miRNA Expression In Blood Research Articles

Investigating the altered expression of miR-486-5p and miR-novel-chr1_40444 in dysglycemia in a South African population.

This study aims to investigate miR-486-5p and miR-novel-chr1_40444 expressions in dysglycemic individuals. Validating RNA-sequencing findings in a larger sample via reverse transcription qPCR (RT-qPCR), we aim to address global diagnostic and screening limitations, using an African cohort as an example. This cross-sectional study involved 1,271 individuals [normoglycemic (n = 974), prediabetic (n = 206), screen-detected type 2 diabetes (n = 91)] from the ongoing Vascular and Metabolic Health (VMH) study in Cape Town, South Africa. Whole blood miRNA expression was assessed using TaqMan-based RT-qPCR, with data normalized to an endogenous control (miR-16-5p). Significant underexpression was observed in prediabetes vs normoglycemia for miR-486-5p (P = 0.038), whilst both miRNAs demonstrated significant upregulation in screen-detected type 2 diabetes vs normoglycemia (miR-486-5p, P = 0.009; miR-novel-chr1_40444, P < 0.001), and screen-detected type 2 diabetes in comparison with prediabetes (miR-486-5p, P < 0.001; miR-novel-chr1_40444, P < 0.001). Multivariable regression analyses revealed pronounced interrelations between miR-novel-chr1_40444 and screen-detected type 2 diabetes in unadjusted and adjusted models (Model 1: P < 0.001, Model 2: P < 0.001, Model 3: P = 0.030). Moreover, receiver operating characteristic (ROC) curves revealed significantly enhanced diagnostic capabilities for screen-detected type 2 diabetes vs either normoglycemia (AUC = 0.971, P < 0.001), non-diabetes (AUC = 0.959, P < 0.001), or prediabetes (AUC = 0.902, P < 0.001) when combining the miRNAs with 2 h postprandial glucose. This study demonstrated the enhanced power of incorporating miRNAs with traditional markers in distinguishing screen-detected type 2 diabetes, warranting further investigations on their unique role in the development of type 2 diabetes.

Inflammatory Changes after Medical Suppression of Suspected Endometriosis for Implantation Failure: Preliminary Results.

Unexplained euploid embryo transfer failure (UEETF) is a frustrating and unanswered conundrum accounting for 30 to 50% of failures in in vitro fertilization using preimplantation genetic testing for aneuploidy (PGT-A). Endometriosis is thought by many to account for most of such losses and menstrual suppression or surgery prior to the next transfer has been reported to be beneficial. In this study, we performed endometrial biopsy in a subset of women with UEETF, testing for the oncogene BCL6 and the histone deacetylase SIRT1. We compared 205 PGT-A cycles outcomes and provide those results following treatment with GnRH agonist versus controls (no treatment). Based on these and previous promising results, we next performed a pilot randomized controlled trial comparing the orally active GnRH antagonist, elagolix, to oral contraceptive pill (OCP) suppression for 2 months before the next euploid embryo transfer, and monitored inflammation and miRNA expression in blood, before and after treatment. These studies support a role for endometriosis in UEETF and suggest that medical suppression of suspected disease with GnRH antagonist prior to the next transfer could improve success rates and address underlying inflammatory and epigenetic changes associated with UEETF.

Peripheral Blood miRNA Expression in Patients with Essential Hypertension in the Han Chinese Population in Hefei, China.

Primary hypertension is a significant risk factor for cardiovascular diseases. However, the pathogenesis of primary hypertension involves multiple biological processes, including the nervous system, circulatory system, endocrine system, and more. Despite extensive research, there is no clear understanding of the regulatory mechanism underlying its pathogenesis. In recent years, miRNAs have gained attention as a regulatory factor capable of modulating the expression of related molecules through gene silencing. Therefore, exploring differentially expressed miRNAs in patients with essential hypertension (EH) may offer a novel approach for future diagnosis and treatment of EH. This study included a total of twenty Han Chinese population samples from Hefei, China. The samples consisted of 10 healthy individuals and 10 patients with EH. Statistical analysis was conducted to analyze the general information of the two-sample groups. High-throughput sequencing and base identification were performed to obtain the original sequencing sequences. These sequences were then annotated using various databases including Rfam, cDNA sequences, species repetitive sequences library, and miRBase database. The number of miRNA species contained in the samples was measured. Next, TPM values were calculated to determine the expression level of each miRNA. The bioinformatics of the differentiated miRNAs were analyzed using the OECloud tool, and RPM values were calculated. Furthermore, the reliability of the expression was analyzed by calculating the area under the Roc curve using the OECloud tools. Statistical analysis revealed no significant differences between the two samples in terms of age distribution, gender composition, smoking history, and alcohol consumption history (P > 0.05). However, there was a notable presence of family genetic history and high BMI in the EH population (P < 0.05). The sequencing results identified a total of 245 miRNAs, out of which 16 miRNAs exhibited differential expression. Among the highly expressed miRNAs were let-7d-5p, miR-101-3p, miR-122-5p, miR-122b-3p, miR-192-5p, and miR-6722-3p. On the other hand, the lowly expressed miRNAs included miR-103a-3p, miR-16-5p, miR-181a-2-3p, miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-221-3p, miR-30d-5p, miR-342-5p, and miR-543. This study initially identified 16 miRNAs that are aberrantly expressed and function in various processes associated with the onset and progression of essential hypertension. These miRNAs have the potential to be targeted for future diagnosis and treatment of EH. However, further samples are required to provide additional support for this study.

MicroRNA classification and discovery for major depressive disorder diagnosis: Towards a robust and interpretable machine learning approach

BackgroundMajor depressive disorder (MDD) is notably underdiagnosed and undertreated due to its complex nature and subjective diagnostic methods. Biomarker identification would help provide a clearer understanding of MDD aetiology. Although machine learning (ML) has been implemented in previous studies to study the alteration of microRNA (miRNA) levels in MDD cases, clinical translation has not been feasible due to the lack of interpretability (i.e. too many miRNAs for consideration) and stability. MethodsThis study applied logistic regression (LR) model to the blood miRNA expression profile to differentiate patients with MDD (n = 60) from healthy controls (HCs, n = 60). Embedded (L1-regularised logistic regression) feature selector was utilised to extract clinically relevant miRNAs, and optimized for clinical application. ResultsPatients with MDD could be differentiated from HCs with the area under the receiver operating characteristic curve (AUC) of 0.81 on testing data when all available miRNAs were considered (which served as a benchmark). Our LR model selected miRNAs up to 5 (known as LR-5 model) emerged as the best model because it achieved a moderate classification ability (AUC = 0.75), relatively high interpretability (feature number = 5) and stability (ϕ̂Z=0.55) compared to the benchmark. The top-ranking miRNAs identified by our model have demonstrated associations with MDD pathways involving cytokine signalling in the immune system, the reelin signalling pathway, programmed cell death and cellular responses to stress. ConclusionThe LR-5 model, which is optimised based on ML design factors, may lead to a robust and clinically usable MDD diagnostic tool.

Phenome-wide association study on miRNA-related sequence variants: the UK Biobank

BackgroundGenetic variants in the coding region could directly affect the structure and expression levels of genes and proteins. However, the importance of variants in the non-coding region, such as microRNAs (miRNAs), remain to be elucidated. Genetic variants in miRNA-related sequences could affect their biogenesis or functionality and ultimately affect disease risk. Yet, their implications and pleiotropic effects on many clinical conditions remain unknown.MethodsHere, we utilised genotyping and hospital records data in the UK Biobank (N = 423,419) to investigate associations between 346 genetic variants in miRNA-related sequences and a wide range of clinical diagnoses through phenome-wide association studies. Further, we tested whether changes in blood miRNA expression levels could affect disease risk through colocalisation and Mendelian randomisation analysis.ResultsWe identified 122 associations for six variants in the seed region of miRNAs, nine variants in the mature region of miRNAs, and 27 variants in the precursor miRNAs. These included associations with hypertension, dyslipidaemia, immune-related disorders, and others. Nineteen miRNAs were associated with multiple diagnoses, with six of them associated with multiple disease categories. The strongest association was reported between rs4285314 in the precursor of miR-3135b and celiac disease risk (odds ratio (OR) per effect allele increase = 0.37, P = 1.8 × 10–162). Colocalisation and Mendelian randomisation analysis highlighted potential causal role of miR-6891-3p in dyslipidaemia.ConclusionsOur study demonstrates the pleiotropic effect of miRNAs and offers insights to their possible clinical importance.

Expression of Circulating MicroRNAs Associated with Obesity and their Relationships with Biochemical Parameters and Health-related Physical Fitness in Children 6 to 10 Years Old in Cali, Colombia.

Obesity is a public health problem worldwide; it has reached pandemic proportions in the last 40 years. Its prevalence in children and adolescents increased from 0.7% to 7.8% between 1975 and 2016. Recently, microRNAs (miRNAs) have been reported as regulatory factors related to molecular functions under different conditions. These can be used as biomarkers of a disease to estimate risks in the early stages. This study aimed to determine the expression levels of miRNAs associated with childhood obesity and their relationships with biochemical parameters and Health-related Physical Fitness (HRPF). This was a descriptive cross-sectional study in which a population of 40 children between 6 and 10 years of age of both sexes from Cali, Colombia, was evaluated; the children were classified as 20 normal-weight and 20 obese. Blood biochemistry, HRPF, and miRNA expression levels were determined (hsa-miR-122-5p, hsa-miR-15b-5p, hsa-miR-191-5p, hsa-miR-486-3p, hsa-miR-222-3p. Comparisons were made between the groups, miRNA associations between the studied variables, and linear regression analysis. Twenty normal-weight and 20 obese patients were evaluated. Both groups had an average age of eight years old. The miRNA hsa-miR-122-5p (p < 0.05) was overexpressed in the obese group. According to the linear regression analysis, the amount of adipose tissue may be associated with the production of miRNAs (hsa-miR-15b-5p, hsa-miR-222-3p, hsa-miR-122-5p, and hsamiR- 191-5p). Four miRNAs (hsa-miR-15b-5p, hsa-miR-222-3p, hsa-miR-122-5p, and hsa-miR- 191-5p) are associated with modifications in biochemical variables of HRPF in this group. Adipose tissue mass could be associated with the production of these miRNAs, thus making them biomarkers of childhood obesity risk.

Establishment of a schizophrenia classifier based on peripheral blood signatures and investigation of pathogenic miRNA-mRNA regulation

To date, the diagnosis of schizophrenia (SCZ) mainly relies on patients' or guardians' self-reports and clinical observation, and the pathogenesis of SCZ remains elusive. In this study, we sought to develop a reliable classifier for diagnosing SCZ patients and provide clues to the etiology and pathogenesis of SCZ. Based on the high throughput sequencing analysis of peripheral blood miRNA expression profile and weighted gene co-expression network analysis (WGCNA) in our previous study, we selected eleven hub miRNAs for validation by qRT-PCR in 51 SCZ patients and 51 controls. miR-939-5p, miR-4732-3p let-7d-3p, and miR-142-3p were confirmed to be significantly up-regulated, and miR-30e-3p and miR-23a-3p were down-regulated in SCZ patients. miR-30e-3p with the most considerable fold change and statistically significance was selected for targeting validation. We first performed bioinformatics prediction followed by qRT-PCR and verified the up-regulation of potential target mRNAs (ABI1, NMT1, HMGB1) expression. Next, we found that the expression level of ABI1 was significantly up-regulated in SH-SY5Y cells transfected with miR-30e-3p mimics. Lastly, we conducted a luciferase assay in 293T cells confirming that miR-30e-3p could directly bind with the 3′untranslated region (3′-UTR) of ABI1, revealing that miR-30e-3p might play a role in the polymerization of neuronal actin and the reconstruction of the cytoskeleton via the downstream regulation of ABI1. In addition, we constructed a classifier by a series of bioinformatics algorithms and evaluated its diagnostic performance. It appears that the classifier consists of miRNAs and mRNAs possess a better discrimination performance than individual miRNA or mRNA in SCZ.

Integrated Tissue and Blood miRNA Expression Profiles Identify Novel Biomarkers for Accurate Non-Invasive Diagnosis of Breast Cancer: Preliminary Results and Future Clinical Implications.

We aimed to identify miRNAs that were closely related to breast cancer (BRCA). By integrating several methods including significance analysis of microarrays, fold change, Pearson's correlation analysis, t test, and receiver operating characteristic analysis, we developed a decision-tree-based scoring algorithm, called Optimized Scoring Mechanism for Primary Synergy MicroRNAs (O-PSM). Five synergy miRNAs (hsa-miR-139-5p, hsa-miR-331-3p, hsa-miR-342-5p, hsa-miR-486-5p, and hsa-miR-654-3p) were identified using O-PSM, which were used to distinguish normal samples from pathological ones, and showed good results in blood data and in multiple sets of tissue data. These five miRNAs showed accurate categorization efficiency in BRCA typing and staging and had better categorization efficiency than experimentally verified miRNAs. In the Protein-Protein Interaction (PPI) network, the target genes of hsa-miR-342-5p have the most regulatory relationships, which regulate carcinogenesis proliferation and metastasis by regulating Glycosaminoglycan biosynthesis and the Rap1 signaling pathway. Moreover, hsa-miR-342-5p showed potential clinical application in survival analysis. We also used O-PSM to generate an R package uploaded on github (SuFei-lab/OPSM accessed on 22 October 2021). We believe that miRNAs included in O-PSM could have clinical implications for diagnosis, prognostic stratification and treatment of BRCA, proposing potential significant biomarkers that could be utilized to design personalized treatment plans in BRCA patients in the future.

Prenatal exposure to outdoor air pollution and miRNA expression in cord blood at birth: the NELA study

Prenatal exposure to outdoor air pollution and miRNA expression in cord blood at birth: the NELA study

Exosome miRNA Expression in Umbilical Cord Blood of High-Parity Sows Regulates Their Reproductive Potential.

Simple SummaryIncreasing female reproductive efficiency, including the litter size and weight of piglets, is one of the biggest challenges in the swine industry. During the gestation period, the umbilical cord facilitates placenta–fetal communication; thus, it plays an indispensable role in intrauterine embryonic development and fitness. Herein, we analyzed the molecular mechanism in declining reproductive potential in high-parity sows by assessing the changes in the umbilical cord blood. Firstly, the best reproductive performance was at parity 3–7, gradually decreasing after parity 8 and angiogenesis was repressed in high-parity sows. Moreover, exosomes derived from multiparous sows exhibited pro-angiogenesis properties but were diminished in exosomes derived from high-parity sows. Additionally, the angiogenesis of sows was significantly decreased, increasing the risk of disease with the increase in parity, greatly limiting the reproductive potential of the sows. At the same time, miR-188-5p expression may play an important role in regulating the lifespan and reproductive potential of sows. These findings demonstrated that miRNAs in umbilical cord blood exosomes play a central role in intrauterine development and suggested novel insights on reproductive potential, which provide a reference for increasing the sow reproductive efficiency.The objective of modern pig breeding is to improve the genetic reproduction performance potential of sows, including the litter size and weight of piglets. During the gestation period, the umbilical cord facilitates placenta–fetal communication; thus, it plays an indispensable role in intrauterine embryonic development and fitness. Herein, we analyzed the molecular mechanism in declining reproductive potential in high-parity sows by assessing the changes in the umbilical cord blood. Firstly, we analyzed the reproductive characteristics data of sows, followed by histological analysis of the umbilical cord phenotype. Next, we evaluated the effect of umbilical cord blood exosomes (UCB-EXO) on angiogenesis. Finally, the miRNA expression in UCB-EXO from high-parity sows with poor reproductive performance (OS) and multiparous sows with excellent reproductive performance (MS) was assessed. Overall, the best reproductive performance was at parity 3–7, gradually decreasing after parity 8 and angiogenesis was repressed in OS. However, exosomes derived from MS (Exo-MS) exhibited pro-angiogenesis properties but were diminished in exosomes derived from OS (Exo-OS). Additionally, the angiogenesis of sows was significantly decreased, increasing the risk of disease with the increase in parity, greatly limiting the reproductive potential of the sows. At the same time, miR-188-5p expression in Exo-OS was significantly higher than in Exo-MS (p < 0.01), implying that it may play an important role in regulating the lifespan and reproductive potential of sows. These findings demonstrated that miRNAs in UCB-EXO play a central role in intrauterine development. Further, the findings suggest novel insights on reproductive potential, which provide a reference for increasing the sow reproductive efficiency.

MicroRNA therapeutic targets in neonatal hypoxic-ischemic brain injury: a narrative review.

Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. Despite the use of therapeutic hypothermia, more than one in four survivors suffer from major developmental disabilities-an indication of the critical need for more effective therapies. MicroRNAs (miRNA) have the potential to act as biomarkers and/or therapeutic targets in neonatal HIBI as a step toward improving outcomes in this high-risk population. This review summarizes the current literature around the use of cord blood and postnatal circulating blood miRNA expression for diagnosis or prognosis in human infants with hypoxic-ischemic encephalopathy, as well as animal studies assessing endogenous brain miRNA expression and potential for therapeutic targeting of miRNA expression for neuroprotection. Ultimately, the lack of knowledge regarding brain specificity of circulating miRNAs and the temporal variability in expression currently limit the use of miRNAs as biomarkers. However, given their broad effect profile, ease of administration, and small size allowing for effective blood-brain barrier crossing, miRNAs represent promising therapeutic targets for improving brain injury and reducing developmental impairments in neonates after HIBI. IMPACT: The high morbidity and mortality of neonatal hypoxic-ischemic brain injury (HIBI) despite current therapies demonstrates a need for developing more sensitive biomarkers and superior therapeutic options. MicroRNAs have been evaluated both as biomarkers and therapeutic options after neonatal HIBI. The limited knowledge regarding brain specificity of circulating microRNAs and temporal variability in expression currently limit the use of microRNAs as biomarkers. Future studies comparing the neuroprotective effects of modulating microRNA expression must consider temporal changes in the endogenous expression to determine appropriate timing of therapy, while also optimizing techniques for delivery.

The potential of three whole blood microRNAs to predict outcome and monitor treatment response in sarcoid-bearing equids

MicroRNAs (miRNAs) have been proposed as biomarkers for equine sarcoid (ES) disease. In this study, the suitability of three whole blood miRNAs to diagnose ES and to predict and monitor the outcome of therapy was explored. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), expression levels of eca-miR-127, eca-miR-379, and eca-miR-432 in whole blood of ES-affected equids before and at least one year after therapy were compared to those of unaffected control equids. Associations of age, sex, species, diagnosis, and therapy outcome with miRNA expression levels were examined using general linear models. In total, 48 ES-affected equids and 47 control equids were recruited. From the affected animals, 31 responded favorably to treatment, and 17 demonstrated a failure of therapy. None of the tested miRNAs were influenced by age. Male equids showed increased expression of eca-miR-127 compared to females and horses showed higher expression levels of eca-miR-379 and eca-miR-432 than donkeys. Eca-miR-127 was confirmed as a diagnostic discriminator between ES-affected and control equids. No difference in miRNA profiles before therapy was found when comparing ES-affected equids with success vs. failure of therapy. Eca-miR-379 and eca-miR-432 decreased over time in horses where therapy was successful, but not in those cases where it failed. Biological variables influence equine whole blood miRNA expression, which may complicate biomarker validation. While none of the tested miRNAs could predict the response to therapy in ES-affected equids and eca-miR-127 showed poor diagnostic accuracy for ES, eca-miR-379 and eca-miR-432 miRNAs might allow refinement of monitoring of success of ES therapy.

Ultrasensitive Detection of Ribonucleic Acid Biomarkers Using Portable Sensing Platforms Based on Organic Electrochemical Transistors.

The analysis of ribonucleic acid (RNA) plays an important role in the early diagnosis of diseases and will greatly benefit patients with a higher cure rate. However, the low abundance of RNA in physiological environments requires ultrahigh sensitivity of a detection technology. Here, we construct a portable and smart-phone-controlled biosensing platform based on disposable organic electrochemical transistors for ultrasensitive analysis of microRNA (miRNA) biomarkers within 1 h. Due to their inherent amplification function, the devices can detect miRNA cancer biomarkers from little-volume solutions with concentrations down to 10-14 M. The devices can distinguish blood miRNA expression levels at different cancer stages using a 4T1 mouse tumor model. The technique for ultrasensitive and fast detection of RNA biomarkers with high selectivity opens a window for mobile diagnosis of various diseases with low cost.

Nitric oxide-related gene and microRNA expression in peripheral blood in pregnancy vary by self-reported race

ABSTRACT Adverse pregnancy outcomes disproportionately affect non-Hispanic (NH) Black patients in the United States. Structural racism has been associated with increased psychosocial distress and inflammation and may trigger oxidative stress. Thus, the nitric oxide (NO) pathway (involved in the regulation of inflammation and oxidative stress) may partly explain the underlying disparities in obstetric outcomes. Cohort study of 154 pregnant patients with high-risk obstetric histories; n = 212 mRNAs and n = 108 microRNAs (miRNAs) in the NO pathway were evaluated in circulating white blood cells. NO pathway mRNA and miRNA transcript counts were compared by self-reported race; NH Black patients were compared with women of other races/ethnicities. Finally, miRNA-mRNA expression levels were correlated. Twenty-two genes (q < 0.10) were differentially expressed in self-identified NH Black individuals. Superoxide dismutase 1 (SOD1), interleukin-8 (IL-8), dynein light chain LC8-type 1 (DYNLL1), glutathione peroxidase 4 (GPX4), and glutathione peroxidase 1 (GPX1) were the five most differentially expressed genes among NH Black patients compared to other patients. There were 63 significantly correlated miRNA-mRNA pairs (q < 0.10) demonstrating potential miRNA regulation of associated target mRNA expression. Ten miRNAs that were identified as members of significant miRNA-mRNA pairs were also differentially expressed among NH Black patients (q < 0.10). These findings support an association between NO pathway and inflammation and infection-related mRNA and miRNA expression in blood drawn during pregnancy and patient race/ethnicity. These findings may reflect key differences in the biology of inflammatory gene dysregulation that occurs in response to the stress of systemic racism and that underlies disparities in pregnancy outcomes.

Circulating miRNAs as Promising Biomarkers to Evaluate ECMO Treatment Responses in ARDS Patients

The use of extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) has increased in the last decade. However, mortality remains high, and the complexity of ECMO requires individualized treatment. There are some biomarkers to monitor progression and predict clinical outcomes of ARDS. This project aims to advance the management of ARDS patients treated with ECMO by exploring miRNA expression in whole blood. The analysis was conducted on two groups with different length of ECMO: Group A (longer runs) and group B (shorter runs). We analyzed miRNAs before ECMO cannulation, and at 7 and 14 days of ECMO support. Our results showed that in the group B patients, 11 deregulated miRNAs were identified, and showed an opposite trend of expression compared to the group A patients. In silico analysis revealed that these 11 miRNAs were related to processes involved in the pathogenesis and evolution of ARDS. This scenario could represent homeostatic mechanisms by which, in ECMO responsive patients, pathways activated during ARDS progression are switched-off. Circulating miRNAs could represent promising biomarkers to monitor the evolution of ARDS under ECMO support. Further studies may shed light on this topic to improve a personalized approach in such a complex setting of patients.

Evaluation of miRNA as Biomarkers of Emotional Valence in Pigs.

Simple SummaryIt is widely recognized that the assessment of animal welfare should include measures of positive emotional (affective) state. Existing behavioral and physiological indicators of a positive affective state frequently lack sensitivity, objectivity or are unsuitable in a production environment. Therefore, there is a need to develop new approaches to accurately and objectively measure a positive emotional state in animals, including novel molecular markers such a miRNA. These biomarkers must be measurable in the peripheral circulation and provide an accurate account of the physiological and molecular activity in regions of the brain associated with emotional processing. Further, such markers require validation against established behavioral and physiological indices. Here we investigated the efficacy of circulating miRNA as biomarkers of emotional state in the pig.The ability to assess the welfare of animals is dependent on our ability to accurately determine their emotional (affective) state, with particular emphasis being placed on the identification of positive emotions. The challenge remains that current physiological and behavioral indices are either unable to distinguish between positive and negative emotional states, or they are simply not suitable for a production environment. Therefore, the development of novel measures of animal emotion is a necessity. Here we investigated the efficacy of microRNA (miRNA) in the brain and blood as biomarkers of emotional state in the pig. Female Large White × Landrace pigs (n = 24) were selected at weaning and trained to perform a judgment bias test (JBT), before being exposed for 5 weeks to either enriched (n = 12) or barren housing (n = 12) conditions. Pigs were tested on the JBT once prior to treatment, and immediately following treatment. MiRNA and neurotransmitters were analyzed in blood and brain tissue after euthanasia. Treatment had no effect on the outcomes of the JBT. There was also no effect of treatment on miRNA expression in blood or the brain (FDR p > 0.05). However, pigs exposed to enriched housing had elevated dopamine within the striatum compared to pigs in barren housing (p = 0.02). The results imply that either (a) miRNAs are not likely to be valid biomarkers of a positive affective state, at least under the type of conditions employed in this study, or (b) that the study design used to modify affective state was not able to create differential affective states, and therefore establish the validity of miRNA as biomarkers.

Pharmacogenomic Effects of β-Blocker Use on Femoral Neck Bone Mineral Density.

ContextRecent studies have shown that β-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to nonusers, likely due to the suppression of adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects.ObjectiveTo investigate potential single-nucleotide variations (SNVs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy x-ray absorptiometry, and genetic data from the Framingham Heart Study’s (FHS) Offspring Cohort. We then sought to validate our top 4 genetic findings using data from the Rotterdam Study, the BPROOF Study, the Malta Osteoporosis Fracture Study (MOFS), and the Hertfordshire Cohort Study.MethodsWe used sex-stratified linear mixed models to determine SNVs that had a significant interaction effect with BB use on femoral neck (FN) BMD across 11 gene regions. We also evaluated the association of our top SNVs from the FHS with microRNA (miRNA) expression in blood and identified potential miRNA-mediated mechanisms by which these SNVs may affect FN BMD.ResultsOne variation (rs11124190 in HDAC4) was validated in females using data from the Rotterdam Study, while another (rs12414657 in ADRB1) was validated in females using data from the MOFS. We performed an exploratory meta-analysis of all 5 studies for these variations, which further validated our findings.ConclusionThis analysis provides a starting point for investigating the pharmacogenomic effects of BB use on BMD measures.

Umbilical cord miRNAs to predict neonatal early onset sepsis.

ObjectiveTo determine if miRNA (miR) expression in umbilical cord blood and umbilical cord tissue differs between neonates with early onset sepsis (EOS) versus neonates without true infection.MethodsRetrospective case-control study design of human patients with EOS (n = 8), presumed sepsis (N = 12) and non-infected control patients (N = 21). Differential expression of >300 miRs was examined using the MIHS-3001ZE-miScript miRNA PCR Array Human miFinder 384HC. Expression levels of miRs were normalized using the global Ct mean of expressed miR and compared between groups. Data analysis was performed using GeneGlobe data analysis software. Ratios of over and under-expressed miRs were calculated and compared between groups using receiver operating characteristic (ROC) curves.ResultsBoth umbilical cord plasma and umbilical cord tissue revealed several miRs with differential expression with little overlap between the two specimen types. The most overexpressed miR in plasma of EOS patients was miR-211-5p and the most overexpressed in EOS cord tissue was miR-223-5p. ROC curves comparing the ratios of over and under-expressed miRs for EOS patients and controls resulted in an area under the curve of 0.787 for cord plasma (miR-211-5p/miR-142-3p) and 0.988 for umbilical cord tissue (miR-223-5p/miR-22-3p), indicating good discrimination.ConclusionsmiRs show differential expression in EOS versus non-infected controls and presumed sepsis. A ratio of over and under-expressed miRs can provide a potentially sensitive and specific diagnostic test for EOS.

Mid-pregnancy maternal blood nitric oxide-related gene and miRNA expression are associated with preterm birth.

Aim: The nitric oxide (NO) pathway modulates inflammation and may influence birth timing. Patients & methods: Case-control analysis of 136 pregnant women with RNA obtained <28weeks; n=212 mRNAs and n=108 miRNAs in the NO pathway were evaluated. NO-pathway mRNA and miRNA transcript counts in women delivering preterm versus at term were compared, miRNA-mRNA expression levels correlated and prediction models generated. Results: Fourteen genes were differentially expressed in women delivering <37weeks; 13/14 were also differentially expressed in those delivering <34weeks (q<0.10) versus term births. Multiple miRNA-mRNA pairs were correlated. Models with gene expression better predicted prematurity than models with only clinical or nongenomic predictors. Conclusion: Maternal blood NO pathway-related mRNA and miRNA expression is associated with prematurity.

Longitudinal evaluation of whole blood miRNA expression in firefighters

BackgroundDysregulated microRNA (miRNA) expression could provide a mechanism linking firefighter exposure to increased cancer risk.ObjectiveTo determine if changes in longitudinal miRNA expression in firefighters are associated with occupational exposures.MethodsWhole blood MiRNA was evaluated in 52 new recruits prior to live-fire training and 20–37 months later. Linear mixed effects models adjusted for age, ethnicity, BMI, and batch effects were used to determine associations separately for all fires and structure fires only between employment duration, cumulative fire-hours and fire-runs, and time since most recent fire with (1) nine a priori and (2) the full array of 799 miRNAs.ResultsFor multivariable models including all fires, two a priori miRNAs were associated with employment duration and four with time since most recent fire. For multivariable models restricted to structure fires, three a priori miRNAs were associated with employment duration and one with fire-runs. Additional miRNAs from the full array were associated with employment duration for all fires and/or structure fires. In general, tumor suppressive miRNAs decreased and oncogenic miRNAs increased with exposure.SignificanceChanges in miRNAs may serve as biomarkers of exposure effects and a mechanism for increased cancer risk in firefighters.