Spatial Metabolomics and Imaging Mass Spectrometry in the Age of Artificial Intelligence DOI Open Access
Theodore Alexandrov

Annual Review of Biomedical Data Science, Journal Year: 2020, Volume and Issue: 3(1), P. 61 - 87

Published: April 14, 2020

Spatial metabolomics is an emerging field of omics research that has enabled localizing metabolites, lipids, and drugs in tissue sections, a feat considered impossible just two decades ago. its enabling technology—imaging mass spectrometry—generate big hyperspectral imaging data have motivated the development tailored computational methods at intersection image analysis. Experimental developments recently opened doors to applications spatial life sciences biomedicine. At same time, these advances coincided with rapid evolution machine learning, deep artificial intelligence, which are transforming our everyday promise revolutionize biology healthcare. Here, we introduce through eyes scientist, review outstanding challenges, provide look into future, discuss opportunities granted by ongoing convergence human intelligence.

Language: Английский

Hepatocellular carcinoma DOI Open Access
Josep M. Llovet, Robin Kate Kelley, Augusto Villanueva

et al.

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: Jan. 21, 2021

Language: Английский

Citations

4606
Mechanisms and disease consequences of nonalcoholic fatty liver disease DOI Creative Commons
Rohit Loomba, Scott L. Friedman, Gerald I. Shulman

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(10), P. 2537 - 2564

Published: May 1, 2021

Language: Английский

Citations

1308
Immunotherapies for hepatocellular carcinoma DOI
Josep M. Llovet, Florian Castet, Mathias Heikenwälder

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(3), P. 151 - 172

Published: Nov. 11, 2021

Language: Английский

Citations

1211
NASH limits anti-tumour surveillance in immunotherapy-treated HCC DOI Creative Commons
Dominik Pfister, Nicolás Gonzalo Núñez, Roser Pinyol

et al.

Nature, Journal Year: 2021, Volume and Issue: 592(7854), P. 450 - 456

Published: March 24, 2021

Abstract Hepatocellular carcinoma (HCC) can have viral or non-viral causes 1–5 . Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification patients optimal response to therapy unmet need 6,7 Here we report the progressive accumulation exhausted, unconventionally activated CD8 + PD1 T cells in NASH-affected livers. In preclinical models NASH-induced therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded within tumours did not lead tumour regression, which indicates that immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led increase incidence NASH–HCC and number size nodules, correlated with increased hepatic CXCR6 , TOX TNF cells. The HCC triggered by prevented depletion neutralization, suggesting help induce NASH–HCC, rather than invigorating executing surveillance. We found similar phenotypic functional profiles from humans NAFLD NASH. A meta-analysis three randomized phase III clinical trials tested inhibitors PDL1 (programmed death-ligand 1) more 1,600 advanced revealed improve survival two additional cohorts, NASH-driven who received anti-PDL1 showed reduced overall compared other aetiologies. Collectively, these data show particularly might be less responsive immunotherapy, probably owing NASH-related aberrant cell activation causing tissue damage leads impaired Our provide a rationale according underlying aetiology studies as primary adjuvant treatment.

Language: Английский

Citations

954
Evolving therapeutic landscape of advanced hepatocellular carcinoma DOI
Chen Yang, Hailin Zhang,

Linmeng Zhang

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 20(4), P. 203 - 222

Published: Nov. 11, 2022

Language: Английский

Citations

454
The immunological and metabolic landscape in primary and metastatic liver cancer DOI
Xin Li, Pierluigi Ramadori, Dominik Pfister

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(9), P. 541 - 557

Published: July 29, 2021

Language: Английский

Citations

416
Immune cell-mediated features of non-alcoholic steatohepatitis DOI Creative Commons
Thierry Huby, Emmanuel L. Gautier

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(7), P. 429 - 443

Published: Nov. 5, 2021

Non-alcoholic fatty liver disease (NAFLD) includes a range of hepatic manifestations, starting with steatosis and potentially evolving towards non-alcoholic steatohepatitis (NASH), cirrhosis or even hepatocellular carcinoma. NAFLD is major health burden, its incidence increasing worldwide. Although it primarily disturbed metabolism, involves several immune cell-mediated inflammatory processes, particularly when reaching the stage NASH, at which point inflammation becomes integral to progression disease. The cell landscape diverse steady state further evolves during NASH direct consequences for severity. In this Review, we discuss current concepts related role cells in onset NASH. A better understanding mechanisms by contribute pathogenesis should aid design innovative drugs target therapeutic options are limited. (NASH) serious chronic disorder prevalence Metabolic nature, also mobilizes system. Here, Huby Gautier knowledge regarding how subsets affect progression.

Language: Английский

Citations

402
Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis DOI
Olivier Govaere, Simon Cockell, Dina Tiniakos

et al.

Science Translational Medicine, Journal Year: 2020, Volume and Issue: 12(572)

Published: Dec. 2, 2020

A 25-gene expression signature associates with progression of fibrosing steatohepatitis in independent NAFLD cohorts.

Language: Английский

Citations

331
Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits DOI Creative Commons
Moritz Peiseler, Robert F. Schwabe, Jochen Hampe

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1136 - 1160

Published: June 22, 2022

Language: Английский

Citations

323
Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy DOI Open Access
John Y.L. Chiang, Jessica M. Ferrell

AJP Gastrointestinal and Liver Physiology, Journal Year: 2020, Volume and Issue: 318(3), P. G554 - G573

Published: Jan. 27, 2020

Bile acid synthesis is the most significant pathway for catabolism of cholesterol and maintenance whole body homeostasis. acids are physiological detergents that absorb, distribute, metabolize, excrete nutrients, drugs, xenobiotics. also signal molecules metabolic integrators activate nuclear farnesoid X receptor (FXR) membrane Takeda G protein-coupled 5 (TGR5; i.e., bile 1) to regulate glucose, lipid, energy metabolism. The gut-to-liver axis plays a critical role in transformation primary secondary acids, regulation maintain composition within pool, homeostasis prevent hyperglycemia, dyslipidemia, obesity, diabetes. High-fat high-calorie diets, dysbiosis, alcohol, disruption sleep circadian rhythms cause diseases, including alcoholic nonalcoholic fatty liver diabetes, cardiovascular disease. acid-based drugs target receptors being developed treatment diseases liver.

Language: Английский

Citations

305