Cardiac protection of wogonin in mice with pulmonary fibrosis by regulating Sirt1/ γ-H2AX pathway DOI Creative Commons
Libo Wang,

Fei Lin,

Runran Miao

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 14, 2025

Background Clinical evidence suggests that pulmonary fibrosis (PF) and heart failure (HF) often co-exist; however, the specific impact of PF on HF remains underexplored. This gap in understanding complicates management treatment patients with PF. Objectives To investigate effects cardiac function myocardial using a mouse model evaluate therapeutic potential wogonin, flavonoid compound known for its anti-PF properties. Methods A was established via intratracheal administration bleomycin (BLM). Starting day 8 post-BLM treatment, wogonin (50 mg/kg) intraperitoneally administered every 2 days weeks. Cardiac assessed echocardiography, while evaluated through Masson staining. In vitro , H9C2 cardiomyocytes were exposed to CoCl or H O 24 h without (20 μM) treatment. Apoptosis DNA damage markers analysed immunofluorescence, immunoblotting, Comet assay. The interaction between Sirt1 examined biotin-affinity pulldown assays molecular docking simulations. Results Mice exhibited significant dysfunction fibrosis. Wogonin markedly improved ejection fraction attenuated mice. Mechanistic studies revealed alleviated cardiomyocyte apoptosis by upregulating downregulating γ-H2AX expression. Docking simulations predicted forms stable complex hydrogen-bonding hydrophobic interactions, which further validated assays. Conclusion exerts protective against mice modulating Sirt1/γ-H2AX-mediated pathways reduce apoptosis. These findings suggest as agent managing associated

Language: Английский

Molecular Engineering of Melanin for Enhanced Biological γ-ray Protection DOI Creative Commons
Wei Cao,

Ruotong Deng,

Yuxi Li

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract The escalating utilization of ionizing radiation across medicine and industry, coupled with the relentless global nuclear rivalry, underscoring paramount urgency effective radioprotective materials. Conventional materials such as lead concrete are widely used, lead-free have also emerged to solve problems cumbersome toxic lead, metal-containing micro/nano polymers. Nevertheless, there is still a significant challenge in meeting urgent need for lightweight biocompatible alternatives. To tackle this challenge, work utilizes molecular engineering melanin develop panel novel metal-free enhanced conjugation, heightened physical shielding against antioxidant properties. Remarkably, engineered demonstrated unprecedented in vivo γ-ray protection, increasing mice survival from 0–100%.

Language: Английский

Citations

0
Establishing a Prognostic Model Correlates to Inflammatory Response Pathways for Prostate Cancer via Multiomic Analysis of Lactylation‐Related Genes DOI Creative Commons
Qinglong Du, Chen Meng, Wenchao Zhang

et al.

International Journal of Genomics, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Prostate cancer (PCa) continues to pose substantial clinical challenges, with molecular heterogeneity significantly impacting therapeutic decision‐making and disease trajectories. Emerging evidence implicates protein lactylation—a novel epigenetic regulatory mechanism—in oncogenic processes, though its prognostic relevance in PCa remains underexplored. Through integrative bioinformatics interrogation of lactylation‐associated signatures, we established correlations using multivariable feature selection methodologies. Initial screening via differential expression analysis (limma package) coupled Cox proportional hazards modeling revealed 11 survival‐favorable regulators 16 hazard‐associated elements linked biochemical recurrence. To enhance predictive precision, ensemble machine learning frameworks were implemented, culminating a 10‐gene lactylation signature demonstrating robust discriminative capacity (concordance index = 0.738) across both primary (TCGA‐PRAD) external validation cohorts (DKFZ). Multivariable regression confirmed the score’s independence, exhibiting prominent associations clinicopathological parameters including tumor staging metastatic potential. The developed clinical‐molecular nomogram achieved superior accuracy (C − > 0.7) through synergistic integration biological covariates. Tumor microenvironment deconvolution uncovered distinct immunological landscapes, high‐risk stratification correlating enriched stromal infiltration immunosuppressive phenotypes. Pathway enrichment analyses implicated chromatin remodeling processes cytokine‐mediated inflammatory cascades as potential mechanistic drivers divergence. Therapeutic vulnerability profiling demonstrated response patterns: low‐risk patients exhibited enhanced immune checkpoint inhibitor responsiveness, whereas subgroups showed selective chemosensitivity docetaxel mitoxantrone. Functional PC‐3 models AK5 silencing induced proapoptotic effects, suppressed migration invasion, modulated regulation CD276 coexpression. These multimodal findings position dynamics, particularly AK5‐mediated pathways, promising targets biomarkers management.

Language: Английский

Citations

0
Aloe‐Emodin Improves Mitophagy in Alzheimer's Disease via Activating the AMPK/PGC‐1α/SIRT3 Signaling Pathway DOI Creative Commons
Yulu Wang, Yanqi Ge,

Siyu Hua

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)

Published: March 1, 2025

Impaired mitophagy results in the accumulation of defective mitochondria that are unable to be cleared effectively Alzheimer's disease (AD). Aloe-emodin (AE), a key component traditional Chinese medicine Rhubarb, exhibits neuroprotective effects against disease, though underlying mechanism remains unclear. Studying aloe-emodin's role enhancing is vital for improving cognitive function and reducing neuronal damage disease. The APP/PS1 double transgenic mice were adopted as models AD assess aloe-emodin upon its impact on hippocampal neurons. Additionally, we investigated regulatory mechanisms proteins within aforementioned pathway, morphological characteristics mitophagy-related proteins. An neuron model was developed using Aβ25-35 evaluate mitochondrial function, protein expression such pathway mitophagy. This approach aims elucidate relation AD. AE activates neurons, improves dysfunction, reduces damage, alleviates symptoms mice. AMPK, PGC-1α SIRT3. Increased SIRT3 promotes regulates When autophagy enhanced, Beclin1, LC3, P62, Parkin, PINK1-related changes. Further vitro experiments showed can enhance cell models. membrane potential, GSH, ROS Ca2+ levels gradually recover, alleviating pathological manifestations Knocking down leads increased reduction HT22 cells. Experimental show activate through AMPK/PGC-1α/SIRT3 alleviate dysfunction AD, reduce

Language: Английский

Citations

0
Prognostic value of tryptophan catabolism-base scores in acute myocardial infarction patients DOI Creative Commons
Ye Wang, Pengyan Wu,

Zhanchao Chen

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Mechanisms for Regulatory Effects of Exercise on Metabolic Diseases from the Lactate–Lactylation Perspective DOI Open Access

G Chen,

Jinchao Liu,

Yongbin Guo

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3469 - 3469

Published: April 8, 2025

Metabolic diseases, including cardiovascular type 2 diabetes mellitus (T2DM), osteoporosis, and non-alcoholic fatty liver disease (NAFLD), constitute a major global health burden associated with chronic morbidity mortality. Lactate, once considered as metabolic byproduct, has emerged key regulator of cellular reprogramming through lactylation, novel post-translational modification (PTM) that dynamically couples flux to chromatin remodeling. Lactylation exerts dual regulatory roles signaling molecule via GPR81/GPR4-mediated pathways substrate for the covalent histones enzymes. Pathologically, hyperlactatemia suppresses mitochondrial biogenesis, driving cardiomyopathy epigenetic silencing oxidative metabolism genes. Conversely, exercise-induced lactate surges transiently enhance insulin sensitivity AMPK/PGC-1α/GLUT4 signaling, resolve inflammation GPR81-mediated M2 macrophage polarization, restore function lactylation-dependent pathways. This review delineates lactylation spatiotemporal rheostat: dysregulation perpetuates disorders, whereas acute exercise-mediated remodels transcriptional networks homeostasis. Future research should integrate multiomics clarify lactylation’s dynamics, tissue-specific thresholds, metabolism–immunity interactions, metabolic–epigenetic crosstalk precision management diseases.

Language: Английский

Citations

0
Cardiac protection of wogonin in mice with pulmonary fibrosis by regulating Sirt1/ γ-H2AX pathway DOI Creative Commons
Libo Wang,

Fei Lin,

Runran Miao

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 14, 2025

Background Clinical evidence suggests that pulmonary fibrosis (PF) and heart failure (HF) often co-exist; however, the specific impact of PF on HF remains underexplored. This gap in understanding complicates management treatment patients with PF. Objectives To investigate effects cardiac function myocardial using a mouse model evaluate therapeutic potential wogonin, flavonoid compound known for its anti-PF properties. Methods A was established via intratracheal administration bleomycin (BLM). Starting day 8 post-BLM treatment, wogonin (50 mg/kg) intraperitoneally administered every 2 days weeks. Cardiac assessed echocardiography, while evaluated through Masson staining. In vitro , H9C2 cardiomyocytes were exposed to CoCl or H O 24 h without (20 μM) treatment. Apoptosis DNA damage markers analysed immunofluorescence, immunoblotting, Comet assay. The interaction between Sirt1 examined biotin-affinity pulldown assays molecular docking simulations. Results Mice exhibited significant dysfunction fibrosis. Wogonin markedly improved ejection fraction attenuated mice. Mechanistic studies revealed alleviated cardiomyocyte apoptosis by upregulating downregulating γ-H2AX expression. Docking simulations predicted forms stable complex hydrogen-bonding hydrophobic interactions, which further validated assays. Conclusion exerts protective against mice modulating Sirt1/γ-H2AX-mediated pathways reduce apoptosis. These findings suggest as agent managing associated

Language: Английский

Citations

0