Опубликована: Янв. 1, 2024
Язык: Английский
Advanced Science, Год журнала: 2024, Номер 11(31)
Опубликована: Июнь 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.
Язык: Английский
Процитировано
6
Analytical Chemistry, Год журнала: 2025, Номер unknown
Опубликована: Фев. 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.
Язык: Английский
Процитировано
0
Frontiers in Oncology, Год журнала: 2025, Номер 15
Опубликована: Апрель 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.
Язык: Английский
Процитировано
0
BMC Cancer, Год журнала: 2024, Номер 24(1)
Опубликована: Ноя. 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.
Язык: Английский
Процитировано
3
Nutrients, Год журнала: 2024, Номер 16(22), С. 3789 - 3789
Опубликована: Ноя. 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
Язык: Английский
Процитировано
2
European Journal of Pharmacology, Год журнала: 2024, Номер unknown, С. 177074 - 177074
Опубликована: Окт. 1, 2024
Язык: Английский
Процитировано
0
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0