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The differential diagnosis of erosive osteoarthritis of the hand (EHOA) and psoriatic arthritis (PsA) is challenging, especially considering the absence of specific diagnostic biomarkers. The aim of the present study was to evaluate whether a pattern of microRNAs (miRNAs) (miR-21, miR-140, miR-146a, miR-155, miR-181a, miR-223), pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-17a, IL-23a, and tumor necrosis factor (TNF)-α], and adipokines (adiponectin, chemerin, leptin, resistin, and visfatin) could help to differentiate EHOA from PsA. Fifty patients with EHOA, fifty patients with PsA, and fifty healthy subjects (HS) were studied. The gene expression of miRNAs and cytokines were evaluated by real-time PCR from peripheral blood mononuclear cells and serum levels of cytokines and adipokines were quantified by ELISA in PsA and EHOA patients and HS. Gene expression showed the significant up-regulation of the analyzed miRNAs in EHOA and PsA patients as compared to HS and higher miR-155 in EHOA vs. PsA patients. The expression levels of IL-1β and IL-6 did not show any significant differences between EHOA and PsA, while IL-17a and IL-23a were significantly up-regulated in PsA compared to EHOA. Circulating TNF-α levels were higher in EHOA compared to PsA, while PsA patients exhibited significantly elevated levels of IL-23a. The combination of miR-155 with C-reactive protein enhanced the ability to differentiate EHOA from PsA, further supporting the potential of miR-155 as a diagnostic biomarker.

Recent studies have revealed the critical role of several microRNAs (miRNAs) in energy homeostasis and metabolic processes and suggest that circulating miRNAs can be used as early predictors of weight loss in the design of precision nutrition. Thus, the aim of this study was to investigate circulating adiposity‐related miRNAs as biomarkers of the response to two specific weight loss dietary treatments. The expression of 86 miRNAs was investigated in plasma of 78 subjects with obesity randomized to two different diets [moderately high‐protein diet (n = 38) and low‐fat diet (n = 40)] and in 25 eutrophic controls (BMI ≤ 25 kg/m2). Bioinformatic analyses were performed to explore the target genes and biological pathways regulated by the dysregulated miRNAs. As results, 26 miRNAs were found differently expressed in eutrophic and volunteers with obesity. Moreover, 7 miRNAs (miR‐130a‐3p, miR‐142‐5p, miR‐144‐5p, miR‐15a‐5p, miR‐22‐3p, miR‐221‐3p and miR‐29c‐3p) were differentially expressed between responders and non‐responders to a low‐fat diet. Furthermore, after adjustment for basal glucose levels, 1‐SD increase in miR‐22‐3p expression was associated with reduction in the risk of non‐response to low‐fat diet [OR = 0.181, 95% CI (0.084‐0.947), P = .043]. Bioinformatic analyses evidenced that these 7 miRNAs regulate the expression of genes participating in important metabolic pathways. Conclusively, 7 circulating miRNAs related to adiposity could be used for predicting the response to a low‐fat diet intervention prescribed to lose weight.

MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 (n = 50) 300 mg or αTF (n = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis.

Transient ischemic attack (TIA) refers to a momentary neurologic deficit caused by focal cerebral, spinal or retinal ischemic insult. TIA is associated with a high risk of impending acute ischemic stroke (AIS), a neurologic dysfunction characterized by focal cerebral, spinal or retinal infarction. Understanding the differences in molecular pathways in AIS and TIA has merit for deciphering the underlying cause for neuronal deficits with long-term effects and high risks of morbidity and mortality. In this study, we performed comprehensive investigations into the circulating microRNA (miRNA) profiles of AIS (n = 191) and TIA (n = 61) patients. We performed RNA-Seq on serum samples collected within 24 hrs of clinical diagnosis and randomly divided the study populations into discovery and validation cohorts. We identified a panel of 11 differentially regulated miRNAs at FDR < 0.05. Hsa-miR-548c-5p, -20a-5p, -18a-5p, -484, -652-3p, -486-3p, -24-3p, -181a-5p and -222-3p were upregulated, while hsa-miR-500a-3p and -206 were downregulated in AIS patients compared to TIA patients. We also probed the previously validated gene targets of our identified miRNA panel to highlight the molecular pathways affected in AIS. Moreover, we developed a multivariate classifier with potential utilization as a discriminative biomarker for AIS and TIA patients. The underlying molecular pathways in AIS compared to TIA may be explored further in functional studies for therapeutic targeting in clinical translation.

The potential of extracellular circulating microRNAs (miRNAs) as non-invasive biomarkers of atrial fibrillation (AF) has been confirmed by a number of recent studies. However, the current data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and methodological differences. In this work, we attempted to fulfill the basic pre-analytical requirements provided for circulating miRNA studies for application to paroxysmal atrial fibrillation (PAF) research. We used quantitative PCR (qPCR) to determine the relative plasma levels of circulating miRNAs expressed in the heart or associated with atrial remodeling or fibrillation with reported altered plasma/serum levels in AF: miR-146a-5p, miR-150-5p, miR-19a-3p, miR-21-5p, miR-29b-3p, miR-320a-3p, miR-328-3p, miR-375-3p, and miR-409-3p. First, in a cohort of 90 adult outpatient clinic patients, we found that the plasma level of miR-320a-3p was elevated in PAF patients compared to healthy controls and hypertensive patients without AF. We further analyzed the impact of medication therapies on miRNA relative levels and found elevated miR-320a-3p levels in patients receiving angiotensin-converting-enzyme inhibitors (ACEI) therapy. Additionally, we found that miR-320a-3p, miR-21-5p, and miR-146a-5p plasma levels positively correlated with the CHA2DS2-Vasc score and were elevated in subjects with CHA2DS2-Vasc ≥ 2. Our results indicate that, amongst the analyzed miRNAs, miR-320a-3p may be considered as a potential PAF circulating plasma biomarker, leading to speculation as to whether this miRNA is a marker of platelet state change due to ACEI therapy.

Background Early diagnosis is critical to reduce the mortality caused by nasopharyngeal carcinoma (NPC). MicroRNAs (miRNAs) are dysregulated and play important roles in carcinogenesis. Therefore, this study aimed to identify diagnostically relevant circulating miRNA signatures in patients with NPC. Methods Total RNA was extracted from whole blood samples obtained from 120 patients with NPC, 30 patients with head-neck tumors (HNT), and 30 healthy subjects (HSs), and examined by using a custom microarray. The expression levels of four miRNAs identified by using the microarray were validated with quantitative real-time reverse transcription polymerase chain reaction. The 120 patients with NPC and 30 HSs were randomly assigned to training group-1 and validation group-1, respectively. By using significance analysis of microarray (SAM), the specific miRNA expression profiles in whole blood from patients with NPC are obtained. By using lasso regression and adaptive boosting, a diagnostic signature was identified in training group-1, and its accuracy was verified in validation group-1. By using the same methods, another signature to distinguish patients with NPC from those with HNT and HSs was identified in training group-2 and confirmed in validation group-2. Results There were 117 differentially expressed miRNAs (upregulated and downregulated fold change ≥ 1.5) between the patients with NPC and HSs, among which an 8-miRNA signature was identified with 96.43% sensitivity and 100% specificity [area under the curve (AUC) = 0.995] to diagnose NPC in training group-1 and 86.11% sensitivity and 88.89% specificity (AUC = 0.941) in validation group-1. Compared with traditional Epstein–Barr virus (EBV) seromarkers, this signature was more specific for NPC. Furthermore, a 16-miRNA signature to differentiate NPC from HNT and HS (HNT-HS) was established from 164 differentially expressed miRNAs, which diagnosed NPC and HNT-HS with 100% accuracy (AUC = 1.000) in training group-2 and 87.04% (AUC = 0.924) in validation group-2. Conclusions The present study identified two miRNA signatures for the highly accurate diagnosis and differential diagnosis of patients with NPC from HSs and patients with HNT. The identified miRNAs might represent novel serological biomarkers and potential therapeutic targets for NPC.

Chemotherapy-induced peripheral neuropathy (CiPN) is a serious adverse effect in the clinic, but nonclinical assessment methods in animal studies are limited to labor intensive behavioral tests or semi-quantitative microscopic evaluation. Hence, microRNA (miRNA) biomarkers and automated in-life behavioral tracking were assessed for their utility as non-invasive methods. To address the lack of diagnostic biomarkers, we explored miR-124, miR-183 and miR-338 in a CiPN model induced by paclitaxel, a well-known neurotoxic agent. In addition, conventional and Vium's innovative Digital Vivarium technology-based in-life behavioral tests and postmortem microscopic examination of the dorsal root ganglion (DRG) and the sciatic nerve were performed. Terminal blood was collected on days 8 or 16, after 20 mg/kg paclitaxel was administered every other day for total of 4 or 7 doses, respectively, for plasma miRNA quantification by RT-qPCR. DRG and sciatic nerve samples were collected from mice sacrificed on day 16 for miRNA quantification. Among the three miRNAs analyzed, only miR-124 was statistically significantly increased (5 fold and 10 fold on day 8 and day 16, respectively). The increase in circulating miR-124 correlated with cold allodynia and axonal degeneration in both DRG and sciatic nerve. Automated home cage motion analysis revealed for the first time that nighttime motion was significantly decreased (P < 0.05) in paclitaxel-dosed animals. Although both increase in circulating miR-124 and decrease in nighttime motion are compelling, our results provide positive evidence warranting further testing using additional peripheral nerve toxicants and diverse experimental CiPN models.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in adults in developed countries. CVD encompasses many diseased states, including hypertension, coronary artery disease and atherosclerosis. Studies in animal models and human studies have elucidated the contribution of many genetic factors, including non-coding RNAs. Non-coding RNAs are RNAs not translated into protein, involved in gene expression regulation post-transcriptionally and implicated in CVD. Of these, circular RNAs (circRNAs) and microRNAs are relevant. CircRNAs are created by the back-splicing of pre-messenger RNA and have been underexplored as contributors to CVD. These circRNAs may also act as biomarkers of human disease, as they can be extracted from whole blood, plasma, saliva and seminal fluid. CircRNAs have recently been implicated in various disease processes, including hypertension and other cardiovascular disease. This review article will explore the promising and emerging roles of circRNAs as potential biomarkers and therapeutic targets in CVD, in particular hypertension.

miRNAs are small non-coding RNAs of about 18–25 nucleotides that negatively regulate gene expression at the post-transcriptional level. It was reported that a deregulation of their expression patterns correlates to the onset and progression of various diseases. Recently, these molecules have been identified in a great plethora of biological fluids, and have also been proposed as potential diagnostic and prognostic biomarkers. Actually, real time quantitative polymerase chain reaction is the most widely used approach for circulating miRNAs (c-miRNAs) expression profiling. Nevertheless, the debate on the choice of the most suitable endogenous reference genes for c-miRNAs expression levels normalization is still open. In this regard, numerous research groups are focusing their efforts upon identifying specific, highly stable, endogenous c-mRNAs. The aim of this review is to provide an overview on the reference genes currently used in the study of various pathologies, offering to researchers the opportunity to select the appropriate molecules for c-miRNA levels normalization, when their choosing is based upon literature data.

Background Sarcopenia frequently occurs in metastatic cancer patients. Emerging evidence has revealed that various secretory products from metastatic tumours can influence host organs and promote sarcopenia in patients with malignancies. Furthermore, the biological functions of microRNAs in cell‐to‐cell communication by incorporating into neighbouring or distal cells, which have been gradually elucidated in various diseases, including sarcopenia, have been elucidated. Methods We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using pre‐operative computed tomography imaging in 183 colorectal cancer (CRC) patients. miR‐203 expression levels in CRC tissues and pre‐operative serum were evaluated using quantitative polymerase chain reaction. Functional analysis of miR‐203 overexpression was investigated in human skeletal muscle cells (SkMCs), and cells were analysed for proliferation and apoptosis. Expressions of several putative miR‐203 target genes (CASP3, CASP10, BIRC5, BMI1, BIRC2, and BIRC3) in SKMCs were validated. Results A total of 183 patients (108 men and 75 women) were included. The median age of enrolled patients at diagnosis was 68.0 years (range 35–89 years). High IMAC status significantly correlated with female gender (P = 0.004) and older age (P = 0.0003); however, no other clinicopathological factors correlated with IMAC status in CRC patients. In contrast, decreased PMI significantly correlated with female gender (P = 0.006) and all well‐established disease development factors, including advanced T stage (P = 0.035), presence of venous invasion (P = 0.034), lymphovascular invasion (P = 0.012), lymph node (P = 0.001), distant metastasis (P = 0.002), and advanced Union for International Cancer Control tumour–node–metastasis stage classification (P = 0.0004). Although both high IMAC status and low PMI status significantly correlated with poor overall survival (IMAC: P = 0.0002; PMI: P < 0.0001; log‐rank test) and disease‐free survival (IMAC: P = 0.0003; PMI: P = 0.0002; log‐rank test), multivariate Cox's regression analysis revealed that low PMI was an independent prognostic factor for both overall survival (hazard ratio: 4.69, 95% confidence interval (CI): 2.19–10, P = 0.0001) and disease‐free survival (hazard ratio: 2.33, 95% CI: 1.14–4.77, P = 0.021) in CRC patients. Serum miR‐203 expression negatively correlated with pre‐operative PMI level (P = 0.0001, ρ = −0.25), and multivariate logistic regression analysis revealed that elevated serum miR‐203 was an independent risk factor for myopenia (low PMI) in CRC patients (odds ratio: 5.16, 95% CI: 1.8–14.8, P = 0.002). Overexpression of miR‐203 inhibited cell proliferation and induced apoptosis via down‐regulation of BIRC5 (survivin) expression in human SkMC line. Conclusions Assessment of serum miR‐203 expression could be used for risk assessment of myopenia, and miR‐203 might be a novel therapeutic target for inhibition of myopenia in CRC.