Osteoarthritis and microRNAs: Do They Provide Novel Insights into the Pathophysiology of This Degenerative Disorder?

Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases in older adults and a leading cause of disability. Recent research studies have evidenced the importance of mi-croRNAs (miRs) in the pathogenesis of OA. In the present review, we focused on current literature findings on dysregulated miRs involved in the pathophysiology of OA. From the 35 case-control studies including OA patients compared to healthy controls, a total of 54 human miRs were identified to be dysregulated in OA. In total, 41 miRs were involved in the pathophysiological processes of OA, including apoptosis, inflammation, and proliferation, having either a protective or a progressive role in OA. The discovery of altered miR levels in OA patients compared to healthy controls determines a better understanding of the molecular mechanisms involved in the pathophysiology of OA and could open novel horizons in the field of orthopedics.

Uncovering the Roles of MicroRNAs in Major Depressive Disorder: From Candidate Diagnostic Biomarkers to Treatment Response Indicators.

Major depressive disorder (MDD) is a recurrent debilitating illness that represents a major health burden due to its increasing worldwide prevalence, unclear pathological mechanism, nonresponsive treatment, and lack of reliable and specific diagnostic biomarkers. Recently, microRNA species (miRs) have gained particular interest because they have the ability to post-transcriptionally regulate gene expression by modulating mRNA stability and translation in a cohesive fashion. By regulating entire genetic circuitries, miRs have been shown to have dysregulated expression levels in blood samples from MDD patients, when compared to healthy subjects. In addition, antidepressant treatment (AD) also appears to alter the expression pattern of several miRs. Therefore, we critically and systematically reviewed herein the studies assessing the potential biomarker role of several candidate miRs for MDD, as well as treatment response monitoring indicators, in order to enrich the current knowledge and facilitate possible diagnostic biomarker development for MDD, which could aid in reducing both patients' burden and open novel avenues toward a better understanding of MDD neurobiology.

Untargeted Plasma Metabolomic Profiling in Patients with Major Depressive Disorder Using Ultra-High Performance Liquid Chromatography Coupled with Mass Spectrometry.

Major depressive disorder (MDD) is a neuropsychiatric illness with an increasing incidence and a shortfall of efficient diagnostic tools. Interview-based diagnostic tools and clinical examination often lead to misdiagnosis and inefficient systematic treatment selection. Diagnostic and treatment monitoring biomarkers are warranted for MDD. Thus, the emerging field of metabolomics is a promising tool capable of portraying the metabolic repertoire of biomolecules from biological samples in a minimally invasive fashion. Herein, we report an untargeted metabolomic profiling performed in plasma samples of 11 MDD patients, at baseline (MDD1) and at 12 weeks following antidepressant therapy with escitalopram (MDD2), and in 11 healthy controls (C), using ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-(ESI+)-MS). We found two putative metabolites ((phosphatidylserine PS (16:0/16:1) and phosphatidic acid PA (18:1/18:0)) as having statistically significant increased levels in plasma samples of MDD1 patients compared to healthy subjects. ROC analysis revealed an AUC value of 0.876 for PS (16:0/16:1), suggesting a potential diagnostic biomarker role. In addition, PS (18:3/20:4) was significantly decreased in MDD2 group compared to MDD1, with AUC value of 0.785.

Distribution of microRNAs associated with major depressive disorder among blood compartments.

OBJECTIVE: Major depressive disorder (MDD) is a recurrent disorder with an increasing incidence. Alterations in key signaling pathways of the nervous system, such as the Wnt and MAPK pathways, mediated through microRNAs (miRNAs) provide crucial information regarding the etiopathology of MDD. We aimed to analyze whether the heterogeneity of literature findings regarding differential expression of miRNAs in the blood could arise from their different distributions among blood compartments. METHODS: We performed a pilot study analyzing the differential expression of miR-26a, miR-494, miR-30c, miR-93, and miR-101 and investigated their levels in white blood cells, total plasma (TP), exosomes from plasma, and exosome depleted plasma (EDP) in patients with MDD before and after antidepressant treatment with escitalopram and in healthy controls. RESULTS: MiR-494 was more abundant in EDP, and miR-26a and miR-30c were predominantly more abundant in TP relative to other blood compartments. Moreover, miR-30c, miR-101, and miR-26a, were significantly downregulated in TP of patients with MDD compared with controls. After antidepressant treatment, only miR-494 was significantly differently expressed in EDP. CONCLUSIONS: This proof-of-principle study suggests that identifying the miRNA abundance in different blood compartments is crucial for biomarker development and could enrich the current knowledge regarding MDD pathophysiology.