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 receptor-1 (PAR-1) and PAR-2. Recent findings suggest that PAR-2 plays a crucial role in fibro-proliferative diseases such as fibrosis, tissue remodeling and cancer and point towards FXa as the important mediator coordinating the interface between coagulation and disease progression. Here, we provide an overview of the FXa signaling pathways that mediate its effects in pathophysiology and explore the potential therapeutic implications of targeting FXa; in terms of arresting disease progression, the modulation of FXa activity might be more important than the modulation of FVIIa or thrombin.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Borensztajn K,Peppelenbosch MP,Spek CAdoi
10.1016/j.molmed.2008.08.001subject
Has Abstractpub_date
2008-10-01 00:00:00pages
429-40issue
10eissn
1471-4914issn
1471-499Xpii
S1471-4914(08)00161-5journal_volume
14pub_type
杂志文章,评审abstract：:During the past decade, successful gene therapies for immunodeficiencies were finally brought to the clinic. This was accomplished through new gene therapy vectors and improved procedures for genetic modification of autologous hematopoietic stem cells. For HIV, autologous hematopoietic stem cell (HSC) gene therapy wit...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2014.08.004
更新日期：2014-11-01 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：: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：: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：: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：:Many infectious agents elicit a type I interferon response but, until recently, the molecular details that coordinate interferon (IFN)-alpha and -beta expression during infection were unknown. Innate immune pattern recognition receptors, including Toll-like receptors and cytoplasmic RNA helicases such as retinoic acid...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2005.07.006
更新日期：2005-09-01 00:00:00
abstract：:The systemic inflammatory response is biologically complex, redundant, and activated by both infectious and noninfectious triggers. Its manipulation can cause both benefit and harm. More than 100 randomized clinical trials have tested the hypothesis that modulating the septic response to infection can improve survival...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2014.01.007
更新日期：2014-04-01 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：: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：: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：:Senescent cells drive ageing and the associated loss in health and lifespan. Whether this is mediated by systemic signalling remained unclear. Recently, Xu et al. [1] (Nat. Med. 2018;24:1246-1256) answered this question by injecting senescent cells into young mice and observing a long-lasting increase in frailty and m...
journal_title：Trends in molecular medicine
pub_type： 评论,杂志文章
doi：10.1016/j.molmed.2018.09.003
更新日期：2018-11-01 00:00:00
abstract：:Ten years ago, the linkage between mutations in the gene coding for the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) and the neurodegenerative disease known as familial amyotrophic lateral sclerosis (FALS) was established. This finding has prompted a myriad of new studies in experimental models aimed at invest...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2004.06.009
更新日期：2004-08-01 00:00:00
abstract：:While preclinical studies have reported improvement of behavioral deficits in the Ts65Dn mouse model of Down syndrome (DS), translation to human clinical trials to improve cognition in individuals with DS has had a poor success record. Timing of the intervention, choice of animal models, strategy for drug selection, a...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2019.10.001
更新日期：2020-02-01 00:00:00
abstract：:Aging is characterized by irreversible loss of physiological integrity, often accompanied by an organism's loss of function and increased vulnerability to death. Defects in the mechanisms preserving cellular homeostasis over time may give rise to accelerated aging. Somatic cell reprogramming of aged cells can be assoc...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2016.05.010
更新日期：2016-08-01 00:00:00
abstract：:Caspase-mediated apoptosis is a major hindrance to tumour growth and metastasis. Accordingly, defects in signalling pathways leading to the activation of caspases are common in tumours. Moreover, many tumour cells can unexpectedly survive the activation of caspases. As a result, caspase-independent cell death programm...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/s1471-4914(02)02328-6
更新日期：2002-05-01 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：:Mechanisms underlying antipsychotic cardiometabolic adverse effects are incompletely understood. This hampers the identification of high-risk patients, low-risk antipsychotics and preventive/ameliorative treatments. Recent clinical, molecular and genetic data suggest that: (i) antipsychotic-naïve samples provide the g...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2010.10.010
更新日期：2011-02-01 00:00:00
abstract：:Carcinoma of the gastrointestinal tract is the most common internal malignancy affecting men and women in Western countries. Chronic intestinal inflammation, especially of the colon, is also a Western disease and correlates with a significantly increased risk of developing cancer. This has suggested that the immune pr...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/s1471-4914(01)02107-4
更新日期：2001-10-01 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：:Recently revised diagnostic guidelines for Alzheimer's disease (AD) emphasise the use of biomarkers, heralding a paradigm shift towards a more biological definition of the disorder. Currently available biomarkers offer added diagnostic accuracy in certain situations, but their performance in terms of early diagnostic ...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2013.10.001
更新日期：2014-01-01 00:00:00
abstract：:Post-transcriptional RNA editing generates novel gene products by changing the coding sequence of the transcript from that in the genome. Two classes of RNA editing exist in mammals, each of which involves an enzymatic deamination. These reactions have stringent sequence and structural requirements for their target RN...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/s1471-4914(03)00032-7
更新日期：2003-04-01 00:00:00
abstract：:Genome sequencing has the potential for stratified cancer treatment and improved diagnostics for rare disorders. However, sequencing needs to be utilised in risk stratification on a population scale to deepen the impact on the health system by addressing common diseases, where individual genomic variants have variable...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2014.04.001
更新日期：2014-09-01 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：:Alterations in circulating lipids and ectopic lipid deposition impact on the risk of developing cardiovascular and metabolic diseases. Lipoprotein lipase (LPL) hydrolyzes fatty acids (FAs) from triglyceride (TAG)-rich lipoproteins including very low density lipoproteins (VLDLs) and chylomicrons, and regulates their di...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2019.05.010
更新日期：2019-08-01 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：: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：: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：:One hypothesis for the etiology of neuropsychiatric disorders proposes that viral infection contributes to the induction of neuronal system dysfunction, resulting in a wide range of behavioral abnormalities. Recent research in molecular biology supports this hypothesis and refocuses on the role of viral infection in t...
journal_title：Trends in molecular medicine
pub_type： 杂志文章
doi：10.1016/j.molmed.2003.12.001
更新日期：2004-02-01 00:00:00
abstract：:Genetically engineered mouse models have revolutionized the study of pancreatic cancer, but have several technical and practical limitations. A new adeno-associated virus (AAV)-driven somatic genome-editing model of pancreatic ductal adenocarcinoma reported by Ideno et al. (Lab. Invest. published online February 6, 20...
journal_title：Trends in molecular medicine
pub_type： 信件
doi：10.1016/j.molmed.2019.02.012
更新日期：2019-05-01 00:00:00
abstract：:Many organs throughout the body maintain epithelial homeostasis by employing a mucosal barrier which acts as a lubricant and helps to preserve a near-sterile epithelium. Goblet cells are largely responsible for secreting components of this mucosal barrier and represent a major cellular component of the innate defense ...
journal_title：Trends in molecular medicine
pub_type： 杂志文章,评审
doi：10.1016/j.molmed.2015.06.003
更新日期：2015-08-01 00:00:00
