Galactin-8 DNA methylation mediates macrophage autophagy through the MAPK/mTOR pathway to alleviate atherosclerosis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

DNA methylation modifications are an important mechanism affecting the process of atherosclerosis (AS). Previous studies have shown that Galectin-8 (GAL8) level is associated with sudden death coronary heart disease or acute events disease. However, GAL8 and gene expression in AS has not been elucidated, prompting us to carry out further research on it. ApoE-/- mice were used establish model, inhibitor DO05 MAPK/mTOR UO126 for intervention. Pyrosequencing was detect changes levels mouse aorta between groups. ROC curve analysis performed assess relationship atherosclerosis. Aortic staining hematoxylin eosin (H&E) observe aortic intima, plaque area, characteristics secondary lesions within plaque. Oil Red O lipid deposition arterial plaques macrophages. Movat number foam cells Immunohistochemistry (IHC) Western blot quantify localization methyltransferase1 (DNMT1), GAL8, pathway proteins, Light Chain3 (LC3), Beclin1, Sequestosome1 (p62), Tumor Necrosis Factor-α (TNF-α), other proteins. Immunofluorescence (IF) fluorescence intensity LC3, Monocyte chemoattractant protein-1(MCP-1), Detection autophagosomes macrophages by transmission electron microscopy also performed. The cell model induced human monocytes (THP-1) co-cultured using siRNAs targeting DO05, UO126. DNMT1 detected blot; red each group, p62, TNF-α quantitatively determined blot. protein, TNF-α, GAL-8 promoter region harbors six CpG sites susceptible methylation. Following inhibition, DC05 group displayed a significant decrease across all compared C57 Conversely, exhibited increased at first three loci relative group. revealed as independent risk factor atherosclerosis: along inflammation-related proteins MCP-1, MMP9, upregulated lesion while autophagy-related LC3 Beclin1 downregulated. Additionally, phosphorylated After inhibiting DNA, up-regulated, macrophage autophagy inhibited, inflammation increased, atherosclerotic aggravated. direct inhibition activity pathway, weakened, inflammatory response aggravated, specific knockdown siRNA cells, above phenomenon reversed, promoted, reduced, degree alleviated. related progression atherosclerosis, its hypomethylation can aggravate lesions. may be through regulation slow down macrophages, then plaques. Targeting new target diagnosis treatment

Language: Английский

---

Childhood exposure to danger increases Black youths’ alcohol consumption, accelerated aging, and cardiac risk as young adults: A test of the incubation hypothesis

Development and Psychopathology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: April 28, 2025

Abstract Using the dual-pathway framework (Beach et al., 2022a), we tested a Neuro-immune Network (NIN) hypothesis: i.e., that chronically elevated inflammatory processes may have delayed (i.e., incubation) effects on young adult substance use, leading to negative health outcomes. In sample of 449 participants in Family and Community Health Study who were followed from age 10 29, examined non-self-report index alcohol consumption (EAC). By controlling self-reported use at transition adulthood, able isolate significant (incubation) effect childhood exposure danger EAC (β = −.157, p .006), which contributed significantly worse aging outomes. Indirect outcomes via were: GrimAge (IE .010, [.002, .024]), Cardiac Risk −.004, [−.011, −.001]), DunedinPACE .002, [.000, .008]). exploratory analyses potential sex differences effects, showing slightly stronger incubation for men women. Results support NIN hypothesis immune pathway contributes resulting accelerated cardiac risk behavior.

Language: Английский

---

Heavy alcohol consumption but not smoking predicts mortality in patients with acute coronary syndrome

Epigenetics, Journal Year: 2024, Volume and Issue: 19(1)

Published: Nov. 27, 2024

The relationship of heavy alcohol consumption (HAC) and smoking to mortality in those with CHD, mechanisms through which these effects are elicited not clear. In order improve our understanding, we examined the Alcohol T-Scores (ATS), an epigenetic biomarker chronic HAC, cg05575921 methylation, a intensity, all-cause degree coronary artery obstruction cohort 217 subjects admitted for CHD-related acute syndrome (ACS). We found that 65% had ATS values indicative HAC. values, but were significantly associated (p < 0.02) subsequent proband death (total 28 deaths) Cox Proportional Hazards model showing slightly larger effect levels than age on survival (overall model, p 0.003). Subjects highest decile scores 2.4-fold increase risk as compared lowest decile. contrast, methylation 0.003) scores, inversely obstruction. Only 2 referred treatment either or drinking. conclude HAC is underappreciated driver mortality, ACS who smoke much less likely have significant upon cardiac imaging substance use may be underutilized CHD.

Language: Английский

---

The Reversion of the Epigenetic Signature of Coronary Heart Disease in Response to Smoking Cessation

Genes, Journal Year: 2023, Volume and Issue: 14(6), P. 1233 - 1233

Published: June 8, 2023

Coronary heart disease (CHD) is the leading cause of death worldwide. However, current diagnostic tools for CHD, such as coronary computed tomography angiography (CCTA), are poorly suited monitoring treatment response. Recently, we have introduced an artificial-intelligence-guided integrated genetic-epigenetic test CHD whose core consists six assays that determine methylation in pathways known to moderate pathogenesis CHD. whether at these loci sufficiently dynamic guide response unknown. To hypothesis, examined relationship changes cg05575921, a generally accepted marker smoking intensity, using DNA from cohort 39 subjects undergoing 90-day cessation intervention and methylation-sensitive digital PCR (MSdPCR). We found epigenetic intensity were significantly associated with reversion CHD-associated signature five MSdPCR predictor sites: cg03725309, cg12586707, cg04988978, cg17901584, cg21161138. conclude methylation-based approaches could be scalable method assessing clinical effectiveness interventions, further studies understand responsiveness measures other forms order.

Language: Английский

---

Precision Epigenetics Provides a Scalable Pathway for Improving Coronary Heart Disease Care Globally

Epigenomics, Journal Year: 2023, Volume and Issue: 15(16), P. 805 - 818

Published: Aug. 1, 2023

Coronary heart disease (CHD) is the world's leading cause of death. Up to 90% all CHD deaths are preventable, but effective prevention this mortality requires more scalable, precise methods for assessing status and monitoring treatment response. Unfortunately, current diagnostic have barriers implementation, particularly in rural areas lower-income countries. This gap may be bridged by highly scalable advances DNA methylation testing artificial intelligence. Herein, we review prior studies related alone combination with other biovariables. We compare these new established diagnosing CHD. Finally, outline pathways through which methylation-based allow democratization improved globally.

Language: Английский

---

Fetal heart diseases and neonatal mortality: Risk factors and management

Archives of Gynecology and Obstetrics, Journal Year: 2024, Volume and Issue: 310(5), P. 2497 - 2505

Published: Sept. 30, 2024

Language: Английский

---

Two Clinically Implementable Digital PCR Assessments of DNA Methylation for Diagnosing Heavy Alcohol Consumption

Epigenomes, Journal Year: 2024, Volume and Issue: 9(1), P. 1 - 1

Published: Dec. 24, 2024

Heavy alcohol consumption (HAC) has a profound adverse effect on human health. Unfortunately, there is relative lack of tools that are easily implementable in clinical settings and can be used to supplement self-reporting the diagnosis management HAC. In part, this paucity due limitations currently available biological measures mismatch between needs clinicians managing We first review pros cons existing measures. Next, we underlying theory performance characteristics two recently developed methylation-sensitive digital PCR (MSdPCR) assays, referred as Alcohol T Score (ATS) ZSCAN25, for assessment chronic recent HAC, respectively. Finally, outline paradigm improving use disorders by utilizing these new markers consumption. conclude further studies understand test each epigenetic larger, diverse populations order.

Language: Английский

---

Menu Engineering on Food to Increase Revenue at Laku Café, Gading Serpong

Jurnal Syntax Transformation, Journal Year: 2023, Volume and Issue: 4(12), P. 114 - 122

Published: Dec. 28, 2023

The Food and Beverage industry is an that has existed developed for a long time until now. sector engaged in the manufacture serving of food beverages also provides services to customers. Merdeka (2022) emphasizes part hospitality centered on beverage which aims achieve customer satisfaction. method used descriptive research with qualitative approach. Research data collection was carried out using documentation studies determine level menu profitability engineering system. Based results analysis, it can be concluded among items sold, there are several less popular menus bring low profits. There many ways increase revenue, including: increasing attractiveness menu, prices by switching cheaper raw materials same quality, reducing portion sizes or creating combination packages other have costs, removing from list. menu.

Language: Английский

---

A retrospective case-control study for Clinical Validation of mutated ZNF208 as a novel biomarker of fatal blast crisis in Chronic Myeloid Leukemia

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 15, 2024

Abstract The hallmark of Chronic Myeloid Leukemia (CML) is Philadelphia chromosome t(9:22), which leads to formation BCR-ABL1 fusion oncogene. induces genetic instability, causing the progression chronic myeloid leukemia from manageable Phase (CP-CML) accelerated phase (AP-CML) and ultimately lethal blast crisis (BC-CML). precise mechanism responsible for CML are not well comprehended, there a lack specific molecular biomarkers advanced CML. Mutations in transcription factors (TFs) have significant role cancer initiation, relapses, invasion, metastasis, resistance anti-cancer drugs. Recently, our group reported association novel factor, ZNF208, with was dire need clinical validation this biomarker. Therefore, aim study clinically validate mutated ZNF208 as biomarker larger cohort AP- BC-CML patients using control-case studies. A total 73 (N=73) King Saud University Medical City Riyadh Abdulaziz National Guard Hospital, Al-Ahsa, Saudi Arabia were enrolled (2020-2023), experimental (cases) consisting AP-CML (n=20) (n=12). controls consisted age/sex matched CP-CML (n=41). approved by Research Ethics Committees participating institutes all provided informed consent study. Clinical evaluations conducted according guidelines established European LeukemiaNet 2020. Targeted resequencing ZNF 208 employed Illumina NextSeq500 instrument (Illumina, San Diego, CA, USA) mutations confirmed Sanger sequencing. Both next generation sequencing identified missense mutation (c.64G>A) ZNF208. 56 (93.3) and12 (100) CP-, respectively, while none (0%) or healthy genomic databases (p=0.0001). studies show that very AP-and patients. other such proteins may cause carcinogenesis interacting KAP-1 repressor silence many target genes thus prove be drug targets well. we recommend carrying out prospective trials further its utilization decision, investigating pathogenesis investigate potential Simple Summary type blood caused oncogene, leading instability changes. This results advancement (CP) an (AP) finally (BC). development known, dearth dependable shared indicators. Transcription class molecules that, when altered, significantly contribute cancer, including has been factor gene associated BC-CML. Here, carried targeted resequencing. detected 0 (0%), respectively (p=0.0001) demonstrating high specificity shows progression. We

Language: Английский

---

The Use of Precision Epigenetic Methods for the Diagnosis and Care of Stable Coronary Heart Disease Reduces Healthcare Costs

Advances in Therapy, Journal Year: 2024, Volume and Issue: 41(6), P. 2367 - 2380

Published: April 25, 2024

The cost of secondary prevention coronary heart disease (CHD) is continuing to increase, with a substantial portion this acceleration being driven by the expense confirmatory diagnostic testing. Conceivably, newly developed precision epigenetic technologies could drive down these costs. However, at current time, their impact on overall for CHD care poorly understood. We hypothesized that use developed, highly sensitive, and specific test, PrecisionCHD, decrease costs prevention.

Language: Английский

---