Abstract:
:Although significant progress has been made in understanding autoimmunity, no immunotherapy to effectively halt immune-mediated destruction of β cells in type 1 diabetes (T1D) is currently available. For successful immunotherapy it will be necessary to identify novel drug targets as well as robust immunologic biomarkers to predict disease heterogeneity and patient responsiveness. Inhibition of immune checkpoint mechanisms represents a novel and effective strategy in tumor immunotherapy. Because they are fundamental to rewiring immune circuits, the underlying mechanisms could be therapeutically enhanced and used as biomarkers in T1D. We examine here current knowledge of immune checkpoint molecules in T1D. One specific immune checkpoint mechanism, namely tryptophan metabolism, may meet the need for a valid drug target and robust biomarker in the quest for effective and personalized immunotherapy in T1D.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Orabona C,Mondanelli G,Puccetti P,Grohmann Udoi
10.1016/j.molmed.2018.08.005subject
Has Abstractpub_date
2018-11-01 00:00:00pages
931-941issue
11eissn
1471-4914issn
1471-499Xpii
S1471-4914(18)30177-1journal_volume
24pub_type
杂志文章,评审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::Physicians have, for over a century, attempted to harness the potential therapeutic power of the immune system to treat patients with cancer. The discovery that cancer regression can be achieved by immune rejection of tumour antigens theoretically allows the eradication of neoplastic cells without toxicity to normal t...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2004.02.006
更新日期:2004-04-01 00:00:00
abstract::Chronic hepatitis C is a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. Although current treatment options are limited, progress in understanding the molecular virology of hepatitis C has led to the identification of novel antiviral targets. Moreover, in vitro and in vivo model systems have b...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(02)02395-x
更新日期:2002-10-01 00:00:00
abstract::To prevent duplication or loss of genomic regions during DNA replication, it is essential that the entire genome is copied precisely once every S phase. Cells achieve this by mutually exclusive regulation of origin firing and licensing. A crucial protein that is involved in origin licensing is chromatin licensing and ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2006.08.004
更新日期:2006-10-01 00:00:00
abstract::Cyclic dipeptides (CDPs) are a group of hormone-like molecules that are evolutionarily conserved from bacteria to humans. In bacteria, CDPs are used in quorum sensing (QS) to communicate information about population size and to regulate a behavioural switch from symbiosis with their host to virulence. In mammals, CDPs...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2014.08.003
更新日期:2014-10-01 00:00:00
abstract::The surfaces of all vertebrate cells are decorated with a dense and complex array of sugar chains, which are mostly attached to proteins and lipids. Most soluble secreted proteins are also similarly decorated with such glycans. Sialic acids are a diverse family of sugar units with a nine-carbon backbone that are typic...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2008.06.002
更新日期:2008-08-01 00:00:00
abstract::Inflammatory signaling underlies many diseases, from arthritis to cancer. Our understanding of inflammation has thus far been limited to the world of proteins, because we are only just beginning to understand the role that noncoding RNAs (ncRNA) might play. It is now clear that ncRNA do not constitute transcriptional ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.11.003
更新日期:2018-01-01 00:00:00
abstract::Rheumatoid arthritis (RA) is a multifactorial immune disease exhibiting diverse clinical responses to specific therapeutic agents. Such heterogeneity reflects variable activation of signaling pathways. Consequently, RA physiopathology has been linked to many immune cells and factors, with controversial observations fo...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2018.02.001
更新日期:2018-04-01 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 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::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::Anxiety-related and metabolic disorders are under intense research focus. Anxiety-induced microRNAs (miRNAs) are emerging as regulators that are not only capable of suppressing inflammation but can also induce metabolic syndrome-related processes. We summarize here evidence linking miRNA pathways which share regulator...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2016.07.001
更新日期:2016-09-01 00:00:00
abstract::There is much evidence suggesting that there is a strong relationship between the deterioration of brain lipid homeostasis, vascular changes and the pathogenesis of Alzheimer's disease (AD). These associations include: (1). recognition that a key cholesterol transporter, apolipoprotein E type 4, acts a major genetic r...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(03)00007-8
更新日期:2003-03-01 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::The B cell arm of the immune response becomes activated soon after HIV-1 transmission, yet the initial antibody response does not control HIV-1 replication, and it takes months for neutralizing antibodies to develop against the autologous virus. Antibodies that can be broadly protective are made only in a minority of ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2010.10.008
更新日期:2011-02-01 00:00:00
abstract::The efficacy of drugs administered by traditional routes is limited by numerous biological barriers that preclude reaching the intended site of action. Further, full body systemic exposure leads to dose-limiting, off-target side effects. Topical formulations may provide more efficacious drug and nucleic acid delivery ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2020.12.001
更新日期:2021-01-04 00:00:00
abstract::Pyocyanin (PCN) is a blue redox-active secondary metabolite that is produced by Pseudomonas aeruginosa. PCN is readily recovered in large quantities in sputum from patients with cystic fibrosis who are infected by P. aeruginosa. Despite in vitro studies demonstrating that PCN interferes with multiple cellular function...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2004.10.002
更新日期:2004-12-01 00:00:00
abstract::In 1999, Tesarik and Greco reported that they could predict the developmental potential of human zygotes from a single static evaluation of their pronuclei. This was based on the distribution and number of specific nuclear organelles - the nucleoli. Recent studies in mice show that nucleoli play a key role in parental...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2015.09.005
更新日期:2015-11-01 00:00:00
abstract::Nitric-oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs), which consist of an NSAID with an NO-donating moiety covalently attached to it, promise to contribute significantly towards the development of effective chemoprevention strategies against cancer. NO-NSAIDs inhibit the growth of cultured cancer cel...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2004.05.004
更新日期:2004-07-01 00:00:00
abstract::The transcription factor SOX9 is crucial for multiple aspects of development. Mutations in SOX9 cause campomelic dysplasia, a haploinsufficiency disorder concordant with the expression profile of SOX9 during embryogenesis. The mechanistic understanding of development has revealed roles for SOX9 in regulating cartilage...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2010.12.001
更新日期:2011-03-01 00:00:00
abstract::Hypoxia-inducible factor 1 (HIF-1) controls oxygen delivery (via angiogenesis) and metabolic adaptation to hypoxia (via glycolysis). HIF-1 consists of a constitutively expressed HIF-1 beta subunit and an oxygen- and growth-factor-regulated HIF-1 alpha subunit. In xenografts, tumor growth and angiogenesis are correlate...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(02)02317-1
更新日期:2002-01-01 00:00:00
abstract::In acute organ failure, rapid compensation of function loss assures survival. Dedifferentiation and/or proliferation of surviving parenchymal cells could imply a transient (and potentially fatal) impairment of residual functional performance. However, evolution has selected two flexible life-saving mechanisms acting s...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.02.006
更新日期:2019-05-01 00:00:00
abstract::Endogenous brain repair after stroke involves a set of highly interactive processes, such as angiogenesis, neurogenesis, oligodendrogenesis, synaptogenesis, and axonal outgrowth, which together orchestrate neurological recovery. During the past several years, there have been advances in our understanding of miRNAs and...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2015.07.005
更新日期:2015-09-01 00:00:00
abstract::The Hedgehog (Hh) cascade controls cell proliferation, differentiation and patterning of tissues during embryogenesis but is largely suppressed in the adult. The Hh pathway can become reactivated in cancer. Here, we assimilate data from recent studies to understand how and when the Hh pathway is turned on to aid the n...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2010.05.003
更新日期:2010-08-01 00:00:00
abstract::Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Remarkably, ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover. This contradictory a...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2009.07.001
更新日期:2009-09-01 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::The social amoeba Dictyostelium discoideum is increasingly being used as a simple model for the investigation of problems that are relevant to human health. This article focuses on several recent examples of Dictyostelium-based biomedical research, including the analysis of immune-cell disease and chemotaxis, centroso...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2006.07.003
更新日期:2006-09-01 00:00:00
abstract::Since the discovery that IgE antibodies mediate allergy, decades of research have unraveled complex mechanisms associated with conventional immunotherapy and the vital protagonists that shape 'immune tolerance' to allergens. Debate exists on what should constitute the dominant effector mechanism in driving rational dr...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2020.01.007
更新日期:2020-04-01 00:00:00
abstract::Non-viral DNA vectors have several advantages over viral vectors. For example, virus production is expensive and there are safety concerns regarding viral manipulations. In addition, the size of the delivered plasmid is limited by the size of the viral capsid, whereas this is not a problem with non-viral vectors. The ...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/s1471-4914(03)00005-4
更新日期:2003-02-01 00:00:00
abstract::Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease. It leads to irreversible joint damage, physical handicap, and reduced life expectancy. The past two decades have seen considerable therapeutic advances with the development of biologic treatments to block proinflammatory cytokines or modulate...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2016.01.005
更新日期:2016-03-01 00:00:00