Tensor decomposition of multi-dimensional splicing events across multiple tissues to identify splicing-mediated risk genes associated with complex traits.

Identifying risk genes associated with complex traits remains challenging. Integrating gene expression data with Genome-Wide Association Study (GWAS) through Transcriptome-Wide Association Study (TWAS) methods has discovered candidate risk genes for various complex traits. Splicing, which explains a comparable heritability of complex traits as gene expression, is under-explored due to its multidimensionality.

Serum microRNA expression quantitative trait loci in children with asthma colocalize with asthma-related GWAS results.

Asthma poses a significant public health burden. Despite identifying more than a hundred genetic risk loci in genome-wide association studies (GWAS), the underlying functional mechanisms remain poorly understood. Studying omics, especially microRNAs (miRNAs), is a promising approach to facilitate our understanding of the biological pathways of asthma.

Toxicity and risk assessment of landfill leachate on the earthworm, Eisenia fetida.

Landfill leachates have complex cocktails of metals, pesticides and polycyclic aromatic hydrocarbons (PAHs), posing significant yet often overlooked ecological risks through mixture toxicity. This study unveils how seasonal monsoon dynamics amplify leachate contaminant levels from the Dubagga landfill site, Lucknow (India), triggering cascading physiological and molecular disruptions in the earthworm, Eisenia fetida, upon acute and chronic exposures. Post-monsoon leachate contained 1841 μg L PAHs, 196 μg L pesticides and 10,710 μg L metal - a 150-fold increase in chemical diversity compared to pre-monsoon samples.

Advanced glycation end products are biomolecular biomarkers for proliferative diabetic retinopathy.

The present study examines the role of advanced glycation end products (AGEs) as biomolecular biomarkers for proliferative diabetic retinopathy (PDR). A cross-sectional study with a total of 80 consecutive cases of type 2 diabetes mellitus (DM) was divided into no retinopathy (NoDR) ( n = 20), non-proliferative diabetic retinopathy (NPDR) ( n = 20), PDR ( n = 20), and controls ( n = 20). AGEs were assessed by assay of N-carboxymethyl-lysine (Nε-CML).

A Genetics-guided Integrative Framework for Drug Repurposing: Identifying Anti-hypertensive Drug Telmisartan for Type 2 Diabetes.

Drug development is a long and costly process, and repurposing existing drugs for use toward a different disease or condition may serve as a cost-effective alternative. As drug targets with genetic support have a doubled success rate, genetics-informed drug repurposing holds promise in translating genetic findings into therapeutics. In this study, we developed a Genetics Informed Network-based Drug Repurposing via in silico Perturbation (GIN-DRIP) framework and applied the framework to repurpose drugs for type-2 diabetes (T2D).

Peripheral blood miRNAs are associated with airflow below threshold in children with asthma.

Background: MicroRNAs (miRNAs) are crucial post-transcriptional regulators involved in inflammatory diseases, such as asthma. Poor lung function and airflow issues in childhood are linked to the development of chronic obstructive pulmonary disease (COPD) in adulthood.

Methods: We analyzed small RNA-Seq data from 365 peripheral whole blood samples from the Genetics of Asthma in Costa Rica Study (GACRS) for association with airflow levels measured by FEV1/FVC.

Bioremediation of polyaromatic hydrocarbon polluted sewage sludge soil employing a bacterial consortium and phytotoxicity evaluation.

A consortium of five distinct bacterial strains was evaluated for their ability to biodegrade multiple polyaromatic hydrocarbons (PAHs) in sewage sludge under microcosm studies. The presence of PAHs was determined from the sludge samples collected during pre- and post-monsoon seasons from three different wastewater treatment plants (WWTPs). Among the 16 PAHs found, the lowest concentration detected was 1.

Toxicity assessment of wastewater treatment plant sludge using .

Globally, sewage sludge is produced in large quantities as a by-product in wastewater treatment plants (WWTPs), which have organic and inorganic contaminants. Due to its high caloric value, this sludge is used as manure in agricultural fields. For this, regular sludge monitoring is necessary to understand the potential risks and limit the release of toxic substances into the environment.

Circulating microRNAs associated with bronchodilator response in childhood asthma.

Background: Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.

MiR-107 and Its Association With House Dust Mite Sensitisation: Implications for Asthma.

Introduction: MicroRNAs (miRNAs) have been linked to allergic diseases but their effects on sensitisation to allergens in individuals with asthma are unknown. We aimed to identify miRNAs associated with house dust mite (HDM) sensitisation in childhood asthma.

Methods: Serum samples from 1126 children with asthma who participated in the Genetics of Asthma in Costa Rica Study (GACRS) were profiled for 304 miRNAs.

Circulating miRNAs associate with historical childhood asthma hospitalization in different serum vitamin D groups.

Background: Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels.

Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma.

Background: Lung function trajectories (LFTs) have been shown to be an important measure of long-term health in asthma. While there is a growing body of metabolomic studies on asthma status and other phenotypes, there are no prospective studies of the relationship between metabolomics and LFTs or their genomic determinants.

Methods: We utilized ordinal logistic regression to identify plasma metabolite principal components associated with four previously-published LFTs in children from the Childhood Asthma Management Program (CAMP) (n = 660).

Oral Release Kinetics, Biodistribution, and Excretion of Dopants from Barium-Containing Bioactive Glass in Rats.

: Inorganic biomaterials are biologically active and are used as implants and drug delivery system. They have therapeutically active elements present in their framework that are released in the physiological milieu. Release of these dopants above the supraphysiological limit may produce adverse effects and physicochemical interactions with the loaded drugs.

A novel piwi-interacting RNA associates with type 2-high asthma phenotypes.

Background: Piwi-interacting RNAs (piRNAs), comprising the largest noncoding RNA group, regulate transcriptional processes. Whether piRNAs are associated with type 2 (T2)-high asthma is unknown.

Objective: We sought to investigate the association between piRNAs and T2-high asthma in childhood asthma.

Polygenic risk scores identify heterogeneity in asthma and chronic obstructive pulmonary disease.

Background: Asthma and chronic obstructive pulmonary disease (COPD) have distinct and overlapping genetic and clinical features.

Objective: We sought to test the hypothesis that polygenic risk scores (PRSs) for asthma (PRS) and spirometry (FEV and FEV/forced vital capacity; PRS) would demonstrate differential associations with asthma, COPD, and asthma-COPD overlap (ACO).

Methods: We developed and tested 2 asthma PRSs and applied the higher performing PRS and a previously published PRS to research (Genetic Epidemiology of COPD study and Childhood Asthma Management Program, with spirometry) and electronic health record-based (Mass General Brigham Biobank and Genetic Epidemiology Research on Adult Health and Aging [GERA]) studies.

Circulating MicroRNAs associated with Bronchodilator Response in Childhood Asthma.

Rationale: Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.

Systems Genomics Reveals microRNA Regulation of ICS Response in Childhood Asthma.

Background: Asthmatic patients' responses to inhaled corticosteroids (ICS) are variable and difficult to quantify. We have previously defined a Cross-sectional Asthma STEroid Response (CASTER) measure of ICS response. MicroRNAs (miRNAs) have shown strong effects on asthma and inflammatory processes.

Recent miRNA Research in Asthma.

Purpose Of Review: The study of microRNA in asthma has revealed a vibrant new level of gene regulation underlying asthma pathology. Several miRNAs have been shown to be important in asthma, influencing various biological mechanisms which lead to asthma pathology and symptoms. In addition, miRNAs have been proposed as biomarkers of asthma affection status, asthma severity, and asthma treatment response.

Neuronal miR-29a protects from obesity in adult mice.

Objective: Obesity, a growing threat to the modern society, represents an imbalance of metabolic queues that normally signal to the arcuate hypothalamic nucleus, a critical brain region sensing and regulating energy homeostasis. This is achieved by various neurons many of which developmentally originate from the proopiomelanocortin (POMC)-expressing lineage. Within the mature neurons originating from this lineage, we aimed to identify non-coding genes in control of metabolic function in the adulthood.

Blood miRNAs Are Linked to Frequent Asthma Exacerbations in Childhood Asthma and Adult COPD.

MicroRNAs have been independently associated with asthma and COPD; however, it is unclear if microRNA associations will overlap when evaluating retrospective acute exacerbations. We hypothesized that peripheral blood microRNAs would be associated with retrospective acute asthma exacerbations in a pediatric asthma cohort and that such associations may also be relevant to acute COPD exacerbations. We conducted small-RNA sequencing on 374 whole-blood samples from children with asthma ages 6-14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS) and 450 current and former adult smokers with and without COPD who participated in the COPDGene study.

Seasonal Variation in miR-328-3p and let-7d-3p Are Associated With Seasonal Allergies and Asthma Symptoms in Children.

Objective: MicroRNAs (miRs) are small non-coding RNA molecules of around 18-22 nucleotides that are key regulators of many biologic processes, particularly inflammation. The purpose of this study was to determine the association of circulating miRs from asthmatic children with seasonal variation in allergic inflammation and asthma symptoms.

Methods: We used available small RNA sequencing on blood serum from 398 children with mild-to-moderate asthma from the Childhood Asthma Management Program.

Circulating MicroRNA: Incident Asthma Prediction and Vitamin D Effect Modification.

Of children with recurrent wheezing in early childhood, approximately half go on to develop asthma. MicroRNAs have been described as excellent non-invasive biomarkers due to their prognostic utility. We hypothesized that circulating microRNAs can predict incident asthma and that that prediction might be modified by vitamin D.

COPD-associated miR-145-5p is downregulated in early-decline FEV trajectories in childhood asthma.

Background: Many microRNAs (miRNAs) have been associated with asthma and chronic obstructive pulmonary disease (COPD). Longitudinal lung function growth trajectories of children with asthma-normal growth, reduced growth (RG), early decline (ED), and RG with an ED (RGED)-have been observed, with RG and RGED associated with adverse outcomes, including COPD.

Objective: Our aim was to determine whether circulating miRNAs from an early age in children with asthma would be prognostic of reduced lung function growth patterns over the next 16 years.

MicroRNAs are indispensable for the proliferation and differentiation of adult neural progenitor cells in mice.

More than two decades after the discovery of adult neurogenesis in humans, researchers still struggle to elucidate the underlying transcriptional and post-transcriptional mechanisms. RNA interference is a crucially important process in the central nervous system, and its role in adult neurogenesis is poorly understood. In this work, we address the role of Dicer-dependent microRNA biogenesis in neuronal differentiation of adult neural stem cells within the subventricular zone of the mouse brain.