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Trends in Molecular Medicine

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https://www.readbyqxmd.com/read/28196625/-did-he-who-made-the-lamb-make-thee-new-developments-in-treating-the-fearful-symmetry-of-acute-myeloid-leukemia
#1
REVIEW
Gabriela Brumatti, Najoua Lalaoui, Andrew H Wei, John Silke
Malignant cells must circumvent endogenous cell death pathways to survive and develop into cancers. Acquired cell death resistance also sets up malignant cells to survive anticancer therapies. Acute Myeloid Leukemia (AML) is an aggressive blood cancer characterized by high relapse rate and resistance to cytotoxic therapies. Recent collaborative profiling projects have led to a greater understanding of the 'fearful symmetry' of the genomic landscape of AML, and point to the development of novel potential therapies that can overcome factors linked to chemoresistance...
February 11, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28188103/kidney-organoids-a-translational-journey
#2
REVIEW
Ryuji Morizane, Joseph V Bonventre
Human pluripotent stem cells (hPSCs) are attractive sources for regenerative medicine and disease modeling in vitro. Directed hPSC differentiation approaches have derived from knowledge of cell development in vivo rather than from stochastic cell differentiation. Moreover, there has been great success in the generation of 3D organ-buds termed 'organoids' from hPSCs; these consist of a variety of cell types in vitro that mimic organs in vivo. The organoid bears great potential in the study of human diseases in vitro, especially when combined with CRISPR/Cas9-based genome-editing...
February 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28188102/mitochondrial-dynamics-coupling-mitochondrial-fitness-with-healthy-aging
#3
REVIEW
David Sebastián, Manuel Palacín, Antonio Zorzano
Aging is associated with a decline in mitochondrial function and the accumulation of abnormal mitochondria. However, the precise mechanisms by which aging promotes these mitochondrial alterations and the role of the latter in aging are still not fully understood. Mitochondrial dynamics is a key process regulating mitochondrial function and quality. Altered expression of some mitochondrial dynamics proteins has been recently associated with aging and with age-related alterations in yeast, Caenorhabditis elegans, mice, and humans...
February 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28185790/immune-regulation-of-antibody-access-to-neuronal-tissues
#4
REVIEW
Akiko Iwasaki
This review highlights recent advances in how the innate and adaptive immune systems control the blood-brain barrier (BBB) and the blood-nerve barrier (BNB). Interferons and TAM receptors play key roles in innate immune control of the BBB. Cells of the adaptive immune system, particularly CD4(+) T cells, take distinct routes to enter neural tissues and mediate immune surveillance. Furthermore, T cell-mediated opening of the BBB and the BNB is crucial to allow antibody access and thereby block the replication of neurotropic viruses...
February 6, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28185789/type-i-interferons-modulate-cd8-t-cell-immunity-to-mrna-vaccines
#5
REVIEW
Ans De Beuckelaer, Johan Grooten, Stefaan De Koker
mRNA vaccines have emerged as potent tools to elicit antitumor T cell immunity. They are characterized by a strong induction of type I interferons (IFNs), potent inflammatory cytokines affecting T cell differentiation and survival. Recent reports have attributed opposing roles for type I IFNs in modulating CD8+ T cell immunity to mRNA vaccines, from profoundly stimulatory to strongly inhibitory. The mechanisms behind this duality are unclear. Disentangling the factors governing the beneficial or detrimental impact of type I IFNs on CD8+ T cell responses is vital to the design of mRNA vaccines of increased potency...
February 6, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28173976/targeting-pfkfb3-in-the-endothelium-for-cancer-therapy
#6
Qi Yang, Peng Hou
In a recent article published in Cancer Cell, Cantelmo et al. showed that inhibition of endothelium glycolysis by targeting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) significantly impaired tumor metastasis by normalizing tumor vessels. In addition, as a promising therapeutic strategy, tumor vessel normalization by PFKFB3 blockade also improved the delivery and efficacy of chemotherapy.
February 4, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28162910/direct-effects-of-anti-angiogenic-therapies-on-tumor-cells-vegf-signaling
#7
REVIEW
Thomas Simon, Teresa Gagliano, Georgios Giamas
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 conditions induced by AAT. However, strategies targeting these mechanisms of resistance are still failing to improve treatments. Furthermore, a potential direct impact of AAT on tumor cells cannot be overlooked...
February 2, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28162909/biallelic-irf8-mutations-causing-nk-cell-deficiency
#8
Alejandro López-Soto, Seila Lorenzo-Herrero, Segundo Gonzalez
Human primary immunodeficiencies result in an exacerbated susceptibility to contracting infectious diseases. Recent work by Mace et al., published in the Journal of Clinical Investigation, unveils a novel genetic cause for the development of familial natural killer (NK) cell deficiency: a biallelic compound heterozygous mutation in IRF8, which leads to impaired NK cell development and cytotoxic activity.
February 2, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28129958/cell-based-therapeutics-making-a-faustian-pact-with-biology
#9
REVIEW
Daniel J Woodsworth, Robert A Holt
The diversity and specialization found in biological molecules, pathways, and cells is staggering, and should be exploited for therapeutic use. Through evolution these biological systems have attained a level of functionality that would be impossible to recapitulate with de novo assembly. To adapt these systems for therapeutic applications it will be often necessary to re-engineer molecules and pathways to yield novel sensory, control, and effector modules for insertion into existing, specialized cellular chassis...
January 24, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28126271/antibody-antibiotic-conjugates-a-novel-therapeutic-platform-against-bacterial-infections
#10
REVIEW
Sanjeev Mariathasan, Man-Wah Tan
Antibodies are potent components of the immune repertoire and have been successfully exploited to treat bacterial infections. Recently an antibody-antibiotic conjugate (AAC) that combines key attributes of an antibody and antibiotic has been shown to be efficacious against Staphylococcus aureus infection. An AAC has three components: an antibiotic payload to kill bacteria, an antibody to target delivery of the payload to bacteria, and a linker attaching the payload to the antibody. With increasing understanding of the biology and pathophysiology of S...
January 23, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28117227/beta-cell-fragility-as-a-common-underlying-risk-factor-in-type-1-and-type-2-diabetes
#11
REVIEW
Adrian Liston, John A Todd, Vasiliki Lagou
Type 1 and type 2 diabetes are distinct clinical entities primarily driven by autoimmunity and metabolic dysfunction, respectively. However, there is a growing appreciation that they may share an etiopathological factor, namely the role of variation in beta-cell sensitivity to stress factors. Increased sensitivity increases the risk of beta-cell death or insulin secretion dysfunction. The beta-cell fragility model proposes that this variation contributes to the risk of developing either type 1 or type 2 diabetes, in the presence of immunological and/or metabolic stress factors...
January 20, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28111024/mitochondrial-dysfunction-and-neurodegeneration-in-lysosomal-storage-disorders
#12
REVIEW
Nicoletta Plotegher, Michael R Duchen
Lysosomal storage disorders (LSDs) are rare inherited debilitating and often fatal disorders. Caused by mutations affecting lysosomal proteins, LSDs are characterized by the accumulation of undegraded material in lysosomes and by lysosomal dysfunction. Although LSDs are multisystemic diseases, the majority display neurologic symptoms and neurodegeneration. Only recently has a role emerged for mitochondrial dysfunction in the pathophysiology of LSDs, suggesting an impact of lysosomal dysfunction on mitochondria...
January 19, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28109721/inflammasome-priming-in-sterile-inflammatory-disease
#13
REVIEW
Meghana N Patel, Richard G Carroll, Silvia Galván-Peña, Evanna L Mills, Robin Olden, Martha Triantafilou, Amaya I Wolf, Clare E Bryant, Kathy Triantafilou, Seth L Masters
The inflammasome is a cytoplasmic protein complex that processes interleukins (IL)-1β and IL-18, and drives a form of cell death known as pyroptosis. Oligomerization of this complex is actually the second step of activation, and a priming step must occur first. This involves transcriptional upregulation of pro-IL-1β, inflammasome sensor NLRP3, or the non-canonical inflammasome sensor caspase-11. An additional aspect of priming is the post-translational modification of particular inflammasome constituents...
January 18, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28108112/the-olfactory-neural-epithelium-as-a-tool-in-neuroscience
#14
Joëlle Lavoie, Patricia Gassó Astorga, Hadar Segal-Gavish, YeeWen Candace Wu, Youjin Chung, Nicola G Cascella, Akira Sawa, Koko Ishizuka
Capturing both dynamic changes (state) and persistent signatures (trait) directly associated with disease at the molecular level is crucial in modern medicine. The olfactory neural epithelium, easily accessible in clinical settings, is a promising surrogate model in translational brain medicine, complementing the limitations in current engineered cell models.
January 17, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28110838/molecular-imaging-of-abdominal-aortic-aneurysms
#15
REVIEW
Julia Brangsch, Carolin Reimann, Federico Collettini, Ralf Buchert, René M Botnar, Marcus R Makowski
Abdominal aortic aneurysms (AAAs) represent a vascular disease with severe complications. AAAs are currently the overall 10th leading cause of death in western countries and their incidence is rising. Although different diagnostic techniques are currently available in clinical practice, including ultrasound (US), magnetic resonance imaging (MRI), and computed tomography (CT), imaging-based prediction of life-threatening complications such as aneurysm-rupture remains challenging. Molecular imaging provides a novel diagnostic approach for in vivo visualization of biological processes and pathological alterations at a cellular and molecular level...
January 16, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28089302/germinal-center-lymphocyte-ratios-and-successful-hiv-vaccines
#16
Paula Gonzalez-Figueroa, Jonathan A Roco, Carola G Vinuesa
Current HIV vaccines are poor inducers of neutralizing antibodies (nAbs). A recent study in Cell Reports used serial fine-needle aspirates from rhesus macaque lymph nodes following HIV-1 surface envelope glycoprotein (Env) trimer immunization, generating a substantial production of HIV-1 nAbs. A remarkable correlation was found between antibody titers and a high frequency and ratio of germinal center B and T follicular helper (TFH) lymphocytes.
January 11, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28082126/metabolic-syndrome-one-speckled-stone-kills-a-flock-of-birds
#17
Ylva Bonde, Bo Angelin
Effectively treating metabolic syndrome and its progression to type 2 diabetes, steatohepatitis and cardiovascular disease remain a major clinical challenge. The use of a novel engineered molecule that combines thyroid hormone and glucagon to target liver and adipose tissue might provide a new 'magic bullet' with exciting future prospects.
January 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28041781/the-fountain-of-youth-by-targeting-senescent-cells
#18
REVIEW
Peter L J de Keizer
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner...
December 20, 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28041565/the-fountain-of-youth-by-targeting-senescent-cells
#19
REVIEW
Peter L J de Keizer
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27989642/microrna-regulation-of-rna-virus-replication-and-pathogenesis
#20
REVIEW
Derek W Trobaugh, William B Klimstra
microRNAs (miRNAs) are non-coding RNAs that regulate many processes within a cell by manipulating protein levels through direct binding to mRNA and influencing translation efficiency, or mRNA abundance. Recent evidence demonstrates that miRNAs can also affect RNA virus replication and pathogenesis through direct binding to the RNA virus genome or through virus-mediated changes in the host transcriptome. Here, we review the current knowledge on the interaction between RNA viruses and cellular miRNAs. We also discuss how cell and tissue-specific expression of miRNAs can directly affect viral pathogenesis...
January 2017: Trends in Molecular Medicine
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