Lipid Nanoparticle‐Mediated Delivery of CRISPR‐Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism

Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)

Published: June 18, 2024

Abstract Non‐alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, reported to exacerbate steatosis NAFLD mice and patients, indicating its probability being therapeutic target for treatment. In this study, the potential Rubicon blockage investigated. Lipid nanoparticles carrying Rubicon‐specific CRISPR‐Cas9 components exhibited accumulation, cell internalization, knockdown. A single administration results attenuated lipid deposition steatosis, lower circulating levels decreased adipocyte size mice. Furthermore, increase phosphatidylcholine phosphatidylethanolamine can be observed livers after silencing, along regulatory effects on metabolism‐related genes such as CD36, Gpcpd1, Chka, Lpin2. The indicate that knockdown improves glycerophospholipid metabolism thereby ameliorates progression, which provides strategy therapy via restoration Rubicon.

Language: Английский

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Analyzing the Cholesteryl Ester Fraction in Lipid Droplets with a Polarity-Ultrasensitive Fluorescence Lifetime Probe

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Quantifying the lipid composition of cellular droplets (LDs) in situ is challenging but crucial for understanding metabolic diseases. Here, we propose a fluorescence lifetime imaging method based on polarity-sensitive probe (LD660) analyzing LDs. The emits strong at 660 nm only apolar LD environments, with dielectric constants 2–4, and outperforms Nile red imaging. Importantly, LD660 increases incremental fraction cholesteryl ester neutral mixtures. Using microscopy LD660, imaged quantified fractions LDs cells tissues. It found that macrophages surrounding hepatocytes fatty liver diseases show significantly higher contents than other hepatocytes. This finding suggests may serve as potential indicator degree hepatic steatosis.

Language: Английский

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Regulation of PEST-containing nuclear proteins in cancer cells: implications for cancer biology and therapy

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 22, 2025

The PEST-containing nuclear protein (PCNP) is a involved in the regulation of cell cycle progression, degradation, and tumorigenesis. PCNP contains PEST sequence, polypeptide structural motif rich proline (P), glutamic acid (E), serine (S), threonine (T), which serves as proteolytic recognition signal. degradation specific proteins via sequence plays crucial role modulating signaling pathways that control growth, differentiation, apoptosis, stress responses. primarily degraded through ubiquitin-proteasome system (UPS) calpain pathway, with phosphorylation residues further accelerating its degradation. ubiquitination by ring finger NIRF an E3 ligase-dependent manner well documented, along involvement MAPK PI3K/AKT/mTOR pathways. Additionally, implicated p53-mediated arrest are essential for inhibiting tumor growth. To explore cancer, this review examines effects on proliferation, apoptosis lung adenocarcinoma, thyroid ovarian other malignancies derived from glandular epithelial cells. By focusing regulatory mechanisms, study provides scientific basis research biological functions development cancer progression.

Language: Английский

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Early-life antibiotic exposure aggravate the metabolic dysfunction-associated steatotic liver disease associated hepatocellular carcinoma

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: Nov. 6, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) asscociated hepatocellular carcinoma (HCC) is becoming a growing concern in global healthcare. The early-life gut microbiota plays crucial role maintaining healthy. However, the impact of dysbiosis on advancement MASLD-HCC remains inadequately understood. In present study, we investigated development streptozotocin and high-fat diet (STZ-HFD) induced mouse model. We recorded body weight lifespan, dynamically monitored level alanine aminotransferase (ALT), aspartate (AST), triglyceride (TG), total cholesterol (T-CHO) blood glucose serum monthly. addition, examined various immune cells liver, such as T cells, B NK NKT αβT γδT macrophage MDSC by flow cytometry conducted liquid chromatography mass spectrometry (LC–MS) based analysis tissue from control antibiotic exposure mice (early-Abx) mice. found that early-Abx suffered more severe tumor burden further confirmed hepatocytes were all disturbed. Importantly, alters metabolic profiling especially glycerophospholipids lipid accumulation. Furthermore, exposed to antibiotics showed disturbances metabolism developed insulin resistance. Collectively, our findings revealed accelerated progression impairing hepatocytes, homeostasis metabolites persistently, highlighting importance MASLD-HCC.

Language: Английский

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Quercetin’s Potential in MASLD: Investigating the Role of Autophagy and Key Molecular Pathways in Liver Steatosis and Inflammation

Nutrients, Journal Year: 2024, Volume and Issue: 16(22), P. 3789 - 3789

Published: Nov. 5, 2024

Metabolic dysfunction-associated fatty liver disease (MASLD) is a widespread disorder characterized by excessive fat accumulation in the liver, commonly associated with metabolic syndrome components such as obesity, diabetes, and dyslipidemia. With global prevalence of up to 30%, MASLD projected affect over 100 million people U.S. 20 Europe 2030. The ranges from Steatotic Lived Disease (SLD) more severe forms like steatohepatitis (MASH), which can progress cirrhosis hepatocellular carcinoma. Autophagy, cellular process crucial for lipid metabolism homeostasis, often impaired MASLD, leading increased hepatic inflammation. Key autophagy-related proteins, Beclin1, LC3A, SQSTM1 (p62), CD36, Perilipin 3, play significant roles regulating this process. Disruption these proteins contributes pathogenesis MASLD. Quercetin, natural polyphenolic flavonoid antioxidant anti-inflammatory properties, has promising results mitigating It may reduce accumulation, improve mitochondrial function, enhance autophagy. However, further research needed elucidate its mechanisms validate therapeutic potential clinical settings. This underscores need continued investigation into autophagy novel treatments

Language: Английский

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Integrated metabolomics and network pharmacology analysis to reveal the protective effect of Complanatoside A on nonalcoholic fatty liver disease

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 177074 - 177074

Published: Oct. 1, 2024

Language: Английский

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Qing-Kai-Ling Oral Liquid Ameliorates Nonalcoholic Fatty Liver Disease Via Gut-Liver Axis And Driving Scfas to Regulate the Ampk/Cidea/Ppargc1a Signaling Pathway

Published: Jan. 1, 2024

Language: Английский

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