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https://www.readbyqxmd.com/read/27933538/systems-genetics-of-liver-fibrosis
#1
Rabea A Hall, Frank Lammert
This systems genetics analysis comprises quantitative measurements of hepatic fibrogenesis in mouse models and mapping of quantitative traits in mouse genetic reference populations. It is part of a large mapping project of fibrogenic genes including the analyses of experimental crosses from different inbred mouse strains. Extensive quantitative trait loci (QTL) mapping of fibrosis phenotypes and liver expression profiling in combination with in silico mapping facilitated the identification of QTL regions and underlying candidate genes that confer fibrosis susceptibility also in humans...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933467/osteosarcoma-overview
#2
REVIEW
Brock A Lindsey, Justin E Markel, Eugenie S Kleinerman
Osteosarcoma (OS) is the most common primary malignancy of bone and patients with metastatic disease or recurrences continue to have very poor outcomes. Unfortunately, little prognostic improvement has been generated from the last 20 years of research and a new perspective is warranted. OS is extremely heterogeneous in both its origins and manifestations. Although multiple associations have been made between the development of osteosarcoma and race, gender, age, various genomic alterations, and exposure situations among others, the etiology remains unclear and controversial...
December 8, 2016: Rheumatology and Therapy
https://www.readbyqxmd.com/read/27933306/significant-changes-in-endogenous-retinal-gene-expression-assessed-1-year-after-a-single-intraocular-injection-of-aav-cntf-or-aav-bdnf
#3
Chrisna J LeVaillant, Anil Sharma, Jill Muhling, Lachlan Pg Wheeler, Greg S Cozens, Mats Hellström, Jennifer Rodger, Alan R Harvey
Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV) vectors encoding brain-derived neurotrophic factor (BDNF) or ciliary derived neurotrophic factor (CNTF) promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933277/lectins-from-synadenium-carinatum-scll-and-artocarpus-heterophyllus-artinm-are-able-to-induce-beneficial-immunomodulatory-effects-in-a-murine-model-for-treatment-of-toxoplasma-gondii-infection
#4
Eliézer L P Ramos, Silas S Santana, Murilo V Silva, Fernanda M Santiago, Tiago W P Mineo, José R Mineo
Infection by Toxoplasma gondii affects around one-third of world population and the treatment for patients presenting toxoplasmosis clinically manifested disease is mainly based by a combination of sulfadiazine, pyrimethamine, and folinic acid. However, this therapeutic protocol is significantly toxic, causing relevant dose-related bone marrow damage. Thus, it is necessary to improve new approaches to investigate the usefulness of more effective and non-toxic agents for treatment of patients with toxoplasmosis...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27932984/curcumin-suppressed-activation-of-dendritic-cells-via-jak-stat-socs-signal-in-mice-with-experimental-colitis
#5
Hai-Mei Zhao, Rong Xu, Xiao-Ying Huang, Shao-Min Cheng, Min-Fang Huang, Hai-Yang Yue, Xin Wang, Yong Zou, Ai-Ping Lu, Duan-Yong Liu
Dendritic cells (DCs) play a pivotal role as initiators in the pathogenesis of inflammatory bowel disease and are regulated by the JAK/STAT/SOCS signaling pathway. As a potent anti-inflammatory compound, curcumin represents a viable treatment alternative or adjunctive therapy in the management of chronic inflammatory bowel disease (IBD). The mechanism of curcumin treated IBD on DCs is not completely understood. In the present study, we explored the mechanism of curcumin treated experimental colitis by observing activation of DCs via JAK/STAT/SOCS signaling pathway in colitis mice...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932944/role-of-homocysteine-in-the-ischemic-stroke-and-development-of-ischemic-tolerance
#6
REVIEW
Ján Lehotský, Barbara Tothová, Maria Kovalská, Dušan Dobrota, Anna Beňová, Dagmar Kalenská, Peter Kaplán
Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27932800/timps-versatile-extracellular-regulators-in-cancer
#7
Hartland W Jackson, Virginie Defamie, Paul Waterhouse, Rama Khokha
A compelling long-term goal of cancer biology is to understand the crucial players during tumorigenesis in order to develop new interventions. Here, we review how the four non-redundant tissue inhibitors of metalloproteinases (TIMPs) regulate the pericellular proteolysis of a vast range of matrix and cell surface proteins, generating simultaneous effects on tumour architecture and cell signalling. Experimental studies demonstrate the contribution of TIMPs to the majority of cancer hallmarks, and human cancers invariably show TIMP deregulation in the tumour or stroma...
December 9, 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27932591/the-cellular-diversity-of-the-pedunculopontine-nucleus-relevance-to-behavior-in-health-and-aspects-of-parkinson-s-disease
#8
REVIEW
Ilse S Pienaar, Anthony Vernon, Philip Winn
The pedunculopontine nucleus (PPN) is a rostral brainstem structure that has extensive connections with basal ganglia nuclei and the thalamus. Through these the PPN contributes to neural circuits that effect cortical and hippocampal activity. The PPN also has descending connections to nuclei of the pontine and medullary reticular formations, deep cerebellar nuclei, and the spinal cord. Interest in the PPN has increased dramatically since it was first suggested to be a novel target for treating patients with Parkinson's disease who are refractory to medication...
December 7, 2016: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/27932504/expression-of-cav1-3-calcium-channel-in-the-human-and-mouse-colon-post-transcriptional-inhibition-by-ifn%C3%AE
#9
Vijayababu M Radhakrishnan, Maryam M Gilpatrick, Nouralhoda Dehdashti, Pawel R Kiela, Fayez K Ghishan
It has been hypothesized that apically expressed L-type Ca(2+) channel Cav1.3 (encoded by CACNA1D gene) contributes towards an alternative TRPV6-independent route of intestinal epithelial Ca(2+) absorption, especially during digestion when high luminal concentration of Ca(2+) and other nutrients limit TRPV6 contribution. We and others have implicated altered expression and activity of key mediators of intestinal and renal Ca(2+) (re)absorption as contributors to negative systemic Ca2+ balance and bone loss in intestinal inflammation...
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27932294/large-scale-structure-based-prediction-and-identification-of-novel-protease-substrates-using-computational-protein-design
#10
Manasi A Pethe, Aliza B Rubenstein, Sagar D Khare
Characterizing the substrate specificity of protease enzymes is critical for illuminating the molecular basis of their diverse and complex roles in a wide array of biological processes. Rapid and accurate prediction of their extended substrate specificity would also aid in the design of custom proteases capable of selectively and controllably cleaving biotechnologically or therapeutically relevant targets. However, current in silico approaches for protease specificity prediction, rely on, and are therefore limited by, machine learning of sequence patterns in known experimental data...
December 5, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27931938/improving-the-secretory-capacity-of-chinese-hamster-ovary-cells-by-ectopic-expression-of-effector-genes-lessons-learned-and-future-directions
#11
REVIEW
Henning Gram Hansen, Nuša Pristovšek, Helene Faustrup Kildegaard, Gyun Min Lee
Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottlenecks in the biosynthetic pathway of r-proteins remain to be solved. To this end, the ectopic expression of transgenes (effector genes) offers great engineering potential. However, studies on effector genes have in some cases led to inconsistent results...
December 5, 2016: Biotechnology Advances
https://www.readbyqxmd.com/read/27931886/neurobiological-after-effects-of-non-invasive-brain-stimulation
#12
REVIEW
G Cirillo, G Di Pino, F Capone, F Ranieri, L Florio, V Todisco, G Tedeschi, K Funke, V Di Lazzaro
BACKGROUND: In recent years, many studies have evaluated the effects of noninvasive brain stimulation (NIBS) techniques for the treatment of several neurological and psychiatric disorders. Positive results led to approval of NIBS for some of these conditions by the Food and Drug Administration in the USA. The therapeutic effects of NIBS have been related to bi-directional changes in cortical excitability with the direction of change depending on the choice of stimulation protocol. Although after-effects are mostly short lived, complex neurobiological mechanisms related to changes in synaptic excitability bear the potential to further induce therapy-relevant lasting changes...
November 17, 2016: Brain Stimulation
https://www.readbyqxmd.com/read/27931680/reactivation-or-reinfection-in-adult-tuberculosis-is-that-the-question
#13
Pere-Joan Cardona
Looking at the chapter on "natural history" in any tuberculosis (TB) reference book, there is a kind of certainty regarding TB in adults. That is the concept of "post-primary" TB described as the reactivation of dormant bacilli hidden in an old lesion developed during infancy due to a type of local immunosuppression. Intriguingly, this concept involves at least two major uncertainties: how can dormant bacilli remain for such a long period, almost a lifetime, in an old lesion, taking into account granuloma dynamism; and what sort of local immunosuppression is the one that facilitates reactivation? The controversy between reactivation and exogenous reinfection as the cause of active TB started very soon in TB research...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27930695/coordinated-activation-of-vegf-vegfr-2-and-ppar%C3%AE-pathways-by-a-multi-component-chinese-medicine-dhi-accelerated-recovery-from-peripheral-arterial-disease-in-type-2-diabetic-mice
#14
Shuang He, Tiechan Zhao, Hao Guo, Yanzhi Meng, Gangjian Qin, David A Goukassian, Jihong Han, Xuimei Gao, Yan Zhu
Diabetic mellitus (DM) patients are at an increased risk of developing peripheral arterial disease (PAD). Danhong injection (DHI) is a Chinese patent medicine widely used for several cardiovascular indications but the mechanism of action is not well-understood. We investigated the therapeutic potential of DHI on experimental PAD in mice with chemically induced as well as genetic (KKAy) type 2 DM and the overlapping signaling pathways regulating both therapeutic angiogenesis and glucose homeostasis. Compared with normal genetic background wild type (WT) mice, both DM mice showed impaired perfusion recovery in hind-limb ischemia (HLI) model...
2016: PloS One
https://www.readbyqxmd.com/read/27929421/ghrelin-attenuates-intestinal-barrier-dysfunction-following-intracerebral-hemorrhage-in-mice
#15
Yijun Cheng, Yongxu Wei, Wenlei Yang, Yu Cai, Bin Chen, Guoyuan Yang, Hanbing Shang, Weiguo Zhao
Intestinal barrier dysfunction remains a critical problem in patients with intracerebral hemorrhage (ICH) and is associated with poor prognosis. Ghrelin, a brain-gut peptide, has been shown to exert protection in animal models of gastrointestinal injury. However, the effect of ghrelin on intestinal barrier dysfunction post-ICH and its possible underlying mechanisms are still unknown. This study was designed to investigate whether ghrelin administration attenuates intestinal barrier dysfunction in experimental ICH using an intrastriatal autologous blood infusion mouse model...
December 6, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27929168/a-computational-study-of-self-assembled-hexapeptide-inhibitors-against-amyloid-%C3%AE-a%C3%AE-aggregation
#16
Yuan Qiao, Mingzhen Zhang, Ya'nan Liang, Jie Zheng, Guizhao Liang
The fibrillation and deposition of amyloid-β (Aβ) peptides in human brains are pathologically linked to Alzheimer's disease (AD). Development of different inhibitors (peptides, organic molecules, and nanoparticles) to prevent Aβ aggregation becomes a promising therapeutic strategy for AD treatment. We recently propose a "like-interacts-like" design principle to computationally design/screen and experimentally validate a new set of hexapeptide inhibitors with completely different sequences from the Aβ sequence...
December 8, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27928466/metabolic-positron-emission-tomography-imaging-of-cancer-pairing-lipid-metabolism-with-glycolysis
#17
EDITORIAL
Sandi A Kwee, John Lim
The limitations of fluorine-18 fluorodeoxy-D-glucose (FDG) in detecting some cancers has prompted a longstanding search for other positron emission tomography (PET) tracers to complement the imaging of glycolysis in oncology, with much attention paid to lipogenesis based on observations that the production of various lipid and lipid-containing compounds is increased in most cancers. Radiolabeled analogs of choline and acetate have now been used as oncologic PET probes for over a decade, showing convincingly improved detection sensitivity over FDG for certain cancers...
November 28, 2016: World Journal of Radiology
https://www.readbyqxmd.com/read/27928028/mitochondrial-pyruvate-carrier-regulates-autophagy-inflammation-and-neurodegeneration-in-experimental-models-of-parkinson-s-disease
#18
Anamitra Ghosh, Trevor Tyson, Sonia George, Erin N Hildebrandt, Jennifer A Steiner, Zachary Madaj, Emily Schulz, Emily Machiela, William G McDonald, Martha L Escobar Galvis, Jeffrey H Kordower, Jeremy M Van Raamsdonk, Jerry R Colca, Patrik Brundin
Mitochondrial and autophagic dysfunction as well as neuroinflammation are involved in the pathophysiology of Parkinson's disease (PD). We hypothesized that targeting the mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mTOR (mammalian target of rapamycin) activation, might attenuate neurodegeneration of nigral dopaminergic neurons in animal models of PD. To test this, we used MSDC-0160, a compound that specifically targets MPC, to reduce its activity. MSDC-0160 protected against 1-methyl-4-phenylpyridinium (MPP(+)) insult in murine and cultured human midbrain dopamine neurons and in an α-synuclein-based Caenorhabditis elegans model...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27927932/ethical-clinical-translation-of-stem-cell-interventions-for-neurologic-disease
#19
David J Cote, Annelien L Bredenoord, Timothy R Smith, Mario Ammirati, Jannick Brennum, Ivar Mendez, Ahmed S Ammar, Naci Balak, Gene Bolles, Ignatius Ngene Esene, Tiit Mathiesen, Marike L Broekman
The application of stem cell transplants in clinical practice has increased in frequency in recent years. Many of the stem cell transplants in neurologic diseases, including stroke, Parkinson disease, spinal cord injury, and demyelinating diseases, are unproven-they have not been tested in prospective, controlled clinical trials and have not become accepted therapies. Stem cell transplant procedures currently being carried out have therapeutic aims, but are frequently experimental and unregulated, and could potentially put patients at risk...
December 7, 2016: Neurology
https://www.readbyqxmd.com/read/27927771/propagation-of-thrombosis-by-neutrophils-and-extracellular-nucleosome-networks
#20
Susanne Pfeiler, Konstantin Stark, Steffen Massberg, Bernd Engelmann
Neutrophils, early mediators of innate immune defense, are recruited to developing thrombi in different types of thrombosis. They amplify intravascular coagulation by stimulating the tissue factor-dependent extrinsic pathway via inactivation of endogenous anticoagulants, enhancing factor XII activation or decreasing plasmin generation. Neutrophil-dependent prothrombotic mechanisms are supported by the externalization of decondensed nucleosomes and granule proteins that together form neutrophil extracellular traps...
December 7, 2016: Haematologica
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