HAND2-AS1 associates with outcomes of acute coronary syndrome and regulates cell viability of vascular endothelial cells.

OBJECTIVE: Acute coronary syndrome (ACS) is an emergency and severe disorder of the cardiovascular system. This paper assessed the expression of plasma HAND2-AS1 in patients with ACS, researched its diagnostic and prognostic significance, and studied its possible mechanism for participating in ACS. METHODS: The concentration of HAND2-AS1 of 101 included patients with ACS was certified by qRT-PCR and its possible diagnostic function was revealed by the receiver operating characteristic (ROC) curve. All patients were followed up for 6 months after percutaneous coronary intervention (PCI) therapy and Kaplan-Meier (K-M) curve and COX regression analysis was performed to estimate the short-term prognostic value of HAND2-AS1 in ACS. The interrelationship between HAND2-AS1 and Gensini score and endothelial injury was identified via Pearson correlation. The function of HAND2-AS1 on the viability, migration, and apoptosis of human umbilical vein endothelial cells (HUVECs) was estimated by the Cell Counting Kit-8 (CCK-8), Transwell chamber, and flow cytometry. RESULTS: In ACS patients, the expression of serum HAND2-AS1 was prominently decreased and closely correlated with the Gensini score. The decreased HAND2-AS1 expression was of diagnostic significance. Declined plasma HAND2-AS1 was observed in patients with the major adverse cardio-cerebrovascular event (MACCE) and was an independent risk for the poor prognosis of ACS patients. In the cell model, upregulation of HAND2-AS1 improved cell viability and migration and inhibited cell apoptosis. CONCLUSION: HAND2-AS1 was an independent biomarker for the diagnosis and prognosis of ACS. HAND2-AS1 might be involved in ACS development by regulating endothelial damage.

Mechanism of DYRK1a in myocardial ischemia-reperfusion injury by regulating ferroptosis of cardiomyocytes.

This study aimed to explore the role and mechanism of DYRK1a regulating ferroptosis of cardiomyocytes during myocardial ischemia-reperfusion injury (MIRI). H9c2 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) were used as MIRI cell models and transfected with sh-DYRK1a or/and erastin. Cell viability, apoptosis, and DYRK1a mRNA/protein expression were measured accordingly. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were determined. The expression of ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, and TFR1) was detected using western blotting. The MIRI rat model was established to explore the possible role of DYRK1a suppression in cell injury and ferroptosis. OGD/R cells showed elevated mRNA and protein expression for DYRK1a. OGD/R cells transfected with sh-DYRK1a showed elevated cell viability, GSH content, increased GPX4 and SLC7A11 expression, suppressed iron content, MDA, ROS, ACSL4, and TFR1 expression, and reduced apoptosis rate, whereas co-transfection of sh-DYRK1a with erastin reversed the attenuation of sh-DYRK1a on MIRI. The suppressive effect of sh-DYRK1a on MI/R injury was confirmed in an MIRI rat model. DYRK1a mediates ferroptosis of cardiomyocytes to deteriorate MIRI progression.

[Inhibitory effect and mechanism of bone marrow mesenchymal stem cells on inflammation in rats with multiple organ dysfunction syndrome].

Objective To observe the anti-inflammatory effect and mechanism of bone marrow mesenchymal stem cell (BMSC) on multiple organ dysfunction syndrome (MODS) rats. Methods SD rats were randomly divided into control group, model group and BMSC group, with 10 rats in each group. Rats in model group and BMSC group were intraperitoneally injected with 7 mg/kg lipopolysaccharide (LPS) to establish MODS models. Rat BMSCs were cultured in vitro, and the fourth generation cells were used for experiments. The rats in BMSC group were injected with 1×106 BMSCs through the tail vein, and the rats in control group and model group were injected with the same amount of normal saline through the tail vein. 72 hours after MODS model was established, blood oxygen partial pressure (PaO2) and arterial carbon dioxide partial pressure (PaCO2) were detected by blood gas analyzer. ELISA were used to detect the bilirubin (TB), albumin (ALB), serum creatinine (Scr), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cyclic adenosine monophosphate (cAMP). HE staining was performed to observe pathological changes in lung, liver and kidney tissues. Western blot analysis was used to detect the protein expression of protein kinase A (PKA) and nuclear factor kappa-B p65 (NF-κB p65) in tissues of lung, liver and kidney. Results Compared with control group, PaO2 in model group and BMSC group significantly decreased, while the PaCO2 significantly increased. TB, Cr, BUN, TNF-α and IL-6 levels was found increased, and ALB and cAMP levels was found decreased, along with the decreased PKA protein expression levels in lung, liver and kidney tissues, and increased NF-κB p65 protein expression levels. Compared with model group, PaO2 in BMSC group increased significantly, while its PaCO2 decreased markedly. It's also detected decreased TB, Cr, BUN, TNF-α and IL-6 levels, increased ALB and cAMP levels, as well as increased PKA protein expression levels in lung, liver and kidney tissues, and decreased NF-κB p65 protein expression levels. Conclusion BMSCs can reduce the damaged organ function and inhibit the release of inflammatory factors in MODS rats. The mechanism may be related to the change of cAMP/PKA/NF-κB signaling pathway.

Pathogens distribution and drug resistance in patients with acute cerebral infarction complicated with diabetes and nosocomial pulmonary infection.

BACKGROUND: This study aims to investigate the pathogen distribution and drug resistance in patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection. METHODS: From August 2015 to December 2017, 172 pathogenic bacterial strains from patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection in our hospital were identified, and the drug sensitivity was analyzed. RESULTS: Among these 172 strains of pathogenic bacteria, gram negative bacteria was the main cause of pulmonary infection in hospitalized patients with acute cerebral infarction, accounting for 75.6% of all pathogens. Furthermore, 80% of diabetic patients with cerebral infarction had lung infection induced by gram negative bacteria, which was significantly higher than that in non-diabetic patients (72.2%). Moreover, the drug resistance rate in the diabetic group (68.3%) was significantly higher than that in the non-diabetic group (54.3%). Gram positive bacteria accounted for 19.1% of all pathogenic bacteria. The infection rate of gram-positive bacteria in diabetic patients with cerebral infarction was 14.7%, which was lower than that in the non-diabetic group (22.6%). The drug-resistance rate was higher in the diabetic group (45.5%) than in the non-diabetic group (28.2%). Furthermore, the fungal infection rate in patients with lung infection in these two groups was 5.3 and 5.2%, respectively, and fungi presented with high sensitivity to commonly used antifungal agents. CONCLUSION: In patients with acute cerebral infarction complicated with diabetes mellitus and nosocomial pulmonary infection, the majority of pathogens are multidrug-resistant gram negative bacilli. Pathogen culture should be conducted as soon as possible before using antibiotics, and antimicrobial agents should be reasonably used according to drug sensitivity test results.

Clg2p interacts with Clf and ClUrase to regulate appressorium formation, pathogenicity and conidial morphology in Curvularia lunata.

Ras is a small GTPase that regulates numerous processes in the cellular development and morphogenesis of many organisms. In this study, we identified and functionally characterized the Clg2p gene of Curvularia lunata, which is homologous with the Ras protein. The Clg2p deletion mutant (ΔClg2p) had altered appressorium formation and conidial morphology and produced fewer, smaller lesions compared with the wild-type strain. When a dominant Clg2p allele was introduced into the mutant, all of these defective phenotypes were completely restored. To further understand the regulation of Clg2p in appressorium formation and conidial morphology, and its role in pathogenicity, seven Clg2p-interacting proteins were screened using a yeast two-hybrid assay. Two of these proteins, Clf, a homologue of Mst11, which corresponds to MAP kinase kinase kinase in Magnaporthe oryzae, and urate oxidase (designated ClUrase) were functionally characterized. Clg2p specifically interacted with Clf through its RA domain to regulate appressorium formation and pathogenicity, whereas the Clg2p-ClUrase interaction regulated conidial morphology without affecting fungal pathogenicity. This report is the first to elucidate the regulatory mechanism of the key Ras protein Clg2p in C. lunata.