Early Prone Position Ventilation in the Efficacy for Severe Hypoxemia and Neurological Complications Following Acute Type A Aortic Dissection (TAAD) Surgery.

OBJECTIVE: To analyze the efficacy of early prone position ventilation in the treatment of severe hypoxemia after surgery for acute type A aortic dissection (TAAD). METHODS: The patients were divided into a control group and a treatment group. Parameters assessed included blood gas analysis indicators [arterial oxygen partial pressure (PaO2). RESULTS: (1) Blood gas analysis: Before treatment, there was no significant difference in PaO2, SpO2, and OI levels between the two groups; after treatment, the PaO2, SpO2, and OI levels in both groups significantly increased compared to pre-treatment, with a more pronounced improvement in the treatment group than in the control group (p < 0.05). (2) Hemodynamics: Before treatment, there was no significant difference in MAP and HR levels between the two groups; after treatment, the MAP levels increased significantly in both groups compared to pre-treatment, while HR levels decreased significantly, with no significant difference between the groups. (3) Prognosis recovery: MV time, ICU stay, and total hospital stay were significantly lower in the treatment group than in the control group; the 30-day mortality rate was 14.58% in the control group and 12.50% in the treatment group, with no significant difference in 30-day mortality rate between the groups. CONCLUSION: Early prone position ventilation has shown promising application in the treatment of severe hypoxemia after TAAD surgery. Compared to traditional supine position ventilation, the use of early prone position ventilation can further improve blood gas analysis indicators in patients, and shorten MV time, ICU stay, and total hospital stay, thereby accelerating patient recovery.

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux.

PURPOSE: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). METHODS: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosis-related genes were measured. RESULTS: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. CONCLUSIONS: It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

Purpose: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). Methods: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosisrelated genes were measured. Results: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. Conclusion: It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/ miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

Silencing of Long Noncoding RNA MIAT Contributes to Relieving Sepsis-Induced Myocardial Depression via the NF-κB Axis.

INTRODUCTION: Sepsis represents a life-threatening disease caused by a series of infections, which may be complicated with severe myocardial depression (MD). Long noncoding RNAs (lncRNAs) are closely related to sepsis-induced myocardial depression (SIMD). This study aimed to seek out the mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in the growth of SIMD. METHODS: Venous blood samples were collected from 62 patients with sepsis; the sepsis rat model was established with 15 mg/kg lipopolysaccharide (LPS), and the H9C2 cardiomyocyte injury model was established with 1 µg/mL LPS. In the rat and cardiomyocyte models, MIAT was inhibited. The expression of MIAT in normal tissues and SIMD tissues was detected. Then, the functional assays of MIAT were performed in rats and H9C2 cells for detection of cardiac function, hemodynamics, inflammation response, myocardial function, oxidative stress, tissue stainings, and cardiomyocyte viability and apoptosis. Western blot analysis was used to measure the levels of apoptosis-related proteins and the nuclear factor kappa B (NF-κB) axis-related proteins. RESULTS: MIAT was highly expressed in SIMD patients. Silencing MIAT alleviated inflammation and apoptosis and improved myocardial function in SIMD rats by downregulating the NF-κB axis. In LPS-induced H9C2 cardiomyocytes, silencing MIAT alleviated inflammation and oxidative stress and inhibited apoptosis by downregulating the NF-κB axis, thus mitigating cardiomyocyte injury. CONCLUSIONS: MIAT could assist the diagnosis of SIMD and might affect the progression of SIMD by regulating the NF-κB pathway.

Periostin renders cardiomyocytes vulnerable to acute myocardial infarction via pro-apoptosis.

AIMS: As a severe cardiovascular disease, acute myocardial infarction (AMI) could trigger congestive heart failure. Periostin (Postn) has been elucidated to be dramatically up-regulated in myocardial infarction. Abundant expression of Postn was also observed in the infarct border of human and mouse hearts with AMI. This work is dedicated to explore the mechanism through which Postn exerts its functions on AMI. METHODS AND RESULTS: The expression of Postn in AMI mice and hypoxia-treated neonatal mouse cardiomyocytes (NMCMs) was quantified by qRT-PCR. The biological functions of Postn in AMI were explored by trypan blue, TUNEL, flow cytometry analysis, and JC-1 assays. Luciferase activity or MS2-RIP or RNA pull-down assay was performed to study the interaction between genes. Postn exhibited up-regulated expression in AMI mice and hypoxia-treated NMCMs. Functional assays indicated that cell apoptosis in NMCMs was promoted via the treatment of hypoxia. And Postn shortage could alleviate cell apoptosis in hypoxia-induced NMCMs. Postn was verified to bind to mmu-miR-203-3p and be down-regulated by miR-203-3p overexpression. Postn and miR-203-3p were spotted to coexist with small nucleolar RNA host gene 8 (Snhg8) in RNA-induced silencing complex. The affinity between Snhg8 and miR-203-3p was confirmed. Afterwards, Snhg8 was validated to promote cell apoptosis in hypoxia-induced NMCMs partially dependent on Postn. Furthermore, vascular endothelial growth factor A (Vegfa) was revealed to bind to miR-203-3p and be implicated in the Snhg8-mediated AML cell apoptosis and angiogenesis. CONCLUSIONS: miR-203-3p availability is antagonized by Snhg8 for Postn and Vegfa-induced AMI progression.

Anti-inflammatory cytokine IL10 loaded cRGD liposomes for the targeted treatment of atherosclerosis.

AIM: Atherosclerosis (AS) is one of the main causes of cardiovascular disease which might lead to myocardial infarction or stroke and further leads to fatality. METHOD: In this study, we have designed an anti-inflammatory cytokine interleukin-10 (IL10) delivery system to effectively alleviate the inflammation of atherosclerosis plaque. The targeted delivery of IL10 to the atherosclerotic plaques was achieved by cRGD conjugated liposomes (IL10-cRGD-Lip). RESULTS: The IL10-cRGD-Lip of size 179.4 ± 10.91 nm having PDI 0.14 ± 0.04 with a surface charge of +18.34 ± 1.36 mV was prepared. The in-vitro analysis clearly suggests that IL10-cRGD-Lip sustains the release of IL10 and could significantly reduce ROS and NO. The immuno-staining results revealed that IL-1ß and TNF-α were down-regulated after the treatment with IL10-cRGD-Lip in Lipopolysaccharide (LPS) stimulated RAW 264.7 cells. CONCLUSION: the in-vitro results clearly suggest that anti-inflammatory cytokine IL10 could be used for the cure of inflammatory maladies including atherosclerosis.

Evaluation of a novel paclitaxel-eluting stent with a bioabsorbable polymeric surface coating in the porcine artery injury model.

PURPOSE: Drug-eluting stents (DES) are unique in allowing sustained release after a single short intervention. The challenge with DES still remaining is the optimal combination of a biocompatible drug-eluting matrix including an antiproliferative drug. We studied the role of a novel paclitaxel-eluting stent with a bioabsorbable polymer coating in preventing vascular restenosis in the porcine artery injury model. MATERIAL AND METHODS: Bare metal stents (BMS); polymer-coated-only stents (POLY); and polymer-based paclitaxel-eluting stents (PACL) were randomly implanted in pig femoral arteries. The dose density of paclitaxel was 1 microg/mm2 with in vitro studies demonstrating a gradual elution over a course of 6 month. RESULTS: After 1-, 3- and 6-month follow-up, respectively, the animals underwent angiographic restudy and were terminated for histomorphometrical and histopathological analyses. At 1 month, the PACL group had the lowest histological percent stenosis when compared to the BMS and POLY groups (20 +/- 4% vs 39 +/- 6% and 41 +/- 6%, respectively, P < 0.05). At 3 months, the PACL group still presents the lowest level of histological percent stenosis among the three groups (27 +/- 6% vs 50 +/- 10% and 46 +/- 5%, respectively, P < 0.01). Six months later, the PACL group showed a similar histological percent stenosis as the BMS and POLY groups (44 +/- 9% vs 56 +/- 11% and 53 +/- 9%, respectively, P = 0.145). CONCLUSIONS: This study shows favourable vascular compatibility and efficacy for a novel DES to inhibit in-stent neointima formation and preserve lumen area in the porcine artery model.