Emerging role of ferroptosis in metabolic dysfunction-associated steatotic liver disease: revisiting hepatic lipid peroxidation

EBioMedicine, Год журнала: 2024, Номер 102, С. 105088 - 105088

Опубликована: Март 26, 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is characterised by cell death of parenchymal liver cells which interact with their microenvironment to drive disease activity and fibrosis. The identification the major type could pave way towards pharmacotherapy for MASH. To date, increasing evidence suggest a regulated death, named ferroptosis, occurs through iron-catalysed peroxidation polyunsaturated fatty acids (PUFA) in membrane phospholipids. Lipid enjoys renewed interest light as druggable target This review recapitulates molecular mechanisms ferroptosis physiology, human MASH critically appraises results targeting preclinical models. Rewiring redox, iron PUFA metabolism creates proferroptotic environment involved MASH-related hepatocellular carcinoma (HCC) development. Ferroptosis induction might be promising novel approach eradicate HCC, while its inhibition ameliorate progression.

Язык: Английский

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Machine Learning Enabled Photoacoustic Spectroscopy for Noninvasive Assessment of Breast Tumor Progression In Vivo: A Preclinical Study

ACS Sensors, Год журнала: 2024, Номер 9(2), С. 589 - 601

Опубликована: Янв. 30, 2024

Breast cancer is a dreaded disease affecting women the most in cancer-related deaths over other cancers. However, early diagnosis of can help increase survival rates. The existing breast tools do not support disease. Therefore, there great need to develop diagnostic for this cancer. Photoacoustic spectroscopy (PAS), being very sensitive biochemical changes, be relied upon its application detecting tumors vivo. With motivation, current study, an aseptic chamber integrated photoacoustic (PA) probe was designed and developed monitor tumor progression vivo, established nude mice. device served dual purpose transporting tumor-bearing animals laboratory from animal house performing PA experiments same chamber, maintaining sterility. In induced mice by MCF-7 cells injection corresponding spectra at different time points (day 0, 5, 10, 15, 20) vivo animals. recorded were subsequently preprocessed, wavelet-transformed, subjected filter-based feature selection algorithm. selected top 20 features, minimum redundancy maximum relevance (mRMR) algorithm, then used build input matrix machine learning (ML)-based classification data. performance models demonstrated 100% specificity, whereas sensitivity 95, 100, 92.5, 85% points, day 20, respectively. These results suggest potential signal-based preclinical model. signal contains information on changes associated with progression, emphasizing translational strength toward diagnosis.

Язык: Английский

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Nanomedicine‐encouraged cellular autophagy promoters favor liver fibrosis progression reversal

View, Год журнала: 2024, Номер 5(3)

Опубликована: Апрель 23, 2024

Abstract Liver fibrosis is a major risk factor for hepatocellular carcinoma origin, and its progression not only correlates with oxidative stress inflammation, but also encouraged by autophagy hold‐up. Therefore, new solutions to effectively attenuate inflammation coincidently favor are highly demanded reverse liver fibrosis, even hamper escalation into carcinoma. Herein, the porous manganese‐substituted Prussian blue (PMPB) analogs harnessed activate autophagy, scavenge reactive oxygen species (ROS), suppress therapy. PMPB can inhibit macrophage activation, facilitate eradicate ROS, blockade cellular cross‐talk, thus impeding further progression. Moreover, favorable spontaneous capture of Kupffer cells allows more accumulation in significantly injury collagen deposition, thereby inhibiting fibrosis. PMPB‐based nanomedicine shows great potentials promoting eliminating protecting hepatocytes from stress‐arised damages, which eventually extent holding promise clinical translation treating

Язык: Английский

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Ferroptosis is a targetable detrimental factor in metabolic dysfunction-associated steatotic liver disease

Cell Death and Differentiation, Год журнала: 2024, Номер 31(9), С. 1113 - 1126

Опубликована: Июль 26, 2024

There is an unmet clinical need for pharmacologic treatment metabolic dysfunction-associated steatotic liver disease (MASLD). Hepatocyte cell death a hallmark of this highly prevalent chronic disease, but the dominant type remains uncertain. Here we report that ferroptosis, iron-catalyzed mode regulated death, contributes to MASLD. Unsupervised clustering in cohort biopsy-proven MASLD patients revealed subgroup with hepatic ferroptosis signature and lower glutathione peroxidase 4 (GPX4) levels. Likewise, reduced defenses was discerned public transcriptomics datasets. Four weeks choline-deficient L-amino acid-defined high-fat diet (CDAHFD) induced mice. Gpx4 overexpression did not affect steatohepatitis, instead CDAHFD protected from morbidity due hepatocyte-specific knockout. The inhibitor UAMC-3203 attenuated steatosis alanine aminotransferase second model, i.e., high-fructose (HFHFD). effect monounsaturated saturated fatty acids supplementation on susceptibility assessed human HepG2 cells. Fat-laden showed drop defenses, increased phosphatidylglycerol two polyunsaturated acid (PUFA) lipid tails, sustained sensitivity. In conclusion, study identified as detrimental factor patients. Unexpectedly, non-PUFA hepatocytes altered bilayer composition maintain Based findings vivo models, inhibition represents promising therapeutic target

Язык: Английский

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Illuminating life processes by vibrational probes

Nature Methods, Год журнала: 2025, Номер 22(5), С. 928 - 944

Опубликована: Май 1, 2025

Язык: Английский

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Targeting metabolic reprogramming in hepatocellular carcinoma to overcome therapeutic resistance: A comprehensive review

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 116021 - 116021

Опубликована: Дек. 20, 2023

Hepatocellular carcinoma (HCC) poses a heavy burden on human health with high morbidity and mortality rates. Systematic therapy is crucial for advanced mid-term HCC, but faces significant challenge from therapeutic resistance, weakening drug effectiveness. Metabolic reprogramming has gained attention as key contributor to resistance. Cells change their metabolism meet energy demands, adapt growth needs, or resist environmental pressures. Understanding enzyme expression patterns metabolic pathway interactions vital comprehend HCC occurrence, development, treatment Exploring pathways essential identify breakthrough points treatment. Targeting enzymes inhibitors addressing these points. Inhibitors, combined systemic drugs, can alleviate prolong overall survival offer patients chance radical resection. Advances in research methods, genomics metabolomics cells organoids, help build the network. Recent progress biomaterials nanotechnology impacts targeting effectiveness, providing new solutions This review focuses changes, interactions, inhibitors, delivery reprogramming, offering valuable references approaches

Язык: Английский

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Organelle-Targeted Laurdans Measure Heterogeneity in Subcellular Membranes and Their Responses to Saturated Lipid Stress

ACS Chemical Biology, Год журнала: 2024, Номер 19(8), С. 1773 - 1785

Опубликована: Июль 29, 2024

Organelles feature characteristic lipid compositions that lead to differences in membrane properties. In cells, ordering and fluidity are commonly measured using the solvatochromic dye Laurdan, whose fluorescence is sensitive packing. As a general lipophilic dye, Laurdan stains all hydrophobic environments cells; therefore, it challenging characterize properties specific organelles or assess their responses pharmacological treatments intact cells. Here, we describe synthesis application of Laurdan-derived probes read out packing individual cellular organelles. The set organelle-targeted Laurdans (OTL) localizes ER, mitochondria, lysosomes, Golgi compartments with high specificity while retaining spectral resolution needed detect biological changes ordering. We show ratiometric imaging OTLs can resolve heterogeneity within as well resulting from inhibition trafficking bioenergetic processes. apply these organelle-specific saturated stress. While ER lysosomal exogenous fatty acids, mitochondrial membranes protected. then use sort populations cells based on acid diet, highlighting ability organelle-localized distinguish between metabolic state. These results expand repertoire targeted demonstrate interrogating dysregulation.

Язык: Английский

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Discrimination of lipid composition and cellular localization in human liver tissues by stimulated Raman scattering microscopy

Journal of Biomedical Optics, Год журнала: 2024, Номер 29(01)

Опубликована: Янв. 24, 2024

SignificanceThe molecular mechanisms driving the progression from nonalcoholic fatty liver (NAFL) to fibrosing steatohepatitis (NASH) are insufficiently understood. Techniques enabling characterization of different lipid species with both chemical and spatial information can provide valuable insights into their contributions disease progression.AimWe extend utility stimulated Raman scattering (SRS) microscopy characterize quantify in tissue sections patients NAFL NASH.ApproachWe applied a dual-band hyperspectral SRS system for imaging C–H stretching fingerprint regions. The same were imaged polarization detecting birefringent liquid crystals tissues.ResultsOur analysis pipeline provides accurate classification quantification free cholesterol, saturated cholesteryl esters (CEs), unsaturated CE, triglycerides sections. subcellular resolution enables investigations heterogeneous distribution which has been under-examined previous studies. We also discovered that crystals, previously found be associated NASH development, predominantly composed CE.ConclusionsOur method allows detailed composition human tissues further investigation potential mechanism progression.

Язык: Английский

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Stain-Free Histopathology with Stimulated Raman Scattering Microscopy

Analytical Chemistry, Год журнала: 2024, Номер 96(20), С. 7907 - 7925

Опубликована: Май 7, 2024

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTStain-Free Histopathology with Stimulated Raman Scattering MicroscopyLiyang MaLiyang MaState Key Laboratory of Surface Physics and Department Physics, Academy for Engineering Technology, Micro Nano Photonic Structures (Ministry Education), Shanghai Metasurfaces Light Manipulation, Fudan University, 200433, ChinaMore by Liyang MaView Biographyhttps://orcid.org/0009-0007-8820-1403, Kuan LuoKuan LuoState LuoView Biographyhttps://orcid.org/0009-0001-2661-1577, Zhijie LiuZhijie LiuState LiuView Biography, Minbiao Ji*Minbiao JiState China*Email: [email protected]More JiView Biographyhttps://orcid.org/0000-0002-9066-4008Cite this: Anal. Chem. 2024, 96, 20, 7907–7925Publication Date (Web):May 7, 2024Publication History Received20 April 2024Accepted24 2024Revised23 2024Published online7 May inissue 21 2024https://pubs.acs.org/doi/10.1021/acs.analchem.4c02061https://doi.org/10.1021/acs.analchem.4c02061review-articleACS PublicationsCopyright © 2024 American Chemical SocietyRequest reuse permissionsArticle Views425Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated to reflect usage leading up last few days.Citations number other articles citing this article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score is a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com additional details score social media presence given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biological imaging,Cancer,Central nervous system,Microscopy,Raman scattering Get e-Alerts

Язык: Английский

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Delivery of Eicosapentaenoic acid-loaded cellulose nanocrystal alleviates liver fibrosis via modulating phospholipids and apoptotic regulators

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 97, С. 105796 - 105796

Опубликована: Май 16, 2024

Язык: Английский

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