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BackgroundThe molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.ObjectivesTo assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.MethodsOur study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM2.5, O3, NO2, and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis.ResultsWe found 151 significant associations between levels of PM2.5, O3, NO2, and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O3, long-term exposure to PM2.5, and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease.ConclusionOur results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warranted.

BackgroundWhile the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes.MethodsWe examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM2.5, NO2, O3, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses.ResultsWe found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease.ConclusionsAir pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.

BackgroundAging-related cognitive decline is an early symptom of Alzheimer's disease and other dementias, and on its own can have substantial consequences on an individual's ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. We leverage the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men.MethodsThis study includes data from up to 530 NAS participants (median age: 71.0 years) collected from 1996 to 2013, with a total of 1,331 person-visits (equal to 2,471 years of follow up). Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). Plasma miRNAs were profiled using small RNA sequencing. Associations of expression of 381 miRNAs with current cognitive function and rate of change in cognitive function were assessed using linear regression (N = 457) and linear mixed models (N = 530), respectively.ResultsIn adjusted models, levels of 2 plasma miRNAs were associated with higher MMSE scores (p < 0.05). Expression of 33 plasma miRNAs was associated with rate of change in MMSE scores over time (p < 0.05). Enriched KEGG pathways for miRNAs associated with concurrent MMSE and MMSE trajectory included Hippo signaling and extracellular matrix-receptor interactions. Gene targets of miRNAs associated with MMSE trajectory were additionally associated with prion diseases and fatty acid biosynthesis.ConclusionsCirculating miRNAs were associated with both cross-sectional cognitive function and rate of change in cognitive function among cognitively normal men. Further research is needed to elucidate the potential functions of these miRNAs in the CNS and investigate relationships with other neurological outcomes.

Simple Summary: Pasteurella multocida (Pm) infection can cause pasteurellosis in goats. Currently, the mechanisms of Pm infection in goats are limited. In this study, the effects of Pm infection to goats were characterized from the aspects of histopathology, miRNA and mRNA expression dynamics in lung of goats infected for 1, 2, 5 and 7 days and the clinical symptoms of animals. We further revealed the potential role of differentially expressed RNAs, which are commonly involved in and regulate the host immune reaction to the Pm infection. The differentially expressed genes were mapped to marker genes of the immune cells in the lung, which further confirmed the cells detected by the histopathological method. Pasteurella multocida (Pm) infection causes severe respiratory disease in goats. We investigated the effects of the Pm infection intratracheally on the histopathology, miRNA and mRNA expression dynamics in the lung of goats infected for 1, 2, 5 and 7 days. Pm infection caused fever, which significantly (p < 0.05) increased the body temperature of the goats from day 1 to 5. Haemotoxylin–eosin staining of the infected lung tissue showed characteristics of suppurative pneumonia with inflammatory cells infiltration and the lung structure destruction. During the Pm infection of the goats, compared with the control group, there were 3080, 3508, 2716 and 2675 differentially expressed genes and 42, 69, 91 and 108 significantly expressed miRNAs (|log2Fold Change| > 1, p < 0.05) in the Pm_d1, Pm_d2, Pm_d5 and Pm_d7 groups, respectively. Five miRNAs and nine immune-related genes were selected for confirmation by reverse transcription–polymerase chain reaction. The results indicated that the expression patterns of the miRNAs and genes were consistent with those determined by next-generation sequencing. The differentially expressed genes were enriched in cytokine–cytokine receptor interaction, cell adhesion molecules, complement and coagulation cascades, tight junction and phagosome Kyoto Encyclopedia of Genes and Genomes pathways and cytokine production, leukocyte migration, myeloid leukocyte migration, cell periphery, plasma membrane, extracellular region part, extracellular region and other Gene Ontology terms. The differentially expressed genes were mapped to marker genes in human and mouse lung cells. The results showed the presence of some marker genes of the immune cells. Compared with the CK group, five miRNAs and 892 common genes were differentially expressed in the Pm_d1, Pm_d2, Pm_d5 and Pm_d7 groups. The target relationships between the common 5 miRNAs and 892 differentially expressed genes were explored and the miRNAs involved in the host immune reaction may act through the target genes. Our study characterized goats' reaction in the lung from histopathological and molecular changes upon Pm infection, which will provide valuable information for understanding the responses in goats during Pm infection. [ABSTRACT FROM AUTHOR]

Autophagy is a treatment target for many disorders, including cancer, and its specific role is becoming increasingly well known. In tumors, researchers pay attention to microribonucleic acids (miRNAs) with regulatory effects to develop more effective therapeutic drugs for autophagy and find new therapeutic targets. Various studies have shown that autophagy-related miRNAs play an irreplaceable role in different tumors, such as miR-495, miR-30, and miR-101. These miRNAs are associated with autophagy resistance in gastric cancer, non-small cell lung cancer, and cervical cancer. In recent years, autophagy-related miRNAs have also been reported to play a role in autophagy in urinary system tumors. This article reviews the regulatory effects of autophagy-related miRNAs in kidney, bladder, and prostate cancer and provides new ideas for targeted therapy of the three major tumors of the urinary system. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are inflammatory demyelinating diseases of the central nervous system. Exosomal microRNAs (miRNAs) are emerging biomarkers for demyelinating diseases. In this study, 52 aquaporin-4 antibody serum-positive NMOSD patients, 18 relapsing-remitting multiple sclerosis (RRMS) patients and 17 healthy controls (HCs) were included for the next-generation sequencing (NGS). To validate the NGS results, the valuable miRNAs were selected for validation by real-time quantitative polymerase chain reaction in another cohort of patients, comprising 31 NMOSD patients and 14 HCs. In addition, these miRNAs were also validated in a longitudinal study. NGS data revealed the exosomal miRNAs profile in NMOSD patients was different from HCs. Among those potential exosomal miRNAs which can distinguish NMOSD status, hsa-miR-122-3p and hsa-miR-200a-5p were the most abundant miRNAs. In addition, hsa-miR-122-3p and hsa-miR-200a-5p were significantly upregulated in the serum exosome of relapsing NMOSD compared with that in remitting NMOSD. Hsa-miR-122-3p and hsa-miR-200a-5p had positive correlations with disease severity in NMOSD patients. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the MAPK, Wnt and Ras signaling pathways were enriched. Further biological function analysis demonstrated that these two miRNAs might be involved in the immunoregulation of NMOSD pathogenesis. Our results indicated that miRNAs delivered by exosomes could be applied as potential biomarkers for NMOSD. [ABSTRACT FROM AUTHOR]

Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is associated with microRNA (miRNA) dysregulation. miRNA are key regulators in many physiological processes. It is thus of public health concern to understand the relationships between POPs and miRNA as related to health outcomes. This systematic review evaluated the relationship between widely recognized, intentionally manufactured, POPs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB]), with miRNA expression in both human and animal studies. We used PubMed and Embase to systematically search the literature up to September 29th, 2023. Search results for human and animal studies were included if they incorporated at least one POP of interest in relation to at least one miRNA. Data were synthesized to determine the direction and significance of associations between POPs and miRNA. We utilized ingenuity pathway analysis to review disease pathways for miRNA that were associated with POPs. Our search identified 38 eligible studies: 9 in humans and 29 in model organisms. PFAS were associated with decreased expression of miR-19, miR-193b, and miR-92b, as well as increased expression of miR-128, miR-199a-3p, and miR-26b across species. PCBs were associated with increased expression of miR-15a, miR-1537, miR-21, miR-22-3p, miR-223, miR-30b, and miR-34a, as well as decreased expression of miR-130a and let-7b in both humans and animals. Pathway analysis for POP-associated miRNA identified pathways related to carcinogenesis. This is the first systematic review of the association of POPs with miRNA in humans and model organisms. Large-scale prospective human studies are warranted to examine the role of miRNA as mediators between POPs and health outcomes. [ABSTRACT FROM AUTHOR]