Cell Death Discovery, Год журнала: 2024, Номер 10(1)
Опубликована: Сен. 7, 2024
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Окт. 14, 2024
Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against
Язык: Английский
Процитировано
50
Redox Biology, Год журнала: 2023, Номер 68, С. 102963 - 102963
Опубликована: Ноя. 16, 2023
Non-alcoholic fatty liver disease (NAFLD) is a potentially serious that affects 30 % of the global population and poses significant risk to human health. However, date, no safe, effective appropriate treatment modalities are available. In recent years, ferroptosis has emerged as mode cell death been found play key regulatory role in development NAFLD. this study, we arbutin (ARB), natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits onset ameliorates high-fat diet-induced NAFLD vivo vitro. Using reverse docking, identified demethylase fat mass obesity-related protein (FTO) potential target ARB. Subsequent mechanistic studies revealed ARB plays controlling methylation SLC7A11 gene through inhibition FTO. addition, demonstrated could alleviate Our findings identify FTO/SLC7A11 axis therapeutic for Specifically, show alleviates by acting on pathway inhibit ferroptosis.
Язык: Английский
Процитировано
36
Molecular Medicine, Год журнала: 2023, Номер 29(1)
Опубликована: Сен. 28, 2023
Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications type 2 diabetes mellitus (T2DM). The pathogenesis NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well genetic and environmental factors. Liraglutide has been used to control blood sugar. But impact liraglutide on T2DM-associated remains unclear. In this study, we investigated potential molecular mechanisms inhibiting ferroptosis for improves NAFLD.Mice were fed high-fat-diet injected with streptozotocin mimic gene expression in was analysed by RNA-seq. fast glucose measured during period ferrostatin-1 administration. Hematoxylin eosin staining evaluate pathological changes liver. occurrence hepatic lipid peroxidation vivo. mechanism inhibition vitro cell culture.Liraglutide not only improved metabolism, but also ameliorated tissue damage livers. Transcriptomic analysis indicated that regulates metabolism related signaling AMPK ACC. Furthermore, inhibitor rather than other death inhibitors rescued viability presence high glucose. Mechanistically, liraglutide-induced activation phosphorylated ACC, while compound C blocked liraglutide-mediated suppression ferroptosis. Moreover, restored function T2DM mice vivo.These findings indicate ameliorates NAFLD, which possibly through AMPK/ACC pathway
Язык: Английский
Процитировано
33
Frontiers in Pharmacology, Год журнала: 2023, Номер 14
Опубликована: Март 21, 2023
Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced that highly related to metabolic disorders and induced by high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as protective bioactive polyphenol in green tea the ability protect against non-alcoholic disease, but molecular mechanism remains poorly deciphered. Ferroptosis plays vital role progression of experimental evidence ferroptosis inhibition limited. Hence, our study aimed investigate effect mechanisms on hepatic mitigate injury diet-fed mice. Methods: Fifty male C57BL/6 mice were fed either standard chow (SCD), diet, or administered ferrostatin-1 (a ferroptosis-specific inhibitor) for 12 weeks. Liver injury, lipid accumulation, steatosis, oxidative stress, iron overload, marker proteins examined. In vitro , steatotic L-02 cells used explore underlying mechanism. Results: research, we found notably alleviated decreased overload inhibited diet-induced murine model disease. experiments, using mitochondrial reactive oxygen species (MtROS) scavenger (Mito-TEMPO), remarkably stress reducing level cells. Conclusion: Taken together, results revealed may exert effects lipotoxicity inhibiting species-mediated ferroptosis. Findings from provide new insight into prevention treatment strategies pathological processes.
Язык: Английский
Процитировано
28
Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11
Опубликована: Май 16, 2023
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of worldwide. These conditions can lead to cirrhosis, cancer, failure, other related ailments. At present, transplantation remains sole treatment option for end-stage NASH, a rapidly growing socioeconomic burden. Kupffer cells (KCs) dominant population macrophages that reside in liver, playing crucial role innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, triggering immune responses. Moreover, they interact with during pathogenesis NAFLD, this crosstalk may either delay or exacerbate progression. Stimulation by endogenous signals triggers activation KCs, resulting expression various inflammatory factors chemokines, such NLRP3, TNF-α, IL-1B, IL-6, contributing cascade. In past 5 years, significant advances have been made understanding biological properties functions KCs including their interactions tissue molecules, underlying molecular mechanisms, signaling pathways, relevant therapeutic interventions. Having comprehensive these mechanisms characteristics enormous potential guiding future strategies prevention NAFLD.
Язык: Английский
Процитировано
28
Frontiers in Pharmacology, Год журнала: 2024, Номер 14
Опубликована: Янв. 19, 2024
In light of a global rise in the number patients with type 2 diabetes mellitus (T2DM) and obesity, non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated (MAFLD) or steatotic (MASLD), has become leading cause hepatocellular carcinoma (HCC), annual occurrence MASLD-driven HCC expected to increase by 45%–130% 2030. Although MASLD serious major public health threat globally, exact molecular mechanisms mediating remain an open problem, necessitating future investigation. Meanwhile, emerging studies are focusing on utility bioactive compounds halt progression HCC. this review, we first briefly review recent progress possible pathogenesis for We then discuss application mitigate through different modulatory encompassing anti-inflammatory, lipid metabolic, gut microbial pathways, providing valuable information treatment prevention Nonetheless, clinical research exploring effectiveness herbal medicines is still warranted.
Язык: Английский
Процитировано
11
Chemical Engineering Journal, Год журнала: 2024, Номер 484, С. 149518 - 149518
Опубликована: Фев. 10, 2024
Язык: Английский
Процитировано
10
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Фев. 14, 2024
In the past 11 years, there has been a surge in studies exploring regulatory effect of Traditional Chinese Medicine (TCM) on ferroptosis. However, significant gap persists comprehensive scientometric analysis and scientific mapping research, especially tracking evolution, primary contributors, emerging research focal points. This study aims to comprehensively update advancements targeting ferroptosis with various TCMs during previous years. The data, covering period from 1 January 2012, 30 November 2023, were retrieved Web Science database. For in-depth visualized analyses, series advanced analytical instruments employed. findings highlight China’s predominant role, accounting for 71.99% total publications significantly shaping this domain. Noteworthy productivity was observed at institutions, including Guangzhou University Medicine, Chengdu Zhejiang University. Thomas Efferth emerged as foremost author within field, while Frontiers Pharmacology boasted highest publication count. pinpointed hepatocellular carcinoma, chemical drug-induced liver injury, mitochondrial diseases, acute kidney failure most critical disorders addressed realm. offers bibliometric evaluation, enhancing our understanding present status TCM therapy managing ferroptosis-related diseases. Consequently, it aids both seasoned researchers newcomers by accelerating access vital information fostering innovative concept extraction specialized field.
Язык: Английский
Процитировано
10
Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(6), С. 221 - 221
Опубликована: Июнь 20, 2024
The endoplasmic reticulum (ER) played an important role in the folding, assembly and post-translational modification of proteins. ER homeostasis could be disrupted by accumulation misfolded proteins, elevated reactive oxygen species (ROS) levels, abnormal Ca2+ signaling, which was referred to stress (ERS). Ferroptosis a unique programmed cell death model mediated iron-dependent phospholipid peroxidation multiple signaling pathways. changes mitochondrial structure, damage glutathione peroxidase 4 (GPX4) excess iron were main characteristics ferroptosis. ROS produced ferroptosis can interfere with activity protein-folding enzymes, leading large amounts unfolded thus causing ERS. On contrary, increase ERS level promote ion lipid peroxide, up-regulation related genes. At present, studies on relationship between one-sided lack in-depth interaction mechanism. This review aimed explore molecular mechanism cross-talk ERS, provide new strategies targets for treatment liver diseases.
Язык: Английский
Процитировано
9
Metabolites, Год журнала: 2024, Номер 14(4), С. 218 - 218
Опубликована: Апрель 12, 2024
Metabolic-associated fatty liver disease (MAFLD), characterized primarily by hepatic steatosis, has become the most prevalent worldwide, affecting approximately two-fifths of global population. The pathogenesis MAFLD is extremely complex, and to date, there are no approved therapeutic drugs for clinical use. Considerable evidence indicates that various metabolic disorders play a pivotal role in progression MAFLD, including lipids, carbohydrates, amino acids, micronutrients. In recent years, medicinal properties natural products have attracted widespread attention, numerous studies reported their efficacy ameliorating subsequently alleviating MAFLD. This review aims summarize metabolic-associated pathological mechanisms as well regulate pathways alleviate
Язык: Английский
Процитировано
8