Salivary microRNAs: Diagnostic markers of mild traumatic brain injury in contact-sport

Concussion is difficult to diagnose, particularly when symptoms are atypical or late in presenting. An accurate and timely initial assessment is crucial for clinical management. Cerebral spinal fluid (CSF) and blood markers of traumatic brain injury show promising results but their clinical applicability in concussion has significant limitations. In the study, we explored saliva as a new source of biomarkers of concussion. Saliva samples of concussed players were collected after 48–72 h from concussion and analyzed by high-throughput technologies. A discovery group of 10 concussed rugby professional and semiprofessional athletes and 10 non-concussed matched controls was used for the analysis of 92 inflammatory proteins by the Proseek-Multiplex-Inflammation technology. In addition, saliva samples of 6 concussed and 6 non-concussed athletes were used to screen 800 human microRNAs (miRNAs) by the Nanostring Technology. The results were then validated by RT-qPCR in an enlarged cohort (validation group) comprising 22 concussed athletes. Results showed, no significant variations of the 65 inflammatory proteins detected in saliva between groups but 5 microRNAs, miR-27b-3p (p = 0.016), let-7i-5p (p = 0.001), miR-142-3p (p = 0.008), miR-107 (p = 0.028), miR-135b-5p (p = 0.017) significantly upregulated in concussed athletes. Univariate ROC curve analysis showed that the differentially expressed miRNAs could be considered good classifiers of concussion. Further analyses showed significant correlation between these microRNAs and Reaction Time component of the ImPACT concussion assessment tool. In addition, biocomputation analysis predicted the involvement of these microRNAs in important biological processes that might be related to trauma, such as response to hypoxia, cell death, neurogenesis, axon repair and myelination. Ease of access and non-invasiveness of saliva samples make these biomarkers particularly suitable for concussion assessment

Mechanisms and therapeutic effectiveness of pulsed electromagnetic field therapy in oncology

Cancer is one of the most common causes of death worldwide. Available treatments are associated with numerous side effects and only a low percentage of patients achieve complete remission. Therefore, there is a strong need for new therapeutic strategies. In this regard, pulsed electromagnetic field (PEMF) therapy presents several potential advantages including non-invasiveness, safety, lack of toxicity for non-cancerous cells, and the possibility of being combined with other available therapies. Indeed, PEMF stimulation has already been used in the context of various cancer types including skin, breast, prostate, hepatocellular, lung, ovarian, pancreatic, bladder, thyroid, and colon cancer in vitro and in vivo. At present, only limited application of PEMF in cancer has been documented in humans. In this article, we review the experimental and clinical evidence of PEMF therapy discussing future perspectives in its use in oncology

Mechanisms and therapeutic applications of electromagnetic therapy in Parkinson's disease

© 2015 Vadalà et al. Electromagnetic therapy is a non-invasive and safe approach for the management of several pathological conditions including neurodegenerative diseases. Parkinson's disease is a neurodegenerative pathology caused by abnormal degeneration of dopaminergic neurons in the ventral tegmental area and substantia nigra pars compacta in the midbrain resulting in damage to the basal ganglia. Electromagnetic therapy has been extensively used in the clinical setting in the form of transcranial magnetic stimulation, repetitive transcranial magnetic stimulation, high-frequency transcranial magnetic stimulation and pulsed electromagnetic field therapy which can also be used in the domestic setting. In this review, we discuss the mechanisms and therapeutic applications of electromagnetic therapy to alleviate motor and non-motor deficits that characterize Parkinson's disease

ApoE ε4 Allele Related Alterations in Hippocampal Connectivity in Early Alzheimer’s Disease Support Memory Performance

Background: Whether the presence of the Apolipoprotein E ε4 allele modulates hippocampal connectivity networks in abnormal ageing has yet to be fully clarified. Objective: Allele-dependent differences in this pattern of functional connectivity were investigated in patients with very mild neurodegeneration of the Alzheimer’s type, carriers and non-carriers of the ε4 allele. Method: A seed-based connectivity approach was used. The two groups were similar in demographics, volumetric measures of brain structure, and cognitive profiles. Results: ε4-carriers had increased connectivity between the seed area in the left hippocampus and 1) a left insular/lateral prefrontal region and 2) the contralateral right parietal cortex. Moreover, hippocampus- to-parietal connectivity in the group of ε4 carriers was positively associated with memory performance, indicating that the between-group difference reflects compensatory processes. Retrospective analyses of functional connectivity based on patients from the ADNI initiative confirmed this pattern. Conclusion: We suggest that increased connectivity with areas external to the Default Mode Network (DMN) reflects both compensatory recruitment of additional areas, and pathological interwining between the DMN and the salience network as part of a global ε4-dependent circuital disruption. These differences indicate that the ε4 allele is associated with a more profound degree of DMN network breakdown even in the prodromal stage of neurodegeneration

Serum miR-96-5P and miR-339-5P Are Potential Biomarkers for Multiple System Atrophy and Parkinson's Disease

Parkinson's disease (PD) and Multiple System Atrophy (MSA) are progressive neurodegenerative diseases with overlap of symptoms in early stages of disease. No reliable biomarker exists and the diagnosis is mainly based on clinical features. Several studies suggest that miRNAs are involved in PD and MSA pathogenesis. Our goal was to study two serum circulating microRNAs (miR-96-5p and miR-339-5p) as novel biomarkers for the differential diagnosis between PD and MSA. Serum samples were obtained from 51 PD patients, 52 MSA patients and 56 healthy controls (HC). We measured levels of miRNAs using quantitative PCR and compared the levels of miR-96-5p and miR-339-5p among PD, MSA and HC groups using a one-way analysis of variance. Correlations between miRNA expression and clinical data were calculated using Pearson's rho test. We used the miRTarBase to detect miRNA targets and STRING to evaluate co-expression relationship among target genes. MiR-96-5p was significantly increased in MSA patients compared with HC (Fold change (fc): 3.6; p = 0.0001) while it was decreased in PD patients compared with HC (Fold change: 4; p = 0.0002). Higher miR-96-5P levels were directly related to longer disease duration in MSA patients. We observed a significant increase of miR-339-5p in MSA patients compared with PD patients (fc: 2.5; p = 0.00013). miR-339-5p was increased in MSA patients compared with HC (fc: 2.4; p = 0.002). We identified 32 target genes of miR-96-5p and miR-339-5p, some of which are involved in neurodegenerative diseases. The study of those miRNAs could be useful to identify non-invasive biomarkers for early differential diagnosis between PD and MSA