Pathogenic Roles of MicroRNA in the Development of Asthma

Asthma is a common and chronic inflammatory disease. Pathogenic mechanism underlying asthma is complicated. The inflammatory reactions in asthma have been recognized to involve mast cells, eosinophils, lymphocytes (T cells, B cells), macrophages, and dendritic cells. MicroRNA (miRNA, miR) is a group of small noncoding RNAs with 21–25 nucleotides (nt) in length, which impact biologic responses through the regulation of mRNA transcription and/or translation. MicroRNAs are related to developmental processes of many immunologic diseases. Most studies showed that regulation of miRNAs to their targeting genes appears to play an important role in the development of asthma. This chapter has discussed altered expression of miRNAs in cells and tissues from patients with asthma, in order to better understand the mechanics of pathogenesis of asthma. In addition, the regulation of miRNAs as a novel therapeutic approach will require a deeper understanding of their function and mechanism of action

Ubiquitin-Proteasome-Collagen (CUP) Pathway in Preterm Premature Rupture of Fetal Membranes

Spontaneous preterm birth (sPTB) occurs before 37 gestational weeks, with preterm premature rupture of the membranes (PPROM) and spontaneous preterm labor (sPTL) as the predominant adverse outcomes. Previously, we identified altered expression of long non-coding RNAs (lncRNAs) and message RNAs (mRNAs) related to the ubiquitin proteasome system (UPS) in human placentas following pregnancy loss and PTB. We therefore hypothesized that similar mechanisms might underlie PPROM. In the current study, nine pairs of ubiquitin-proteasome-collagen (CUP) pathway–related mRNAs and associated lncRNAs were found to be differentially expressed in PPROM and sPTL. Pathway analysis showed that the functions of their protein products were inter-connected by ring finger protein. Twenty variants including five mutations were identified in CUP-related genes in sPTL samples. Copy number variations were found in COL19A1, COL28A1, COL5A1, and UBAP2 of sPTL samples. The results reinforced our previous findings and indicated the association of the CUP pathway with the development of sPTL and PPROM. This association was due not only to the genetic variation, but also to the epigenetic regulatory function of lncRNAs. Furthermore, the findings suggested that the loss of collagen content in PPROM could result from degradation and/or suppressed expression of collagens

MicroRNA 27b-3p Modulates SYK in Pediatric Asthma Induced by Dust Mites

The PI3K-AKT pathway is known to regulate cytokines in dust mite-induced pediatric asthma. However, the underlying molecular steps involved are not clear. In order to clarify further the molecular steps, this study investigated the expression of certain genes and the involvement of miRNAs in the PI3K-AKT pathway, which might affect the resultant cytokine-secretion. in-vivo and in-vitro ELISA, qRT-PCR and microarrays analyses were used in this study. A down-expression of miRNA-27b-3p in dust mite induced asthma group (group D) was found by microarray analysis. This was confirmed by qRT-PCR that found the miRNA-27b-3p transcripts that regulated the expression of SYK and EGFR were also significantly decreased (p < 0.01) in group D. The transcript levels of the SYK and PI3K genes were higher, while those of EGFR were lower in the former group. Meanwhile, we found significant differences in plasma concentrations of some cytokines between the dust mite-induced asthma subjects and the healthy controls. On the other hand, this correlated with the finding that the transcripts of SYK and its downstream PI3K were decreased in HBE transfected with miRNA-27b-3p, but were increased in HBE transfected with the inhibitor in vitro. Our results indicate that the differential expression of the miRNAs in dust mite-induced pediatric asthma may regulate their target gene SYK and may have an impact on the PI3K-AKT pathway associated with the production of cytokines. These findings should add new insight into the pathogenesis of pediatric asthma

Similarity of DMD gene deletion and duplication in the Chinese patients compared to global populations

© 2008 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Epigenetic Regulation of Th2 Response in Asthma by Non-Coding RNAs

Asthma is a common chronic inflammatory disease. Pathogenic mechanism underlying asthma is complex. The inflammatory response of asthma includes lymphocytes (T, B cells), ILC2, eosinophils and other types of immune and inflammatory cells. T CD4+ T helper 2 cells (Th2 cells) are thought to play a central role in regulating the phenotype of allergic asthma. Asthma is often closely associated with Th1/Th2 cell imbalance. Non-coding RNAs (ncRNAs) are non-protein coding RNA molecules in the transcriptome, mainly including microRNAs (miRNAs), long non-coding RNAs and circRNAs, etc., which are widely found in eukaryotic transcriptome and participate in the regulation of a variety of biological processes. ncRNAs are considered to function as modulators of the immune system. Their biological changes represent an important mechanism for the development of immune-mediated diseases. This chapter mainly discusses the epigenetic regulation of Th2 cells and their cytokines in asthma by non-coding RNAs. It helps us to better understand the pathogenesis of asthma and find potential asthma biomarkers

Reduced expression in preterm birth of sFLT-1 and PlGF with a high sFLT-1/PlGF ratio in extracellular vesicles suggests a potential biomarker

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases of preterm birth and 38 control cases. Our results showed that both sFLT-1 (P=0.0014) and PlGF (P=0.0032) were significantly downregulated in cases of preterm birth compared to controls, while the sFLT-1/PIGF ratio was significantly (P=0.0008) increased in EVs-EXs, but not in maternal plasma. Our results suggest that this reduced expression of sFLT-1 and PlGF with an elevated sFLT-1/PlGF ratio in EVs-EXs may represent a potential biomarker for prediction of PTB

Genetic Testing in Emerging Economies (GenTEE)

Drivers, barriers and opportunities for genetic testing services in emerging economies: the GenTEE (Genetic Testing in Emerging Economies) project Background: Due to the epidemiological transition in the emerging economies of China, East Asia, India, Latin America, the Middle East and South Africa, these economies are facing (i) an increasing proportion of morbidity and mortality due to congenital and genetic conditions, (ii) a rising need for genetic services to improve patient outcomes and overall population health. These economies are facing the challenge how: (i) to ensure the successful translation of genetic/genomics laboratory and academic research into quality assured pathways, (ii) to develop a service delivery infrastructure that leads to equitable and affordable access to high quality genetic/genomic testing services. Objectives: (i) to document and compare current practices and the state of genetic service provision in eight emerging economies: Argentina, Brazil, China, Egypt, India, Oman, Philippines and South Africa, (ii) to identify current knowledge gaps and unmet service needs. The GenTEE international project is intended to inform policy decisions for the challenges of delivering equitable high quality genetic services and to promote international collaboration for capacity building. Methods: (i) a standardized survey that is the first of its worldwide that allows comparison of services internationally across a number of key dimensions by using a core set of indicators, selected by the GenTEE consortium for their relevance and comparability, (ii) capacity building demonstration projects. To date, the GenTEE project has completed its survey that maps the current state of genetic services in the participating countries and identifies current drivers, barriers and opportunities for genetic services development. Results: There is no equitable access to genetic services in all countries mainly due to financial barriers (underfunded fragmented public services, out-of-pocket expenses tend to be the norm for genetic testing services), geographical barriers (concentration of services in main cities) and skill gaps, resulting in inequitable services or delayed access. The development of services in the private sector is opportunistic and mostly technology and market driven. There is a marked lack of standard operating procedures and agreed quality assessment processes for new technologies. Discussion: International collaborative networks can provide support for capacity building and help to strengthen the provision of quality genetic/genomic services in emerging economies.JRC.I.1-Chemical Assessment and Testin

Setting research priorities to improve global newborn health and prevent stillbirths by 2025.

BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. METHODS: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. RESULTS: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. CONCLUSION: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed