The discovery of ferroptosis has brought a revolutionary breakthrough in heart failure treatment, and natural products, as a significant source of drug discovery, are gradually demonstrating their extraordinary potential in regulating ferroptosis and alleviating heart failure symptoms. In addition to chemically synthesized small molecule compounds, natural products have attracted attention as an important source for discovering compounds that target ferroptosis in treating heart failure.

Systematically summarize and analyze the research progress on improving heart failure through natural products' modulation of the ferroptosis pathway.

By comprehensively searching authoritative databases like PubMed, Web of Science, and China National Knowledge Infrastructure with keywords such as "heart failure", "cardiovascular disease", "heart disease", "ferroptosis", "natural products", "active compounds", "traditional Chinese medicine formulas", "traditional Chinese medicine", and "acupuncture", we aim to systematically review the mechanism of ferroptosis and its link with heart failure. We also want to explore natural small-molecule compounds, traditional Chinese medicine formulas, and acupuncture therapies that can inhibit ferroptosis to improve heart failure.

In this review, we not only trace the evolution of the concept of ferroptosis and clearly distinguish it from other forms of cell death but also establish a comprehensive theoretical framework encompassing core mechanisms such as iron overload and system xc-/GSH/GPX4 imbalance, along with multiple auxiliary pathways. On this basis, we innovatively link ferroptosis with various types of heart failure, covering classic heart failure types and extending our research to pre-heart failure conditions such as arrhythmia and aortic aneurysm, providing new insights for early intervention in heart failure. Importantly, this article systematically integrates multiple strategies of natural products for interfering with ferroptosis, ranging from monomeric compounds and bioactive components to crude extracts and further to traditional Chinese medicine formulae. In addition, non-pharmacological means such as acupuncture are also included.

This study fills the gap in the systematic description of the relationship between ferroptosis and heart failure and the therapeutic strategies of natural products, aiming to provide patients with more diverse treatment options and promote the development of the heart failure treatment field.

The albumin-to-alkaline phosphatase ratio (AAPR) is a predictor of several disease outcomes. However, there is no study about AAPR and acute ischemic stroke outcomes. This study aims to investigate the relationship between AAPR and a 3-month unfavorable outcome in patients with acute ischemic stroke.

This prospective cohort study included 2084 patients with acute ischemic stroke in South Korea. After applying strict exclusion criteria, 1,886 patients were included in our analysis and divided into three groups based on AAPR tertiles. An unfavorable outcome was defined as a 3-month modified Rankin scale (mRS) score > 2. Logistic regression analysis and smooth curve fitting analysis were applied to investigate the relationship between AAPR and unfavorable outcomes. Subgroup analysis was also performed to assess whether influencing factors changed the association between AAPR and unfavorable outcomes.

After adjusting for potential confounders, multivariate analysis showed that AAPR was significantly associated with a 3-month unfavorable outcome (OR 0.18, 95% CI 0.09-0.35, p < 0.001). The smooth curve fitting analysis showed a nonlinear relationship between AAPR and a 3-month unfavorable outcome. The infection point was 0.588 according to the recursive method, and the threshold analysis showed when AAPR was ≤0.588, with the per unit increase of AAPR, the 3-month unfavorable outcome risk decreased by 96% (OR 0.04, 95% CI 0.01-0.2, p < 0.001). However, when AAPR was >0.588, there was no negative correlation between AAPR and a 3-month unfavorable outcome (OR 0.33, 95% CI 0.08-1.3, p = 0.112).

This study is the first to suggest a non-linear relationship between AAPR and a 3-month unfavorable outcome of acute ischemic stroke. AAPR was negatively correlated with a 3-month unfavorable outcome when AAPR was <0.588.

Research on predictive models for hospital mortality in patients who have survived 24 h following cardiopulmonary resuscitation (CPR) is limited. We aim to explore the factors associated with hospital mortality in these patients and develop a predictive model to aid clinical decision-making and enhance the survival rates of patients post-resuscitation.

We sourced the data from a retrospective study within the Dryad dataset, dividing patients who suffered cardiac arrest following CPR into a training set and a validation set at a 7:3 ratio. We identified variables linked to hospital mortality in the training set using Least Absolute Shrinkage and Selection Operator (LASSO) regression, as well as univariate and multivariate logistic analyses. Utilizing these variables, we developed a prognostic nomogram for predicting mortality post-CPR. Calibration curves, the area under receiver operating curves (ROC), decision curve analysis (DCA), and clinical impact curve were used to assess the discriminability, accuracy, and clinical utility of the nomogram.

The study population comprised 374 patients, with 262 allocated to the training group and 112 to the validation group. Of these, 213 patients were dead in the hospital. Multivariate logistic analysis revealed age (OR 1.05, 95% CI: 1.03-1.08), witnessed arrest (OR 0.28, 95% CI: 0.11-0.73), time to return of spontaneous circulation (ROSC) (OR 1.05, 95% CI: 1.02-1.08), non-shockable rhythm (OR 3.41, 95% CI: 1.61-7.18), alkaline phosphatase (OR 1.01, 95% CI: 1-1.01), and sequential organ failure assessment (SOFA) (OR 1.27, 95% CI: 1.15-1.4) were independent risk factors for hospital mortality for patients who survived 24 h after CPR. ROC of the nomogram showed the AUC in the training and validation group was 0.827 and 0.817, respectively. Calibration curves, DCA, and clinical impact curve demonstrated the nomogram with good accuracy and clinical utility.

Our prediction model had accurate predictive value for hospital mortality in patients who survived 24 h after CPR, which will be beneficial for assisting in identifying high-risk patients and intervention. Further confirmation of the model's accuracy required external validation data.

Peritoneal dialysis (PD) serves as a vital renal replacement therapy for patients with end-stage kidney disease (ESKD). γ-Gamma-glutamyl transferase (γ-GGT) is a recognized predictor of oxidative stress and mortality. This study aimed to assess the prognostic significance of γ-GGT in predicting all-cause and cardiovascular mortality among PD patients.

A retrospective study was conducted, enrolling 640 PD patients from a single center. The one-year, three-year, and five-year mortality rates for all causes and cardiovascular causes were evaluated. Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed.

Within five years of initiating PD, the observed all-cause mortality rates at one, three, and five years were 11.72%, 16.09%, and 23.44%, while cardiovascular mortality rates were 2.97%, 7.34%, and 11.09%, respectively. Lower γ-GGT levels were associated with decreased all-cause mortality during one-, three-, and five-year follow-ups, along with reduced cardiovascular mortality in the first and third years, as indicated by Kaplan-Meier analysis on median γ-GGT groupings. Multivariate Cox regression analysis showed significantly decreased hazard ratios (HRs) for one- to five-year all-cause mortality and cardiovascular mortality in the lower γ-GGT group compared to higher groups. However, when sex differences were eliminated using separate tertile groupings for males and females, only the one- and three-year all-cause mortality rates demonstrated significantly reduced hazard ratios (HRs) in the lower γ-GGT groups.

This retrospective study suggests that γ-GGT levels have prognostic significance in predicting one- and three-year all-cause mortality among PD patients when accounting for sex differences.

To investigate the association of methyltransferase-like protein 14 (METTL14) expression with coronary heart disease (CHD).

Three hundred and sixteen patients who attended Henan Provincial People's Hospital between June 2019 and February 2021 with principal symptoms of pain or tightness in the chest and who underwent coronary angiography for definitive diagnosis were enrolled. The uric acid, TG, TC, LDL-C, HDL-C, apolipoprotein A1, free fatty acid, lipoprotein a, homocysteine, CRP, and SAA levels were examined. The levels of METTL14, TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 were evaluated by ELISA.

Patients with CHD had significantly higher m6A methyltransferase activity. In addition, the incidence of diabetes and hypertension, as well as the concentrations of TC, CRP, and SAA were higher in CHD patients. Patients with coronary lesion branches also had significantly increased TG, LDL-C, CRP, and SAA levels. TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 expression was also markedly increased in the CHD group (P < 0.001) as was the expression of METTL14 (P < 0.001). The METTL14 expression levels also differed significantly in relation to the number of branches with lesions (P < 0.01) and were correlated with SAA, VCAM-1, ICAM-1, IL-6, and the Gensini score. ROC curve analyses of METTL14 in CHD indicated an AUC of 0.881 (0.679, 0.894) with a cut-off value of 342.37, a sensitivity of 77%, and a specificity of 84%. MCP-1, VCAM-1, IL-6, SAA, and METTL14 were found to independently predict CHD risk.

METTL14 levels were found to be positively associated with inflammatory markers and to be an independent predictor of CHD risk.

γ-glutamyl transferase (GGT), the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the neutrophil-to-lymphocyte ratio (NLR) are prognostic biomarkers in several cardiovascular diseases, but their relevance in pulmonary hypertension (PH) is not fully understood. We aimed to assess their prognostic value in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH).

We retrospectively analyzed 731 incident patients with idiopathic PAH or CTEPH who entered the Giessen PH registry during 1993-2019. A risk stratification score based on GGT, AST/ALT ratio, and NLR tertiles was compared with a truncated version of the European Society of Cardiology/European Respiratory Society (ESC/ERS) risk stratification scheme. Associations with survival were evaluated using Kaplan-Meier and Cox regression analyses. External validation was performed in 311 patients with various types of PAH or CTEPH from a second German center.

GGT levels, AST/ALT, and NLR independently predicted mortality at baseline and during follow-up. The scoring system based on these biomarkers predicted mortality at baseline and during follow-up (both log-rank p < 0.001; hazard ratio [95% confidence interval], high vs low risk: baseline, 7.6 [3.9, 15.0]; follow-up, 13.3 [4.8, 37.1]). Five-year survival of low, intermediate, and high risk groups was 92%, 76%, and 51%, respectively, at baseline and 95%, 78%, and 50%, respectively, during follow-up. Our scoring system showed characteristics comparable to the ESC/ERS scheme, and predicted mortality in the validation cohort.

GGT, AST/ALT, and NLR were reliable prognostic biomarkers at baseline and during follow-up, with predictive power comparable to the gold standard for risk stratification.

This paper presents a highly sensitive sensing system for alkaline phosphatase by room temperature phosphorescence of Mn doped ZnS quantum dots and pyrophosphate. The sensing system has intense room temperature phosphorescence emission in the absence of alkaline phosphatase. The phosphorescence is quenched gradually with the addition of alkaline phosphatase. The emission "on" without alkaline phosphatase may be attributed to the increased probability of charge transfer from one of surface traps to the dopant bands of another resulted from the shortened dot-to-dot distance by the strong chelation of pyrophosphate and Zn²⁺ ion and the hydrogen bonding between pyrophosphate and β-cyclodextrin. The addition of alkaline phosphatase causes pyrophosphate hydrolyzed to orthophosphate and the dot-to-dot distance of quantum dots back to the normal, and then the phosphorescence "off". The factors affecting the sensing system performance were also optimized. Under the optimal experimental conditions, the linear range for alkaline phosphatase is determined as 0.2-10 U/L with a LOD at 0.045 U/L. The recovery of human serum was determined from 93.75%-103.03%, indicating a potential application in biomedical diagnosis. Furthermore, an RTP-based "INHIBIT" logic gate using the doped ZnS quantum dots was also presented.

This meta-analysis assessed the prognostic value of serum γ-glutamyltransferase (GGT) level for cardiovascular (CV) and all-cause mortality in patients with coronary artery disease (CAD). We conducted a systematic literature search of PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, and Weipu databases until December 2018. Observational studies investigating the prognostic role of serum GGT level for CV and all-cause mortality in patients with CAD were included. Pooled risk ratios (RR) with 95% confidence intervals (CI) for the highest versus the lowest GGT level were used to summarize the prognostic value. Twelve studies involving 12 531 patients with CAD were included. Meta-analysis showed that elevated GGT level was significantly associated with higher risk of CV mortality (RR: 2.04; 95% CI: 1.57-2.64) and all-cause mortality (RR: 1.49; 95% CI: 1.27-1.74) in patients with CAD. This meta-analysis suggests that elevated serum GGT levels are an independent predictor of CV and all-cause mortality in patients with CAD. Determination of GGT level may improve the prediction of CV and all-cause mortality in patients with CAD.

Gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) are commonly used liver function markers. We performed a dose-response meta-analysis to investigate the association between liver enzymes and cardiovascular disease (CVD) mortality in prospective cohort studies. We conducted a systematic search up to April 2018 in Medline/PubMed, Scopus, Cochrane, and Embase databases. Combined hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a random-effects model as described by DerSimonian and Laird. Dose-response analysis was also carried out. Twenty-three studies with 1 067 922 participants reported association between GGT and CVD mortality and were included in our analysis. Pooled results showed a significant association between GGT and risk of CVD mortality (HR: 1.62; 95% CI: 1.47-1.78, P=0.001, P-heterogeneity=0.001) and it was HR: 0.87; 95% CI: 0.73-1.07; P=0.221, P-heterogeneity=0.028, for ALT. There was a direct association between baseline levels of ALP and AST/ALT ratio with CVD mortality (HR: 1.45; 95% CI: 1.11-1.89; P=0.005, P-heterogeneity=0.026, and HR: 2.20; 95% CI: 1.60-3.04; P=0.001, P-heterogeneity=0.540, respectively). Pooled results did not show any significant association between AST and the risk of CVD mortality (HR: 1.20; 95% CI: 0.83-1.73; P=0.313, P-heterogeneity=0.024). Moreover, there was a significant nonlinear association between GGT and ALP levels and the risk of CVD mortality (P=0.008 and 0.016, respectively). Our dose-response meta-analysis revealed a direct relationship between GGT and ALP levels and the risk of CVD mortality. High levels of GGT, ALP and AST/ALT were associated with an increased CVD mortality rate.