Functions and novel regulatory mechanisms of key glycolytic enzymes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling of the pulmonary vasculature and elevated pulmonary arterial pressure, ultimately leading to right heart failure and death. Despite its clinical significance, the precise molecular mechanisms driving PAH pathogenesis warrant confirmation. Compelling evidence indicates that during the development of PAH, pulmonary vascular cells exhibit a preference for energy generation through aerobic glycolysis, known as the "Warburg effect", even in well-oxygenated conditions. This metabolic shift results in imbalanced metabolism, increased proliferation, and severe pulmonary vascular remodeling. Exploring the Warburg effect and its interplay with glycolytic enzymes in the context of PAH has yielded current insights into emerging drug candidates targeting enzymes and intermediates involved in glucose metabolism. This sheds light on both opportunities and challenges in the realm of antiglycolytic therapy for PAH.

Serum Albumin for Short-Term Poor Prognosis in Patients With Acute Pulmonary Embolism: A Clinical Study Based on a Database.

The relationship between serum albumin (ALB) and short-term prognosis in patients with acute pulmonary embolism (APE) remains unclear. We investigated the predictive value of ALB for short-term prognosis in APE patients using our hospital pulmonary embolism (PE) database (384 patients consecutively collected). Logistic regression analysis and nomograms were applied to construct the predictive model, and validation was assessed. A total of 340 APE patients were included, with a 30-day all-cause mortality rate of 8.5%. The incidence of hypoalbuminemia was 15.9%. The odds ratio (OR) for short-term mortality in patients with high ALB was 0.89 (0.886, 95% CI: 0.812-0.967). Additionally, we created a nomogram for individualized mortality risk prediction. Receiver operating characteristic (ROC) curve analysis showed that the diagnostic area under the curve (AUC) of ALB was 0.758 (95% CI 0.683-0.833), and the best cut-off value was 33.85 g/L. Optimal simplified Pulmonary Embolism Severity Index (sPESI) (ALB combined sPESI) AUC was 0.835 (95% CI 0.775-0.896). Baseline hypoalbuminemia may be an independent prognostic indicator of short-term mortality in patients with APE.

Nitrogen and Biochar Addition Affected Plant Traits and Nitrous Oxide Emission From Cinnamomum camphora.

Atmospheric nitrous oxide (N2O) increase contributes substantially to global climate change due to its large global warming potential. Soil N2O emissions have been widely studied, but plants have so far been ignored, even though they are known as an important source of N2O. The specific objectives of this study are to (1) reveal the effects of nitrogen and biochar addition on plant functional traits and N2O emission of Cinnamomum camphora seedlings; (2) find out the possible leaf traits affecting plant N2O emissions. The effects of nitrogen and biochar on plant functional traits and N2O emissions from plants using C. camphora seedlings were investigated. Plant N2O emissions, growth, each organ biomass, each organ nutrient allocation, gas exchange parameters, and chlorophyll fluorescence parameters of C. camphora seedlings were measured. Further investigation of the relationships between plant N2O emission and leaf traits was performed by simple linear regression analysis, principal component analysis (PCA), and structural equation model (SEM). It was found that nitrogen addition profoundly increased cumulative plant N2O emissions (+109.25%), which contributed substantially to the atmosphere's N2O budget in forest ecosystems. Plant N2O emissions had a strong correlation to leaf traits (leaf TN, P n , G s , C i , Tr, WUE L , α, ETR max, I k , Fv/Fm, Y(II), and SPAD). Structural equation modelling revealed that leaf TN, leaf TP, P n , C i , Tr, WUE L , α, ETR max, and I k were key traits regulating the effects of plants on N2O emissions. These results provide a direction for understanding the mechanism of N2O emission from plants and provide a theoretical basis for formulating corresponding emission reduction schemes.

Plasma Angiopoietin-2 as a Promising Biomarker for the Prognosis of Acute Pulmonary Embolism.

BACKGROUND: Endothelial damage is one of the pathogenic conditions of acute pulmonary embolism (APE). The essential role of angiogenin, ribonuclease A family, member 2 (Ang-2) in APE remains unclear. This study aimed to investigate the predictive value of Ang-2 in the clinical outcomes of patients with APE. METHODS: Plasma Ang-2 levels were measured by an enzyme-linked immunosorbent assay kit using a DuoSet methodology in 118 APE patients and 53 healthy controls. Baseline data relevant to mortality over time were obtained from hospital databases or by patient's follow-up (median follow-up time: 25.0 ± 13.2 months). The main outcome was all-cause mortality. RESULTS: Plasma Ang-2 level was significantly higher in APE patients than in healthy controls (p < 0.001). Patients dying during the first 30 days presented higher baseline levels of Ang-2 than the survivors (p < 0.001). Patients dying during the follow-up also showed higher baseline levels of Ang-2 than the survivors (p < 0.001). The multi-variable logistic regression analysis showed that the N-terminal propeptide of B-type natriuretic peptide (NT-proBNP) [odds ratio (OR): 19.8; 95% CI: 1.5 - 255.8; p = 0.022] and Ang-2 (OR: 9.9; 95% CI: 1.4 - 70.5; p = 0.022) emerged as independent predictors of the 30-day mortality. Furthermore, the multivariable Cox's regression identified plasma Ang-2 [hazards ratio (HR): 1.35; 95% CI: 1.10 - 1.66; p = 0.004] as an independent predictor of long-term mortality in patients with APE. CONCLUSIONS: A high circulating level of Ang-2 can be considered as an independent predictor for the poor outcome of APE and may serve as a biomarker for the risk stratification in patients with APE.

Efficacy and safety of Sildenafil treatment in pulmonary hypertension caused by chronic obstructive pulmonary disease: A meta-analysis.

AIMS: Pulmonary hypertension (PH) is a severe and prevalent complication of chronic obstructive pulmonary disease (COPD), with low quality of life and poor prognosis. This study was designed to evaluate the efficacy and safety of Sildenafil in the treatment of PH caused by COPD (COPD-PH) and provide reference for clinical treatment. MATERIALS AND METHODS: We systematically searched PubMed, EMBASE, Cochrane Library, Clinical Trials.gov databases, Wanfang Data and CNKI for comprehensive literature reporting Sildenafil for randomized controlled trials (RCT) of COPD-PH. Quality assessment, data analysis used the modified Jadad scale and RevMan5.3 software. KEY FINDINGS: A total of 9 RCTs involving 579 patients were included in our study. The primary outcome measure was Six minutes walking distance (6MWD). Secondary observations were Pulmonary artery systolic pressure (PASP), Borg dyspnea index, and Survey scale (SF-36). Our data demonstrate that Sildenafil can improve 6WMD [29.64, 95% CI (13.78, 45.50), P < 0.00001] and PASP [-7.86, 95% CI (-11.26, -4.46) P < 0.00001] of COPD-PH, compared with the control group. However, SF-36 [2.64, 95% CI (-6.85, 12.14) P = 0.59] and Borg dyspnea index [-0.28, 95% CI (-1.08, 0.52) P = 0.49] have no significant difference between those two groups. Adverse reactions in the Sildenafil treatment group were tolerated headaches and digestive symptoms, which were relatively safe. SIGNIFICANCE: Available clinical evidence indicates that Sildenafil seems to be safe and effective for COPD-PH and can improve the patients' 6WMD. However, large-sample, high-quality multicenter RCTs are still needed to provide stronger evidence-based medical evidence.

Efficacy and safety of levosimendan in patients with acute right heart failure: A meta-analysis.

AIMS: Right heart failure (RHF), which is caused by a variety of heart and lung diseases, has a high morbidity and mortality rate. Levosimendan is a cardiac inotropic drug and vasodilator. The effect of levosimendan on RHF remains unclear. We sought to evaluate the efficacy and safety of levosimendan in patients with acute RHF. MATERIALS AND METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov to identify studies reporting the efficacy and safety of levosimendan for the treatment of RHF. KEY FINDINGS: Ten trials, including 359 participants from 6 RCTs and 4 self-controlled trials, were evaluated. In the 6 RCTs, we found that patients treated with levosimendan for 24h showed a significant increase in tricuspid annular plane systolic excursion [1.53; 95% CI (0.54, 2.53); P=0.002] and ejection fraction [3.59; 95% CI (1.21, 5.98); P=0.003] as well as a significant reduction in systolic pulmonary artery pressure [-6.15; 95% CI (-9.29, -3.02); P=0.0001] and pulmonary vascular resistance [-39.48; 95% CI (-65.59, -13.38); P=0.003], whereas changes in mean pulmonary pressure were nonsignificant. Adverse events did not significantly differ between the two groups. SIGNIFICANCE: Our study shows that levosimendan exhibits short-term efficacy for treating RHF in patients with a variety of heart and lung diseases. Additional strict multicentre RCTs with long follow-up times and large sample sizes are required to further validate the efficacy and safety of this treatment.

MiR-557 works as a tumor suppressor in human lung cancers by negatively regulating LEF1 expression.

MicroRNAs play an important role in regulating post-transcriptional gene expression in the progression of various human cancers. In this study, we investigated the role of microRNA-557 in human lung cancer cells. The molecular mechanism of microRNA-557 was also clarified in the proliferation and invasion of human lung cancer cells. Our results showed microRNA-557 levels were obviously decreased in clinical lung cancer specimens and lung cancer cell lines. Cell viability of A549 and NCI-H460 cells transfected with microRNA-557 mimics was significantly decreased than those transfected with negative control mimics. MicroRNA-557 promoted cell death of A549 and NCI-H460 but did not affect the cell apoptosis of lung cancer cells. Overexpression of microRNA-557 inhibited cell invasion of A549 and NCI-H460 cells. TargetScan analysis showed that microRNA-557 might target 3' untranslated region of lymphocyte enhancement factor 1, and the western blotting results showed that transfection of microRNA-557 mimics significantly decreased the levels of lymphocyte enhancement factor 1 in A549 and H460 cells. MicroRNA-557 might work as a tumor suppressor by negatively regulating the expression of lymphocyte enhancement factor 1 in lung cancer cells.

The values of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in predicting 30 day mortality in patients with acute pulmonary embolism.

BACKGROUND: vAcute pulmonary embolism (PE) is a life threatening disease. The treatment options depend on the severity of the disease and the mortality varies widely depending on the severity of the condition. It is important to identify patients who are at high risk of mortality. The aim of the present study was to explore the prognostic alues of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) for 30-day mortality in patients with acute PE. METHODS: The study included 321 patients admitted to our university hospital between January 2013 and May 2015 with the diagnosis of acute PE. Multivariable risk models were developed to assess the predictive values of the NLR and PLR for 30-day mortality. Discrimination was evaluated using receiver operating characteristic (ROC) curves. RESULTS: Two hundred forty-eight patients met our selection criteria. Twenty of them died within 30 days of hospital admission. NLR was found to be an independent predicator after other confounding factors were adjusted in the model. For 1 unit of increase of NLR, the risk of 30-day mortality rose about 13  % (OR = 1.13,95 % CI: 1.04-1.23). The area under ROC for NLR is 0.79 (95 %CI: 0.703-0.880). PLR was associated with 30-day mortality in univariate analysis but the predicative ability diminished with inclusion of other predicators in multivariable model. CONCLUSIONS: NLR is readily available predicator for short-term mortality. It could be a useful indicator for identifying high risk population and guiding clinical management of acute PE.