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https://www.readbyqxmd.com/read/27933657/analysis-of-temozolomide-resistance-in-low-grade-gliomas-by-using-a-mechanistic-mathematical-model
#1
Edouard Ollier, Pauline Mazzocco, Damien Ricard, Gentian Kaloshi, Ahmed Idbaih, Agusti Alentorn, Dimitri Psimaras, Jérôme Honnorat, Jean-Yves Delattre, Emmanuel Grenier, François Ducray, Adeline Samson
Understanding how tumours develop resistance to chemotherapy is a major issue in oncology. When treated with temozolomide (TMZ), an oral alkylating chemotherapy drug, most low-grade gliomas (LGG) show an initial volume decrease but this effect is rarely long lasting. In addition, it has been suggested that TMZ may drive tumour progression in a subset of patients as a result of acquired resistance. Using longitudinal tumour size measurements from 121 patients, the aim of the present study was to develop a semi-mechanistic mathematical model to determine whether resistance of LGG to TMZ was more likely to result from primary and/or from chemotherapy-induced acquired resistance that may contribute to tumour progression...
December 9, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27933336/shp-1-activation-inhibits-vascular-smooth-muscle-cell-proliferation-and-intimal-hyperplasia-in-a-rodent-model-of-insulin-resistance-and-diabetes
#2
Weier Qi, Qian Li, Chong Wee Liew, Christian Rask-Madsen, Samuel M Lockhart, Lars Melholt Rasmussen, Yu Xia, Xuanchun Wang, Mogher Khamaisi, Kevin Croce, George L King
AIMS/HYPOTHESIS: Accelerated migration and proliferation of vascular smooth muscle cells (VSMCs) enhances arterial restenosis after angioplasty in insulin resistance and diabetes. Elevation of Src homology 2-containing protein tyrosine phosphatase 1 (SHP-1) induces apoptosis in the microvasculature. However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. METHODS: We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes...
December 9, 2016: Diabetologia
https://www.readbyqxmd.com/read/27933316/systemic-therapy-with-oncolytic-myxoma-virus-cures-established-residual-multiple-myeloma-in-mice
#3
Eric Bartee, Mee Y Bartee, Bjarne Bogen, Xue-Zhong Yu
Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. It has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells during autologous transplant...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933082/rna-seq-transcriptome-response-of-flax-linum-usitatissimum-l-to-the-pathogenic-fungus-fusarium-oxysporum-f-sp-lini
#4
Leonardo Galindo-González, Michael K Deyholos
Fusarium oxysporum f. sp. lini is a hemibiotrophic fungus that causes wilt in flax. Along with rust, fusarium wilt has become an important factor in flax production worldwide. Resistant flax cultivars have been used to manage the disease, but the resistance varies, depending on the interactions between specific cultivars and isolates of the pathogen. This interaction has a strong molecular basis, but no genomic information is available on how the plant responds to attempted infection, to inform breeding programs on potential candidate genes to evaluate or improve resistance across cultivars...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27933062/no-role-for-mast-cells-in-obesity-related-metabolic-dysregulation
#5
Jindřich Chmelař, Antonios Chatzigeorgiou, Kyoung-Jin Chung, Marta Prucnal, David Voehringer, Axel Roers, Triantafyllos Chavakis
Obesity-related adipose tissue (AT) inflammation that promotes metabolic dysregulation is associated with increased AT mast cell numbers. Mast cells are potent inducers of inflammatory responses and could potentially contribute to obesity-induced AT inflammation and metabolic dysregulation. Conflicting findings were reported on obesity-related metabolic dysfunction in mast cell-deficient mice, thus creating a controversy that has not been resolved to date. Whereas traditional Kit hypomorphic mast cell-deficient strains featured reduced diet-induced obesity and diabetes, a Kit-independent model of mast cell deficiency, Cpa3(Cre/+) mice, displayed no alterations in obesity and insulin sensitivity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27933037/blad-containing-oligomer-fungicidal-activity-on-human-pathogenic-yeasts-from-the-outside-to-the-inside-of-the-target-cell
#6
Ana M Pinheiro, Alexandra Carreira, Filipe Rollo, Rui Fernandes, Ricardo B Ferreira, Sara A Monteiro
Blad polypeptide comprises residues 109-281 of Lupinus albus β-conglutin precursor. It occurs naturally as a major subunit of an edible, 210 kDa oligomer which accumulates to high levels, exclusively in the cotyledons of Lupinus seedlings between the 4th and 14th day after the onset of germination. Blad-containing oligomer (BCO) exhibits a potent and broad spectrum fungicide activity toward plant pathogens and is now on sale in the US under the tradename Fracture(TM). In this work we demonstrate its antifungal activity toward human pathogens and provide some insights on its mode of action...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932979/madagascine-induces-vasodilatation-via-activation-of-ampk
#7
Dapeng Chen, Bochao Lv, Sei Kobayashi, Yongjian Xiong, Pengyuan Sun, Yuan Lin, Salvatore Genovese, Francesco Epifano, Shanshan Hou, Fusheng Tang, Yunyan Ji, Dandan Yu
Madagascine (3-isopentenyloxyemodin) can be chemically synthesized or purified from several Rhamnus species, and it is found to have more potent biological activities than the parent compound emodin. The aim of this study is to characterize the vasodilatory effect of madagascine on vasoconstriction and sphingosylphosphorylcholine induced vasospasm in ex vivo and reveal the potential mechanisms in vitro. The effects of madagascine on vasoconstriction of rat mesenteric resistance arteries (MRAs) induced by K(+), methoxamine, and endothelin-1 were, respectively, studied...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932946/increased-brain-neurotensin-and-ntsr2-lead-to-weak-nociception-in-ntsr3-sortilin-knockout-mice
#8
Christelle Devader, Sébastien Moreno, Morgane Roulot, Emmanuel Deval, Thomas Dix, Carlos R Morales, Jean Mazella
The neuropeptide neurotensin (NT) elicits numerous pharmacological effects through three different receptors (NTSR1, NTSR2, and NTSR3 also called sortilin). Pharmacological approaches and generation of NTSR1 and NTSR2-deficient mice allowed to determine the NT-induced antipsychotic like behavior, the inhibitory of weak fear memory and the nociceptive signaling in a rat formalin tonic pain model to NTSR1. Conversely, the effects of NT on thermal and tonic nociceptions were mediated by NTSR2. However, the role of NTSR3/sortilin on the neurotensinergic system was not investigated...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27932936/riboflavin-along-with-antibiotics-balances-reactive-oxygen-species-and-inflammatory-cytokines-and-controls-staphylococcus-aureus-infection-by-boosting-murine-macrophage-function-and-regulates-inflammation
#9
Somrita Dey, Biswadev Bishayi
BACKGROUND: Macrophages serve as intracellular reservoirs of S. aureus. Recent in vitro studies have confirmed high level resistance by S. aureus to macrophage mediated killing and the intracellular persistence of Staphylococci may play an important role in the pathogenesis. Since this localization protects them from both cell-mediated and humoral immune responses, therefore, a successful anti-staphylococcal therapy should include the elimination of intracellular bacteria, further protecting the host cells from staphylococci-induced cell death...
2016: Journal of Inflammation
https://www.readbyqxmd.com/read/27932681/acute-intermittent-hypoxia-in-rats-activates-muscle-proteolytic-pathways-through-a-glucocorticoid-dependent-mechanism
#10
Franciele Przygodda, Leandro Henrique Manfredi, Juliano Machado, Dawit A P Gonçalves, Neusa Maria Zanon, Leni G H Bonagamba, Benedito H Machado, Isis do Carmo Kettelhut, Luiz C C Navegantes
Although it is well known that chronic hypoxia induces muscle wasting, the effects of intermit-tent hypoxia on skeletal muscle protein metabolism remains unclear. We hypothesized that acute intermittent hypoxia (AIH), a challenge that activates the hypothalamic-pituitary-adrenal axis, would alter muscle protein homeostasis through a glucocorticoid-dependent mechanism. Three-week-old rats were submitted to adrenalectomy (ADX) and exposed to 8 h of AIH (6% O2 for 40s at 9 min intervals). Animals were sacrificed and the soleus and extensor digitorum longus (EDL) muscles were harvested and incubated in vitro for measurements of protein turn-over...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27932679/tendon-collagen-synthesis-declines-with-immobilization-in-elderly-humans-no-effect-of-anti-inflammatory-medication
#11
Kasper Dideriksen, Anders Ploug Boesen, Søren Reitelseder, Christian Couppe, Rene Brüggebusch Svensson, Peter Schjerling, S Peter Magnusson, Lars Holm, Michael Kjaer
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are used as pain killers during periods of unloading caused by traumatic occurrences or diseases. However, it is unknown how the tendon protein turnover and mechanical properties responds to unloading and subsequent loading in elderly humans, and especially whether NSAIDs affect tendon adaptation during such periods. Thus, we studied the influence of NSAID upon the human patellar tendon protein synthesis and mechanical properties during immobilization and subsequent rehabilitating resistance training...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27932674/metabolic-adaptations-in-skeletal-muscle-after-84-days-bed-rest-with-and-without-concurrent-flywheel-resistance-exercise
#12
José Maria Irimia, Mario Guerrero, Paula Rodriguez-Miguelez, Joan Aureli Cadefau, Per A Tesch, Roser Cussó, Rodrigo Fernandez-Gonzalo
As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n=9) or without (BR; n=12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1) and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α) and myostatin, were analysed in samples from m...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27932618/the-roles-of-unfolded-protein-response-pathways-in-chlamydia-pathogenesis
#13
Zenas George, Yusuf Omosun, Anthony A Azenabor, James Partin, Kahaliah Joseph, Debra Ellerson, Qing He, Francis Eko, Claudiu Bandea, Pavel Svoboda, Jan Pohl, Carolyn M Black, Joseph U Igietseme
Chlamydia is an obligate intracellular bacterium that relies on host cell for essential nutrients and ATP for a productive infection. Although the unfolded protein response (UPR) plays a major role in certain microbial infectivity, its role in chlamydial pathogenesis is unknown. We hypothesized that Chlamydia induces UPR and exploits it to upregulate host cell uptake and metabolism of glucose, production of ATP, phospholipids and other molecules required for its replicative development and host survival. Using a combination of biochemical and pathway inhibition assays, we showed that the three UPR pathway transducers: Protein kinase RNA-activated (PKR)-like ER kinase (PERK), Inositol-requiring enzyme-1α (IRE1α), and Activating transcription factor-6α (ATF6α) were activated during Chlamydia infection...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27932481/modeling-monogenic-human-nephrotic-syndrome-in-the-drosophila-garland-cell-nephrocyte
#14
Tobias Hermle, Daniela A Braun, Martin Helmstädter, Tobias B Huber, Friedhelm Hildebrandt
Steroid-resistant nephrotic syndrome is characterized by podocyte dysfunction. Drosophila garland cell nephrocytes are podocyte-like cells and thus provide a potential in vivo model in which to study the pathogenesis of nephrotic syndrome. However, relevant pathomechanisms of nephrotic syndrome have not been studied in nephrocytes. Here, we discovered that two Drosophila slit diaphragm proteins, orthologs of the human genes encoding nephrin and nephrin-like protein 1, colocalize within a fingerprint-like staining pattern that correlates with ultrastructural morphology...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27932314/tis21-btg2-inhibits-doxorubicin-induced-stress-fiber-vimentin-networks-via-nox4-ros-abi2-drf-linked-signal-cascade
#15
In Kyoung Lim, Jung-A Choi, Eun Young Kim, Bit Na Kim, Soohyun Jang, Min Sook Ryu, Sang-Hee Shim
Activities of TIS21(/BTG2) gene regulating cancer cell senescence were investigated in hepatoma cells by using low dose doxorubicin (Doxo, 100ng/mL). Treatment of Huh7 cells with Doxo increased linear actin nucleation e.g., transverse arcs and ventral stress fibers, as opposed to loss of filopodia. The linear actin nucleation was accompanied with thick vimentin networks at periphery of the cells, when examined by super-resolution STED microscope. However, expression of TIS21 inhibited ABI2-DRF pathway by inhibiting DRF expression and reducing ABI2 protein stability...
December 5, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27932311/daclatasvir-prevents-hepatitis-c-virus-by-blocking-transfer-of-viral-genome-to-assembly-sites
#16
Bertrand Boson, Solène Denolly, Fanny Turlure, Christophe Chamot, Marlène Dreux, François-Loïc Cosset
BACKGROUND & AIMS: Daclatasvir is a direct-acting antiviral agent and potent inhibitor of NS5A, which is involved in replication of the hepatitis C virus (HCV) genome, presumably via membranous web shaping, and assembly of new virions, likely via transfer of the HCV RNA genome to viral particle assembly sites. Daclatasvir inhibits the formation of new membranous web structures and, ultimately, of replication complex vesicles, but also inhibits an early assembly step. We investigated the relationship between daclatasvir-induced clustering of HCV proteins, intracellular localization of viral RNAs and inhibition of viral particle assembly...
December 5, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27932295/the-interconnections-between-autophagy-and-integrin-mediated-cell-adhesion
#17
REVIEW
Ariadne Vlahakis, Jayanta Debnath
Autophagy is a cellular degradation process integral for promoting cellular adaptation during metabolic stress while also functioning as a cellular homeostatic mechanism. Mounting evidence also demonstrates that autophagy is induced upon loss of integrin-mediated cell attachments to the surrounding extracellular matrix (ECM). Analogous to its established cytoprotective role during nutrient starvation, autophagy protects cells from detachment-induced cell death, termed anoikis. Here, we review the significance of autophagy as an anoikis resistance pathway, focusing on the intracellular signals associated with integrins that modulate the autophagy response and dictate the balance between cell death and survival following loss of cell-matrix contact...
December 5, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27932173/a-case-report-of-severe-hepatic-artery-vasospasm-induced-by-hepatic-arterial-buffer-response-after-liver-transplantation
#18
Y Hiraki, K Uchida, S Nishida, D M Levi, G Selvaggi, A Tekin, J Fan, T Froud, A G Tzakis
The management of severe hepatic artery vasospasm soon after liver transplantation (LT) is challenging because it can lead to hepatic artery thrombosis and subsequent graft failure. A 61-year-old man with hepatitis C cirrhosis and portal vein thrombosis received a deceased donor LT. On postoperative day 1, Doppler ultrasonography revealed a high-resistance waveform in the hepatic artery. Angiography showed severe vasospasm of the donor hepatic artery on postoperative day 3. Strong hepatic arterial buffer response (HABR) was considered for this etiology due to high portal vein velocity...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932059/classical-transient-receptor-potential-trpc6-channels-support-myofibroblast-differentiation-and-development-of-experimental-pulmonary-fibrosis
#19
Katharina Hofmann, Susanne Fiedler, Sarah Vierkotten, Jonas Weber, Stephan Klee, Jie Jia, Wolfgang Zwickenpflug, Veit Flockerzi, Ursula Storch, Ali Önder Yildirim, Thomas Gudermann, Melanie Königshoff, Alexander Dietrich
Pulmonary fibrosis (PF) is a chronic progressive lung disease without effective medical treatment options leading to respiratory failure and death within 3-5 years of diagnosis. The pathological process of PF is driven by aberrant wound-healing involving fibroblasts and myofibroblasts differentiated by secreted profibrotic transforming growth factor β (TGF-β1). Classical transient receptor potential 6 (TRPC6), a Na(+)- and Ca(2+)-permeable cation channel, is able to promote myofibroblast conversion of primary rat cardiac and human dermal fibroblasts and TRPC6-deficiency impaired wound healing after injury...
December 5, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27932039/anaerobic-digestion-of-nitrogen-rich-poultry-manure-impact-of-thermophilic-biogas-process-on-metal-release-and-microbial-resistances
#20
Reshma Anjum, Elisabeth Grohmann, Niclas Krakat
Poultry manure is a nitrogen rich fertilizer, which is usually recycled and spread on agricultural fields. Due to its high nutrient content, chicken manure is considered to be one of the most valuable animal wastes as organic fertilizer. However, when chicken litter is applied in its native form, concerns are raised as such fertilizers also include high amounts of antibiotic resistant pathogenic Bacteria and heavy metals. We studied the impact of an anaerobic thermophilic digestion process on poultry manure...
December 5, 2016: Chemosphere
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