Neurotropin alleviates cognitive impairment by inhibiting TLR4/MyD88/NF-κB inflammation signaling pathway in mice with vascular dementia.

Vascular dementia (VD) is the second most common cause of dementia after Alzheimer's disease. Neuroinflammation contributes to pathogenesis of VD. Neurotropin (NTP) is an analgesic that has been shown to suppress inflammation and neural repair. But its effects on VD are still unclear. Therefore, this study aimed to investigate the therapeutic effects and potential mechanisms of NTP in the VD model mice established by bilateral common carotid artery stenosis method. In VD mice, we found that NTP treatment increased cerebral blood flow by Laser speckle imaging, reduced neuron loss by Nissl, HE and immunochemistry staining, attenuated white matter damage by magnetic resonance imaging and ultrastructural damage by transmission electron microscope, improved cognitive functions by new object recognition test and three-chamber test, Y maze test and Morris water maze test, inhibited significantly glial activation by immunofluorescence methods, reduced the expression of TLR4, down-regulated expression of MyD88 and phosphorylation of NF-κB P65, decreased the levels of pro-inflammatory cytokines IL-1ß, IL-6 and TNFα. Further, we showed that administration of a TLR4 inhibitor TAK242 had a similar effect to NTP, while the TLR4 agonist CRX-527 attenuated the effect of NTP in the VD mice. Collectively, our study suggested that NTP alleviates cognitive impairment by inhibiting TLR4/MyD88/NF-κB inflammation signaling pathway in the VD mice. Thus, NTP may be a promising therapeutic approach and a potential TLR4 inhibitor for VD.

High-Frequency Repetitive Magnetic Stimulation at the Sacrum Alleviates Chronic Constipation in Parkinson's Patients.

Objective: This study was to investigate the therapeutic effect of high-frequency repetitive magnetic stimulation (HF-rMS) at the sacrum for chronic constipation in Parkinson's patients (PD). Materials and Methods: Eventually 48 PD patients were enrolled from July 2019 to October 2020, and randomly divided into the HF-rMS group (the intervention group, n = 24) and the sham HF-rMS group (the control group, n = 24). The intervention group received HF-rMS at the sacrum, whereas the control group received ineffective magnetic stimulation. We performed clinical evaluation before and after HF-rMS treatment, including constipation score scale (KESS questionnaire), Unified Parkinson's Disease Rating Scale (UPDRS-III exercise examination), Hoehn-Yahr (H-Y) stage of motor function; simple mental status scale (MMSE), anxiety/depression table (HAD-A/HAD-D), the activity of daily living (ADL), and quality of life scale for patients with constipation (PAC-QOL) to evaluate symptoms and satisfaction of PD patients with chronic constipation. Results: There was no significant difference in the clinical characteristics between the two groups. As compared to the control group, the HF-rMS group displayed a larger change (pre and posttreatment) in the KESS scores of PD patients with chronic constipation, suggesting a significant improvement. Moreover, HF-rMS significantly promoted the mood, activity of daily living, and quality of life of PD patients when comparing the alteration of HAD-A/HAD-D scores, ADL scores, and PAC-QOL scores between the two groups. Finally, there was no significant difference in the change of the UPDRS III score and the MMSE score between the two groups. Conclusion: HF-rMS at the sacrum can improve chronic constipation in PD patients.

Action recognition based on multimode fusion for VR online platform.

The current popular online communication platforms can convey information only in the form of text, voice, pictures, and other electronic means. The richness and reliability of information is not comparable to traditional face-to-face communication. The use of virtual reality (VR) technology for online communication is a viable alternative to face-to-face communication. In the current VR online communication platform, users are in a virtual world in the form of avatars, which can achieve "face-to-face" communication to a certain extent. However, the actions of the avatar do not follow the user, which makes the communication process less realistic. Decision-makers need to make decisions based on the behavior of VR users, but there are no effective methods for action data collection in VR environments. In our work, three modalities of nine actions from VR users are collected using a virtual reality head-mounted display (VR HMD) built-in sensors, RGB cameras and human pose estimation. Using these data and advanced multimodal fusion action recognition networks, we obtained a high accuracy action recognition model. In addition, we take advantage of the VR HMD to collect 3D position data and design a 2D key point augmentation scheme for VR users. Using the augmented 2D key point data and VR HMD sensor data, we can train action recognition models with high accuracy and strong stability. In data collection and experimental work, we focus our research on classroom scenes, and the results can be extended to other scenes.

Transcriptome Sequencing of CeRNA Network Constructing in Status Epilepticus Mice Treated by Low-Frequency Repetitive Transcranial Magnetic Stimulation.

It is shown that great progress was recently made in the treatment of repetitive transcranial magnetic stimulation (rTMS) for neurological and psychiatric diseases. This study aimed to address how rTMS exerted it therapeutic effects by regulating competitive endogenous RNAs (ceRNAs) of lncRNA-miRNA-mRNA. The distinction of lncRNA, miRNA and mRNA expression in male status epilepticus (SE) mice treated by two different ways, low-frequency rTMS (LF-rTMS) vs. sham rTMS, was analyzed by high-throughput sequencing. The Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. Gene-Gene Cross Linkage Network was established; pivotal genes were screened out. qRT-PCR was used to verify gene-gene interactions. Our results showed that there were 1615 lncRNAs, 510 mRNAs, and 17 miRNAs differentially which were expressed between the LF-rTMS group and the sham rTMS group. The expression difference of these lncRNAs, mRNAs, and miRNAs by microarray detection were consistent with the results by qPCR. GO functional enrichment showed that immune-associated molecular mechanisms, biological processes, and GABA-A receptor activity played a role in SE mice treated with LF-rTMS. KEGG pathway enrichment analysis revealed that differentially expressed genes were correlated to T cell receptor signaling pathway, primary immune deficiency and Th17 cell differentiation signaling pathway. Gene-gene cross linkage network was established on the basis of Pearson's correlation coefficient and miRNA. In conclusion, LF-rTMS alleviates SE through regulating the GABA-A receptor activity transmission, improving immune functions, and biological processes, suggesting the underlying ceRNA molecular mechanisms of LF-rTMS treatment for epilepsy.

Inflammatory mechanisms of Ginkgo Biloba extract in improving memory functions through lncRNA-COX2/NF-κB pathway in mice with status epilepticus.

PURPOSE: This study was to explore whether Ginkgo biloba extract (GBE) improve memory impairment by alleviating neuroinflammation signaling in mice with status epilepticus. METHODS: The status epilepticus (SE) mice model was established by pilocarpine and treated with 100 mg / kg of GBE for 14 days. Spontaneous alternation of Y-maze and new object recognition were used to explore memory impairment. To examine glial cell activation, we performed immunohistochemistry and immunofluorescence staining. The activation of NF-κB signaling and the expression level of lncRNA-COX2 were detected by Western blot and qRT-PCR, respectively. Adeno-associated virus lncRNA-COX2 was injected into mice for overexpression of lncRNA-COX2. RESULTS: After GBE treatment, the spontaneous alternation rate and the recognition coefficient in SE mice were both increased. Moreover, activation of glial cells, NF-κB signaling and lncRNA-COX2 were significantly decreased in SE mice. In the GBE-treated SE mice with lncRNA-COX2 overexpression, NF-κB signaling was up-regulated again; the reduced level of inflammation factors was reversed; the GBE-rescued spontaneous alternation rate of Y-maze was eliminated. CONCLUSION: Our results suggested that GBE reduces the hippocampal inflammation by down-regulating lncRNA-COX2 / NF-κB signaling in the SE mice, leading to the decrease of neuronal damage and the improvement of memory functions.