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https://www.readbyqxmd.com/read/29352443/baculovirus-based-gene-silencing-of-humanin-for-the-treatment-of-pituitary-tumors
#1
María Florencia Gottardo, Matías L Pidre, Camila Zuccato, Antonela S Asad, Mercedes Imsen, Gabriela Jaita, Marianela Candolfi, Víctor Romanowski, Adriana Seilicovich
Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN) and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective action. In the present study, we aimed to evaluate whether endogenous HNr plays an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including the coding sequences for shHNr and dTomato fluorescent reporter gene was developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role in pituitary tumor cells...
January 19, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29352310/leishmania-proteophosphoglycans-regurgitated-from-infected-sand-flies-accelerate-dermal-wound-repair-and-exacerbate-leishmaniasis-via-insulin-like-growth-factor-1-dependent-signalling
#2
Emilie Giraud, Tereza Lěstinová, Tamsyn Derrick, Oihane Martin, Rod J Dillon, Petr Volf, Ingrid Műller, Paul A Bates, Matthew E Rogers
Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352272/nuclear-p53-mediated-repression-of-autophagy-involves-pink1-transcriptional-down-regulation
#3
Thomas Goiran, Eric Duplan, Lila Rouland, Wejdane El Manaa, Inger Lauritzen, Julie Dunys, Han You, Frédéric Checler, Cristine Alves da Costa
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352047/patients-with-desmoplastic-melanoma-may-respond-to-pd-1-blockade
#4
(no author information available yet)
PD-1 blockade achieved responses in 70% of patients with desmoplastic melanoma in a retrospective analysis.
January 19, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29352039/disrupting-cd147-rap2-interaction-abrogates-erythrocyte-invasion-by-plasmodium-falciparum
#5
Meng-Yao Zhang, Yang Zhang, Xiao-Dong Wu, Kun Zhang, Peng Lin, Hui-Jie Bian, Min-Min Qin, Wan Huang, Ding Wei, Zhao Zhang, Jiao Wu, Ruo Chen, Fei Feng, Bin Wang, Gang Nan, Ping Zhu, Zhi-Nan Chen
Effective vaccines against Plasmodium falciparum malaria are still lacking and the molecular mechanism of the host-parasite interaction is not fully understood. Here we demonstrate that the interaction of RAP2, a parasite secreted rhoptry protein functioning in the parasitophorous vacuole formation stage of the invasion, and CD147 on host erythrocyte is essential for erythrocyte invasion by Plasmodium falciparum and is independent from all previously identified interactions involved. Importantly, the blockade of the CD147-RAP2 interaction by HP6H8, a humanized CD147 antibody, completely abolished the parasite invasion with both cure and preventative functions in a humanized mouse model...
January 19, 2018: Blood
https://www.readbyqxmd.com/read/29352025/state-of-the-art-and-future-directions-for-extinction-as-a-translational-model-for-fear-and-anxiety
#6
REVIEW
Michelle G Craske, Dirk Hermans, Bram Vervliet
Through advances in both basic and clinical scientific research, Pavlovian fear conditioning and extinction have become an exemplary translational model for understanding and treating anxiety disorders. Discoveries in associative and neurobiological mechanisms underlying extinction have informed techniques for optimizing exposure therapy that enhance the formation of inhibitory associations and their consolidation and retrieval over time and context. Strategies that enhance formation include maximizing prediction-error correction by violating expectancies, deepened extinction, occasional reinforced extinction, attentional control and removal of safety signals/behaviours...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29351986/phase-ii-study-of-oral-jak1-jak2-inhibitor-ruxolitinib-in-advanced-relapsed-refractory-hodgkin-lymphoma
#7
Eric Van den Neste, Marc André, Thomas Gastinne, Aspasia Stamatoullas, Corinne Haioun, Amine Belhabri, Oumedaly Reman, Olivier Casasnovas, Hervé Guesquieres, Gregor Verhoef, Marie-José Claessen, Hélène A Poirel, Marie-Christine Copin, Romain Dubois, Peter Vandenberghe, Ioanna-Andrea Stoian, Anne S Cottereau, Sarah Bailly, Laurent Knoops, Franck Morschhauser
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351487/contribution-of-parasympathetic-muscarinic-augmentation-of-insulin-secretion-to-olanzapine-induced-hyperinsulinemia
#8
Michael R Rickels, Elys M Perez, Amy J Peleckis, Erica Alshehabi, Huong-Lan Nguyen, Darko Stefanovski, Karl Rickels, Karen L Teff
Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized fifteen healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet and activity controlled inpatient conditions...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351473/sympathetically-mediated-cardiac-responses-to-isolated-muscle-metaboreflex-activation-following-exercise-are-modulated-by-body-position-in-humans
#9
André L Teixeira, Mauricio Daher, Mayara Souza, Plinio Santos Ramos, James P Fisher, Lauro C Vianna
Isolated muscle metaboreflex activation with post-handgrip exercise ischemia (PEI) increases sympathetic nerve activity and partially maintains the exercise-induced increase in blood pressure, but a smaller heart rate (HR) response occurs. The cardiopulmonary baroreceptors, mechanically sensitive receptors that respond to changes in central blood volume and pressure, are strongly associated with changes in body position and upon activation elicit reflex sympathoinhibition. Here, we tested the hypothesis that postural changes modulate the sympathetically-mediated cardiac response to PEI in humans...
December 15, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351463/intermediary-metabolism-and-fatty-acid-oxidation-novel-targets-of-electron-transport-chain-driven-injury-during-ischemia-and-reperfusion
#10
Qun Chen, Masood S Younus, Jeremy Thompson, Ying Hu, John M Hollander, Edward J Lesnefsky
BACKGROUND: Cardiac ischemia-reperfusion (IR) damages the electron transport chain (ETC) causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during IR. METHODS: Isolated-perfused mouse (C57BL/6) hearts underwent 25 min global ischemia (37{degree sign}C) and 30 min reperfusion...
December 29, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351428/control-of-appetite-blood-glucose-and-blood-pressure-during-melanocortin-4-receptor-activation-in-normoglycemic-and-diabetic-npy-deficient-mice
#11
Alexandre A da Silva, John Nathan Freeman, John E Hall, Jussara M do Carmo
Although central melanocortin 4 receptor (MC4R) blockade abolishes the CNS-mediated anorexogenic, antidiabetic and cardiovascular actions of leptin, chronic MC4R stimulation fails to completely mimic leptin's effects. Because neuropeptide Y (NPY) and MC4R exert opposite effects on cardiovascular and metabolic functions, we tested its role in offsetting the long-term actions of MC4R activation. Wild-type (WT) and NPY-deficient (NPY-/-) mice were implanted with telemetry probes for measuring mean arterial pressure (MAP) and heart rate (HR) 24-h/d...
December 20, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29350913/environmentally-triggerable-retinoic-acid-inducible-gene-i-agonists-using-synthetic-polymer-overhangs
#12
Christian R Palmer, Max E Jacobson, Olga Fedorova, Anna M Pyle, John T Wilson
Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) that potently activates antiviral innate immunity upon recognition of 5' triphosphorylated double-stranded RNA (pppRNA). Accordingly, RNA ligands of the RIG-I pathway have recently emerged as promising antiviral agents, vaccine adjuvants, and cancer immunotherapeutics. However, RIG-I is expressed constitutively in virtually all cell types, and therefore administration of RIG-I agonists causes risk for systemic inflammation and possible dose-limiting toxicities...
January 19, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29350794/the-role-of-electrodiagnosis-with-long-exercise-test-in-mcardle-disease
#13
Claudio Semplicini, Marianne Hézode-Arzel, Pascal Laforêt, Anthony Béhin, Sarah Leonard-Louis, Jean-Yves Hogrel, François Petit, Bruno Eymard, Tanya Stojkovic, Emmanuel Fournier
INTRODUCTION: We evaluated the role of an electrodiagnsotic provocative test (long exercise test, LET) in McArdle disease. METHODS: Twenty-five McArdle patients and two control groups underwent an electrodiagnsotic protocol with LET, consisting of recording the compound muscle action potential (CMAP) before and after 5 minutes of isometric contraction. RESULTS: LET disclosed a post-exercise decrease in CMAP amplitude in 23/25 McArdle patients...
January 19, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#14
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29348907/microsatellite-stability-and-mismatch-repair-proficiency-in-nasopharyngeal-carcinoma-may-not-predict-programmed-death-1-blockade-resistance
#15
Xiyi Liao, Liang Zhao, Sangang Wu, Hua Zheng, Haojun Chen, Huan Zhang, ZiJing Wang, Qin Lin
The US FDA granted accelerated approval to pembrolizumab for microsatellite instability-high and mismatch repair deficient cancers. The response of programmed death-1 blockade in mismatch repair proficiency (pMMR) colorectal cancer is very poor, however, whether such treatment is effective in pMMR nasopharyngeal carcinoma (NPC) remains unknown. We report a case of a 51-year-old man with NPC. PET-CT scan revealed a space-occupying lesion in the left lung, and the pathologic result confirmed the occupying lesion originated from NPC...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348870/n%C3%AE%C2%B5-carboxymethyl-lysine-promotes-calcium-deposition-in-vsmcs-via-intracellular-oxidative-stress-induced-pdk4-activation-and-alters-glucose-metabolism
#16
Wen-Qi Ma, Xi-Qiong Han, Ying Wang, Xin Wang, Yi Zhu, Nai-Feng Liu
Diabetes and vascular calcification are intrinsically linked. We previously reported that advanced glycation end products (AGEs) accelerate calcium deposition in vascular smooth muscle cells (VSMCs) via excessive oxidative stress. However, the underlying mechanism remains poorly understood. Pyruvate dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in cellular energy metabolism. Since hyperactivation of PDK4 has been reported in calcified vessels and in patients with diabetes mellitus, inhibition of PDK4 expression may be a strategy for the prevention of diabetic vascular calcification...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#17
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29348253/multifunctional-role-of-chymase-in-acute-and-chronic-tissue-injury-and-remodeling
#18
REVIEW
Louis J Dell'Italia, James F Collawn, Carlos M Ferrario
Chymase is the most efficient Ang II (angiotensin II)-forming enzyme in the human body and has been implicated in a wide variety of human diseases that also implicate its many other protease actions. Largely thought to be the product of mast cells, the identification of other cellular sources including cardiac fibroblasts and vascular endothelial cells demonstrates a more widely dispersed production and distribution system in various tissues. Furthermore, newly emerging evidence for its intracellular presence in cardiomyocytes and smooth muscle cells opens an entirely new compartment of chymase-mediated actions that were previously thought to be limited to the extracellular space...
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29348127/murine-chronic-graft-versus-host-disease-proteome-profiling-discovers-ccl15-as-a-novel-biomarker-in-patients
#19
Jing Du, Ryan Flynn, Katelyn Paz, Hong-Gang Ren, Yuko Ogata, Qing Zhang, Philip R Gafken, Barry E Storer, Nathan H Roy, Janis K Burkhardt, Wendy Mathews, Jakub Tolar, Stephanie J Lee, Bruce R Blazar, Sophie Paczesny
Improved diagnostic and treatment methods are needed for chronic graft-versus-host disease (cGVHD), the leading cause of late non-relapse mortality (NRM) in long-term survivors of allogenic hematopoietic cell transplantation (allo-HCT). Validated biomarkers that facilitate disease diagnosis, and classification generally are lacking in cGVHD. Here, we conducted whole serum proteomics analysis of a well-established murine multi-organ system cGVHD model. We discovered 4 up-regulated proteins during cGVHD that are targetable by genetic ablation or blocking antibodies, including the RAS and JUN kinase activator, CRKL, and CXCL7, CCL8 and CCL9 chemokines...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29348090/pharmacological-validation-of-the-folkloric-uses-of-cyperus-rotundus-l-in-different-ailments-an-in-vivo-and-in-vitro-research
#20
Musaddique Hussain, Hafiz Muhammad Waqas, Ikhlaq Hussain, Abdul Majeed, Shahid Masood Raza, Khalid Hussain Janbaz
In vivo and in vitro research study was conducted on Cyperus rotundus to evaluate the sound mechanistic background in the treatment of gastrointestinal, bronchial and vascular disorders as well as in pain, emesis, pyrexia and bacterial infections. Results showed that crude extract of Cyperus rotundus (Cr.Cr) exhibited the dose-dependent spasmolytic effect in rabbit jejunum by inhibiting the spontaneous and K+ (80 mM)-induced contractions. Pretreatment of tissue with Cr. Cr caused the rightward shift of calcium concentration response curves, similar to verapamil...
January 2018: Pakistan Journal of Pharmaceutical Sciences
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