Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

A Grafting Strategy for the Design of Improved G-Quadruplex Aptamers and High-Activity DNAzymes

Nucleic acid aptamers are generally obtained by in vitro selection. Some have G-rich consensus sequences with ability to fold into the four-stranded structures known as G-quadruplexes. A few G-quadruplex aptamers have proven to bind hemin to form a new class of DNAzyme with the peroxidase-like activity, which can be significantly promoted by appending an appropriate base-pairing duplex onto the G-quadruplex structures of aptamers. Knowing the structural role of base pairing, here we introduce a novel grafting strategy for the design of improved G-quadruplex aptamers and high-activity DNAzymes. To demonstrate this strategy, three existing G-quadruplex aptamers are chosen as the first generation. A base-pairing DNA duplex is grafted onto the G-quadruplex motif of the first generation aptamers. Consequently, three new aptamers with the quadruplex/duplex DNA structures are produced as the second generation. The hemin-binding affinities and DNAzyme functions of the second generation aptamers are characterized and compared with the first generation. The results indicate three G-quadruplex aptamers obtained by the grafting strategy have more excellent properties than the corresponding original aptamers. Our findings suggest that, if the structures and functions of existing aptamers are thoroughly known, the grafting strategy can be facilely utilized to improve the aptamer properties and thereby producing better next-generation aptamers. This provides a simple but effective approach to the design of nucleic acid aptamers and DNAzymes

Potential antiviral effects of pantethine against SARS-CoV-2

Abstract SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection.Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome.</jats:p

Thermal approach to evaluate the sintering–crystallization ability in a nepheline–forsterite-based glass-ceramics

A glass in the SiO2–Al2O3–MgO–Na2O system was formulated using a non-conventional silica source and other pure raw materials. The thermal stability and crystallization mechanism have been studied by means of differential scanning calorimetry (DSC). Besides, the glass ability to sintering–crystallization has been examined by optical dilatometry, a non-contact technique allowing the acquisition of dilatometric data in the viscoelastic temperature region. The experimental data were confirmed with theoretical equations. X-ray diffraction and field emission scanning electron microscopy were used to verify the crystallization study and electron scanning microscopy to examine the fired sample microstructures. The prevalent crystallization mechanism has been evaluated from different parameters derived from characteristic temperatures of non-isothermal DSC curves, namely the working range (ΔT TS), reduced glass transition temperature (T gr), and the dissimilarity in crystallization temperature (ΔT p) between fine (<63 µm) and coarse (fragment) glass samples.Peer reviewe

Acúmulo e liberação de P, K, Ca e Mg em crotalária e milheto solteiros e consorciados

As características das leguminosas e gramíneas usadas como plantas de cobertura são bastante conhecidas, mas a velocidade com que os nutrientes associados à biomassa vegetal tornam-se disponíveis às culturas é ainda pouco estudada. O objetivo deste trabalho foi determinar o acúmulo e a taxa de liberação de nutrientes de crotalária e milheto solteiros ou consorciados. O delineamento experimental adotado foi blocos ao acaso, com quatro repetições. Os tratamentos foram crotalária, milheto, crotalária + milheto e vegetação espontânea. O acúmulo de P e Mg foi influenciado pela produção de massa, com valores elevados na crotalária, enquanto o acúmulo de Ca resultou tanto do maior teor quanto da maior produção de massa nos tratamentos com a leguminosa. A liberação de nutrientes dos resíduos apresentou dinâmica semelhante, com duas fases distintas: a primeira com taxas mais elevadas nos primeiros 15 dias e a segunda mais lenta a partir dessa fase. As taxas de liberação de K, Ca e Mg foram semelhantes, independentemente dos tratamentos. Os resíduos da crotalária apresentaram maior liberação de P do que as da vegetação espontânea, com meia vida de 11 dias e a vegetação espontânea de 17 dias. O Ca foi liberado mais lentamente do que os demais nutrientes, e o Mg mais rapidamente. As plantas espontâneas e o milheto apresentam importante potencial na reciclagem de K, e a crotalária se destacou na reciclagem de Ca e Mg