Lv,Qi-Long Li,Hong Zhang,Chu-Tao Chen,Hao-Mei Tian
We have previously reported that the expression of miR-34c-5p was up-regulated during acupuncture treatment in the setting of a cerebral ischemia/reperfusion injury (CIRI), indicating that miR-34c-5p plays an important role in healing from a CIRI-induced brain injury. This study sought to evaluate the effects of acupuncture on miR-34c-5p expression and autophagy in the forward and reverse directions using a rat focal cerebral ischemia/reperfusion model. After 120 minutes of middle cerebral artery occlusion and reperfusion, rats were treated with acupuncture at the "Dazhui" (DU20), "Baihui" (DU26) and "Renzhong" (DU14) points. Neurologic function deficit score, cerebral infarct area ratio, neuronal apoptosis and miR-34c-5p expression were evaluated 72 hr after treatment. The autophagy agonist RAPA and the antagonist 3MA were used to evaluate the neuro protective effects of autophagy-mediated acupuncture. We found that acupuncture treatment improved autophagy in the brain tissue of CIRI rats. Acupuncture reversed the negative effects of 3MA on CIRI, and acupuncture combined with RAPA further enhanced autophagy. We also found that acupuncture could increase miR-34c-5p expression in hippocampal neurons after ischemia/reperfusion. Acupuncture and a miR-34c agomir were able to enhance autophagy, improve neurologic deficits, and reduce the cerebral infarct area ratio and apoptosis rate by promoting the expression of miR-34c-5p. Silencing miR-34c resulted in a significantly reduced activating effect of acupuncture on autophagy and increased apoptosis, neurologic deficit symptoms, and cerebral infarct area ratio. This confirms that acupuncture can upregulate miR-34c-5p expression, which is beneficial in the treatment of CIRI.
研究领域:
神经科学
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分子生物学
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中医
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药理学
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产品关联
DOI
PubMed
高影响因子
Biomedical Optics Express
·
2025
·Vol. 16
·期 5
·2033-2046
·
IF 3.2
Binbin Zeng,Huaiwu Fu,Cong Wu,Xudong Zhang,Tianran Li,Qiong Xu,Yayun Qian,Yayun Qian,Ruirui Yang,Ruirui Yang
In this study, we constructed a SERS assay platform that can be used for the ultrasensitive detection of cerebral infarction (CI)-associated miR-106a-5p based on the recognition competition strategy and the highly efficient catalytic activity of Au@Pt NRs nanoenzymes. When the target miR-106a-5p is present in the detection solution, it binds to the nucleic acid aptamer (cDNA), leading to the detachment of its complementary strand (H1) carrying Au@Pt NRs from the surface of AuNHs, and the oxidation of TMB is reduced, resulting in the decrease of SERS signal. In addition, this method enables single-step, ultrasensitive detection of target miRNAs in patient serum with a limit of detection (LOD) of 0.96 fM, which is consistent with the results of real-time quantitative polymerase chain reaction (qRT-PCR) and fluorescence. This method provides a novel approach for the effective detection of miRNAs, which is of great clinical value for the early detection of CI.
研究领域:
生物传感器
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纳米技术
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分子诊断学
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生物医学工程
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RNA检测
✓ 已验证
产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Xiaodan Tan,Wenjia Guo,Zhe Peng,Chao Gu,Pu Xiang,Yujun Tu,Huizhi Fei,Xia Liu,Yi Lu,Miaomiao Li,Hong Wang,Ying Luo,Junqing Yang
Based on the previous studies, this study was carried out to explore the interaction of LncRNA-Malat1/miR-211-5p in cerebral ischemia reperfusion injury (CIRI). Firstly, the expression changes of LncRNA-MALAT1 and miR-211-5p in ischemia patients’ blood were determined, and the binding sites of them were predicted by bioinformatics. Furthermore, middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established in adult male SD rats , and primary neuronal oxygen-glucose deprivation/reoxygen-glucose reoxygenation (OGD/R) was established in vitro. The results showed that LncRNA-MALAT1 was significantly up-regulated and miR-211-5p down-regulated in the peripheral blood of patients with ischemic stroke, and the expression changes were negatively correlated. Bioinformatics prediction results showed that LncRNA-MALAT1 had a binding site with miR-211-5p. We also found that LncRNA-Malat1 was significantly up-regulated while miR-211-5p down-regulated in rat cortex tissue and primary neurons treated with OGD/R. In addition, lentivirus interfered with LV-Malat1-RNAi decreased the expression of LncRNA-Malat1 and promoted the up-regulation of miR-211-5p. Combination of LV-Malat1-RNAi and miR-211-5p inhibitor significantly reversed the protective effect of down-regulation of LncRNA-Malat1. Inhibition of LncRNA-Malat1 expression alleviated the neurological deficit score after MCAO/R, improved histopathological damage, and reduced the size of cerebral infarction . Combined administration of LV-Malat1-RNAi + Antagomir-211-5p reversed these effects above. In short, our data suggest that LncRNA-Malat is involved in the occurrence and development of cerebral ischemia reperfusion injury by acting on miR-211-5p and is then regulating the expression of COX-2.
研究领域:
神经科学
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分子生物学
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医学遗传学
✓ 已验证
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2021
·Vol. 9
·期 2
·
IF 7.171
Huidi Wang,Wei Song,Qiheng Wu,Xuxuan Gao,Jie Li,Chuhong Tan,Hongwei Zhou,Jiajia Zhu,Yan He,Jia Yin
The complication of type 2 diabetes (T2D) exacerbates brain infarction in acute ischemic stroke (AIS). Because butyrate-producing bacteria are decreased in T2D and butyrate has been reported to be associated with attenuated brain injury in AIS, we hypothesize that administering butyrate could ameliorate T2D-associated exacerbation of brain infarction in AIS. Therefore, we first validated that Chinese AIS patients with T2D comorbidity have significantly lower levels of fecal butyrate-producing bacteria and butyrate than AIS patients without T2D. Then, we performed a 4-week intervention in T2D mice receiving either sodium butyrate (SB) or sodium chloride (NaCl) and found that SB improved the diabetic phenotype, altered the gut microbiota, and ameliorated brain injury after stroke. Fecal samples were collected from T2D mice after SB or NaCl treatment and were transplanted into antibiotic-treated C57BL/6 mice. After 2 weeks of transplantation, the gut microbiota profile and butyrate level of recipient mice were tested, and then the recipient mice were subjected to ischemic stroke. Stroke mice that received gut microbiota from SB-treated mice had a smaller cerebral infarct volume than mice that received gut microbiota from NaCl-treated mice. This protection was also associated with improvements in gut barrier function, reduced serum levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and proinflammatory cytokines, and improvements in the blood-brain barrier.IMPORTANCE Ischemic stroke is a major global health burden, and T2D is a well-known comorbidity that aggravates brain injury after ischemic stroke. However, the underlying mechanism by which T2D exacerbates stroke injury has not been completely elucidated. A large amount of evidence suggests that the gut microbiota composition affects stroke outcomes. Our results showed that the gut microbiota of T2D aggravated brain injury after ischemic stroke and could be modified by SB to afford neuroprotection against stroke injury. These findings suggest that supplementation with SB is a potential therapeutic strategy for T2D patients with ischemic stroke.
研究领域:
神经科学
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药理学
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微生物学
·
代谢疾病
✓ 已验证
DOI
PubMed
高影响因子
Journal of Chemistry
·
2021
·Vol. 2021
·期 1
·5685596
·
IF 2.506
Jia Ma,Jianer Wang,Yuping He,Yiwei Huang,Yejun Chen
Solvothermal reaction of 4,4’,4’-nitrilotribenzoic acid (H 3 TCA) with Ca(NO 3 ) 2 ·4H 2 O and Cd(NO 3 ) 2 ·4H 2 O successfully afforded a heterometallic compound, that is, [Cd 2 Ca(TCA) 2 (DMA) 2 (H 2 O) 3 ] n ·2n(DMA) ( 1 , DMA = N,N’-dimethylacetamide). The structure of 1 was further characterized through EA, diffraction of single crystal X-ray, and thermogravimetric analysis (TGA) together with powder X-ray diffraction (PXRD). Moreover, complex 1 ’s luminescent performance in solid state was also discussed at environmental temperature. The applications on the ischemic cerebral infarction therapy were evaluated, and the specific mechanism was investigated at the same time. Firstly, the hypersensitivity C-reactive protein (hs-CRP) content in human brain microvascular endothelial cell (HBMEC) was measured with real-time reverse transcription-polymerase chain reaction (RT-PCR). Then, interleukin-18 and interleukin-1 β content released through the HBMEC was detected with enzyme-linked immunosorbent assay (ELISA).
研究领域:
生物无机化学
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神经药理学
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炎症生物学
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转化医学
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分子影像学
✓ 已验证
DOI
高影响因子
Journal of Integrative Neuroscience
·
2024
·Vol. 23
·期 11
·196
·
IF 2.5
Yan Shi,Yufeng Yang,Juntong Liu,Jinling Zheng
Background:
Avicularin (AL), an ingredient of Banxia, has anti-inflammatory properties in cerebral disease and regulates polarization of macrophages, but its effects on ischemic stroke (IS) damage have not been studied.
Methods:
In vivo, AL was administered by oral gavage to middle cerebral artery occlusion/reperfusion (MCAO/R) C57BL/6J mice in doses of 1.25, 2.5, and 5 mg/kg/day for seven days, and, in vitro, AL was added to treat oxygen-glucose deprivation (OGD)-BV2 cells. Modified neurological severity score, Triphenyltetrazolium chloride (TTC) staining, brain-water-content detection, TdT-mediated dUTP nick-end labeling (TUNEL) assay, flow cytometry, immunofluorescence assay, Enzyme linked immunosorbent assay (ELISA), and Western-blot analysis were used to investigate the functions and mechanism of the effect of AL treatment on IS. The exosomes of AL-treated microglia were studied by transmission electron microscope (TEM), nanoparticle tracking analyzer (NTA), and Western-blot analysis.
Results:
AL treatment reduced the neurological severity score, infarct volume, brain-water content, neuronal apoptosis, and the release of inflammatory factors, that were induced by MCAO/R. Notably, M2 microglia polarization was promoted but M1 microglia polarization was inhibited by AL in the ischemic penumbra of MCAO/R mice. Subsequently, anti-inflammatory and polarization-regulating effects of AL were verified in vitro. Suppressed NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation was found in the ischemic penumbra of animal and Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) cells treated with AL, as evidenced by decreasing NLRP3-inflammasome-related protein and downstream factors. After AL treatment, the anti-apoptosis effect of microglial exosomes on OGD/R primary cortical neurons was increased.
Conclusion:
AL reduce inflammatory responses and neuron death of IS-associated models by regulating microglia polarization by the NLRP3 pathway and by affecting microglial exosomes.
研究领域:
神经科学
·
药理学
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分子生物学
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细胞生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2021
·
IF 5.33
Chao Gu,Junqing Yang,Ying Luo,Dongzhi Ran,Xiaodan Tan,Pu Xiang,Huizhi Fei,Yi Lu,Wenjia Guo,Yujun Tu,Xia Liu,Hong Wang
Zinc and ring finger 2 (ZNRF2), an E3 ubiquitin ligase , plays a crucial role in many diseases . However, its role in cerebral ischemia/reperfusion injury (CIRI) still remains unknown. In this study, the function and molecular mechanism of ZNRF2 in CIRI in vivo and vitro was studied. ZNRF2 was found to be dramatically downregulated in CIRI. Overexpression of ZNRF2 could significantly reduce the neurological deficit, brain infarct volume and histopathological damage of cortex in middle cerebral artery occlusion/reperfusion. Concomitantly, overexpression of ZNRF2 increased the primary neuronal viability and decreased the neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation (OGD/R). Mechanistically, overexpression of ZNRF2 inhibited the over-induction of autophagy induced by OGD/R which was abolished by mTORC1 inhibitor rapamycin . It can be concluded that ZNRF2 plays a protective effect in CIRI and the underlying mechanism may be related to the inhibition of mTORC1-mediated autophagy.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Bing Chun Yan,Jianwen Cao,Jiajia Liu,Yunhao Gu,Zhuobin Xu,Dandan Li,Lizeng Gao
Cerebral ischemic stroke stimulates excessive reactive oxygen species, which lead to blood–brain-barrier disruption, neuron death, and aggravated cerebral infarction. Thus, it is critical to develop an antioxidant strategy for stroke treatment. Herein, we report a dietary strategy to promote stroke healing using iron oxide (Fe3O4) nanoparticles with intrinsic enzyme-like activities. We find that Fe3O4 nanozymes exhibit triple enzyme-like activities, peroxidase, catalase, and superoxide dismutase, thus potentially possessing the ability to regulate the ROS level. Importantly, intragastric administration of PEG-modified Fe3O4 nanozymes significantly reduces cerebral infarction and neuronal death in a rodent model following cerebral ischemic stroke. Ex vivo analysis shows that PEG-modified Fe3O4 nanozymes localize in the cerebral vasculature, ameliorate local redox state with decreased malondialdehyde and increased Cu/Zn SOD, and facilitate blood–brain-barrier recovery by elevating ZO-1 and Claudin-5 in the hippocampus. Altogether, our results suggest that dietary PEG-modified Fe3O4 nanozymes can facilitate blood–brain-barrier reconstruction and protect neurons following ischemic stroke.
研究领域:
神经科学
·
纳米技术
·
药理学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2019
·
IF 5.574
Runzhi Chen,Ying Xu,Peng Wu,Hao Zhou,Yi Lasanajak,Yingying Fang,Lan Tang,Ling Ye,Xing Li,Zheng Cai,Jie Zhao
The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus , and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.
研究领域:
神经病学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Alexandria Engineering Journal
·
2024
·
IF 6.2
Huiyuan Peng,Weihua Guo,Jinsong Wang,Weili Xia,Yu Xiong,Wenhua Xu,Weibo Dai,Feng Zheng
Addressing the devastating and often irreversible effects of stroke necessitates innovative therapeutic strategies that go beyond the limitations of current treatments. This study heralds a promising interdisciplinary approach by employing LAP/PDA composite nanomaterials integrated into silk fibroin-based hydrogels. These engineered materials not only demonstrated significantly enhanced mechanical properties, but also showed excellent biocompatibility when co-cultured with human mesenchymal stem cells (hMSCs). Importantly, the application of these composite hydrogels in stroke models yielded remarkable therapeutic outcomes. The results indicated a substantial reduction in cerebral infarction volumes, improved survival rates of transplanted hMSCs, and increased neurogenesis, underlining their transformative potential in stroke management. Molecular markers such as AQP4, α-DG, and β-DG were also explored, revealing modulated astrocyte activation and cellular signaling pathways. In summary, the composite LAP/PDA nanomaterials, in conjunction with hMSCs and Brain-Derived Neurotrophic Factor (BDNF), unveil a compelling and multifaceted approach for addressing the unmet needs in stroke treatment, thereby opening new avenues in regenerative medicine and tissue engineering.
研究领域:
神经科学
·
再生医学
·
组织工程
·
纳米技术
·
干细胞生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）