Prognostic factors of MINOCA and their possible mechanisms

Preventive Medicine Reports, Journal Year: 2024, Volume and Issue: 39, P. 102643 - 102643

Published: Feb. 4, 2024

Despite not showing substantial stenosis of coronary arteries, Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) presents myocardial ischemia injury, thus having a grave prognosis and high risk long-term complications. This necessitates increased clinical attention exploration its root causes to prevent similar crisis.

Language: Английский

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CD36-mediated uptake of oxidized LDL induces double-negative regulatory T cell ferroptosis in metabolic dysfunction-associated steatotic liver disease

Metabolism, Journal Year: 2024, Volume and Issue: 164, P. 156127 - 156127

Published: Dec. 30, 2024

Language: Английский

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ABCA1-mediated nascent HDL formation is precisely regulated by the plasma membrane cholesterol

Journal of Lipid Research, Journal Year: 2025, Volume and Issue: unknown, P. 100762 - 100762

Published: Feb. 1, 2025

Intracellular cholesterol transport is essential for maintaining cellular homeostasis. ABCA1 continuously moves from the inner leaflet to outer of plasma membrane (PM) maintain low levels. When PM levels exceed ER levels, which are maintained at approximately 5 mol% by complex sterol regulatory element-binding protein (SREBP) and SREBP cleavage-activating (SCAP), Aster-A/GramD1a transports excess ER. Furthermore, removes promoting its efflux as nascent high-density lipoprotein (HDL) particles. Thus, homeostasis coordinated action SCAP-SREBP, Aster-A/GramD1a, ABCA1. While regulation SCAP-SREBP well-understood, mechanism governing activity remain less understood. In this study, we investigated impact on ABCA1-mediated phosphatidylcholine (PC) efflux. Cells were treated with various concentrations methyl-β-cyclodextrin (MβCD) or MβCD-cholesterol 30 minutes modulate We found that initial velocities both PC dependent solely despite being substrates Intriguingly, when dropped below 70% level observed in cells cultured presence 10% FBS, ceased, even abundant PM. Our findings suggest HDL formation precisely regulated optimal

Language: Английский

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Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis

Published: Feb. 20, 2025

Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate which cannot either import, store or catabolize acids restrict by both common and divergent anti-microbial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction same fails rescue growth. work expands our understanding how homeostasis impacts macrophage.

Language: Английский

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Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 3, 2025

Aberrant lipid metabolism is a well-recognized hallmark of cancer. Notably, breast cancer (BC) arises from lipid-rich microenvironment and depends significantly on metabolic reprogramming to fulfill its developmental requirements. In this review, we revisit the pivotal role in BC, underscoring impact progression tumor microenvironment. Firstly, delineate overall landscape highlighting roles patient prognosis. Given that lipids can also act as signaling molecules, next describe exchanges between BC cells other cellular components Additionally, summarize therapeutic potential targeting aspects processes, lipid-related transcription factors immunotherapy BC. Finally, discuss possibilities problems associated with clinical applications lipid‑targeted therapy propose new research directions advances spatiotemporal multi-omics.

Language: Английский

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Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 13, 2025

Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host-derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyses demonstrate cannot either import, store, or catabolize acids restrict by both common and divergent antimicrobial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy, nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction same fails rescue growth. work expands our understanding how host homeostasis impacts macrophage.

Language: Английский

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Osteopontin in Chronic Inflammatory Diseases: Mechanisms, Biomarker Potential, and Therapeutic Strategies

Biology, Journal Year: 2025, Volume and Issue: 14(4), P. 428 - 428

Published: April 16, 2025

Chronic inflammatory diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), atherosclerosis, and bowel disease (IBD), pose major global health concerns. These disorders are marked by persistent inflammation, immune system dysfunction, tissue injury, fibrosis, ultimately leading to severe organ dysfunction diminished quality of life. Osteopontin (OPN), a multifunctional extracellular matrix protein, plays crucial role in regulation, remodeling. It promotes cell recruitment, stimulates pro-inflammatory cytokine production, contributes fibrosis through interactions with integrins CD44 receptors. Additionally, OPN activates key pathways, including NF-κB, MAPK, PI3K/Akt, further aggravating damage chronic conditions. Our review highlights the its potential biomarker, therapeutic implications. We explore promising preclinical approaches, monoclonal antibodies, small molecule inhibitors, natural compounds like curcumin, which have demonstrated mitigating OPN-driven inflammation. However, challenges persist selectively targeting while maintaining essential physiological roles, bone remodeling wound healing. offers insights into strategies future research directions.

Language: Английский

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Model systems to study Mycobacterium tuberculosis infections: an overview of scientific potential and impediments

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: May 8, 2025

Despite years of global efforts to combat tuberculosis (TB), Mycobacterium (Mtb), the causative agent this disease, continues haunt humankind making TB elimination a distant task. To comprehend pathogenic nuances organism, various in vitro, ex vivo and experimental models have been employed by researchers. This review focuses on salient features as well pros cons model systems for research. In vitro macrophage infection extensively used studying Mtb physiology. Animal provided us with great wealth information immensely contributed understanding pathogenesis host responses during infection. Additionally, they evaluation anti-mycobacterial drug therapy determining efficacy potential vaccine candidates. Advancements 'omics' based approaches enhanced our about host-pathogen interface. Although animal cornerstone research, none them is ideal that gives complete picture human infection, disease progression. Further, also discusses newer including three dimensional (3D)-tissue models, lung-on-chip model, granuloma their limitations TB. Thus, converging gained from tandem experiments will ultimately bridge gap exists

Language: Английский

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From malaria fighter to diabetes guardian: the emerging role of artesunate in treating diabetes and diabetic complications

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

Published: May 22, 2025

Diabetes mellitus (DM) is a metabolic disease influenced by both genetic and environmental factors. The global incidence of DM rising, its multiple complications seriously affect patients’ quality life create huge economic burden. At present, the prevention treatment mainly rely on oral or subcutaneous drugs, although drugs are more acceptable, they may produce side effects have limited effect diabetic complications. Artesunate (ART) first-line antimalarial drug widely used worldwide. Whether orally intravenously, ART has high bioavailability excellent pharmacokinetic properties in humans, shown good tolerance safety patients ages. Recent pharmacological studies that, except for properties, also wide range therapeutic potential This review aims to synthesize latest research results, summarize discuss current role mechanism improving diabetes complications, provide theoretical basis subsequent exploration anti-diabetes development new antidiabetic agents based ART, which great clinical significance strengthening

Language: Английский

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Atf3-mediated metabolic reprogramming in hepatic macrophage orchestrates metabolic dysfunction–associated steatohepatitis

Science Advances, Journal Year: 2024, Volume and Issue: 10(30)

Published: July 24, 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is regulated by complex interplay between the macrophages and surrounding cells in liver. Here, we show that Atf3 regulates glucose-fatty acid cycle attenuates hepatocyte steatosis, fibrogenesis hepatic stellate (HSCs). Overexpression of protects against development MASH Western diet-fed mice, whereas ablation has opposite effect. Mechanistically, improves reduction fatty oxidation induced glucose via forkhead box O1 (FoxO1) Cd36. inhibits FoxO1 activity blocking Hdac1-mediated deacetylation at K242, K245, K262 increases Zdhhc4/5-mediated CD36 palmitoylation C3, C7, C464, C466; furthermore, macrophage decreases hepatocytes lipogenesis HSCs activation retinol binding protein 4 (Rbp4). Anti-Rbp4 can prevent progression deficiency macrophages. This study identifies as a regulator cycle. Targeting or Rbp4 may be plausible therapeutic strategy for MASH.

Language: Английский

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