Interactions between circulating inflammatory factors and autism spectrum disorder: a bidirectional Mendelian randomization study in European population.

Background: Extensive observational studies have reported an association between inflammatory factors and autism spectrum disorder (ASD), but their causal relationships remain unclear. This study aims to offer deeper insight into causal relationships between circulating inflammatory factors and ASD. Methods: Two-sample bidirectional Mendelian randomization (MR) analysis method was used in this study. The genetic variation of 91 circulating inflammatory factors was obtained from the genome-wide association study (GWAS) database of European ancestry. The germline GWAS summary data for ASD were also obtained (18,381 ASD cases and 27,969 controls). Single nucleotide polymorphisms robustly associated with the 91 inflammatory factors were used as instrumental variables. The random-effects inverse-variance weighted method was used as the primary analysis, and the Bonferroni correction for multiple comparisons was applied. Sensitivity tests were carried out to assess the validity of the causal relationship. Results: The forward MR analysis results suggest that levels of sulfotransferase 1A1, natural killer cell receptor 2B4, T-cell surface glycoprotein CD5, Fms-related tyrosine kinase 3 ligand, and tumor necrosis factor-related apoptosis-inducing ligand are positively associated with the occurrence of ASD, while levels of interleukin-7, interleukin-2 receptor subunit beta, and interleukin-2 are inversely associated with the occurrence of ASD. In addition, matrix metalloproteinase-10, caspase 8, tumor necrosis factor-related activation-induced cytokine, and C-C motif chemokine 19 were considered downstream consequences of ASD. Conclusion: This MR study identified additional inflammatory factors in patients with ASD relative to previous studies, and raised a possibility of ASD-caused immune abnormalities. These identified inflammatory factors may be potential biomarkers of immunologic dysfunction in ASD.

Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.

The hippocampus is one of the brain areas affected by autism spectrum disorder (ASD). Individuals with ASD typically have impairments in hippocampus-dependent learning, memory, language ability, emotional regulation, and cognitive map creation. However, the pathological changes in the hippocampus that result in these cognitive deficits in ASD are not yet fully understood. In the present review, we will first summarize the hippocampal involvement in individuals with ASD. We will then provide an overview of hippocampal structural and functional abnormalities in genetic, environment-induced, and idiopathic animal models of ASD. Finally, we will discuss some pharmacological and non-pharmacological interventions that show positive impacts on the structure and function of the hippocampus in animal models of ASD. A further comprehension of hippocampal aberrations in ASD might elucidate their influence on the manifestation of this developmental disorder and provide clues for forthcoming diagnostic and therapeutic innovation.

Therapeutic efficacy and pharmacological mechanism of Yindan Xinnaotong soft capsule on acute ischemic stroke: a meta-analysis and network pharmacology analysis.

Yindan Xinnaotong soft capsule (YDXNT), a traditional Chinese medicine preparation, has shown a promising effect in the treatment of acute ischemic stroke (AIS). The goal of this study was to investigate the therapeutic effects and pharmacological mechanisms of YDXNT on AIS. Randomized controlled trials were searched and screened. Review Manager 5.4 was used for a meta-analysis. Active ingredients and targets of YDXNT were extracted from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. AIS-related targets were retrieved from GeneCards, OMIM, and DrugBank databases. We constructed PPI and ingredient-target networks, performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and conducted molecular docking. The YDXNT group had a higher total effective rate and a higher Barthel Index score. YDXNT reduced the low-density lipoprotein cholesterol and the whole blood viscosity at high and shear rates. Our study identified 313 ingredients and 1196 common targets. The key ingredients were mainly quercetin, neocryptotanshinone II, miltionone I, neotanshinone C, and tanshiquinone B, and the key targets were mainly SRC, MAPK3, AKT1, MAPK1, and JUN. GO analysis showed that the core targets mainly involved in atherosclerosis and neural apoptosis. The core pathways were lipid and atherosclerosis, PI3K-Akt, MAPK, and other pathways. Key ingredients exhibited robust binding interactions with core targets. YDXNT could effectively improve the total effective rate, ability of daily life, blood lipids, and blood viscosity. Antiatherosclerotic and neuroprotective effects are the main pharmacological mechanisms.Registration number: CRD42023400127.

Bibliometric analysis of global research trends on regulatory T cells in neurological diseases.

This bibliometric study aimed to summarize and visualize the current research status, emerging trends, and research hotspots of regulatory T (Treg) cells in neurological diseases. Relevant documents were retrieved from the Web of Science Core Collection. Tableau Public, VOSviewer, and CiteSpace software were used to perform bibliometric analysis and network visualization. A total of 2,739 documents were included, and research on Treg cells in neurological diseases is still in a prolific period. The documents included in the research were sourced from 85 countries/regions, with the majority of them originating from the United States, and 2,811 organizations, with a significant proportion of them coming from Harvard Medical School. Howard E Gendelman was the most prolific author in this research area. Considering the number of documents and citations, impact factors, and JCR partitions, Frontiers in Immunology was the most popular journal in this research area. Keywords "multiple sclerosis," "inflammation," "regulatory T cells," "neuroinflammation," "autoimmunity," "cytokines," and "immunomodulation" were identified as high-frequency keywords. Additionally, "gut microbiota" has recently emerged as a new topic of interest. The study of Treg cells in neurological diseases continues to be a hot topic. Immunomodulation, gut microbiota, and cytokines represent the current research hotspots and frontiers in this field. Treg cell-based immunomodulatory approaches have shown immense potential in the treatment of neurological diseases. Modifying gut microbiota or regulating cytokines to boost the numbers and functions of Treg cells represents a promising therapeutic strategy for neurological diseases.

Effect of different constraint-induced movement therapy protocols on recovery of stroke survivors with upper extremity dysfunction: a systematic review and network meta-analysis.

We aimed to assess and rank comparative efficacy of different constraint-induced movement therapy (CIMT) protocols on motor function of upper extremity and activities of daily living (ADL) in stroke survivors. A comprehensive search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library to identify randomized controlled trials on CIMT. Included studies were evaluated using the revised Cochrane risk of bias tool. Then a random-effects network meta-analysis was performed within a frequentist framework using Stata v16.0. Of the 1150 studies retrieved, 44 studies with 1779 participants were included. In terms of motor recovery of upper extremity, CIMT combined with trunk restraint, in which the less affected arm was constrained at least 4 h but no more than 6 h per day, ranked as the most effective intervention for the improvement of the Fugl-Meyer Assessment-Upper Extremity and the Action Research Arm Test score. In terms of ADL improvement, constraining the less affected arm for at least 4 h but no more than 6 h per day in CIMT combined with trunk restraint, was found to significantly improve the Motor Activity Log of quality of movement scale and amount of use scale score. The protocol of CIMT combined with trunk restraint, in which the less affected arm was constrained at least 4 h but no more than 6 h per day, ranked the highest in this analysis and might be considered in practice.

Music-based interventions for unilateral spatial neglect: A systematic review.

This study aimed to evaluate the effects of music-based interventions on unilateral spatial neglect. Five databases were retrieved prior to May 5, 2022. A range of study designs were considered, including randomized controlled trials, controlled clinical trials, cohorts, and case series/reports. Types of music-based interventions were not limited. Methodological quality of randomized trials were evaluated using the RoB 2 tool, and the RoBiNT scale was utilized to assess the quality of case studies. Two authors independently summarized main results for assessments. Search strategies identified 186 potentially relevant articles, and 10 articles were collected for in-depth analysis. Preliminary results showed that USN patients performed better in cancellation tests than bisection tests after music-based intervention. In summary, pleasant music listening may have a beneficial effect on the visual attention of USN patients, and it can be hypothesized that this is related to the positive mood and emotions of patients induced by music. Music with a dynamic auditory stimulus as a new music listening programme in USN rehabilitation is worthy of further investigation. Instrument playing intervention can be considered as a multisensory stimulation to ameliorate neglect performance via multiple mechanisms. However, current results only support the short-term positive effects of music-based interventions on USN.

Exosomes in the Field of Neuroscience: A Scientometric Study and Visualization Analysis.

Exosomes have received great attention for their diagnostic, therapeutic, and prognostic roles in the field of neuroscience over the past decade. This scientometric study aimed to quantitatively and qualitatively evaluate knowledge structure, hot topics, and research trends of studies about exosomes in the field of neuroscience using visualization tools. Web of Science Core collection databases were searched for relevant publications between 2005 and 2021. The Carrot2 online system, BICOMB, gCLUTO, and Ucinet software were utilized for key word analysis, and co-citations analyses were conducted in Citespace and VOSviewer. Altogether, 21 high-frequency key words were collected from 856 included articles, and 5 clusters were identified through biclustering analyses. The strategic diagram and social network analysis further determined research hotspots and trends. Co-citation analysis results revealed a few crucial works that contributed to the development of research on exosomes in the field of neuroscience. Moreover, the important sources that had contributed to the development of this field were identified. Our findings suggested that Alzheimer's disease-related research remained a hot topic in this field till now, and recent researchers had extended their scopes to more cognitive impairments. Importantly, researches related to exosomes in multiple sclerosis and Parkinson's disease were promising. While exosomes in acute central nervous system injury had not been sufficiently investigated, with continuous improvement in exosome-based delivery technology, this subject might make a breakthrough in terms of therapeutic innovations in the immediate future.

Exploring Active Compounds and Mechanisms of Angong Niuhuang Wan on Ischemic Stroke Based on Network Pharmacology and Molecular Docking.

Methods: The chemical ingredients of ANW were retrieved from TCMSP, TCMID, and literature. We predicted the potential targets of active ingredients by PubChem, Swiss Target Prediction, and STITCH databases. The targets related to ischemic stroke were retrieved using GeneCards, DisGeNET, DrugBank, TTD, and GEO databases. Subsequently, Venn diagrams were used to identify common targets of active ingredients and ischemic stroke. Protein-protein interaction (PPI) network was structured with STRING platform and Cytoscape 3.8.2. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of key targets were performed in the Metascape database. Finally, molecular docking was conducted by AutoDock Tools and PyMOL software. Results: A total of 2391 targets were identified for 230 active ingredients of ANW, and 1386 of them overlapped with ischemic stroke targets. The key active ingredients were mainly quercetin, ß-estradiol, berberine, wogonin, and ß-sitosterol, and the key targets were also identified, including IL-6, AKT1, MAPK3, PIK3CA, and TNF. The biological process (BP) results indicated that ANW may have therapeutic effects through response oxidative stress, inflammatory response, cellular response to lipid, and response to nutrient levels. Furthermore, the ingredients of ANW were predicted to have therapeutic effects on ischemic stroke via the HIF-1 signaling pathway, FoxO signaling pathway, chemokine signaling pathway, fluid shear stress and atherosclerosis, and neurotrophin signaling pathway. The molecular docking results all showed that the core ingredients were strong binding activity with the core targets. Conclusion: In conclusion, the bioinformatics and pharmacological results reveal that counteracting oxidative stress, suppressing inflammation, inhibiting the development of AS, and even protecting neurological function are critical pathways for ANW in the treatment of ischemic stroke. These results may help to elucidate the mechanism of ANW on ischemic stroke for experimental studies and clinical applications.

Effects of sling exercise therapy on post-stroke walking impairment: a systematic review and meta-analysis.

Walking impairment is a common consequence of stroke, resulting in long-term disability. Trunk muscle strength has been proven to be associated with post-stroke walking performance. As a type of trunk training, sling exercise therapy (SET) has been widely used to improve the trunk function in stroke patients. The purpose of this systematic review was to investigate the efficacy of SET on post-stroke walking impairment. Seven databases were systematically searched for eligible studies from their inception to 1 August 2021. Review Manager 5.3 software was used for this meta-analysis. The overall quality of included studies was evaluated by the physiotherapy evidence database scale. Twenty-five randomized controlled trials involving 1504 patients were included (23 in China and two in South Korea). In summary, SET more effectively improved the walking ability of post-stroke patients than conventional physical therapy or trunk training. The pooled analysis demonstrated that SET had positive effects on the 10 m maximum walking speed, integrated electromyography value of rectus femoris, biceps femoris and gastrocnemius, functional ambulation category, timed up and go test, and step length. At least in East Asia, our findings support SET to manage the post-stroke walking impairment.

Effect of probiotics on the nutritional status of severe stroke patients with nasal feeding that receive enteral nutrition: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Malnutrition is commonly observed after stroke and is closely associated with poor clinical outcomes. So, early nutrition support is particularly crucial for severe stroke patients. However, a significant number of critically ill patients are intolerant to enteral nutrition (EN). Probiotics have been widely used in malnutrition by various diseases and have a low incidence of enteral intolerance. So, we aim to elucidate the efficacy of probiotics in EN in improving the nutritional status and clinical prognosis of severe stroke patients with nasal feeding. METHOD: Embase, PubMed, Sinomed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and Vip Journal Integration Platform were searched from inception to March 31, 2021. Randomized controlled trials that applied probiotics in patients with severe stroke were included. The data were extracted and the risk of bias was assessed independently by 2 evaluators. RESULTS: Twenty-four studies comprising 2003 participants of randomized controlled trials were included. The result of pooled analyses showed that probiotics in EN were associated with better outcomes than EN alone on Glasgow Coma Scale score (mean difference [MD] = 1.03, 95% confidence intervals [CI]: 0.78-1.27; P < .00001), infection events (odds ratio [OR] = 0.25, 95% CI: 0.15-0.43; P < .00001), rate of intestinal flora dysbiosis (OR = 0.24, 95% CI: 0.12-0.48; P < .0001), gastrointestinal complications (OR = 0.25, 95% CI: 0.16-0.37, P < .00001), time to reach target nutrition (MD = -1.80, 95% CI: -2.42 to 1.18, P < .00001), prealbumin content (MD = 25.83, 95% CI: 13.68-37.99, P < .0001). CONCLUSION: Our results demonstrated that probiotics supplementation might be an effective intervention for improving the clinical prognosis in severe stroke patients with nasal feeding, but no significant effect on increasing muscle circumference.