Abstract:
:Non-alcoholic steatohepatitis (NASH), a cause of cirrhosis and hepatocellular carcinoma, is characterized by fatty infiltration of the liver, inflammation, hepatocellular damage and fibrosis. Progress has been made in understanding the molecular and cellular mechanisms implicated in the pathogenesis of this condition, therefore, we here review recent developments regarding the basic mechanisms of NASH development. Accumulation of triglycerides in the hepatocytes is the result of increased inflow of free fatty acids and de novo lipogenesis. Steatosis leads to lipotoxicity, which causes apoptosis, necrosis, generation of oxidative stress and inflammation. The resulting chronic injury activates a fibrogenic response that leads eventually to end-stage liver disease. A better understanding of these mechanisms is crucial for the design of novel diagnostic and therapeutic strategies.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Marra F,Gastaldelli A,Svegliati Baroni G,Tell G,Tiribelli Cdoi
10.1016/j.molmed.2007.12.003subject
Has Abstractpub_date
2008-02-01 00:00:00pages
72-81issue
2eissn
1471-4914issn
1471-499Xpii
S1471-4914(08)00020-8journal_volume
14pub_type
杂志文章,评审abstract::BAX is a formidable BCL-2 family protein that executes cellular suicide in response to physiologic and pathologic stress. A new article in Nature Chemical Biology (Garner et al.https://doi.org/10.1038/s41589-018-0223-0) reports small molecules that inhibit the conformational activation of BAX, informing a pharmacologi...
journal_title:Trends in molecular medicine
pub_type: 信件
doi:10.1016/j.molmed.2019.02.008
更新日期:2019-04-01 00:00:00
abstract::In the coming years, molecular diagnostics will continue to be of critical importance to public health worldwide. It will facilitate the detection and characterization of disease, as well as monitoring of the drug response, and will assist in the identification of genetic modifiers and disease susceptibility. A wide r...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/s1471-4914(02)02331-6
更新日期:2002-06-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is a common lethal genetic disorder, characterized by the progressive development of fluid-filled cysts in the kidney, pancreas and liver, and anomalies of the cardiovascular system. Mutations in PKD1 and PKD2, which encode the transmembrane proteins polycystin-1 (P...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/s1471-4914(03)00073-x
更新日期:2003-06-01 00:00:00
abstract::House dust mite (HDM) allergy is a frequent inflammatory disease found worldwide. Although allergen-specific CD4(+) Th2 cells orchestrate the HDM allergic response, notably through induction of IgE directed towards mite allergens, recent studies have demonstrated that innate immunity activation also plays a critical r...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2011.05.014
更新日期:2011-10-01 00:00:00
abstract::The deregulation of tyrosine kinase receptors (RTKs) is frequent in human tumors and is often associated with the acquisition of an aggressive phenotype. The Met oncogene, encoding the RTK for hepatocyte growth factor (HGF), controls genetic programs leading to cell growth, invasion and protection from apoptosis. The ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.04.005
更新日期:2005-06-01 00:00:00
abstract::Recurrent pregnancy loss (RPL), which occurs in 0.5%-1% of total pregnancies, is usually defined as three or more consecutive spontaneous abortions before 20 weeks of gestation. Although an immunology-based etiology underlying unexplained RPL has been demonstrated, the exact molecular mechanisms are still poorly under...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2007.05.005
更新日期:2007-07-01 00:00:00
abstract::Despite advances in treatment for glioblastoma multiforme (GBM), patient prognosis remains poor. Although there is growing evidence that molecular targeting could translate into better survival for GBM, current clinical data show limited impact on survival. Recent progress in GBM genomics implicate several activated p...
journal_title:Trends in molecular medicine
pub_type: 临床试验,杂志文章,评审
doi:10.1016/j.molmed.2011.01.011
更新日期:2011-06-01 00:00:00
abstract::The past few years have seen the identification of PTPN22 and the confirmation of CTLA-4 as common autoimmune disease genes. Together with MHC and INS, these developments have increased the collection of confirmed susceptibility loci for autoimmunity. In this article, the latest developments related to these genes and...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.12.005
更新日期:2006-02-01 00:00:00
abstract::Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of m...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2020.01.009
更新日期:2020-05-01 00:00:00
abstract::BRCA2 was identified in 1995, one year after BRCA1. In terms of knowledge of the function of its product, BRCA2 has remained the less well-characterised gene. Both BRCA1 and BRCA2 are closely implicated in the repair of double-strand breaks in DNA by homologous recombination, but beyond that a function for BRCA2 has b...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.02.003
更新日期:2005-04-01 00:00:00
abstract::Invariant natural killer T (iNKT) cells are innate lymphocytes with unique specificity for glycolipid antigens and remarkable immunomodulatory properties. The role of costimulatory interactions in iNKT cell responses has recently come under scrutiny. Although iNKT cells and their prototype glycolipid agonist α-galacto...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2010.10.007
更新日期:2011-02-01 00:00:00
abstract::Ten percent of inherited diseases are caused by premature termination codon (PTC) mutations that lead to degradation of the mRNA template and to the production of a non-functional, truncated polypeptide. In addition, many acquired mutations in cancer introduce similar PTCs. In 1999, proof-of-concept for treating these...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2012.09.008
更新日期:2012-11-01 00:00:00
abstract::Accumulating evidence supports the important role for epigenetic changes in modulating clinical parameters of complex disorders, including neurodegenerative disease. Several conditions, including fragile X syndrome and Huntington's disease are caused by trinucleotide repeat (TNR) expansions in or near specific genes. ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2013.07.007
更新日期:2013-11-01 00:00:00
abstract::Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently, exercise-dependent mobilization of NK cells was found to play a central role in exercise-mediated protection against cancer. Here, we review the link betwe...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2016.05.007
更新日期:2016-07-01 00:00:00
abstract::Rearrangements of the MLL gene, which is located at chromosome 11q23, are associated with aggressive acute leukemias in both children and adults. MLL regulates Hox gene expression through direct promoter binding and histone modification. MLL rearrangements occurring in leukemia include MLL fusion genes, partial tandem...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2004.08.005
更新日期:2004-10-01 00:00:00
abstract::H(2)O(2) is a reactive oxygen species that has drawn much interest because of its role as a second messenger in receptor-mediated signaling. Mammalian 2-Cys peroxiredoxins have been shown to eliminate efficiently the H(2)O(2) generated in response to receptor stimulation. 2-Cys peroxiredoxins are members of a novel pe...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.10.006
更新日期:2005-12-01 00:00:00
abstract::The proteins encoded by the breast-cancer-susceptibility genes, BRCA1 and BRCA2, have recently been implicated in DNA-repair processes, thereby improving our understanding of how the loss of these genes contributes to cancer initiation and progression. It appears that the role of BRCA1 in DNA repair, which could invol...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(02)02434-6
更新日期:2002-12-01 00:00:00
abstract::The innate immune system uses pattern recognition receptors (PRRs) to sense invading microbes and initiate a rapid protective response. PRRs bind and are activated by structural motifs, such as nucleic acids or bacterial and fungal cell wall components, collectively known as pathogen-associated molecular patterns. PRR...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2009.06.003
更新日期:2009-08-01 00:00:00
abstract::Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics availabl...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.08.002
更新日期:2017-10-01 00:00:00
abstract::The majority of biomedical and biological research relies on a few molecular biology techniques. Here we show that eight key molecular biology techniques would not exist without basic biological research. We also find that the scientific reward system does not sufficiently value basic biological research into molecula...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2018.12.003
更新日期:2019-02-01 00:00:00
abstract::Recent studies have shown that male reproductive function is modulated via the mitogen-activated protein kinase (MAPK) cascade. The MAPK cascade is involved in numerous male reproductive processes, including spermatogenesis, sperm maturation and activation, capacitation and acrosome reaction, before fertilization of t...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2009.02.002
更新日期:2009-04-01 00:00:00
abstract::Prion diseases are infectious neurodegenerative fatal disorders. There are currently no treatments or cures. Considerable evidence suggests that the infectious agent is an abnormally folded protein that promotes or seeds its normal cellular isoform to fold into the infectious form. However, the precise mechanism and f...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2005.08.006
更新日期:2005-10-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially lethal monogenic disorder, with more than 12 million cases worldwide. The two causative genes for ADPKD, PKD1 and PKD2, encode protein products polycystin-1 (PC1) and polycystin-2 (PC2 or TRPP2), respectively. Recent data have shed lig...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2014.01.004
更新日期:2014-05-01 00:00:00
abstract::During fertilization, the spermatozoon penetrates through the cumulus cells and the zona pellucida that surrounds the oocyte, before it binds and fuses with the oocyte plasma membrane to induce activation. In vitro fertilization (IVF) studies performed in non-human mammals have contributed extensive knowledge regardin...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(01)01957-8
更新日期:2001-04-01 00:00:00
abstract::Despite years of investigation, it is still not known why iron levels are abnormally high in some regions of the brain in neurodegenerative disorders. Also, it is not clear whether iron accumulation in the brain is an initial event that causes neuronal death or is a consequence of the disease process. Here, we propose...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(00)01910-9
更新日期:2001-03-01 00:00:00
abstract::Defects in the regulation of apoptosis (programmed cell death) contribute to many diseases, including pathologies associated with cell loss (e.g. stroke, heart failure, neurodegeneration and AIDS), and disorders characterized by a failure to eliminate harmful cells (e.g. cancer, autoimmunity). Apoptosis is caused by a...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(01)02026-3
更新日期:2001-07-01 00:00:00
abstract::Activated factor Xa (FXa) is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. Long considered a passive bystander, it is now evident that FXa exerts direct effects on a wide variety of cell types via activation of its two main receptors, protease-activated rece...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2008.08.001
更新日期:2008-10-01 00:00:00
abstract::miRNAs are small noncoding RNAs known to post-transcriptionally regulate gene expression. miRNAs are expressed in the heart where they regulate multiple pathophysiological processes. The discovery of stable cardiac miRNAs in the bloodstream has also motivated the investigation of their potential as biomarkers. This re...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2014.10.006
更新日期:2014-12-01 00:00:00
abstract::Sex differences have been clinically documented in numerous neurodegenerative diseases and yet the reasons for these differences are not well understood. Recent studies have found that microglia, the innate immune cells of the central nervous system, are a key cell type involved in neurodegenerative diseases. This cel...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.05.001
更新日期:2019-09-01 00:00:00
abstract::Migraine is a complex, disabling disorder of the brain that manifests itself as attacks of often severe, throbbing head pain with sensory sensitivity to light, sound and head movement. There is a clear familial tendency to migraine, which has been well defined in a rare autosomal dominant form of familial hemiplegic m...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2006.11.005
更新日期:2007-01-01 00:00:00