Co-Exposure to Ammonia and Lipopolysaccharide-Induced Impaired Energy Metabolism via the miR-1599/HK2 Axis and Triggered Autophagy, ER Stress, and Apoptosis in Chicken Cardiomyocytes

Poultry Science, Journal Year: 2025, Volume and Issue: 104(4), P. 104965 - 104965

Published: March 1, 2025

Ammonia (NH3) and lipopolysaccharide (LPS), common pollutants in poultry farming environments, pose significant health risks by disrupting cellular processes. Although previous studies have demonstrated the individual effect of NH3 or LPS on human animal health, mechanisms underlying their combined impact chicken heart tissue remain poorly understood. In this study, we established a cardiotoxicity model to investigate effects and/or exposure energy metabolism, autophagy, endoplasmic reticulum (ER) stress, apoptosis cardiomyocytes. Our findings indicated that or/and reduced ATPase activity ATP content, led downregulation HK2, PK, PDHX, SDH, upregulation AMPK, resulting impaired metabolism Additionally, found gga-miR-1599/HK2 axis as key regulator involved LPS-induced impairment. The impairment activated AMPK/mTOR pathway, which subsequently triggered evidenced Beclin, LC3-I, LC3-II. Furthermore, decreased mTOR expression induced ER markers such ATF6, GRP78, IRE1, PERK. turn, increased CHOP expression, downregulated Bcl-2 upregulated Bim, elevated levels Bax, caspase-9, caspase-3, ultimately triggering apoptosis. This study provides valuable insights into co-exposure identifies potential molecular targets for mitigating these adverse effects.

Language: Английский

---

Disruption of the eEF1A1/ARID3A/PKC‐δ Complex by Neferine Inhibits Macrophage Glycolytic Reprogramming in Atherosclerosis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Abstract Glycolytic reprogramming of macrophages is a decisive factor in atherosclerosis (AS) plaque formation. Eukaryotic elongation 1A1 (eEF1A1) plays an important role protein synthesis, ubiquitination degradation, and nuclear translocation. However, the potential function eEF1A1 AS has not yet been fully understood. Here, natural small molecule neferine (Nef), which targets to suppress macrophage glycolytic discovered. In this work, chemical genetics non‐modified target confirmation assays are used confirm that direct Nef. Mechanically, Nef disrupted formation eEF1A1/ARID3A/PKC‐δ complex, inhibits phosphorylation ARID3A at Thr491, consequently prevents its Meanwhile, it verified transcriptional regulator enolase 2 (ENO2), enzyme process. suppresses ENO2 transcription activation by affecting binding promoter region ENO2, results inhibition transformation from M1 M2. Collectively, these findings provide attractive future direction for therapy inhibiting ARID3A/ENO2‐mediated targeting eEF1A1.

Language: Английский

---

The attenuated hepatic clearance of propionate increases cardiac oxidative stress in propionic acidemia

Basic Research in Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 11, 2024

Language: Английский

---

Association between lactate dehydrogenase levels and all-cause mortality in ICU patients with heart failure: a retrospective analysis of the MIMIC-IV database

BMC Cardiovascular Disorders, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 29, 2025

Heart failure (HF) patients admitted to the intensive care unit (ICU) often face high short-term mortality rates. This study aims investigate relationship between lactate dehydrogenase (LDH) levels and all-cause in critically ill with HF. Data from MIMIC-IV database were extracted for subjects eligible HF diagnosis. We utilized restricted cubic spline (RCS) method, Kaplan-Meier (K-M) survival curves, Cox regression analysis assess association patients. Overlap weighting (OW) subgroup employed enhance robustness reliability of study. A total 3,065 enrolled this RCS revealed a nonlinear LDH risk HF, hazard ratio (HR) > 1 when exceeded 315 U/L. The K-M curve indicated lower rates shorter times ≥ Elevated independently associated increased in-hospital 1-year rates, adjusted HR 1.39 (95% CI: 1.16, 1.67) 1.29 1.14, 1.45), respectively. results remained consistently robust OW analyses. significantly an ICU-admitted Further randomized trials are needed confirm association.

Language: Английский

---

Pyruvate dehydrogenase alleviates macrophage autophagy in Hcy-induced ApoE<sup>-/-</sup> mice

Acta Biochimica et Biophysica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Macrophages play a protective role in atherosclerosis, whereas homocysteine (Hcy) is recognized as an independent risk factor for atherosclerosis. Defects macrophage autophagy contribute to the formation of atherosclerotic plaques, and dysregulated energy metabolism closely linked process autophagy. However, regulation by pyruvate dehydrogenase (PDH), key component PDH complex involved metabolic homeostasis, remains poorly understood context atherosclerosis induced Hcy. In our study, proteomic profiling identifies 748 upregulated proteins 760 downregulated Hcy-treated macrophages. KEGG pathway analysis reveals significant enrichment differentially expressed metabolism-related pathways, including those related biosynthesis amino acids, carbon metabolism, glycolysis/gluconeogenesis. Additionally, we explore mediating Hcy-induced ApoE -/- mice. The results show marked reduction expression activity macrophages, leading impaired Notably, activation enhances assembly initiator ULK1-FIP200-Atg13 through modulation AMPK/mTOR signaling pathway, suggesting potential therapeutic target

Language: Английский

---

Combined analysis of single-cell and bulk transcriptome sequencing data identifies critical glycolysis genes in idiopathic pulmonary arterial hypertension

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 26, 2025

Abnormal glycolytic metabolism plays a significant role in pulmonary vascular remodeling idiopathic arterial hypertension (IPAH), yet the specific mechanisms remain unclear. The primary objective of this study is to investigate key regulatory glycolysis IPAH. Bulk and single-cell sequencing data obtained from IPAH patient tissue samples were downloaded GEO database. scMetabolism AUCcell analyses carried out quantify metabolic activity identify main cell types regulating glycolysis, respectively. ssGSEA method was used assess each bulk sample within data. Differential analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) conducted genes associated with samples. Single-cell monocrotaline (MCT)-induced model PH rats utilized validate expression these genes. indicated that patients displayed increased activity, which primarily regulated by fibroblasts. Similarly, transcriptomic revealed increase patients. WGCNA, PPI integrated further identified insulin-like growth factor-1 (IGF1), lysyl-tRNA synthetase (KARS), caspase-3 (CASP3), cyclin-dependent kinase inhibitor 2 A (CDKN2A) as fibroblast-mediated IGF1, KARS, CASP3, CDKN2A also observed our vivo PH. Our identifies IPAH, provides basis for development targeted therapies.

Language: Английский

---

The allergenic potential of enolases: physiological and pathophysiological insights

Current Opinion in Allergy and Clinical Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

This review gives an overview on the current knowledge of physiological and pathophysiological features enolases how these might contribute to enzymes' allergenic properties. It summarizes most recent literature raises questions that need be answered in future gain a better understanding role allergic diseases. The identification two novel enolases, from London plane tree whiff, further supports uniqueness this allergen family: occurrence three major kingdoms life capability induce symptoms via inhalation, ingestion, skin contact. importance as molecules is widely accepted. However, studies linking biochemical with their potential allergies are still needed. would about induction diseases, improve specificity sensitivity allergy diagnosis enable development patient-tailored prophylactic therapeutic approaches.

Language: Английский

---

Aspalathin-Rich Unfermented Aspalathus linearsis Extract Mitigates Vascular Endothelial Inflammation by Inhibiting the TNF-α/Hexokinase 2/NF-κB Signaling Pathway

Journal of Agriculture and Food Research, Journal Year: 2025, Volume and Issue: unknown, P. 101882 - 101882

Published: April 1, 2025

Language: Английский

---

Gut microbiome-based noninvasive diagnostic model to predict acute coronary syndromes

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 11, 2024

Background Previous studies have shown that alterations in the gut microbiota are closely associated with Acute Coronary Syndrome (ACS) development. However, value of for early diagnosis ACS remains understudied. Methods We recruited 66 volunteers, including 29 patients a first and 37 healthy volunteers during same period, collected their fecal samples, sequenced V4 region 16S rRNA gene. Functional prediction was performed using PICRUSt2. Subsequently, we constructed nomogram corresponding webpage based on microbial markers to assist ACS. The diagnostic performance usefulness model were analyzed boostrap internal validation, calibration curves, decision curve analysis (DCA). Results Compared controls, diversity composition community markedly abnormal. Potentially pathogenic genera such as Streptococcus Acinetobacter significantly increased group, whereas certain SCFA-producing Blautia Agathobacter depleted. In addition, correlation clinical indicators, observed be level inflammation severity coronary atherosclerosis. Finally, variables developed an area under receiver operating characteristic (ROC) (AUC) 0.963 (95% CI: 0.925–1) AUC 0.948 0.549–0.641) bootstrap validation. curves show good consistency between actual predicted probabilities. DCA showed had high net benefit applications. Conclusion Our study is characterize function populations Southwest China demonstrates potential effect non-invasive marker

Language: Английский

---

Cell cycle arrest of cardiomyocytes in the context of cardiac regeneration

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: April 28, 2025

The limited capacity of adult mammalian cardiomyocytes to undergo cell division and proliferation is one the key factors contributing heart failure. In newborn mice, cardiac occurs during a brief window, but this proliferative diminishes by 7 days after birth. Current studies on regeneration focused elucidating changes in regulatory within before aiming determine whether potential association between these cycle arrest cardiomyocytes. Facilitating re-entry into or reversing their exit from it represents critical strategy for regeneration. This paper provides an overview role regeneration, briefly describes cardiomyocyte systematically summarizes regulation cardiomyocytes, metabolic mechanisms underlying arrest. Additionally, we highlight development cardiovascular disease drugs targeting status clinical treatment. Our goal outline strategies promoting repair following injury, while also pointing toward future research directions that may offer new technologies prospects treating diseases, such as myocardial infarction, arrhythmia

Language: Английский

---