Previous study has well documented the anti-apoptotic effects of miR-590 on oxidized low-density lipoprotein (ox-LDL)-treated endothelial cells (ECs). However, the mechanism underlying the ...anti-apoptotic effects of miR-590 in ox-LDL-treated ECs remains to be further addressed.
ApoE
mice fed with a high-fat diet (HFD) and human aortic endothelial cells (HAECs) treated with ox-LDL were used as
and
models of atherosclerosis. The expressions of miR-590 and toll-like receptor 4 (TLR4) were detected by quantitative real-time PCR and Western blot, respectively. Atherosclerotic lesion analysis was performed using Evans blue and hematoxylin-eosin staining. Cell proliferation was assessed by MTT assay. Apoptosis was examined using flow cytometry analysis and Western blot analysis of Cleaved poly (ADP-ribose) polymerase (PARP) and Cleaved Caspase-3 levels. The effect of miR-590 on TLR4/nuclear factor kappa B (NF-κB) pathway was evaluated by Western blot. Binding between miR-590 and TLR4 was confirmed by luciferase reporter assay and Western blot.
miR-590 was downregulated in the aorta tissues from HFD-fed apoE
mice and ox-LDL-treated HAECs. miR-590 overexpression inhibited atherosclerotic lesion in HFD-induced apoE
mice and promoted proliferation and inhibited apoptosis of ox-LDL-treated HAECs. Additionally, TLR4 was identified as a direct target of miR-590 in ox-LDL-treated HAECs. Moreover, anti-miR-590 reversed TLR4 knockdown-mediated promotion of cell proliferation and suppression of apoptosis in ox-LDL-treated HAECs. miR-590 overexpression suppressed the TLR4/NF-κB pathway, and inhibition of the TLR4/NF-κB pathway promoted cell proliferation and impeded apoptosis in ox-LDL-treated HAECs.
miR-590 promoted proliferation and blocked ox-LDL-induced apoptosis in HAECs through inhibition of the TLR4/NF-κB pathway.
Tissue engineering is a rapidly developing field with many potential clinical applications in tissue and organ regeneration. The development of a mature and stable vasculature within these engineered ...tissues (ET) remains a significant obstacle. Currently, several growth factors (GFs) have been identified to play key roles within in vivo angiogenesis, including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), FGF and angiopoietins. In this article we attempt to build on in vivo principles to review the single, dual and multiple GF release systems and their effects on promoting angiogenesis. We conclude that multiple GF release systems offer superior results compared to single and dual systems with more stable, mature and larger vessels produced. However, with more complex release systems this raises other problems such as increased cost and significant GF–GF interactions. Upstream regulators and pericyte-coated scaffolds could provide viable alternative to circumnavigate these issues.
Background
Systemic lupus erythematosus (SLE) patients have a higher risk of acute myocardial infarction (AMI) compared to the general population. However, the underlying common mechanism of this ...association is not fully understood. This study aims to investigate the molecular mechanism of this complication.
Methods
Gene expression profiles of SLE (GSE50772) and AMI (GSE66360) were obtained from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) in SLE and AMI were identified, and functional annotation, protein-protein interaction (PPI) network analysis, module construction, and hub gene identification were performed. Additionally, transcription factor (TF)-gene regulatory network and TF-miRNA regulatory network were constructed for the hub genes.
Results
70 common DEGs (7 downregulated genes and 63 upregulated genes) were identified and were mostly enriched in signaling pathways such as the IL-17 signaling pathway, TNF signaling pathway, lipid metabolism, and atherosclerosis. Using cytoHubba, 12 significant hub genes were identified, including IL1B, TNF, FOS, CXCL8, JUN, PTGS2, FN1, EGR1, CXCL1, DUSP1, MMP9, and ZFP36.
Conclusions
This study reveals a common pathogenesis of SLE and AMI and provides new perspectives for further mechanism research. The identified common pathways and hub genes may have important clinical implications for the prevention and treatment of AMI in SLE patients.
Ventricular septal rupture (VSR) is a mechanical complication of acute myocardial infarction (AMI), and its mortality has not decreased significantly in recent decades. However, no clinical model has ...been developed to predict short-term mortality in patients with post-infarction VSR (PIVSR). This study aimed to develop a nomogram to predict the 30-day mortality by using the clinical characteristics of hospitalized patients with PIVSR. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis was used to construct a nomogram by R. The model was evaluated by the area under the curve (AUC), calibration curve and decision curve analysis (DCA). The bootstrap method was used to validate the model internally. As a result, a nomogram was constructed by using six variables, including CRRT, mechanical ventilation, PPCI, WBC, PASP and methods of treatment. The AUC of the prediction model was 0.96 (0.93, 0.98). The prediction model was well calibrated. The DCA showed that if the threshold probability was between 15% and 95%, the nomogram model would provide a net benefit. The well-constructed and evaluated nomogram can be beneficial to clinicians to predict the risk of death within 30 days in patients with PIVSR.
Endothelial dysfunction induced by chronic inflammation has been considered one of the most important mechanisms behind a variety of cardiovascular diseases. Extensive efforts have been made in past ...decades to explore the underlying mechanisms of endothelial dysfunction and to develop new therapeutic agents for the treatment of cardiovascular diseases. Zafirlukast, a selective antagonist of CysLT receptor 1 (CysLT1R), has been licensed by the U.S. Food and Drug Administration (FDA) for the treatment of asthma. In this study, we found that zafirlukast possesses beneficial protective effects on endothelial cells from TNF-α-induced inflammatory response and injury. Our results indicate that TNF-α treatment induces CysLT1R expression. The addition of zafirlukast to culture media suppressed TNF-α-induced expression of endothelial vascular adhesion molecules, such as ICAM-1, VCAM-1, and induction of cytokines, including IL-1β, IL-6, and IL-8. Zafirlukast also ameliorated production of reactive oxygen species (ROS) and adhesion of monocytes to endothelial cells induced by TNF-α. Mechanistically, we demonstrate that zafirlukast suppresses MAPK kinase p38 and NF-κB activation to inhibit inflammatory mediators. Collectively, our findings provide insights into the mechanisms of a potential therapeutic strategy for endothelial dysfunction-related diseases and shed light on the possible application of zafirlukast in cardiovascular diseases such as atherosclerosis.
•The replicated experimental annual burns in freshwater wetlands in three-year period.•Thrice burns increase the soil P content but decrease the stem and leaf P content.•Autumn burns facilitate the ...transfer of P in plants to soil compared to spring.•The increase in time after burning causes a decrease in litter necromass P density.•The once-a-year autumn burn will be an important tool to promote wetland P cycling.
Fire is an important disturbance of wetland P reservoirs by changing the distribution of P in soils and plants. However, the effects of various fire regimes on the distribution of P in wetlands are not known. In a three-year burn experiment, we evaluated the effects of three burn factors on the P distribution of plants (stem, leaf, and litter) and soils (upper and lowerlayer soil) in the freshwater wetlands of China's Sanjiang Plain. We discovered that when burn frequency increased, soil P content and total plant biomass P also increased. Soil P content peaked at a high of 2198.0 ± 559.0 mg kg−1 after three burns. Three burns increased C. angustifolia biomass and therefore increased total plant biomass P. However, the increase in time after burning caused stem and leaf P content and litter necromass density P to decrease, suggesting a steady transfer of plant P to the soil. Furthermore, the stem biomass P density in September after the three burns was higher in spring burns than in autumn burns (1231.0 ± 129.0 mg m−2 after spring burns compared to 542.0 ± 176.0 mg m−2 after autumn burns). The transfer of litter P to the soil was hindered by spring burns, which conserved more P in the litter than autumn burns, which was the opposite of what was found for litter necromass P. Compared to spring burns, frequent autumn burns will hasten the transfer of plant P to the soil, preserving more P in the soil. Thus, conducting once-a-year prescribed burning in the autumn will be an important tool for improving P cycling in freshwater wetlands compared to spring.
The incidence of mortality is considerable after ST-elevation myocardial infarction (STEMI) hospitalization; risk assessment is needed to guide postdischarge management. Age shock index (SI) and age ...modified shock index (MSI) were described as useful prognosis instruments; nevertheless, their predictive effect on short and long-term postdischarge mortality has not yet been sufficiently confirmed.
This analysis included 3389 prospective patients enrolled from 2016 to 2018. Endpoints were postdischarge mortality within 30 days and from 30 days to 1 year. Hazard ratios (HRs) were evaluated by Cox proportional-hazards regression. Predictive performances were assessed by area under the curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI) and decision curve analysis (DCA) and compared with TIMI risk score and GRACE score.
The AUCs were 0.753, 0.746 for age SI and 0.755, 0.755 for age MSI for short- and long-term postdischarge mortality. No significant AUC differences and NRI were observed compared with the classic scores; decreased IDI was observed especially for long-term postdischarge mortality. Multivariate analysis revealed significantly higher short- and long-term postdischarge mortality for patients with high age SI (HR: 5.44 (2.73-10.85), 5.34(3.18-8.96)), high age MSI (HR: 4.17(1.78-9.79), 5.75(3.20-10.31)) compared to counterparts with low indices. DCA observed comparable clinical usefulness for predicting short-term postdischarge mortality. Furthermore, age SI and age MSI were not significantly associated with postdischarge prognosis for patients who received fibrinolysis.
Age SI and age MSI were valuable instruments to identify high postdischarge mortality with comparable predictive ability compared with the classic scores, especially for events within 30 days after hospitalization.
This study investigates how dynamic fluctuations in matrix stiffness affect the behavior of cardiac fibroblasts (CFs) within a three-dimensional (3D) hydrogel environment. Using hybrid hydrogels with ...tunable stiffness, we created an in vitro model to mimic the varying stiffness of the cardiac microenvironment. By manipulating hydrogel stiffness, we examined CF responses, particularly the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation. Our findings reveal that increased matrix stiffness promotes the differentiation of CFs into myofibroblasts, while matrix softening reverses this process. Additionally, we identified the role of focal adhesions and integrin β1 in mediating stiffness-induced phenotypic switching. This study provides significant insights into the mechanobiology of cardiac fibrosis and suggests that modulating matrix stiffness could be a potential therapeutic strategy for treating cardiovascular diseases.
•Chemical stability of peatlands carbon pool (CSPCP) were evaluated by OM properties.•Historical CSPCP in two peatlands in summer monsoon margin were evaluated.•The difference of CSPCP in two ...peatlands was mainly affected by carbohydrate contents.•Local precipitation and fire events were two factors that affected CSPCP.•Intense fire events promoted more carbohydrate accumulated and decreased CSPCP.
The response of carbon pools in peatlands during the last millennium is important for global carbon cycling and is a potential indicator for paleoenvironmental research. Herein, we compared the stability and accumulation of carbon pools between the Hongtu peatland (HT, east site) and the Jintao peatland (JT, west site) in the northern Great Khingan Mountains, spanning the last 700 (HT) and 1000 (JT) years. Peat humification, aromatic and carbohydrate contents, and carbon accumulation rates in these two peat cores were analyzed to better understand the environmental impacts on the stability of carbon pools in these peatlands during the last millennium. The average carbon accumulation rates and the aromatic contents in the HT (23.09 ± 7.28 g C m−2 yr−1 and 28.0 ± 2.2%, respectively) and JT (23.96 ± 6.07 g C m−2 yr−1 and 27.8 ± 0.6%, respectively) were similar. The higher carbohydrate contents in the HT peatland than that in the JT peatland (35.8 ± 2.8% vs 27.8 ± 4.4%) indicated that the stability of carbon pools in the HT peatland were weaker than those in the JT peatland. Local precipitation and fire events may be the two major factors driving the varying stability of carbon pools in these two sites. Especially, at 250–200 cal yr BP, intense fire events may have promoted herb growth and high carbohydrate content in the accumulated plant litter, which ultimately produced higher carbohydrate and lower aromatic contents in the JT peatland than nearby periods. The paleoenvironmental conditions in the studied regions reconstructed by organic matter properties also suggested that the climate forcing mechanisms in the eastern and western sides of the northern Great Khingan Mountains were different and influenced by different degrees by the East Asian monsoon and westerlies.
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