Background:Chronic heart failure (CHF) is a common clinical syndrome characterized by reduced exercise capacity, diminished quality of life (QoL), and unfavorable cardiovascular outcomes. Conventional cardiac rehabilitation often requires moderate-to-high-intensity exercise, which may be tolerated poorly by many CHF patients. Low-intensity mind-body interventions, such as traditional Chinese exercises (TCEs), are potentially more suitable; however, the evidence from existing studies is fragmented and sometimes inconsistent. Thus, this study aimed to conduct an umbrella review of systematic reviews (SRs) and meta-analyses (MAs) to evaluate the effectiveness of TCEs in improving exercise capacity, QoL, and cardiovascular function in patients with CHF. Methods:An umbrella review of SRs/MAs was conducted by searching English and Chinese databases without language limits and focusing on randomized controlled trials (RCTs) that assessed the additional benefit of TCEs in individuals with CHF. Methodological quality was appraised using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) checklist and the Risk of Bias in Systematic Reviews (ROBIS) instrument. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was utilized to quantify the certainty of evidence. Individual trial data were retrieved, and re-meta-analyses were performed using standard statistical procedures, with publication bias assessed via Egger's test. Results:A total of 15 SRs/MAs were included, encompassing 65 original trials. Our re-meta-analysis indicated that TCEs were associated with substantially longer 6-minute walk test (6-MWT) values, improved QoL measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), higher left ventricular ejection fraction (LVEF), reduced B-type natriuretic peptide (BNP) levels, and enhanced maximal oxygen consumption (VO2max). Baduanjin exhibited a particularly robust effect on lowering N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, while Yijinjing yielded comparatively greater improvements in VO2max. Nonetheless, limitations such as suboptimal methodological quality and overlapping study samples require cautious interpretation. Conclusions:TCEs may serve as a beneficial adjunct to standard care for CHF, improving exercise capacity, QoL, and key cardiac markers. Large, rigorous RCTs with extended follow-up are needed to confirm the durability of TCEs and further define the role of these exercises in comprehensive CHF rehabilitation. The PROSPERO Registration:CRD420251003129 (https://www.crd.york.ac.uk/PROSPERO/view/CRD420251003129).

BackgroundIt remains unclear whether cardiovascular-kidney-metabolic (CKM) syndrome and genetic susceptibility are associated with cancer incidence. This study aims to evaluate the associations between CKM health status, genetic susceptibility, and cancer incidence, and to develop a machine learning-based prediction model for cancer risk in patients with advanced CKM syndrome.MethodsThis study included 399,034 UK Biobank participants (389,289 with genetic data). CKM health was categorized into stages 0–4. Genetic susceptibility was assessed via a polygenic risk score (PRS). Associations were evaluated using Cox proportional hazard models. For participants with advanced CKM, candidate predictors were screened via the Boruta algorithm, LASSO regression, and multivariable logistic regression. Eight machine learning models were constructed and validated, and their predictive discrimination, calibration performance, and clinical practical value were further assessed. Additionally, Shapley Additive Explanations (SHAP) were adopted to interpret the internal mechanism of the optimal model. The dose–response relationship was assessed using restricted cubic splines (RCS), and mediation analysis was further performed to explore the underlying mechanism of the observed associations.ResultsDuring a median follow-up of 13.7 years, 48,247 incident cancer cases were identified. Compared to CKM stage 0, multivariable-adjusted hazard ratios (HRs) were 1.01 (95% CI: 0.91-1.12) for stage 1, 1.21 (1.10–1.33) for stage 2, and 2.17 (1.95–2.42) for advanced CKM (stage 3–4). Participants with high PRS and advanced CKM faced the highest cancer risk (HR 3.24, 95% CI 2.68–3.93). A total of 14 predictors were retained after screening. The GBM model achieved the best predictive performance (test AUC = 0.801). A web-based calculator was developed to realize individualized cancer risk prediction. RCS analyses indicated that diastolic blood pressure (Pnonlinearity<0.05), neutrophil count(Pnonlinearity<0.05), alkaline phosphatase (Pnonlinearity=0.001), and TyG-BMI (Pnonlinearity<0.05) were significantly and nonlinearly associated with cancer risk. Total bilirubin the strongest positive mediating effect, explaining 44.45% of the total association (P < 0.001).ConclusionsAdvanced CKM syndrome independently increases incident cancer risk, and this elevated risk is significantly amplified by high genetic susceptibility. The validated GBM model provides an interpretable tool for individualized risk estimation, which serves as a valuable complementary tool for clinical risk stratification and cancer patients with, cancer.

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide, yet effective treatment options remain limited. Hesperetin (HES), a natural flavonoid, shows potential for ameliorating NAFLD, but its underlying mechanisms are not fully understood. This study aimed to investigate the effects of HES on NAFLD and its molecular mechanisms in vivo and in vitro. We found that HES alleviated hepatic steatosis and inflammation in rats fed a high-fat diet. In a free fatty acid-exposed HepG2 cell model, HES significantly attenuated lipid accumulation and the release of inflammatory cytokines. Mechanistically, HES activated the farnesoid X receptor (FXR) signaling pathway, leading to the upregulation of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11)-two key inhibitors of ferroptosis-while concurrently suppressing the nuclear factor kappa-B (NF-κB) pathway. Molecular docking analysis indicated that HES binds stably to the ligand-binding pocket of FXR with a predicted affinity of -8.2 kcal/mol. The dependency of these effects on FXR was confirmed using FXR-specific siRNA in HepG2 cells. Additionally, HES enhanced the cellular antioxidant defense, in part through FXR-independent upregulation of the glutamate-cysteine ligase catalytic subunit (GCLC). In conclusion, our results demonstrate that HES inhibits hepatocyte steatosis via FXR-dependent suppression of ferroptosis and inflammation, coupled with FXR-independent enhancement of antioxidant capacity. These findings position HES as a promising candidate FXR activator for NAFLD treatment.

Background S100A8/A9, a critical danger-associated molecular pattern, amplifies inflammatory responses and exacerbates myocardial ischemia-reperfusion injury (MIRI) through Toll-like receptor 4 (TLR4) signaling. Although S100A8/A9-TLR4-related signaling has been implicated in MIRI pathogenesis, effective pharmacological interventions for MIRI remain limited. Purpose This study investigated whether Liqi Huoxue Dripping Pills (Lqhxdw), a traditional Chinese medicine, alleviates MIRI in association with modulation of the S100A8/A9-TLR4-ERK-related signaling axis and elucidated the downstream mechanisms involving mitochondrial dysfunction and ferroptosis. Methods A rat MIRI model was established by temporary LAD ligation, followed by 7-day Lqhxdw treatment. An in vitro hypoxia/reoxygenation (H/R) model was established using drug-containing serum. Transcriptomic profiling, network pharmacology, and molecular docking were performed to identify candidate therapeutic targets. Rescue experiments with recombinant S100A8/A9 (rS100A8/A9), pharmacological pathway validation using U0126, ferroptosis inhibitor rescue using ferrostatin-1, and in vivo pharmacological validation using TAK-242 were performed to support the proposed mechanistic framework. Mitochondrial function and ferroptosis were assessed by Seahorse XF analysis, biochemical assays, fluorescent probes, and transmission electron microscopy. Results Lqhxdw treatment dose-dependently improved cardiac function, attenuated histopathological damage, and reduced myocardial injury biomarkers. Transcriptomic analysis identified S100a8/S100a9 as significantly upregulated genes following MIRI, with negative correlations to mitochondrial Complex I subunits. Molecular docking predicted favorable binding affinity of Lqhxdw components to TLR4. Experimentally, Lqhxdw reduced S100A8/A9-TLR4 co-localization, suppressed TLR4/ERK phosphorylation, and restored the PGC-1α/NRF1/NDUFA9 axis. Seahorse analysis demonstrated restored mitochondrial respiration. Ferroptosis markers were markedly attenuated by Lqhxdw treatment. Critically, exogenous rS100A8/A9 partially reversed these protective effects. Pharmacological validation using U0126 partly restored PGC-1α and NRF1 expression under rS100A8/A9 stimulation, supporting the involvement of ERK upstream of mitochondrial regulatory changes. Ferrostatin-1 rescue experiments provided functional support for the involvement of ferroptosis. In vivo validation with TAK-242 showed regulatory directions broadly consistent with those of Lqhxdw on iron homeostasis markers and NF-κB-associated inflammatory readouts. Conclusion This study provides pharmacological and functional evidence supporting a mechanistic framework in which Lqhxdw attenuates MIRI in association with suppression of S100A8/A9-TLR4-ERK-related signaling, restoration of PGC-1α-mediated mitochondrial biogenesis, and attenuation of ferroptosis. These findings identify S100A8/A9-TLR4-ERK as a biologically relevant signaling framework in MIRI and support the potential clinical application of Lqhxdw in ischemic heart disease.

BackgroundThe associations of the triglyceride-glucose (TyG) index and its derived indices with the progression of cardiovascular-kidney-metabolic (CKM) syndrome remain poorly elucidated.MethodsWe conducted a systematic review and dose-response meta-analysis of 80 observational studies encompassing populations within CKM stages 0–3, evaluating TyG, TyG-BMI, TyG-WC, TyG-WHtR, and CTI for all-cause mortality, cardiovascular disease (CVD) mortality, and CVD incidence (including stroke, coronary heart disease, heart failure and major adverse cardiovascular events). A one-stage mixed-effects approach was used, supplemented by subgroup, meta-regression, leave-one-out, and trim-and-fill analyses.ResultsIn both continuous (per 1-SD increment) and categorical (highest vs. lowest) analyses, TyG-derived indices generally demonstrated stronger risk associations with target outcomes than TyG alone. Notably, CTI, TyG-WC, and TyG-WHtR exhibited higher risk associations. In the highest-category analysis, TyG-WC yielded the most pronounced risk for CVD mortality (RR = 1.52, 95% CI: 1.35–1.70, 95% PI: 1.26–1.82). CTI was associated with a 57% increase in incident CVD (RR = 1.57, 95% CI: 1.33–1.85, 95% PI: 1.00–2.46). Conversely, TyG-BMI showed non-significant associations with mortality-related outcomes (P > 0.05), though it predicted a 51% risk increase for incident CVD (RR = 1.51, 95% CI: 1.36–1.67, 95% PI: 1.05–2.16). Subgroup analysis indicated that these positive associations were pronounced in CKM stages 1–3 but entirely non-significant in stage 0 and the obesity subgroup had a significant impact on the risk of mortality. Dose-response analyses revealed a significant non-linear U-shaped association of the TyG index with all-cause mortality (Pnon-linearity < 0.0001; nadir = 8.90). For CVD mortality, the overall association was significant (Poverall = 0.005; nadir = 8.91), whereas a monotonic increasing trend was observed for CVD incidence (Poverall = 0.0014). In sensitivity analyses excluding participants with cancer or consumptive diseases at baseline, as well as those in CKM stage 0, the U-shaped patterns remained stable (mortality nadir shifted to 9.1).ConclusionsTyG-derived indices, particularly TyG-WC, TyG-WHtR, and CTI, show stronger risk associations than the TyG index for cardiovascular risk assessment in CKM populations, whereas the clinical utility of TyG-BMI is relatively limited. Moderate elevations in TyG were associated with lower mortality risk within a certain range, though the non-linear association was confirmed only for all-cause mortality.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251111362, identifier CRD420251111362.

Background: Currently, there is a scarcity of research exploring the connection between work schedules and coronary heart disease (CHD) or angina. Previous studies on the associations between work schedules and CHD or angina have been primarily limited to specific occupations, particular genders, small sample sizes, or narrow regional focus. This study aims to evaluate the potential association between work schedules and CHD or angina among adults in the United States. Methods: In this cross-sectional study, we selected 13,147 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey 2005–2010 and 2017–2020 cycles. We computed adjusted odds ratio (OR) and 95 % confidence interval (CI) utilizing multivariate logistic regression models. Meticulous subgroup analyses were conducted to ensure the reliability and consistency of our findings. Propensity score assessments were implemented to enhance the comparability between daytime workers and evening or night workers, thereby facilitating a more accurate estimation. Results: Among the participants, 216 were diagnosed with CHD, while 125 were diagnosed with angina. Evening or night workers exhibited a prevalence of CHD that was 1.87 times higher than that of daytime workers (OR: 1.87, 95 % CI: 1.19–2.95, P = 0.007). Furthermore, evening or night workers exhibited a prevalence of angina that was 1.81 times higher than that of daytime workers (OR: 1.81, 95 % CI: 1.05–3.12, P = 0.033). Our findings demonstrated robustness and reliability through subgroup analyses and propensity score assessments. Conclusions: In conclusion, evening or night work schedules were associated with increased CHD and angina risk. Further research should explore biological mechanisms for prevention in this population.

This study addresses limitations of mainstream approaches in traditional Chinese medicine (TCM) data mining by developing the SinoMedminer R package and its Shiny web application. The R package's core functionalities include data cleaning, transformation, TCM attribute statistics, association rule exploration and analysis, clustering analysis, co-occurrence network analysis, formula similarity analysis, formula identification, and dosage analysis. This package enables efficient project analyses without requiring complex coding. The accompanying Shiny web application provides an interactive, menu-driven interface for users without programming knowledge. SinoMedminer combines the computational power of a programming language with user-friendly accessibility, significantly enhancing the efficiency and standardization of TCM data mining research. A deployed server platform further simplifies access and usability by allowing direct utilization of the Shiny application. By optimizing data processing and analysis workflows, SinoMedminer enhances big data handling capabilities, accelerates research progress and product development, and promotes the integration of digital technologies into TCM research and clinical practice.

The DNA-Dependent Protein Kinase catalytic subunit (DNA-PKcs) acts as a principal executor in the DNA damage response (DDR), mediating the phosphorylation of a broad spectrum of substrates integral to DNA repair and apoptosis. This investigation seeks to discern the possible association and mechanisms linking hyperglycemia-induced ferroptosis and DNA-PKcs in DCM. This data exhibits a substantial activation of DNAPKcs- dependent DDR in mice with streptozotocin-induced DCM. However, deletion of DNA-PKcs in cardiomyocytes notably mitigates DNA damage, enhances heart function and dampens the inflammatory response. Co-IP/MS analysis and subsequent validation experiments demonstrate that DNA-PKcs directly interacts with and phosphorylates YAP1 at Thr226. This phosphorylation event facilitates the nuclear retention of YAP1, where it intensifies the transcription of ferroptosis-associated genes. Knockin mice expressing a nonphosphorylatable T226A YAP1 mutant display decreased ferroptosis, reduced myocardial fibrosis and improved heart function. Taken together, this study unravels that DDR acts as an intracellular stress damage sensor, perceiving hyperglycemic conditions and subsequently transmitting the damage signal to incite ferroptosis through the interplay between DNA-PKcs and YAP1. This novel insight suggests that the DNA-PKcs-mediated YAP1 phosphorylation and the ferroptosis activation could be the promising therapeutic targets for the management of DCM.

ETHNOPHARMACOLOGICAL RELEVANCE:Wenxia Changfu formula (WCF), a traditional Chinese herbal medicine, has shown therapeutic potential for treating lung cancer in clinical practice. Metastasis is the main cause of mortality in lung cancer patients, reprogramming tumor-associated macrophages (TAMs) represents a promising strategy. AIM OF THIS STUDY:This study aims to investigate the effects of WCF on metastasis of Lewis lung cancer (LLC) cells and to elucidate the underlying mechanisms. METHODS:RAW264.7 cells were differentiated into M2 macrophages, and conditioned medium from macrophages with different interventions was used to culture LLC cells. The effects of WCF on tumor migration and invasion were evaluated. Specific markers of macrophage polarization, non-targeted metabolomics, lipid content, and the PPAR-γ/CD36 pathway in macrophages were analyzed. To investigate the in vivo effects of WCF on metastasis, a mouse model was established using LLC-luciferase (LLC-Luc) cells, macrophages were depleted upon clodronate liposome administration. RESULTS:WCF effectively inhibited M2-like polarization of macrophages, as evidenced by reduced expression of CD206 and Arg-1, while promoting M1-like polarization, with increased expression of CD86, IL-1β, and TNF-α. These changes were correlated with decreased migration and invasion of LLC cells. In vivo, WCF treatment significantly decreased the fluorescence intensity of LLC-Luc cells, with no significant difference observed between WCF and clodronate liposome interventions. Furthermore, WCF regulated fatty acid metabolism, decreased lipid accumulation, and suppressed the PPAR-γ/CD36 pathway in M2 macrophages. CONCLUSION:WCF inhibits the metastasis of LLC cells by reprogramming TAMs, mediated by the PPAR-γ/CD36 pathway and fatty acid metabolism.

AIMS:The three key and direct risk factors for the significant health issue prevalent worldwide, ischaemic heart disease(IHD), are high fasting plasma glucose (HFPG), high low-density lipoprotein (HLDL) and high systolic blood pressure (HSBP) in metabolic syndrome (MetS). A comprehensive study is essential to present the most recent global epidemiological trends. METHODS:IHD data attributable to HFPG, HLDL and HSBP (3H) were obtained from the Global Burden of Disease Study (GBD) 2021. The absolute burden was manifested in the number of death cases and disability-adjusted life years (DALY). The relative burden was quantified through the age-standardized mortality rate (ASMR) and the age-standardized DALY rate (ASDR). Estimated annual percentage change (EAPC) was used to measure trends. RESULTS:HSBP caused the greatest IHD burden, followed by HLDL, which was much higher than HFPG. The IHD burden associated with HLDL and HSBP were more alike and notably different from HFPG. From 1990 to 2021, ASDR for HSBP and HLDL-related IHD generally declined, with the EAPC of -1.28 (95% CI: -1.34, -1.23) and -1.38 (95% CI: -1.44, -1.33). But the trend was less pronounced for HFPG-related IHD, with the EAPC of -0.90 (95% CI: -2.25, 0.46). The absolute burden was higher in men under 80 and peaked 5-10 years earlier than women. Compared to HSBP and HLDL, HFPG caused a significant increase in burden in low-middle and low socio-demographic index (SDI) regions. The high-middle SDI region, which originally had the highest burden, showed a clear downward trend after 2005 and was gradually overtaken by the low-middle region. Eastern Europe, Central Asia, North Africa and the Middle East had the highest burden among the regions with the same SDI level in Europe, Asia and Africa. CONCLUSION:The HFPG-related IHD burden should be managed differently from HSBP and HLDL. Particular attention should be paid to men, older age groups and regions with low-middle SDI.

Rationale: Dilated cardiomyopathy (DCM) is a severe cardiac condition characterized by ventricular dilation and systolic dysfunction, often leading to heart failure. While the DNA damage response (DDR) pathway is increasingly implicated in DCM pathogenesis, the precise mechanisms linking DDR activation to specific pathological features like adverse extracellular matrix (ECM) remodeling and fibrosis remain poorly understood. Interferon-inducible protein 16 (IFI16), a known DNA sensor involved in DDR and inflammatory signaling, emerges as a potential mediator in this process. This study aimed to investigate the role of the DDR-IFI16 axis in DCM, specifically exploring its connection to ECM dysregulation and cardiac dysfunction, and to evaluate its potential as a therapeutic target. Methods: W This study integrated bioinformatics analyses of human cardiac transcriptomic datasets with experimental validation in a doxorubicin-induced murine DCM model. Cardiac function was assessed by echocardiography. Key molecular pathways were investigated using qPCR, ELISA, and enrichment analyses. Mechanistic roles were tested via pharmacological DDR inhibition in vivo and targeted IFI16 siRNA knockdown in vitro, followed by analysis of fibrosis, cell viability, and cytotoxicity markers. Results: Bioinformatic analyses consistently revealed activation of DDR and cytosolic DNA sensing pathways across human iPSC-CM models and ex vivo DCM heart tissue. WGCNA identified a key gene module strongly associated with DCM, co-enriched for DDR, DNA replication, and ECM/TGF-β signaling pathways. Single-cell RNA-seq analysis confirmed significant IFI16 upregulation in human DCM samples. High IFI16 expression strongly correlated with pathways governing 'Extracellular matrix organization' and key fibrotic genes. Experimental validation in the doxorubicin mouse model confirmed DDR activation. Crucially, in vivo treatment with the DDR inhibitor NU7441 significantly attenuated IFI16 upregulation, ameliorated cardiac dysfunction, and decreased cardiac fibrosis markers. Complementarily, in vitro knockdown of IFI16 significantly reduced pro-fibrotic markers, increased cell viability, and decreased cell injury. Conclusions: Our findings delineate a novel pathogenic axis in DCM where nuclear stress-induced DDR activation drives the upregulation of the DNA sensor IFI16. IFI16 acts as a critical mediator linking DDR signaling to pathological ECM remodeling and fibrosis. Pharmacological inhibition of the upstream DDR pathway effectively mitigates IFI16 induction, attenuates cardiac fibrosis, and improves cardiac function. This study identifies the DDR-IFI16-ECM remodeling axis as a crucial contributor to DCM pathogenesis and highlights its potential as a therapeutic target for mitigating adverse cardiac remodeling and dysfunction.

ABSTRACT:Antithrombotic therapy can prevent recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE). It is, however, associated with an increased risk for major bleeding. This meta-analysis systematically reviewed the evidence regarding the duration of antithrombotic therapy to assess benefits and harms. We systematically searched for randomized controlled trials (RCTs) that compared shorter (3-6 months) with longer (>6 months) courses of anticoagulation for the primary treatment of venous thromboembolism (VTE) or that compared discontinued with indefinite antithrombotic therapy for the secondary prevention of VTE. Pairs of reviewers screened the eligible trials and collected data. This study included 22 RCTs (11 617 participants). Pooled estimates showed that, for the primary treatment of unprovoked VTE, VTE provoked by chronic risk factors or transient risk factors, treating patients with a longer course (>6 months) of anticoagulation, as opposed to a shorter course (3-6 months), probably reduced recurrent PE (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.42-1.02) and DVT (RR, 0.85; 95% CI, 0.63-1.14), but it was associated with increased mortality (RR, 1.43; 95% CI, 0.85-2.41) (moderate certainty) and a higher risk for major bleeding (RR, 2.02; 95% CI, 1.02-3.98; high certainty). For the secondary prevention of unprovoked VTE and VTE provoked by chronic risk factors, when compared with discontinuing treatment, indefinite anticoagulation therapy was associated with decreased mortality (RR, 0.54; 95% CI, 0.36-0.81), a reduction in recurrent PE (RR, 0.25; 95% CI, 0.16-0.41) and DVT (RR, 0.15; 95% CI, 0.10-0.21), and an increase in the risk for bleeding (RR, 1.98; 95% CI, 1.18-3.30), all supported by high certainty. Indefinite antiplatelet therapy may be associated with decreased mortality (RR, 0.95; 95% CI: 0.53-1.68; low certainty), probably a reduction in recurrent PE (RR, 0.65; 95% CI, 0.41-1.03) and DVT (RR, 0.44; 95% CI, 0.17-1.13) (moderate certainty), and may increase the risk for bleeding (RR, 1.28; 95% CI, 0.48-3.41; low certainty). In summary, for the primary treatment of all types of VTE, shorter (3-6 months) duration of anticoagulation is more beneficial. For the secondary prevention of unprovoked VTE or VTE provoked by chronic risk factors, indefinite antithrombotic treatment is more beneficial.

To standardize and harmonize pharmacist-led cholesterol-lowering medication therapy management (MTM) for patients with carotid atherosclerosis and plaque, the Expert Consensus on Lipid-Lowering Pharmacotherapy Management in Patients with Carotid Atherosclerosis and Plaque was developed under the leadership of the PLA General Hospital. This consensus establishes a systematic framework spanning the full-cycle management process: data collection, analytical evaluation, intervention implementation, and long-term follow-up, supported by standardized protocols, documentation forms, and assessment tools. It prioritizes seven evidence-based evaluation domains: therapeutic efficacy, drug selection, dosing appropriateness, adverse reactions, drug-drug/food interactions, cost-effectiveness, and medication adherence. By integrating practical workflows with clinical decision-support tools, the consensus aims to optimize therapeutic outcomes, mitigate safety risks, and provide actionable guidance for healthcare professionals managing this high-risk population.

EDITORIAL article Front. Pharmacol., 03 July 2023Sec. Ethnopharmacology Volume 14 - 2023 | https://doi.org/10.3389/fphar.2023.1236821

BACKGROUND:Heart failure (HF) represents an advanced stage of various cardiovascular disorders, with its elevated admission rates and resultant health economic burden posing an ongoing global concern. PURPOSE:To evaluate the health and economic benefits of herbal medicine (HM) for patients with HF. STUDY DESIGN:Population-based cohort study. METHODS:A five-year retrospective cohort study was carried out at a nationally recognized hospital in China. The study utilized propensity score matching (PSM) to match patients with HF. Chi-square tests were used to analyze dichotomous variables, and t-tests were employed for continuous variables. Logistic regression was used to examine hospital readmission rates, while multiple linear regression was utilized to evaluate direct medical costs. Statistical significance was set at p < 0.05. RESULTS:After implementing PSM, 1924 HF patients were included in the analysis. The study identified two significant risk factors affecting the readmission rates: age over 65 years (adjusted odds ratio (OR) = 1.25, 95 % confidence interval (CI) [1.02, 1.53]) and smoking (adjusted OR = 1.31, 95 % CI [1.01, 1.70]). Additionally, patients who received adjunctive HM treatment exhibited a significantly lower readmission rate compared to those without HM treatment (adjusted OR = 0.76, 95 % CI [0.64, 0.92]). Furthermore, the use of HM during patient hospitalization did not significantly impact direct medical expenses but instead provided positive health economic benefits (incremental cost-effectiveness ratio (ICER) = 98.52). Factors influencing direct routine medical costs included over 65 years of age (Coef = 60.78, 95 % CI [36.25, 85.31]), and cardiac function classification (New York Heart Association (NYHA) III: Coef = 1979.92, 95 % CI [1401.82, 2558.03]; NYHA IV: Coef = 6052.48, 95 % CI [5166.59, 6938.38]). CONCLUSIONS:The integration of HM in patients with HF reduced readmission rates without a notable increase in direct medical costs, and the expense of HM remains an economically range indicating positive health economic outcomes.

The presence of endotoxemia is strongly linked to the development of endothelial dysfunction and disruption of myocardial microvascular reactivity. These factors play a crucial role in the progression of endotoxemic cardiomyopathy. Sepsis-related multiorgan damage involves the participation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). However, whether DNA-PKcs contributes to endothelial dysfunction and myocardial microvascular dysfunction during endotoxemia remains unclear. Hence, we conducted experiments in mice subjected to lipopolysaccharide (LPS)-induced endotoxemic cardiomyopathy, as well as assays in primary mouse cardiac microvascular endothelial cells. Results showed that endothelial-cell-specific DNA-PKcs ablation markedly attenuated DNA damage, sustained microvessel perfusion, improved endothelial barrier function, inhibited capillary inflammation, restored endothelium-dependent vasodilation, and improved heart function under endotoxemic conditions. Furthermore, we show that upon LPS stress, DNA-PKcs recognizes a TQ motif in cofilin2 and consequently induces its phosphorylation at Thr25. Phosphorylated cofilin2 shows increased affinity for F-actin and promotes F-actin depolymerization, resulting into disruption of the endothelial barrier integrity, microvascular inflammation, and defective eNOS-dependent vasodilation. Accordingly, cofilin2-knockin mice expressing a phospho-defective (T25A) cofilin2 mutant protein showed improved endothelial integrity and myocardial microvascular function upon induction of endotoxemic cardiomyopathy. These findings highlight a novel mechanism whereby DNA-PKcs mediates cofilin2Thr25 phosphorylation and subsequent F-actin depolymerization to contribute to endotoxemia-related cardiac microvascular dysfunction.

BackgroundGinkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published.ObjectiveThis overview aims to assess the quality of related SRs and MAs.Search strategy: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022.Inclusion criteria: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included.Data extraction and analysis: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted.ResultsTwenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores.ConclusionGBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS.

Background: In recent years, oats' effect on lowering serum cholesterol has been recognized. However, no systematic reviews summarized the effect of daily consumption of oat-based products on serum lipids in patients with dyslipidemia. Methods: We searched eight databases and two clinical trial registries from inception to July 31, 2023. We included randomized controlled trials (RCTs) evaluating the efficacy of oat-based products (≥4 weeks) on lipid levels or cardiovascular events in patients with dyslipidemia. Two authors independently screened articles, extracted data and assessed the risk of bias of included studies with Cochrane risk-of-bias tool 2.0. We used STATA 17.0 to conduct meta-analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. Results: We finally included 17 eligible trials with 1731 subjects. The oat intervention varied from oat β-glucan-based products to oat bran-based products and wholegrain oat. Overall, the risk of bias of included trials was high or some concerns were noted because of the inadequate randomization, allocation concealment, and inappropriate data analysis method. Compared to the placebo or usual diet, one study indicated that oat-based products have no significant difference in major cardiovascular events. Pooled estimates showed that oat-based products may result in a large reduction in LDL-C (WMD, -0.24 mmol L-1; 95% CI: -0.33, -0.15) (moderate certainty) and TC (WMD, -0.32 mmol L-1; 95% CI: -0.48, -0.17) (moderate certainty). Compared to other diets (mainly other cereals), oat-based products probably reduce the level of LDL-C (WMD, -0.17 mmol L-1; 95% CI: -0.25, -0.08) (moderate certainty) and TC (WMD, -0.21 mmol L-1; 95% CI: -0.30, -0.12) (moderate certainty). Both groups showed that oat-based products had little effect on HDL-C and TG (moderate certainty). Oat-related adverse events were mostly gastrointestinal such as diarrhea, nausea, and flatulence being the most prevalent. Conclusions: Oat-based products may reduce TC and LDL-C, but have little effect on TG, HDL-C, and major cardiovascular events in patients with dyslipidemia.

AbstractBackgroundThe induction of mitochondrial quality control (MQC) mechanisms is essential for the re‐establishment of mitochondrial homeostasis and cellular bioenergetics during periods of stress. Although MQC activation has cardioprotective effects in various cardiovascular diseases, its precise role and regulatory mechanisms in alcoholic cardiomyopathy (ACM) remain incompletely understood.MethodsWe explored whether two mitochondria‐related proteins, phosphoglycerate mutase 5 (Pgam5) and prohibitin 2 (Phb2), influence MQC in male mice during ACM.ResultsMyocardial Pgam5 expression was upregulated in a male mouse model of ACM. Notably, following ACM induction, heart dysfunction was markedly reversed in male cardiomyocyte‐specific Pgam5 knockout (Pgam5cKO) mice. Meanwhile, in alcohol‐treated male mouse‐derived neonatal cardiomyocytes, Pgam5 depletion preserved cell survival and restored mitochondrial dynamics, mitophagy, mitochondrial biogenesis and the mitochondrial unfolded protein response (mtUPR). We further found that in alcohol‐treated cardiomyocyte, Pgam5 binds Phb2 and induces its dephosphorylation at Ser91. Alternative transduction of phospho‐mimetic (Phb2S91D) and phospho‐defective (Phb2S9A) Phb2 mutants attenuated and enhanced, respectively, alcohol‐related mitochondrial dysfunction in cardiomyocytes. Moreover, transgenic male mice expressing Phb2S91D were resistant to alcohol‐induced heart dysfunction.ConclusionsWe conclude that ACM‐induced Pgam5 upregulation results in Pgam5‐dependent Phb2S91 dephosphorylation, leading to MQC destabilisation and mitochondrial dysfunction in heart. Therefore, modulating the Pgam5/Phb2 interaction could potentially offer a novel therapeutic strategy for ACM in male mice.Highlights Pgam5 knockout attenuates alcohol‐induced cardiac histopathology and heart dysfunction in male mice. Pgam5 KO reduces alcohol‐induced myocardial inflammation, lipid peroxidation and metabolic dysfunction in male mice. Pgam5 depletion protects mitochondrial function in alcohol‐exposed male mouse cardiomyocytes. Pgam5 depletion normalises MQC in ACM. EtOH impairs MQC through inducing Phb2 dephosphorylation at Ser91. Pgam5 interacts with Phb2 and induces Phb2 dephosphorylation. Transgenic mice expressing a Ser91 phospho‐mimetic Phb2 mutant are resistant to ACM.