Editorial: Inflammatory responses on the road from NASH to HCC: pathogenic mechanisms and possible therapeutic strategies DOI Creative Commons
Miroslaw Kornek, Tim Hendrikx, Salvatore Sutti

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 1, 2024

Non-alcoholic fatty liver disease (NAFLD) was recently renamed to metabolic dysfunctionassociated (MASLD) emphasize the dysfunctions that most often accompany its manifestation [1]. MASLD covers a spectrum of diseases, ranging from simple steatosis dysfunction-associated steatohepatitis (MASH), clinical condition characterized by steatosis, hepatocellular injury, and inflammation with or without fibrosis MASH can further progress cirrhosis and, in certain fraction patients, carcinoma (HCC) [2]. Multiple factors sustain transition advanced stages, but emerging evidence indicates chronic as driving force underlying process Therefore, understanding cellular molecular mechanisms responsible for inflammatory responses may lay foundations treatments counteract complications.In this article collection, authors summarized recent advances concerning modulation associated MASH.Growing hepatokines mediate key steps MASLD/MASH [3,4]. Foglia colleagues addressed issue exploring pathological implications histidine-rich glycoprotein (HRG) MASH-related carcinogenesis. HGR is which interacts several molecules modulates essential biological processes [5]. The found HRG levels increase parallel severity, genetic deletion protects mice HCC ecting multiple pathways.Hepatokines, like other molecules, e ects triggering specific receptors, transduce complex signals [6]. Apostolo et al. reviewed TAM receptors (Tyro 3, Axl MerTK) HCC. described along common ligand Growth Arrest Specific (GAS) 6, support development MASH. Indeed, Gas6/TAM axis stimulates activation, survival proliferation hepatic stellate cells (HSCs). TAM/Gas6 system also promotes induction signalling pathways involved tumour growth dissemination. Furthermore, it lead resistance sorafenib cells, so much pharmacological targeting restores cell sensitivity sorafenib. Grøndal investigates MASH, observing soluble form (sAxl) preclinical models MASLD/MASH, responses, suggesting sAxl represent an early marker MASLD/MASH. mechanistic involvement reporting inhibition reduces fibrosis. investigated ameliorates describing has immunomodulatory action lowering expression pro-inflammatory mediators abundance NK various dendritic (DC) subsets.Besides TAM, additional families contribute protease-activated (PARs). PARs are substrate proteases capable cutting extracellular N-terminus sequence, becomes agonist themselves [7]. Villano Pontisso current available data on PAR2 activation drives impairing insulin pathway causing (IR) steatosis. activating HSCs. supports transformation inhibiting AMPK-mediated autophagy metastatization via PI3K/AKT signaling pathway. Consistently, antagonists inhibit experimental MASH.MASH-associated involve immune subsets belonging innate adaptive immunity branches, such macrophages (MFs), (DCs), NK/NKT T/B-lymphocytes [8][9][10]. These influence microenvironment secreting cyto/chemokines mediating progression [11]. Saueret analyzed investigating secretome derived di erentially polarized human primary monocytes/macrophages "classical" stimuli MFs (TNF-α, IL-4 IL13) (IL-15) fail HSCs vitro. Conversely, hyperactivation phorbol 12-myristate 13-acetate (PMA), non-specific agent, strong Overall, these results reflect nature fibrogenic suggest act vivo HSCs.Pinto Lukacs-Kornek complexity reviewing contribution DCs disease. They emphasized capacity interact initiate acting antigen-presenting both T B-lymphocytes. However, they have brought light controversial currently existing related precise remains poorly defined, investigations needed.The represents crucial mechanism [12]. governing reciprocal interactions between still characterized. Provera role costimulatory ICOS (ICOS-L), finding possible crosstalk CD8 + T-lymphocytes TREM2 monocyte-derived (MoMFs) then observed disruption ICOS/ICOS-L improves histological features faction MoMFs. MoMFs mediated dyad pool MoMFs, contributing MASH.Altogether, discussed present research topic summarize elaborate corroborated view critical player progression. Finally, highlighted potential biomarkers targets exploitable fighting

Language: Английский

Clinical Applications of Artificial Intelligence (AI) in Human Cancer: Is It Time to Update the Diagnostic and Predictive Models in Managing Hepatocellular Carcinoma (HCC)? DOI Creative Commons
Mario Romeo, Marcello Dallio, Carmine Napolitano

et al.

Diagnostics, Journal Year: 2025, Volume and Issue: 15(3), P. 252 - 252

Published: Jan. 22, 2025

In recent years, novel findings have progressively and promisingly supported the potential role of Artificial intelligence (AI) in transforming management various neoplasms, including hepatocellular carcinoma (HCC). HCC represents most common primary liver cancer. Alarmingly, incidence is dramatically increasing worldwide due to simultaneous “pandemic” spreading metabolic dysfunction-associated steatotic disease (MASLD). MASLD currently constitutes leading cause chronic hepatic damage (steatosis steatohepatitis), fibrosis, cirrhosis, configuring a scenario where an onset has been reported even early stage. On other hand, serious plague, significantly burdening outcomes hepatitis B (HBV) C (HCV) virus-infected patients. Despite progress this cancer, overall prognosis for advanced-stage patients continues be poor, suggesting absolute need develop personalized healthcare strategies further. “cold war”, machine learning techniques neural networks are emerging as weapons, able identify patterns biomarkers that would normally escaped human observation. Using advanced algorithms, AI can analyze large volumes clinical data medical images (including routinely obtained ultrasound data) with elevated accuracy, facilitating diagnosis, improving performance predictive models, supporting multidisciplinary (oncologist, gastroenterologist, surgeon, radiologist) team opting best “tailored” individual treatment. Additionally, contribute enhancing effectiveness metabolomics–radiomics-based promoting identification specific HCC-pathogenetic molecules new targets realizing therapeutic regimens. era precision medicine, integrating into routine practice appears promising frontier, opening avenues cancer research

Language: Английский

Citations

2
Effects of Selected Food Additives on the Gut Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) DOI Creative Commons
Sara Jarmakiewicz-Czaja, Aneta Sokal, Rafał Filip

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(2), P. 192 - 192

Published: Jan. 22, 2025

The purpose of this article is to present selected food additives as disruptors normal intestinal homeostasis with a potential impact on the development metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive literature search was conducted in three major electronic databases: PubMed, ScienceDirect, and Google Scholar. MASLD prevalent condition that closely related global rise obesity. Its pathogenesis multifactorial, genetic, environmental, factors playing key role. “multiple-hit” hypothesis suggests Western-style diet, rich ultra-processed foods, saturated fats, additives, combined low physical activity, contributes obesity, which promotes lipid accumulation liver. Recent studies underscore role impaired MASLD. Food including preservatives, emulsifiers, sweeteners, affect gut health function. Selected preservatives inhibit pathogenic microorganisms but disrupt microbiota, leading changes permeability dysfunction. Some emulsifiers thickeners can cause inflammation alter microbiome, contributing steatosis. Furthermore, use sweeteners such sucralose aspartame has been linked metabolism microbial composition, turn disorders.

Language: Английский

Citations

1
Inflammation in MASLD Progression and Cancer DOI Creative Commons
Yeon Soo Kim,

Y. C. Park,

Hyunsoo Rho

et al.

JHEP Reports, Journal Year: 2025, Volume and Issue: unknown, P. 101414 - 101414

Published: April 1, 2025

Language: Английский

Citations

0
Targeting Metabolism: Innovative Therapies for MASLD Unveiled DOI Open Access
Weixin Wang, Xin Gao, Wei Niu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4077 - 4077

Published: April 25, 2025

The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted critical role metabolism in disease’s pathophysiology. This innovative nomenclature signifies a shift from previous designation non-alcoholic fatty (NAFLD), emphasizing condition’s progressive nature. Simultaneously, MASLD become one most prevalent diseases worldwide, highlighting urgent need for research to elucidate its etiology and develop effective treatment strategies. review examines delineates revised definition MASLD, exploring epidemiology pathological changes occurring at various stages disease. Additionally, it identifies metabolically relevant targets within provides summary latest targeted drugs under development, including those clinical some preclinical stages. finishes with look ahead future therapy goal summarizing providing fresh ideas insights.

Language: Английский

Citations

0
Editorial: Inflammatory responses on the road from NASH to HCC: pathogenic mechanisms and possible therapeutic strategies DOI Creative Commons
Miroslaw Kornek, Tim Hendrikx, Salvatore Sutti

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 1, 2024

Non-alcoholic fatty liver disease (NAFLD) was recently renamed to metabolic dysfunctionassociated (MASLD) emphasize the dysfunctions that most often accompany its manifestation [1]. MASLD covers a spectrum of diseases, ranging from simple steatosis dysfunction-associated steatohepatitis (MASH), clinical condition characterized by steatosis, hepatocellular injury, and inflammation with or without fibrosis MASH can further progress cirrhosis and, in certain fraction patients, carcinoma (HCC) [2]. Multiple factors sustain transition advanced stages, but emerging evidence indicates chronic as driving force underlying process Therefore, understanding cellular molecular mechanisms responsible for inflammatory responses may lay foundations treatments counteract complications.In this article collection, authors summarized recent advances concerning modulation associated MASH.Growing hepatokines mediate key steps MASLD/MASH [3,4]. Foglia colleagues addressed issue exploring pathological implications histidine-rich glycoprotein (HRG) MASH-related carcinogenesis. HGR is which interacts several molecules modulates essential biological processes [5]. The found HRG levels increase parallel severity, genetic deletion protects mice HCC ecting multiple pathways.Hepatokines, like other molecules, e ects triggering specific receptors, transduce complex signals [6]. Apostolo et al. reviewed TAM receptors (Tyro 3, Axl MerTK) HCC. described along common ligand Growth Arrest Specific (GAS) 6, support development MASH. Indeed, Gas6/TAM axis stimulates activation, survival proliferation hepatic stellate cells (HSCs). TAM/Gas6 system also promotes induction signalling pathways involved tumour growth dissemination. Furthermore, it lead resistance sorafenib cells, so much pharmacological targeting restores cell sensitivity sorafenib. Grøndal investigates MASH, observing soluble form (sAxl) preclinical models MASLD/MASH, responses, suggesting sAxl represent an early marker MASLD/MASH. mechanistic involvement reporting inhibition reduces fibrosis. investigated ameliorates describing has immunomodulatory action lowering expression pro-inflammatory mediators abundance NK various dendritic (DC) subsets.Besides TAM, additional families contribute protease-activated (PARs). PARs are substrate proteases capable cutting extracellular N-terminus sequence, becomes agonist themselves [7]. Villano Pontisso current available data on PAR2 activation drives impairing insulin pathway causing (IR) steatosis. activating HSCs. supports transformation inhibiting AMPK-mediated autophagy metastatization via PI3K/AKT signaling pathway. Consistently, antagonists inhibit experimental MASH.MASH-associated involve immune subsets belonging innate adaptive immunity branches, such macrophages (MFs), (DCs), NK/NKT T/B-lymphocytes [8][9][10]. These influence microenvironment secreting cyto/chemokines mediating progression [11]. Saueret analyzed investigating secretome derived di erentially polarized human primary monocytes/macrophages "classical" stimuli MFs (TNF-α, IL-4 IL13) (IL-15) fail HSCs vitro. Conversely, hyperactivation phorbol 12-myristate 13-acetate (PMA), non-specific agent, strong Overall, these results reflect nature fibrogenic suggest act vivo HSCs.Pinto Lukacs-Kornek complexity reviewing contribution DCs disease. They emphasized capacity interact initiate acting antigen-presenting both T B-lymphocytes. However, they have brought light controversial currently existing related precise remains poorly defined, investigations needed.The represents crucial mechanism [12]. governing reciprocal interactions between still characterized. Provera role costimulatory ICOS (ICOS-L), finding possible crosstalk CD8 + T-lymphocytes TREM2 monocyte-derived (MoMFs) then observed disruption ICOS/ICOS-L improves histological features faction MoMFs. MoMFs mediated dyad pool MoMFs, contributing MASH.Altogether, discussed present research topic summarize elaborate corroborated view critical player progression. Finally, highlighted potential biomarkers targets exploitable fighting

Language: Английский

Citations

0