Role of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress DOI Creative Commons

Sabira Mohammed,

Evan H. Nicklas,

Nidheesh Thadathil

и другие.

Free Radical Biology and Medicine, Год журнала: 2021, Номер 164, С. 315 - 328

Опубликована: Янв. 12, 2021

Mice deficient in the antioxidant enzyme Cu/Zn-superoxide dismutase (Sod1-/- or Sod1KO mice) have increased oxidative stress, show accelerated aging and develop spontaneous hepatocellular carcinoma (HCC) with age. Similar to humans, HCC development mice progresses from non-alcoholic fatty liver disease (NAFLD) steatohepatitis (NASH) fibrosis, which eventually HCC. Oxidative stress plays a role NAFLD NASH progression, inflammation is main mechanism that drives progression fibrosis. Because necroptosis major source of inflammation, we tested hypothesis fibrosis mice. Phosphorylation MLKL (P-MLKL), well-accepted marker necroptosis, expression protein were significantly livers compared wild type (WT) indicating necroptosis. Similarly, phosphorylation RIPK3 levels also increased. Markers pro-inflammatory M1 macrophages, NLRP3 inflammasome, transcript cytokines chemokines, e.g., TNFα, IL-6, IL-1β, Ccl2 are associated human NASH, Expression enzymes heat shock proteins, markers oncogenic transcription factor STAT3 upregulated autophagy was downregulated Short term treatment necrostatin-1s (Nec-1s), inhibitor, reversed these conditions. Our data for first time necroptosis-mediated contributes mouse model aging, exhibits progressive development.

Язык: Английский

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

и другие.

Nature Reviews Disease Primers, Год журнала: 2021, Номер 7(1)

Опубликована: Янв. 21, 2021

Язык: Английский

Процитировано

4587
Inflammation in obesity, diabetes, and related disorders DOI Creative Commons
Theresa V. Rohm, Daniel T. Meier, Jerrold M. Olefsky

и другие.

Immunity, Год журнала: 2022, Номер 55(1), С. 31 - 55

Опубликована: Янв. 1, 2022

Язык: Английский

Процитировано

1181
Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma DOI Creative Commons
Danyu Du, Chan Liu,

Mengyao Qin

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2021, Номер 12(2), С. 558 - 580

Опубликована: Сен. 27, 2021

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies treat HCC, such as targeted tyrosine kinase inhibitors, immune based and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation progression driven by reprogramming metabolism, particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal new nomenclature non-alcoholic (NAFLD), indicates growing appreciation metabolism the pathogenesis disease, thereby suggesting targeting abnormal treatment. In this review, we introduce directions highlighting targets glucose, acid, amino acid glutamine which are suitable intervention. We also summarize discuss agents studies deregulated Furthermore, opportunities challenges discovery development therapy discussed.

Язык: Английский

Процитировано

388
Targeting innate immune mediators in type 1 and type 2 diabetes DOI
Marc Y. Donath, Charles A. Dinarello, Thomas Mandrup‐Poulsen

и другие.

Nature reviews. Immunology, Год журнала: 2019, Номер 19(12), С. 734 - 746

Опубликована: Сен. 9, 2019

Язык: Английский

Процитировано

336
Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment DOI
Josep M. Llovet, Catherine E. Willoughby, Amit G. Singal

и другие.

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2023, Номер 20(8), С. 487 - 503

Опубликована: Март 17, 2023

Язык: Английский

Процитировано

199
Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments DOI Creative Commons
Cheng Peng, Alastair G. Stewart, Owen L. Woodman

и другие.

Frontiers in Pharmacology, Год журнала: 2020, Номер 11

Опубликована: Дек. 3, 2020

Non-alcoholic steatohepatitis (NASH) develops from non-alcoholic fatty liver disease (NAFLD). Currently, around 25% of the population is estimated to have NAFLD, and NAFLD patients are NASH. NASH typically characterized by steatosis inflammation, fibrosis driven metabolic disruptions such as obesity, diabetes, dyslipidemia. with significant increased risk developing cirrhosis failure. second leading cause for transplant in United States. More importantly, hepatocellular carcinoma has also been highlighted recent studies. Patients may years before progressing into Although pathogenesis not completely understood, current “multiple-hits” hypothesis suggests that addition fat accumulation, elevated oxidative ER stress drive inflammation fibrosis. The development clinically relevant animal models pharmacological treatments hampered limited understanding mechanism a lack sensitive, non-invasive diagnostic tools. most pre-clinical divided three main groups which includes: genetic models, diet-induced, toxin + diet-induced models. dietary mimic natural course humans, often only induce mild injury. Many rapidly disruption serious injury, but without their own shortcomings. This review provides an overview evaluation currently existing update on available interventions managing well agents undergoing clinical trials treatment

Язык: Английский

Процитировано

192
FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome DOI
Fuming Li,

Peiwei Huangyang,

Michelle Burrows

и другие.

Nature Cell Biology, Год журнала: 2020, Номер 22(6), С. 728 - 739

Опубликована: Май 4, 2020

Язык: Английский

Процитировано

157
The immunobiology of hepatocellular carcinoma in humans and mice: Basic concepts and therapeutic implications DOI Open Access
Jiajie Hou, Haiyan Zhang, Beicheng Sun

и другие.

Journal of Hepatology, Год журнала: 2019, Номер 72(1), С. 167 - 182

Опубликована: Авг. 23, 2019

Язык: Английский

Процитировано

154
XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis DOI
Aleksandra Deczkowska, Eyal David, Pierluigi Ramadori

и другие.

Nature Medicine, Год журнала: 2021, Номер 27(6), С. 1043 - 1054

Опубликована: Май 20, 2021

Язык: Английский

Процитировано

146
Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis DOI Creative Commons
Junliang Kuang,

Jieyi Wang,

Yitao Li

и другие.

Cell Metabolism, Год журнала: 2023, Номер 35(10), С. 1752 - 1766.e8

Опубликована: Авг. 16, 2023

Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged distinct mechanistic pathways implicated in development NAFLD. Here, we report group gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with presence and severity HDCA treatment has been shown to alleviate NAFLD multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) upregulating hepatic CYP7B1. Additionally, significantly increased abundances probiotic species such Parabacteroides distasonis, which enhances lipid catabolism through acid-hepatic peroxisome proliferator-activated alpha (PPARα) signaling, turn upregulates FXR. These findings suggest therapeutic potential for treating NAFLD, unique mechanism simultaneously activating CYP7B1 PPARα.

Язык: Английский

Процитировано

133