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Trends in Molecular Medicine

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https://www.readbyqxmd.com/read/30017531/crispr-stressed-about-p53
#1
Miguel Foronda, Lukas E Dow
Two recent reports show that, in some contexts, CRISPR-mediated genome editing can lead to a p53-mediated stress response and cell-cycle arrest. These findings may help to explain why CRISPR-mediated genetic manipulation in different cell types leads to dissimilar outcomes, and highlights the need for a better understanding of the factors that influence effective genome editing in vitro and in vivo.
July 13, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/30006148/the-impact-of-systemic-inflammation-on-neurodevelopment
#2
REVIEW
Nona M Jiang, Maureen Cowan, Shannon N Moonah, William A Petri
Inflammatory mediators affect the brain during development. Neurodevelopmental disorders such as autism spectrum disorders, cognitive impairment, cerebral palsy, epilepsy, and schizophrenia have been linked to early life inflammation. Recent advances have shown the effects of systemic inflammation on children's neurodevelopment. We discuss the potential mechanisms by which inflammatory molecules can exert their effects on the developing brain and consider the roles of MHC class I molecules, the HPA axis, glial cells, and monoamine metabolism...
July 10, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/30006147/pluripotent-stem-cell-platforms-for-drug-discovery
#3
REVIEW
Kevin G Chen, Barbara S Mallon, Kyeyoon Park, Pamela G Robey, Ronald D G McKay, Michael M Gottesman, Wei Zheng
Use of human pluripotent stem cells (hPSCs) and their differentiated derivatives have led to recent proof-of-principle drug discoveries, defining a pathway to the implementation of hPSC-based drug discovery (hPDD). Current hPDD strategies, however, have inevitable conceptual biases and technological limitations, including the dimensionality of cell-culture methods, cell maturity and functionality, experimental variability, and data reproducibility. In this review, we dissect representative hPDD systems via analysis of hPSC-based 2D-monolayers, 3D culture, and organoids...
July 10, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29983335/seeing-the-light-after-25-years-of-retinal-gene-therapy
#4
REVIEW
Ivana Trapani, Alberto Auricchio
The retina has been at the forefront of translational gene therapy. Proof-of-concept that gene therapy could restore vision in a large animal led to the initiation of the first successful clinical trials and, in turn, to the recent approval of the first gene therapy product for an ocular disease. As dozens of clinical trials of retinal gene therapy have begun, new challenges are identified, which include delivery of large genes, counteracting gain-of-function mutations, and safe and effective gene transfer to diseased retinas...
July 5, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29980480/katalin-susztak
#5
(no author information available yet)
No abstract text is available yet for this article.
July 3, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29980479/exercise-training-as-therapy-for-cancer-induced-cardiac-cachexia
#6
REVIEW
J M M Antunes, Rita M P Ferreira, Daniel Moreira-Gonçalves
Cancer-induced cardiac cachexia is an insidious syndrome with a dramatic impact on a patient's quality of life and survival. Since exercise training provides several cardiovascular benefits in both physiological and pathological conditions (e.g., athletes and patients with heart failure, respectively), its use as a preventive and/or therapeutic tool for cancer-induced cardiac cachexia has been hypothesized. Existing evidence on the effects of exercise training in this particular setting is limited, but points towards a beneficial outcome...
July 3, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29945758/ipsc-derived-enterocyte-like-cells-for-drug-absorption-and-metabolism-studies
#7
REVIEW
Maria Helena Macedo, Francisca Araújo, Elena Martínez, Cristina Barrias, Bruno Sarmento
Intestinal cell models have been widely studied and used to evaluate absorption and metabolism of drugs in the small intestine, constituting valuable tools as a first approach to evaluate the behavior of new drugs. However, such cell models might not be able to fully predict the absorption mechanisms and metabolic pathways of the tested compounds. In recent years, induced pluripotent stem cells (iPSCs) differentiated into enterocyte-like cells have been proposed as more biorelevant intestinal models. In this review, we describe mechanisms underlying the differentiation of iPSCs into enterocyte-like cells, appraise the usefulness of these cells in tridimensional intestinal models, and discuss their suitability to be used in the future for drug screening...
June 23, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29934283/axon-regeneration-antagonistic-signaling-pairs-in-neuronal-polarization
#8
REVIEW
Sophie M Hapak, Sourav Ghosh, Carla V Rothlin
Genome-wide screens, proteomics, and candidate-based approaches have identified numerous genes associated with neuronal regeneration following central nervous system (CNS) injury. Despite significant progress, functional recovery remains a challenge, even in model systems. Neuronal function depends on segregation of axonal versus dendritic domains. A key to functional recovery may lie in recapitulating the developmental signals that instruct axon specification and growth in adult neurons post-injury. Theoretically, binary activator-inhibitor elements operating as a Turing-like system within neurons can specify axonal versus dendritic domains and promote axon growth...
June 19, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29886044/apol1-the-balance-imposed-by-infection-selection-and-kidney-disease
#9
REVIEW
Pazit Beckerman, Katalin Susztak
Chronic kidney disease (CKD) affects millions of people and constitutes a major health and financial burden worldwide. People of African descent are at an increased risk of developing kidney disease, which is mostly explained by two variants in the Apolipoprotein L1 (APOL1) gene that are found only in people of west African origin. It is hypothesized that these variants were genetically selected due to the protection they afford against African sleeping sickness, caused by the parasite Trypanosoma brucei. Targeting mutant APOL1 could have substantial therapeutic potential for treating kidney disease...
June 6, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29747910/stroke-promotes-systemic-endothelial-inflammation-and-atherosclerosis
#10
Ruslan Rust, Anna-Sophie Hofer, Martin E Schwab
Patients who survive a stroke have an increased risk for recurrent vascular events. The mechanisms underlying the events are barely understood. A recent study suggests that stroke-enhanced atherosclerosis is induced through brain-released alarmins, which lead to systemic vascular inflammation and plaque formation. Interfering with these processes may lead to novel therapeutic approaches.
May 7, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29884540/focus-on-fundamentals-achieving-effective-nanoparticle-targeting
#11
REVIEW
Gregory T Tietjen, Laura G Bracaglia, W Mark Saltzman, Jordan S Pober
Successful molecular targeting of nanoparticle drug carriers can enhance therapeutic specificity and reduce systemic toxicity. Typically, ligands specific for cognate receptors expressed on the intended target cell type are conjugated to the nanoparticle surface. This approach, often called active targeting, seems to imply that the conjugated ligand imbues the nanoparticle with homing capacity. However, ligand-receptor interactions are mediated by short-range forces and cannot produce magnetic-like attraction over larger distances...
July 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29880309/beyond-cell-death-new-functions-for-tnf-family-cytokines-in-autoimmunity-and-tumor-immunotherapy
#12
REVIEW
Fei Yi, Nicholas Frazzette, Anthony C Cruz, Christopher A Klebanoff, Richard M Siegel
Originally discovered as an inducer of apoptosis, the TNF-family receptor Fas (CD95, APO-1, TNFRSF6) has more recently been found to have functions beyond cell death, including T cell co-stimulation and promoting terminal differentiation of CD4+ and CD8+ T cells. Other TNF family members also discovered as apoptosis inducers, such as TRAIL (APO-2L, TNFSF10), can promote inflammation through caspase-8. Surprisingly, non-apoptotic signaling through Fas can protect from the autoimmunity seen in Fas deficiency independently from the cell death inducing functions of the receptor...
July 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29807705/the-way-of-tau-secretion-and-synaptic-dysfunction
#13
Dena B Dubal
Tau, a microtubule-associated protein, is linked to many neurodegenerative diseases, including Alzheimer's disease (AD). A recent study uncovered a new pathway for its secretion, leading to its transcellular uptake, while another study found that tau secreted from human induced pluripotent stem cells (iPSCs) modeling trisomy 21-related AD caused synaptic impairment in rats. These findings could inform tau-directed therapies.
July 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29804923/reshaping-the-immune-tumor-microenvironment-through-ire1-signaling
#14
REVIEW
Camila Rubio-Patiño, Jozef P Bossowski, Eric Chevet, Jean-Ehrland Ricci
The ability of a tumor cell to cope with environmental and intracellular stress depends on its capacity to activate appropriate adaptive pathways. As such, the endoplasmic reticulum (ER) adjusts the adaptive capacity of tumor cells by engaging the unfolded protein response (UPR). The UPR maintains the functionality of the secretory pathway, thereby allowing tumor cells to shape their microenvironment, thus likely determining the nature of the tumor immune response. Consequently, this makes the UPR very relevant in the context of cancer therapeutics...
July 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29802036/building-blood-vessels-with-vascular-progenitor-cells
#15
REVIEW
Thomas Colunga, Stephen Dalton
Vascular progenitor cells have been identified from perivascular cell fractions and peripheral blood and bone marrow mononuclear fractions. These vascular progenitors share the ability to generate some of the vascular lineages, including endothelial cells, smooth muscle cells, and pericytes. The potential therapeutic uses for vascular progenitor cells are broad and relate to stroke, ischemic disease, and to the engineering of whole organs and tissues that require a vascular component. This review summarizes the best-characterized sources of vascular progenitor cells and discusses advances in 3D printing and electrospinning using blended polymers for the creation of biomimetic vascular grafts...
July 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29802035/a-dna-nanorobot-uprises-against-cancer
#16
Hari R Singh, Enzo Kopperger, Friedrich C Simmel
DNA-based nanorobots have been shown to sense and respond to molecular triggers, such as intracellular pH and cell surface receptors. A recent report describes DNA nanorobots as potential cancer therapeutic agents that can be programmed to trigger coagulation inside blood vessels at the tumor site, starving tumor cells to death.
July 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29773319/advancements-in-nanomedicine-for-multiple-myeloma
#17
REVIEW
Alexandre Detappe, Mark Bustoros, Tarek H Mouhieddine, P Peter Ghoroghchian
In the past decades, considerable progress has been made in our understanding and treatment of multiple myeloma. Several challenges remain including our abilities to longitudinally image tumor responses to treatment, to combine various therapeutic agents with different mechanisms of action but with overlapping toxicities, and to efficiently harness the power of the immune system to augment remission and/or to induce permanent cures. Nanomedicine may help to address many of these outstanding issues, affording novel diagnostic capabilities and offering disruptive technologies that promise to revolutionize treatment...
June 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29751974/chemiexcitation-and-its-implications-for-disease
#18
REVIEW
Douglas E Brash, Leticia C P Goncalves, Etelvino J H Bechara
Quantum mechanics rarely extends to molecular medicine. Recently, the pigment melanin was found to be susceptible to chemiexcitation, in which an electron is chemically excited to a high-energy molecular orbital. In invertebrates, chemiexcitation causes bioluminescence; in mammals, a higher-energy process involving melanin transfers energy to DNA without photons, creating the lethal and mutagenic cyclobutane pyrimidine dimer that can cause melanoma. This process is initiated by NO and O2 - radicals, the formation of which can be triggered by ultraviolet light or inflammation...
June 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29731353/advances-in-meningeal-immunity
#19
REVIEW
Rejane Rua, Dorian B McGavern
The central nervous system (CNS) is an immunologically specialized tissue protected by a blood-brain barrier. The CNS parenchyma is enveloped by a series of overlapping membranes that are collectively referred to as the meninges. The meninges provide an additional CNS barrier, harbor a diverse array of resident immune cells, and serve as a crucial interface with the periphery. Recent studies have significantly advanced our understanding of meningeal immunity, demonstrating how a complex immune landscape influences CNS functions under steady-state and inflammatory conditions...
June 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29731352/vaccinating-with-stem-cells-to-stop-cancer
#20
Yared Hailemichael, Manisha Singh, Willem Overwijk
In a recent study, Kooreman and colleagues identify a set of genes expressed in both induced pluripotent stem cells (iPSCs) and cancer cells. Vaccination of mice with iPSCs induces prophylactic and therapeutic anticancer immunity to shared antigens, opening a possible avenue towards rapid generation of iPSC-based, personalized cancer vaccines.
June 2018: Trends in Molecular Medicine
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