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INTERNATIONAL JOURNAL OF NEUROSCIENCE · 2021 · IF 2.292

Protective effects of repetitive transcranial magnetic stimulation against 6-OHDA-induced Parkinson’s symptoms in a mice model: the key role of miR-409-3p/PDHB axis

Hongyan Wang,Huaiqing Gao

Aim Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique showing improvement effects on Parkinson’s disease (PD). Multiple microRNAs (miRs) are dys-expressed during the progression of PD. In the current study, the potential involvement of miRs in the anti-PD effects of rTMS was explored.Methods PD symptoms were induced in mice with 6-OHDA. The expression profile of miRs influenced by rTMS in PD mice was detected by microarray technique and validated by RT-qPCR detection. The PD mice were treated with rTMS and the changes in cognitive behaviors, substantia nigra neuron number, brain histology, and Aβ1-42 level were detected. The activity of miR-409-3p/PDHB axis was also detected to preliminarily explain the interaction between miRs and rTMS.Results The detection of microarray showed that 266 miRs were dys-expressed in PD mice after the administration of rTMS, including 101 up-regulated ones and 146 down-regulated ones. With validation by RT-qPCR detection, miR-409-3p was selected for subsequent assays. Administrations of rTMS improved cognitive behaviors of mice, increased neuron number, and attenuated brain injuries induced by 6-OHDA. The cerebrospinal fluid (CSF) level of Aβ1-42 was induced, while the brain level of Aβ1-42 was suppressed by rTMS. Regarding miR-409-3p/PDHB axis, rTMS administrations suppressed miR-409-3p level and increased the expression of PDHB.Conclusion Administrations of rTMS showed considerable protective effects on brain tissues against PD-induced injuries, which was associated with the changes in miR levels. The current study demonstrated that the inhibition of miR-409-3p by rTMS contributed to the attenuation of PD by inducing PDHB.

CAS / MDL: 50-81-7
研究领域: 神经科学 · 分子生物学
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Multimodal Locomotion and Dynamic Interaction of Hydrogel Microdisks at the Air–Water Interface under Magnetic and Light Stimuli

Yifan Cheng,Shilu Zhu,Hui Ma,Shengting Zhang,Kun Wei,Shiyu Wu,Yongkang Tang,Ping Liu,Tingting Luo,Guangli Liu,Runhuai Yang

The potential applications of hydrogel microrobots in biomedicine and environmental exploration have sparked significant interest in understanding their behavior under multiphysical fields. This study explores the multimodal locomotion and dynamic interaction of hydrogel microrobots at the air–water interface under magnetic and light stimuli. A pair of hydrogel microrobots at the air–water interface exhibits a transition from cooperative, combined rotation to interactive behavior, involving both rotation and revolution under the influence of a rotating magnetic field (RMF), and a shift from attraction to separation under near-infrared (NIR) light, demonstrating the dynamic modulation of their behaviors in response to different stimuli. Notably, the behavioral patterns of multiple hydrogel microrobots under multiphysical fields indicate that NIR light can enhance interactive motion behaviors under RMFs and extend the range of motion trajectories. Dynamic models for each condition are established and analyzed based on dynamic equilibrium, and their behavior can be modulated by parameters such as magnetic particle concentration, magnetic field frequency, and NIR light intensity. This work introduces a novel strategy for regulating and controlling the dynamic behaviors of hydrogel microrobots, offering new insights into their multiphysical field locomotion.

研究领域: 生物医学工程 · 材料科学 · 机器人学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Magnetic field enabled spin-state reconfiguration for highly sensitive paper-based photoelectrochemical bioanalysis

Xiaoran Tan,Jiaxin Liang,Haihan Yu,Yuanyuan Chen,Li Shan,Shenguang Ge,Lina Zhang,Li Li,Jinghua Yu

Efficient carrier separation plays an utterly pivotal role in enhancing the sensitivity of photoelectrochemical (PEC) analysis. Here we report a concise yet powerful strategy of electron spin polarization induced by magnetic stimulation, to effectively modulate the efficiency of charge separation in a paper-based PEC (μ-PEC) sensing system. The electronic configuration of the sulfur-defected CdIn 2 S 4 /FeOOH photoactive matrix and ferromagnetic ZnFe 2 O 4 signal label were regulated via the electron parallel alignment along with spin state flip and reconstruction at particular active sites under external magnetic field, significantly facilitating the separation of photoinduced carriers. As a proof-of-concept application, the magnetic-triggerable spin-state reconfiguration coupled with enzymatic catalytic precipitation reaction was developed for detection of chlorpyrifos with a wide linear range of 10 -2.5 -10 6 ng mL −1 and low detection limit of 0.67 pg mL −1 . This work provides the basis for understanding the role of magnetic stimulus in tailoring charge separation and constructing a universal strategy for high performance μ-PEC bioanalysis.

研究领域: 生物分析 · 材料科学 · 环境监测
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Nanoscale · 2019 ·Vol. 11 ·期 39 ·18081-18089 · IF 6.97

Remote and real time control of an FVIO–enzyme hybrid nanocatalyst using magnetic stimulation

Ran Xiong,Wenting Zhang,Yifan Zhang,Ye Zhang,Yimin Chen,Yuan He,Haiming Fan

Remote modulation of nanoscale biochemical processes in a living system using magnetic stimulation is appealing but is restricted by the lack of a highly efficient nanomediator which can deliver timely and effective response to biological molecules under an external magnetic field. Herein, we report the development of a novel nanocatalyst based on a ferrimagnetic vortex-domain nanoring (FVIO)–enzyme hybrid that enables real-time modulation of enzymatic catalysis under an alternating magnetic field (AMF). The role of the FVIO is to provide localized heating immediately upon exposure to an AMF, which efficiently and selectively promotes the activity of conjugated enzymes on the surface. The reaction rate of the as-fabricated FVIO–β-Gal hybrid was shown to be boosted up to 180% of its initial value by localized heat generated under an AMF of 550 Oe in less than 2 s and without heating up the bulk solution. Moreover, the degree of activity acceleration was shown to be tunable by increasing the strength of the AMF. The concept of remote magnetic stimulation of enzymatic reactions has been further applied to other enzymes (e.g. FVIO–KPC and FVIO–GOx), demonstrating the general applicability of this strategy. Since almost all metabolic processes in cells rely on enzymatic catalysis to sustain life, the FVIO–enzyme system developed in this work provides a valuable nanoplatform for spatiotemporally manipulating biochemical reactions, which might pave the way for future remote manipulation of living organisms.

研究领域: 纳米技术 · 生物化学 · 分子生物学 · 催化
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MOLECULAR AND CELLULAR BIOCHEMISTRY · 2019 ·Vol. 458 ·期 1 ·71-78 · IF 2.884

Repetitive transcranial magnetic stimulation protects mice against 6-OHDA-induced Parkinson’s disease symptoms by regulating brain amyloid β1–42 level

Ba Fang,Zhou Yuxin,Zhou Jie,Chen Xueyun

Repetitive transcranial magnetic stimulation (rTMS) is a technique protecting neurons against diverse neurodegenerative disorders by delivering magnetic stimuli into the brain through the intact scalp. In the current study, the protection effect of rTMS on Parkinson’s disease (PD) and the associated mechanism driving the treatment were explored. The PD symptoms were induced using 6-OHDA in mice, and the effect of rTMS of two frequencies (1 Hz and 10 Hz) on the cognitive behaviors and neuron viability was detected. Afterwards, the level of Aβ 1–42 and activity of MKK7-ERK-Fos-APP axis under the administration of rTMS were recorded as well. The intracranial injection of 6-OHDA impaired the cognitive behaviors of the mice in the test of Morris water maze as well as reducing the viability and number of neurons in PD mice. After the treatment of rTMS of both frequencies, the cognitive function of mice was improved and the neuron viability and number were restored in mice brain tissues. The administration of rTMS also increased the cerebrospinal fluid (CSF) level of Aβ 1–42 in PD mice, which was accompanied by the suppressed levels of p-MKK7, p-ERK1/2, p–c-Fos, and APP. Moreover, the effect of rTMS on mice nerve system was all exerted in a frequency-dependent manner. In conclusion, the findings outlined in the current study affirmed the protection effect of rTMS against PD. The anti-PD function of rTMS was associated with the suppression of MKK7-ERK-Fos-APP axis, which subsequently resulted in the increased CSF Aβ 1–42 level and decreased brain Aβ 1–42 level.

CAS / MDL: 50-81-7
研究领域: 神经科学 · 药理学 · 神经退行性疾病
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Journal of Neuroinflammation · 2024 ·Vol. 21 ·期 1 ·1-25 · IF 9.3

Synergistic effects of repeated transcranial magnetic stimulation and mesenchymal stem cells transplantation on alleviating neuroinflammation and PANoptosis in cerebral ischemia

Cheng Shimei,Lu Qiying,Liu Qiuli,Ma Yuanchen,Chen Jinshuo,Lu Di,Huang Mudan,Huang Yinong,Zhao Erming,Luo Jing,Zheng Haiqing

Background Neuronal death is the primary cause of poor outcomes in cerebral ischemia. The inflammatory infiltration in the early phase of ischemic stroke plays a vital role in triggering neuronal death. Either transplantation of mesenchymal stem cells (MSCs) derived from humans or repetitive transcranial magnetic stimulation (rTMS) have respectively proved to be neuroprotective and anti-inflammatory in cerebral ischemia. However, either treatment above has its limitations. Whether these two therapies have synergistic effects on improving neurological function and the underlying mechanisms remains unclear. This investigation aims to elucidate the synergistic effects and underlying mechanisms of MSCs combined with rTMS treatment on the neurological function recovery post-ischemia.Methods A Sprague-Dawley rat model of cerebral infarction was induced via transient middle cerebral artery occlusion (tMCAO). The rats were divided into five groups (n = 50): sham, tMCAO, rTMS, MSCs, and MSCs + rTMS groups. Transplantation of human umbilical cord MSCs and rTMS intervention were performed 24 h post-stroke. Neurological function was further assessed via several behavioral tests and the 2,3,5-triphenyltetrazolium chloride (TTC) staining companied with Nissl staining were used to assess neuronal survival. TUNEL staining, western blotting, immunofluorescence, immunohistochemistry, ELISA, and flow cytometry were employed to measure the levels of neuroinflammation and PANoptosis. The molecular mechanisms underlying the special role of rTMS in the combined therapy were distinguished with transcriptome sequencing via PC12 cells in oxygen-glucose deprivation/reoxygenation (OGD/R) conditions.Results The combined therapy efficiently reduced lesion volume and improved neuronal survival (P < 0.05), subsequently improving functional recovery after ischemic stroke. MSCs + rTMS treatment ameliorated the PANoptosis in neurons (P < 0.05), accompanied by decreased levels of inflammatory factors in the cerebral tissue and serum during the subacute phase of cerebral infarction. To further explore the roles of either therapy on synergistic effect, we found that the transplanted MSCs primarily localized in the spleen and reduced cerebral inflammatory infiltration after ischemia via suppressed splenic inflammation. Meanwhile, rTMS significantly protects neurons from PANoptosis in MSCs-inhibited inflammatory conditions by downregulating REST unveiled by transcriptome sequencing.Conclusion sOur study elucidates an unidentified mechanism by which the combination of MSCs and rTMS could synergistically promote neuronal survival and suppress neuroinflammation during the subacute phase of cerebral infarction, thus improving neurological outcomes. The downregulating REST induced by rTMS may potentially contribute to the neuroprotective effect against PANoptosis in MSCs-inhibited inflammatory conditions. These results are expected to provide novel insights into the mechanisms of MSCs and rTMS combination therapy in synergistically protecting against cerebral ischemia injury and potential targets underlying neuronal PANoptosis in the early phase of stroke.

CAS / MDL: 64-19-7
研究领域: 神经科学 · 干细胞生物学 · 神经病学 · 免疫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2019 · IF 3.973

Cobalt nanowire-based multifunctional platform for targeted chemo-photothermal synergistic cancer therapy

Huang Zhu,Jiuhong Deng,Yuanyi Yang,Yunfei Li,Jiacheng Shi,Jiankui Zhao,Yi Deng,Xianchun Chen,Weizhong Yang

Cobalt nanowires (CoNWs) simultaneously possessing advantages in photothermal effect, targeting drug delivery and photoacoustic imaging property are hopefully promising strategies to further improve the treatment efficiency and reduce the side effects of cancer chemotherapy. Herein, a unique cobalt-based structure decorated with graphene oxide (GO) and polyethylene glycol (PEG) is fabricated through a facile approach. The resultant nanohybrids show relatively low cytotoxicity, favorable biocompatibility as well as inherit the outstanding properties of cobalt. Moreover, CoNWs decorated with GO and PEG (CoNWs-GO-PEG) can load therapeutic drug molecules (e.g., doxorubicin, DOX) with a high drug loading capacity (992.91 mg/g), and simultaneously they are responsive to pH, NIR (near-infrared) irradiation and magnetism stimulation. Accordingly, CoNWs-GO-PEG-DOX shows the satisfactory effect of eliminating cancer cells with synergistic chemo-photothermal therapy in vitro. Current work provides a solid demonstration of the potential of CoNWs-GO-PEG for serving as a targeted antitumor agent in synergistic chemo-photothermal therapy.

CAS / MDL: 25316-40-9
研究领域: 纳米技术 · 生物医学工程 · 癌症治疗 · 材料科学
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Materials Today Chemistry · 2022 · IF 7.613

Enhancing non-invasive brain stimulation with non-invasively delivered nanoparticles for improving stroke recovery

Y. Hong,J. Wang,J. Li,Z. Xu,X. Yang,M. Bai,P. Gong,Y. Xie,X. Zhang,P. Xu,X. Chen,R. Li,X. Liu,G. Ruan,G. Xu

Nanoparticles have great potential in remote neural stimulation with physical fields, but translation of these approaches to the medical arena faces enormous challenges, especially due to the use of highly invasive brain delivery of nanoparticles. Here we explore an alternative strategy through employing non-invasive brain delivery of nanoparticles. Non-invasive brain delivery of superparamagnetic iron oxide nanoparticles (SPIONs) in rats is performed by combining several complementary methods. The thus-delivered nanoparticles (called Tat-SPIONs) are found to enhance the neural stimulation effects of transcranial magnetic stimulation (TMS), a clinically-used non-invasive brain stimulation device, as analyzed by electrophysiological, biochemical, and behavioral experiments. In particular, ischemic stroke rats treated by non-invasively delivered Tat-SPIONs coupled with TMS show significant improvement in stroke recovery in terms of general health status, motor-sensory function, and cognitive function, compared to those treated by TMS alone. Importantly, mechanistic studies by experiments and numerical simulation suggest that the neural stimulation enhancement is mediated by neuroplasticity at least in part, is caused by a magnetoelectric rather than magnetothermal effect, and is generated primarily by those Tat-SPIONs associated with neurons’ plasma membranes . This further implies that the excellent membrane-binding ability of Tat peptide is crucial for SPION-enhanced TMS. Tat-SPIONs exhibit minimal toxicity and neuroinflammation, and are clearable from major organs. The presented technology platform paves the way for medical applications of nanoparticles in remote brain stimulation with physical fields for stroke as well as other neurological disorders.

研究领域: 神经科学 · 纳米技术 · 生物医学工程 · 临床神经学
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Biomaterials Science · 2019 ·Vol. 7 ·期 6 ·2297-2307 · IF 5.251

Enhancing the effects of transcranial magnetic stimulation with intravenously injected magnetic nanoparticles

Rongrong Li,Jun Wang,Xiaoya Yu,Pengfei Xu,Shuai Zhang,Jinhua Xu,Yongjie Bai,Zhengze Dai,Yuxiang Sun,Ruidong Ye,Xinfeng Liu,Gang Ruan,Gelin Xu

Transcranial magnetic stimulation (TMS) is a non-invasive and clinically approved method for treating neurological disorders. However, the relatively weak intracranial electric current induced by TMS is an obvious inferiority which can only produce limited treatment effects in clinical application. The present study aimed to investigate the possibility of enhancing the effects of TMS with intravenously administrated magnetic nanoparticles. To facilitate crossing of the blood–brain barrier (BBB), the superparamagnetic iron oxide nanoparticles (SPIONs) were coated with carboxylated chitosan and poly(ethylene glycol). To aid the nanoparticles in crossing the BBB and targeting the predesigned brain regions, an external permanent magnet was attached to the foreheads of the rats before the intravenous administration of SPIONs. The electrophysiological tests showed that the maximum MEP amplitude recorded in an individual rat was significantly higher in the SPIONs + magnet group than in the saline group (5.78 ± 2.54 vs. 1.80 ± 1.55 mV, P = 0.015). In the M1 region, biochemical tests detected that the number density of c-fos positive cells in the SPIONs + magnet group was 3.44 fold that of the saline group. These results suggest that intravenously injected SPIONs can enhance the effects of TMS in treating neurological disorders.

CAS / MDL: 9012-76-4
研究领域: 神经科学 · 生物医学工程 · 纳米技术 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE · 2023 · IF 6.2

Identification of Clec7a as the therapeutic target of rTMS in alleviating Parkinson's disease: targeting neuroinflammation

Xue-Yun Chen,Si-Ning Feng,Yin Bao,Yu-Xin Zhou,Fang Ba

Parkinson's disease (PD) is a neurodegenerative disease. Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic tool in PD. High-throughput sequencing was performed to screen potential therapeutic targets in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. The candidate gene, Clec7a, was screened out and validated. Clec7a is a pattern recognition receptor involved in neuroinflammation. The higher expression of Clec7a was observed in the substantia nigra (SN) and striatum of PD rats with dopaminergic neurons damage and was mainly localized in the microglial. Adeno-associated virus (AAV)-mediated specific knockdown of Clec7a in microglial alleviated 6-OHDA induced motor deficits and nigrostriatal dopaminergic neuron damage of rats, as evidenced by the increase of tyrosine hydroxylase (TH) -positive neurons in SN, as well as dopaminergic nerve fibers in the striatum. Clec7a knockdown restrained the neuroinflammation by suppressing inflammatory factors (IFN-γ, TNF-α, IL-1β, IL-18, and IL-6) release in SN, which might result from enhanced Arg-1 expression (M2 polarization) and defective inducible nitric oxide synthase (iNOS) expression (M1 polarization). The same phenomena were also observed in the LPS inflammatory rat model of PD. In vitro, α-synuclein fibrils induced upregulation of Clec7a expression and microglia polarization to a pro-inflammatory state of BV2 cells, leading to increased release of cytokines. However, Clec7a knockdown reversed those changes and induced a shift to an anti-inflammatory phenotype in BV2 cells. In conclusion, our study suggested that Clec7a was involved in PD pathogenesis, and its inhibition might protect rats from PD by depressing neuroinflammation through microglial polarization.

CAS / MDL: 636-00-0 47165-04-8
研究领域: 神经科学 · 神经退行性疾病 · 治疗干预 · 炎症 · 分子生物学
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