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Trends in Molecular Medicine

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https://www.readbyqxmd.com/read/28803703/viral-hijacking-of-formins-in-neurodevelopmental-pathologies
#1
REVIEW
Karen Racicot, Sarah VanOeveren, Art Alberts
The 2015 Zika virus (ZIKV) outbreak caused global concern when it was determined to cause microcephaly, hearing loss, and other neurodevelopmental manifestations upon fetal exposure. Significant progress has been made in our understanding of the interactions between ZIKV and the pregnant host, but there is still a critical need to understand how ZIKV and other neurotropic viruses affect fetal neurodevelopment. Diaphanous-related formins (Diaphs) have recently been identified as microcephaly-associated proteins in humans and mice...
August 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28801069/hsc-niche-biology-and-hsc-expansion-ex-vivo
#2
REVIEW
Sachin Kumar, Hartmut Geiger
Hematopoietic stem cell (HSC) transplantation can restore a new functional hematopoietic system in recipients in cases where the system of the recipient is not functional or for example is leukemic. However, the number of available donor HSCs is often too low for successful transplantation. Expansion of HSCs and thus HSC self-renewal ex vivo would greatly improve transplantation therapy in the clinic. In vivo, HSCs expand significantly in the niche, but establishing protocols that result in HSC expansion ex vivo remains challenging...
August 8, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28797787/t-cell-exhaustion-an-epigenetically-imprinted-phenotypic-and-functional-makeover
#3
Francesca Alfei, Dietmar Zehn
A recent article in Cell demonstrates that the absence of a single DNA methyltransferase, Dnmt3a, prevents cytotoxic T cells from acquiring the hypofunctional or exhausted phenotype typically seen in chronic viral infections and tumors. Upon establishing a causal relationship between exhaustion-associated epigenetic changes and reduced CD8(+) T cell function, the authors provided mechanistic evidence that exhaustion constitutes a specific differentiation program.
August 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28789830/sphingosine-kinase-1-a-potential-therapeutic-target-in-pulmonary-arterial-hypertension
#4
REVIEW
Nigel J Pyne, Susan Pyne
Sphingosine kinase 1 (SphK1) knockout mice are protected against pulmonary hypertension and expression levels of the enzyme are increased in the lungs of pulmonary arterial hypertensive (PAH) patients. Moreover, sphingosine 1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arterial smooth muscle cell models. Therefore, SphK1 might be a novel target for treatment of PAH. However, in our opinion, more refined strategies to target SphK1 are needed because this enzyme is protective against endothelial dysfunction and can become resistant to SphK1 inhibitors in vascular smooth muscle, thereby potentially limiting their effectiveness in PAH...
August 5, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28789829/a-topical-solution-to-the-sunless-tanning-problem
#5
Helen T Michael, Glenn Merlino
Skin cancer is the most commonly diagnosed type of cancer and is strongly associated with UV exposure and skin pigmentation. Recent advances in pharmacologic non-UV tanning methods open the possibility of preventing melanoma and non-melanoma skin cancer, especially in people who do not tan in the sun.
August 5, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28781061/dissecting-glioma-invasiveness-in-a-3d-organotypic-model
#6
Paolo Codega, Ingo K Mellinghoff
Diffuse brain infiltration by tumor cells is a hallmark of glioma. Molecular mechanisms of brain invasion are poorly understood due to the difficulty to model this process in culture. A new study published in Cell Reports developed a three-dimensional organotypic model and identified interferon regulatory factor 3 (IRF3) as repressor of glioma invasion.
August 3, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28774478/putting-glioblastoma-in-its-place-irf3-inhibits-invasion
#7
Siobhan S Pattwell, Eric C Holland
With an unsurpassed capacity for invasion into normal brain tissue, glioblastoma multiforme is the most lethal primary brain tumor. New research suggests that altering a subset of extracellular matrix factors, including interferon regulatory factor (IRF)3 and casein kinase (CK)2, may decrease the migratory potential of these aggressive tumors.
July 31, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28739207/obstructive-sleep-apnea-and-hallmarks-of-aging
#8
REVIEW
Laetitia S Gaspar, Ana Rita Álvaro, Joaquim Moita, Cláudia Cavadas
Obstructive sleep apnea (OSA) is one of the most common sleep disorders. Since aging is a risk factor for OSA development, it is expected that its prevalence will increase with the current increase in life span. In recent years, several studies have shown that OSA potentially contributes to functional decline, mainly prompted by chronic intermittent hypoxia and sleep fragmentation. Here, we propose that OSA might anticipate/aggravate aging by inducing cellular and molecular impairments that characterize the aging process, such as stem cell exhaustion, telomere attrition and epigenetic changes...
July 21, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28735817/osteosarcoma-molecular-pathogenesis-and-ipsc-modeling
#9
REVIEW
Yu-Hsuan Lin, Brittany E Jewell, Julian Gingold, Linchao Lu, Ruiying Zhao, Lisa L Wang, Dung-Fang Lee
Rare hereditary disorders provide unequivocal evidence of the importance of genes in human disease pathogenesis. Familial syndromes that predispose to osteosarcomagenesis are invaluable in understanding the underlying genetics of this malignancy. Recently, patient-derived induced pluripotent stem cells (iPSCs) have been successfully utilized to model Li-Fraumeni syndrome (LFS)-associated bone malignancy, demonstrating that iPSCs can serve as an in vitro disease model to elucidate osteosarcoma etiology. We provide here an overview of osteosarcoma predisposition syndromes and review recently established iPSC disease models for these familial syndromes...
July 20, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28732688/molecular-pathophysiology-of-gout
#10
REVIEW
Jyaysi Desai, Stefanie Steiger, Hans-Joachim Anders
Three contradictory clinical presentations of gout have puzzled clinicians and basic scientists for some time: first, the crescendo of sterile inflammation in acute gouty arthritis; second, its spontaneous resolution, despite monosodium urate (MSU) crystal persistence in the synovium; and third, immune anergy to MSU crystal masses observed in tophaceous or visceral gout. Here, we provide an update on the molecular pathophysiology of these gout manifestations, namely, how MSU crystals can trigger the auto-amplification loop of necroinflammation underlying the crescendo of acute gouty arthritis...
July 18, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28732687/selective-therapeutic-intervention-a-challenge-against-off-target-effects
#11
Filip Rázga, Veronika Némethová
Despite the massive global spend on biology-driven drug discovery, tackling the issue of side effects and adverse events resulting from drug promiscuity represents a persistent challenge. Although delivering authentic medical innovations today is more complex than ever, minimization of off-target effects should be a priority.
July 18, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28716624/recent-advances-in-mitochondrial-aminoacyl-trna-synthetases-and-disease
#12
REVIEW
Marie Sissler, Ligia Elena González-Serrano, Eric Westhof
Dysfunctions in mitochondria - the powerhouses of the cell - lead to several human pathologies. Because mitochondria integrate nuclear and mitochondrial genetic systems, they are richly intertwined with cellular activities. The nucleus-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key components of the mitochondrial translation apparatus. Mutations in these enzymes predominantly affect the central nervous system (CNS) but also target other organs. Comparable mutations in mt-aaRSs can lead to vastly diverse diseases, occurring at different stages in life, and within different tissues; this represents a confounding issue...
July 14, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28697885/neutralizing-the-threat-pan-ebolavirus-antibodies-close-the-loop
#13
Chad E Mire, Thomas W Geisbert
The glycoprotein (GP) of ebolaviruses participates in a critical membrane fusion process to establish infection of a cell and therefore, represents an important target of both vaccines and antivirals. The latest reports on pan-ebolavirus monoclonal antibodies in small animal models may offer promising outcomes and insight into how best to target the GP in vaccine and antiviral discovery.
July 8, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28694141/amylin-receptor-a-potential-therapeutic-target-for-alzheimer-s-disease
#14
REVIEW
Wen Fu, Aarti Patel, Ryoichi Kimura, Rania Soudy, Jack H Jhamandas
Alzheimer'sdisease (AD) is a progressive neurodegenerative disorder, characterized by senile plaques constituting extracellular deposits of β-amyloid (Aβ) fibrils. Since Aβ accumulation in the brain is considered an early event preceding, by decades, cognitive dysfunction, disease-modifying treatments are aimed at facilitating clearance of this protein from the brain or ameliorating its toxic effects. Recent studies have identified the amylin receptor as a capable mediator of the deleterious actions of Aβ and furthermore, administration of amylin receptor-based peptides has been shown to improve spatial memory and learning in transgenic mouse models of AD...
July 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28576602/biomarkers-of-human-pluripotent-stem-cell-derived-cardiac-lineages
#15
REVIEW
Rhys J P Skelton, Timothy J Kamp, David A Elliott, Reza Ardehali
Human pluripotent stem cells (hPSCs) offer a practical source for the de novo generation of cardiac tissues and a unique opportunity to investigate cardiovascular lineage commitment. Numerous strategies have focused on the in vitro production of cardiomyocytes, smooth muscle, and endothelium from hPSCs. However, these differentiation protocols often yield undesired cell types. Thus, establishing a set of stage-specific markers for pure cardiac subpopulations will assist in defining the hierarchy of cardiac differentiation, aid in the development of cellular therapy, and facilitate drug screening and disease modeling...
May 30, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28576601/linc-ing-the-noncoding-genome-to-heart-function-beating-hypertrophy
#16
Shambhabi Chatterjee, Christian Bär, Thomas Thum
The principal event of aberrant gene expression occurs in numerous disorders and syndromes, including heart failure. LncRNAs may constitute powerful treatment targets because they intensively interact with their genetic environment, as they are important regulators of genetic networks. Recent advances on the functional roles of lncRNAs in cardiac hypertrophy are expected to usher improved therapeutic strategies.
May 30, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28648962/exosomes-as-reconfigurable-therapeutic-systems
#17
REVIEW
R Steven Conlan, Simone Pisano, Marta I Oliveira, Mauro Ferrari, I Mendes Pinto
Historically, small molecules, including steroid hormones and cytokines, have been attributed a role in paracrine and endocrine signaling, and now include a new player: biological nanoparticles, or 'exosomes'. Generated intracellularly, and defined simply as nanoparticulate packages of signaling moieties, exosomes have emerged as vehicles for highly specialized local and distant intercellular communication. Exosomes are increasingly being recognized as contributing factors in many diseases, and their potential as biomarkers and in therapeutics is rapidly emerging...
May 29, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28648961/uterine-fluid-in-pregnancy-a-biological-and-clinical-outlook
#18
REVIEW
Ying Zhang, Qiang Wang, Hongmei Wang, Enkui Duan
Once considered a simple medium for sperm and embryo transport, the functional spectrum of uterine fluid is now expanding. Novel molecular players, such as extracellular vesicles and mobile RNAs, have been detected in the uterine fluid of livestock, rodents, and humans. These novel molecules, together with previously known ions and proteins, ensure uterine fluid homeostasis and facilitate embryo-maternal interactions. Here, we propose that these molecules may also carry information that mirrors maternal environmental exposure and possibly relay such information to the embryo via uterine fluid, generating long-term epigenetic effects on the offspring via embryonic and placental programming...
May 25, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28694140/mirnas-in-b-cell-development-and-lymphomagenesis
#19
REVIEW
Maryaline Coffre, Sergei B Koralov
B lymphocytes are essential for an efficient immune response against a variety of pathogens. A large fraction of hematologic malignancies is of B cell origin, suggesting that the development and activation of B cells need to be tightly regulated. In recent years, increasing evidence has emerged demonstrating that microRNAs (miRNAs) - a class of non-coding RNAs that control gene expression - are involved in the regulation of B cell development and function. We provide here an overview of the current knowledge on the role of miRNAs and their relevant targets in B cell development, B cell activation, and B cell malignant transformation...
August 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28648185/exosomes-as-reconfigurable-therapeutic-systems
#20
REVIEW
R Steven Conlan, Simone Pisano, Marta I Oliveira, Mauro Ferrari, I Mendes Pinto
Historically, small molecules, including steroid hormones and cytokines, have been attributed a role in paracrine and endocrine signaling, and now include a new player: biological nanoparticles, or 'exosomes'. Generated intracellularly, and defined simply as nanoparticulate packages of signaling moieties, exosomes have emerged as vehicles for highly specialized local and distant intercellular communication. Exosomes are increasingly being recognized as contributing factors in many diseases, and their potential as biomarkers and in therapeutics is rapidly emerging...
July 2017: Trends in Molecular Medicine
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