To investigate the characteristic of circulating microparticle in patients with acute myocardial infarction (AMI) and its possible mechanism of promoting coagulation.
Infection-associated inflammation and coagulation are critical pathologies in sepsis-induced acute lung injury (ALI). This study aimed to investigate the effects of microRNA-363-3p (miR-363-3p) on sepsis-induced ALI and explore the underlying mechanisms. A cecal ligation and puncture-induced septic mouse model was established. The results of this study suggested that miR-363-3p was highly expressed in lung tissues of septic mice. Knockdown of miR-363-3p attenuated sepsis-induced histopathological damage, the inflammation response and oxidative stress in lung tissues. Furthermore, knockdown of miR-363-3p reduced the formation of platelet-derived microparticles and thrombin generation in blood samples of septic mice. Downregulation of miR-363-3p suppressed sphingosine-1-phosphate receptor 1 (S1PR1) expression in lung tissues and subsequently inactivated the nuclear factor kappa-B ligand (NF-κB) signaling. A luciferase reporter assay confirmed that miR-363-3p directly targeted the 3'-UTR of the mouse S1pr1 mRNA. Collectively, our study suggests that inactivation of NF-κB signaling is involved in the miR-363-3p/S1PR1 axis-mediated protective effect on septic ALI.
Sepsis typically results in enhanced coagulation system activation and microthrombus formation. Microparticle (MP) production promotes coagulation and enhances pro-coagulation. This study investigated how circulating MP levels and tissue factor-bearing MP (TF+-MP) activity caused coagulation in patients with septic disseminated intravascular coagulation (DIC).Thirty patients with septic DIC and 30 healthy controls were studied from December 2017 to March 2019. Patient blood samples were collected at enrolment (day 1) and on days 3 and 5; DIC scores and Sequential Organ Failure Assessment (SOFA) scores were recorded. TF+-MP activity was measured using TF-dependent factor Xa generation experiments. Circulating MP concentrations were determined by MP capture assay. Clotting factor activity, antithrombin level, soluble thrombomodulin, and serum tissue factor pathway inhibitor (TFPI) concentrations were measured.Patients with septic DIC had lower circulating MP levels than healthy control patients. Circulating MP levels in patients with septic DIC were positively correlated with DIC scores and negatively correlated with coagulation factors, but TF+-MP activity did not correlate with clotting factor levels and TFPI.In patients with septic DIC, circulating MP levels are important in promoting coagulation activation and increasing clotting factor consumption. TF+-MP activity may not be the main form of active TF.
Background: The effects of CD44, via the anti-inflammatory functions of autophagy, on lung injuries following pulmonary contusion (PC) and cell apoptosis were investigated. Methods: Acute lung injury (ALI) mouse models were established by inducing lung injury via PC. This injury was verified using hematoxylin and eosin (H&E) staining, following which bronchoalveolar lavage fluid (BALF) was collected from these mice for analysis and further experimentation. CD44, LC3 I/II ratio, Beclin-1, and p62 expression levels in A549 cells were determined using immunohistochemistry, and western blot assays. CCK-8, flow cytometry, and acridine orange/ethidium bromide (AO/EB) fluorescence staining were used to quantify cell growth induced by BALF. LC3 II and LC3 I expression was determined through immunofluorescence. CD44-knockdown mice were used to demonstrate lung function after PC. Results: The successful establishment of the ALI mouse models, created via PC was confirmed by an enhanced inflammatory response in the lung tissue, markers of cell autophagy. The ALI mice were found to have elevated CD44 expression. The viability of A549 cells exposed to BALF was downregulated, while the knockdown of CD44 promoted this effect. AO/EB and flow cytometry also indicated that the knockdown of CD44 promoted the cell apoptosis induced by BALF. Western blot analysis showed that knockdown of CD44 can inhibit LC3 I/II, p62, and Beclin-1 expression induced by BALF exposure. Additionally, knockdown of CD44 in mice was found to promote PC-induced lung injury through the attenuation of autophagy. Conclusions: Knockdown CD44 was shown to inhibit cell growth and induced cell apoptosis via autophagy signaling pathways, promote mice with ALI induced by PC in vivo and in vitro.
Background Sepsis is often accompanied by the formation of disseminated intravascular coagulation (DIC). Microparticles can exert their procoagulant and proinflammatory properties in a variety of ways. The purpose of this study was to investigate the relationship between microparticle-associated tissue factor activity (TF+-MP activity) and the inflammatory response. Methods Data from a total of 31 DIC patients with sepsis and 31 non-DIC patients with sepsis admitted to the ICU of the First Affiliated Hospital of Harbin Medical University from December 2017 to March 2019 were collected. Blood samples were collected and DIC scores were calculated on the day of enrollment. The hospital’s clinical laboratory completed routine blood, procalcitonin, and C-reactive protein tests. TF+-MP activity was measured using a tissue factor-dependent FXa generation assay. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels were determined using ELISA kits. Results Compared with the non-DIC group, the DIC group had higher levels of leukocytes, neutrophils, procalcitonin, C-reactive protein, IL-1β, and TNF-α, and more severe inflammatory reactions. TF+-MP activity in the DIC group was higher than that in the non-DIC group. In sepsis patients, TF+-MP activity was strongly correlated with inflammatory response indices and DIC scores. Conclusion TF+-MP activity may play a major role in promoting inflammatory response in septic DIC.
Abstract Objectives: This study investigates the clinical features and pulmonary functions of COVID-19 pneumonia survivors at 3 or 6 months after diagnosis in the Heilongjiang Province, China. Methods: Forty-six patients with COVID-19 pneumonia diagnosed since February 2020 were enrolled in this study for follow-up in July 2020. These patients were categorized into three groups: Group A (n=24) and Group B (n=11) who were diagnosed with moderate or severe pneumonia and followed up at three months after diagnosis; Group C (n=11) who were diagnosed with severe pneumonia and followed up at six months after diagnosis. Data on pulmonary function, arterial blood gas analysis, chest CT, blood test, antibody test, and health-related quality of life during hospitalization and at the follow-up visits were collected and analyzed. Results: Abnormal PO 2 (A-a) was more prevalent in severe cases (Group B and C) than in moderate cases (Group A). Pulmonary dysfunction was common in this cohort. Abnormal CT scores of severe cases (Group B and C) were significantly higher than that of moderate cases (Group A). During the follow-up, lung abnormalities gradually resolved in the first 3 months (Group A and B), however, further resolution was not significant from 3 months to 6 months (Group B and C). Conclusion: Although pulmonary interstitial changes due to COVID-19 pneumonia gradually reverse over time, pulmonary dysfunction is common and appears to persist at least up to 6 months in patients recovered from COVID-19 pneumonia.
The present study aimed to screen for differentially expressed extracellular microRNAs (miRNAs) during the development of acute pancreatitis (AP) and validate the miRNA expression in the plasma of patients with AP. The culture medium of taurolithocholic acid‑3 sulfate‑treated rat pancreatic acinar AR42J cells was collected to extract total RNA for miRNA microarray analysis. Compared with the miRNA test results of the AP rats in the GEO databases, the differentially expressed extracellular miRNAs were screened. The TargetScan, miRanda, and PicTar programs were used for target gene prediction of the identified miRNAs, and gene ontology‑biological processes (GO‑BP) functional annotation was performed. Finally, the results from the combined microarray analyses (in vitro cell line and in vivo rat samples) were validated using plasma samples from patients with mild and moderately severe AP by reverse transcription‑polymerase chain reaction. The results demonstrated that extracellular miR‑24 was differentially expressed by microarray and bioinformatics analysis in both the cell line and the animal model of AP. Bioinformatics prediction analysis revealed that downstream target genes of miR‑24 included Vav2, Syk, Lhcgr, Slc9a3r1, Cacnb1, Cacna1b, Bcl10, and Fgd3. Functional enrichment analysis revealed that the main GO‑BP predicted functional presentations were positive regulation of calcium‑mediated signaling, activation of c‑Jun N‑terminal kinase activity, calcium ion transport, regulation of Rho protein signal transduction, negative regulation of the protein kinase B signaling cascade, and the T cell receptor signaling pathway. Validation analysis for the plasma miR‑24 expression in humans revealed a significant upregulation of miR‑24 in the plasma samples of AP patients compared with the healthy controls, while no significant difference was observed in the miR‑24 expression between the mild and the moderately severe AP groups. The present study confirmed the high expression of miR‑24 in peripheral blood during AP, suggesting that miR‑24 might have an intercellular communication role contributing to the AP‑associated distant organ injury.
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