Yun Yu

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with poorly understood etiology. Increasing evidence suggest that inflammation may play a critical role in the pathogenesis of ALS. Several studies have demonstrated altered levels of blood cytokines in ALS, but results were inconsistent. Therefore, we did a systematic review of studies comparing blood inflammatory cytokines between ALS patients and control subjects, and quantitatively combined the clinical data with a meta-analysis. The systematic review of Pubmed and Web of Science identified 25 studies encompassing 812 ALS patients and 639 control subjects. Random-effects meta-analysis demonstrated that blood tumor necrosis factor-α (TNF; Hedges' g = 0.655; p = 0.001), TNF receptor 1 (Hedges' g = 0.741; p < 0.001), interleukin 6 (IL-6; Hedges' g = 0.25; p = 0.005), IL-1β (Hedges' g = 0.296; p = 0.038), IL-8 (Hedges' g = 0.449; p < 0.001) and vascular endothelial growth factor (Hedges' g = 0.891; p = 0.003) levels were significantly elevated in patients with ALS compared with control subjects. These results substantially enhance our knowledge of the inflammatory response in ALS, and peripheral blood inflammatory cytokines may be used as diagnostic biomarkers for ALS in the future.

Genetic variants conferring risk for schizophrenia (SCZ) have been extensively studied, but the role of posttranscriptional mechanisms in SCZ is not well studied. Here we performed the first genome-wide microRNA (miRNA) expression profiling in serum-derived exosome from 49 first-episode, drug-free SCZ patients and 46 controls and identified miRNAs and co-regulated modules that were perturbed in SCZ. Putative targets of these SCZ-affected miRNAs were enriched strongly for genes that have been implicated in protein glycosylation and were also related to neurotransmitter receptor and dendrite (spine) development. We validated several differentially expressed blood exosomal miRNAs in 100 SCZ patients as compared with 100 controls by quantitative reverse transcription-polymerase chain reaction. The potential regulatory relationships between several SCZ-affected miRNAs and their putative target genes were also validated. These include hsa-miR-206, which is the most upregulated miRNA in the blood exosomes of SCZ patients and that previously reported to regulate brain-derived neurotrophic factor expression, which we showed reduced mRNA and protein levels in the blood of SCZ patients. In addition, we found 11 miRNAs in blood exosomes from the miRNA sequence data that can be used to classify samples from SCZ patients and control subjects with close to 90% accuracy in the training samples, and approximately 75% accuracy in the testing samples. Our findings support a role for exosomal miRNA dysregulation in SCZ pathophysiology and provide a rich data set and framework for future analyses of miRNAs in the disease, and our data also suggest that blood exosomal miRNAs are promising biomarkers for SCZ.

Posttraumatic stress disorder (PTSD) is a serious psychosis leading to cognitive impairment. To restore cognitive functions for patients, the main treatments are based on medication or rehabilitation training but with limited effectiveness and strong side effects. Here, we demonstrate a new treatment approach for PTSD by using terahertz (THz) photons stimulating the hippocampal CA3 subregion. We verified that this method can nonthermally restore cognitive function in PTSD rats in vivo. After THz photon irradiation, the PTSD rats' recognitive index improved by about 10% in a novel object recognition test, the PTSD rats' accuracy improved by about 100% in a shuttler box test, the PTSD rats' numbers to identify target box was about 5 times lower in a Barnes maze test, and the rate of staying in new arm increased by approximately 40% in a Y-maze test. Further experimental studies found that THz photon (34.5 THz) irradiation could improve the expression of NR2B (increased by nearly 40%) and phosphorylated NR2B (increased by about 50%). In addition, molecular dynamics simulations showed that THz photons at a frequency of 34.5 THz are mainly absorbed by the pocket of glutamate receptors rather than by glutamate molecules. Moreover, the binding between glutamate receptors and glutamate molecules was increased by THz photons. This study offers a nondrug, nonthermal approach to regulate the binding between the excitatory neurotransmitter (glutamate) and NR2B. By increasing synaptic plasticity, it effectively improves the cognitive function of animals with PTSD, providing a promising treatment strategy for NR2B-related cognitive disorders.

Background: Multiple sclerosis (MS) biomarker identification is important for the pathogenesis research and diagnosis in routine clinical practice. The CSF and blood cytokines as potential biomarkers to inform MS pathogenesis, diagnosis and response to treatment have been assessed in numerous studies. However, there have been no comprehensive meta-analyses to pool cytokine data and address their diagnostic performance. We systematically reviewed the literature with meta-analyses to assess the alteration levels of cytokines and chemokines in MS. Methods: We searched PubMed and Web of Science for articles published between January 1, 1990 and April 30, 2018 for this systematic review and meta-analysis. Data were extracted from 226 included studies encompassing 13526 MS patients and 8428 controls. Biomarker performance was rated by a random-effects meta-analysis based on the standard mean difference between cytokine concentration in patients with MS and controls or patients before and after treatments. Results: Of the 26 CSF cytokines and 37 blood cytokines for potential differentiation between MS patients and controls, random-effects meta-analysis showed that 13 CSF cytokines and 21 blood cytokines were significantly increased in MS patients when compared with controls. Interestingly, TNF-α, CXCL8, IL-15, IL-12p40 and CXCL13 were increased in both blood and CSF of MS patients. For those cytokines were analyzed in at least ten studies, differentiation between case and control was strong for CSF CXCL13, blood IL-2R and blood IL-23; CSF CXCL8, blood IL-2 and blood IL-17 also had good performance to differentiate between MS patients and controls, whereas those of CSF TNF-α and blood TNF-α, CXCL8, IL-12, IFN-γ were moderate. Furthermore, CSF IL-15, CCL19, CCL11, CCL-3 and blood CCL20, IL-12p40, IL-21, IL-17F, IL-22 had large effective sizes when differentiating between MS patients and controls, but with relatively small number of studies (three to seven studies). Conclusion: Our findings clarified the circulating cytokine profile in MS, which provide targets for the disease modifying treatments, and suggest that cytokines have the potential to be used as biomarkers for MS.

// Yan Zhang 1 , Meng Che 1 , Jing Yuan 1 , Yun Yu 1 , Chang Cao 1 , Xiao-Yan Qin 1 and Yong Cheng 1 1 Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China Correspondence to: Yong Cheng, email: yongcheng@muc.edu.cn Keywords: cytokine, inflammation, Down syndrome, meta-analysis, systematic review Received: July 26, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: September 03, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: September 19, 2017 ABSTRACT Evidence suggests that immune system alterations in Down syndrome (DS) may be early events that drive neuropathological and cognitive changes of Alzheimer&rsquo;s disease. The primary objective of this meta-analysis was to investigate whether there is an abnormal cytokine profile in DS patients when compared with healthy control (HC) subjects. A systematic search of Pubmed and Web of Science identified 19 studies with 957 DS patients and 541 HC subjects for this meta-analysis. Random effects meta-analysis demonstrated that patients with DS had significantly increased circulating tumor necrosis factor-&alpha; (Hedges&rsquo; g = 1.045, 95% confidence interval (CI) = 0.192 to 1.898, p = 0.016), interleukin (IL)-1&beta; (Hedges&rsquo; g = 0.696, 95% confidence CI = 0.149 to 1.242, p = 0.013), interferon-&gamma; (Hedges&rsquo; g = 0.978, 95% CI = 0.417 to 1.539, p = 0.001) and neopterin (Hedges&rsquo; g = 0.815, 95% CI = 0.423 to 1.207, p &lt; 0.001) levels compared to HC subjects. No significant differences were found between patients with DS and controls for concentrations of IL-4, IL-6, IL8 and IL-10. In addition, most of the cytokine data in this meta-analysis were from children with DS and HC, and subgroup analysis showed that children with DS had elevated tumor necrosis factor-&alpha;, IL-1&beta; and interferon-&gamma; levels when compared with controls. Taken together, these results demonstrated that patients (children) with DS are accompanied by increased circulating cytokine tumor necrosis factor-&alpha;, IL-1&beta; and interferon-&gamma; levels, strengthening the clinical evidence that patients (children) with DS are accompanied by an abnormal inflammatory response.