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 for diseases and conditions affecting mucosal tissues, but the mucus protecting our epithelial surfaces is a formidable barrier. Here, we describe recent advances in mucus-penetrating approaches for drug and nucleic acid delivery to the ocular surface, the female reproductive tract, the gastrointestinal tract, and the airways.
journal_name
Trends Mol Medjournal_title
Trends in molecular medicineauthors
Zierden HC,Josyula A,Shapiro RL,Hsueh HT,Hanes J,Ensign LMdoi
10.1016/j.molmed.2020.12.001subject
Has Abstractpub_date
2021-01-04 00:00:00eissn
1471-4914issn
1471-499Xpii
S1471-4914(20)30314-2pub_type
杂志文章,评审abstract::Ten percent of the population worldwide suffers from chronic kidney disease (CKD), characterized by fibrotic changes in the kidney. Fibrosis is associated with loss of epithelial parenchyma, and accumulation of myofibroblasts, fibrillary collagen, and inflammatory cells. Two recent papers highlight the critical role o...
journal_title:Trends in molecular medicine
pub_type: 评论,杂志文章
doi:10.1016/j.molmed.2015.11.009
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abstract::Innate immunity is the first line of defense against invading pathogens. A family of Toll-like receptors (TLRs) acts as primary sensors that detect a wide variety of microbial components and elicit innate immune responses. All TLR signaling pathways culminate in activation of the transcription factor nuclear factor-ka...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2007.09.002
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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::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::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 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::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::Accumulating evidence has revealed that immunogenic cell death triggered by particular chemotherapeutic agents plays a critical role in harnessing antitumor immunity to clinical responses. However, negative regulatory pathways exist which suppress the induction of effective immune responses by a broad spectrum of anti...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2013.06.001
更新日期:2013-09-01 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::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::Recent whole exome sequencing studies in humans have provided novel insight into the importance of the ephrinB2-EphB4-RASA1 signaling axis in cerebrovascular development, corroborating and extending previous work in model systems. Here, we aim to review the human cerebrovascular phenotypes associated with ephrinB2-Eph...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.01.009
更新日期:2019-04-01 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::Small intestine bacterial overgrowth (SIBO) occurs when colonic quantities of commensal bacteria are present in the small bowel. SIBO is associated with conditions of disrupted gastrointestinal (GI) motility leading to stasis of luminal contents. Recent data show that SIBO is also found in children living in unsanitar...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2014.11.001
更新日期:2015-01-01 00:00:00
abstract::Carbon monoxide, long considered only as a toxic gas, has recently been shown to mediate potent anti-inflammatory and other salutary effects in rodents when it is used at low doses. Carbon monoxide is one of the products of the degradation of heme by heme oxygenase 1. Until recently, these beneficial effects of carbon...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2006.06.007
更新日期:2006-08-01 00:00:00
abstract::Many fundamental questions about sleep remain unanswered. The presence of sleep across phyla suggests that it must serve a basic cellular and/or molecular function. Microarray studies, performed in several model systems, have identified classes of genes that are sleep-state regulated. This has led to the following con...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2008.12.002
更新日期:2009-02-01 00:00:00
abstract::Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-β (Aβ) plaques, their clearance may be clinically more efficacious than removing Aβ when cognitive defic...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2015.03.003
更新日期:2015-06-01 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::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::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::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
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abstract::Large genome-wide association studies (GWAS) have identified loci that are associated with complex traits and diseases, but index variants are often not causal and reside in non-coding regions of the genome. To gain a better understanding of the relevant biological mechanisms, intermediate traits such as gene expressi...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2019.10.004
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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::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::Over recent decades anti-angiogenic therapies (AATs) have produced promising results in the treatment of different malignancies. Unfortunately, resistance often develops and patients ultimately relapse. In an attempt to elucidate the causes of recurrence, most studies have focused on tumor responses to hypoxic conditi...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2017.01.002
更新日期:2017-03-01 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::Phagocytosis is used not only for immune defense but may also be used to obtain nutrients, as observed when tumor cells feed upon neighboring cells during "tumor cell cannibalism". The TM9 protein TM9SF4, important in canonical phagocytosis, is involved in this cannibalism by metastatic cells and may represent a novel...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2011.09.001
更新日期:2012-01-01 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::Environmental effects on the materno-foetal interaction determine birth outcomes that predict health over the lifespan. Thus, maternal undernutrition or stress associate with low birth weight, leading to an increased risk of metabolic and cardiovascular illness in the offspring. We argue that these effects are, in par...
journal_title:Trends in molecular medicine
pub_type: 杂志文章
doi:10.1016/j.molmed.2007.05.003
更新日期:2007-07-01 00:00:00
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::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 biomarke...
journal_title:Trends in molecular medicine
pub_type: 杂志文章,评审
doi:10.1016/j.molmed.2018.08.005
更新日期:2018-11-01 00:00:00