Enhancement of motor imagery training efficiency by an online adaptive training paradigm integrated with error related potential.

Objective. Motor imagery (MI) is a process of autonomously modulating the motor area to rehearse action mentally without actual execution. Based on the neuroplasticity of the cerebral cortex, MI can promote the functional rehabilitation of the injured cerebral cortex motor area. However, it usually takes several days to a few months to train individuals to acquire the necessary MI ability to control rehabilitation equipment in current studies, which greatly limits the clinical application of rehabilitation training systems based on the MI brain-computer interface (BCI).Approach. A novel MI training paradigm combined with the error related potential (ErrP) is proposed, and online adaptive training of the MI classifier was performed using ErrP. ErrP is used to correct the output of the MI classification to obtain a higher accuracy of kinesthetic feedback based on the imagination intention of subjects while generating simulated labels for MI online adaptive training. In this way, we improved the MI training efficiency. Thirteen subjects were randomly divided into an experimental group using the proposed paradigm and a control group using the traditional MI training paradigm to participate in six MI training experiments.Main results. The proposed paradigm enabled the experimental group to obtain a higher event-related desynchronization modulation level in the contralateral brain region compared with the control group and 69.76% online classification accuracy of MI after three MI training experiments. The online classification accuracy reached 72.76% and the whole system recognized the MI intention of the subjects with an online accuracy of 82.61% after six experiments.Significance. Compared with the conventional unimodal MI training strategy, the proposed approach enables subjects to use the MI-BCI based system directly and achieve a better performance after only three training experiments with training left and right hands simultaneously. This greatly improves the usability of the MI-BCI-based rehabilitation system and makes it more convenient for clinical use.

Steady-state auditory motion based potentials evoked by intermittent periodic virtual sound source and the effect of auditory noise on EEG enhancement.

Hearing is one of the most important human perception forms, and humans can capture the movement of sound in complex environments. On the basis of this phenomenon, this study explored the possibility of eliciting a steady-state brain response in an intermittent periodic motion sound source. In this study, a novel discrete continuous and orderly change of sound source positions stimulation paradigm was designed based on virtual sound using head-related transfer functions (HRTFs). And then the auditory motion stimulation paradigms with different noise levels were designed by changing the signal-to-noise ratio (SNR). The characteristics of brain response and the effects of different noises on brain response were studied by analyzing electroencephalogram (EEG) signals evoked by the proposed stimulation. Experimental results showed that the proposed paradigm could elicit a novel steady-state auditory evoked potential (AEP), i.e., steady-state motion auditory evoked potential (SSMAEP). And moderate noise could enhance SSMAEP amplitude and corresponding brain connectivity. This study enriches the types of AEPs and provides insights into the mechanism of brain processing of motion sound sources and the impact of noise on brain processing.

Enhancement of capability for motor imagery using vestibular imbalance stimulation during brain computer interface.

Objective.Motor imagery (MI), based on the theory of mirror neurons and neuroplasticity, can promote motor cortical activation in neurorehabilitation. The strategy of MI based on brain-computer interface (BCI) has been used in rehabilitation training and daily assistance for patients with hemiplegia in recent years. However, it is difficult to maintain the consistency and timeliness of receiving external stimulation to neural activation in most subjects owing to the high variability of electroencephalogram (EEG) representation across trials/subjects. Moreover, in practical application, MI-BCI cannot highly activate the motor cortex and provide stable interaction owing to the weakness of the EEG feature and lack of an effective mode of activation.Approach.In this study, a novel hybrid BCI paradigm based on MI and vestibular stimulation motor imagery (VSMI) was proposed to enhance the capability of feature response for MI. Twelve subjects participated in a group of controlled experiments containing VSMI and MI. Three indicators, namely, activation degree, timeliness, and classification accuracy, were adopted to evaluate the performance of the task.Main results.Vestibular stimulation could significantly strengthen the suppression ofαandßbands of contralateral brain regions during MI, that is, enhance the activation degree of the motor cortex (p< 0.01). Compared with MI, the timeliness of EEG feature-response achieved obvious improvements in VSMI experiments. Moreover, the averaged classification accuracy of VSMI and MI was 80.56% and 69.38%, respectively.Significance.The experimental results indicate that specific vestibular activity contributes to the oscillations of the motor cortex and has a positive effect on spontaneous imagery, which provides a novel MI paradigm and enables the preliminary exploration of sensorimotor integration of MI.

Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-κB and Ras/Raf/MEK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza glabra L., a traditional medicinal, has a history of thousands of years. It is widely used in clinic and has been listed in Chinese Pharmacopoeia. Licochalcone A is a phenolic chalcone compound and a characteristic chalcone of Glycyrrhiza glabra L. It has many pharmacological activities, such as anti-cancer, anti-inflammatory, anti-viral and anti-angiogenic activities. AIM OF THE STUDY: In this study, we explored the anti-tumor activity and potential mechanism of licochalcone A in vitro and in vivo. MATERIALS AND METHODS: In vitro, the mechanism of licochalcone A at inhibiting PD-L1 expression was investigated by molecular docking, western blotting, RT-PCR, flow cytometry, immunofluorescence and immunoprecipitation assays. The co-culture model of T cells and tumor cells was used to detect the activity of cytotoxic T lymphocytes. Colony formation, EdU labelling and apoptosis assays were used to detect changes in cellular proliferation and apoptosis. In vivo, anti-tumor activity of licochalcone A was assessed in a xenograft model of HCT116 cells. RESULTS: In the present study, we found that licochalcone A suppressed the expression of programmed cell death ligand-1 (PD-L1), which plays a key role in regulating the immune response. In addition, licochalcone A inhibited the expressions of p65 and Ras. Immunoprecipitation experiment showed that licochalcone A suppressed the expression of PD-L1 by blocking the interaction between p65 and Ras. In the co-culture model of T cells and tumor cells, licochalcone A pretreatment enhanced the activity of cytotoxic T lymphocytes and restored the ability to kill tumor cells. In addition, we showed that licochalcone A inhibited cell proliferation and promoted cell apoptosis by targeting PD-L1. In vivo xenograft assay confirmed that licochalcone A inhibited the growth of tumor xenografts. CONCLUSION: In general, these results reveal the previously unknown properties of licochalcone A and provide new insights into the anticancer mechanism of this compound.

Antidepressive Effect of Arctiin by Attenuating Neuroinflammation via HMGB1/TLR4- and TNF-α/TNFR1-Mediated NF-κB Activation.

Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components in Fructus arctii and exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-like effects. However, the antidepressant-like effects of arctiin, its precursor, remain unknown. In this study, we investigated the antidepressant-like effects of arctiin and its underlying mechanisms by in vivo and in vitro experiments in mice. Our results showed that arctiin significantly attenuated sucrose consumption and increased the immobility time in tail suspension and forced swimming tests. Arctiin decreased neuronal damage in the prefrontal cortex (PFC) of the brain. Arctiin also attenuated the levels of three inflammatory mediators, indoleamine 2,3-dioxygenase, 5-hydroxytryptamine, and dopamine, that were elevated in the PFC or serum of chronic unpredictable mild stress (CUMS)-exposed mice. Arctiin reduced excessive activation of microglia and neuroinflammation by reducing high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)- and tumor necrosis factor-α (TNF-α)/TNF receptor 1 (TNFR1)-mediated nuclear factor-kappa B (NF-κB) activation in the PFC of CUMS-exposed mice and HMGB1- or TNF-α-stimulated primary cultured microglia. These findings demonstrate that arctiin ameliorates depression by inhibiting the activation of microglia and inflammation via the HMGB1/TLR4 and TNF-α/TNFR1 signaling pathways.

Convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer.

BACKGROUND: Aberrant activation of STAT3 is frequently encountered and promotes survival, cellular proliferation, migration, invasion and angiogenesis in tumor cell. Convallatoxin, triterpenoid ingredient, exhibits anticancer pharmacological properties. PURPOSE: In this work, we investigated the anticancer potential of convallatoxin and explored whether convallatoxin mediates its effect through interference with the STAT3 activation in colorectal cancer cells. METHODS: In vitro, the underlying mechanisms of convallatoxin at inhibiting STAT3 activation were investigated by homology modeling and molecular docking, luciferase reporter assay, MTT assay, RT-PCR, Western blotting and immunofluorescence assays. Changes in cellular proliferation, apoptosis, migration, invasion and angiogenesis were analyzed by EdU labeling assay, colony formation assay, flow cytometry assay, wound-healing assay, matrigel transwell invasion assay and tube formation assays. And in vivo, antitumor activity of convallatoxin was assessed in a murine xenograft model of HCT116 cells. RESULTS: Convallatoxin decreased the viability of colorectal cancer lines. Moreover, convallatoxin reduced the P-STAT3 (T705) via the JAK1, JAK2, and Src pathways and inhibited serine-727 phosphorylation of STAT3 via the PI3K-AKT-mTOR-STAT3 pathways in colorectal cancer cells. Interestingly, we discovered the crosstalk between mTOR and JAK2 in mTOR/STAT3 and JAK/STAT3 pathways, which collaboratively regulated STAT3 activation and convallatoxin play a role in it. Convallatoxin also downregulated the expression of target genes involved cell survival (e.g., Survivin, Bcl-xl, Bcl-2), proliferation (e.g., Cyclin D1), metastasis (e.g., MMP-9), and angiogenesis (e.g., VEGF). Indeed, we found that convallatoxin inhibited tube formation, migration, and invasion of endothelial cells, and inhibited the proliferation. Finally, in vivo observations were confirmed by showing antitumor activity of convallatoxin in a murine xenograft model. CONCLUSION: The result of the current study show that convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer cells and indicate that convallatoxin could be a valuable candidate for the development of colorectal cancer therapeutic.

Quantifying mode mixing and leakage in multivariate empirical mode decomposition and application in motor imagery-based brain-computer interface system.

Improper selection of the number and the amplitude of noise channels in noise-assisted multivariate empirical mode decomposition (NA-MEMD) would induce mode mixing and leakage in the obtained intrinsic mode functions (IMF), which would degrade the performance in applications like brain-computer interface (BCI) systems based on motor imagery. A measurement (ML-index) using no prior knowledge of the underlying components of the original signals was proposed to quantify the amount of mode mixing and leakage of IMFs. Both synthetic signals and electroencephalography (EEG) recordings from motor imagery experiments were used to test the validity. The BCI classification performance using NA-MEMD with the optimal parameters selected based on the ML-index was compared with the performance under the non-optimal parameter condition and the performance using the conventional filtering method. Test on synthetic signals demonstrated the ML-index can effectively quantify the amount of mode mixing and leakage, and help to improve the accuracy of extracting the underlying components. Test on EEG recordings showed the BCI classification performance can be significantly improved under the optimal parameter condition. This study provided a method to quantify the amount of mode mixing and leakage in IMFs and realized the optimization of the parameters associated with noise channels in NA-MEMD. Graphical abstract One of the synthetic multivariate signals comprised four components oscillating at different rates (middle column). Noise-assisted multivariate empirical mode decomposition (noise-assisted MEMD) was used to extract different components. Mode mixing issue occurred under the non-optimal parameter condition (left column). The issue was alleviated under the optimal parameter condition (right column) which can be obtained with the proposed method in this study.

A review: Motor rehabilitation after stroke with control based on human intent.

Strokes are a leading cause of acquired disability worldwide, and there is a significant need for novel interventions and further research to facilitate functional motor recovery in stroke patients. This article reviews motor rehabilitation methods for stroke survivors with a focus on rehabilitation controlled by human motor intent. The review begins with the neurodevelopmental principles of motor rehabilitation that provide the neuroscientific basis for intuitively controlled rehabilitation, followed by a review of methods allowing human motor intent detection, biofeedback approaches, and quantitative motor rehabilitation assessment. Challenges for future advances in motor rehabilitation after stroke using intuitively controlled approaches are addressed.

A new kaurane diterpenoid from Isodon inflexus.

A new 7,20-epoxy kaurane diterpenoid, 15-acetyldemethylkamebacetal A (1) and six known kaurane diterpenoids (2-7) were isolated from the aerial parts of Isodon inflexus in nuclear transcription factor-κB (NF-κB)-dependent reporter gene assay-guided fractionation. Their chemical structures were determined on the basis of extensive spectroscopic analysis (UV, IR, MS, 1D- and 2D-NMR) and comparison with literature data. The isolated compounds were evaluated for their inhibitory effects on TNF-α-induced NF-κB activation, and all compounds exhibited NF-κB inhibitory activities with IC50 values ranging from 1.91 to 20.15 µM.

Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa.

Five iridoid glycosides were isolated from the MeOH extract of Hedyotis diffusa, and their structures were elucidated as E-6-O-p-methoxycinnamoyl scandoside methyl ester (1), Z-6-O-p-methoxycinnamoyl scandoside methyl ester (2), E-6-O-p-feruloyl scandoside methyl ester (3), E-6-O-p-coumaroyl scandoside methyl ester (4), and Z-6-O-p-coumaroyl scandoside methyl ester (5) by interpretation of their spectroscopic data. All the isolated compounds were evaluated for human neutrophil elastase inhibitory effect, and compound 1 showed potent activity with an IC(50) value of 18.0muM. The molecular docking simulation suggested a structural model for the inhibition of human neutrophil elastase by compound 1.

21-Methylmelianodiols from Poncirus trifoliata as inhibitors of interleukin-5 bioactivity in Pro-B cells.

Interleukin (IL)-5 plays an important role in the progression of allergic inflammation. Here, we have isolated 21alpha-methylmelianodiol and 21beta-methylmelianodiol from Poncirus trifoliata (L.) Raf., a plant of the Rutaceae family, as the inhibitors of IL-5-dependent growth of Y16 pro-B cells by bioassay-guided fractionation. 21alpha-Methylmelianodiol and 21beta-methylmelianodiol inhibited IL-5-dependent growth of Y16 cells in a dose-dependent manner with IC (50) values of 17 microM and 15 microM, respectively. A positive control, tyrphostin AG-490, exhibited an IC (50) value of 23 microM on IL-5 bioactivity. Further, we have documented that 21alpha-methylmelianodiol and 21beta-methylmelianodiol cause G1 arrest of IL-5-induced cell cycle progression of Y16 cells, and also reduce IL-5-dependent survival of the cells by apoptosis. This study could provide a pharmacological potential for P. trifoliata in treatment of IL-5-associated inflammatory disorders.