International journal of molecular sciences
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Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3-11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. ⋯ Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.
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We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. ⋯ In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following nerve injury.
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Burn-induced heart dysfunction is a key factor for patient mortality. However, the molecular mechanisms are not yet fully elucidated. This study sought to understand whether burn-induced heart dysfunction is associated with cardiac mitochondrial dysfunction and interruption of the PDE5A-cGMP-PKG pathway. ⋯ Sildenafil, a inhibitor of the PDE5A-cGMP-PKG pathway, preserved the mitochondrial structure, respiratory chain efficiency and energy status in cardiac tissue. Furthermore, sildenafil treatment significantly restored ADP-conjugated respiration in burned groups. In conclusion, cardiac mitochondrial damage contributes to burn-induced heart dysfunction via the PDE5A-cGMP-PKG pathway.
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Multipotent mesenchymal stem cells (MSCs) possess regenerative properties and have been shown to improve outcomes and survival in acute and chronic lung diseases, but there have been some safety concerns raised related to MSC-based therapy. Subsequent studies have demonstrated that many of the regenerative effects of MSCs can be attributed to the MSC-derived secretome, which contains soluble factors and extracellular vesicles (EVs). ⋯ To date, the use of MSC-derived EVs as a treatment for lung disease has been conducted primarily in in vitro or pre-clinical animal models. In this review, we will discuss the current published research investigating the use of EVs as a potential therapeutic for acute lung injury/acute respiratory distress syndrome (ALI/ARDS), bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), asthma, and silicosis.
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Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings.
(1) Background: Pericytes are involved in intraplaque neovascularization of advanced and complicated atherosclerotic lesions. However, the role of pericytes in human carotid plaques is unclear. An unstable carotid plaque that shows high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) is often a cause of ischemic stroke. ⋯ The density of the CD34-positive neovessels was equivalent in both groups. However, the NG2- and CD146-positive neovessels had significantly higher densities in the TOF-HIS group than in the TOF-IIS group. (4) Conclusion: The presence of a high-intensity signal on TOF-MRA in carotid plaques was associated with intraplaque hemorrhage and few pericytes in intraplaque neovessels. These findings may contribute to the development of new therapeutic strategies focusing on pericytes.