Studying microRNAs in osteoarthritis: Critical overview of different analytical approaches

MicroRNAs are small non-coding RNA species with the ability to post-transcriptionally control the expression of multiple genes, that have gained substantial interest because of their expression alterations that accompanies aging and possible age-related pathologies. Given the constant rise in the number of patients suffering from age-related diseases –due to the increase of the aging population in the western world- the exploration of the role of specific microRNAs in the etiopathology of these diseases is expected to have great impact. Degenerative arthritis or osteoarthritis is of the most common age-related diseases and possible the one with the most limited therapeutic options. In this review therefore, we highlight recent advances considering the implication of microRNAs in processes known to contribute to the development of this disease. We also critically present the analytical approaches adopted so far, in an attempt to facilitate the acknowledgment of the necessary experimental tactic that will lead to the establishment of microRNAs as biomarkers and/or therapeutic agents for this age-related pathology. © 2018 Elsevier B.V

Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS)

Background: Pharmacogenomics describes the link between gene variations (polymorphisms) and drug responses. In view of the implementation of precision medicine in personalized healthcare, pharmacogenetic tests have recently been introduced in the clinical practice. However, the translational aspects of such tests have been limited due to the lack of robust population-based evidence. Materials: In this paper we present a novel pharmacogenetic panel (iDNA Genomics-PGx–CNS or PGx–CNS), consisting of 24 single nucleotide polymorphisms (SNPs) on 13 genes involved in the signaling or/and the metabolism of 28 approved drugs currently administered to treat diseases of the Central Nervous System (CNS). We have tested the PGx–CNS panel on 501 patient-derived DNA samples from a southeastern European population and applied biostatistical analyses on the pharmacogenetic associations involving drug selection, dosing and the risk of adverse drug events (ADEs). Results: Results reveal the occurrences of each SNP in the sample and a strong correlation with the European population. Nonlinear principal component analysis strongly indicates co-occurrences of certain variants. The metabolization efficiency (poor, intermediate, extensive, ultra-rapid) and the frequency of clinical useful pharmacogenetic, associations in the population (drug relevance), are also described, along with four exemplar clinical cases illustrating the strong potential of the PGx–CNS panel, as a companion diagnostic assay. It is noted that pharmacogenetic associations involving copy number variations (CNVs) or the HLA gene were not included in this analysis. Conclusions: Overall, results illustrate that the PGx–CNS panel is a valuable tool supporting therapeutic medical decisions, urging its broad clinical implementation. © 2021, The Author(s)

Perceptions of children and their parents about the pain experienced during their hospitalization and its impact on parents' quality of life

Objective: The aim of the study was to assess pain levels and perceptions concerning pain by both children and their parents during hospitalization, as well as the impact of that pain upon parents' quality of life.Methods: The sample of the study consisted of 92 pediatric cancer patients, 159 pediatric patients with musculoskeletal problems and one of their parents. The study was performed between November 2010 and May 2011. The Pediatric Pain Questionnaire (Parent Version) and the PedsQL-Family Impact Module were used for pain assessment and the quality of life by the parents. Young patients completed the pediatric version of the Pediatric Pain Questionnaire for the evaluation of pediatric pain. Pain was measured by using the Wong-Baker facial pain scale, included in both parent and child version of the Pediatric Pain Questionnaire. This rating scale is recommended for children 3 years and older.Results: Young patients reported higher acute pain scores than their parents (z = -2.5, P = 0.011; 99% confidence interval: 0.008-0.013). Young patients with orthopedic disorders had higher acute and chronic pain scores in comparison to their parents' reports (z = -3.4, P = 0.001; 99% confidence interval: 0.000-0.001 and z = -2.3, P = 0.021; 99% confidence interval: 0.017-0.025, respectively). Girls reported higher pain scores than boys (z = -2.0, P = 0.047; 99% CI: 0.041-0.052).Conclusions: Parental reports tended to underestimated children's pain, especially acute pain. The sex of children, the age and the marital status affect the perceptions of both children and their parents about pain. The parental quality of life is affected especially when the pain is caused by life-threatening diseases such as cancer. However, it improves as the treatment of their children is completed with no complications. © The Author 2016. Published by Oxford University Press. All rights reserved

Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n= 12) and healthy individuals (n= 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p< 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression. © 2017 The Author(s)

A pharmacogenetic study of ABCB1 polymorphisms and cyclosporine treatment response in patients with psoriasis in the Greek population

Psoriasis affects 2-3% of the population, causing significant morbidity and financial burden. Innmunosuppressive drugs such as cyclosporine are first line systemic therapies for moderate-to-severe forms. However, patients exhibit heterogeneity in their response to therapy, possibly due to genetic factors. The aim of the present study was to assess the ABCB1 T-129C, G1199A, C1236T, G2677T and C3435T single-nucleotide polymorphisms (SNPs) as candidate predictive markers of response to cyclosporine treatment in 84 psoriasis patients. 62% of the patients were defined as responders and 38% as nonresponders. All SNPs complied with Hardy-Weinberg equilibrium. SNP and haplotype analyses were performed to access responsiveness to treatment. Association analysis revealed statistically significant association of SNP 3435T with negative response (P=0.0075), a result that was further validated in haplotype analysis. This study is the first in the field of the pharmacogenetics of cyclosporine in psoriasis whose results merit further exploitation in larger independent cohorts

Additional file 1: of Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes

ROC analysis of miRNA expression values for OA and control serum samples. (DOCX 18 kb

Additional file 2: of Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes

Pathway enrichment analysis for target genes of hsa-miR-33b-3p, hsa-miR-140-3p and hsa-miR-671-3p using DAVID database (p < 0.05). (XLSX 29 kb