In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now ...defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology.
MicroRNAs (miRNAs) are small noncoding RNAs that suppress the abundance of partially complementary mRNAs and inhibit their translation. Each miRNA can regulate hundreds of mRNAs, sometimes strongly ...but often weakly, to mediate a diverse array of biological functions, including proliferation, cell signaling, differentiation, stress responses and DNA repair, cell adhesion and motility, inflammation, cell survival, senescence, and apoptosis, all intimately related to cancer initiation, treatment response, and metastasis. The expression and activity of miRNAs are spatially and temporally controlled. Global miRNA expression is reduced in many cancers. In addition, the expression and processing of cancer-related miRNAs that act as oncogenes ("oncomiRs") or tumor suppressors are often dysregulated in cancer. In this review, we summarize emerging knowledge about how miRNA biogenesis and gene silencing are altered to promote cancer.
MicroRNAs (miRNAs) are a class of small noncoding RNA which exert post-transcriptional gene regulation activity by targeting messenger RNAs. miRNAs have been found to be involved in various ...fundamental biological processes and deregulation of miRNAs is known to result in pathological conditions. In this review, we provide an overview of recent discoveries on the role played by this class of molecules in lung development and in pulmonary diseases, such as asthma, cystic fibrosis, chronic obstructive pulmonary disease, and pulmonary artery hypertension. Considering the relevant role of these miRNAs under physiological and pathological conditions, they represent new clinical targets as well as diagnostic and prognostic tools. Therefore, this review pays special attention to recent advances and possible future directions for the use of miRNAs for clinical applications.
The phenotype of vascular smooth muscle cells (VSMCs) is dynamically regulated in response to various stimuli. In a cellular process known as phenotype switching, VSMCs alternate between a ...contractile and synthetic phenotype state. Deregulation of phenotype switching is associated with vascular disorders such as atherosclerosis, restenosis after angioplasty, and pulmonary hypertension. An important role for microRNAs (miRNAs) in VSMC development and phenotype switching has recently been uncovered. Individual miRNAs are involved in promoting both contractile and synthetic VSMC phenotype. In this review, we summarize recent advances in the understanding of miRNA function in the regulation of VSMC phenotype regulation.
microRNAs are small, non-coding RNAs that influence diverse biological functions through the repression of target genes during normal development and pathological responses. Widespread use of ...microRNA arrays to profile microRNA expression has indicated that the levels of many microRNAs are altered during development and disease. These findings have prompted a great deal of investigation into the mechanism and function of microRNA-mediated repression. However, the mechanisms which govern the regulation of microRNA biogenesis and activity are just beginning to be uncovered. Following transcription, mature microRNA are generated through a series of coordinated processing events mediated by large protein complexes. It is increasingly clear that microRNA biogenesis does not proceed in a 'one-size-fits-all' manner. Rather, individual classes of microRNAs are differentially regulated through the association of regulatory factors with the core microRNA biogenesis machinery. Here, we review the regulation of microRNA biogenesis and activity, with particular focus on mechanisms of post-transcriptional control. Further understanding of the regulation of microRNA biogenesis and activity will undoubtedly provide important insights into normal development as well as pathological conditions such as cardiovascular disease and cancer.
Objective : The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented changes in people’s lifestyles. Since then, our lifestyle has remained different from what it used to be in the ...pre-pandemic era. This study investigated the long-term impact of the COVID-19 pandemic on secular changes in metabolic parameters in Japanese workers. Methods : A total of 519 eligible subjects completed fiscal year (FY) 2017, FY2019 and FY2021 surveys. Comparison between pre-COVID-19 (Δpre-covid19 : FY2019-2017) and during COVID-19 (Δcovid19 : FY2021-2019) was performed in each sex. Results : Increment of diastolic blood pressure (DBP) in Δcovid19 was significantly greater than that in Δpre-covid19 (Δpre-covid19 to Δcovid19 : 0.22 ± 6.17 to 2.59 ± 6.69 mmHg, p = 0.0002 in males, -0.18 ± 6.26 to 2.16 ± 6.60 mmHg, p = 0.01 in females). In females, increments of waist circumference and fasting plasma glucose in Δcovid19 were also significantly greater than those in Δpre-covid19 (both p < 0.05). Conversely, increments of BMI and body fat in Δcovid19 were significantly smaller than those in Δpre-covid19 in males (both p < 0.05). Conclusion : Our findings suggest that there was an apparent metabolic impact of the COVID-19 pandemic on DBP increment in Japanese workers. In addition, COVID-19 may have influenced males and females differently in relation to glucose metabolism and anthropometric measurements related to obesity / adiposity. J. Med. Invest. 71 : 47-53, February, 2024
microRNAs (miRNAs) are small non-coding RNAs conserved in metazoans. Depletion of miRNAs results in embryonic lethality, suggesting they are essential for embryogenesis. Similarly, pathways induced ...by growth factors of the transforming growth factor β (TGF-β) superfamily control cell growth, differentiation, and development. Recently Smad proteins, the signal transducers of the TGF-β pathway, were found to regulate miRNA expression, which, in turn, affects expression of numerous proteins. Smads modulate miRNA expression through both transcriptional and post-transcriptional mechanisms illustrating the complexity of gene regulation by TGF-β. In this chapter we summarize the current knowledge of mechanisms underlying Smad-mediated regulation of miRNA biogenesis.
MicroRNAs (miRNAs) are a class of ~22 nt non-coding RNAs that control diverse biological functions in animals, plants and unicellular eukaryotes by promoting degradation or inhibition of translation ...of target mRNAs. miRNA expression is often tissue specific and developmentally regulated. Aberrant expression of miRNAs has been linked to developmental abnormalities and human diseases, including cancer and cardiovascular disorders. The recent identification of mechanisms of miRNA biogenesis regulation uncovers that various factors or growth factor signalling pathways control every step of the miRNA biogenesis pathway. Here, we review the mechanisms that control the regulation of miRNA biogenesis discovered in human cells. Further understanding of the mechanisms that control of miRNA biogenesis may allow the development of tools to modulate the expression of specific miRNAs, which is crucial for the development of novel therapies for human disorders derived from aberrant expression of miRNAs.
There is little evidence of the effectiveness of aromatherapy massage in palliative care despite its popularity.
This study aimed to investigate the effects of a 30-minute single session of ...aromatherapy massage at night time on quality of sleep and fatigue in palliative care.
A randomized controlled trial from January 2018 to March 2019. After being stratified by sex, participants were randomly assigned to an aromatherapy massage group and a control group. The effects of aromatherapy massage were evaluated on the massage day and the next day using the Richards-Campbell Sleep Questionnaire and the Brief Fatigue Inventory.
Of the 74 participants, data of 27 participants in the treatment group and 30 participants in the control group were analyzed. Analysis of covariance indicated that quality of sleep and fatigue did not improve owing to the aromatherapy massage, although usual fatigue in preceding 24 hours and enjoyment of life subscales of the Brief Fatigue Inventory showed signs of contribution (P = 0.07 and 0.09, respectively). Post hoc analyses indicated that higher age and performance status were factors with moderate correlation with better sleep (P = 0.03; r = 0.45 and P = 0.03; r = 0.40, respectively), and that older patients tended to experience greater improvement in fatigue (P = 0.02; r = −0.47).
A single aromatherapy massage session is no more effective than not having a massage in improving sleep quality in palliative care settings. However, older patients and those in poor health conditions may benefit from aromatherapy massage.
Upon ligand binding, bone morphogenetic protein (BMP) receptors form active tetrameric complexes, comprised of two type I and two type II receptors, which then transmit signals to SMAD proteins. The ...link between receptor tetramerization and the mechanism of kinase activation, however, has not been elucidated. Here, using hydrogen deuterium exchange mass spectrometry (HDX-MS), small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, combined with analysis of SMAD signaling, we show that the kinase domain of the type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes. Formation of this dimer is essential for ligand-induced receptor signaling and is targeted by mutations in BMPR2 in patients with pulmonary arterial hypertension (PAH). We further show that the type I/type II kinase domain heterodimer serves as the scaffold for assembly of the active tetrameric receptor complexes to enable phosphorylation of the GS domain and activation of SMADs.
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