DNA damage and repair in the hematopoietic system DOI Creative Commons

Niu Li,

Hongzhu Chen, Jian Wang

et al.

Acta Biochimica et Biophysica Sinica, Journal Year: 2022, Volume and Issue: 54(6), P. 847 - 857

Published: Jan. 1, 2022

Although hematopoietic stem cells (HSCs) in the bone marrow are a state of quiescence, they harbor self-renewal capacity and pluripotency to differentiate into mature blood when needed, which is key maintain homeostasis. Importantly, HSCs characterized by their long lifespan ( e. g., up 60 months for mice), display characteristics aging, vulnerable various endogenous exogenous genotoxic stresses. Generally, DNA damage endogenous, typically induced reactive oxygen species (ROS), aldehydes, replication stress. Mammalian have evolved complex efficient repair system cope with lesions genomic stability. The machinery has its own characteristics. For instance, Fanconi anemia (FA)/BRCA pathway particularly important system, as it can limit caused inter-strand crosslinks, oxidative stress, stress prevent FA occurrence. In addition, prefer utilize classical non-homologous end-joining pathway, essential V(D)J rearrangement developing lymphocytes involved double-strand break stability long-term quiescent state. contrast, base excision less system. this review, we summarize impact types on HSC function review our knowledge corresponding mechanisms related human genetic diseases.

Language: Английский

Alcohol-associated liver disease DOI Creative Commons
Bryan Mackowiak, Yaojie Fu, Luca Maccioni

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(3)

Published: Feb. 1, 2024

Alcohol-associated liver disease (ALD) is a major cause of chronic worldwide, and comprises spectrum several different disorders, including simple steatosis, steatohepatitis, cirrhosis, superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field ALD over last 20 years, pathogenesis remains obscure, there are currently no FDA-approved drugs for treatment ALD. In this Review, we discuss new insights into therapeutic targets ALD, utilizing study multiomics other cutting-edge approaches. The potential translation these studies clinical practice therapy deliberated. We also preclinical models interplay metabolic dysfunction, alcohol-associated cancer, heterogeneity some translational research prospects

Language: Английский

Citations

115

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease DOI Creative Commons

Chuyun Yan,

Wanting Hu,

Jinqi Tu

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 4, 2023

Abstract Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being leading cause chronic disease. Many metabolic enzymes, including dehydrogenases such as ADH, CYP2E1, CATacetaldehyde ALDHsand nonoxidative metabolizing enzymes SULT, UGT, FAEES, are involved metabolism ethanol, main component beverages. Ethanol changes functional or expression profiles various regulatory factors, kinases, transcription microRNAs. Therefore, underlying mechanisms ALD complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, oxidative stress. Moreover, recent evidence demonstrated that gut-liver axis plays critical role pathogenesis. For example, ethanol damages intestinal barrier, resulting release endotoxins alterations flora content bile acid metabolism. However, therapies show low effectiveness. this review summarizes pathways highly influential pathogenic factors pathology with aim new therapeutic insights.

Language: Английский

Citations

59

Targeting Nrf2/Keap1 signaling pathway by bioactive natural agents: Possible therapeutic strategy to combat liver disease DOI
Ravichandran Jayasuriya, Dhamodharan Umapathy, Daoud Ali

et al.

Phytomedicine, Journal Year: 2021, Volume and Issue: 92, P. 153755 - 153755

Published: Sept. 17, 2021

Language: Английский

Citations

69

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets DOI Creative Commons
Jie Xia, Siqin Li, Suling Liu

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(1)

Published: Jan. 16, 2023

The family of aldehyde dehydrogenases (ALDHs) contains 19 isozymes and is involved in the oxidation endogenous exogenous aldehydes to carboxylic acids, which contributes cellular tissue homeostasis. ALDHs play essential parts detoxification, biosynthesis, antioxidants, are important value for cell proliferation, differentiation, survival normal body tissues. However, frequently dysregulated associated with various diseases like Alzheimer's disease, Parkinson's especially solid tumors. Notably, involvement tumor progression responsible maintenance stem-cell-like phenotype, triggering rapid aggressive clinical progressions. have captured increasing attention as biomarkers disease diagnosis prognosis. Nevertheless, these require further longitudinal studies large populations broad application. This review summarizes our current knowledge regarding potential tumors several non-tumor diseases, well recent advances understanding functions underlying molecular mechanisms development. Finally, we discuss therapeutic therapy an emphasis on their implications.

Language: Английский

Citations

41

Alcohol-associated bowel disease: new insights into pathogenesis DOI Creative Commons
Luca Maccioni, Yaojie Fu,

Yves Horsmans

et al.

eGastroenterology, Journal Year: 2023, Volume and Issue: 1(1), P. e100013 - e100013

Published: Aug. 1, 2023

Excessive alcohol drinking can cause pathological changes including carcinogenesis in the digestive tract from mouth to large intestine, but underlying mechanisms are not fully understood. In this review, we discuss effects of on small and intestinal functions, such as leaky gut, dysbiosis alterations epithelium gut immune dysfunctions, commonly referred alcohol-associated bowel disease (ABD). To date, detailed mechanistic insights into ABD lacking. Accumulating evidence suggests a pathogenic role ethanol metabolism dysfunctions tract. Ethanol generates acetaldehyde acetate, which could potentially promote functional disruptions microbial host components barrier along gastrointestinal The potential involvement acetate pathogenesis ABD, cancer, is discussed. We also highlight some gaps knowledge existing field ABD. Finally, future directions exploring generated during chronic intake various pathologies affecting different sites

Language: Английский

Citations

28

Hepatocellular carcinoma and lipid metabolism: Novel targets and therapeutic strategies DOI

Lu-Qi Cao,

Yuhao Xie, Joshua S. Fleishman

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 597, P. 217061 - 217061

Published: June 13, 2024

Language: Английский

Citations

10

Oxidative stress in alcoholic liver disease, focusing on proteins, nucleic acids, and lipids: A review DOI

Weiwen Lai,

Jiahua Zhang,

Jiawei Sun

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 278, P. 134809 - 134809

Published: Aug. 16, 2024

Language: Английский

Citations

10

Hepatic and Extra-Hepatic Metabolism of Propylene Glycol Ethers in the Context of Central Nervous System Toxicity DOI Creative Commons
Sophie Werner, David Pamies, Marie‐Gabrielle Zurich

et al.

Toxicology, Journal Year: 2025, Volume and Issue: 512, P. 154081 - 154081

Published: Feb. 8, 2025

Language: Английский

Citations

1

Alcoholic liver disease: a new insight into the pathogenesis of liver disease DOI

Seol Hee Park,

Young‐Sun Lee,

Jae-Min Sim

et al.

Archives of Pharmacal Research, Journal Year: 2022, Volume and Issue: 45(7), P. 447 - 459

Published: June 27, 2022

Language: Английский

Citations

33

A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity DOI Open Access
Yujia Liu,

Takumi Myojin,

Kexin Li

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1762 - 1762

Published: Feb. 3, 2022

Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for aldehyde metabolism. Since ALDH polymorphism leads to accumulation of acetaldehyde, we considered that enhancement liver activity by certain food ingredients could help prevent alcohol-induced chronic diseases. Here, evaluated modulating effects 3-hydroxyphenylacetic acid (OPAC), metabolite quercetin glycosides, on and acetaldehyde-induced cytotoxicity in cultured cell models. OPAC significantly enhanced total not only mouse hepatoma Hepa1c1c7 cells, but also human HepG2 cells. increased nuclear level aryl hydrocarbon receptor (AhR), AhR-dependent reporter gene expression, though factor erythroid-2-related 2 (Nrf2)-dependent one. The pretreatment at concentration required upregulation completely inhibited cytotoxicity. Silencing AhR impaired resistant effect against acetaldehyde. These results strongly suggested protects cells from cytotoxicity, mainly through Nrf2-independent activity. Our findings suggest has a protective potential hepatocyte models offer new preventive possibility glycosides targeting

Language: Английский

Citations

30